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WHAT YOU SHOULD HAVE READ BUT….2012




                 rhinitis
Attilio Boner
University of
Verona, Italy
Validation of a self-questionnaire for assessing the
   control of allergic rhinitis. Demoly CEA 2011;41:860
                         Improvement of impact of allergic rhinitis
                         on sleep and work life (on a numeric scale
                        from 0 for ‘no signs’ to 10 for ‘very intense’)
 A self-assessment       at inclusion and day 15 after treatment.
  global score for
  allergic rhinitis
  control
  (five items scored
  from 1 to 5
  assessing the
  rhinitis over the
  2 previous weeks).

 902 patients.
Validation of a self-questionnaire for assessing the
   control of allergic rhinitis. Demoly CEA 2011;41:860
                            Improvement of impact of allergic
                         rhinitis on social and physical activities
                        (on a numeric scale from 0 for ‘no signs’ to
 A self-assessment        10 for ‘very intense’) at inclusion and
                                  day 15 after treatment.
  global score for
  allergic rhinitis
  control (five items
  scored from
  1 to 5 assessing
  the rhinitis over
  the 2 previous
  weeks).

 902 patients.
Validation of a self-questionnaire for assessing the
 control of allergic rhinitis. Demoly CEA 2011;41:860
•Rhinitis prevalence
Can early household exposure influence the development
of rhinitis symptoms in infancy? Findings from the PARIS
birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303

                                    Prevalence at age 18 months of

                              6.0 –
 Infants at age 18 months.
                                                              5.4%
                              5.0 –
 Presence of rhinitis        4.0 –
  symptoms (runny nose,
  blocked nose, sneezing      3.0 –
                                         3.8%
  in the absence of a cold)   2.0 –
  combined with biological
                              1.0 –
  atopy.
                              0 0
                                      Allergic rhinitis   Nonallergic rhinitis
Can early household exposure influence the development
of rhinitis symptoms in infancy? Findings from the PARIS
birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303

                                      OR for allergic rhinitis
                              4.0 –
 Infants at age 18 months.
                              3.0 –
 Presence of rhinitis                       3.15
  symptoms (runny nose,       2.0 –
  blocked nose, sneezing
  in the absence of a cold)   1.0 –
  combined with biological
  atopy.                      0 0
                                      Presence of cockroaches
                                            in the home
Can early household exposure influence the development
of rhinitis symptoms in infancy? Findings from the PARIS
birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303

                                     OR for nonallergic rhinitis
                               2.0 –
 Infants at age 18 months.
                               1.5 –            1.87
 Presence of rhinitis
  symptoms (runny              1.0 –
  nose, blocked
  nose, sneezing      in the   0.5 –
  absence of a cold)
  combined with biological     0 0
                                        Presence of particle-board
  atopy.                               furniture less than 12 months
                                         old in the child's bedroom
Natural course and comorbidities of allergic and
          nonallergic rhinitis in children
                Westman JACI 2012;129:403
                                    Proportion of children
                        % pts       with allergic rhinitis*

                         20 –
Birth cohort of
 2024 children.
                         15 –                               14%
IgEs against
 8 common                10 –
 inhaled allergens
 was available.          05 –
Age 4 and 8 yrs.                   5%
                          0
                                 4 years                   8 years
                          *allergic rhinitis = rhinitis with sensitization
                                           to allergens.
Natural course and comorbidities of allergic and
          nonallergic rhinitis in children
               Westman JACI 2012;129:403
                                   Proportion of children
                       % pts       with allergic rhinitis*
  Of the children
       with             20 –
Birth cohort of
 allergic rhinitis
 2024 children.
 when they were         15 –                               14%
   4 against
IgEs years old,
 8 common
 12% underwent          10 –
 inhaled allergens
 was remission
     available.         05 –
   by the time
     4 and 8 yrs.
Agethey were                      5%
                         0
   8 years old.                 4 years                   8 years
                         *allergic rhinitis = rhinitis with sensitization
                                          to allergens.
Natural course and comorbidities of allergic and
          nonallergic rhinitis in children
                Westman JACI 2012;129:403
                                    Proportion of children
                        % pts      with nonallergic rhinitis*

                         20 –
Birth cohort of
 2024 children.
                         15 –
IgEs against
 8 common                10 –
 inhaled allergens
 was available.          05 –        8%
                                                             6%
Age 4 and 8 yrs.
                          0
                                  4 years                 8 years
                                *nonallergic rhinitis = rhinitis without
                                      sensitization to allergens.
Natural course and comorbidities of allergic and
          nonallergic rhinitis in children
               Westman JACI 2012;129:403
                                   Proportion of children
                       % pts      with nonallergic rhinitis*
 Of the children
                        20 –
        with
Birth cohort of
nonallergic rhinitis
 2024 children.
                        15 –
IgEs against were
  when they
 8 common old,
    4 years             10 –
 73% underwent
 inhaled allergens
 was remission
     available.         05 –        8%
                                                            6%
Age 4 and 8 period
 during the yrs.
 of development.         0
                                 4 years                 8 years
                               *nonallergic rhinitis = rhinitis without
                                     sensitization to allergens.
Natural course and comorbidities of allergic and
          nonallergic rhinitis in children
                Westman JACI 2012;129:403

                                     % children with
                                ORAL ALLERGY SYNDROME
Birth cohort of         30 –
 2024 children.
IgEs against            20 –             25%
 8 common
 inhaled allergens
                         10 –
 was available.
Age 4 and 8 yrs.
                          0
                                  If allergic rhinitis at the
                                        age of 8 years
Natural course and comorbidities of allergic and
         nonallergic rhinitis in children
               Westman JACI 2012;129:403


Conclusions

Fewer preschool-age children with allergic rhinitis
undergo remission than do those with nonallergic rhinitis.
Sensitization to inhaled allergens at an early age (4 years)
precedes the development of allergic rhinitis, whereas
symptoms of rhinitis do not.
Oral allergy syndrome is common among 8-year-olds with
allergic rhinitis.
Trends in the prevalence of asthma and allergic
        rhinitis in Italy between 1991 and 2010
              R. de Marco, Eur Respir J 2012;39:883

                                    Overall mean prevalence
 The same screening
  questionnaire by mail
  or phone.

 Random samples of the
  general population
  (age 20–44 yrs).

 (1991–1993; n=6,031)
  (1998–2000; n=18,873)
  (2007–2010; n=10,494)
Trends in the prevalence of asthma and allergic
        rhinitis in Italy between 1991 and 2010
              R. de Marco, Eur Respir J 2012;39:883

                                    Overall mean prevalence
 The same screening
     The asthma epidemic
  questionnaire by mail
  or is not over in Italy.
      phone.
   During the past 20 yrs,
    asthma prevalence has
 Random samples of the
      increased by 38%,
  general population
  (age 20–44 with a similar
  in parallel yrs).
   increase in asthma-like
         symptoms and
 (1991–1993; n=6,031)
        allergic rhinitis.
  (1998–2000; n=18,873)
  (2007–2010; n=10,494)
The protective effect of farm milk consumption on
   childhood asthma and atopy: the GABRIELA study
                     Loss JACI 2011;128:766

                                     OR for asthma
                            1.0 –
 Farm milk consumption.
 8334 school-aged
  children.

                                       0.59
                            0.5 –
 800 cow’s milk samples
  collected at the
  participants’
  homes, viable bacterial
  counts, whey protein       0
  levels and total fat                For raw milk
  content.                            consumption
The protective effect of farm milk consumption on
   childhood asthma and atopy: the GABRIELA study
                      Loss JACI 2011;128:766

                                      OR for asthma
                             1.0 –
 Farm milk consumption.
 8334 school-aged
  children. farm milk
      Boiled
 800 did not show a
                                        0.59
                             0.5 –
       cow’s milk samples
         protective
  collected at the
           effect.
  participants’ homes,
  viable bacterial counts,
  whey protein levels and     0
  total fat content.                   For raw milk
                                       consumption
The protective effect of farm milk consumption on
   childhood asthma and atopy: the GABRIELA study
                      Loss JACI 2011;128:766

                                     OR for hay fever
                             1.0 –
 Farm milk consumption.
 8334 school-aged
  children.
                             0.5 –
 800 cow’s milk samples
  collected at the
  participants’ homes,
                                        0.51
  viable bacterial counts,
  whey protein levels and     0
  total fat content.                    For raw milk
                                        consumption
The protective effect of farm milk consumption on
   childhood asthma and atopy: the GABRIELA study
                     Loss JACI 2011;128:766

                                    OR for hay fever
                            1.0 –
 Farm milk consumption.
 8334 school-aged
  children. farm milk
      Boiled
 800 did not show a
       cow’s milk samples   0.5 –
         protective
  collected at the
           effect.
  participants’
                                       0.51
  homes, viable bacterial
  counts, whey protein       0
  levels and total fat                 For raw milk
  content.                             consumption
The protective effect of farm milk consumption on
 childhood asthma and atopy: the GABRIELA study
                    Loss JACI 2011;128:766




 Total viable bacterial counts and total fat content of milk
  were not significantly related to asthma or atopy.
 Increased levels of the whey proteins BSA (aOR for highest
  vs lowest levels and asthma, 0.53; 95% CI 0.30-
  0.97),       α-lactalbumin (aOR for interquartile range and
  asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR
  for interquartile range and asthma, 0.62; 95% CI, 0.39-
  0.97), however,         were inversely associated with
  asthma but not with atopy.
The protective effect of farm milk consumption on
 childhood asthma and atopy: the GABRIELA study
                   Loss JACI 2011;128:766




 Total viable bacterial counts and total fat content of milk
  were not significantly related to asthma raw milk
            The protective effect of or atopy.
             consumption on asthma might be
                     associated with BSA
 Increased levels of the whey proteins the (aOR for highest
  vs lowest levels and asthma, 0.53; 95% CI 0.30-
  0.97),      whey protein(aOR for interquartile range and
               α-lactalbumin fraction of milk.
  asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR
  for interquartile range and asthma, 0.62; 95% CI, 0.39-
  0.97), however,         were inversely associated with
  asthma but not with atopy.
House dust mite sensitization in toddlers predicts current
     wheeze at age 12 years Lodge JACI 2011;128:782
                               Prevalence of sensitization
                             (and 95% CI) at age 6 months
                                (n=560), 1 year (n=551),
 Birth cohort of 620             and 2 years (n=459).
  children oversampled for
  familial allergy.
 SPTs to 6 allergens at
  ages 6, 12, and 24 mo.
 Wheeze and eczema
  recorded during
  the first 2 yrs.
 Current wheeze recorded
  at age 12 yrs.
House dust mite sensitization in toddlers predicts current
     wheeze at age 12 years Lodge JACI 2011;128:782
                             7 –   OR for wheeze at 12 yrs
                             6 –
                                                  6.37
 Birth cohort of 620        5 –
  children oversampled for   4 –
  familial allergy.
 SPTs to 6 allergens at     3 –
  ages 6, 12, and 24 mo.            3.31
                             2 –
 Wheeze and eczema
  recorded during            1 –
  the first 2 yrs.
                             0
 Current wheeze recorded
                                    Age 1 yr     Age 2 yrs
  at age 12 yrs.
                                    SPT (+) for mite dust
House dust mite sensitization in toddlers predicts current
     wheeze at age 12 years Lodge JACI 2011;128:782

                             80 –
                                    % children wheezing at age 12 yrs

                                        75%
                             70 –

                             60 –
 Birth cohort of 620
  children oversampled for   50 –
  familial allergy.          40 –
 SPTs to 6 allergens at
  ages 6, 12, and 24 mo.
 Wheeze and eczema
                             30 –

                             20 –
                                                      36%
  recorded during            10 –
  the first 2 yrs.
                             0
 Current wheeze recorded
                                       Sensitized   Not Sensitized
  at age 12 yrs.
                                          Wheezing at age 1
House dust mite sensitization in toddlers predicts current
     wheeze at age 12 years Lodge JACI 2011;128:782

                             80 –
                                    % children wheezing at age 12 yrs
                             70 –

 Birth cohort of 620
  children oversampled for
                             60 –

                             50 –
                                        67%
  familial allergy.          40 –
 SPTs to 6 allergens at
                                                      35%
                             30 –
  ages 6, 12, and 24 mo.
 Wheeze and eczema          20 –
  recorded during            10 –
  the first 2 yrs.
                             0
 Current wheeze recorded
                                        SPT (+)        SPT (-)
  at age 12 yrs.
                                          Eczema at age 1
                                              and mite
House dust mite sensitization in toddlers predicts current
     wheeze at age 12 years Lodge JACI 2011;128:782

                               80 –
                                      % children wheezing at age 12 yrs
                               70 –
       HDM sensitization
 Birthat age 1 or 2 yrs
        cohort of 620
         in wheezing and
  children oversampled for
                               60 –

                               50 –
                                          67%
  familial allergy. children
      eczematous               40 –
      at increased familial
 SPTs to 6 allergens at
                                                        35%
                               30 –
            allergy risk
  ages 6, 12, and 24 mo.
        predicts asthma
 Wheeze and eczema            20 –
  recorded duringinform
         and may               10 –
  themanagement of these
      first 2 yrs.
                               0
 Current wheeze group.
        high-risk recorded
                                          SPT (+)        SPT (-)
  at age 12 yrs.
                                            Eczema at age 1
                                                and mite
Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
      an international population-based cohort study
                     Matheson JACI 2011;128:816
                                    HR for women developing
                                    rhinitis compared to men

 1992-1994 community-
  based samples
                            1.0 –
                                                  1.36
  of 20-44 yr-old people.

                                    0.63
                            0.5 –
 48 centers in 22
  countries.
 8486 participants.         0
                                    Childhood      Adulthood
                                             During
Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
      an international population-based cohort study
                   Matheson JACI 2011;128:816

        Cumulative probability of     Cumulative probability of
          rhinitis by gender in         rhinitis by gender in
        subjects who are atopic.    subjects who are non atopic.
Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
      an international population-based cohort study
                     Matheson JACI 2011;128:816

                                    HR for developing rhinitis
                            1.0 –



                                          0.84
 1992-1994 community-
  based samples
  of 20-44 yr-old people.   0.5 –

 48 centers in 22
  countries.
                             0
 8486 participants.                Early contact with children
                                     in the family or day care
                                         before age 5 yrs.
Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
      an international population-based cohort study
                     Matheson JACI 2011;128:816

                                    HR for developing rhinitis
                            1.0 –



                                            0.5
 1992-1994 community-
  based samples
  of 20-44 yr-old people.   0.5 –

 48 centers in 22
  countries.
                             0
 8486 participants.                 Early childhood pets or
                                     growing up on a farm.
Early-life risk factors and incidence of rhinitis: results
from the European Community Respiratory Health Study-
      an international population-based cohort study
                   Matheson JACI 2011;128:816

                                     HR for developing rhinitis
     Protective effects      1.0 –
   of early contact with

                                             0.5
 1992-1994 and animals
    children community-
  based samples
      were suggested
  offor incident rhinitis,
     20-44 yr-old people.    0.5 –

 48 with risk patterns
     centers in 22
  countries. age window
   varying by
     and atopic status
 8486 participants. .
                              0
                                      Early childhood pets or
                                      growing up on a farm.
•Rhinitis
   •risk factors
•Protective factors
The influence of gender and atopy on the natural
     history of rhinitis in the first 18 years of life
                 Kurukulaaratchy      CEA 2011;41:851
                        Changes in atopic and non-atopic rhinitis prevalence
                         for boys and girls over the first 18 years of life

 Natural history
  of rhinitis up to
  18 years of age.

 Isle of Wight birth
  cohort recruited in
  1989 (n = 1456).

 Questionnaire and
  skin prick tests.
The influence of gender and atopy on the natural
     history of rhinitis in the first 18 years of life
                Kurukulaaratchy       CEA 2011;41:851
                        Changes in atopic and non-atopic rhinitis prevalence
                         for boys and girls over the first 18 years of life

 Natural history
     Atopic rhinitis
  of rhinitis up to
         becomes
  18 years of age.
   increasingly common
     as children grow
 Isle of Wight birth
            into
  cohort recruited in
    adolescents, with
  1989 (n = 1456).
         stronger
 Questionnaireto male
   associations and
          gender.
  skin prick tests.
The influence of gender and atopy on the natural
     history of rhinitis in the first 18 years of life
                 Kurukulaaratchy      CEA 2011;41:851
                        Changes in atopic and non-atopic rhinitis prevalence
                         for boys and girls over the first 18 years of life

 Natural history
  ofNon-atopic to
     rhinitis up rhinitis
      shows a female
  18 years of age.
   predominance at 18
 Isle of Wight birth
    years as girls „grow
  cohort it more during
    into‟ recruited in
        (n = 1456).
  1989 adolescence.

 Questionnaire and
  skin prick tests.
Gestational age at birth and risk of allergic rhinitis
  in young adulthood. Crump JACI 2011;127:1173



                                    For subjects born extremely
                                   preterm (23-28 weeks) OR for
 630,090 infants born in
  Sweden including 27,953    1.0 –
  born preterm (<37 wks).

