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Pediatrics International (2014) 56, 441450 doi: 10.1111/ped.12389

Guideline

Japanese pediatric guideline for the treatment and management of

bronchial asthma 2012

Yuhei Hamasaki,1,2 Yoichi Kohno,2,4 Motohiro Ebisawa,2,5 Naomi Kondo,2,3 Sankei Nishima,2 Toshiyuki Nishimuta,2
Akihiro Morikawa,2 Yukoh Aihara,2 Akira Akasawa,2 Yuichi Adachi,2 Hirokazu Arakawa,2 Toshiichi Ikebe,2 Kunio Ichikawa,2
Toshishige Inoue,2 Tsutomu Iwata,2 Atsuo Urisu,2 Yukihiro Ohya,2 Kenji Okada,2 Hiroshi Odajima,2 Toshio Katsunuma,2
Makoto Kameda,2 Kazuyuki Kurihara,2 Tatsuo Sakamoto,2 Naoki Shimojo,2 Yutaka Suehiro,2 Kenichi Tokuyama,2
Mitsuhiko Nambu,2 Takao Fujisawa,2 Takehiko Matsui,2 Tomoyo Matsubara,2 Mitsufumi Mayumi,2 Hiroyuki Mochizuki,2
Koichi Yamaguchi2 and Shigemi Yoshihara2
1
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, 2Japanese Society of Pediatric Allergy and Clinical
Immunology, 3Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, 4Department of Pediatrics,
Graduate School of Medicine, Chiba University, Chiba and 5National Hospital Organization, Sagamihara National Hospital,
Kanagawa, Japan

Abstract A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published
in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as
maintaining a well-controlled level for an extended period in which the child patient can lead a trouble-free daily life,
not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic
goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii)
educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily
life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other
symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous
versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special
attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic
asthmatic conditions after the disease is established.

Key words asthma, asthma exacerbation, guideline, long-term management.

The Japanese Society of Pediatric Allergy and Clinical Immunol-
ogy (JSPACI) published the first guideline for childhood asthma
(Japanese pediatric guideline for the treatment and prevention of
bronchial asthma [JPGL]) in the year 2000. It was revised three
times (2002, 2005, 2008), each in response to the progress in the
strategy of asthma management and also to the introduction of
new medications into clinical practice.1,2 Also, the mortality from
asthma-related events has been in decline. During more than 3
years since the last revision (JPGL2008), asthma mortality in the
pediatric age group showed a further decrease. The year 2010 had
only 10 patients younger than 19 years of age who died from
asthma-related events. The JPGL thus plays an important role in
the treatment and management of childhood asthma in this
country.
From the therapeutic point of view, the concept of controlling
asthma-related symptoms at a satisfactory level has been
accepted as an important strategy for long-term asthma manage-
Correspondence: Yuhei Hamasaki, MD, Department of Pediatrics,
Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga-City
849-8501, Japan. Email: hamasaki@cc.saga-u.ac.jp
Received 19 March 2014; accepted 1 May 2014.
ment.3 In the new version of the guideline, JPGL2012, this inter-
nationally adopted concept is accepted as mostly valid in Japan as
well; however, we pediatricians should always set our ultimate
goal at a higher level.4
Definition, pathophysiology, diagnosis
and classification
Childhood asthma is defined as a respiratory disease that pre-
sents repeated wheezing, dyspnea and prolonged expiration
time by paroxysmal airway constriction. Although these symp-
toms usually resolve or disappear in time without any treatment
or by medical intervention, death occurs on rare occasions.
Airway constriction is caused by airway smooth muscle con-
traction, submucosal edema and hyper-excretion from mucosal
glands. Fundamental pathophysiology is airway hyper-
responsiveness closely associated with chronic airway inflam-
mation that results in irreversible structural changes, such as
smooth muscle hyperplasia, mucosal fibrosis and thickening of
the basement membrane (airway remodeling). Childhood
asthma is considered to develop from genetic traits in conjunc-
tion with environmental factors.5 In a large population of

