13 bronchiectasis-dr khinchi

Bronchiectasis
Dr Yog Raj Khinchi

Chronic Bronchitis
Definition
ADULTS: Productive cough daily
for 3 months/year for 2
consecutive years.

CHILDREN: Productive cough of
>2 months duration or recurrent
episodes of productive cough >4
times/year.

Bronchitis is a state of
increased mucus
production, with or without
adequate mucociliary
transport, that requires cough
for clearance of airway
secretions.

Airway
Stimulus/Injury

Increasing Secretion Production

Increased Effective Secretion
Mucociliary Cough Inspissation Airway
Clearance Obstruction
Recurrent/Persistent

Chronic Bronchitis: Underlying
Conditions
Chronic Airway • Asthma
Infection/Inflammation: • Cystic Fibrosis
• Aspiration syndromes
• Chronic foreign body
• Tuberculosis

Primary Host Defense • Ciliary dyskinesias
Abnormalities: • Immunodeficiencies
• Congenital
• Acquired (HIV)

Inefficient Cough • Airway compression
Syndromes: • Trachobronchomalacia
• Neuromuscular weakness
• Tracheostomies
• Bronchiolitis obliterans

Bronchiectasis
Pathogenesis
Airway Injury +
Secretion Stimuli

Secretion Stasis Infection

Airway Destruction +
Airway Dilation

CF vs. Idiopathic Bronchiectasis

CYSTIC IDIOPATHIC
FIBROSIS BRONCHIECTATIS

Multi-organ Involvement Sinopulmonary
Involvement
Diffuse Multifocal

Pseudomones Mouth Flora

Tenacious Secretions Mucoid/Coughable

50% Bronchodilator 50% Bronchodilator
Response Response
Progressive Outcome Variable Outcome

Treatments for Idiopathic (Post-Infectious)
Bronchiectasis
Reduce Secretion • Reduce Irritant Exposure
Production: • Reduce Aspiration Events
• Reduce GER

Reduce Infection Exposure: • Dental Hygiene
Antibiotics for: Upper Airway
Lower Airway
Exacerbations
Promote Secretion • Chest Physiotherapy
Clearance:
Reduce Airway Obstruction: • ?Bronchodilators
• Inhaled Steroids

Prevent Infection: • Immunizations
• ?Palivizumab, Flu shots
• Pneumococcal vaccine (7 + 23 valent)

Bronchiectasis
• Irreversible, abnormal dilatation of one or more
bronchi, with chronic airway inflammation.
Associated chronic cough, sputum
production, recurrent chest infections, airflow
obstruction, and malaise
• Prevalence unknown (not common)
• Pathological endpoint with many underlying causes

Pathogens associated with exacerbations and
disease progression in bronchiectasis
• Non-tuberculosis
Haemophilus influenzae mycobacteria
Haemophilus parainfluenzae – M. avium complex (MAC)
Pseudomonas aeruginosa – M. kansasii
– M. chelonae
– M. fortuitum
Streptococcus pneumoniae
– M. malmoense
Moraxella catarrhalis – M. xenopi
Staphylocccus aureus
• Aspergillus-related
Stenotrophomonas maltophilia
Gram-negative enterobacter
disease

Causes / associations of bronchiectasis
• Idiopathic
• Postinfectious
• Humoral immunodeficiency
• Allergic bronchopulmonary aspergillosis (ABPA)
• Aspiration/GI reflux
• Rheumatoid arthritis
• Youngs Syndrome
• Cystic Fibrosis
• Ciliary dysfunction
• Ulcerative colitis
• Panbronchiolitis
• Congenital
• Yellow nail syndrome

Evidence for dysregulated immunity in
bronchiectasis
• Increased susceptibility to infection - bacterial, non-
tuberculous mycobacterial (NTM), and aspergillus-related
lung disease
• Associated with autoimmune disease such as the
inflammatory bowel disease, ulcerative colitis
• Neutrophils are markedly raised, as predicted from high local
levels IL-8
• Associated with immune deficiency syndromes such as TAP
deficiency syndrome

Bronchiectasis associated with increased
susceptibility to specific pathogens
• Non-tuberculosis
Haemophilus influenzae mycobacteria
Haemophilus parainfluenzae – M. avium complex (MAC)
Pseudomonas aeruginosa – M. kansasii
– M. chelonae
– M. fortuitum
Streptococcus pneumoniae
– M. malmoense
Moraxella catarrhalis – M. xenopi
Staphylocccus aureus
• Aspergillus-related
Stenotrophomonas maltophilia
Gram-negative enterobacter
disease

Bronchiectasis associated with
autoimmune disease

• Rheumatoid arthritis
• Systemic lupus erythematosus
• Relapsing polychondritis
• Inflammatory bowel disease -
Ulcerative colitis and Crohn’s
disease

Suppurative Lung Disease
• Bronchiectasis
• Lung abcess
• Empyema

Brochiectasis
• Def:destructive lung disease :chronic permanent and
abnormal dilatation of bronchial wall with variable
inflammatory process in the lung. Chronic bronchial
sepsis
• Pathology: non-inflammatory:congenital
acquired:
Bronchial wall dilatation.
excess mucus.
loss of connective tissue support
inflammation with metaplasia of ciliated
epithelium to squamous or columnar + micro-abcess formation.
Collapsibility of the wall leads to obstructive defect on spirometry.

Notes
• Bronchiectasis is of two types:
1- Dry: there is dilatation, destruction,
but no purulent secretion.
2- Suppurative (refers to chronic
bronchial sepsis): this is
bronchiectasis that have suppuration
( pus formation).

