Guía Asma Soc. Japonesa

Pediatrics International (2010) 52, 319–326 doi: 10.1111/j.1442-200X.2009.03010.x

Japan Today ped_3010 319..326

Japanese pediatric guidelines for the treatment and management of
bronchial asthma 2008

Naomi Kondo,1,5 Toshiyuki Nishimuta,2,5 Sankei Nishima,3,5 Akihiro Morikawa,4,5 Yukoh Aihara,5 Toru Akasaka,5
Akira Akasawa,5 Yuichi Adachi,5 Hirokazu Arakawa,5 Takao Ikarashi,5 Toshiichi Ikebe,5 Toshishige Inoue,5 Tsutomu Iwata,5
Atsuo Urisu,5 Motohiro Ebisawa,5 Yukihiro Ohya,5 Kenji Okada,5 Hiroshi Odajima,5 Toshio Katsunuma,5 Makoto Kameda,5
Kazuyuki Kurihara,5 Yoichi Kohno,5 Tatsuo Sakamoto,5 Naoki Shimojo,5 Yutaka Suehiro,5 Kenichi Tokuyama,5
Mitsuhiko Nambu,5 Yuhei Hamasaki,5 Takao Fujisawa,5 Takehiko Matsui,5 Tomoyo Matsubara,5 Mitsufumi Mayumi,5
Tokuko Mukoyama,5 Hiroyuki Mochizuki,5 Koichi Yamaguchi5 and Shigemi Yoshihara5
1
Department of Pediatrics, Graduate School of Medicine, Gifu University, 5Japanese Society of Pediatric Allergy and
Clinical Immunology, Gifu, 2National Hospital Organization, Shimoshizu National Hospital, Chiba, 3Department of
Pediatrics, National Fukuoka Hospital, Fukuoka and 4Department of Pediatrics and Developmental Medicine, Gunma
University, Graduate School of Medicine, Gunma, Japan

Abstract The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008
(JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008.
In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the
Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity;
recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis
on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report
concerning JPGL 2005.

Key words acute attacks, childhood asthma, prevention, guideline, long-term management.

After the publication of the first version of the Japanese Pediatric and recurrent symptoms of airway narrowing, including episodes
Guidelines for the Treatment and Management of Bronchial of dyspnea, wheezing, and coughing. Patients commonly show
Asthma (JPGL) in 2000, the pediatric asthma mortality rate bronchial hyperresponsiveness associated with chronic allergic
decreased in Japan. However, the methodology of asthma treat- inflammation of the airway, mainly due to environmental
ment has evolved over the years, and the JPGL were revised in allergens.4,5
2002, 2005, and 20081,2 by the Japanese Society of Pediatric Similarly to adult asthma, childhood asthma is also consid-
Allergy and Clinical Immunology (JSPACI). In the JPGL 2008, ered to be a chronic inflammatory airway disease. However, there
we revised our recommendations on the basis of the JPGL 2005. are some differences between children and adults in the mecha-
The JPGL 2008 is different to the Global Initiative for Asthma nism of an asthma attack, and the pathophysiology of asthma
(GINA) guideline 20063 in that it contains the following items: a attacks in children is not fully understood.
classification system of asthma severity; recommendations for An assessment of the severity of a patient’s asthma attacks is
long-term management organized by age; a special mention essential in developing a plan for the adequate treatment and
of infantile asthma; and an emphasis on prevention and early management of the disease. Childhood asthma attacks are clas-
intervention.1 sified into four stages of severity: mild attacks, moderate attacks,
Here we show a summary of the JPGL 2008 revising our severe attacks, and acute respiratory failure. The criteria for each
previous report concerning JPGL 2005.4 of these stages are shown in Table 1.
With regard to the percentage of peak expiratory flow (PEF),
Definition, pathophysiology, diagnosis, and GINA guidelines and other guidelines established in Japan have
classification of childhood asthma adopted PEF measured after b2-agonist inhalation, as a reference
In previous years, asthma was defined as a respiratory disease point. This PEF reflects airflow limitation and reversibility, and is
involving a chronic airway inflammation, airway remodeling, useful for evaluating the severity of attacks.6 In the JPGL 2008,
similarly to JPGL 2005, it is recommended that PEF should be
measured both before and after b2-agonist inhalation.
Correspondence: Naomi Kondo, md phd, Department of Pediatrics,
Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu Regarding the severity of asthma, the classification system
501-1194, Japan. Email: nkondo@gifu-u.ac.jp outlined by the JSPACI has been used for a long time and it
Received 5 November 2009; accepted 19 November 2009. includes mild asthma, moderate asthma, and severe asthma.