2014 Japan Pediatric Society

442 Y Hamasaki et al.
asthma patients, immunoglobulin (Ig)E-mediated allergic reac-
tion is an initial step of airway inflammation that induces infil-
tration of inflammatory cells, such as neutrophils, Th2
lymphocytes, mast cells and eosinophils, which in turn release
various cytokines, chemokines and chemical mediators.612
Once airway hyper-responsiveness is established, various exac-
erbating factors, including tobacco smoke, cold air, and virus
infection, can cause asthma symptoms to surface; that is, symp-
toms associated with airway constriction and airflow limitation.
Although it has been reported that airway remodeling is found
in childhood asthma, it is not clear whether the remodeling is
the result of chronic inflammation or it develops by other inde-
pendent mechanisms.1315
A diagnosis of childhood asthma is made on the basis of the
patients history, clinical symptoms, respiratory functions and
allergic predisposition, after exclusion of other respiratory and
cardiac diseases indicating similar clinical symptoms and signs.
Childhood asthma is a heterogeneous disease that presents a
variety of pathophysiological conditions. In most of the patients
with childhood asthma, specific IgE antibodies to airborne anti-
gens are elevated (atopic asthma), while in some patients those
specific antibodies are not found (non-atopic asthma). In Japan,
mites in house dust are the most common and significant antigens
in atopic asthma. Recently, however, different asthma phenotypes
in the infantile period have been discussed. Martinez et al. classify
wheezing infants into three subtypes: transient early wheezers,
non-atopic wheezers and IgE-associated wheezers.16 Brand et al.,
on the other hand, classify wheezes that infants present with into
two subtypes: multi-trigger wheeze and episodic (viral-induced)
wheeze.17 In JPGL2012, a diagnosis of infantile asthma is made
when an episode of wheezing in the expiratory phase occurs three
times independently, regardless of complications due to respira-
tory infection. Infantile asthma based on the JPGL may therefore
include various pathophysiological conditions.
Asthma severity
In asthma severity, JPGL2012 follows the classification of the
previous version, JPGL2008, which consists of intermittent, mild
persistent, moderate persistent, and severe persistent asthma.
Asthma severity is basically evaluated in the absence of control-
ler (for long-term management) drugs. Long-term management
in the JPGL2012 guideline is divided into four steps that match
the respective ranks of the severity of asthma. If controller drugs
are already prescribed, the true asthma severity should be
determined with the present treatment taken into consideration.
For example, even if the apparent severity of a patient in
treatment step 2 is determined as mild persistent, the true
severity should really be moderate persistent, which is what their
intersection point mild persistent asthma and step 2 represents
(Tables 1,2).
A comparison of ranks of asthma severity between JPGL2012
and international guidelines, such as those by the Global Initia-
tive for Asthma (GINA) and the Expert Panel Report 3 (EPR-3),
reveals one-stage differences: intermittent, mild persistent, and
moderate persistent in GINA, for example, approximately corre-
spond to mild persistent, moderate persistent, and severe persis-
2014 Japan Pediatric Society
Table 1 Definition of asthma severity in Japanese pediatric guideline
for prevention and treatment of childhood asthma 2012
Asthma severity Symptoms
Intermittent Seasonal cough and/or wheeze (23
times/year). Sometimes dyspnea also, but
recovers soon with SABA
Mild persistent Cough and/or mild wheezing; more than
1/month, less than 1/week. Sometimes
dyspnea also, but it does not continue for
long enough to disturb daily life
Moderate persistent Cough and/or mild wheezing; more than
1/week, but not everyday. Sometimes
progresses to moderate to severe
exacerbation, and disturbs daily life
Severe persistent Cough and/or mild wheezing occurs
everyday. Moderate to severe
exacerbation occurs 12/week, disturbing
daily life and sleep
Most severe persistent Asthma symptoms continue despite the
(sub-class) treatment for severe persistent asthma.
Frequent asthma exacerbations requiring
treatment at emergency room and
hospitalization. Daily life is disturbed to
a large extent
SABA, short-acting -agonist.
tent in the JPGL2012. Severe persistent in the GINA guidelines
and the EPR-3 is close to the most severe persistent sub-group
in the severe persistent rank of the JPGL2012. In the case of
symptoms occurring less than once a week, the grade is taken as
intermittent in both the GINA and EPR-3 guidelines, but it is
mild persistent in the JPGL2012. This scheme makes the JPGL
more useful in the management of childhood asthma because it
helps the clinician diagnose the disease earlier and begin the
treatment with anti-inflammatory drugs sooner.
Epidemiology of childhood asthma
Prevalence of childhood asthma
In this country, the prevalence of asthma as determined by the
American Thoracic Society Division of Lung Diseases is 2.8
6.5%. The prevalence in school children has been increasing in
the last 2 decades according to a survey targeting children at the
same elementary schools in the same area.18 In general, data
shows the following: (i) asthma is more common among
juveniles, particularly among male children, and more specifi-
cally among male infants; (ii) the prevalence varies twofold or
more between regions; and (iii) the prevalence is higher in chil-
dren with a family history of allergic diseases. Children with a
higher body mass index (>90th percentiles) indicate higher preva-
lence of asthma from infancy to adolescence.19 Prevalence of
childhood asthma in Japan is ranked at the middle of various
countries in the world.
Complications
Allergic rhinitis, allergic conjunctivitis, and atopic dermatitis are
common as coexisting allergic diseases caused by the same
mechanism as asthma. Their respective complication rates are
52.8%, 24.4% and 30.9%.20