Pathogenesis
• Vicious cycle:
infectious insult & impaired drainage &/or defect in host defence

• Role of positive :
genetic susceptibilty
family history

Notes
• Normally, in healthy individuals the immune system and
mechanical system (cilia function) are intact, resulting in
good clearance of microorganisms leading to recovery.
• Therefore, with impaired cilia function and/or host defense
a vicious cycle (ongoing inflammation) will occur leading to
bronchiectasis.
• People with family history and genetic susceptibility (e.g a-
1 antitrypsin deficiency), when having a microbial insult,
they can not clear it probably because of defective immune
and/or mechanical drainage system.
• The most important organisms are: H.influenza,
encapsulated streptococcus pneumoniae, and
pseudomonus.

Classification
Spectrum:
• 1.follicular cylindrical:transmural inflammation, loss of bronchial
elastic tissue, mucosal edema; post infectious
• 2.Saccular:ulceration ,craters; general dilatation specially terminal
(saccules).
(varicose:distortion by scarring and obstructions)
• 3. Atelactatic:
localised, could be secondary to 1, or 2.importance to site and
distribution: lobar or segmental.

Notes
• Another type of classification is:
1- follicular cylindrical it is called follicular
because of presence of lymphoid follicles in the
bronchus. But it is generally called cylindrical
because it is transmural and localized to one
bronchus.
2- saccular: so called because there are succule
like formation at the terminal part of the
bronchus.
- varicose: this is when you have two types
together cylindrical and saccular.

Causes of bronchiectasis

Congenital:elastic bronchial wall def.
other congenital abnormalities,lung sequestration

Mechanical bronchial obstruction:
Intrinsic and extrinsic:
Lymph node or scaring :post-TB
Foreign body: selective lobes
Child vs adult

Notes
• Causes:
1- congenital:in fetus, the lung is not mature enough because
its blood supply is deprived, therefore making it liable to
bronchiectasis.
2- bronchial obstruction: the process of obstruction will cause
stagnation of secretion which will then start the process of
microbial infection leading to abcess formation and then
tissue destruction, hence bronchiectasis.
- Bronchial obstruction can be intrinsic (in wall or lumen) or
extrinsic (external compression).

Cont’d Notes
- TB produces both intrinsic (by scarring) and extrensic
(compression by lymph node).
• The common site of obstruction is the right posterior upper
lobe.
• Obstruction of airways in children can be caused by inhaling
a foreign body, and the inhalation of a foreign body also
leads to lung abcess.
• Obstruction in adults can occur due to inhaling chemicals or
impaired gastroesophageal reflex and aspiration.

*Cont’d Causes
*Inflammatory pneumonitis
-Aspiration:chemical ,gastric
-Inhalation: fumes

*Granulomata and fibrosis:
sarcoidosis ,TB,IPF

*Immunological over-response: ABPA (allergic bronchial pulmonary
aspergellosis), post lung transplant

*Immune deficiency
Primary: children: hypogammaglobinaemia:repeated
sinopulmonary infection
Secondary: AIDS, CA

Cont’d Causes
*Mucociliary clearance defects
-Genetic
-Primary ciliary dyskinesia :cilia abnormal
50% Kartegner’s:S.I, sinusitis Bronchiectasis.
-Cystic Fibrosis: abnormal mucus content.
*Acquired: -Young’s: sinusitis ,bronchiectasis ,obstructive azoospermia.
Abnormal mucus.
- -Post-infective bronchial damage:measles, pertussis.
MAI.Viral.Mycoplasma
- Toxins: SO2,smoking, lidocaine. Asthma.
*Rheumatic and systemic inflammatory diseases:e.g IBD (inflammatory
bowel disease).
*Idiopathic (including diffuse panbronchiolitis), good % with no cause

Notes
• In cystic fibrosis, the cilia is normal but the mucus is
abnormal because there is a block in the chlorine
channel (not responsive to cyclic AMP) causing the
mucus to become more sticky. This disease is
characterized by increased Na and Cl in sweat, which is
detected by sweating test.
• Kartegner syndrome: is a type of primary ciliary
dyskinesia which is also associated with sinusitis,
bronchiectasis, and transposition of the viscera.
• Young’s disease is characterized by high lipid content of
mucus.
• Idiopathic: panbronchiolitis (responsive to macrolide) is
found mainly in Japanese and East Asia.

Cont’s Notes
• ABPA causes hyper immune activity.
• Atypical mycobacterial infection and
uncontrolled asthma can cause
abnormal cilia.

*Mucociliary clearance defects
• *Genetic: Cystic fibrosis: AR, Gene
mutation,chromosome 7,Transmembrane conductance
regulator pr-CFTR
commonest:deletion at 508
impairment of chloride channel.non respondent cyclic-
AMP. Cl- and water not excreted but Na and its water
absorbed ,mucus get thickened.Sweat content of Na , Cl
altered.

Clinical manifestation of cystic fibrosis

Primary
• Bronchiectasis *Nasal polyps
• Bronchiolitis, bronchitis * Cirrhosis
• Infertility * Meconium ileus
• Pancreatic insufficiency
• Pneumonia
• Salt loss

Secondary
*Atelectasis * Allergic bronchopulmonary
*Clubbing aspergillosis
*Malabsorption * cholelithiasis
*Heat prostration * Cor pulmonale
*Hypochloraemic * Conductive hearing loss
hypokalaemic alkalosis * Diabetes mellitus

Diagnosis of Bronchiectasis
• 1.History: usually :muco-purulent sputum, cough.
occasionally recurrent hemoptysis, recurrent fever
Less specific : dyspnea, wheeze ,pleuritic pain
• 2.Examination: Early: normal

nowadays:clubbing 3%,crackles70%
rarely :Core pulmonale( right ventricular
hypertrophy due to pulmonary hypertension),CCF.

Notes
The most important sign is is abundant productive cough
increasing with lying down.
• The second important manifestations are lung abcess,
infective emboli, clubbing and amyloidosis (AA type).
• How hemoptysis occurs?
An insult causes injury, followed by healing and
neovascularization. These new formed blood vessels are
weak and fragile, hence easily ruptured causing
hemoptysis.
- Wheeze: musical sounds produced by air passing through
narrowed airways (during inspiration & expiration).
- Crackles (crepitations): non-musical sounds mainly heard
during inspiration caused by reopening of occluded small
airways.