© 2010 Japan Pediatric Society

320 N Kondo et al.

However, we adopted the GINA guidelines as a model for JPGL

(mmHg)
PaCO2

41–60
2002: intermittent, mild persistent, moderate persistent, and

<41
<41

>60
severe persistent asthma (Table 2). The long-term management
criteria in the JPGL 2008 were also divided into four steps that
were coordinated with the GINA or Japanese adult asthma guide-

air) (%)

92–95
(Room
SpO2
lines. However, a step for the same condition is graded to be more

396

291
<91
severe in JPGL 2008 than in other guidelines, in order for it to be
more useful in clinical practice for childhood asthma. For
example, in the case of symptoms occurring less than once a
inhalation (%)
After b2

week, the grade is intermittent in the GINA guidelines, but it is
mild persistent in JPGL 2008 as well as in JPGL 2005.
50–80

n.m.
>80

<50
PEFR

Epidemiology of childhood asthma
inhalation (%)

At present, two survey methods are utilized in Japan: the Inter-
Before b2

national Study of Asthma and Allergies in Childhood (ISAAC)7
30–60

and the American Thoracic Society – Division of Lung Diseases
n.m.

(ATS-DLD) modified Japanese version.8 The ISAAC survey
>60

<30

includes cases of asthma ranging from mild to severe, and the
ATS-DLD survey includes only typical cases of asthma with
n.m. not measured; PaCO2, carbon dioxide partial pressure; PEFR, peak expiratory flow rate; SpO2, oxygen saturation.
Respiratory

dyspnea. Therefore, the reported prevalence is different depend-
Unstable
rate

ing on the survey method used. The prevalence of asthma symp-
↑↑
↑↑

toms determined using ISAAC is 2–2.5-fold higher than that
↑

determined using ATS-DLD. ATS-DLD is often used in Japan,
which shows a 7–8% prevalence of asthma.
Cyanosis

Nishima et al. reported that the prevalence of asthma based on
(-)
(-)
(1)
(+)

an ATS-DLD survey performed in elementary schools at the
same time each year was 3.2% in 1982, 4.6% in 1992, and 6.5%
in 2002, indicating a twofold increase within 20 years.9,10 These
results show that the prevalence of asthma in Japan is increasing,
Leaning forward

particularly in children. The JPGL 2008 revision includes the
Posture

Lying down

latest epidemiological data.
Sitting
Symptoms

–

Risk factors and prevention of asthma in infants
and children
of expiration
Prolongation

The risk factors for childhood asthma are listed in the JPGL 2008,
(++)
(++)

as shown in Table 3. The assessment of newborns and infants is
(-)
(+)

important for evaluating the risk factors for childhood asthma.
The influences of smoking during pregnancy and viral respiratory
infections including respiratory syncytial virus, rhinovirus, and
Retraction

influenza virus as risk factors for asthma development and
(-)–(+)

asthma exacerbation are becoming more obvious.11,12
(++)
(++)
(+)

Three levels of prevention have been described and, in relation
to asthma, include primary, secondary and tertiary preventions as
shown in Table 4.13
Table 1 Severity of asthma attack

Breathless
wheezing

A prerequisite for establishing any form of preventive strategy
(1)–(-)
(++)
(++)

is to have reliable markers that predict the progression of a
(1)

disease, but to date there are no such markers available for
asthma. At all levels of prevention, many of the issues remain
speculative and have yet to be tested in appropriate long-term
Respiratory attack
Moderate attack

controlled clinical studies, though many such studies are in
Severe attack

progress.
Mild attack

The usefulness of early intervention with inhaled corticoster-
oids and other anti-inflammatory drugs in the early phase of
asthma development has also been discussed in the JPGL 2008.