Table 2 How to identify real asthma severity in patients who are being treated with anti-asthma drugs
Asthma severity decided
from patients symptoms
Step 1
without considering
current treatment-step
Intermittent asthma Intermittent asthma Mild persistent
Mild persistent asthma Mild persistent Moderate persistent
Moderate persistent asthma Moderate persistent Severe persistent
Severe persistent asthma Severe persistent Severe persistent
Death from asthma
Mortality from asthma during childhood has markedly decreased
throughout the years since the publication of the JPGL. The
number of deaths in patients with asthma aged 019 years was 10
in 2010.21 Suffocation is the leading cause of death in acute
asthma exacerbation. Death occurs mostly in patients with severe
persistent asthma, but sometimes patients with moderate or mild
persistent asthma also die from its exacerbation.
Prognosis
The remission rate is lower in cases that are more serious in
severity. Remission is defined as an asymptomatic status without
any treatment. A remission status that continues for 5 years or
longer is considered a clinical cure. Furthermore, if respiratory
function and airway hyper-responsiveness recover to normal
levels, the status is determined as functional cure.
Risk factors and prevention
Childhood asthma is considered to originate from genetic traits
that are prone to produce IgE against allergens. At the same time,
various environmental risk factors are at work, such as respira-
tory infections, exercise, tobacco smoking, weather conditions
and air pollution. Eliminating exacerbating factors from the
immediate environment of each patient is essential to the preven-
tion and management of asthma. It is therefore extremely impor-
tant that a clinician take the patients history carefully to identify
specific allergens and exacerbation factors. Also, for primary
prevention, it is strongly recommended that a patient avoid active
and passive smoking. For secondary and tertiary prevention, the
patient must avoid inhalation of allergens, including house dust
mites, as well as other non-specific irritants, such as tobacco
smoke and chemical substances. Respiratory viral infections,
specifically from rhinovirus and respiratory syncytial virus, are
obvious risk factors for asthma development and asthma
exacerbation.2225
According to some reports, inhaled glucocorticosteroid may
not change the natural course of childhood asthma, but it does
prevent asthma exacerbation, leading to improved quality of life
(QOL).26
Respiratory function and other indices for
diagnosis of asthma and its severity
Respiratory function tests and other objective indices are useful
for diagnosis, decision on treatment step, and monitoring of
control levels. Spirometric measurement, peak flow meter moni-
Pediatric guideline for asthma 443
Current treatment-step
Step 2 Step 3 Step 4
Moderate persistent Severe persistent
Severe persistent Severe persistent
Severe persistent Most severe persistent
Severe persistent Most severe persistent
toring, and blood gas analysis give data with which to assess
airflow limitation. Nitric oxide (NO) concentration in expiratory
breath by NO analyzer and cell classification analysis in sputum
reflects airway inflammation. Airway hyper- responsiveness is
determined by detection of the concentration at which forced
expiratory volume in 1 s (FEV1) starts decreasing when gradu-
ally increasing concentrations of methacholine, acetylcholine or
histamine are inhaled.
The impulse oscillometry analyzer has been introduced into
the practice of pediatric respiratory medicine, which offers the
possibility of detecting segmental airway obstruction.27
Acute exacerbation and treatment
Intensity of asthma exacerbation is determined by respiratory
conditions, including results of respiratory function tests, level of
consciousness, and living matters, such as state of speaking,
feeding and sleeping. Measurement of percutaneous oxygen satu-
ration (SpO2) is another important index that indicates the inten-
sity of asthma exacerbation. The intensity is classified into four
levels: mild exacerbation, moderate exacerbation, severe exacer-
bation, and respiratory failure. The criteria by which to judge
intensity of asthma exacerbation are shown in Table 3.
Treatment of asthma exacerbation at home
First of all, what is important is to fully educate patients and/or
caregivers on how to correctly determine the signs and symptoms
of critical levels of exacerbation. In the absence of signs of
critical levels of exacerbation, the patient can be treated with
inhalation of -2 agonist at home, followed by observation. The
patient should be taken to medical facilities without delay when
dyspnea continues or worsens. Taking earlier, often immediate,
action is recommended in babies and infants. When the patient
exhibits signs of critical levels of exacerbation, he/she should be
taken to emergency hospital, and on the way there, inhalation
treatment with -2 agonist can be repeated every 2030 min.
Prompt action is compulsory in severe exacerbation and respira-
tory failure.
Treatment of asthma exacerbation at the hospital
If a patient is at moderate or severe exacerbation level, or in
respiratory failure, he/she should be treated at the hospital. Once
at the emergency department, the intensity, duration and cause
of exacerbation should be assessed. The patients history of
exacerbation and medical treatment on such occasions is also
evaluated before a treatment plan is determined. For evaluation of
2014 Japan Pediatric Society
444 Y Hamasaki et al.