Investigation
• Sputum: gram stain,selective media ( it is done not to
miss certain organisms),semi –quantitative
• !!TB, fungal
• CXR: early volume loss,vascular crowdening
late:cylindrical tramline,cystic.
• Disribution: central ABPA,
LL: idiopathic
UL: CF or variant

Investigation
• Bronchogram: surgery
• HRCT: standard
• Sinus X-Ray
• PFT: normal,obstructive,air trapping
• Specific: Ig level:IgA (in immunocompromised
patients).
• precipitin level is measured in skin, sputum and serum. If it
is high in 2 out of the 3 sites, we think of ABPA.
• Brochoscopy

Notes
• Bronchogram: do a bronchoscope then inject a
dye. It is done when you are planning for
surgery.
• HRCT= high resolution CT scan.
• Sinus X-ray is done to rule out sinusitis
• PFT is early normal, later:obstruction/ air
trappin
• Bronchoscopy is indicated in case of hemoptysis
and it is important to rule out obstructive
lesions (e.g. foreign bodies) and TB. These
three conditions are not responding to
antibiotics.

Notes
• The previous slide shows CT taken
during inspiration.
• Usually, a blood vessel has a
bronchus beside it that has the same
size.
• So, if you see a bronchus larger than
the accompanied vessel then suspect
bronchiectasis.

Notes
• The previous CT was taken for the
same patient during full
expiration, which is better than the
full inspiratory CT.

Cont’d investigation
• UGI Endoscopy
• Anti protease level
• Sweat test
• Genetic studies
• Rh. Factor

Complication
• Mostly: infective
exacerbation,haemoptysis
• Rarely now: metastatic spread of
infection empyema
amyloidosis clubbing
joint pain
• Note: certain complications are rare because of early
detection.

Management
• Prevention:
• Medical treatment:control infection ,bronchial hygiene
• Antibiotic:acute exacerbation: cover I.infl., strep.
Prophylactic:several protocols: commoner :
10days/Month or 10 days alternate with 10 free days.
• Bronchodilator
• IV Ig if deficient
• Oral Steroid:only ABPA vs inhaled steroids
• Mucolyte :debatable.role of ACC ( N-acetylcystin
which is antioxidant), DNAs
• Anti-fungal :itracanazole: ABPA
• Future treatment:Antiprotease replacement
• CF treatment (very complicated)

Notes
• Management of bronchiectasis includes:
- 1- Giving Igs for immunocompromised patients.
- 2- Vaccination for H. influenza, pneumococcus and
influenza.
- 3- Screening for TB (very important).
- 4- Bronchodilators (almost always given).
- 5- Steroids (only for ABPA because of the
hyperimmunity).
- 6- mucolytics: make sputum more liquid and less viscus
(not important except DNAs in cystic fibrosis patients to
improve their lung function).

Cont’d management
Physiotherapy
Corner stone:Postural drainage,
hydration ,nebulized saline
*Surgery:
.Massive haemoptysis: > 600ml/day.
.Localized troublesome resectable bronchiectasis
.Palliative for important stump.

Notes
- physiotherapy: teach the patient how to drain his lung
(lungs should be drained daily).
- Surgery: is indicated:
1- when there is severe hemoptysis
2- if one lobe causing problems to the patient, so you
resect it to prevent damage to other lobes
3- if you have a diffuse lung disease and one particular area
which is more problematic, then you resect it.
- Mild hemoptysis: loss of 200-300ml/day.
- Moderate hemoptysis: loss of 300-600ml/day.
- Severe hemoptysis: loss of > 600ml/day.

Cont’d management
Haemoptysis:
*Mild: antibiotic
*Severe: surgery or bronchial artery embolization
Lung Transplant: always double.
- Indication for transplantation: bilateral, advanced, and
bleeding bronchiectasis.
- 2 lungs should be transplanted because if you transplant
one lung only, the diseased lung you left in the body can
affect the new transplanted lung to become also
infected.

“Chronic dilation of the bronchi marked by
fetid breath and paroxysmal coughing, with
the expectoration of mucopurulent
matter.”

Morphological types
• Cylindrical or tubular bronchiectasis

• Varicose

• saccular or cystic bronchiectasis

Bronchiectasis

• Causes and pathogenesis
• Microbiology /common pathogens
• Therapeutic Goals

Bronchiectasis
Worldwide, infection is the primary cause
– M. Tuberculosis
– Childhood illnesses
• Rubeola, B. Pertussis

Childhood Infections M. Tb.

Infection

Inflammation

Bronchiectasis

Altered development

Inflammation

Characteristics across etiologies:
- Persistent
- Neutrophil dominant
- Pro-inflammatory cytokines (IL-
8, IL-1, TNF-a)
- Low anti-inflammatory cytokines
(IL-10)

Airway Damage
Failure to Resolve Inflammation

– Inappropriate inflammation
e.g. ABPM, CF (?)

