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Global Strategy for Asthma Management and Prevention
                                   in Children 5 Years and Younger


...
Reviewers                                             Patrick Manning, MD
                                                ...
Global Strategy for Asthma Management and Prevention
                                       in Children 5 Years and Younge...
PREFACE

Each year, the Global Initiative for Asthma (GINA) updates its                            B, C, and D) according ...
during pregnancy and/or lactation, pollutants (particularly
                  INTRODUCTION                                ...
POLLUTANTS                                                            PSYCHOSOCIAL FACTORS
Maternal smoking during pregnan...
SYMPTOMS                                                            CLINICAL HISTORY
Symptoms in this age group that may i...
DIFFERENTIAL DIAGNOSIS                                            Data from a U.S. cohort study6 led to the description of...
ASTHMA EDUCATION                                                    Although exacerbations may occur in children after mon...
Table 2. Levels of Asthma Control in Children 5 Years and Younger*

           Characteristic                         Cont...
Controller Medications                                                 centage of patients experiencing an asthma attack w...
Oral and systemic glucocorticosteroids                           TREATMENT STRATEGY
Because of the side effects associated...
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
Gina Under5 Report
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Gina Under5 Report

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Gina Under5 Report

  1. 1. CO PY RI GH TE D MA TE RI AL , DO NO TA ® LT ER OR RE PR OD U CE . GLOBAL STRATEGY FOR THE DIAGNOSIS AND MANAGEMENT OF ASTHMA IN CHILDREN 5 YEARS AND YOUNGER Available at www.ginasthma.org FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  2. 2. CO PY RI GH TE D MA TE RI AL , DO NO TA LT ER OR RE PR OD U CE . Disclaimer: Although the recommendations of this document are based on the best published evidence, it is the responsibility of practicing physicians to consider the cost, benefits and risks of all treatments prescribed in young children, with due reference to recommendations and licensed formulations, dosing, and indications for use in their country. FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  3. 3. Global Strategy for Asthma Management and Prevention in Children 5 Years and Younger Executive Committee (2008) GINA Science Committee Eric D. Bateman, MD, Chair Mark FitzGerald, MD, Chair Cape Town, South Africa Vancouver, BC, Canada CO Louis-Philippe Boulet, MD Peter J. Barnes, MD PY Sainte-Foy, Quebec, Canada London, England, UK RI Alvaro Cruz, MD Neil Barnes, MD GH Salvador, Brazil London, England, UK TE Mark FitzGerald, MD Eric D. Bateman, MD D Vancouver, BC, Canada Cape Town, South Africa MA Tari Haahtela, MD *Allan Becker, MD TE Helsinki, Finland Winnipeg, Manitoba, Canada RI Mark Levy, MD Jeffrey M. Drazen, MD AL London, England, UK Boston, MA, USA , DO Paul O'Byrne, MD *Robert F. Lemanske, Jr, MD Ontario, Canada Madison, WI, USA NO Ken Ohta, MD Paul O'Byrne, MD Tokyo, Japan TA Hamilton, Ontario, Canada LT Pierluigi Paggiaro, MD Ken Ohta. MD, PhD Pisa, Italy Tokyo, Japan ER *Soren Erik Pedersen, MD Soren Erik Pedersen, MD OR Kolding, Denmark Kolding, Denmark RE *Manuel Soto-Quiroz, MD Emilio Pizzichini, MD San José, Costa Rica Florianópolis, Brazil PR Wan-Cheng Tan, MD Helen K. Reddel, MD OD Vancouver, BC, Canada NSW, Australia U CE *Gary W. Wong, MD Sean D. Sullivan, PhD Hong Kong ROC Seattle, WA, USA . Sally E. Wenzel, M.D. Pittsburgh, PA, USA *Heather J. Zar, MD Cape Town, South Africa i *Participants in Panel to develop the report. Also included was Peter D. Sly MD, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia. FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  4. 4. Reviewers Patrick Manning, MD Dublin, Ireland Hans Bisgaard, MD, DMSci Copenhagen, Denmark Yousser Mohammad, MD Gazal Dib, MD Jacque de Blic, MD Samira Mohammad, MD Paris, France Fatmeh Dmeiraoui, MD CO Lattakia, Syria Johan De Jongste, MD Rotterdam, The Netherlands. PY Hugo E. Neffen, MD Santa Fe, Argentina RI Renato Stein, MD GH Rio Grande do Sul, Brazil Lexley M Pinto Pereira, MBBS, MD Trinidad, West Indies TE Stan Szefler, MD Denver, CO, USA Petr Pohunek, MD D Czech Republic MA Göran Wennergren, MD Göteborg, Sweden Young Soo Shim, MD TE Seoul, Korea RI GINA Assembly Members Haluk Turktas, MD AL Submitting Comments Bulent Karadag, MD , Bulent Sekerel, MD DO Carlos E. Baena-Cagnani, MD Hasan Yuksel, MD Cordoba, Argentina Ankara, stanbul, Manisa, Turkey NO Chunxue Bai, MD, PhD Chen Yu Zhi, MD TA Shanghai, China Beijing, P.R.China LT Hisbello da Silva Campos, MD Rio De Janeiro, RJ Brazil ER Motohiro Ebisawa, MD, Ph.D OR Kanagawa, Japan RE Aziz Koleilat, MD Beirut, Lebanon PR Le Thi Tuyet Lan, MD, PhD OD Ho Chi Minh City, Viet Nam U CE Sohei Makino, MD Shigemi Yoshihara, MD . Dokkyo, Japan Eva Mantzouranis, MD Heraklion, Crete, Greece ii FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  5. 