 Prescription of nasal      0.5 –    0.70
  corticosteroids and oral                            0.45
  antihistamines             0.0
                                       Nasal          Both nasal
 age, 25.5-37.0 yrs.              corticosteroid   corticosteroid
                                    prescription       and oral
                                                    antihistamine
                                                     prescription
Gestational age at birth and risk of allergic rhinitis
  in young adulthood. Crump JACI 2011;127:1173


     These findings suggest
    that low gestational age        For subjects born extremely
      at birth independent        preterm (23-28 weeks) OR for
 630,090 infants born in
        of fetal growth is
  Sweden including 27,953     1.0 –
        associated with a
  born preterm (<37 wks).
        decreased risk of
 Prescription of nasal young 0.5 –
    allergic rhinitis in             0.70
  corticosteroids and oral
       adulthood, possibly                         0.45
  antihistaminesa protective 0.0
    because of
                                       Nasal         Both nasal
        effect of earlier
 age, 25.5-37.0 yrs.             corticosteroid corticosteroid
    exposure to pathogens.          prescription      and oral
                                                   antihistamine
                                                    prescription
Staphylococcal enterotoxin B compromises
   the immune tolerant status in the airway mucosa.
                 Liu T, Clin Exp Allergy 2012;42:375

1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced
   by the bacterium Staphylococcus aureus. SEB may contaminate
   ingested food and induce gastrointestinal dysfunction.
   SEB interferes with the function of the immune system
   in the airway mucosa, such as to be involved in the pathogenesis
   of airway allergy.
2) Integrin alphavbeta6 (avb6) is produced by epithelial cells
   in response to external stimuli, such as wound and inflammation.
   Our recent study data also show that intestinal epithelial cells
   express detectable avb6 that has protelytic activity and can convert
   the precursor of transforming growth factor (TGF)β into the active
   form of TGFβ. TGFβ plays a critical role in the Treg development.
   Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase
   (ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.
Staphylococcal enterotoxin B compromises
   the immune tolerant status in the airway mucosa.
                 Liu T, Clin Exp Allergy 2012;42:375

1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced
   by the bacterium Staphylococcus aureus. SEB may contaminate
   ingested food and induce gastrointestinal dysfunction. in avb6
      The increases in SEB and decreases
   SEB interferes with the function of the immune system
   in the airway mucosa, such as to be involvedassociated
              in nasal epithelium are in the pathogenesis
   of airway allergy. compromises of immune tolerance
        with the
                      in the nasal mucosa.
2) Integrin alphavbeta6 (avb6) is produced by epithelial cells
   in response SEB has stimuli,ability wound and inflammation.
               to external the such as to suppress
   Our recent study data also show that intestinal epithelial cells
   express detectable avb6 that has protelyticavb6 and can convert
                     the expression of activity
                     in nasal epithelial cells.
   the precursor of transforming growth factor (TGF)β into the active
   form of TGFβ. TGFβ plays a critical role in the Treg development.
   Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase
   (ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.
Staphylococcal enterotoxin B compromises
    the immune tolerant status in the airway mucosa.
                 Liu T, Clin Exp Allergy 2012;42:375
                                         Avb6 expression is suppressed in the
                                         allergic rhinitis (AR) nasal epithelium
• The immune tolerant components,
  tolerogenic dendritic cells (TolDC)                          P<0.01

  & regulatory T cells (Treg), were
  assessed in the surgically removed
  nasal mucosa from patients
  with allergic rhinitis (AR)
                                          Staphylococcal enterotoxin B (SEB)
  or non-AR chronic rhinitis.             levels are increased in the allergic
                                                rhinitis nasal epithelium.
• Contents of Staphylococcal
  enterotoxin B & integrin alphavbeta6                      P<0.01
  (avb6) in the nasal epithelium
  assessed using enzyme-linked
  immunoassay.
Staphylococcal enterotoxin B compromises
    the immune tolerant status in the airway mucosa.
                Liu T, Clin Exp Allergy 2012;42:375
                                         Avb6 expression is suppressed in the
                                         allergic rhinitis (AR) nasal epithelium
• The immune tolerant
  components, components
          The tolerogenic dendritic
                                                               P<0.01

  cells (TolDC) & regulatory T cells
      of immune tolerance
  (Treg), were assessed in the
  surgically machinery, mucosa
             removed nasal
  from patients & Tregs
          TolDCs           with
                                          Staphylococcal enterotoxin B (SEB)
  allergic rhinitis (AR)
         were suppressed                  levels are increased in the allergic
  or non-AR chronic rhinitis.                   rhinitis nasal epithelium.
              in the AR
• Contents of Staphylococcal
           nasal mucosa.                                    P<0.01
  enterotoxin B & integrin alphavbeta6
  (avb6) in the nasal epithelium
  assessed using enzyme-linked
  immunoassay.
Adaptative immune responses in Staphylococcus aureus
      biofilm-associated chronic rhinosinusitis
                Foreman, Allergy 2011;66:1449


Background: The etiopathogenesis of chronic rhinosinusitis (CRS)
is currently an area of intense debate. Recently, biofilms have
been proposed as a potential environmental trigger in this
disease. In particular, Staphylococcus aureus biofilms appear to
be a predictor of severe disease recalcitrant to current
treatment paradigms.
However, direct causal links between biofilms and host immune
activation are currently lacking. This study aimed to document
both the adaptive immune responses that characterize S. aureus
biofilm–associated CRS and the relative contributions of
staphylococcal superantigens and S. aureus biofilms in the
inflammatory make-up of this disease.
Adaptative immune responses in Staphylococcus aureus
      biofilm-associated chronic rhinosinusitis
                 Foreman, Allergy 2011;66:1449

                                      Staphylococcus aureus
                                           biofilms and
 53 disease subjects;
                                        superantigens are
 15 controls;                             significantly
                                            associated
 Sinonasal mucosa for                        in CRS
  S.aureus and Haemophilus             patients, suggesting
  influenzae biofilms;
                                       the biofilm may be a
 Presence of total and                      nidus for
  superantigen-specific IgE            superantigen-eluting
                                             bacteria.
Adaptative immune responses in Staphylococcus aureus
      biofilm-associated chronic rhinosinusitis
                 Foreman, Allergy 2011;66:1449

                                      Staphylococcus aureus
                                           biofilms and
 53 The presence of
     disease subjects;
        S. aureus                       superantigens are
        biofilms is
 15 controls;                             significantly
      associated with                       associated
 Sinonasal mucosa for
         eosinophilic                         in CRS
  S.aureus and Haemophilus
       inflammation,                   patients, suggesting
  influenzae biofilms;
         across the                    the biofilm may be a
     spectrum of CRS                         nidus for
 Presence of total and
  superantigen-specific IgE            superantigen-eluting
                                             bacteria.
Adaptative immune responses in Staphylococcus aureus
       biofilm-associated chronic rhinosinusitis
                         Foreman, Allergy 2011;66:1449
     Representative images of bacterial biofilms on sinus mucosa using a FISH
(Fluorescence in situ Hybridization) protocol, imaged on the confocal scanning laser
  microscope. Both images demonstrate brightly fluorescing bacterial-sized dots
 surrounded by a less-intense fluorescing blush, thought to represent the matrix.




       (A) H.influenza                                     (B) Staphylococcus
        FISH probe                                         aureus FISH probe
      tagged with Cy3                                     tagged with Alexa488
         fluorophore                                           fluorophore
Early protective and risk factors for allergic rhinitis at
     age 4½ yr Alm Pediat Allergy Immunol 2011;22:398

                                  % children reporting
 A prospective, longitudinal     symptoms of allergic
  study of a cohort of          rhinitis during the least
  children born in the region     year at age 4 ½ yrs
  of western Sweden in 2003.
                                  6 –

 8,176 families.                 5 –

                                  4 –
                                         5.5%
 Questionnaires at               3 –

  6 and 12 months                 2 –
  and at 4½ yr of age.            1 –

                                  0
Early protective and risk factors for allergic rhinitis at
     age 4½ yr Alm Pediat Allergy Immunol 2011;22:398

 1.5 –
 1.0 –
           10.21              OR for allergic rhinitis
 0 9 –
 0 8 –
 0 7 –
 0 6 –
 0 5 –
 0 4 –
 0 3 –
                           3.3
 0 2 –                                2.72        2.21
 0 1 –
                                                              1.97
 0 0
         Sensitisation   Recurrent    Doctor-    Parental     Eczema
           to food        wheeze     diagnosed    rhinitis   first year
          allergens                   eczema
Early protective and risk factors for allergic rhinitis at
     age 4½ yr Alm Pediat Allergy Immunol 2011;22:398

 1.5 –
 1.0 –
           10.21              OR for allergic rhinitis
 0 9 –
 0 8 –
 0 7 –                        The risk was reduced with
 0 6 –                         fish introduction before
 0 5 –
 0 4 –
                                       9 months
 0 3 –
                           3.3
 0 2 –                                2.72        2.21
 0 1 –
                                                              1.97
 0 0
         Sensitisation   Recurrent    Doctor-    Parental     Eczema
           to food        wheeze     diagnosed    rhinitis   first year
          allergens                   eczema
High-Dose Docosahexaenoic Acid Supplementation of
  Preterm Infants: Respiratory and Allergy Outcomes
                 Manley Pediatrics 2011;128:e71

 657 preterm infants 33                  RR of reported hay fever
  weeks’ gestation who                     in all infants at either
  consumed expressed breast                   12 or 18 months
                                  1.0 –
  milk from mothers taking
                                  0.9 –
  either tuna oil                 0.8 –
  (high-DHA diet) or soy oil      0.7 –
  (standard-DHA) capsules.        0.6 –
                                  0.5 –
                                  0.4 –
 Incidence of
  bronchopulmonary dysplasia
                                  0.3 –
                                  0.2 –
                                                 0.41
  (BPD) and parental reporting    0.1 –
                                                   p=0.03
  of atopic conditions over the    0
  first 18 months of life.                       DHA diet
•Rhinitis
etiopathogenesis
Protease-activated receptor 2-dependent fluid secretion
   from airway submucosal glands by house dust mite
    Quantitative
                 extract Cho JACI 2012;129:529
    measurement of
  glandular secretion.
A. Harvest of nasal mucosa
   from the inferior nasal
   turbinate.
B. Experimental setup.
C. Mucus bubbles from
   glands under oil are
   visualized by using
   bright-field microscopy
   and side-light illumination.
D. Example of mucus
   bubbles formed on the
   surface of nasal
   turbinates 30 minutes
   after stimulation with
   HDM extract.
Protease-activated receptor 2-dependent fluid secretion
   from airway submucosal glands by house dust mite
              extract Cho JACI 2012;129:529
Background
The submucosal gland (SMG) is important in the control of airway
surface fluid.
Protease-activated receptor (PAR) 2 contributes to the pathophysiology
of allergies in response to nonspecific allergens bearing proteases and
anion secretion.
House dust mites (HDMs) have abundant proteases that can activate
PAR2, but little is known about the direct effect of HDM on SMG
secretion.

Objective
To investigate the effect of HDMs on glandular secretion and its
mechanism in allergic patients, patients with chronic rhinosinusitis
(CRS), or both.
Protease-activated receptor 2-dependent fluid secretion
   from airway submucosal glands by house dust mite
              extract Cho JACI 2012;129:529

Inferior nasal
                                     1) HDM induced a
 turbinates.
                                     significantly higher
55 patients classified              secretion rate
 into four groups:
                                     and number of
  1. the control,
  2. allergic rhinitis (AR),         responding glands
  3. chronic rhinosinusitis (CRS),   in the AR and
  4. AR + CRS.                       AR+CRS groups
Mucus bubbles from                  than in the
 individual submucosal               control group.
 gland (SMGs).
Protease-activated receptor 2-dependent fluid secretion
   from airway submucosal glands by house dust mite
              extract Cho JACI 2012;129:529

Inferior nasal                      2) Patients in the
 turbinates.                         CRS group, who had no
55 patients classified              HDM-specific IgE,
 into four groups:                   showed a
  1. the control,                     higher response
  2. allergic rhinitis (AR),         than the control group,
  3. chronic rhinosinusitis (CRS),
                                     and its response
  4. AR + CRS.
                                      was suppressed by
Mucus bubbles from                  a PAR2-selective
 individual submucosal               antagonist.
 gland (SMGs).
Protease-activated receptor 2-dependent fluid secretion
   from airway submucosal glands by house dust mite
              extract Cho JACI 2012;129:529
                                        Responses to HDM. Plots of averaged
                                     secretion rates versus time for each group.
Inferior nasal                                       *p < 0.05
 turbinates.
55 patients classified
 into four groups:
  1. the control,
  2. allergic rhinitis (AR),
  3. chronic rhinosinusitis (CRS),
  4. AR + CRS.

Mucus bubbles from
 individual submucosal
 gland (SMGs).
Protease-activated receptor 2-dependent fluid secretion
   from airway submucosal glands by house dust mite
              extract Cho JACI 2012;129:529
                                        Responses to HDM. Plots of averaged
                                     secretion rates versus time for each group.
Inferior nasal                                       *p < 0.05
     Interestingly, patients in
 turbinates.
     the CRS group, who had
55 patients classified IgE
        no HDM-specific
 into four groups:
         antibody, showed a
  1. the control,
     higher response than the
  2. allergic rhinitis (AR), its
       control group, and
  3. chronic rhinosinusitis (CRS),
     response was suppressed
  4. AR + CRS.
        by a PAR2-selective
              antagonist.
Mucus bubbles from
 individual submucosal
 gland (SMGs).
Protease-activated receptor 2-dependent fluid secretion
   from airway submucosal glands by house dust mite
              extract Cho JACI 2012;129:529



   Conclusions

   HDM allergens can induce glandular secretion in patients
   with AR, CRS, or both, and PAR2 represents a possible
   mechanism for nonspecific hyperreactivity in inflammatory
   airway diseases.
Luminal decoration of blood vessels by activated
     perivasal mast cells in allergic rhinitis
           Schaefer, Allergy 2012;67:510
                                           (A) Tissue
                                           accumulation
                                           of mast cells
                                           (b-
                                           tryptase, brown, on
                                           hematoxylin
                                           background staining)
                                           in allergic rhinitis
                                           patient (AR, right)
                                           & healthy control
                                           (left).
                                           (B) Activated
                                           mast cells co-localize
                                           with peripheral
                                           blood vessels in AR
                                           nasal mucosa.
                                           Asterisks indicate
                                           capillary lumen.
Luminal decoration of blood vessels by activated
     perivasal mast cells in allergic rhinitis
           Schaefer, Allergy 2012;67:510

                                           (C) Confocal laser
                                           scanning microscopy
                                           of AR nasal mucosa
                                           stained with
                                           DAPI (nuclei, blue),
                                           anti CD31 (endothelial
                                           cells, green),
                                           & anti CD63var (red).
                                           Arrows indicate
                                           fluorescence signal
                                           transfer
                                           from degranulating
                                           mast cells into the
                                           lumen
                                           of microcapillaries
                                           across
                                           the juxtapositioned
                                           endothelial cells.
Luminal decoration of blood vessels by activated
         perivasal mast cells in allergic rhinitis
                  Schaefer, Allergy 2012;67:510

• Mast cells can discharge exosomes, which are complete,
  membrane-covered vesicles, able to travel long distances with
  the help of the lymphatic system.

• Another novel way: upon triggering, granular membrane factors
  directly traverse from the activated mast cell onto an acceptor
  cell.

• Detected epitope transfer from activated mast cells onto
  neighboring cells by following the localization of CD63var,
  which is a specific molecular marker of human mast cell granuli.

• The new transport mode requires an intimate cellular coupling.
Luminal decoration of blood vessels by activated
          perivasal mast cells in allergic rhinitis
                    Schaefer, Allergy 2012;67:510


• In conclusion, we describe details of a novel intercellular
  communication mechanism, wherein granulated cells can select
  distinguished acceptor cells via receptor–ligand interactions and
  then transfer a set of their own molecules onto them.

• This way mast cells can control, modify or even reprogram
  selected bystander cells and may fundamentally reshape their
  microenvironment in case of an allergic challenge. As mast cells
  frequently co-localize with blood vessels in situ, we propose that
  via this transcytotic channeling, mast cells instantly modulate the
  membrane composition of neighboring endothelium.
Nasal allergen provocation test with multiple
          aeroallergens detects polysensitization in local
             allergic rhinitis. Rondon, JACI 2011;128:1192

Background:
Patients previously given a diagnosis of non-allergic rhinitis (NAR)
might have a new form of local allergic rhinitis (LAR) with
local production of specific IgE antibodies and a positive response
to a nasal allergen provocation test (NAPT).
Objective:
We evaluated an NAPT protocol using multiple aeroallergens
(NAPT-M) for the detection of polysensitization
to several aeroallergens in patients with LAR.

    LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
   NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
          VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
Nasal allergen provocation test with multiple
           aeroallergens detects polysensitization in local
              allergic rhinitis. Rondon, JACI 2011;128:1192

 25 adult patients with Local allergic rhinitis (LAR);
  25 adult patients with Non-allergic rhinitis (NAR).
 All the patients had a history of at least 2 yrs
  of persistent rhinitis with negative skin prick test (SPT) responses
  and serum sIgE levels to the most prevalent aeroallergens.
 - LAR was diagnosed by the presence of a positive response
  to ≥ 1 NAPT-Ss with D pteronyssinus, Alternaria alternata,
  Olea europea, or grass pollen ;
  - NAR by a negative NAPT response.

     LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
    NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
           VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
Nasal allergen provocation test with multiple
           aeroallergens detects polysensitization in local
              allergic rhinitis. Rondon, JACI 2011;128:1192
NAPT-M: Nasal allergen provocation test with multiple allergens
• Symptom-free patients (total VAS <60 mm) were challenged intranasally
  with 2 puffs (100 mL) of saline in each nostril to exclude nasal hyperreactivity.
  If the result was negative, 15 minutes after NAPT-M, we began administrating
  4 consecutive and different reconstituted freeze-dried allergen solutions
  of D pteronyssinus (4 µg/mL), A alternata (0.25 µg/mL), O europea (0.6 µg/mL), and
  grass pollen (0.1 µg/mL; ALK-Abello) at 15-minute intervals.
  2 puffs (100 mL) of the solution at room temperature were applied in each nostril.
• The response to nasal challenge was evaluated based on subjective
  (VAS of nasal-ocular symptoms) and objective (VOL2-6 cm) parameters.
• A positive NAPT-M response was considered to be:
  1) an increase of ≥ 30% in the total VAS score
  2) a decrease of ≥ 30% in the sum of VOL2-6 cm from both nasal cavities.
     LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
    NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
           VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
Nasal allergen provocation test with multiple
      aeroallergens detects polysensitization in local
         allergic rhinitis. Rondon, JACI 2011;128:1192
Nasal levels of tryptase and ECP in patients with LAR after NAPT-Ms.

                                                                                        *
                      *                                                          *
               *
                                                                          *
                                                                    *




* Significant differences (p < 0.05) between baseline and 15 minutes and 1, 2, and 24 hours
                                      after challenge.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
Nasal allergen provocation test with multiple
      aeroallergens detects polysensitization in local
         allergic rhinitis. Rondon, JACI 2011;128:1192
Nasal levels of tryptase and ECP in patients with LAR after NAPT-Ms.

                                                                                        *
                      *                                                          *
               *
                                                                          *
                                                                    *




     There is a clinically relevant polysensitization
* Significant differences (p <aeroallergens and 15 minutes and 1, 2, and 24 hours
                          to 0.05) between baseline in patients
                                      after challenge.
                                        with LAR.
LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
Nasal allergen provocation test with multiple
       aeroallergens detects polysensitization in local
          allergic rhinitis. Rondon, JACI 2011;128:1192
                Number of visits required for the final diagnosis
                         in NAPT-Ms and NAPT-Ss.




 LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
       VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
Nasal allergen provocation test with multiple
       aeroallergens detects polysensitization in local
          allergic rhinitis. Rondon, JACI 2011;128:1192
                Number of visits required for the final diagnosis
                         in NAPT-Ms and NAPT-Ss.

                                                               NAPT-M is a useful,
                                                                specific, sensitive,
                                                                 reproducible, and
                                                               less time-consuming
                                                              in vivo diagnostic test
                                                                 for the screening
                                                              of patients with LAR.



 LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis;
       VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
Comparative evaluation of nasal blood flow and airflow
     in the decongestant response to oxymetazoline
       Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77

 19 healthy adults.                  Decongestive response
                                     in nasal blood flow (NBF)
 Doubling doses of
  oxymetazoline of 25µg,                     P<0.001     P<0.001
  50µg, 100µg, and 200µg at
  20 minute intervals.
 Peak nasal inspiratory flow
  (PNIF) and nasal airway
  resistance (NAR) at baseline
  and after each successive
  dose.                                   1 visit       2 visit
 Nasal blood flow (NBF) using
  laser Doppler Flowmetry.
Comparative evaluation of nasal blood flow and airflow
     in the decongestant response to oxymetazoline
       Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77

 19 healthy adults.                   Peak nasal inspiratory
                                            flow (PNIF)
 Doubling doses of
  oxymetazoline of 25µg,
  50µg, 100µg, and 200µg at               P<0.001      P<0.003
  20 minute intervals.
 Peak nasal inspiratory flow
  (PNIF) and nasal airway
  resistance (NAR) at baseline
  and after each successive
  dose.                                   1 visit       2 visit
 Nasal blood flow (NBF) using
  laser Doppler Flowmetry.
Comparative evaluation of nasal blood flow and airflow
     in the decongestant response to oxymetazoline
       Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77

 19 healthy adults.                       Nasal airway
                                         resistance (NAR)
 Doubling doses of
  oxymetazoline of
  25µg, 50µg, 100µg, and                                  P<0.002
  200µg at 20 minute                         P<0.001
  intervals.
 Peak nasal inspiratory flow
  (PNIF) and nasal airway
  resistance (NAR) at baseline
  and after each successive               1 visit       2 visit
  dose.
 Nasal blood flow (NBF) using
Comparative evaluation of nasal blood flow and airflow
     in the decongestant response to oxymetazoline
       Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77

 19 healthy adults.                       Nasal airway
                                         resistance (NAR)
 Doubling doses offlow using
     Nasal blood
  oxymetazoline of
    laser Doppler flowmetry
  25µg, 50µg, 100µg, and
  200µg at 20 minute and
        is a sensitive                                    P<0.002
                                             P<0.001
    reproducible outcome to
  intervals.
       decongestion with
 Peak nasal inspiratory flow
     oxymetazoline, similar
  (PNIF) and nasal airway
         to nasal patency
  resistance (NAR) at baseline
          and symptoms.
  and after each successive               1 visit       2 visit
  dose.
 Nasal blood flow (NBF) using
Thermographic imaging during nasal peanut challenge may
     be useful in the diagnosis of peanut allergy.
                     Clark, Allergy 2012;67:574




Background: Double-blinded challenges are widely used for diagnosing
food allergy but are time-consuming and cause severe reactions.
Outcome relies on subjective interpretation of symptoms, which leads
to variations in outcome between observers.
Facial thermography combined with nasal peanut challenge was
evaluated as a novel objective indicator of clinical allergy.
Thermographic imaging during nasal peanut challenge may
     be useful in the diagnosis of peanut allergy.
                      Clark, Allergy 2012;67:574

                                Change in mean nasal temperature
                                from baseline (Δt) over time (min)
                               for placebo and active peanut nasal
 16 children with positive              challenge arms.
  peanut challenge.
 Nasal challenge with 10 μg
  peanut protein or placebo.
 Mean skin temperatures
  recorded from
  the mouth & nose using
  infrared thermography
  over 18 min.
Thermographic imaging during nasal peanut challenge may
     be useful in the diagnosis of peanut allergy.
                     Clark, Allergy 2012;67:574

                                Change in mean nasal temperature
     The area under curve       from baseline (Δt) over time (min)
  of nasal skin temperature    for placebo and active peanut nasal
 16 children with elevated
  was significantly positive             challenge arms.
  peanut peanut vs placebo
   after challenge.
      (18.2 vs 4.8°Cmin).
 Nasal maximum increase μg
    The challenge with 10
  peanut protein or placebo.
   in temperature was also
     significantly greater
 Mean aftertemperatures
         skin peanut:
  recorded from +0.9°C.
  mean difference
  the mouth & nose using
  infrared thermography
  over 18 min.
Thermographic imaging during nasal peanut challenge may
     be useful in the diagnosis of peanut allergy.
                     Clark, Allergy 2012;67:574

                                 Change in mean nasal temperature
          Thermography           from baseline (Δt) over time (min)
    can detect inflammation
                                for placebo and active peanut nasal
   caused by nasal challenges
 16 children with positive
   whilst employing 1000-fold
                                          challenge arms.
  peanutpeanut than an oral
    less challenge.
            challenge.
 Nasal challenge with 10 μg
   This novel technique could
  peanut protein or placebo.
    be developed to provide
          a rapid, safe
 Mean skin temperatures
  recorded from clinical
      and objective
           allergy test.
  the mouth & nose using
  infrared thermography
  over 18 min.
Rhinitis and asthma
Comparison of bronchodilator response in patients with
  asthma and healthy subjects using spirometry and
 oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317
                               Linear Regression with 95.00% Mean Prediction Interval


 Impulse oscillometry (IOS)
  is an effort-independent
  pulmonary function
  technique.
 Spirometry.
 Reversibility after
  400 μg salbutamol.
 95 asthmatic and
  61 healthy subjects.         Correlation between percent predicted FEV1
                                and resistance at 5 Hz (R5) at baseline in
                                           patients with asthma
Comparison of bronchodilator response in patients with
  asthma and healthy subjects using spirometry and
 oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317
                               Linear Regression with 95.00% Mean Prediction Interval


 Impulse oscillometry (IOS)
  is an effort-independent
       Low-frequency
  pulmonary function
  technique. as R5 and
       IOS
       spirometry as
 Spirometry.
    FEV1 correlate in
 Reversibility after
       patients with
  400 μg salbutamol.
          asthma.
 95 asthmatic and
  61 healthy subjects.         Correlation between percent predicted FEV1
                                and resistance at 5 Hz (R5) at baseline in
                                           patients with asthma
Comparison of bronchodilator response in patients with
  asthma and healthy subjects using spirometry and
 oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317
               Linear Regression with 95.00% Mean Prediction Interval




 Correlation between percent predicted       Correlation of the bronchodilator response
 FEV1 and and R5 post bronchodilator in    measured as a percentage of predicted change
          patients with asthma                in FEV1 and R5 in patients with asthma.
Relationship between bronchial hyperreactivity and
  bronchodilation in patients with allergic rhinitis
      Ciprandi Ann Allergy Asthma Immunol 2011;106:460

Background
Allergic rhinitis may be considered a risk factor for the onset of
asthma. Recently, it has been reported that forced expiratory
flow between 25% and 75% of vital capacity (FEF25%−75%) may
predict a positive response to bronchodilation test in asthmatic
children. Moreover, bronchial hyperreactivity (BHR) is frequently
detected in AR patients.
Objective
To evaluate the possible relationship between the response to
bronchodilation test and methacholine challenge, also considering
the FEF25%−75% values in a large group of patients with persistent
allergic rhinitis.
Relationship between bronchial hyperreactivity and
    bronchodilation in patients with allergic rhinitis
       Ciprandi Ann Allergy Asthma Immunol 2011;106:460

                                      % AHR patients with
                                      ”positive” results for
 365 consecutive                      bronchodilation test
  AR patients.                   70 –

                                 60 –
 Spirometry, methach
  oline, bronchial
                                 50 –       66%
  challenge, and                 40 –
  bronchodilation (+ if          30 –
  FEV1 > 12% after 400           20 –
  mcg salbutamol).
                                 10 –

                                 00
Relationship between bronchial hyperreactivity and
    bronchodilation in patients with allergic rhinitis
       Ciprandi Ann Allergy Asthma Immunol 2011;106:460


                                      % AHR patients with
                                          severe BHR
 365 consecutive
  AR patients.                   25   – (PC20 < 1mg/mL)

                                 20 –
 Spirometry, methach
  oline, bronchial               15 –
                                          20.8%
  challenge, and
                                 10 –
  bronchodilation (+ if
  FEV1 > 12% after 400           05 –
  mcg salbutamol).
                                 00
Relationship between bronchial hyperreactivity and
    bronchodilation in patients with allergic rhinitis
       Ciprandi Ann Allergy Asthma Immunol 2011;106:460

                                   Boxplot for duration of rhinitis
                                grouped by grade of severity of BHR

 365 consecutive
  AR patients.

 Spirometry, methach
  oline, bronchial
  challenge, and
  bronchodilation (+ if
  FEV1 > 12% after 400
  mcg salbutamol).
Validating childhood symptoms
     with physician-diagnosed allergic rhinitis
      Kim, Ann Allergy Asthma Immunol 2012;108:231



Background: Multiple population-based and
high-risk cohort studies use parental questionnaire
responses to define allergic rhinitis (AR) in children.
Individual questionnaire items have not been validated
by comparison with physician-diagnosed AR (PDAR).

Objective: To identify routine clinical questions that
best agree with a physician diagnosis of AR and can be
used for early case identification.
Validating childhood symptoms
          with physician-diagnosed allergic rhinitis
           Kim, Ann Allergy Asthma Immunol 2012;108:231


 Longitudinal birth cohort study.
 531 children at ages 1 through 4 and 7.
 Questionnaires, physical examinations, skin prick tests (SPT).
 Rhinitis-
  specific                     Rhinitis specific questionnaire
  questionnaire
  items:
  3 stem
  questions and
  4 sub-questions.
Validating childhood symptoms
      with physician-diagnosed allergic rhinitis
       Kim, Ann Allergy Asthma Immunol 2012;108:231
Percent agreement, sensitivity and specificity of
individual questionnaire items compared with
physician-diagnosed allergic rhinitis (PDAR)
Validating childhood symptoms
      with physician-diagnosed allergic rhinitis
       Kim, Ann Allergy Asthma Immunol 2012;108:231
Percent agreement, sensitivity and specificity of
individual questionnaire items compared with
physician-diagnosed allergic rhinitis (PDAR)
Validating childhood symptoms
      with physician-diagnosed allergic rhinitis
       Kim, Ann Allergy Asthma Immunol 2012;108:231
Percent agreement, sensitivity and specificity of
individual questionnaire items compared with
physician-diagnosed allergic rhinitis (PDAR)
     Responses to hayfever and ocular symptoms
    had better specificity and percent agreement
        with PDAR than the ISAAC-validated
       questionnaire item. Combining 2 rhinitis
   questions sharply increases specificity and may
             improve diagnostic accuracy
                of clinical questions.
Prevalence and impact of rhinitis in asthma.
 SACRA, a cross-sectional nation-wide study in Japan
                    Ohta, Allergy 2011;66:1287
                                     % of patients with rhinitis
                               80–

                               70–
 1910 physician.
                               60–     68.5%
                                                         66.2%
 29 518 asthmatics.           50–

                               40–
 Questionnaires on rhinitis
  and asthma based on ARIA     30–
  (Allergic Rhinitis and its   20–
  Impact on Asthma) and
                               10–
  Global Initiative for
  Asthma (GINA);               0
                                     Self-administered   Patients with
                                       questionnaires     physicians-
                                                         administered
Prevalence and impact of rhinitis in asthma.
 SACRA, a cross-sectional nation-wide study in Japan
                    Ohta, Allergy 2011;66:1287
                                     % of patients with uncontrolled
                                      asthma as defined by GINA
                               70–
 1910 physician.              60–

                               50–
 29 518 asthmatics.
                               40–
 Questionnaires on rhinitis   30–                 P<0.05
  and asthma based on ARIA
  (Allergic Rhinitis and its   20–     25.4%
  Impact on Asthma) and        10–                          18%
  Global Initiative for
  Asthma (GINA);               0
                                         YES                 NO
                                      Physician‟s diagnosis of rhinitis
Bronchodilation test in patients with allergic rhinitis
                  Ciprandi, Allergy 2011;66:694

                                  % patients with impaired FEF25-75
                                    values (≤ 65% of predicted)
                           30 –

 1469 consecutive
  patients suffering       20 –
  from persistent
  AR.
                           10 –
                                              18%
 Spirometry and
  bronchodilation
  test in all patients.     0
Bronchodilation test in patients with allergic rhinitis
                  Ciprandi, Allergy 2011;66:694

                                  % patients with FEV1 ≥ 12%
                                        post salbutamol
                           80 –

                           70 –


                                         63%
 1469 consecutive         60 –
  patients suffering       50 –
  from persistent
                           40 –
  AR.
                           30 –
 Spirometry and           20 –
  bronchodilation
                           10 –
  test in all patients.
                            0
Bronchodilation test in patients with allergic rhinitis
                  Ciprandi, Allergy 2011;66:694

                                  % patients with FEV1 ≥ 12%
                                        post salbutamol
                           80 –

                           70 –


                                         63%
 1469 consecutive         60 –
  patients suffering       50 –
  from persistent
                           40 –
  AR.
                           30 –
 Spirometry and           20 –           at risk of
  bronchodilation                          asthma
                           10 –
  test in all patients.                  development
                            0
Bronchodilation test in patients with allergic rhinitis
                  Ciprandi, Allergy 2011;66:694



                                    OR for reversibility
                           20 –

 1469 consecutive
  patients suffering
  from persistent
  AR.                      10 –
                                           11.3
 Spirometry and
  bronchodilation
  test in all patients.    0
                                  Impaired FEF25-75 values and
                                    longer rhinitis duration
Effect of an intranasal corticosteroid on exercise
    induced bronchoconstriction in asthmatic children
                Kersten Pediatr Pulmonol 2012;47:27


 Subjects aged 12–17
  years, with mild-to-
  moderate
  asthma, intermittent
  allergic rhinitis and ≥10%
  fall in FEV1 at a screening
  exercise challenge.