– Impaired clearance of stimuli
Bacteria, mucus, toxins

Airway Damage
Failure to Resolve Inflammation
– Altered Airway Milieu
Proteolytic damage
-e.g. cleaved receptors
-impaired macrophage function*

Oxidant stress
-low antioxidants associated with worse disease
-dysregulation of signaling and cellular function‡


Infection

Inflammation* Impaired Clearance

Bronchiectasis

Altered development

Impaired Clearance
Altered ciliary Function
PCD, smoking, CFTR, Young’s

Mucus rheology
CFTR, Mucoid Ps. A

Dilated or obstructed airways
Impaired cough, foreign bodies, aspiration

Impaired Immunity
Ineffective inflammation

Acquired
Chemo-immunomodulation
Congenital/innate

HIV/AIDS Chemo-Immunosuppression
anti-TNF, MTX, anti-neoplastics

Innate Deficiency
CGD, CVID, Ig’opathy (IFN)

Infection

Inflammation Impaired Clearance
foreign body, CF

Bronchiectasis

Altered development


Innate Deficiency

Infection

Auto-Immune Impaired Clearance
RA, Sjogren’s, IBD Inflammation
ABPM

Bronchiectasis

Altered development


Innate Deficiency

Infection

Auto-Immune Inflammation Impaired Clearance
ABPM

Bronchiectasis

Altered development

Bronchiectasis
Epidemiology and Etiology

Who?
Patients - with altered immune system
- with persistent respiratory symptoms

Why?
Persistent inflammation in the respiratory system

Bronchiectasis Therapy
Decrease inflammation

antibiotics
clearance
– Flutter, IPPV, Vest, Bronchodilators, hypertonic saline

(anti-inflammatory chemotherapy)
– Steroids, macrolides, interferon-gamma, ibuprofen

(surgical resection)

When to suspect bronchiectasis?

Chronic cough, sputum
Coarse rales
Persistent respiratory
symptoms
Recurrent pneumonia
Progressive obstructive lung
disease
Funny bugs

Clinical Characteristics

– Focal – Systemic
• Sputum production • Malnutriton/wasting
– Mild <15 cc/d • Chronic Inflammation
– Moderate 15-150 – “gammaglobulinemia”
cc/d – CRP
– Sed’ rate
– Severe >150 cc/d
– anemia
• Hemoptysis
• Dyspnea
• Chest pain

Antibiotics

Episodic or suppressive antibiotics?

Yes.

Selective pressure vs. suppression of damage

Antibiotics

Con
• Pro Select resistance
– Decrease inflammation Cost
Side effects
– Slow progression adherence difficult (e.g.
– Eradication? Huong et al.)

Antibiotics when to use?

No:
• Yes: Minimal disease without
– Evidence of organism
Patient Intolerant
exacerbation
“Unaffordable”
– Progressive decline
– “Frequent
exacerbator”
– Active inflammation
(?)

Decrease inflammation

Clearance
Immunomodulatory chemotherapy
proposed therapies:
– Steroids
– Macrolides, tetracyclines
– interferon-gamma
– ibuprofen

Bronchopulmonary Hygiene
• removal of respiratory secretions is beneficial
• chest percussion and postural drainage
• chest clapping or cupping
• inflatable vests or mechanical vibrators
• Oral devices that apply positive end-
expiratory pressure maintain the patency of
the airway during exhalation

• Maintaining adequate systemic hydration,
enhanced by nebulization with saline,
• Acetylcysteine delivered by nebulizer thins
secretions
• aerosolized recombinant human DNase
(rhDNase) in patients with cystic fibrosis

Surgery
• Localised bronchiectasis
• Proximal obstructive lesion
• Massive hemoptysis
• Recurrent infections

Vicious loops
Infection

Bronchial
Obstruction Inflammation

Bronchiectasis

Summary
diagnosis management
• History • Treat bronchiectasis
– Prior infections, exposures – Clearance
– Time course – Antibiotics
– Other manifestations? – Immune-modulation
• Chest Imaging • Balance burden of disease vs
– Define region, pattern burden of therapy
• Sputum culture (Sputum, Symptoms, PFT’s, Weight, X-rays)
• Determine causal disease • Other…
– sweat testing – Underlying disease therapy
– immune testing
– serologic testing – Transplantation
– Management of complications
• Collapse, plugs, hemoptysis

Antibiotics
Vicious loop tobramycin
Infection

Bronchial
Obstruction Inflammation
Clearance Anti-inflammatory
Albuterol, DNase, Inhaled steroids
Therapy vest

Bronchiectasis

Bronchiectasis

Dilated airways with frequently
thickened walls

Bronchiectasis: Clinical

Note: Bronchiectasis may happen 2/2 COPD or may be a
separate process with very similar symptoms

Clinical:
• Cough (90 %)
• Daily sputum production (76%)
• Dyspnea (72%)
• Hemoptysis (56%)
• Recurrent pleurisy

Pathophysiology
2 Prerequisites:

• Infectious insult

• Impairment of drainage, airway
obstruction, and/or a defect in host defense.

Pathophys Continued
• Infection:
Bacterial, mycobacterial, esp. ABPA central airway
bronchiectasis

• Airway obstruction:
intraluminal tumor, foreign body, lymph nodes, COPD

• Immunodeficiency:
ciliary dyskinesia, HIV, hypogammaglobulinemia, cystic fibrosis
(obstruction and immunodef.)

Characteristic central bronchiectasis 2/2 ABPA

Note characteristic location in the upper lobes and superior segments of
lower lobes

Exacerbation: Etiology +Rx
Colonization/infection:
• Hemophilus
• Pseudomonas
• MAI
• Aspergillus

Very difficult to distinguish colonization from acute infection with these
bugs.
Psuedomonas colonized more bronchiectasis on CT; increased number
of hospitalizations vs H. flu colonization
Effect of sputum bacteriology on the quality of life of patients with bronchiectasis. Wilson CB; Jones PW; O'Leary CJ; Hansell DM; Cole PJ; Wilson R Eur
Respir J 1997 Aug;10(8):1754-60.