5. Global Strategy for Asthma Management and Prevention in Children 5 Years and Younger TABLE OF CONTENTS PREFACE ........................................................................iv Pharmacotherapy........................................................5 Table 3: Choosing an Inhaler Device CO INTRODUCTION ..............................................................1 for Children with Asthma ........................6 PY Controller Medications..............................................7 Comparisons Between Controller Medications .........8 RI I. RISK FACTORS ASSOCIATED WITH DEVELOPMENT OF ASTHMA..........................1 Reliever Medications ................................................8 GH Aeroallergens .............................................................1 Treatment Strategy .....................................................8 TE House Dust Mites .....................................................1 Who Should be Treated............................................8 Companion animal allergens ....................................1 D Selecting Initial Therapy ...........................................8 Cockroaches ............................................................1 MA Table 4: Low Daily Doses of Inhaled Fungi ........................................................................1 Glucocorticosteroids for Children TE Maternal Dietary Avoidance During Pregnancy 5 Years and Younger ...............................8 RI and/or Lactation..........................................................1 Table 5: Asthma Management Approach Based Polluants ....................................................................2 AL on Control for Children 5 Years Microbes and Their Products......................................2 and Younger.............................................9 , DO Psychosocial Factors .................................................2 When Control is not Achieved ..................................9 Other Risk Factors .....................................................2 Duration and Adjustments to Treatment ...................9 NO Summary....................................................................2 Approach to the Child with Intermittent Wheezing Episodes ..................................................................9 TA II. DIAGNOSIS.................................................................2 Acute Excaberbations ...............................................10 Symptoms ...................................................................3 LT Definition ................................................................10 Wheeze ....................................................................3 Home Action Plan for Family/Caregivers ................10 ER Cough.......................................................................3 Assessment of Severity ..........................................11 OR Breathlessness.........................................................3 Table 6: Initial Assessment of Acute Asthma in Clinical History ............................................................3 Children 5 Years and Younger ...............11 RE Tests for Diagnosis and Monitoring .............................3 Indications for Hospitilization .................................11 Therapeutic Trial ......................................................3 Table 7: Indications for Immediate Referral to PR Test for Atopy ...........................................................3 Hospital (if any of the following are present)............................................11 OD Chest Radiography (x-ray) .......................................3 Differential Diagnosis ..................................................4 Emergency Treatment and Pharmacotherapy ........12 U Assessment of Treatment Response......................12 Table 1: Differential Diagnosis of Asthma in CE Children 5 Years and Younger ..................4 Additional Treatment ..............................................12 . Wheezing Phenotypes ...............................................4 Follow-up of Exacerbations ....................................13 Table 8: Initial Management of Acute Asthma in Children 5 Years and Younger .............13 III. MANAGEMENT AND PHARMACOLOGIC TREATMENT ..............................................................4 Asthma Education .......................................................5 IV. SUMMARY: KEY MESSAGES ...............................14 Asthma Control ...........................................................5 Table 2. Levels of Asthma Control in Children 5 V. REFERENCES .........................................................15 Years and Younger ..................................6 iii FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  6. 6. PREFACE Each year, the Global Initiative for Asthma (GINA) updates its B, C, and D) according to the methodology used in previous guidelines for treatment of asthma, the Global Strategy for GINA documents1 (Table A). Because of the relative paucity many of the recommendations are identified as Evidence D, Asthma Management and Prevention, and makes it available of randomized clinical trials in children 5 years and younger, via the GINA Website at www.ginasthma.org. That guideline CO document provides a unified text and a source document for expert opinion. However, in many of these cases, the expert other GINA documents and resources. Each chapter contains, opinion is based on randomized clinical trial data from studies PY where relevant, details and management advice for specific conducted in older children and adults. The GINA Executive RI age groups including children 5 years and younger, children Committee is aware of the trend toward application of older than 5 years, adolescents, adults, and the elderly. Most GRADE2 technology and is developing a system to slowly GH of the differences between these age groups relate to natural make a transition to this methodology. TE history and co-morbidities, but there are also important differ- ences in the approach to diagnosis, measures for assessing D severity and monitoring control, responses to different classes MA of medications, techniques for engaging with the patient and Eric Bateman, MD his/her family in establishing and maintaining a treatment Chair, GINA Executive Committee TE plan, and the psychosocial challenges presented at different RI stages of life. AL Table A. Description of Levels of Evidence In January 2008, the