the exacerbation level, measurements of SpO2 and peak expira-

all criteria be met. As intensity of exacerbation increases, infants present with seesaw breathing, not shoulder breathing. During expiration and inspiration, distention and depression of the chest
Difficult to determine during tachypnea. During strong exacerbation, the expiratory phase is at least twice as long as the inspiratory phase. There are several criteria. It is not required that
Reduced or eliminated
Respiratory failure

tory flow (PEF) are useful besides clinical signs and symptoms.
Drug-based treatment plans according to the intensity of asthma

Unmeasurable
Unmeasurable
Undetermined

Cannot walk
exacerbation are shown in Table 4.

>60 mmHg
Impossible
Impossible
Disturbed
Confused
Marked
Marked

Marked
Moderate intensity of exacerbation

and abdomen repeat like a seesaw. Exclude intentional abdominal breathing. PaCO2, carbon dioxide partial pressure; PEF, peak expiratory flow; SpO2, oxygen saturation.
<91
(+)

(+)
An initial treatment is inhalation of -2 agonist (0.10.3 mL for
babies and infants, 0.30.5 mL for school children) to keep SpO2
higher than 95% with or without oxygen. Beta-2 agonist
68 years old <30/min

is repeatedly inhaled every 2030 min, maximally 3 times.

Severe exacerbation

Pause after one word

Difficulty in walking

Intravenous injection or per-oral administration of gluco-

Slightly lowered

<4160 mmHg
corticosteroid is considered as an additional treatment. Continu-
Bends forward

ous infusion of aminophylline is another option. But to avoid

Possibly(+)
Apparent

Disturbed
Increased

Difficult

side-effects, it is recommended that the serum concentration of

Marked
Marked

Marked

Excited

<30%
<50%
91%
aminophylline be kept at 815 g/mL. The use of aminophylline
is not recommended for infants younger than 2 years of age.
Patients who are 2 years old or over who respond well to the
treatment can be returned home. Regardless of their age, infants
Marked during walking

who do not respond to the treatment should be admitted to the

Moderate exacerbation

15 years old <40/min

Prefers sitting position

Occasionally wake up

hospital for further treatment.

Pause after phrases
Slightly difficult

Slightly excited

Severe intensity of exacerbation and respiratory failure

<41 mmHg
Increased
Apparent
Apparent

Inhalation of -2 agonist with oxygen should begin immediately.

3060%
5080%
9295%

Continuous inhalation of isoproterenol with oxygen is an

(+)

()

(+)

()

alternative treatment when patients do not respond well to

repeated inhalation of -2 agonist. Intravenous injection of
glucocorticosteroid should be simultaneously started and con-
Pause after one sentence

tinuous infusion of aminophylline should also be considered.

212 months <50/min
Mild exacerbation

Endotracheal intubation and mechanical ventilation must be con-

(+) When in a hurry
Slightly increased

sidered when respiratory condition fails to improve.

Almost normal
Can lie down

<41 mmHg
Nonemild

Can sleep

Long-term management by pharmacotherapy

>60%
>80%
96%
Mild

Although the ultimate goal of asthma therapy is to obtain func-

()

()

()

()
()

tional remission and/or cure, maintaining a patient at a well-

controlled (symptom-free) level by suppressing chronic airway
inflammation for a long-enough period is the pragmatic aim of
Lowering of consciousness

the treatment and management of childhood asthma in daily life.

Essential to that end is an adequate management against acute
(Before 2 inhalation)
Prolonged expiration

(After 2 inhalation)

exacerbation and a good strategy to weaken environmental risk

Retractive breathing

<2 months <60/min

factors, like mites in house dust. The most important and effec-
Respiratory rate

During walking

tive strategy, however, is to use anti-inflammatory drugs appro-

During rest
Orthopnea
Table 3 Intensity of asthma exacerbation

Excitation

priately according to the patients asthma severity. As said before,

Wheezing

Cyanosis

Speech

asthma severity is classified into four levels: intermittent, mild

Sleep
Diet

persistent, moderate persistent and severe persistent. These levels

respectively correspond to treatment steps 1, 2, 3 and 4 of the
pharmacotherapy plan for long-term management of childhood
asthma, each step consisting of two categories of therapies,
Impaired consciousness
Normal respiratory rate

namely basal and additional. There are three pharmacotherapy

Feeling of dyspnea

plans for the long-term management of childhood bronchial

Respiratory status

SpO2 (room air)

asthma depending on the patients age: under 2 years old

(babies), 25 years old (infants), and 615 years old (school
Component

Daily life

children) (Tables 58).