Treatment:
fluoroquinolone

Prevention
• Antibiotics-Controversial:
Consider Macrolide TIW
Cipro qd X 7-14 D/ month

• Bronchial Hygiene, physiotherapy, pulmonary
rehab
• ?bronchodilators, and steroids
• Surgery

Introduction
• Chronic daily cough w/ viscid sputum
• Bronchial wall thickening and luminal dilation
on CT
• Prevalence varies
– Associated w/ ↑age, female
• Management
– Infection control
– ↑ bronchial hygiene
– Surgical resection in selected p’t

Pathophysiology
• Permanent abnormal dilation and destruction
of bronchial walls
• Two factors
– Infection
– Impairment of drainage, airway obstruction,
and/or defect in host defense
• Biomarkers: inflammatory cells or 8-iso-
prostaglandin F(2α) in sputum

Etiology
• Pulmonary infections
– viral, mycoplasma, TB, MAC
• Airway obstruction
• Defective host defenses
• ABPA (allergic bronchopulmonary aspergillosis)
• Rheumatic and other systemic dz
– RA, Sjogren’s syndrome
– Ulcerative colitis
• Dyskinetic cilia
• Cystic fibrosis ← rare in TW
• Cigarette smoking?

Diagnostic Evaluation
• CBC w/ differential
• Ig quantification
• Sputum culture and smear
– bacteria, mycobacteria, fungi
• CXR
– Linear atelectasis, tram track, ring
shadow, irregular peripheral opacities
• HRCT: defining test
• PFT

CXR of Bronchiectasis

Hansell DM - Radiol Clin North Am - 01-JAN-1998; 36(1): 107-28

HRCT
• Sensitivitiy ~97%
• Findings
– Airway dilation
– Lack of tapering of bronchi
– Bronchial wall thickening
– Mucopurulent plugs or debris
– Cyst
– Pneumonia, LAP, emphysema
• Distributions
– Upper lobe
– Central distribution

HRCT

Radiol Clin N Am 43(2005) 513-542

Management
• Infection control
• ↑ bronchial hygiene
• Surgical resection in selected p’t

Infection Control
• Acute exacerbation
– ↑viscous, dark sputum, lassitude, SOB, pleurisy
– Fevers and chills generally absent
– CXR rarely show new infiltrates
– H. influenzae and P. aeruginosa
– FQ is reasonable (eg. ciprofloxacin) for 7~10 days

Prevention
• Daily ciprofloxacin (500~1500mg) in 2~3 doses
• Macrolide daily or three times weekly
• Daily use of a high dose oral antibiotic, such as
amoxicillin 3 g/day
• Aerosolization of an antibiotic
• Intermittent intravenous antibiotics

Problematic Pathogen
• Pseudomonas aeruginosa
– Almost impossible to irradicate
– Wilson CB et al.
• Reduced QoL
• More extensive bronchiectasis on CT
• Increased number of hospitalizations
– Ciprofloxacin quickly develops resistance

Bronchial Hygiene
• Oral hydration
• Nebulization
– Normal saline
– Acetylcyteine
– Recombinant DNAase
– Hypertonic saline, mannitol, dextran, lactose
• Physiotherapy
– Chest percussion
– Prone position
• Bronchodilator? Steroid? NSAID?

Surgical Intervention
• Removal of the most involved segments
• Most common: middle and lower lobe
resecton
• Hemoptysis:
– Bronchial a. embolization
• Lung transplantation

Lung Transplantation
• Overall 1-year survival : 68% (54-91%)
• Overall 5-year survival : 62% (41-83%)
• Subgroup
– SLTX : 1 yr survival 57% (20%-94%) n=4
• Mean FEV1 : 50% predicted (34%-61%),
• Mean FVC : 53% predicted (46-63%)
– 2 lungs : 1 yr survival 73% (51-96%) n = 10
• Mean FEV1 : 73% predicted (58%-97%),
• Mean FVC : 68% predicted (53%-94%)

Chapter 14
Bronchiectasis

C

A
B
E

D

Figure 14–1. Bronchiectasis. A, Varicose bronchiectasis. B, Cylindrical bronchiectasis. C, Saccular
bronchiectasis. Also illustrated are excessive bronchial secretions (D) and atelectasis (E), which are
both common anatomic alterations of the lungs in this disease.

Three Forms of Bronchiectasis
• Varicose bronchiectasis
• Cylindrical bronchiectasis
• Saccular bronchiectasis

Anatomic Alterations of the Lungs

• Chronic dilation and distortion of bronchial airways
• Excessive production of often foul-smelling sputum
• Smooth muscle constriction of bronchial airways
• Hyperinflation of alveoli (air-trapping)
• Atelectasis, consolidation, and parenchymal fibrosis
• Hemorrhage secondary to bronchial arterial erosion

Etiology
• Acquired bronchiectasis
– Recurrent pulmonary infection
– Bronchial obstruction
• Congenital bronchiectasis
– Kartagener’s syndrome
– Hypogammaglobulinemia
– Cystic fibrosis

Overview of the Cardiopulmonary
Clinical Manifestations Associated
with BRONCHIECTASIS
The following clinical manifestations result from
the pathophysiologic mechanisms caused (or
activated) by Atelectasis (see Figure 9-12),
Consolidation (see Figure 9-8), Bronchospasm
(see Figure 9-10), and Excessive Bronchial
Secretions (see Figure 9-11)—the major anatomic
alterations of the lungs associated with
bronchiectasis (see Figure 14-1).

Figure 9-7. Atelectasis clinical scenario.

Figure 9-8. Alveolar consolidation clinical scenario.

Figure 9-9. Increased alveolar-capillary membrane thickness clinical scenario.

Figure 9-10. Bronchospasm clinical scenario (e.g., asthma).

Figure 9-11. Excessive bronchial secretions clinical scenario.