GINA Executive Committee convened a Evidence Sources of Definition , panel of pediatric experts* to prepare a conceptual framework Category Evidence DO for the diagnosis and management of asthma in children 5 A Randomized controlled trials Evidence is from endpoints of (RCTs). Rich body of data. well designed RCTs that years and younger. In this report, Global Strategy for Asthma provide a consistent pattern of NO Management and Prevention in Children 5 Years and findings in the population for which the recommendation Younger, an effort has been made to present the special chal- is made. Category A requires TA substantial numbers of studies lenges that must be taken into account in managing asthma in involving substantial numbers children during the first 5 years of life, including difficulties with of participants. LT diagnosis, the efficacy and safety of drugs and drug delivery ER B Randomized controlled trials Evidence is from endpoints of systems, and the lack of data on new therapies. Approaches to (RCTs). Limited body of data. intervention studies that include only a limited number these issues will vary among populations in the world based of patients, posthoc or OR subgroup analysis of RCTs, or on socioeconomic conditions, genetic diversity, cultural beliefs, meta-analysis of RCTs. In and differences in health care access and delivery. Patients in general, Category B pertains RE when few randomized trials this age group are often managed by pediatricians and gen- exist, they are small in size, eral practitioners who are routinely faced with a wide variety they were undertaken in a PR population that differs from the of issues related to childhood diseases. While this report high- target population of the recom- OD mendation, or the results are lights a number of issues specific to the under-5 age group, the somewhat inconsistent. reader is referred to the Global Strategy for Asthma U Management and Prevention for fuller background on asthma C Nonrandomized trials. Evidence is from outcomes of CE Observational studies. uncontrolled or nonrandomized pathology, pathophysiology, and medications. trials or from observational studies. . Recommendations in this report are made based on the best D Panel consensus judgment. This category is used only in evidence currently available, and are intended to serve as an cases where the provision of initial reference point with the recognition that some recom- some guidance was deemed valuable but the clinical mendations may need to be modified to adapt to the popula- literature addressing the subject was insufficient to tion characteristics and health care resources present in differ- justify placement in one of the ent clinical practice settings. other categories. The Panel Consensus is based on clinical experience or The panel was charged with the responsibility of reviewing the knowledge that does not meet the above-listed criteria. available scientific literature and assigning evidence levels (A, iv *Participants in Panel to develop the report: A. Becker, R. Lemanske, S. Pedersen, P. Sly, M. Soto-Quiros, G. Wong, H. Zar. FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  7. 7. during pregnancy and/or lactation, pollutants (particularly INTRODUCTION environmental tobacco smoke), microbes and their products, and psychosocial factors. However, evidence for avoidance Asthma is the most common chronic disease of childhood measures to prevent asthma is lacking in many cases. and the leading cause of childhood morbidity from chronic disease as measured by school absences, emergency de- AEROALLERGENS partment visits, and hospitalizations3. Asthma typically be- Atopic sensitization to common aeroallergens, especially CO gins in early childhood, with an earlier onset in males than fe- perennial inhalant allergens, is an important risk factor asso- males4-6. Atopy is present in the majority of children with ciated with asthma18. For some children, the earlier in life PY asthma over the age of 3, and allergen-specific sensitization they become sensitized to local allergens the greater their risk RI is one of the most important risk factors for the development for asthma later in life7, especially when sensitization occurs of asthma7. However, no intervention has yet been shown to GH in association with frequent lower respiratory illnesses 8. natural course of the disease8-16 (Evidence A). prevent the development of asthma or to modify the long-term Several types of aeroallergens are particularly important in TE relation to asthma. D Asthma is defined as a chronic inflammatory disorder of the House Dust Mites: A Cochrane analysis questioned the ef- MA airways and is associated with airway hyperresponsiveness fectiveness of house dust mite avoidance for the treatment of that leads to recurrent episodes of wheezing, breathlessness, TE established asthma9. Moreover, there is no evidence that chest tightness, and coughing1. However, in children 5 years anti-house dust mite measures prevent the onset of asthma10-12. RI and younger, the clinical symptoms of asthma are variable AL and non-specific. Furthermore, neither airflow limitation nor Companion Animal Allergens: The relationship between airway inflammation, the main pathologic hallmarks of the exposure and sensitization to allergens from companion ani- , DO condition, can be assessed routinely in this age group. For mals is not clear, and there are insufficent data to recom- this reason, to aid in the diagnosis of asthma in young chil- mend for, or against, the presence of a pet in the home un- NO dren, a symptoms-only descriptive approach that includes the less the child has become sensitized to the pet species13-15, 18. definition of various wheezing phenotypes has been recom- TA mended17. Cockroaches: Exposure to cockroach allergen in the living quarters is associated with the