PaCO2

Anti-inflammatory drugs are the primary drugs used for the

PEF

long-term management of childhood asthma. Among them are

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 Pediatric guideline for asthma 445

Table 4 Treatment of asthma exacerbation in hospital (215 years old)

Mild exacerbation Moderate exacerbation Severe exacerbation Respiratory failure

Initial 2 agonist inhalation O2 inhalation Hospitalization Hospitalization
treatment (SpO2 > 95%) O2 inhalation, intravenous O2 inhalation, intravenous infusion
Repeated 2 agonist inhalation infusion Continuous isoproterenol inhalation
Repeated 2 agonist Steroid administration
inhalation or Continuous infusion of
Continuous aminophylline
isoproterenol inhalation Consider ventilation under respirator
Steroid administration
Consider continuous
infusion of
aminophylline
Additional Repeated 2 agonist Steroid administration Increased dose of Increased dose of continuous
treatment inhalation (intravenous infusion or oral continuous isoproterenol isoproterenol inhalation
administration) inhalation Ventilation under respirator
Aminophylline (intravenous or Ventilation under Acidosis correction
continuous infusion) respirator Consider anesthesia
Consider hospitalization

Every 2030 min; total up to 3 times. Intravenous infusion of aminophylline should be done by experts for childhood asthma.

inhaled corticosteroid (ICS), leukotriene receptor antagonist
(LTRA), disodium cromoglycate (DSCG), long-acting -agonist
(LABA), and theophylline, of which ICS and LTRA are the
principal drugs. JPGL2012 advises that an identical dose of ICS
should be administered in each treatment step regardless of the
age group. And low, medium and high doses of ICS are to be
applied, respectively, to mild persistent, moderate persistent and
severe persistent cases.
Treatment of intermittent asthma (Step 1)
Patients should be treated with short-acting -agonist as the need
arises in asthma exacerbation. No regular medication with con-
troller drugs is necessary. When symptoms continue and/or res-
piratory functions are unstable, long-term treatment with LTRA
or DSCG may be needed. A step-up in treatment should be
considered if a well-controlled level is not attained.

Table 5 Asthma management in children younger than 2 years of age

Step 1 Step 2 Step 3 Step 4

Basal therapy As needed LTRA and/or DSCG ICS (medium dose) ICS (high dose) possibly add LTRA
Additional LTRA and/or ICS (low dose) LTRA LABA (p.o. or adhesive skin patch)
therapy DSCG LABA (p.o. or adhesive skin patch) Theophylline (maintain at 510 mg/mL in
blood concentration) should be considered
LABA is discontinued when good control level is achieved. LABA (p.o.) is defined as the drugs prescribed as twice a day. Theophylline is not
used for patients under 6 months of age. Theophylline is not recommended for patients with history of convulsion. Prescription of theophylline for
patients with fever should be with caution. Strongly recommend that uncontrollable patients with step 3 or step 4 management strategy be referred
to experts in treating severe childhood asthma. DSCG, disodium cromoglycate; ICS, inhaled corticosteroid; LABA, long-acting -agonist;
LTRA, leukotriene receptor antagonist.

Table 6 Asthma management in children 25 years of age

Step 1 Step 2 Step 3 Step 4

Basal SABA as needed LTRA and/or DSCG ICS (medium dose) ICS (high dose) + (possibly add one or more of
therapy and/or ICS the following drugs)
(low dose) LTRA theophylline
LABA or SFC
Additional LTRA and/or LTRA Consider the following increase ICS/SFC to
therapy DSCG LABA or SFC higher doses or p.o. steroid
theophylline (consider)
LABA is discontinued when good control level is achieved. When SFC is started, oral and percutaneous LABA should be discontinued. Addition
of SFC to ICS is acceptable; however, total dose of steroid is limited within the dose of basal therapy. SFC should be used for patients 5 years or
more of age. Uncontrollable patients with step 3 management strategy should be referred to experts in treating severe childhood asthma. As an
additional therapy at step 4, an increase of ICS/SFC to higher doses or p.o. steroid therapy or long-term admission management should be
considered. Patients should be controlled under an expert in severe childhood asthma treatment. DSCG, disodium cromoglycate; ICS, inhaled
corticosteroid; LABA, long-acting -agonist; LTRA, leukotriene receptor antagonist; SABA, short-acting -agonist; SFC, salmeterol/fluticazone
combined drug.