General Management of
Bronchiectasis
General treatment includes:
• Controlling pulmonary infections
• Controlling airway secretions
• Preventing complications

Bronchiectasis
Respiratory care treatment protocols
• Oxygen therapy protocol
• Bronchopulmonary hygiene therapy protocol
• Hyperinflation therapy protocol
• Aerosolized medication protocol
• Mechanical ventilation protocol

Bronchiectasis
Other medications commonly prescribed
by the physician
• Xanthines
• Expectorants
• Antibiotics

BRONCHIECTASIS
RADIOLOGICAL FEATURES

BRONCHIECTASIS
THE CHEST RADIOGRAPH
• Often normal if not severe
• Too many white lines extending from the hila
= tram-tracks
• Elongated (tubular) opacities (white)
• Small circles containing air (black) or fluid and
air (air-fluid level)

MILD BRONCHIECTASIS
Normal chest radiograph
presents with hemoptysis

MODERATE BRONCHIECTASIS
- Coarse white lines
extending out from hila

SEVERE BRONCHIECTASIS

Circle filled
with air

RINGS (CYSTS) CONTAINING AIR-FLUID LEVELS

BRONCHIECTASIS
THE CT SCAN
• Signet ring sign
• Tram-tracks
• String of beads
• Circles filled with air or air and fluid
• Tubular and branching opacities
• Bronchi visible within 1 cm of the pleura
• Scarring

Normal pulmonary
artery (pearl)

Dilated bronchus
(ring)

SIGNET-RING SIGN

Dilated bronchus

BRONCHIECTASIS

Bronchi visible
within 1 cm of
the pleura

String
of beads

BRONCHIECTASIS

Destroyed
lung
(Scarring)

BRONCHIECTASIS

CAUSES OF BRONCHIECTASIS
• Congenital
• Acquired

CONGENITAL CAUSES OF
BRONCHIECTASIS
• Cystic fibrosis
• Immotile cilia syndrome

CYSTIC FIBROSIS
• Diffuse bronchiectasis
• Most severe in the upper lobes

Worse in the
upper lung
zones

CYSTIC FIBROSIS

IMMOTILE CILIA SYNDROME
• Diffuse bronchiectasis
• May have situs inversus (Kartagener’s
syndrome

Bronchiectasis

Dextrocardia

KARTAGENER’S SYNDROME

Bronchiectasis



Dextrocardia

Dilated
bronchus

CAUSES OF ACQUIRED
BRONCHIECTASIS
• Post-infectious
• Post-obstructive
– aspirated foreign body
– slow-growing tumour

POST-INFECTIOUS
BRONCHIECTASIS
• Affects the part of the lung which was
involved with pneumonia
• Often diffuse as most commonly secondary to
a viral pneumonia

POST-OBSTRUCTIVE
BRONCHIECTASIS
• Focal or localized because only distal to the
obstructing lesion
• Dilated bronchi distal to obstruction filled
with mucus instead of air

FOCAL BRONCHIECTASIS

Branching
tubular opacities

Focal bronchiectasis
due to slow-growing
endobronchial tumour

Focal bronchiectasis
due to slow-growing
endobronchial tumour

Dilated bronchi
filled with mucus

Branching
tubular opacity

Dilated bronchi
filled with mucus
instead of air due to
proximal obstruction

PULMONARY EMBOLISM

RADIOLOGICAL FEATURES

Lung - Pathology

Acute Lung Injury

Pulmonary edema

ARDS (Diffuse alveolar damage)

Acute interstitial pneumonia

• Pulmonary Edema
• 1. Hemodynamic disturbances(↑ capillary hydrostatic pressure), MCC-
LVF, Heart failure cells
• 2. ↓ oncotic pressure (Hypoalbuminemia)  Renal
failure, Malnutrition, Cirrhosis
• 3. Microvascular injury - ↑ capillary permeability,
– Seen in ARDS following
a) Infection -viral pneumonia
b) Gases, Aspiration, Drugs--heroin, Paraquat (herbicide)
c) Shock, Trauma, Sepsis, DIC
• ARDS:
• Also known as ***Diffuse Alveolar Damage (DAD)  pulmonary
edema (protein rich)  hyaline membrane disease  hypoxemia
(refractory to oxygen Rx )
• Mortality in 50% of cases
• Clinical Manifestations: respiratory insufficiency, Cyanosis, arterial
hypoxemia  multi-organ failure
• Acute interstitial pneumonia Cause is unknown (Unlike
ARDS) but Radiographic and Pathologic features, mortality similar to
ARDS

• Bronchiectasis
• Infection + permanent dilatation of bronchi
• Causes:
• infections and causes of bronchial obstruction
(FB, mucus plugs, tumors, sequestrations, cystic fibrosis)
• immotile cilia (Kartagener’s )syndrome
(Bronchiectasis, dextrocardia -situs inversus, chronic
sinusitis, and infertility)
• Clinically:
• Chronic cough, productive of purulent sputum
• Dyspnea and orthopnea in severe cases
• later obstructive respiratory insufficiency & Corpulmonale

Bronchiectasis
Gross

• Distended peripheral
bronchi (Due to weakening
of wall)

PRIMARY ANTIBODY
DEFICIENCY
(PAD)
&
BRONCHIECTASIS
(UKPIN / BTS GUIDELINES)

BRONCHIECTASIS
A destructive lung disease characterised by:

 Abnormal & permanent dilatation of medium sized bronchi

 An associated, persistent and variable inflammatory process
producing damage to bronchial elastic and muscular
elements

PATHOLOGY

Neutrophil proteases
(acute infection in a normal or compromised host)

Epithelial injury
+
Structural protein damage

Damaged, dilated airway

Mucous retention / chronic, recurrent infection

Ongoing inflammation / tissue damage / repair

BRONCHIECTASIS - aetiology
 Infection
- pertussis, influenza, measles, TB, necrotising peumonia
 Bronchial obstruction
- mucoid impaction, ABPA
 Congenital anatomical lung abnormality
 Inherited disorders
- ciliary dysfunction
- cystic fibrosis
- alpha-1 AT deficiency
• Undefined (29 - 49%)

BRONCHIECTASIS OF UNDEFINED
REF.
AETIOLOGY NOS. ANALYTE % age ABN.