development of sensitization, LT For all patients with a confirmed diagnosis of asthma, the and sensitization to cockroach allergen is associated with an ER goal of treatment is to achieve control of the clinical manifes- increased risk of developing asthma16. tations of the disease, and maintain this control for prolonged OR periods, with appropriate regard to the safety and cost of the Fungi: Sensitization to Alternaria is a major risk factor not treatment required to achieve this goal. Control of asthma only for the development of asthma in children, but also for its RE can be achieved in a majority of children 5 years and severity19,20. Alternaria is usually considered an outdoor younger with a pharmacologic intervention strategy devel- aeroallergen, but outdoor and indoor concentrations may be PR oped in partnership between the family/caregiver and the similar21. OD health care practitioner. As in older children and adults, in- haled therapy constitutes the cornerstone of asthma treatment MATERNAL DIET DURING U in children 5 years and younger. CE PREGNANCY AND/OR LACTATION . At present, there are insufficient data to support a protective effect of any dietary intervention during pregnancy or lacta- I. RISK FACTORS ASSOCIATED WITH tion in preventing asthma or atopic disease 22,23 . THE DEVELOPMENT OF ASTHMA Breastfeeding itself decreases early childhood wheezing syn- dromes associated with upper and lower respiratory infec- Epidemiologic studies have identified a number of risk factors tions. However, although recommended for its general associated with the development of asthma, including (but health benefits, there is little evidence that breastfeeding pre- not limited to) sensitization to aeroallergens, maternal diet vents development of persistent asthma8, 24-26. 1 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  8. 8. POLLUTANTS PSYCHOSOCIAL FACTORS Maternal smoking during pregnancy and exposure to envi- A child’s social environment may play a role in the develop- ronmental tobacco smoke early in life are associated with a ment and severity of asthma41,42. Stress in family or other pri- greater risk of developing wheezing illnesses in childhood27, mary caregivers during the first year of life is associated with as well as with reduced lung function later in life6. Therefore, an atopic profile and wheeze in infants, and is also associ- every effort should be made to avoid exposing children to to- ated with asthma at age 6 to 8 years43. Maternal distress in bacco smoke28. early life may play a role in the development of childhood CO asthma, especially if the distress continues beyond the post- PY Use of biomass fuels in the home has been associated with partum period44. an increased risk of asthma, increased severity of asthma, RI and exercise-induced bronchospasm in children29,30. This pre- OTHER RISK FACTORS GH sents a problem in much of the world where biomass fuels Children born by Cesarean section have a higher risk of such as wood, charcoal, animal dung, and crop residues are TE asthma than those born by vaginal delivery45, particularly used on a daily basis for cooking and/or heating. Outdoor children of allergic parents46. Paracetamol (acetaminophen) D air pollution related to traffic has been shown to trigger use during pregnancy47 and for fever in the child's first year MA wheezing in the first 3 years of life31. of life48 have been associated with increased prevalence of asthma in children. TE MICROBES AND THEIR PRODUCTS RI Wheezing in early childhood is predominately linked to viral SUMMARY AL infections, especially those due to rhinovirus, respiratory sync- Since the contributions of different risk factors to the develop- tial virus (RSV), Boca virus, and metapneumovirus (MPV)32-34. , ment of asthma vary widely in different societies and homes, DO their relative importance overall may be difficult to assess. The impact of bacterial products and their relationship to the Avoidance of some risk factors requires societal and public NO development of asthma is increasingly a focus of interest and health interventions. However, measures to avoid other risk forms part of the so-called “hygiene hypothesis.” Exposure to factors can be implemented by individual concerned parents TA a farming environment in early life has been associated with as part of their personal preventive strategies for asthma, and a reduced risk of asthma and allergy in children compared to LT these include: those who have not grown up on a farm35,36. In this regard, ER exposure to the lipopolysaccaride endotoxin from microor- • Avoid exposures to atmospheric pollution and particularly ganisms encountered in the farming environment appears to tobacco smoke OR • Provide a calm and nurturing environment (Evidence D). be a potential protective factor, particularly in children with • Avoid unnecessary use of antibiotics in young children specific genetic polymorphisms37. RE Since intestinal flora are the largest source of microbial ex- PR posure for most infants and children, the use of probiotics to II. DIAGNOSIS OD modify the composition of intestinal flora has been proposed Making a diagnosis of asthma in children 5 years and as a method for exploiting this asthma-protective effect of mi- younger may be difficult because episodic respiratory symp- U crobes. While probiotics have been shown to be of some CE toms such as wheezing and cough are also common in chil- benefit in the prevention of atopic dermatitis, no impact on dren who do not have asthma, particularly in those younger the development of asthma has been demonstrated38. . than 3 years49,50. Furthermore, it is not possible to routinely assess both airflow limitation and inflammation in this age Although the use of antibiotics also modifies the composition group. Nevertheless, a diagnosis of asthma in young chil- of intestinal flora, the impact of use of antibiotics early in life dren can often be made based largely on symptom patterns on the risk of developing asthma later in life is controver- and on a careful clinical assessment of family history and sial39,40. Based on available data, it is recommended that physical findings. The presence of atopy or allergic sensiti- particularly broad-spectrum antibiotics should be used with zation provides additional predictive support, as early aller- nized indications (Evidence D). circumspection in this young age group, and only for recog- gic sensitization increases the likelihood that a wheezing child will have asthma7. 