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446 Y Hamasaki et al.

Table 7 Asthma management in children 615 years of age

Step 1 Step 2 Step 3 Step 4

Basal therapy SABA as needed ICS (low dose) and/or ICS (medium dose) ICS (high dose) + (possibly add one or
LTRA and/or DSCG more of the following drugs)
LTRA theophylline
LABA or SFC
Additional therapy LTRA and/or DSCG Theophylline (consider) LTRA theophylline Consider the following:
LABA or SFC increase ICS/SFC to higher doses or
p.o. steroid
LABA is discontinued when good control level is achieved. When SFC is started, oral and percutaneous LABA should be discontinued. Addition
of SFC to ICS is acceptable; however, total steroid dose is limited within the dose of basal therapy. It is recommended that uncontrollable patients
with step 3 management strategy be referred to experts in treating severe childhood asthma. As an additional therapy at step 4, an increase of
ICS/SFC to higher doses or p.o. steroid therapy or long-term admission management should be considered. Patients should be controlled under an
expert in severe childhood asthma treatment. DSCG, disodium cromoglycate; LABA, long-acting -agonist; LTRA, leukotriene receptor antago-
nist; ICS, inhaled corticosteroid; SABA, short-acting -agonist; SFC, salmeterol/fluticazone combined drug.

Treatment of mild persistent asthma (Step 2) tional drug and theophylline should be used with caution for
Basal therapy for step 2 is a low dose of ICS, LTRA and/or DSCG infant patients under 2 years of age.
for the age groups of 25 and 615 years old. For the 25-year
Asthma-management strategy based on
age group, LTRA is the first choice of these three drugs. For the
control levels
under-2-years age group, ICS is not a basal drug but an additional
drug when control level is unsatisfactory. Theophylline is an Control levels are categorized into three grades: well-controlled,
additional drug only for the age group of 615 years old. partially controlled, and poorly controlled levels. Each level is
characterized by presence or absence of the following four
Treatment of moderate persistent asthma (Step 3) indices: subtle asthma symptoms, apparent exacerbation, poor
Basal therapy for step 3 should be done with a medium dose of activities, and frequent use of -2 agonist as rescue treatment
ICS for all age groups of children. LTRA and/or LABA can be (Table 9). Respiratory function indices, such as PEF and flow-
used as additional drugs when control level is unsatisfactory. ICS volume curve, are useful if available. Treatment step can go up or
can be altered to an ICS+LABA combination formula for patients down, approximately every 3 months, according to the patients
over 5 years old. Theophylline is another additional therapy for asthma control level. Points to consider then: whether or not
the age groups of 25 and 615 years old. Theophylline, drugs are taken as instructed, how well or badly environmental
however, should be used with caution for the age group of risk factors are managed, and other personal risks (Fig. 1).
25 years.
Table 9 Asthma control levels
Treatment of severe persistent asthma (Step 4)
For patients at the severity level of step 4, a high dose of ICS Component of control Classification of asthma control
should be used in combination with LABA, LTRA and/or theo- Well- Partially Poorly
phylline as basal therapy for the age groups of 25 years and controlled controlled controlled
615 years old. An ICS+LABA combination formula instead of Mild symptoms None 1/month 1/week
ICS alone can be used as a basal drug for patients over 5 years 1/week
Apparent symptoms None None 1/month
old. For the under-2-years age group, a high dose of ICS is used Interference with None None 1/month
in combination with LTRA as basal therapy. LABA is an addi- normal activity
SABA use for None 1/month 1/week
symptom control 1/week
Table 8 Dose comparison of inhaled corticosteroid
Control levels are evaluated by conditions during the last 4 weeks.
Manufacture of drug Low dose Medium dose High dose Mild symptoms indicate transient cough and/or wheezing induced by
(mcg) (mcg) (mcg) exercise, laughing and crying. Also included are short periods of
Fluticasone 100 200 400 coughing at the time of awakening and during sleep. Apparent symp-
Beclomethasone 100 200 400 toms indicate continuous coughing and wheezing with dyspnea and
Ciclesonide 100 200 400 chest tightness. >80% of predicted/personal best in PEF and/or forced
Budesonide 200 400 800 expiratory volume in 1 s. 0%~<20% of circadian changes in PEF, and
Budesonide inhalation 250 500 1000 <12% of FEV increase by -2 agonist inhalation are preferable as
solution well-controlled conditions. At the time of assessment, hospital admis-
sion due to severe exacerbation, use of oral glucocorticosteroid for
High-doses of inhaled corticosteroid are preferable to use under the symptom control, and seasonal exacerbation in the last 12 months
control of medical doctors with adequate experience in the manage- should be considered. PEF, peak expiratory flow; SABA, short-acting
ment of childhood asthma. -agonist.