Jpn pediatric guidelines for asthma 2008 321

Table 2 Differences in classification of asthma severity

JPGL 2008 GINA 2006
Step1: Intermittent Step1: Intermittent
• Symptoms less than several times a year • Symptoms less than once a week
• Brief exacerbation • Nocturnal symptoms not more than twice a month
Step2: Mild persistent Step2: Mild persistent
• Symptoms less than once a week • Symptoms more than once a week
• Normal daily life • Nocturnal symptoms more than twice a month
Step3: Moderate persistent Step3: Moderate persistent
• Symptoms more than once a week • Symptoms daily
• Sometimes, moderate or severe attack • Nocturnal symptoms more than once a week
Step4: Severe persistent Step4: Severe persistent
• Symptoms daily • Symptoms daily
• Moderate or severe attack more than several times a week • Frequent exacerbations
• Troubles in daily life • Frequent nocturnal symptoms
GINA, Global Initiative for Asthma; JPGL 2008, Japanese Pediatric Guidelines for the Treatment and Management of Asthma 2008.

Acute attacks in childhood asthma measure percutaneous arterial oxygen saturation (SpO2) and PEF
Home management of patients to evaluate the severity of acute attacks (Tables 5–7). Inhaled
b2-agonists should be used as an initial therapy, and a treatment
Asthma symptoms vary widely in severity, ranging from mild suitable for each symptom should then be selected. During mod-
attacks of wheezing to severe acute respiratory failure. Physi- erate attacks, inhaled b2-agonists should be used several times
cians should provide detailed information for home management every 20–30 min. In addition, systemic corticosteroids (by i.v. or
to each patient and/or parent, including how to observe asthmatic p.o.) and/or aminophylline (by drip infusion, the target serum
symptoms and how to use drugs for the control or relief of asthma theophylline concentration is 8–15 mg/mL and ~10 mg/mL in
attacks and timing of visiting a medical facility. Repeated instruc- patients <2 years) should be administered. Administration
tions on the proper inhalation techniques of b2-agonists are also therapy is necessary during severe attacks and for moderate
necessary. attacks that fail to improve despite the therapies. In addition to
Management in a medical facility (Tables 5–7, organized the therapies already mentioned, a continuous inhalation of iso-
by age) proterenol should also be administered during severe attacks and
Management plans should be determined when patients are
admitted to a medical facility for an asthma attack. It is useful to
Table 4 Three levels of prevention for asthma13

Table 3 Potential Risk Factors of Asthma Primary prevention is introduced before exposure to risk factors
known to be associated with a disease.
(1) Host factors • The goal is to prevent the onset of disease in susceptible (at-risk)
1. Family history and gender individuals.
2. Genetic predisposition • This is not yet possible in asthma.
• Allergy (Atopy) • Increasing evidence indicates that allergic sensitization is the most
• Airway hyperresponsiveness common precursor to the development of asthma.
• Obesity and low birthweight • As sensitization can occur antenatally, much of the focus of
3. Genes primary prevention will likely be on perinatal interventions.
(2) Environmental factors Secondary prevention is employed after primary sensitization to
1. Allergens allergen(s) has occurred, but before there is any evidence of
• Inhalations disease.
• Foods • The aim is to prevent the establishment of chronic, persistent
2. Respiratory infections disease in people who are susceptible and who have early signs of
• Virus the disease.
• Mycoplasma, Chlamydia • This is currently being investigated in asthma.
3. Air pollution • Secondary prevention of asthma is likely to focus very specifically
• Passive and active smoking on the first year or two of life.
• Indoor and outdoor air pollutants Tertiary prevention involves avoidance of allergens and nonspecific
• Others triggers when asthma is established.
4. Others • The goal is to prevent exacerbations or illness that would
• Weather changes otherwise occur with exposure to identified allergens or irritants.
• Exercise and hyperventilation • It is considered that tertiary prevention should be introduced when
• Extreme emotional expression the first signs of asthma have occurred.
• Drugs • However, increasing evidence suggests that the histopathology of
• Menstruation the disease is fully established by the time asthma symptoms
• Respiratory complications occur.


322 N Kondo et al.

Table 5 Management of exacerbations in hospital (6–15years)

Mild Moderate Severe Respiratory failure
Initial b2-agonist inhalation Repeat b2-agonist inhalation† Admit to hospital Admit to hospital
O2 inhalation (SpO2 <95%) Repeat b2-agonist inhalation† Continuous isoproterenol
O2 inhalation inhalation
i.v. drip O2 inhalation
Systemic glucocorticosteroids i.v. drip
(i.v.) Repeat systemic
Aminophylline (d.i.v.) glucocorticosteroids (i.v.)
Aminophylline (d.i.v.)
Additional Repeat b2-agonist Systemic glucocorticosteroids Continuous isoproterenol Continuous isoproterenol
inhalation† (i.v. or p.o.) inhalation inhalation
and/or Repeat systemic Correct acidosis
Aminophylline (d.i.v.) glucocorticosteroids (i.v .) Intubation
Consideration for admission to Mechanical ventilation
hospital Anesthetics (consideration)
†
Every 20–30 min, max 3 times. d.i.v., intravenous drip infusion; i.v., intravenous; p.o., per os; SpO2, oxygen saturation.