2 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  9. 9. SYMPTOMS CLINICAL HISTORY Symptoms in this age group that may indicate a diagnosis of For children 5 years and younger with a history of recurrent asthma include wheeze, cough, breathlessness (typically respiratory symptoms; a strong family history of asthma in manifested by patterns of activity limitation), and nocturnal first degree relatives (especially the mother); and/or atopy symptoms/awakenings. presenting as atopic dermatitis, food allergy, and/or allergic rhinitis also make a diagnosis of asthma more likely. Wheeze: Wheeze, the most common symptom associated CO with asthma in children 5 years and younger, has been TESTS FOR DIAGNOSIS AND MONITORING PY strictly defined as a continuous high-pitched sound, some- While no tests diagnose asthma with certainty in young chil- times with musical quality, emitting from the chest during ex- dren, the following may be considered as useful adjuncts in RI piration51. Wheezing occurs in several different patterns but a making a diagnostic decision. GH wheeze that occurs recurrently, during sleep, or with triggers such as activity, laughing, or crying is consistent with a diag- Therapeutic Trial: A trial of treatment with short-acting TE nosis of asthma. bronchodilators and inhaled glucocorticosteroids for at least D ence of asthma (Evidence D). These interventions should be 8 to 12 weeks may provide some guidance as to the pres- Wheezing may be interpreted differently based on the indi- MA vidual observing it (e.g., parent versus clinician), when it is evaluated in terms of how they affect control of daytime and TE being reported (e.g., retrospectively versus in real time), the nocturnal symptoms as well as the frequency of exacerba- environmental context in which it is occurring (e.g., wheeze RI tions requiring increasing doses of inhaled or systemic gluco- may have different presentation patterns in areas of the world corticosteroids. Marked clinical improvement during the AL where parasites with life cycles involving the lung are more treatment and deterioration when it is stopped supports a di- , prevalent), and the cultural context in which it is occurring agnosis of asthma. Due to the variable nature of asthma in DO (e.g., different cultures assign different relative importance to young children, a therapeutic trial may need to be repeated certain symptoms and to diagnosis and treatment of respira- more than once in order to be certain of the diagnosis. NO tory tract diseases in general). Tests for Atopy: Sensitization to allergens can be assessed TA Viral respiratory infections are the most common factors re- using either immediate hypersensitivity skin testing or an in sponsible for acute wheezing episodes in young children, LT vitro method that detects antigen-specific IgE antibody. Skin- and some viral infections (RSV and rhinovirus) are associated prick testing is less reliable for confirming atopy in infants. ER with recurrent wheeze throughout childhood. Since many young children may wheeze with viral infections, deciding Chest Radiograph (X-ray): If there is doubt about the di- OR when the presence of wheezing with infections is truly an ini- agnosis of asthma in a wheezing child, a plain chest radi- tial or recurrent clinical presentation of childhood asthma is ograph may help to exclude structural abnormalities of the RE difficult5. airway (e.g., congenital malformations such as congenital lobar emphysema, vascular ring), chronic infection (e.g. tu- PR Cough: Cough due to asthma is recurrent and/or persistent, berculosis), or other diagnoses. OD and is usually accompanied by some wheezing episodes and breathing difficulties. Nocturnal cough (occurring when Lung function testing, bronchial challenge, and other physi- U the child is asleep) or cough occurring with exercise, laugh- ological tests do not have a major role in the diagnosis of CE ing, or crying in the absence of an apparent respiratory in- asthma in children 5 years and younger due to the inability fection, strongly supports a diagnosis of asthma. The com- of children this age to perform reproducible expiratory ma- . mon cold and other respiratory illnesses are also associated neuvers. Such tests are only possible in specialized centers, with cough. and are undertaken mainly for research purposes. Breathlessness (Terms often used by parents include difficult breathing, heavy breathing, and shortness of breath): Breathlessness that occurs during exercise and is recurrent increases the likelihood of the presentation being due to asthma. In infants and toddlers, crying and laughing are an exercise equivalent. 3 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  10. 