2014 Japan Pediatric Society


Fig. 1 Strategy for long-term management of asthma.
JPGL2012 proposes a strategy for a clinician to maintain the
patient on the well-controlled, or complete, level for a long time,
help the patient keep a high QOL, and prevent airway remodeling
as much as possible.
Well-controlled (complete) level
Well-controlled patients have no apparent asthma exacerbation,
including wheezing and dyspnea, nor limitation of exercise or
activities in daily life. Nor do they present signs and symptoms
that suggest airway hyper-responsiveness, such as transient
coughs, wheezing and/or slight dyspnea, even for a short period.
They have no need to inhale -2 agonist as rescue medication.
Asthma symptom scores on both asthma condition evaluation
charts, the Japanese Pediatric Asthma Control Program and the
Childhood Asthma Control test, are full scores. Daily variations
in PEF are less than 20% and/or keep the score at over 80% of the
patients best score. FEV1 is over 80% of the expected score
and/or improvement after inhalation of -2 agonist is less than
12%.
The set of conditions as above indicates that an adequate
management status is attained. It is important to keep these con-
ditions for as long as possible. A step-down might be considered
Pediatric guideline for asthma 447
when the level of this condition is maintained for more than 3
months without other risk factors, such as an episode of severe
seasonal or periodic exacerbations.
Partially (fairly well) controlled level
Partially (fairly well) controlled patients infrequently have only
subtle asthma symptoms, such as transient coughs, wheezing
and/or slight dyspnea for a limited period when they exercise,
have a big laugh or cry, and wake up in the morning; and phar-
macotherapy is maintained at the present level. These patients
asthma symptoms are indeed controlled fairly well, but it is still
unsatisfactory in pursuit of complete asthma control. A step-up in
the management might be considered if the level cannot be
improved within 3 months, during which patients are adequately
educated about pharmacotherapy, including a re-instruction in
inhalation techniques, and about enlightening procedures to keep
their environment free of risk factors. Diagnosis and other
complications also need to be checked.
Poorly controlled level
Poorly controlled patients frequently (once or more per week)
have subtle asthma symptoms, such as transient coughs,
2014 Japan Pediatric Society
448 Y Hamasaki et al.
wheezing and/or slight dyspnea for a short period, and often
(once or more per month) have an apparent asthma exacerbation.
These patients have difficulties in daily life and need frequently
(once or more per week) to use -2 agonist as rescue medication.
Their management and treatment level are not adequate. Diag-
nosis and evaluation of asthma severity should be re-considered.
Education regarding pharmacotherapy, including re-instruction
of inhalation techniques, should be done, and intervention of
environmental controls is necessary. Step-up of pharmacotherapy
should be considered.
Infantile asthma (patients younger than 2 years
of age)
Children younger than 2 years of age who have experienced
wheezing more than three times on separate occasions are diag-
nosed as having infantile asthma. Wheezing may or may not be
associated with a respiratory infection. In some cases, the diag-
nosis may be difficult to make because children of this age group
often have wheezing associated with respiratory infection. The
reason why we diagnose some infants as having infantile asthma
by somewhat ill-defined criteria is that they should be treated and
managed adequately so that they can enjoy good QOL from as
early a stage as possible.
Patients with infantile asthma have special characteristics, not
only in their anatomy but also in their pathophysiology. The
airway caliber is narrow and lung flexibility and contractility is
less than in older children. Hyper-secretion of mucus, and limited
breathing movements due to a horizontally oriented diaphragm
could easily cause airflow limitation, which induces a rapid exac-
erbation of asthma symptoms. The disease may become a chronic
condition after its establishment in infants in this age group.
Moreover, they cannot subjectively complain of respiratory
failure, and so symptoms must be observed only objectively.
There is therefore a requirement that an early diagnosis must be
made and intervention should be started accordingly for patients
of this age group.
Asthma during adolescence
There are three major problems of asthma in the period from
adolescence to young adulthood: (i) patients show less willing-
ness to adhere to long-term pharmacotherapy; (ii) they increas-
ingly become dependent on -2 agonist; and (iii) they lose
interest in the environmental control associated with exacerba-
tion risk factors against asthma. As a result, it is often the case
that airway remodeling progresses and the mortality rate from
asthma increases. Disturbances in lifestyle due to psychological
stress that is related to friendships, schoolwork, or employment
might contribute to poorer compliance with the doctors advice.
The male-to-female ratio of asthma patients is 1.5:1 before
adolescence, which decreases and comes close to 1:1 during this
period and reverses at around 25 years of age. In severe cases, an
obstructive pattern in flow-volume curve tends to be present and
airway hyper-responsiveness persists during the symptom-free
period, because of the progress in airway remodeling. Patients
having frequent exacerbation in their adolescence possibly carry
the symptoms over into their adulthood. It has been reported that
2014 Japan Pediatric Society
obesity has a close relation to asthma, especially in female
patients. Menstruation may be associated with asthma exacerba-
tion. It is important to improve treatment compliance on the part
of patients in this age group. It may be difficult, but sustained
education and enlightening activities on the patients behalf must
be done with suitable explanations of asthma and individual
treatment plans. Physicians also need to establish a good partner-
ship with their patients.
Check-points for clinicians treating patients with adolescent
asthma are as follows: monitor the patient to keep regular visits to
the clinic; pay attention to lapses in adherence to medication use;
monitor abuses of -2 agonist; clarify the transition of care from
pediatrics to internal medicine; re-evaluate the use or disuse of
ICS; and maintain a good relationship with patients by providing
sufficient information on available drugs and medication plans.
Inhalation and accessory devices
Pharmacotherapy using inhalation devices and accessories is the
mainstay for the long-term treatment and management of asthma
as well as for rescue therapy. It is essential for a clinician to know
what constitutes an adequate selection of inhalation devices and
accessories for patients in each of the different age groups. Have
technical instructions ready that are patient-friendly and/or
caregiver-friendly.
Inhalation techniques should be regularly checked using
actual devices in front of doctors or other health professionals.
Education and enlightening activities
In the management of childhood asthma, how well a patient
adheres to the treatment protocol contributes most to the success
or failure in accomplishing a good control level. Knowledge and
good understanding of the pathophysiology of bronchial asthma,
anti-asthma medications and exacerbating factors help reinforce
good adherence and compliance on the patients part. Explana-
tions according to the developmental stage of the child patient
should be made in easily understandable words. Model struc-
tures, various figures, graphs and illustrations regarding asthma
are useful for better understanding. Education and enlightenment
is intended not only for the patient him/herself but also all
members of the family, especially their main caregivers. The goal
of therapy has to be shared with the patient, family members and
all medical and co-medical staff. Therefore, it is critical to estab-
lish good relationships between doctors and the patients family
members.
Self-monitoring and action plans for the management of
asthma through the behavioral approach can be made available.
Several questionnaires can be utilized to improve the QOL of
patients and family members.2830
Exercise-induced asthma and other activities
Although the pathophysiology of exercise-induced asthma (EIA)
has not been clarified very well, it is proposed that asthma (EIA)
may result from increased osmotic pressure in bronchial epithe-
lium caused by heat and water loss accompanied by hyperventi-
lation, which is in response to hard persistent exercise, especially
under the conditions of dry and cool air. It often occurs in patients