 22 ± 3 days treatment with
                                Exercise induced fall in FEV1 (%) before and
  intranasal fluticasone        after treatment with placebo or fluticasone
  furoate or placebo.           furoate. Data expressed as individual fall in
                                        FEV1 and mean fall in FEV1.
Effect of an intranasal corticosteroid on exercise
    induced bronchoconstriction in asthmatic children
               Kersten Pediatr Pulmonol 2012;47:27


 Subjects aged 12–17
  years, with mild-to-
      The activity limitation
  moderate
     domain score improved
  asthma, intermittent
     significantly within the
  allergic rhinitis and ≥10%
        fluticasone furoate
  fall in FEV1 at a screening
          group (P = 0.03).
  exercise challenge.

 22 ± 3 days treatment with
                                Exercise induced fall in FEV1 (%) before and
  intranasal fluticasone        after treatment with placebo or fluticasone
  furoate or placebo.           furoate. Data expressed as individual fall in
                                        FEV1 and mean fall in FEV1.
Effect of an intranasal corticosteroid on exercise
    induced bronchoconstriction in asthmatic children
               Kersten Pediatr Pulmonol 2012;47:27


 Subjects aged 12–17 years,
      Treatment of allergic
  with mild-to-moderate
       rhinitis in asthmatic
  asthma, intermittent
  allergic rhinitiswith ≥10%
         children and an
             intranasal
  fall in FEV1 at a screening
           corticosteroid
  exercise challenge.
         reduces EIB and
 22 ± 3tends treatment with
          days to improve
          quality of life.
  intranasal fluticasone
                                Exercise induced fall in FEV1 (%) before and
  furoate or placebo.           after treatment with placebo or fluticasone
                                furoate. Data expressed as individual fall in
                                        FEV1 and mean fall in FEV1.
Effect of an intranasal corticosteroid on exercise
induced bronchoconstriction in asthmatic children
            Kersten Pediatr Pulmonol 2012;47:27

    Mean fall in FEV1 at each time point after exercise

  Before and after treatment        Before and after treatment
         with placebo                 with fluticasone furoate
•Rhinitis treatment
general considerations
Chronic rhinosinusitis: epidemiology and medical
        management Hamilos JACI 2011;128:693


            • Chronic rhinosinusitis (CRS) affects
                12.5% of the US population.

• Some association has been found between CRS prevalence and
                air pollution, active cigarette
     smoking,                             secondhand smoke
exposure,                                              perennial
                        allergic rhinitis,
                and gastroesophageal reflux.

                      • The majority of
 pediatric and adult patients with CRS are immune competent.
Chronic rhinosinusitis: epidemiology and medical
     management Hamilos JACI 2011;128:693



            Current consensus definitions
                subclassify CRS into:

      1. CRS without nasal polyposis (CRSsNP),
        2. CRS with nasal polyposis (CRSwNP),
       3. allergic fungal rhinosinusitis (AFRS).
Chronic rhinosinusitis: epidemiology and medical
        management Hamilos JACI 2011;128:693


         • Evaluation and medical management of CRS
    has been the subject of several recent consensus reports.
• The highest level of evidence for treatment for CRSsNP exists
             for saline lavage, intranasal steroids, and
                long-term macrolide antibiotics.
• The highest level of evidence for treatment of CRSwNP exists
   for intranasal steroids, systemic glucocorticoids, and topical
                        steroid irrigations.
    • Sinus surgery followed by use of systemic steroids is
                     recommended for AFRS.
A new instrument for the assessment of patient-defined
      benefit in the treatment of allergic rhinitis
                Franzke, Allergy 2011;66:665
            Mean, standard deviation (SD) and percentage
           of afflicted patients and needs in allergic rhinitis
A new instrument for the assessment of patient-defined
      benefit in the treatment of allergic rhinitis
                Franzke, Allergy 2011;66:665
            Mean, standard deviation (SD) and percentage
           of afflicted patients and needs in allergic rhinitis




                       Needs are scaled from
                       0 “not important at all”
                        to 4 “very important”
•Rhinitis treatment
  anti-histamines
Petasol butenoate complex (Ze 339) relieves allergic
   rhinitis–induced nasal obstruction more effectively
     than desloratadine. Dumitru JACI 2011;127:1515
 Ze 339 is a carbon dioxide extract
   derived from the leaves of a
   special variety (Petzell) of
   Petasites hybridus registered at
   the European Community Plant
   Variety Office.

 In vitro studies show that Ze 339
   blocks degranulation in activated
   immune cell populations and also
   inhibits leukotriene biosynthesis.

 18 subjects with allergic rhinitis
   to grass pollen received Ze
   339, desloratadine, and placebo
   for        5 days before nasal
   allergen challenge with grass pollen
   extract.
Petasol butenoate complex (Ze 339) relieves allergic
     rhinitis–induced nasal obstruction more effectively
       than desloratadine. Dumitru JACI 2011;127:1515
 Ze 339 is a carbon dioxide extract
    derived from the leaves of a
    special variety (Petzell) of
    Petasites hybridus registered at
    the European Community Plant
              Nasal airflow
    Variety Office.
            improvement:
 In vitro studies show that Ze 339
        Ze 339, 2.46 hours;
    blocks degranulation in activated
    immune cell populations and also
         desloratadine, 3.94
    inhibits leukotriene biosynthesis.


            hours allergic rhinitis
    18 subjects with
                     [medians]
    to grass pollen received Ze 339,
    desloratadine, and placebo for
    5 days before nasal allergen
    challenge with grass pollen
    extract.
Petasol butenoate complex (Ze 339) relieves allergic
  rhinitis–induced nasal obstruction more effectively
    than desloratadine. Dumitru JACI 2011;127:1515
            Recovery of nasal obstruction
                                                            Time to RTB value of the symptom of nasal
         Time to return to 90% of basal flow               obstruction (means ± SEMs assessed by means
        (means ± SEMs assessed by means of                  of VAS: Ze 339, 3.2 ± 1.3 hours; placebo,
     rhinomanometry: Ze 339, 5.4 ± 1.6 hours;             8.3 ± 2.4 hours; desloratadine, 4.5 ± 1.2 hours
placebo, 9.1 ± 2.3 hours; desloratadine, 10.7 ± 2.5
                        hours)




                                              RTB = return to baseline
Petasol butenoate complex (Ze 339) relieves allergic
 rhinitis–induced nasal obstruction more effectively
   than desloratadine. Dumitru JACI 2011;127:1515
    Concentrations in picograms per milliliter per milligram of nasal secretion
                  of IL-8 (A) and LTB4(B) in nasal secretions.
Mometasone furoate nasal spray increases the number of
      minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275

 Background: Acute rhinosinusitis
 (ARS) is triggered by viral or,
 uncommonly, bacterial infection,
 causing inflammatory symptoms for
 12 weeks.

 Objective: To investigate effects
 of mometasone furoate nasal spray
 (MFNS) vs amoxicillin and placebo on
 minimal-symptom days.
Mometasone furoate nasal spray increases the number of
      minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275


 Double-blind, parallel-
  group, placebo- and active-                % Minimal symptom days
  controlled 15-day study.
                                      70 –                P<0.004
 Patients 12 years of age or older   60 –
  to MFNS 200 µg 2/daily, MFNS               62.69%
  200 µg 1/daily, amoxicillin 500
                                      50 –
                                                         50.33%         54.35%
  mg 3/daily, or placebo.             40 –
                                      30 –
 Major symptom score (MSS;           20 –
  combined rhinorrhea, postnasal                    P<0.001
                                      10 –
  drip, congestion, sinus
                                      00 –
  headache, facial pain) of≥5 and
  ≤12 (maximum: 15) for 7 to 28               MFNS            Placebo   Amoxicillin
                                              2/daily
  days.
Mometasone furoate nasal spray increases the number of
      minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275


 Double-blind, parallel-group,
  placebo- and active- µg
       MFNS 200                              % Minimal symptom days
   2/daily significantly
  controlled 15-day study.
                                                          P<0.004
 Patients increased or older
                                      70 –
            12 years of age           60 –
     minimal-symptom
  to MFNS 200 µg 2/daily, MFNS               62.69%
                                      50 –
                                                         50.33%         54.35%
    days vs amoxicillin
  200 µg 1/daily, amoxicillin 500
                                      40 –
  mg 3/daily, or placebo.
          or placebo                  30 –
          in patients
 Major symptom score (MSS;           20 –
  combined rhinorrhea, postnasal                    P<0.001
          with ARS.
  drip, congestion, sinus headache,
                                      10 –
                                      00 –
  facial pain) of≥5 and ≤12
  (maximum: 15) for 7 to 28 days.             MFNS            Placebo   Amoxicillin
                                              2/daily
Mometasone furoate nasal spray increases the number of
      minimal-symptom days in patients with acute
rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275


      Results of this
 Double-blind, parallel-group,
  placebo- intranasal
           and active-                       % Minimal symptom days
  controlled 15-day study.
  corticosteroids (INS)               70 –                P<0.004
 Patients 12 years of age or it
    therapy indicate older            60 –
  to MFNS 200 µg 2/daily, MFNS               62.69%
          can improve 500             50 –                              54.35%
  200 µg 1/daily, amoxicillin                            50.33%
         outcomes and
  mg 3/daily, or placebo.             40 –

     potentially reduce               30 –
 Major symptom score (MSS;
         inappropriate
  combined rhinorrhea, postnasal
                                      20 –
                                                    P<0.001
                                      10 –
        antibiotic use.
  drip, congestion, sinus headache,
                                      00 –
  facial pain) of≥5 and ≤12
  (maximum: 15) for 7 to 28 days.             MFNS            Placebo   Amoxicillin
                                              2/daily
Impact of mometasone furoate nasal spray on individual
 ocular symptoms of allergic rhinitis: a meta-analysis
                 Bielory, Allergy 2011;66:686




    3132 patients.

    A meta-analysis of 10 randomized, placebo-controlled.

    Efficacy of MFNS 200 mcg daily in relieving ocular
     allergy symptoms, including itching/burning, redness, and
     tearing/watering in both with nasal symptoms of
     seasonal (SAR) and nasal symptoms of perennial (PAR).
Impact of mometasone furoate nasal spray on individual
 ocular symptoms of allergic rhinitis: a meta-analysis
                    Bielory, Allergy 2011;66:686
 Improvement in tearing, itching, and redness in patients with SAR trated
                         with MFNS for 2 weeks
Impact of mometasone furoate nasal spray on individual
 ocular symptoms of allergic rhinitis: a meta-analysis
                     Bielory, Allergy 2011;66:686
  Improvement in tearing, itching, and redness in patients with PAR trated
                          with MFNS for 30 days
Impact of mometasone furoate nasal spray on individual
 ocular symptoms of allergic rhinitis: a meta-analysis
                      Bielory, Allergy 2011;66:686
   Improvement in tearing, itching, and redness in patients with PAR trated
                           with MFNS for 30 days




In both SAR
 and PAR all
  individual
    ocular
  symptoms
were reduced
 in patients
treated with
   MFNS.
Ocular symptoms in nonspecific conjunctival hyperreactivity
         Mourão Ann Allergy Asthma Immunol 2011;107:29




  Background
  Ocular symptoms can be triggered by nonspecific environmental
  factors, characterizing conjunctival hyperreactivity (CHR).

  Objective
  To examine CHR in subjects with ocular symptoms by means of
  a hyperosmolar conjunctival provocation test (HCPT).
Ocular symptoms in nonspecific conjunctival hyperreactivity
          Mourão Ann Allergy Asthma Immunol 2011;107:29

                                         Digital images of positive HCPT.
 63 subjects with ocular complaints     (A) Technician's analysis: number
  (itching, redness, or tearing)         of red dots, 2521; number of
                                         blue dots, 8717.
  considered allergic if tests were      (B) Technician's analysis: number
  positive to at least 1 allergen.       of red dots, 2521; number of
                                         blue dots, 8717.
 Hyperosmolar Conjunctival
  Provocation Test (HCPT) with serial
                                         A
  diluted glucose concentrations was
  positive if it produced conjunctival
  hyperemia up to a 50% solution.
 Digital images were analyzed by        B
  2 observers who marked redness
  in the challenged eyes in red
  (GIMP 2.6.5 software).
Ocular symptoms in nonspecific conjunctival hyperreactivity
            Mourão Ann Allergy Asthma Immunol 2011;107:29


Hyperosmolar conjunctival provocation     Cumulative frequency of positive HCPT
test with serial glucose concentrations     in allergic and nonallergic subjects
  in allergic and nonallergic subjects
Ocular symptoms in nonspecific conjunctival hyperreactivity
           Mourão Ann Allergy Asthma Immunol 2011;107:29

              HCPT indentified CHR in allergic as well as in
Hyperosmolar conjunctival subjects. Allergic subjects exhibited
           non-allergic provocation       Cumulative frequency of positive HCPT
test with serial glucose concentrations     in allergic and nonallergic subjects
                more CHR than did non-allergic subjects.
  in allergic and nonallergic subjects
Allergic Conjunctivitis and Dry Eye Syndrome
            Hom, Ann Allergy Asthma Immunol 2012;108:163



1. Allergic Conjunctivitis (AC) and Dry Eye Syndrome (DES) are
   2 of the most common anterior inflammatory disorders of the eye.

2. The prevalence of DES is 5%-35% of the population.
   Up to 40% of the general US population has reported
   ocular symptoms consistent with AC.

3. Both conditions have a strong effect on quality of life.
   When measured with questionnaires reflecting quality of
   life,     DES and AC can have the same effect on quality of life
   as moderate angina.
Allergic Conjunctivitis and Dry Eye Syndrome
          Hom, Ann Allergy Asthma Immunol 2012;108:163


                  Subjective evaluation of symptom of dryness
                   or frequency of dryness score definitions.


 Self-reported
  - itchiness
  - dryness
  - redness.
 689 patients
  5-90 yrs.
Allergic Conjunctivitis and Dry Eye Syndrome
          Hom, Ann Allergy Asthma Immunol 2012;108:163


                                 Clinically significant itch.



 Self-reported
  - itchiness
  - dryness
  - redness.
 689 patients
  5-90 yrs.
Allergic Conjunctivitis and Dry Eye Syndrome
            Hom, Ann Allergy Asthma Immunol 2012;108:163


                                   Clinically significant itch.



 Self-reported
    - Clinically
      itchiness
    -significant
      dryness
    -itchiness
      redness.
    was found in
   689 patients
       28.2%
    5-90 yrs.
    of patients.
Allergic Conjunctivitis and Dry Eye Syndrome
          Hom, Ann Allergy Asthma Immunol 2012;108:163




 Self-reported
  - itchiness
  - dryness
  - redness.
 689 patients
  5-90 yrs.
Allergic Conjunctivitis and Dry Eye Syndrome
   Hom, Ann Allergy Asthma Immunol 2012;108:163

 Itch & Redness                 Itch & Dryness




Dryness & Redness           Itch, Dryness & Redness
Allergic Conjunctivitis and Dry Eye Syndrome
    Hom, Ann Allergy Asthma Immunol 2012;108:163

  Itch & Redness                  Itch & Dryness




 Most patients with “itchy eyes” consistent with AC
         also have dry eyes and redness.
 Dryness & Redness
These results suggest that some symptomatic & Redness
                              Itch, Dryness patients
    concomitantly have features of AC and DES.
Conjunctival provocation with airborne allergen
     in patients with atopic keratoconjunctivitis
            Nivenius, Clin Exp Allergy 2012;42:58



Background Atopic keratoconjunctivitis (AKC)
is a chronic eye disease with periods of exacerbations.
Many patients experience no obvious seasonal
variation, although
a majority of patients are allergic to common airborne
allergens.
Objective To investigate the allergic reaction, to
conjunctival provocation with airborne allergens, in
patients with AKC.
Conjunctival provocation with airborne allergen
         in patients with atopic keratoconjunctivitis
                    Nivenius, Clin Exp Allergy 2012;42:58
 11 patients with AKC
  and birch and/or grass
  pollen allergy
                                           Atopic keratoconjunctivitis patient,
 5 patients with                               10 min after provocation
  seasonal allergic conjunctivitis (SAC)   with birch allergen in the right eye
  & 5 healthy subjects.                    and dilution buffer only in the left.
 Challenge in 1 eye with the
  allergen, to which the patient was
  reactive,
  & with dilution buffer in the other.
 Signs & symptoms from both eyes
  at 10 min, 8h and 48h.
                                                    allergen
 Tear fluid for cytokine analyses
  at baseline and at 8h and 48h.
Conjunctival provocation with airborne allergen
        in patients with atopic keratoconjunctivitis
                Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.




         Atopic             Seasonal allergic           Healthy
Conjunctival provocation with airborne allergen
        in patients with atopic keratoconjunctivitis
                Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.