Table 6 Management of exacerbations in hospital (2–5years)

Initial b2-agonist Repeat b2-agonist inhalation† Admit to hospital Admit to hospital
inhalation O2 inhalation (SpO2 <95%) Repeat b2-agonist inhalation† Continuous isoproterenol
Aminophylline (d.i.v.)‡ glucocorticosteroids (i.v.)
Aminophylline (d.i.v.)‡
Additional Repeat b2-agonist Systemic glucocorticosteroids Continuous isoproterenol Continuous isoproterenol
inhalation† (i.v. or p.o.) inhalation inhalation
and/or Repeat systemic Correct acidosis
Aminophylline (d.i.v.)‡ glucocorticosteroids (i.v.) Intubation
Consideration for admission to Mechanical ventilation
hospital Anesthetics (consideration)
†
Every 20–30 min, max 3 times. ‡A well-informed pediatrician is required. d.i.v., intravenous drip infusion; i.v., intravenous; p.o., per os; SpO2,
oxygen saturation.

Table 7 Management of exacerbations in hospital (<2 years)

Initial b2-agonist Repeat b2-agonist inhalation† Admit to hospital Admit to hospital
inhalation O2 inhalation (SpO2 <95%) Repeat b2-agonist inhalation† Continuous isoproterenol
glucocorticosteroids (i.v.)
Additional Repeat b2-agonist Admit to hospital Continuous isoproterenol Intubation
inhalation† Systemic glucocorticosteroids inhalation Mechanical ventilation
(i.v. or p.o.) Repeat systemic Aminophylline (d.i.v.)
i.v. drip glucocorticosteroids (i.v.) (consideration)‡
Aminophylline (d.i.v) Aminophylline (d.i.v.) Anesthetics (consideration)
(consideration)‡ (consideration)‡
†
Every 20–30 min. max 3 times. ‡Exercise caution. A well-informed pediatrician is required. d.i.v., intravenous drip infusion; i.v., intravenous;
p.o., per os; SpO2, oxygen saturation.



respiratory failure.14 If the respiratory condition fails to improve, need for b2-agonists; (ii) no symptoms, including nocturnal
endotracheal intubation and mechanical ventilation must be con- symptoms; (iii) no absence from school classes; (iv) no limita-
sidered. Oxygen inhalation can also be considered during mod- tions on activities, including exercise; (v) minor PEF circadian
erate attacks, and the SpO2 should be maintained at 95% or variation; (vi) normal PEF; and (vii) normal airway hypersensi-
higher (Tables 5–7). tivity (no exacerbation despite exercise or cool air aspiration).
The therapy regimen can also be utilized for infantile asthma, The final aim is the remission and cure of the asthma.
except for the use of aminophylline. When administering When satisfactory asthma control is maintained for several
aminophylline by drip infusion, theophylline metabolism varies weeks or months, the treatment can be stepped down carefully, as
according to fever and other factors. The serum theophylline long as the symptom-free condition is maintained. At each step-
concentration should therefore be monitored as closely as pos- down, the b2-agonist use should be reduced first. If poor control
sible, and the dosage should be corrected to 210 mg/mL. It is is observed, the treatment should be immediately stepped up.
assumed that infantile asthma patients are usually hospitalized in Once satisfactory control of asthma is obtained, treatment can be
the middle of an attack, and steroid administration, fluid therapy cautiously stepped down again.
and continuous i.v. infusion of aminophylline should be consid- As severity is changed by the therapies administered (appar-
ered with caution to avoid overdosing the patient. ent severity), the actual severity should be determined consider-
ing the therapies, as shown in Table 11.
Medication plan for long-term management of In JPGL 2008, the Japanese Pediatric Asthma Control
childhood asthma Program (JPAC) and Childhood Asthma Control test (C-ACT)
The medication plan in the JPGL 2008 as well as the JPGL 2005 are shown for the judgment of a successful long-term
is divided into three age brackets: older children, younger chil- management.15,16
dren, and infants. The medication plan for long-term manage-
ment was simplified and reconstructed in the JPGL 2008 and Treatment of intermittent asthma (step 1)
inhaled corticosteroids (ICS) and other anti-inflammatory drugs In intermittent asthma, symptomatic therapy is administered to
are the recommended treatment options (Tables 8–10). each patient (Tables 8–10).
An important factor in the long-term medication plan is
continuous monitoring in order to control asthma symptoms. Treatment of mild persistent asthma (step 2)
Regular follow-up monitoring should be performed every 1 or 2 In older children, ICS are used as the first-choice medication, and
months, including a record of symptoms in an asthma diary, 100 mg/day of fluticasone propionate (FP) or hydrofluoroalkane
measurement of PEF, sleep and exercise habits, and the (HFA)-beclomethasone dipropionate (BDP) should be adminis-
frequency of b2-agonist use. tered twice daily (morning and night) using auxiliary equipment
The control of childhood asthma can be achieved in almost all such as a mask (Table 8). Leukotriene receptor antagonists
patients. Successful control is defined as follows: (i) a minimal (LTRA) and/or disodium cromoglycate (DSCG) are used alone