Hilton & Doyle 53 IgG/A/M 0 -
1978
Murphy et al 23 IgG/A/M, Gsub 0 -
1984
Barker et al 30 IgG/A/M, Gsub 37 Panhypoγ (9/30)
1987 IgM (2/30)
De Gracia et al 65 Gsub, Hib 48 IgG2
1996 Hib (10/19)
Hill et al 89 Gsub 6 IgG4
1998
Stead et al 56 IgG/A/M, Gsub 23 IgG4
2002 Hib, Pneum Pneum (1/29)

BRONCHIECTASIS
Pasteur et al. Am J Respir Crit Care Med (2000) 162, 1277-1284

ASSOCIATION n %
Idiopathic 80 53
ABPA 11 7
PAD 11 7
Neutrophil defect 1 <1
Rheumatoid disease 4 3
Ulcerative colitis 2 <1
Ciliary dysfunction 3 1.5
Young’s syndrome 5 3
Cystic fibrosis 4 3
Post-infectious 44 9
Aspiration/reflux 6 4
Other defineable 2 <1

BRONCHIECTASIS in PAD
CVID
• 53% (Hausser et al 1983)
• 44% (Watts et al 1986)
• 18% (Hermazewski & Webster 1993)
• 20% (UK PAD Audit 1993-96)
• 27% (‘chronic lung disease’) (Cunningham Rundles 1999)
• 58% (Garcia 2001)
• 43% (Busse et al 2002)

XLA
• 7% (Hermazewski & Webster 1993)
• 12% (UK PAD Audit 1993-96)
• 20% (Quartier et al 1999)

RESPIRATORY INFECTIONS

Figure 2 Types of infection in the 37 patients receiving
immunoglobulin replacement treatment. The numbers of each type
of infection are listed by each chart section.

DIAGNOSTIC DELAY
 Average: diagnosis - 6.3 years
treatment - additional 3.9
 Diagnostic delay > 2 years:  risk of bronchiectasis
sinusitis
iron deficiency
(UK PAD Audit 1993-96) 3

 Strongest predictor of chronic pulmonary disease in treated
patients is established lung disease at time of presentation
n= XLAx10, CVIDx12
IMIg x 18, IVIg x 3, FFP x 1 (all + daily antibiotic)
(Sweinberg et al 1991) 3

UK PAD AUDIT 1993-96
Development of bronchiectasis following diagnosis:

<1980 1981-87 >1988
77% 70% 42%

CHRONIC LUNG DISEASE in PAD

Damage sustained prior to active treatment

and/or

Continued inflammation despite treatment

AIMS
Define evidence-based guidelines relevant to:

 investigation level appropriate to screen for
significant antibody deficiency in all patients with
bronchiectasis

 diagnosis & management of bronchiectasis
complicating primary antibody deficiency

GUIDELINES
 Simple  Valid
 Evidence-based  Reproducible
 Consistent with  Reliable
existing, recognised standards • Involving & representative of
 Realistic key disciplines
 Explicit  Clinically applicable
 Clear & well documented  Clinically flexible
 Credible & widely supported  Scheduled for review
 Results orientated (outcomes)

GUIDELINES
LITERATURE REVIEW DATABASES

 Ovid Online Collection
 Meta-analyses - Medline, preMedline
 Systematic reviews - CINAHL, EMBASE
 RCTs - Journals@ovid
 EBM Reviews
 Longitudinal studies
- Cochrane Systematic Reviews
 Case control/cohort studies - Cochrane Controlled Trials
 Case reports/case series - Effectiveness Reviews Abstracts
- ACP Journal Club
 Expert opinions
 Allied & Complementary
Medicine
 Specialty Contacts

GUIDELINES
EVIDENCE RECOMMENDATION
1 A
2 B
3 C
4 D
(Good Practice Points)
SIGN, RCPCH, BTS

DIAGNOSIS
PRIMARY ANTIBODY DEFICIENCY

 Humoral abnormalities are common in bronchiectasis 3
 Respiratory Physician + Immunologist 4
 Diagnosis of significant antibody deficiency should entail use of
established and widely accepted criteria: 4

- Primary Immunodeficiency Diseases. Report of an IUIS Scientific Group
Clinical & Experimental Immunology 1999 (118), Suppl 1:1-34
- Diagnostic Criteria for Primary Immunodeficiencies.
Clinical Immunology 1999 (93), 190-197
- Practice parameters for the Diagnosis & Management of Immunodeficiency.
Annals of Allergy, Asthma & Immunology 1996 (76), 282-294

PFTs
- Reversible/irreversible bronchial obstruction
- Granulomatous disease etc.

 Correlate poorly with Radiology (bronchiectasis) 3
- Pulmonary abnormalities in patients with primary hypogammaglobulinaemia
Kainulainen et al. Jounal of Allergy & Clinical Immunology (1999) 104, 1031-1036
- Pulmonary manifestations of hypogammaglobulinaemia
Dukes et al. Thorax (1978) 33, 603-607
- Radiologic findings of adult primary immunodeficiency disorders: contribution of CT
Obregon et al. Chest (1994) 106, 490-495

• Static volumes/flow-volume loops

RADIOLOGY - CXR
Bronchiectasis

- vessel ‘crowding’
- loss of vessel markings
- tramline/ring shadows
- cystic lesions/ air-fluid levels
- evidence of TB

Poor:
 diagnostic sensitivity
 monitoring of progression
3

RADIOLOGY - HRCT
- bronchial dilatation
- bronchial wall thickening
- classification (pathology)

 sensitivity (97%) > CXR 3
 chromosomal radiosensitivity
- plain CXR (x 3 days background)
- HRCT: x 30-40
- conventional CT: x 200
• ? routine baseline
• ? (a)symptomatic monitoring

UNSUSPECTED DISEASE
(Clinical v CXR v HRCT)