                                                 A significant
                                                    change
                                              from baseline was
                                                 documented
                                              at 10 min for AKC
                                                    & SAC
                                              patients, while no
                                                    change
                                                  was seen in
                                                    healthy
                                                   controls.
         Atopic             Seasonal allergic        Healthy
Conjunctival provocation with airborne allergen
        in patients with atopic keratoconjunctivitis
                Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.


                                                  In this single
                                                  dose allergen
                                                    provocation
                                                      study,
                                                   AKC patients
                                                responded with a
                                                      typical
                                                  IgE-mediated
                                                allergic reaction.


         Atopic             Seasonal allergic           Healthy
Conjunctival provocation with airborne allergen
        in patients with atopic keratoconjunctivitis
                Nivenius, Clin Exp Allergy 2012;42:58
Total symptom score in the provoked eyes. Median linked by black line.


                                                     An increase
                                                in cytokines at 48 h
                                                 after the challenge
                                                  was demonstrated
                                                   and might, with
                                                further studies, give
                                                     us a better
                                                understanding of the
                                                        nature
                                                  of inflammation in
                                                         AKC.


         Atopic             Seasonal allergic           Healthy
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                                  Lambiase JACI 2011;128:896


• Vernal keratoconjunctivitis (VKC)
  is a severe allergic disease.

• Treatment involves topical antiallergic agents, which are effective in patients with
   mild disease, whereas most patients with severe disease require some topical steroid
   therapy.
• The physician’s primary objective with the patient with VKC     is to prevent and
   minimize acute flare-ups, as well as          to treat them when they do occur with
   the safest therapy available.
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                            Lambiase JACI 2011;128:896
                                                           Study design.




 Crossover 2 yr study.

 Efficacy and safety of
  0.05% topical cyclosporine
  in patients with VKC.

 Ability of 0.05%
  cyclosporine to prevent
  flare-ups vs topical
  Ketotifen 0.025%                                       AE; adverse event
                                                         CsA; cyclosporine
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                            Lambiase JACI 2011;128:896




 Crossover 2 yr study.

 Efficacy and safety of
  0.05% topical cyclosporine
  in patients with VKC.

 Ability of 0.05%
  cyclosporine to prevent
  flare-ups vs topical
  Ketotifen 0.025%
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                             Lambiase JACI 2011;128:896



  The number of recurrences was
    significantly reduced when
    patients were treated with
 Crossover 2 cyclosporine
       0.05%
               yr study.
 Efficacy with safety of
           and respect
  0.05% topical cyclosporine
       to 0.025% ketotifen.
  in patients with VKC.
 Ability of 0.05%
  cyclosporine to prevent
  flare-ups.
 The efficacy of a higher
  dose, 0.1%, was compared
  with 0.15% dexamethasone
  during acute relapses.
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                         Lambiase JACI 2011;128:896




    The cyclosporine
         group had
 Crossover 2 yr study.
        significantly
 Efficacy and safety of
  0.05% topical cyclosporine
  in patients periods free
   longer with VKC.
       of recurrences
 Ability of 0.05%
  cyclosporine to prevent the
    compared with
  flare-ups.
 Theketotifen higher
       efficacy of a group
  dose, 0.1%, was compared
  with 0.15% dexamethasone
  during acute relapses.
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                            Lambiase JACI 2011;128:896




 Crossover 2 yr study.

 Efficacy and safety of
  0.05% topical cyclosporine
  in patients with VKC.

 Ability of 0.05%
  cyclosporine to prevent
  flare-ups vs topical
  Ketotifen 0.025%
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                           Lambiase JACI 2011;128:896



        Itching, photophobia,
      and conjunctival hyperemia
           scores showed
 Crossover 2 yr study.
      significant amelioration
 Efficacy and safety of
  0.05%patients treated with
      in topical cyclosporine
  in patients with VKC.
        0.05% cyclosporine eye
 Ability of 0.05%
    drops compared with those
  cyclosporine to prevent
      seen in patients treated
  flare-ups.
 The with 0.025% ketotifen
       efficacy of a higher
  dose, 0.1%,eye compared
              was drops.
  with 0.15% dexamethasone
  during acute relapses.
Topical cyclosporine prevents seasonal recurrences of
  vernal keratoconjunctivitis in a randomized, double-
            masked, controlled 2-year study
                            Lambiase JACI 2011;128:896

                                               OR for recurrence
                                    3 –
                                                    p= 0.031




                                                 2.44
 Crossover 2 yr study.
                                    2 –
 Efficacy and safety of
  0.05% topical cyclosporine
  in patients with VKC.             1 –

 Ability of 0.05%
  cyclosporine to prevent
  flare-ups vs topical              0
                                          Patients treated with ketiofen
  Ketotifen 0.025%
                                             vs patients treated with
                                                   cyclosporine.
POLIPOSI NASALE
Nasal nitric oxide as a measure of osteomeatal complex
                     patency in nasal polyps
          McKinlay Ann Allergy Asthma Immunol 2011;107:179

                                 Nasal nitric oxide (nNO) levels according
                                to computed tomographic (CT) scan results

 Consecutive nonsmoking
  patients with nasal polyp
  disease.

 Rhinosinusitis extent
  staged by CT scans of
  the paranasal sinuses.
•Oxidative stress
 •in rhinitis and
 •nasal poliposis
Oxidative stress induces unfolding protein response and
inflammation in nasal polyposis. Jeanson, Allergy 2012;67:403




Background: Nasal polyposis, a chronic inflammatory disease
affecting the upper airways, is a valuable and accessible model
to investigate the mechanisms underlying chronic inflammation.
The main objective of this study was to investigate a potential
involvement of the unfolded protein response (UPR) in the context
of oxidative stress and inflammation in nasal epithelial cells from
nasal polyps (NP).
Oxidative stress induces unfolding protein response and
inflammation in nasal polyposis. Jeanson, Allergy 2012;67:403




 Epithelial cells
  from NP (n=20)               Proteomics analysis
  & normal mucosa (n=15).      of human nasal epithelial cells
                               in culture revealed the activation
 Analyzed by                  of the unfolded protein response
  global proteomic approach    in NP.
  & cell biology techniques.
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What 2012 rhinitis & sinusitis & poliposis
What 2012 rhinitis & sinusitis & poliposis
What 2012 rhinitis & sinusitis & poliposis

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What 2012 rhinitis & sinusitis & poliposis