with severe persistent or uncontrolled asthma. It is important for
a clinician and a caregiver to be well aware of the characteristics
of EIA and have a sufficient knowledge to manage it, because
activities of children are often restricted at school, in the nursery
or at home. A fundamental strategy against EIA is to keep a
well-controlled level in daily life by using sufficient pharmaco-
logical treatment and avoidance of exacerbation factors. In order
to prevent EIA, warm-ups are needed before exercise. Preventive
use of medication is also available.3133
Conclusion
A new edition of the JPGL, namely the JPGL2012, was intro-
duced, which reflects recent progresses in asthma treatment and
management for children. The most important change from the
previous version is to introduce an asthma-management strategy
based on the patients asthma control level, the concept of which
was introduced for the first time in the GINA 2006 guidelines. In
this version of the JPGL, well-controlled level is set as com-
pletely controlled status without subtle symptoms, such as even a
short period of wheezing and/or cough. It is important to main-
tain a well-controlled state for a long enough period, which in
turn affords good QOL and may ultimately result in remission
and cure. Anti-inflammatory medicines, that is, ICS (including
ICS+LABA combination and LTRA) are the most important
drugs for the treatment of chronic airway inflammation initiated
with an immediate type of allergic reaction.
A long-term management with anti-inflammatory controller
drugs, elimination of airborne antigens, such as house dust mites,
animal products and molds from the patients living environment,
and enlightenment and education about bronchial asthma are the
three fundamental factors for the treatment and management of
childhood asthma.
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