10. DIFFERENTIAL DIAGNOSIS Data from a U.S. cohort study6 led to the description of three wheezing phenotypes: transient wheeze (symptoms begin Although a variety of tools have been described above to and end before the age of 3 years), persistent wheeze (symp- aid the clinician in making a diagnosis of asthma in children toms begin before the age of 3 years and continue beyond 5 years and younger, it must be emphasized that a definite the age of 6 years), and late-onset wheeze (symptoms begin diagnosis in this young age group is challenging and has after the age of 3 years). important clinical consequences. Thus, alternative causes CO that can lead to respiratory symptoms of wheeze, cough, The clinical usefulness of the phenotypes described by the an asthma diagnosis is arrived at49 (Table 1). and breathlessness must be considered and excluded before ERS Task Group17 or based on data from the U.S. cohort PY study6 remains a subject of active investigation. Children RI with asthma may have any of these phenotypes, but asthma TABLE 1: Differential Diagnosis of Asthma in GH occurs much more rarely in the episodic wheeze and tran- Children 5 Years and Younger sient wheeze phenotypes compared to the other phenotypes. TE Infections A number of other publications provide additional insights D • Recurrent respiratory tract infections into wheezing phenotypes and their relationship to children 5 • Chronic rhino-sinusitis years and younger with asthma6,52,53. MA • Tuberculosis TE Congenital problems To aid in the early identification, in the clinical setting, of chil- • Tracheomalacia dren 5 years and younger who wheeze and are at high risk RI • Cystic fibrosis • Bronchopulmonary dysplasia of developing persistent asthma symptoms, a number of risk AL • Congenital malformation causing narrowing profiles have been evaluated54-57. One such predictive as- of the intrathoracic airways , • Primary ciliary dyskinesia syndrome sessment, the Asthma Predictive Index (API), is recommended DO • Immune deficiency for children with four or more wheezing episodes in a year • Congenital heart disease and is based on information obtained from the Tucson (USA) NO Mechanical problems Respiratory Study55. One study has shown that a child with a • Foreign body aspiration positive API has a 4- to 10- fold greater chance of developing TA • Gastroesophageal reflux asthma between the ages of 6 and 13, while 95% of children C). The applicability and validation of the API in other coun- LT with a negative API remained free of asthma55,57 (Evidence Neonatal or very early onset of symptoms (associated with ER failure to thrive), symptoms associated with vomiting, or focal tries and clinical situations is awaited. lung or cardiovascular signs, suggest an alternative diagnosis OR and indicate the need for further investigations. RE WHEEZING PHENOTYPES Recurrent wheezing occurs in a large proportion of children III. MANAGEMENT AND PR five years and younger. However, not all of this wheezing in- PHARMACOLOGIC CONTROL OD dicates asthma. Several phenotypes of wheezing disorders in this age group have been recognized in epidemiologic For all patients with a confirmed diagnosis of asthma, the U studies. CE goal of treatment is to achieve control of the clinical manifes- tations of the disease, and maintain this control for prolonged . Early childhood wheezing has been classified by a Task periods, with appropriate regard to the safety and cost of the Group convened by the European Respiratory Society (ERS)17 treatment required to achieve this goal. Control of asthma as either episodic wheeze (wheezing during discrete time pe- can be achieved in a majority of children 5 years and riods, often in association with clinical evidence of a common younger with a pharmacologic intervention strategy devel- cold, with absence of wheeze between episodes) or multiple- oped in partnership between the family/caregiver and the trigger wheeze (wheezing that occurs as episodic exacerba- health care practitioner. As in older children and adults, in- tions as above, but also with symptoms including cough and in children 5 years and younger (Evidence A). haled therapy constitutes the cornerstone of asthma treatment wheeze occurring between these episodes, during sleep or with triggers such as activity, laughing, or crying). 4 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  11. 11. ASTHMA EDUCATION Although exacerbations may occur in children after months Asthma education should be provided to family members of apparent clinical control, the risk is greater in patients and caregivers of wheezy children 5 years and younger whose current control is poor. On the other hand, the “fu- ture risk” of harm caused by excessive doses of medica- (Evidence D). An educational package should contain a when wheeze is suspected to be caused by asthma tions, or inappropriate treatment such as the prolonged use basic explanation about asthma and the factors that influence of high doses of inhaled or systemic glucocorticosteroids, must also be avoided by ensuring that treatment is appro- it, instruction about correct inhalation technique and the im- CO priate and reduced to the lowest level that maintains satis- portance of adherence to the prescribed medication regime, factory current clinical control. PY and a description of how to recognize when asthma control is deteriorating, the medications to administer when this oc- RI Defining satisfactory current clinical asthma control in chil- curs, and when to seek medical assistance. Randomized GH dren 5 years and younger is problematic, since health care controlled trials in older children and adults have demon- providers are almost exclusively dependent on the reports strated that the use of a written asthma management plan TE of the child’s family members and caregivers who might be along with careful verbal explanation of the treatment regime unaware either of the presence of asthma symptoms, or of D can improve asthma control. For children 5 years and the fact that they represent uncontrolled asthma. Moreover, MA younger who cannot reliably perform lung function measure- as with the diagnosis of asthma, lung function testing is not ments, asthma management plans based on the levels of res- TE feasible as a means to monitor control in children of this piratory symptoms have