  • 1. WHAT YOU SHOULD HAVE READ BUT….2012  rhinitis Attilio Boner University of Verona, Italy
  • 2. Validation of a self-questionnaire for assessing the control of allergic rhinitis. Demoly CEA 2011;41:860 Improvement of impact of allergic rhinitis on sleep and work life (on a numeric scale from 0 for ‘no signs’ to 10 for ‘very intense’)  A self-assessment at inclusion and day 15 after treatment. global score for allergic rhinitis control (five items scored from 1 to 5 assessing the rhinitis over the 2 previous weeks).  902 patients.
  • 3. Validation of a self-questionnaire for assessing the control of allergic rhinitis. Demoly CEA 2011;41:860 Improvement of impact of allergic rhinitis on social and physical activities (on a numeric scale from 0 for ‘no signs’ to  A self-assessment 10 for ‘very intense’) at inclusion and day 15 after treatment. global score for allergic rhinitis control (five items scored from 1 to 5 assessing the rhinitis over the 2 previous weeks).  902 patients.
  • 4. Validation of a self-questionnaire for assessing the control of allergic rhinitis. Demoly CEA 2011;41:860
  • 6. Can early household exposure influence the development of rhinitis symptoms in infancy? Findings from the PARIS birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303 Prevalence at age 18 months of 6.0 –  Infants at age 18 months. 5.4% 5.0 –  Presence of rhinitis 4.0 – symptoms (runny nose, blocked nose, sneezing 3.0 – 3.8% in the absence of a cold) 2.0 – combined with biological 1.0 – atopy. 0 0 Allergic rhinitis Nonallergic rhinitis
  • 7. Can early household exposure influence the development of rhinitis symptoms in infancy? Findings from the PARIS birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303 OR for allergic rhinitis 4.0 –  Infants at age 18 months. 3.0 –  Presence of rhinitis 3.15 symptoms (runny nose, 2.0 – blocked nose, sneezing in the absence of a cold) 1.0 – combined with biological atopy. 0 0 Presence of cockroaches in the home
  • 8. Can early household exposure influence the development of rhinitis symptoms in infancy? Findings from the PARIS birth cohort. Herr Ann Allergy Asthma Immunol 2011;107:303 OR for nonallergic rhinitis 2.0 –  Infants at age 18 months. 1.5 – 1.87  Presence of rhinitis symptoms (runny 1.0 – nose, blocked nose, sneezing in the 0.5 – absence of a cold) combined with biological 0 0 Presence of particle-board atopy. furniture less than 12 months old in the child's bedroom
  • 9. Natural course and comorbidities of allergic and nonallergic rhinitis in children Westman JACI 2012;129:403 Proportion of children % pts with allergic rhinitis* 20 – Birth cohort of 2024 children. 15 – 14% IgEs against 8 common 10 – inhaled allergens was available. 05 – Age 4 and 8 yrs. 5% 0 4 years 8 years *allergic rhinitis = rhinitis with sensitization to allergens.
  • 10. Natural course and comorbidities of allergic and nonallergic rhinitis in children Westman JACI 2012;129:403 Proportion of children % pts with allergic rhinitis* Of the children with 20 – Birth cohort of allergic rhinitis 2024 children. when they were 15 – 14% 4 against IgEs years old, 8 common 12% underwent 10 – inhaled allergens was remission available. 05 – by the time 4 and 8 yrs. Agethey were 5% 0 8 years old. 4 years 8 years *allergic rhinitis = rhinitis with sensitization to allergens.
  • 11. Natural course and comorbidities of allergic and nonallergic rhinitis in children Westman JACI 2012;129:403 Proportion of children % pts with nonallergic rhinitis* 20 – Birth cohort of 2024 children. 15 – IgEs against 8 common 10 – inhaled allergens was available. 05 – 8% 6% Age 4 and 8 yrs. 0 4 years 8 years *nonallergic rhinitis = rhinitis without sensitization to allergens.
  • 12. Natural course and comorbidities of allergic and nonallergic rhinitis in children Westman JACI 2012;129:403 Proportion of children % pts with nonallergic rhinitis* Of the children 20 – with Birth cohort of nonallergic rhinitis 2024 children. 15 – IgEs against were when they 8 common old, 4 years 10 – 73% underwent inhaled allergens was remission available. 05 – 8% 6% Age 4 and 8 period during the yrs. of development. 0 4 years 8 years *nonallergic rhinitis = rhinitis without sensitization to allergens.
  • 13. Natural course and comorbidities of allergic and nonallergic rhinitis in children Westman JACI 2012;129:403 % children with ORAL ALLERGY SYNDROME Birth cohort of 30 – 2024 children. IgEs against 20 – 25% 8 common inhaled allergens 10 – was available. Age 4 and 8 yrs. 0 If allergic rhinitis at the age of 8 years
  • 14. Natural course and comorbidities of allergic and nonallergic rhinitis in children Westman JACI 2012;129:403 Conclusions Fewer preschool-age children with allergic rhinitis undergo remission than do those with nonallergic rhinitis. Sensitization to inhaled allergens at an early age (4 years) precedes the development of allergic rhinitis, whereas symptoms of rhinitis do not. Oral allergy syndrome is common among 8-year-olds with allergic rhinitis.
  • 15. Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010 R. de Marco, Eur Respir J 2012;39:883 Overall mean prevalence  The same screening questionnaire by mail or phone.  Random samples of the general population (age 20–44 yrs).  (1991–1993; n=6,031) (1998–2000; n=18,873) (2007–2010; n=10,494)
  • 16. Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010 R. de Marco, Eur Respir J 2012;39:883 Overall mean prevalence  The same screening The asthma epidemic questionnaire by mail or is not over in Italy. phone. During the past 20 yrs, asthma prevalence has  Random samples of the increased by 38%, general population (age 20–44 with a similar in parallel yrs). increase in asthma-like symptoms and  (1991–1993; n=6,031) allergic rhinitis. (1998–2000; n=18,873) (2007–2010; n=10,494)
  • 17. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study Loss JACI 2011;128:766 OR for asthma 1.0 –  Farm milk consumption.  8334 school-aged children. 0.59 0.5 –  800 cow’s milk samples collected at the participants’ homes, viable bacterial counts, whey protein 0 levels and total fat For raw milk content. consumption
  • 18. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study Loss JACI 2011;128:766 OR for asthma 1.0 –  Farm milk consumption.  8334 school-aged children. farm milk Boiled  800 did not show a 0.59 0.5 – cow’s milk samples protective collected at the effect. participants’ homes, viable bacterial counts, whey protein levels and 0 total fat content. For raw milk consumption
  • 19. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study Loss JACI 2011;128:766 OR for hay fever 1.0 –  Farm milk consumption.  8334 school-aged children. 0.5 –  800 cow’s milk samples collected at the participants’ homes, 0.51 viable bacterial counts, whey protein levels and 0 total fat content. For raw milk consumption
  • 20. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study Loss JACI 2011;128:766 OR for hay fever 1.0 –  Farm milk consumption.  8334 school-aged children. farm milk Boiled  800 did not show a cow’s milk samples 0.5 – protective collected at the effect. participants’ 0.51 homes, viable bacterial counts, whey protein 0 levels and total fat For raw milk content. consumption
  • 21. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study Loss JACI 2011;128:766  Total viable bacterial counts and total fat content of milk were not significantly related to asthma or atopy.  Increased levels of the whey proteins BSA (aOR for highest vs lowest levels and asthma, 0.53; 95% CI 0.30- 0.97), α-lactalbumin (aOR for interquartile range and asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR for interquartile range and asthma, 0.62; 95% CI, 0.39- 0.97), however, were inversely associated with asthma but not with atopy.
  • 22. The protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study Loss JACI 2011;128:766  Total viable bacterial counts and total fat content of milk were not significantly related to asthma raw milk The protective effect of or atopy. consumption on asthma might be associated with BSA  Increased levels of the whey proteins the (aOR for highest vs lowest levels and asthma, 0.53; 95% CI 0.30- 0.97), whey protein(aOR for interquartile range and α-lactalbumin fraction of milk. asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR for interquartile range and asthma, 0.62; 95% CI, 0.39- 0.97), however, were inversely associated with asthma but not with atopy.
  • 23. House dust mite sensitization in toddlers predicts current wheeze at age 12 years Lodge JACI 2011;128:782 Prevalence of sensitization (and 95% CI) at age 6 months (n=560), 1 year (n=551),  Birth cohort of 620 and 2 years (n=459). children oversampled for familial allergy.  SPTs to 6 allergens at ages 6, 12, and 24 mo.  Wheeze and eczema recorded during the first 2 yrs.  Current wheeze recorded at age 12 yrs.
  • 24. House dust mite sensitization in toddlers predicts current wheeze at age 12 years Lodge JACI 2011;128:782 7 – OR for wheeze at 12 yrs 6 – 6.37  Birth cohort of 620 5 – children oversampled for 4 – familial allergy.  SPTs to 6 allergens at 3 – ages 6, 12, and 24 mo. 3.31 2 –  Wheeze and eczema recorded during 1 – the first 2 yrs. 0  Current wheeze recorded Age 1 yr Age 2 yrs at age 12 yrs. SPT (+) for mite dust
  • 25. House dust mite sensitization in toddlers predicts current wheeze at age 12 years Lodge JACI 2011;128:782 80 – % children wheezing at age 12 yrs 75% 70 – 60 –  Birth cohort of 620 children oversampled for 50 – familial allergy. 40 –  SPTs to 6 allergens at ages 6, 12, and 24 mo.  Wheeze and eczema 30 – 20 – 36% recorded during 10 – the first 2 yrs. 0  Current wheeze recorded Sensitized Not Sensitized at age 12 yrs. Wheezing at age 1
  • 26. House dust mite sensitization in toddlers predicts current wheeze at age 12 years Lodge JACI 2011;128:782 80 – % children wheezing at age 12 yrs 70 –  Birth cohort of 620 children oversampled for 60 – 50 – 67% familial allergy. 40 –  SPTs to 6 allergens at 35% 30 – ages 6, 12, and 24 mo.  Wheeze and eczema 20 – recorded during 10 – the first 2 yrs. 0  Current wheeze recorded SPT (+) SPT (-) at age 12 yrs. Eczema at age 1 and mite
  • 27. House dust mite sensitization in toddlers predicts current wheeze at age 12 years Lodge JACI 2011;128:782 80 – % children wheezing at age 12 yrs 70 – HDM sensitization  Birthat age 1 or 2 yrs cohort of 620 in wheezing and children oversampled for 60 – 50 – 67% familial allergy. children eczematous 40 – at increased familial  SPTs to 6 allergens at 35% 30 – allergy risk ages 6, 12, and 24 mo. predicts asthma  Wheeze and eczema 20 – recorded duringinform and may 10 – themanagement of these first 2 yrs. 0  Current wheeze group. high-risk recorded SPT (+) SPT (-) at age 12 yrs. Eczema at age 1 and mite
  • 28. Early-life risk factors and incidence of rhinitis: results from the European Community Respiratory Health Study- an international population-based cohort study Matheson JACI 2011;128:816 HR for women developing rhinitis compared to men  1992-1994 community- based samples 1.0 – 1.36 of 20-44 yr-old people. 0.63 0.5 –  48 centers in 22 countries.  8486 participants. 0 Childhood Adulthood During
  • 29. Early-life risk factors and incidence of rhinitis: results from the European Community Respiratory Health Study- an international population-based cohort study Matheson JACI 2011;128:816 Cumulative probability of Cumulative probability of rhinitis by gender in rhinitis by gender in subjects who are atopic. subjects who are non atopic.
  • 30. Early-life risk factors and incidence of rhinitis: results from the European Community Respiratory Health Study- an international population-based cohort study Matheson JACI 2011;128:816 HR for developing rhinitis 1.0 – 0.84  1992-1994 community- based samples of 20-44 yr-old people. 0.5 –  48 centers in 22 countries. 0  8486 participants. Early contact with children in the family or day care before age 5 yrs.
  • 31. Early-life risk factors and incidence of rhinitis: results from the European Community Respiratory Health Study- an international population-based cohort study Matheson JACI 2011;128:816 HR for developing rhinitis 1.0 – 0.5  1992-1994 community- based samples of 20-44 yr-old people. 0.5 –  48 centers in 22 countries. 0  8486 participants. Early childhood pets or growing up on a farm.
  • 32. Early-life risk factors and incidence of rhinitis: results from the European Community Respiratory Health Study- an international population-based cohort study Matheson JACI 2011;128:816 HR for developing rhinitis Protective effects 1.0 – of early contact with 0.5  1992-1994 and animals children community- based samples were suggested offor incident rhinitis, 20-44 yr-old people. 0.5 –  48 with risk patterns centers in 22 countries. age window varying by and atopic status  8486 participants. . 0 Early childhood pets or growing up on a farm.
  • 33. •Rhinitis •risk factors •Protective factors
  • 34. The influence of gender and atopy on the natural history of rhinitis in the first 18 years of life Kurukulaaratchy CEA 2011;41:851 Changes in atopic and non-atopic rhinitis prevalence for boys and girls over the first 18 years of life  Natural history of rhinitis up to 18 years of age.  Isle of Wight birth cohort recruited in 1989 (n = 1456).  Questionnaire and skin prick tests.
  • 35. The influence of gender and atopy on the natural history of rhinitis in the first 18 years of life Kurukulaaratchy CEA 2011;41:851 Changes in atopic and non-atopic rhinitis prevalence for boys and girls over the first 18 years of life  Natural history Atopic rhinitis of rhinitis up to becomes 18 years of age. increasingly common as children grow  Isle of Wight birth into cohort recruited in adolescents, with 1989 (n = 1456). stronger  Questionnaireto male associations and gender. skin prick tests.
  • 36. The influence of gender and atopy on the natural history of rhinitis in the first 18 years of life Kurukulaaratchy CEA 2011;41:851 Changes in atopic and non-atopic rhinitis prevalence for boys and girls over the first 18 years of life  Natural history ofNon-atopic to rhinitis up rhinitis shows a female 18 years of age. predominance at 18  Isle of Wight birth years as girls „grow cohort it more during into‟ recruited in (n = 1456). 1989 adolescence.  Questionnaire and skin prick tests.
  • 37. Gestational age at birth and risk of allergic rhinitis in young adulthood. Crump JACI 2011;127:1173 For subjects born extremely preterm (23-28 weeks) OR for  630,090 infants born in Sweden including 27,953 1.0 – born preterm (<37 wks).  Prescription of nasal 0.5 – 0.70 corticosteroids and oral 0.45 antihistamines 0.0 Nasal Both nasal  age, 25.5-37.0 yrs. corticosteroid corticosteroid prescription and oral antihistamine prescription
  • 38. Gestational age at birth and risk of allergic rhinitis in young adulthood. Crump JACI 2011;127:1173 These findings suggest that low gestational age For subjects born extremely at birth independent preterm (23-28 weeks) OR for  630,090 infants born in of fetal growth is Sweden including 27,953 1.0 – associated with a born preterm (<37 wks). decreased risk of  Prescription of nasal young 0.5 – allergic rhinitis in 0.70 corticosteroids and oral adulthood, possibly 0.45 antihistaminesa protective 0.0 because of Nasal Both nasal effect of earlier  age, 25.5-37.0 yrs. corticosteroid corticosteroid exposure to pathogens. prescription and oral antihistamine prescription
  • 39. Staphylococcal enterotoxin B compromises the immune tolerant status in the airway mucosa. Liu T, Clin Exp Allergy 2012;42:375 1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced by the bacterium Staphylococcus aureus. SEB may contaminate ingested food and induce gastrointestinal dysfunction. SEB interferes with the function of the immune system in the airway mucosa, such as to be involved in the pathogenesis of airway allergy. 2) Integrin alphavbeta6 (avb6) is produced by epithelial cells in response to external stimuli, such as wound and inflammation. Our recent study data also show that intestinal epithelial cells express detectable avb6 that has protelytic activity and can convert the precursor of transforming growth factor (TGF)β into the active form of TGFβ. TGFβ plays a critical role in the Treg development. Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase (ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.
  • 40. Staphylococcal enterotoxin B compromises the immune tolerant status in the airway mucosa. Liu T, Clin Exp Allergy 2012;42:375 1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced by the bacterium Staphylococcus aureus. SEB may contaminate ingested food and induce gastrointestinal dysfunction. in avb6 The increases in SEB and decreases SEB interferes with the function of the immune system in the airway mucosa, such as to be involvedassociated in nasal epithelium are in the pathogenesis of airway allergy. compromises of immune tolerance with the in the nasal mucosa. 2) Integrin alphavbeta6 (avb6) is produced by epithelial cells in response SEB has stimuli,ability wound and inflammation. to external the such as to suppress Our recent study data also show that intestinal epithelial cells express detectable avb6 that has protelyticavb6 and can convert the expression of activity in nasal epithelial cells. the precursor of transforming growth factor (TGF)β into the active form of TGFβ. TGFβ plays a critical role in the Treg development. Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase (ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.
  • 41. Staphylococcal enterotoxin B compromises the immune tolerant status in the airway mucosa. Liu T, Clin Exp Allergy 2012;42:375 Avb6 expression is suppressed in the allergic rhinitis (AR) nasal epithelium • The immune tolerant components, tolerogenic dendritic cells (TolDC) P<0.01 & regulatory T cells (Treg), were assessed in the surgically removed nasal mucosa from patients with allergic rhinitis (AR) Staphylococcal enterotoxin B (SEB) or non-AR chronic rhinitis. levels are increased in the allergic rhinitis nasal epithelium. • Contents of Staphylococcal enterotoxin B & integrin alphavbeta6 P<0.01 (avb6) in the nasal epithelium assessed using enzyme-linked immunoassay.
  • 42. Staphylococcal enterotoxin B compromises the immune tolerant status in the airway mucosa. Liu T, Clin Exp Allergy 2012;42:375 Avb6 expression is suppressed in the allergic rhinitis (AR) nasal epithelium • The immune tolerant components, components The tolerogenic dendritic P<0.01 cells (TolDC) & regulatory T cells of immune tolerance (Treg), were assessed in the surgically machinery, mucosa removed nasal from patients & Tregs TolDCs with Staphylococcal enterotoxin B (SEB) allergic rhinitis (AR) were suppressed levels are increased in the allergic or non-AR chronic rhinitis. rhinitis nasal epithelium. in the AR • Contents of Staphylococcal nasal mucosa. P<0.01 enterotoxin B & integrin alphavbeta6 (avb6) in the nasal epithelium assessed using enzyme-linked immunoassay.
  • 43. Adaptative immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis Foreman, Allergy 2011;66:1449 Background: The etiopathogenesis of chronic rhinosinusitis (CRS) is currently an area of intense debate. Recently, biofilms have been proposed as a potential environmental trigger in this disease. In particular, Staphylococcus aureus biofilms appear to be a predictor of severe disease recalcitrant to current treatment paradigms. However, direct causal links between biofilms and host immune activation are currently lacking. This study aimed to document both the adaptive immune responses that characterize S. aureus biofilm–associated CRS and the relative contributions of staphylococcal superantigens and S. aureus biofilms in the inflammatory make-up of this disease.
  • 44. Adaptative immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis Foreman, Allergy 2011;66:1449 Staphylococcus aureus biofilms and  53 disease subjects; superantigens are  15 controls; significantly associated  Sinonasal mucosa for in CRS S.aureus and Haemophilus patients, suggesting influenzae biofilms; the biofilm may be a  Presence of total and nidus for superantigen-specific IgE superantigen-eluting bacteria.
  • 45. Adaptative immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis Foreman, Allergy 2011;66:1449 Staphylococcus aureus biofilms and  53 The presence of disease subjects; S. aureus superantigens are biofilms is  15 controls; significantly associated with associated  Sinonasal mucosa for eosinophilic in CRS S.aureus and Haemophilus inflammation, patients, suggesting influenzae biofilms; across the the biofilm may be a spectrum of CRS nidus for  Presence of total and superantigen-specific IgE superantigen-eluting bacteria.
  • 46. Adaptative immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis Foreman, Allergy 2011;66:1449 Representative images of bacterial biofilms on sinus mucosa using a FISH (Fluorescence in situ Hybridization) protocol, imaged on the confocal scanning laser microscope. Both images demonstrate brightly fluorescing bacterial-sized dots surrounded by a less-intense fluorescing blush, thought to represent the matrix. (A) H.influenza (B) Staphylococcus FISH probe aureus FISH probe tagged with Cy3 tagged with Alexa488 fluorophore fluorophore