Table 8 Long-term asthma management (6–15 years)

Step 1 Step 2 Step 3 Step 4
Basic Symptomatic therapy ICS ICS ICS
(FP or BDP (FP or BDP 100–200 mg/day) (FP or BDP 200- 400 mg/day)
100 mg/day)
or plus one or more
• LTRA† • LTRA†
and/or • Sustained-release theophylline (p.o.)
• DSCG • DSCG
• LABA
(tape, p.o. or LABA inhalation)
Or
SFC (100/200 mg/day) only
Additional • LTRA† Sustained-release plus one or more Glucocorticosteroids (p.o.)
theophylline (p.o.)
and/or • LTRA† (Short-term consideration)
• DSCG • Sustained-release theophylline (p.o.) Hospitalization at a medical institution
• DSCG (consideration)
• LABA
(tape, p.o. or LABA inhalation)
or
SFC (50/100–100/200 mg/day) only
†
There are anti-allergic drugs such as histamine H1 antagonists and Th2 cytokine inhibitors other than LTRA. BDP, beclomethasone dipropi-
onate; DSCG, disodium cromoglycate; FP, fluticasone propionate; ICS, inhaled corticosteroids; LABA, long-acting b2-agonists; LTRA, leukotriene
receptor antagonist; p.o., per os; SFC, salmeterol/fluticasone propionate combination.


324 N Kondo et al.

Table 9 Long-term asthma management (2–5 years)

Basic Symptomatic • LTRA† ICS (FP or BDP 100–150 mg/day , ICS (FP or BDP 150–300 mg/day,
therapy
and/or BIS 0.5 mg/day) BIS 1.0 mg/day)
• DSCG‡ plus one or more
or • LTRA†
ICS (FP or BDP • DSCG‡
50–100 mg/day,
BIS 0.25 mg/day) • Sustained-release theophylline (p.o.)§
• LABA (tape, p.o. or
LABA inhalation)
Additional • LTRA† • Sustained-release plus one or more
theophylline (p.o.)§
and/or • LTRA†
• DSCG • DSCG‡
• Sustained-release theophylline (p.o.)§
• LABA (tape, p.o. or
LABA inhalation)
†
There are anti-allergic drugs such as histamine H1 antagonists and Th2 cytokine inhibitors other than LTRA. ‡If necessary, + b2-agonists
(0.05 mL–0.1 mL). §Be careful of side-effects. BDP, beclomethasone dipropionate; BIS, budesonide inhalation suspension; DSCG, disodium
cromoglycate; FP, fluticasone propionate; ICS, inhaled corticosteroids; LABA, long-acting b2-agonists; LTRA, leukotriene receptor antagonist;
p.o., per os.

or in combination with others, based on symptoms.17,18 Sustained- (BIS) should be used. If a poor response to these therapies is
release theophylline (SRT) is recommended as an option. observed, SRT should be considered (Table 9). The treatment for
In younger children (aged 2–5 years), LTRA, 50–100 mg/day infants <2 years old is shown in Table 10. LTRA and/or DSCG
FP or BDP or 0.25 mg/day budesonide inhalation suspension are used as first-choice medication. In the JPGL 2008 as well as

Table 10 Long-term asthma management (<2 years)