been shown to be just as effective as age. No objective measures to assess clinical control have RI B).. Crucial to a successful asthma education program are a plans based on self-monitoring of lung function58 (Evidence been validated for children younger than 4 years (one such patient-doctor partnership featuring a high level of agree- AL measure has been developed for children aged 4-1161). However, a working scheme based on current expert opin- , regarding the goals of treatment for the child, as well as inten- ment between family or caregiver and healthcare practitioner DO ion presents characteristics of controlled, partly controlled, sive follow-up59 (Evidence D). and uncontrolled asthma for children 5 years and younger NO based on symptoms recognized by family members/care- (Table 2) (Evidence D). givers and the child’s need for reliever/rescue treatment TA ASTHMA CONTROL LT For all patients with a confirmed diagnosis of asthma, the goal of treatment is to achieve control of the clinical manifes- ER tations of the disease and maintain this control for prolonged PHARMACOTHERAPY periods, with appropriate regard to the safety and cost of the Inhaled therapy constitutes the cornerstone of asthma treat- OR for choosing inhalers in children is provided in Table 3. A treatment required to achieve this goal. ment in children 5 years and younger. A general strategy RE The relevance of distinguishing between current control (as pressurized metered-dose inhaler (MDI) with a valved child’s age) is the preferred delivery system62 (Evidence A). spacer (with or without a face mask, depending on the PR assessed by the control or elimination of clinical features of asthma in the recent weeks or months) from “future risk” (the with β 2-agonists. OD This recommendation is based on studies with performed likelihood of future worsening, exacerbations, impaired lung development), and the relationship between these two con- U CE cepts, have not been carefully studied in small children. Spacers come in different designs and, since the dose re- time wheeze, and nighttime β2-agonist use has been found to However, a combination of increased daytime cough, day- ceived may vary considerably from one device to another, . a spacer device that has documented efficacy in young chil- be a strong predictor of an exacerbation in children 5 years dren is recommended. Nebulizers, the only viable alterna- and younger (predicting around 70% of exacerbations, with tive delivery systems in children, should be reserved for the a low false positive rate of 14%60). In contrast, no individual minority of children who cannot be taught effective use of a symptom was predictive of an imminent asthma exacerba- spacer device. tion. This finding indirectly supports the importance of good daily asthma control and the use of composite outcomes in the assessment of asthma control in this age group. 5 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  12. 12. Table 2. Levels of Asthma Control in Children 5 Years and Younger* Characteristic Controlled Partly Controlled Uncontrolled (All of the following) (Any measure (3 or more of features present in any week) of partly controlled asthma in any week) CO Daytime symptoms: None More than twice/week More than twice/week wheezing, cough, (less than twice/week, typically for (typically for short (typically last minutes PY difficult breathing short periods on the order of periods on the order of minutes or hours or recur, but partially RI minutes and rapidly relieved by and rapidly relieved by use of a or fully relieved with use of a rapid-acting rapid-acting bronchodilator) rapid-acting bronchodilator) GH bronchodilator) TE Limitations of None Any Any activities D (child is fully active, (may cough, wheeze, or (may cough, wheeze, or plays and runs without have difficulty breathing during have difficulty breathing during MA limitation or symptoms) exercise, vigorous play, or exercise, vigorous play, or laughing) laughing) TE RI Nocturnal None Any Any symptoms/awakening AL (including no nocturnal (typically coughs during sleep (typically coughs during sleep coughing during sleep) or wakes with cough, wheezing, or wakes with cough, wheezing, , and/or difficult breathing) and/or difficult breathing) DO Need for 2 days/week > 2 days/week > 2 days/week NO reliever/rescue treatment TA *Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate. Although patients with current LT clinical control are less likely to experience exacerbations, they are still at risk during viral upper respiratory tract infections and may ER still have one or more exacerbations per year. OR Table 3: Choosing an Inhaler Device for Children with Asthma RE Age Group Preferred Device Alternative Device PR Younger than Pressurized metered-dose inhaler plus Nebulizer 4 years dedicated spacer with face mask with face mask OD 4-5 years Pressurized metered-dose inhaler plus Pressurized metered-dose inhaler plus U dedicated spacer with mouthpiece dedicated spacer with face mask, CE or . Nebulizer with mouthpiece or face mask Controlled trials in children 5 years and younger are rather lim- from studies in older children and adults, and on expert opin- ited, the patient populations have often not been well charac- ion, the following sections provide recommendations for con- terized with respect to phenotype (including wheezy children troller medications (taken daily on a long-term basis to keep who may or may not have asthma), and different studies have asthma under control) and reliever medications (for use on an used different outcomes and definitions of exacerbations. as-needed basis) for the pharmacologic treatment of asthma in However, based on literature that is available, extrapolations children 5 years and younger. 6 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  13. 