  • 47. Early protective and risk factors for allergic rhinitis at age 4½ yr Alm Pediat Allergy Immunol 2011;22:398 % children reporting  A prospective, longitudinal symptoms of allergic study of a cohort of rhinitis during the least children born in the region year at age 4 ½ yrs of western Sweden in 2003. 6 –  8,176 families. 5 – 4 – 5.5%  Questionnaires at 3 – 6 and 12 months 2 – and at 4½ yr of age. 1 – 0
  • 48. Early protective and risk factors for allergic rhinitis at age 4½ yr Alm Pediat Allergy Immunol 2011;22:398 1.5 – 1.0 – 10.21 OR for allergic rhinitis 0 9 – 0 8 – 0 7 – 0 6 – 0 5 – 0 4 – 0 3 – 3.3 0 2 – 2.72 2.21 0 1 – 1.97 0 0 Sensitisation Recurrent Doctor- Parental Eczema to food wheeze diagnosed rhinitis first year allergens eczema
  • 49. Early protective and risk factors for allergic rhinitis at age 4½ yr Alm Pediat Allergy Immunol 2011;22:398 1.5 – 1.0 – 10.21 OR for allergic rhinitis 0 9 – 0 8 – 0 7 – The risk was reduced with 0 6 – fish introduction before 0 5 – 0 4 – 9 months 0 3 – 3.3 0 2 – 2.72 2.21 0 1 – 1.97 0 0 Sensitisation Recurrent Doctor- Parental Eczema to food wheeze diagnosed rhinitis first year allergens eczema
  • 50. High-Dose Docosahexaenoic Acid Supplementation of Preterm Infants: Respiratory and Allergy Outcomes Manley Pediatrics 2011;128:e71  657 preterm infants 33 RR of reported hay fever weeks’ gestation who in all infants at either consumed expressed breast 12 or 18 months 1.0 – milk from mothers taking 0.9 – either tuna oil 0.8 – (high-DHA diet) or soy oil 0.7 – (standard-DHA) capsules. 0.6 – 0.5 – 0.4 –  Incidence of bronchopulmonary dysplasia 0.3 – 0.2 – 0.41 (BPD) and parental reporting 0.1 – p=0.03 of atopic conditions over the 0 first 18 months of life. DHA diet
  • 52. Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite Quantitative extract Cho JACI 2012;129:529 measurement of glandular secretion. A. Harvest of nasal mucosa from the inferior nasal turbinate. B. Experimental setup. C. Mucus bubbles from glands under oil are visualized by using bright-field microscopy and side-light illumination. D. Example of mucus bubbles formed on the surface of nasal turbinates 30 minutes after stimulation with HDM extract.
  • 53. Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract Cho JACI 2012;129:529 Background The submucosal gland (SMG) is important in the control of airway surface fluid. Protease-activated receptor (PAR) 2 contributes to the pathophysiology of allergies in response to nonspecific allergens bearing proteases and anion secretion. House dust mites (HDMs) have abundant proteases that can activate PAR2, but little is known about the direct effect of HDM on SMG secretion. Objective To investigate the effect of HDMs on glandular secretion and its mechanism in allergic patients, patients with chronic rhinosinusitis (CRS), or both.
  • 54. Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract Cho JACI 2012;129:529 Inferior nasal 1) HDM induced a turbinates. significantly higher 55 patients classified secretion rate into four groups: and number of 1. the control, 2. allergic rhinitis (AR), responding glands 3. chronic rhinosinusitis (CRS), in the AR and 4. AR + CRS. AR+CRS groups Mucus bubbles from than in the individual submucosal control group. gland (SMGs).
  • 55. Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract Cho JACI 2012;129:529 Inferior nasal 2) Patients in the turbinates. CRS group, who had no 55 patients classified HDM-specific IgE, into four groups: showed a 1. the control, higher response 2. allergic rhinitis (AR), than the control group, 3. chronic rhinosinusitis (CRS), and its response 4. AR + CRS. was suppressed by Mucus bubbles from a PAR2-selective individual submucosal antagonist. gland (SMGs).
  • 56. Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract Cho JACI 2012;129:529 Responses to HDM. Plots of averaged secretion rates versus time for each group. Inferior nasal *p < 0.05 turbinates. 55 patients classified into four groups: 1. the control, 2. allergic rhinitis (AR), 3. chronic rhinosinusitis (CRS), 4. AR + CRS. Mucus bubbles from individual submucosal gland (SMGs).
  • 57. Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract Cho JACI 2012;129:529 Responses to HDM. Plots of averaged secretion rates versus time for each group. Inferior nasal *p < 0.05 Interestingly, patients in turbinates. the CRS group, who had 55 patients classified IgE no HDM-specific into four groups: antibody, showed a 1. the control, higher response than the 2. allergic rhinitis (AR), its control group, and 3. chronic rhinosinusitis (CRS), response was suppressed 4. AR + CRS. by a PAR2-selective antagonist. Mucus bubbles from individual submucosal gland (SMGs).
  • 58. Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract Cho JACI 2012;129:529 Conclusions HDM allergens can induce glandular secretion in patients with AR, CRS, or both, and PAR2 represents a possible mechanism for nonspecific hyperreactivity in inflammatory airway diseases.
  • 59. Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis Schaefer, Allergy 2012;67:510 (A) Tissue accumulation of mast cells (b- tryptase, brown, on hematoxylin background staining) in allergic rhinitis patient (AR, right) & healthy control (left). (B) Activated mast cells co-localize with peripheral blood vessels in AR nasal mucosa. Asterisks indicate capillary lumen.
  • 60. Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis Schaefer, Allergy 2012;67:510 (C) Confocal laser scanning microscopy of AR nasal mucosa stained with DAPI (nuclei, blue), anti CD31 (endothelial cells, green), & anti CD63var (red). Arrows indicate fluorescence signal transfer from degranulating mast cells into the lumen of microcapillaries across the juxtapositioned endothelial cells.
  • 61. Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis Schaefer, Allergy 2012;67:510 • Mast cells can discharge exosomes, which are complete, membrane-covered vesicles, able to travel long distances with the help of the lymphatic system. • Another novel way: upon triggering, granular membrane factors directly traverse from the activated mast cell onto an acceptor cell. • Detected epitope transfer from activated mast cells onto neighboring cells by following the localization of CD63var, which is a specific molecular marker of human mast cell granuli. • The new transport mode requires an intimate cellular coupling.
  • 62. Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis Schaefer, Allergy 2012;67:510 • In conclusion, we describe details of a novel intercellular communication mechanism, wherein granulated cells can select distinguished acceptor cells via receptor–ligand interactions and then transfer a set of their own molecules onto them. • This way mast cells can control, modify or even reprogram selected bystander cells and may fundamentally reshape their microenvironment in case of an allergic challenge. As mast cells frequently co-localize with blood vessels in situ, we propose that via this transcytotic channeling, mast cells instantly modulate the membrane composition of neighboring endothelium.
  • 63. Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. Rondon, JACI 2011;128:1192 Background: Patients previously given a diagnosis of non-allergic rhinitis (NAR) might have a new form of local allergic rhinitis (LAR) with local production of specific IgE antibodies and a positive response to a nasal allergen provocation test (NAPT). Objective: We evaluated an NAPT protocol using multiple aeroallergens (NAPT-M) for the detection of polysensitization to several aeroallergens in patients with LAR. LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens; NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis; VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
  • 64. Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. Rondon, JACI 2011;128:1192  25 adult patients with Local allergic rhinitis (LAR); 25 adult patients with Non-allergic rhinitis (NAR).  All the patients had a history of at least 2 yrs of persistent rhinitis with negative skin prick test (SPT) responses and serum sIgE levels to the most prevalent aeroallergens.  - LAR was diagnosed by the presence of a positive response to ≥ 1 NAPT-Ss with D pteronyssinus, Alternaria alternata, Olea europea, or grass pollen ; - NAR by a negative NAPT response. LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens; NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis; VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
  • 65. Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. Rondon, JACI 2011;128:1192 NAPT-M: Nasal allergen provocation test with multiple allergens • Symptom-free patients (total VAS <60 mm) were challenged intranasally with 2 puffs (100 mL) of saline in each nostril to exclude nasal hyperreactivity. If the result was negative, 15 minutes after NAPT-M, we began administrating 4 consecutive and different reconstituted freeze-dried allergen solutions of D pteronyssinus (4 µg/mL), A alternata (0.25 µg/mL), O europea (0.6 µg/mL), and grass pollen (0.1 µg/mL; ALK-Abello) at 15-minute intervals. 2 puffs (100 mL) of the solution at room temperature were applied in each nostril. • The response to nasal challenge was evaluated based on subjective (VAS of nasal-ocular symptoms) and objective (VOL2-6 cm) parameters. • A positive NAPT-M response was considered to be: 1) an increase of ≥ 30% in the total VAS score 2) a decrease of ≥ 30% in the sum of VOL2-6 cm from both nasal cavities. LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens; NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis; VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
  • 66. Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. Rondon, JACI 2011;128:1192 Nasal levels of tryptase and ECP in patients with LAR after NAPT-Ms. * * * * * * * Significant differences (p < 0.05) between baseline and 15 minutes and 1, 2, and 24 hours after challenge. LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
  • 67. Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. Rondon, JACI 2011;128:1192 Nasal levels of tryptase and ECP in patients with LAR after NAPT-Ms. * * * * * * There is a clinically relevant polysensitization * Significant differences (p <aeroallergens and 15 minutes and 1, 2, and 24 hours to 0.05) between baseline in patients after challenge. with LAR. LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens;
  • 68. Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. Rondon, JACI 2011;128:1192 Number of visits required for the final diagnosis in NAPT-Ms and NAPT-Ss. LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens; NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis; VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
  • 69. Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. Rondon, JACI 2011;128:1192 Number of visits required for the final diagnosis in NAPT-Ms and NAPT-Ss. NAPT-M is a useful, specific, sensitive, reproducible, and less time-consuming in vivo diagnostic test for the screening of patients with LAR. LAR: Local allergic rhinitis; NAPT-M: Nasal allergen provocation test with multiple allergens; NAPT-S: Nasal allergen provocation test with a single aeroallergen; NAR: Non-allergic rhinitis; VAS: Visual analog scale; VOL2-6 cm : Volume of the nasal cavity from 2 to 6 cm.
  • 70. Comparative evaluation of nasal blood flow and airflow in the decongestant response to oxymetazoline Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77  19 healthy adults. Decongestive response in nasal blood flow (NBF)  Doubling doses of oxymetazoline of 25µg, P<0.001 P<0.001 50µg, 100µg, and 200µg at 20 minute intervals.  Peak nasal inspiratory flow (PNIF) and nasal airway resistance (NAR) at baseline and after each successive dose. 1 visit 2 visit  Nasal blood flow (NBF) using laser Doppler Flowmetry.
  • 71. Comparative evaluation of nasal blood flow and airflow in the decongestant response to oxymetazoline Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77  19 healthy adults. Peak nasal inspiratory flow (PNIF)  Doubling doses of oxymetazoline of 25µg, 50µg, 100µg, and 200µg at P<0.001 P<0.003 20 minute intervals.  Peak nasal inspiratory flow (PNIF) and nasal airway resistance (NAR) at baseline and after each successive dose. 1 visit 2 visit  Nasal blood flow (NBF) using laser Doppler Flowmetry.
  • 72. Comparative evaluation of nasal blood flow and airflow in the decongestant response to oxymetazoline Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77  19 healthy adults. Nasal airway resistance (NAR)  Doubling doses of oxymetazoline of 25µg, 50µg, 100µg, and P<0.002 200µg at 20 minute P<0.001 intervals.  Peak nasal inspiratory flow (PNIF) and nasal airway resistance (NAR) at baseline and after each successive 1 visit 2 visit dose.  Nasal blood flow (NBF) using
  • 73. Comparative evaluation of nasal blood flow and airflow in the decongestant response to oxymetazoline Vaidyanathan, Ann Allergy Asthma Immunol 2012;108:77  19 healthy adults. Nasal airway resistance (NAR)  Doubling doses offlow using Nasal blood oxymetazoline of laser Doppler flowmetry 25µg, 50µg, 100µg, and 200µg at 20 minute and is a sensitive P<0.002 P<0.001 reproducible outcome to intervals. decongestion with  Peak nasal inspiratory flow oxymetazoline, similar (PNIF) and nasal airway to nasal patency resistance (NAR) at baseline and symptoms. and after each successive 1 visit 2 visit dose.  Nasal blood flow (NBF) using
  • 74. Thermographic imaging during nasal peanut challenge may be useful in the diagnosis of peanut allergy. Clark, Allergy 2012;67:574 Background: Double-blinded challenges are widely used for diagnosing food allergy but are time-consuming and cause severe reactions. Outcome relies on subjective interpretation of symptoms, which leads to variations in outcome between observers. Facial thermography combined with nasal peanut challenge was evaluated as a novel objective indicator of clinical allergy.
  • 75. Thermographic imaging during nasal peanut challenge may be useful in the diagnosis of peanut allergy. Clark, Allergy 2012;67:574 Change in mean nasal temperature from baseline (Δt) over time (min) for placebo and active peanut nasal  16 children with positive challenge arms. peanut challenge.  Nasal challenge with 10 μg peanut protein or placebo.  Mean skin temperatures recorded from the mouth & nose using infrared thermography over 18 min.
  • 76. Thermographic imaging during nasal peanut challenge may be useful in the diagnosis of peanut allergy. Clark, Allergy 2012;67:574 Change in mean nasal temperature The area under curve from baseline (Δt) over time (min) of nasal skin temperature for placebo and active peanut nasal  16 children with elevated was significantly positive challenge arms. peanut peanut vs placebo after challenge. (18.2 vs 4.8°Cmin).  Nasal maximum increase μg The challenge with 10 peanut protein or placebo. in temperature was also significantly greater  Mean aftertemperatures skin peanut: recorded from +0.9°C. mean difference the mouth & nose using infrared thermography over 18 min.
  • 77. Thermographic imaging during nasal peanut challenge may be useful in the diagnosis of peanut allergy. Clark, Allergy 2012;67:574 Change in mean nasal temperature Thermography from baseline (Δt) over time (min) can detect inflammation for placebo and active peanut nasal caused by nasal challenges  16 children with positive whilst employing 1000-fold challenge arms. peanutpeanut than an oral less challenge. challenge.  Nasal challenge with 10 μg This novel technique could peanut protein or placebo. be developed to provide a rapid, safe  Mean skin temperatures recorded from clinical and objective allergy test. the mouth & nose using infrared thermography over 18 min.
  • 79. Comparison of bronchodilator response in patients with asthma and healthy subjects using spirometry and oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317 Linear Regression with 95.00% Mean Prediction Interval  Impulse oscillometry (IOS) is an effort-independent pulmonary function technique.  Spirometry.  Reversibility after 400 μg salbutamol.  95 asthmatic and 61 healthy subjects. Correlation between percent predicted FEV1 and resistance at 5 Hz (R5) at baseline in patients with asthma
  • 80. Comparison of bronchodilator response in patients with asthma and healthy subjects using spirometry and oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317 Linear Regression with 95.00% Mean Prediction Interval  Impulse oscillometry (IOS) is an effort-independent Low-frequency pulmonary function technique. as R5 and IOS spirometry as  Spirometry. FEV1 correlate in  Reversibility after patients with 400 μg salbutamol. asthma.  95 asthmatic and 61 healthy subjects. Correlation between percent predicted FEV1 and resistance at 5 Hz (R5) at baseline in patients with asthma
  • 81. Comparison of bronchodilator response in patients with asthma and healthy subjects using spirometry and oscillometry. Nair Ann Allergy Asthma Immunol 2011;107:317 Linear Regression with 95.00% Mean Prediction Interval Correlation between percent predicted Correlation of the bronchodilator response FEV1 and and R5 post bronchodilator in measured as a percentage of predicted change patients with asthma in FEV1 and R5 in patients with asthma.
  • 82. Relationship between bronchial hyperreactivity and bronchodilation in patients with allergic rhinitis Ciprandi Ann Allergy Asthma Immunol 2011;106:460 Background Allergic rhinitis may be considered a risk factor for the onset of asthma. Recently, it has been reported that forced expiratory flow between 25% and 75% of vital capacity (FEF25%−75%) may predict a positive response to bronchodilation test in asthmatic children. Moreover, bronchial hyperreactivity (BHR) is frequently detected in AR patients. Objective To evaluate the possible relationship between the response to bronchodilation test and methacholine challenge, also considering the FEF25%−75% values in a large group of patients with persistent allergic rhinitis.
  • 83. Relationship between bronchial hyperreactivity and bronchodilation in patients with allergic rhinitis Ciprandi Ann Allergy Asthma Immunol 2011;106:460 % AHR patients with ”positive” results for  365 consecutive bronchodilation test AR patients. 70 – 60 –  Spirometry, methach oline, bronchial 50 – 66% challenge, and 40 – bronchodilation (+ if 30 – FEV1 > 12% after 400 20 – mcg salbutamol). 10 – 00
  • 84. Relationship between bronchial hyperreactivity and bronchodilation in patients with allergic rhinitis Ciprandi Ann Allergy Asthma Immunol 2011;106:460 % AHR patients with severe BHR  365 consecutive AR patients. 25 – (PC20 < 1mg/mL) 20 –  Spirometry, methach oline, bronchial 15 – 20.8% challenge, and 10 – bronchodilation (+ if FEV1 > 12% after 400 05 – mcg salbutamol). 00
  • 85. Relationship between bronchial hyperreactivity and bronchodilation in patients with allergic rhinitis Ciprandi Ann Allergy Asthma Immunol 2011;106:460 Boxplot for duration of rhinitis grouped by grade of severity of BHR  365 consecutive AR patients.  Spirometry, methach oline, bronchial challenge, and bronchodilation (+ if FEV1 > 12% after 400 mcg salbutamol).
  • 86. Validating childhood symptoms with physician-diagnosed allergic rhinitis Kim, Ann Allergy Asthma Immunol 2012;108:231 Background: Multiple population-based and high-risk cohort studies use parental questionnaire responses to define allergic rhinitis (AR) in children. Individual questionnaire items have not been validated by comparison with physician-diagnosed AR (PDAR). Objective: To identify routine clinical questions that best agree with a physician diagnosis of AR and can be used for early case identification.
  • 87. Validating childhood symptoms with physician-diagnosed allergic rhinitis Kim, Ann Allergy Asthma Immunol 2012;108:231  Longitudinal birth cohort study.  531 children at ages 1 through 4 and 7.  Questionnaires, physical examinations, skin prick tests (SPT).  Rhinitis- specific Rhinitis specific questionnaire questionnaire items: 3 stem questions and 4 sub-questions.
  • 88. Validating childhood symptoms with physician-diagnosed allergic rhinitis Kim, Ann Allergy Asthma Immunol 2012;108:231 Percent agreement, sensitivity and specificity of individual questionnaire items compared with physician-diagnosed allergic rhinitis (PDAR)
  • 89. Validating childhood symptoms with physician-diagnosed allergic rhinitis Kim, Ann Allergy Asthma Immunol 2012;108:231 Percent agreement, sensitivity and specificity of individual questionnaire items compared with physician-diagnosed allergic rhinitis (PDAR)
  • 90. Validating childhood symptoms with physician-diagnosed allergic rhinitis Kim, Ann Allergy Asthma Immunol 2012;108:231 Percent agreement, sensitivity and specificity of individual questionnaire items compared with physician-diagnosed allergic rhinitis (PDAR) Responses to hayfever and ocular symptoms had better specificity and percent agreement with PDAR than the ISAAC-validated questionnaire item. Combining 2 rhinitis questions sharply increases specificity and may improve diagnostic accuracy of clinical questions.
  • 91. Prevalence and impact of rhinitis in asthma. SACRA, a cross-sectional nation-wide study in Japan Ohta, Allergy 2011;66:1287 % of patients with rhinitis 80– 70–  1910 physician. 60– 68.5% 66.2%  29 518 asthmatics. 50– 40–  Questionnaires on rhinitis and asthma based on ARIA 30– (Allergic Rhinitis and its 20– Impact on Asthma) and 10– Global Initiative for Asthma (GINA); 0 Self-administered Patients with questionnaires physicians- administered