 Bronchiectasis in Hypogammaglobulinaemia - A Computed
Tomography assessment. Curtin et al. Clinical Radiology (1991) 44, 82-84
 Radiologic Findings of Adult primary Immunodeficiency Disorders.
Obregon et al. Chest (1994)106, 490-495
 Chest High Resolution CT in Adults with Primary Humoral
Immundeficiency. Feydy et al. British Journal of Radiology (1996) 69, 1108-1116
 Clinical Utility of High-Resolution Pulmonary Computed Tomography
in Children with Antibody Deficiency. Manson et al. Pediatric Radiology (1997)
27, 794-798
 The Value of Computed Tomography in the Diagnosis & Management
of Bronchiectasis. Pang et al. Clinical Radiology (1989) 40, 40-44
 Review Article: Imaging in Bronchiectasis. Smith et al. British Journal of
Radiology (1996) 69, 589-593
3

RADIOLOGY
Kainulainen et al 1999

 CVID x 18, XLA x 4  3 year follow-up

CXR HRCT Disease progression (5)
Bronchiectasis 3 16
Serum IgG
Case No T=0 T=36
1 9.9 10.0
2 4.6 6.1
8 3.7 5.1
10 3.7 4.9
21 3.1 5.7

RADIOLOGY - HRCT
RCP Specialty Specific Standards

‘Fit’ patients…….CT scanning should be undertaken in
a minority of patients but usually not more than once a
year or if respiratory function tests or symptoms
deteriorate

JCIA November 2001 4

MANAGEMENT – GENERAL ISSUES

 Shared Care (Immunologist/Respiratory Physician) optimal 4
 Bronchodilators (reversible airflow obstruction)
 Mucolytics - insufficient evidence to evaluate routine use
(Cochrane Database of Systematic Reviews. 3, 2003)
 Physical therapy - insufficient evidence to support or refute usage
 Anti-inflammatory agents

REPLACEMENT THERAPY
 Risk/benefit assessment 4
 IV/Sc routes optimal 2
  pulmonary infections in XLA/CVID (v untreated) 2
 Optimal dosing/frequency/serum IgG level not established
 Tailor route/dose/infusion frequency 3
---------------------------------------------------------------
 Maintain IgG >5g/l 2
 Paediatric target: mid reference range 4
 IgG: >8g/l   infection (v 5g/l, XLA, children) 3
9.4 g/l   infection (v 6.5g/l, XLA/CVID, children/adults) 3
 High v standard doses   infections (no. & duration) 2
 days hospitalised
 serum IgG
 Insidious disease progression despite ‘adequate’ replacement 3

REPLACEMENT THERAPY
High dose v low dose: secondary outcome, pulmonary function
 Eijkhout et al 2001 (randomised, double-blind, multicentre, crossover, n=43)
High dose (mean trough IgG 9.4 g/l): PEFR 37.3 l/min
Standard dose (mean trough IgG 6.5 g/l): PEFR 11.4 l/min NS

 Roifman & Gelfand 1988 (ramdomised, crossover, n=12)
High dose   FVC & FEV1 p<0.01

 Roifman et al 1987 (randomised, crossover, n=12)
Mean FEV1 & FVC high dose phase v low dose phase p<0.01

 Bernatowska et al 1987 (two-dose, crossover, non-randomised, n=13)
High dose  Max. expiratory flow & FEV1 NA

ACUTE INFECTION
MICROBIOLOGY
 Culture & sensitivity routinely in acute setting 3
 Value unclear in chronic situation - confirm original pathogen
- ? emerging resistance
- additional pathogens

ANTIBIOTICS
 Effectiveness established in exacerbations (bronchiectasis) 2
 Higher doses for longer periods 4
 Local treatment protocols 4

ANTIBIOTIC PROPHYLAXIS
 Chronic bronchitis - no place in routine treatment

 Cystic fibrosis benefits - principally staphylococci
- infancy  3/6 years
- ? older children/adults
- ? > 3years treatment
(The Cochrane Library, Oxford. 2, 2003)

• Bronchiectasis - limited meta-analysis (6 RCTs)
- marginal benefit / cautious support
(Evans et al. Thorax 2001)

 No robust data v placebo
 No substantial data v (or additional to) IVIg/SCIg (Silk et al. 1990)
 ? Single intervention in mild antibody deficiency
- not in more severe phenotypes / tissue damage
 Papworth protocol: consider if: > 3 exacerbations / year 4
radiological / PFT deterioration
 ? Eradication/clean-up therapy prior to prophylaxis
- no clear evidence of benefit in antibody deficiency + structural lung damage
 Development of local protocols for management of infections
(esp. with Primary Care) and initiating prophylaxis 4


Percentage of sputum samples growing pathogens
before and after prophylactic ciprofloxacin
70
60
50
all pathogens
40
30 H. Infl (all
%
isolates)
20
H Infl. (resistant
10 to ciprofloxacin)
0
Prior to On
ciprofloxacin ciprofloxacin
(Heelan et al., ESID 2002)

SURGERY
 Diagnostic delay > 2 years:  need for surgical procedures
Adequate
treatment:  lobectomy/pneumonectomy by 95%
(UK PAD Audit 1993-96) 3

 Important treatment option with favourable outcomes
especially in focal bronchiectasis
(Cohen et al 1994, Mansharamani & Koziel 2003) 3

QUESTIONS / ISSUES
 HRCT in routine screening & monitoring
 Radiological changes a primary therapeutic target
- Does HRCT modify our current assumptions about criteria for adequate
treatment of antibody deficiency disorders?
 Correct level of Ig treatment
- arbitrary target serum level (evidence) or individualised (clinical + HRCT factors)
- single intervention universally applicable in all patients (probably not)
- higher doses: expense, complications, limited commodity
 Roles of: antibiotics
anti-inflammatory agents
bronchodilators
aids to airway clearance
 Role of co-factors (e.g. 1AT)
 Selective IgA deficiency

PIN GUIDELINES
 Identify need for focused clinical research
 Encourage debate and discussion
 Reflect uncertainties in the field
 Proscriptive as necessary, flexible where possible

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