Basic Not necessary • LTRA • ICS (FP or BDP 100 mg/day, • ICS (FP or BDP 150–200 mg/day,
(symptomatic and/or BIS 0.25–0.5 mg/day) BIS 0.5–1.0 mg/day)
therapy)
• DSCG (2–4 times/day)† plus one or more
• LTRA
• DSCG (2–4times/day)†
Additional • LTRA • ICS (FP or BDP 50 mg/day, plus one or more • b2-agonists (tape or p.o.)
and/or BIS 0.25 mg/day) • LTRA • Sustained-release theophylline‡
• DSCG • DSCG (2–4times/day)† (consideration) (6 months<)
(2–4 times/day)
• b2-agonists (tape or p.o.) (serum conc. 5–10 mg/mL)
• Sustained-release theophylline‡
(consideration) (6 months<)
(serum conc. 5–10 mg/mL)
†
If necessary, + b2-agonists (0.05 mL–0.1 mL). ‡Exercise caution. Steps 3 and 4 should be carried out by the pediatricians specializing in
allergies. BDP, beclomethasone dipropionate; BIS, budesonide inhalation suspension; DSCG, disodium cromoglycate; FP, fluticasone propionate;
ICS, inhaled corticosteroids; LTRA, leukotriene receptor antagonist; p.o., per os.

Table 11 Apparent severity and actual severity of asthma

Apparent severity Actual severity (severity considering current therapies administered)
determined on the basis of
current symptoms Step 1 Step 2 Step 3 Step 4
Intermittent P Intermittent P Mild P Moderate P Severe P
Mild P Mild P Moderate P Severe P Severe P
Moderate P Moderate P Severe P Severe P Very severe P
Severe P Severe P Severe P Severe P Very severe P
P, persistent.



JPGL 2005, SRT is omitted owing to the possibility of side- erbation of asthma. Respiratory syncytial virus and parainfluenza
effects, which occur more frequently in infants. Theophylline virus are the most common pathogens of bronchiolitis.21
administration is not recommended for children <6 months of age The onset of infantile asthma occurs at <2 years of age, and
because there is no clear evidence of its effectiveness and safety, the disease may become a chronic condition after its establish-
or for children with fever or convulsive diseases. In addition, the ment. Moreover, patients with infantile asthma cannot subjec-
recommended dosage of ICS is 50 mg/day FP or BDP, or tively complain of respiratory failure, and symptoms can be
0.25 mg/day BIS. If a poor response to these drugs is observed, observed only objectively. Therefore, early diagnosis and inter-
the inhalation of a combination of 2 mL of liquid DSCG and vention are required in infancy. The management in a medical
0.05–0.1 mL 0.5% salbutamol solution using a nebulizer is rec- facility for acute attacks and the medication plan for long-term
ommended in younger children or infants. BIS is now available management in infants (infantile asthma) are mentioned above.
for younger children and infants.
Exercise-induced asthma
Treatment of moderate persistent asthma (step 3 )
Exercise-induced asthma (EIA) is an important symptom to be
ICS should be used regularly; 100–200 mg/day FP or BDP in aware of in the management of childhood asthma. EIA often
older children, 100–150 mg/day FP or BDP, or 0.5 mg/day BIS in occurs in patients with severe or uncontrolled asthma, in response
younger children, and 100 mg/day FP or BDP, or 0.25–0.5 mg/ to persistent extreme exercise, and its onset can occur in either
day BIS in infants. In children who have frequent asthma symp- cool or dry air. Children are often very active both at school and
toms despite regular treatment with ICS, additional treatment at home, and the occurrence of EIA may damage their quality of
with LTRA, SRT, or DSCG (+ b2-agonist, if necessary, in life or may cause them to avoid exercise. It is therefore important
younger children or infants) should be considered, regardless of that patients, parents, and teachers have a sufficient understand-
age. In older and younger children, if symptoms persist, long- ing of the mechanism and characteristics of EIA. It is also impor-
acting b2-agonist in the oral or tape forms or long-acting tant to understand that the proper management and the
b2-agonist (LABA) inhalation should be administered at continuation of appropriate physical exercise can lead to an
bedtime.19 improvement in EIA.22
In older children, salmeterol fluticasone propionate combina-
tion (SFC) is also available (Table 8). In infants, if symptoms Asthma during adolescence
persist, a tape or oral b2-agonist is recommended.
The characteristics of asthma in the period from adolescence to
Treatment of severe persistent asthma (step 4 ) young adulthood include a decreasing response to medication
The dosage of ICS should be increased in cases of severe asthma. therapy; a risk of transitioning to adult asthma; an adverse effect
The inhalation of 200–400 mg/day FP or BDP in older children, on menstruation; a disturbed lifestyle due to psychological stress
150–300 mg/day FP or BDP, or 1.0 mg/day BIS in younger chil- related to family, friendships, school work, and employment;
dren, and 150–200 mg/day FP or BDP, or 0.5–1.0 mg/day BIS for lower treatment compliance rates; and an increased mortality rate
infants is recommended. LTRA, SRT, or DSCG (+ b2-agonist, if of asthma.23
necessary, in younger children or infants) should be added regu- The check points for clinicians treating patients with adoles-
larly as a concomitant treatment, on the basis of the symptoms. In cent asthma are as follows: monitoring the patient to avoid irregu-
younger children and older children, LABA (tape, oral, or inha- lar visits to the clinic, attention to lapses in compliance regarding
lation) can be administered. In older children, SFC is also avail- medication use, attention to the abuse of b2-agonist metered-
able. If symptoms persist in older children, the use of short-term dose inhalers, clarification of the transition period in moving
oral prednisolone should be considered. If symptoms persist in from pediatrics to internal medicine, re-evaluation regarding
infants, an oral or tape b2-agonist can be administered and SRT whether or not to use ICS in patients not currently inhaling ICS,
could be considered. However, SRT should be used carefully. and maintenance of the relationship between physician and
patients by providing sufficient information on available medica-
Infantile asthma tion and medication plans.
Infantile asthma, which is defined as asthma in children aged <2 It is important to improve treatment compliance through
years in JPGL 2008, should be identified because infantile effective patient education with suitable explanations of asthma
asthma patients have special characteristics not only in anatomy and individual treatment plans. Physicians also need to establish
but also in pathophysiology. In comparison to older children, the a good partnership with their patients.
internal airway is narrower and there is less lung flexibility and
contractility in younger children.20 Moreover, airflow limitation Asthma death
is more likely in young children than older children owing to The asthma mortality rate in patients aged 5–34 years has risen
factors such as less smooth muscle in airways, hyperplasia of dramatically twice in previous years. The asthma mortality rate
mucus secretion, and limited breathing movement owing to a significantly increased in patients aged 10–14 years during the
horizontally oriented diaphragm. Airflow limitation induces rapid 1960s and had a sevenfold increase in male subjects. During the
exacerbation of asthma symptoms in younger children. Respira- 1980s the rate increased threefold in patients aged 15–29 years,
tory viral infections in infancy influence both the onset and exac- and this increase continued until 1990 before decreasing abruptly