  • 92. Prevalence and impact of rhinitis in asthma. SACRA, a cross-sectional nation-wide study in Japan Ohta, Allergy 2011;66:1287 % of patients with uncontrolled asthma as defined by GINA 70–  1910 physician. 60– 50–  29 518 asthmatics. 40–  Questionnaires on rhinitis 30– P<0.05 and asthma based on ARIA (Allergic Rhinitis and its 20– 25.4% Impact on Asthma) and 10– 18% Global Initiative for Asthma (GINA); 0 YES NO Physician‟s diagnosis of rhinitis
  • 93. Bronchodilation test in patients with allergic rhinitis Ciprandi, Allergy 2011;66:694 % patients with impaired FEF25-75 values (≤ 65% of predicted) 30 –  1469 consecutive patients suffering 20 – from persistent AR. 10 – 18%  Spirometry and bronchodilation test in all patients. 0
  • 94. Bronchodilation test in patients with allergic rhinitis Ciprandi, Allergy 2011;66:694 % patients with FEV1 ≥ 12% post salbutamol 80 – 70 – 63%  1469 consecutive 60 – patients suffering 50 – from persistent 40 – AR. 30 –  Spirometry and 20 – bronchodilation 10 – test in all patients. 0
  • 95. Bronchodilation test in patients with allergic rhinitis Ciprandi, Allergy 2011;66:694 % patients with FEV1 ≥ 12% post salbutamol 80 – 70 – 63%  1469 consecutive 60 – patients suffering 50 – from persistent 40 – AR. 30 –  Spirometry and 20 – at risk of bronchodilation asthma 10 – test in all patients. development 0
  • 96. Bronchodilation test in patients with allergic rhinitis Ciprandi, Allergy 2011;66:694 OR for reversibility 20 –  1469 consecutive patients suffering from persistent AR. 10 – 11.3  Spirometry and bronchodilation test in all patients. 0 Impaired FEF25-75 values and longer rhinitis duration
  • 97. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children Kersten Pediatr Pulmonol 2012;47:27  Subjects aged 12–17 years, with mild-to- moderate asthma, intermittent allergic rhinitis and ≥10% fall in FEV1 at a screening exercise challenge.  22 ± 3 days treatment with Exercise induced fall in FEV1 (%) before and intranasal fluticasone after treatment with placebo or fluticasone furoate or placebo. furoate. Data expressed as individual fall in FEV1 and mean fall in FEV1.
  • 98. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children Kersten Pediatr Pulmonol 2012;47:27  Subjects aged 12–17 years, with mild-to- The activity limitation moderate domain score improved asthma, intermittent significantly within the allergic rhinitis and ≥10% fluticasone furoate fall in FEV1 at a screening group (P = 0.03). exercise challenge.  22 ± 3 days treatment with Exercise induced fall in FEV1 (%) before and intranasal fluticasone after treatment with placebo or fluticasone furoate or placebo. furoate. Data expressed as individual fall in FEV1 and mean fall in FEV1.
  • 99. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children Kersten Pediatr Pulmonol 2012;47:27  Subjects aged 12–17 years, Treatment of allergic with mild-to-moderate rhinitis in asthmatic asthma, intermittent allergic rhinitiswith ≥10% children and an intranasal fall in FEV1 at a screening corticosteroid exercise challenge. reduces EIB and  22 ± 3tends treatment with days to improve quality of life. intranasal fluticasone Exercise induced fall in FEV1 (%) before and furoate or placebo. after treatment with placebo or fluticasone furoate. Data expressed as individual fall in FEV1 and mean fall in FEV1.
  • 100. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children Kersten Pediatr Pulmonol 2012;47:27 Mean fall in FEV1 at each time point after exercise Before and after treatment Before and after treatment with placebo with fluticasone furoate
  • 102. Chronic rhinosinusitis: epidemiology and medical management Hamilos JACI 2011;128:693 • Chronic rhinosinusitis (CRS) affects 12.5% of the US population. • Some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. • The majority of pediatric and adult patients with CRS are immune competent.
  • 103. Chronic rhinosinusitis: epidemiology and medical management Hamilos JACI 2011;128:693 Current consensus definitions subclassify CRS into: 1. CRS without nasal polyposis (CRSsNP), 2. CRS with nasal polyposis (CRSwNP), 3. allergic fungal rhinosinusitis (AFRS).
  • 104. Chronic rhinosinusitis: epidemiology and medical management Hamilos JACI 2011;128:693 • Evaluation and medical management of CRS has been the subject of several recent consensus reports. • The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. • The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. • Sinus surgery followed by use of systemic steroids is recommended for AFRS.
  • 105. A new instrument for the assessment of patient-defined benefit in the treatment of allergic rhinitis Franzke, Allergy 2011;66:665 Mean, standard deviation (SD) and percentage of afflicted patients and needs in allergic rhinitis
  • 106. A new instrument for the assessment of patient-defined benefit in the treatment of allergic rhinitis Franzke, Allergy 2011;66:665 Mean, standard deviation (SD) and percentage of afflicted patients and needs in allergic rhinitis Needs are scaled from 0 “not important at all” to 4 “very important”
  • 107. •Rhinitis treatment anti-histamines
  • 108. Petasol butenoate complex (Ze 339) relieves allergic rhinitis–induced nasal obstruction more effectively than desloratadine. Dumitru JACI 2011;127:1515  Ze 339 is a carbon dioxide extract derived from the leaves of a special variety (Petzell) of Petasites hybridus registered at the European Community Plant Variety Office.  In vitro studies show that Ze 339 blocks degranulation in activated immune cell populations and also inhibits leukotriene biosynthesis.  18 subjects with allergic rhinitis to grass pollen received Ze 339, desloratadine, and placebo for 5 days before nasal allergen challenge with grass pollen extract.
  • 109. Petasol butenoate complex (Ze 339) relieves allergic rhinitis–induced nasal obstruction more effectively than desloratadine. Dumitru JACI 2011;127:1515  Ze 339 is a carbon dioxide extract derived from the leaves of a special variety (Petzell) of Petasites hybridus registered at the European Community Plant Nasal airflow Variety Office. improvement:  In vitro studies show that Ze 339 Ze 339, 2.46 hours; blocks degranulation in activated immune cell populations and also desloratadine, 3.94 inhibits leukotriene biosynthesis.  hours allergic rhinitis 18 subjects with [medians] to grass pollen received Ze 339, desloratadine, and placebo for 5 days before nasal allergen challenge with grass pollen extract.
  • 110. Petasol butenoate complex (Ze 339) relieves allergic rhinitis–induced nasal obstruction more effectively than desloratadine. Dumitru JACI 2011;127:1515 Recovery of nasal obstruction Time to RTB value of the symptom of nasal Time to return to 90% of basal flow obstruction (means ± SEMs assessed by means (means ± SEMs assessed by means of of VAS: Ze 339, 3.2 ± 1.3 hours; placebo, rhinomanometry: Ze 339, 5.4 ± 1.6 hours; 8.3 ± 2.4 hours; desloratadine, 4.5 ± 1.2 hours placebo, 9.1 ± 2.3 hours; desloratadine, 10.7 ± 2.5 hours) RTB = return to baseline
  • 111. Petasol butenoate complex (Ze 339) relieves allergic rhinitis–induced nasal obstruction more effectively than desloratadine. Dumitru JACI 2011;127:1515 Concentrations in picograms per milliliter per milligram of nasal secretion of IL-8 (A) and LTB4(B) in nasal secretions.
  • 112. Mometasone furoate nasal spray increases the number of minimal-symptom days in patients with acute rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275 Background: Acute rhinosinusitis (ARS) is triggered by viral or, uncommonly, bacterial infection, causing inflammatory symptoms for 12 weeks. Objective: To investigate effects of mometasone furoate nasal spray (MFNS) vs amoxicillin and placebo on minimal-symptom days.
  • 113. Mometasone furoate nasal spray increases the number of minimal-symptom days in patients with acute rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275  Double-blind, parallel- group, placebo- and active- % Minimal symptom days controlled 15-day study. 70 – P<0.004  Patients 12 years of age or older 60 – to MFNS 200 µg 2/daily, MFNS 62.69% 200 µg 1/daily, amoxicillin 500 50 – 50.33% 54.35% mg 3/daily, or placebo. 40 – 30 –  Major symptom score (MSS; 20 – combined rhinorrhea, postnasal P<0.001 10 – drip, congestion, sinus 00 – headache, facial pain) of≥5 and ≤12 (maximum: 15) for 7 to 28 MFNS Placebo Amoxicillin 2/daily days.
  • 114. Mometasone furoate nasal spray increases the number of minimal-symptom days in patients with acute rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275  Double-blind, parallel-group, placebo- and active- µg MFNS 200 % Minimal symptom days 2/daily significantly controlled 15-day study. P<0.004  Patients increased or older 70 – 12 years of age 60 – minimal-symptom to MFNS 200 µg 2/daily, MFNS 62.69% 50 – 50.33% 54.35% days vs amoxicillin 200 µg 1/daily, amoxicillin 500 40 – mg 3/daily, or placebo. or placebo 30 – in patients  Major symptom score (MSS; 20 – combined rhinorrhea, postnasal P<0.001 with ARS. drip, congestion, sinus headache, 10 – 00 – facial pain) of≥5 and ≤12 (maximum: 15) for 7 to 28 days. MFNS Placebo Amoxicillin 2/daily
  • 115. Mometasone furoate nasal spray increases the number of minimal-symptom days in patients with acute rhinosinusitis Meltzer, Ann Allergy Asthma Immunol 2012;108:275 Results of this  Double-blind, parallel-group, placebo- intranasal and active- % Minimal symptom days controlled 15-day study. corticosteroids (INS) 70 – P<0.004  Patients 12 years of age or it therapy indicate older 60 – to MFNS 200 µg 2/daily, MFNS 62.69% can improve 500 50 – 54.35% 200 µg 1/daily, amoxicillin 50.33% outcomes and mg 3/daily, or placebo. 40 – potentially reduce 30 –  Major symptom score (MSS; inappropriate combined rhinorrhea, postnasal 20 – P<0.001 10 – antibiotic use. drip, congestion, sinus headache, 00 – facial pain) of≥5 and ≤12 (maximum: 15) for 7 to 28 days. MFNS Placebo Amoxicillin 2/daily
  • 116. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis Bielory, Allergy 2011;66:686  3132 patients.  A meta-analysis of 10 randomized, placebo-controlled.  Efficacy of MFNS 200 mcg daily in relieving ocular allergy symptoms, including itching/burning, redness, and tearing/watering in both with nasal symptoms of seasonal (SAR) and nasal symptoms of perennial (PAR).
  • 117. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis Bielory, Allergy 2011;66:686 Improvement in tearing, itching, and redness in patients with SAR trated with MFNS for 2 weeks
  • 118. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis Bielory, Allergy 2011;66:686 Improvement in tearing, itching, and redness in patients with PAR trated with MFNS for 30 days
  • 119. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis Bielory, Allergy 2011;66:686 Improvement in tearing, itching, and redness in patients with PAR trated with MFNS for 30 days In both SAR and PAR all individual ocular symptoms were reduced in patients treated with MFNS.
  • 120. Ocular symptoms in nonspecific conjunctival hyperreactivity Mourão Ann Allergy Asthma Immunol 2011;107:29 Background Ocular symptoms can be triggered by nonspecific environmental factors, characterizing conjunctival hyperreactivity (CHR). Objective To examine CHR in subjects with ocular symptoms by means of a hyperosmolar conjunctival provocation test (HCPT).
  • 121. Ocular symptoms in nonspecific conjunctival hyperreactivity Mourão Ann Allergy Asthma Immunol 2011;107:29 Digital images of positive HCPT.  63 subjects with ocular complaints (A) Technician's analysis: number (itching, redness, or tearing) of red dots, 2521; number of blue dots, 8717. considered allergic if tests were (B) Technician's analysis: number positive to at least 1 allergen. of red dots, 2521; number of blue dots, 8717.  Hyperosmolar Conjunctival Provocation Test (HCPT) with serial A diluted glucose concentrations was positive if it produced conjunctival hyperemia up to a 50% solution.  Digital images were analyzed by B 2 observers who marked redness in the challenged eyes in red (GIMP 2.6.5 software).
  • 122. Ocular symptoms in nonspecific conjunctival hyperreactivity Mourão Ann Allergy Asthma Immunol 2011;107:29 Hyperosmolar conjunctival provocation Cumulative frequency of positive HCPT test with serial glucose concentrations in allergic and nonallergic subjects in allergic and nonallergic subjects
  • 123. Ocular symptoms in nonspecific conjunctival hyperreactivity Mourão Ann Allergy Asthma Immunol 2011;107:29 HCPT indentified CHR in allergic as well as in Hyperosmolar conjunctival subjects. Allergic subjects exhibited non-allergic provocation Cumulative frequency of positive HCPT test with serial glucose concentrations in allergic and nonallergic subjects more CHR than did non-allergic subjects. in allergic and nonallergic subjects
  • 124. Allergic Conjunctivitis and Dry Eye Syndrome Hom, Ann Allergy Asthma Immunol 2012;108:163 1. Allergic Conjunctivitis (AC) and Dry Eye Syndrome (DES) are 2 of the most common anterior inflammatory disorders of the eye. 2. The prevalence of DES is 5%-35% of the population. Up to 40% of the general US population has reported ocular symptoms consistent with AC. 3. Both conditions have a strong effect on quality of life. When measured with questionnaires reflecting quality of life, DES and AC can have the same effect on quality of life as moderate angina.
  • 125. Allergic Conjunctivitis and Dry Eye Syndrome Hom, Ann Allergy Asthma Immunol 2012;108:163 Subjective evaluation of symptom of dryness or frequency of dryness score definitions.  Self-reported - itchiness - dryness - redness.  689 patients 5-90 yrs.
  • 126. Allergic Conjunctivitis and Dry Eye Syndrome Hom, Ann Allergy Asthma Immunol 2012;108:163 Clinically significant itch.  Self-reported - itchiness - dryness - redness.  689 patients 5-90 yrs.
  • 127. Allergic Conjunctivitis and Dry Eye Syndrome Hom, Ann Allergy Asthma Immunol 2012;108:163 Clinically significant itch.  Self-reported - Clinically itchiness -significant dryness -itchiness redness. was found in  689 patients 28.2% 5-90 yrs. of patients.
  • 128. Allergic Conjunctivitis and Dry Eye Syndrome Hom, Ann Allergy Asthma Immunol 2012;108:163  Self-reported - itchiness - dryness - redness.  689 patients 5-90 yrs.
  • 129. Allergic Conjunctivitis and Dry Eye Syndrome Hom, Ann Allergy Asthma Immunol 2012;108:163 Itch & Redness Itch & Dryness Dryness & Redness Itch, Dryness & Redness
  • 130. Allergic Conjunctivitis and Dry Eye Syndrome Hom, Ann Allergy Asthma Immunol 2012;108:163 Itch & Redness Itch & Dryness Most patients with “itchy eyes” consistent with AC also have dry eyes and redness. Dryness & Redness These results suggest that some symptomatic & Redness Itch, Dryness patients concomitantly have features of AC and DES.
  • 131. Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis Nivenius, Clin Exp Allergy 2012;42:58 Background Atopic keratoconjunctivitis (AKC) is a chronic eye disease with periods of exacerbations. Many patients experience no obvious seasonal variation, although a majority of patients are allergic to common airborne allergens. Objective To investigate the allergic reaction, to conjunctival provocation with airborne allergens, in patients with AKC.
  • 132. Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis Nivenius, Clin Exp Allergy 2012;42:58  11 patients with AKC and birch and/or grass pollen allergy Atopic keratoconjunctivitis patient,  5 patients with 10 min after provocation seasonal allergic conjunctivitis (SAC) with birch allergen in the right eye & 5 healthy subjects. and dilution buffer only in the left.  Challenge in 1 eye with the allergen, to which the patient was reactive, & with dilution buffer in the other.  Signs & symptoms from both eyes at 10 min, 8h and 48h. allergen  Tear fluid for cytokine analyses at baseline and at 8h and 48h.
  • 133. Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis Nivenius, Clin Exp Allergy 2012;42:58 Total symptom score in the provoked eyes. Median linked by black line. Atopic Seasonal allergic Healthy
  • 134. Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis Nivenius, Clin Exp Allergy 2012;42:58 Total symptom score in the provoked eyes. Median linked by black line. A significant change from baseline was documented at 10 min for AKC & SAC patients, while no change was seen in healthy controls. Atopic Seasonal allergic Healthy
  • 135. Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis Nivenius, Clin Exp Allergy 2012;42:58 Total symptom score in the provoked eyes. Median linked by black line. In this single dose allergen provocation study, AKC patients responded with a typical IgE-mediated allergic reaction. Atopic Seasonal allergic Healthy
  • 136. Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis Nivenius, Clin Exp Allergy 2012;42:58 Total symptom score in the provoked eyes. Median linked by black line. An increase in cytokines at 48 h after the challenge was demonstrated and might, with further studies, give us a better understanding of the nature of inflammation in AKC. Atopic Seasonal allergic Healthy
  • 137. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896 • Vernal keratoconjunctivitis (VKC) is a severe allergic disease. • Treatment involves topical antiallergic agents, which are effective in patients with mild disease, whereas most patients with severe disease require some topical steroid therapy. • The physician’s primary objective with the patient with VKC is to prevent and minimize acute flare-ups, as well as to treat them when they do occur with the safest therapy available.
  • 138. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896 Study design.  Crossover 2 yr study.  Efficacy and safety of 0.05% topical cyclosporine in patients with VKC.  Ability of 0.05% cyclosporine to prevent flare-ups vs topical Ketotifen 0.025% AE; adverse event CsA; cyclosporine
  • 139. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896  Crossover 2 yr study.  Efficacy and safety of 0.05% topical cyclosporine in patients with VKC.  Ability of 0.05% cyclosporine to prevent flare-ups vs topical Ketotifen 0.025%
  • 140. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896 The number of recurrences was significantly reduced when patients were treated with  Crossover 2 cyclosporine 0.05% yr study.  Efficacy with safety of and respect 0.05% topical cyclosporine to 0.025% ketotifen. in patients with VKC.  Ability of 0.05% cyclosporine to prevent flare-ups.  The efficacy of a higher dose, 0.1%, was compared with 0.15% dexamethasone during acute relapses.
  • 141. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896 The cyclosporine group had  Crossover 2 yr study. significantly  Efficacy and safety of 0.05% topical cyclosporine in patients periods free longer with VKC. of recurrences  Ability of 0.05% cyclosporine to prevent the compared with flare-ups.  Theketotifen higher efficacy of a group dose, 0.1%, was compared with 0.15% dexamethasone during acute relapses.
  • 142. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896  Crossover 2 yr study.  Efficacy and safety of 0.05% topical cyclosporine in patients with VKC.  Ability of 0.05% cyclosporine to prevent flare-ups vs topical Ketotifen 0.025%
  • 143. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896 Itching, photophobia, and conjunctival hyperemia scores showed  Crossover 2 yr study. significant amelioration  Efficacy and safety of 0.05%patients treated with in topical cyclosporine in patients with VKC. 0.05% cyclosporine eye  Ability of 0.05% drops compared with those cyclosporine to prevent seen in patients treated flare-ups.  The with 0.025% ketotifen efficacy of a higher dose, 0.1%,eye compared was drops. with 0.15% dexamethasone during acute relapses.
  • 144. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double- masked, controlled 2-year study Lambiase JACI 2011;128:896 OR for recurrence 3 – p= 0.031 2.44  Crossover 2 yr study. 2 –  Efficacy and safety of 0.05% topical cyclosporine in patients with VKC. 1 –  Ability of 0.05% cyclosporine to prevent flare-ups vs topical 0 Patients treated with ketiofen Ketotifen 0.025% vs patients treated with cyclosporine.
  • 146. Nasal nitric oxide as a measure of osteomeatal complex patency in nasal polyps McKinlay Ann Allergy Asthma Immunol 2011;107:179 Nasal nitric oxide (nNO) levels according to computed tomographic (CT) scan results  Consecutive nonsmoking patients with nasal polyp disease.  Rhinosinusitis extent staged by CT scans of the paranasal sinuses.
  • 147. •Oxidative stress •in rhinitis and •nasal poliposis
  • 148. Oxidative stress induces unfolding protein response and inflammation in nasal polyposis. Jeanson, Allergy 2012;67:403 Background: Nasal polyposis, a chronic inflammatory disease affecting the upper airways, is a valuable and accessible model to investigate the mechanisms underlying chronic inflammation. The main objective of this study was to investigate a potential involvement of the unfolded protein response (UPR) in the context of oxidative stress and inflammation in nasal epithelial cells from nasal polyps (NP).
  • 149. Oxidative stress induces unfolding protein response and inflammation in nasal polyposis. Jeanson, Allergy 2012;67:403  Epithelial cells from NP (n=20) Proteomics analysis & normal mucosa (n=15). of human nasal epithelial cells in culture revealed the activation  Analyzed by of the unfolded protein response global proteomic approach in NP. & cell biology techniques.