326 N Kondo et al.

in 1995. The asthma mortality rates per 100 000 individuals were methods and same districts. Jpn. J. Pediatr. Allergy Clin. Immunol.
0.2 (male) and 0.1 (female) in patients aged 5–19 years 2003; 17: 255–68.
10 Nishima S, Chisaka H, Fujiwara T et al. Surveys on the prevalence
in 2007.
of pediatric bronchial asthma in Japan: a comparison between the
Factors contributing to the increase in asthma mortality rate 1982, 1992, and 2002 surveys conducted in the same region using
include delays in receiving medical care, and sudden and unex- the same methodology. Allergol. Int. 2009; 58: 37–253.
pected worsening of symptoms. The causes of delays in receiving 11 Hanrahan JP, Tager IB, Segal MR et al. The effect of maternal
medical care include a misunderstanding of asthma severity by smoking during pregnancy on early infant lung function. Am. Rev.
Respir. Dis. 1992; 145: 1129–35.
patients or families and an excessive dependence on b2-agonist
12 Weiss ST, Tager IB, Munoz A, Speizer FE. The relationship of
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Conclusion 13 Global Initiative for Asthma. Global Strategy for Asthma Manage-
The JPGL 2008 is a guideline that provides recommendations for ment and Prevention. NHLBI/WHO Workshop Report. GINA2002.
National Institute of Health, National Heart, Lung , and Blood
standard therapies for childhood asthma under the present con-
Institute, Bethesda, 2002.
ditions in our country, and we emphasize that it is not a textbook 14 Iikura Y, Matsumoto T, Fujita K et al. Continuous isoproterenol
aimed at therapeutic standardization. During asthma treatment inhalation therapy in children with severe asthmatic attack.
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of the Japanese pediatric asthma control program (JPAC).
J. Pediatr. Allergy Clin. Immunol. 2008; 22: 135–45.
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