13. Controller Medications centage of patients experiencing an asthma attack was not Inhaled glucocorticosteroids significantly reduced, but the need for a course of pred- Efficacy: As in older children, several placebo-controlled nisolone was significantly reduced from 28% to 19% of pa- tients78. Montelukast has also been shown to reduce airway studies of inhaled glucocorticosteroids in children 5 years hyperresponsiveness to methacholine76 or hyperventilation and younger with asthma have found statistically significant with cold dry air79. A randomized, placebo-controlled trial clinical effects on a variety of outcomes, including increased of the addition of montelukast to usual asthma therapy CO lung function and number of symptom-free days, and reduced among 42 children aged 2-580 found that this treatment re- symptoms, need for additional medication, caregiver burden, PY duced the number of days with worsening of asthma symp- (Evidence A). However, the dose-response relationships systemic glucocorticosteroid use, and exacerbations57,63-73 toms in boys but not in girls, the number of days with symp- RI toms in the two groups being 7.8% and 3.5%, respectively. GH have been less well studied. The clinical response may differ comes in young children (Evidence A). However, the role of In summary, leukotriene modifiers improve some asthma out- depending on the specific device used for delivery and the TE child’s ability to use it correctly. With correct use of a spacer leukotriene modifiers as add-on therapy in children 5 years device, twice the recommended initial low dose of inhaled D and younger whose asthma is uncontrolled on inhaled glu- lar, long-term treatment in the majority of patients (Table 4)64,68. glucocorticosteroid results in near-maximum benefits as regu- MA cocorticosteroids has not been specifically evaluated. Safety: No safety concerns have been demonstrated from the TE Use of inhaled glucocorticosteroids for up to 2 years has not use of leukotriene modifiers in young children. almost always return when treatment is stopped57 (Evidence B). been documented to induce remission of asthma; symptoms RI Theophylline AL Safety: The majority of studies evaluating the systemic effects Although a few studies in children 5 years and younger sug- , DO of inhaled glucocorticosteroids have been undertaken in chil- gest clinical benefit from regular use of theophylline, the ef- dren older than 5 years. However, the available data in chil- fects are small and mostly non-significant81. The efficacy of dren 5 years and younger suggest that, as in older children, NO costeroids, and side effects are more common (Evidence D). theophylline is less than that of low-dose inhaled glucocorti- clinically effective doses of inhaled glucocorticosteroids are TA Long-acting inhaled β2-agonists safe and the potential risks are well balanced by the clinical costeroids (Table 4) have not been associated with any clini- benefits57,63,73. Generally, low doses of inhaled glucocorti- Long-acting inhaled β2-agonists (LABAs) are bronchodilators, LT ER considered safe63-73 (Evidence A). However, higher doses cally serious adverse systemic effects in clinical trials and are but as long-term therapy for asthma they are only prescribed in combination with an inhaled glucocorticosteroid and are OR have been associated with detectable systemic effects on long-acting inhaled β2-agonists or combination (LABA/gluco- therefore considered controller medications. The effect of both growth and the hypothalamic-pituitary-adrenal (HPA) RE axis57,63-73. These effects are similar to those reported in stud- corticosteroid) products has not been adequately studied in ies of older children, which find no evidence of long-term clin- PR children 5 years and younger. Formoterol and salmeterol ical impact74,75. Local side effects, such as hoarseness and have shown long-lasting bronchodilatory and bronchopro- OD candidiasis, are rare in children 5 years and younger68. tective effects in this age group82. However, there are no Leukotriene modifiers group on the addition of long-acting inhaled β 2-adrenergic published randomized placebo-controlled trials in this age U Efficacy: Leukotriene modifiers reduce viral-induced asthma CE ing inhaled β 2-agonists cannot be recommended in this age agents to inhaled glucocorticosteroids. Therefore, long-act- . symptoms in children ages 2-5 years with a history of inter- mittent asthma76 by reducing the number of protocol-defined group (Evidence D). exacerbations, but do not reduce the frequency of hospital- izations, use of prednisolone, duration of exacerbations, or Cromolyn and nedocromil sodium days without asthma symptoms. Moreover, no effect on post- A Cochrane Review concluded that there was no beneficial bronchiolitic wheeze or cough is seen following hospitaliza- effect of cromolyn therapy in preschool children83,84 and ne- tion with RSV bronchiolitis77. In a three-month study of chil- docromil has not been studied in preschool children. and rescue β 2-agonist use by approximately 6%. The per- dren with persistent wheeze, montelukast reduced symptoms group (Evidence A). Therefore, cromones cannot be recommended in this age 7 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!
  14. 14. Oral and systemic glucocorticosteroids TREATMENT STRATEGY Because of the side effects associated with prolonged use, oral glucocorticosteroids in young children with asthma The goal of asthma treatment, to achieve and maintain con- trol of the disease, can be reached in a majority of children bations, whether viral-induced or otherwise (Evidence D). should be restricted to the treatment of acute severe exacer- 5 years and younger with a pharmacologic intervention strat- egy86 developed in partnership between the family/caregiver Immunotherapy and the health care practitioner. Although validated tools for CO No studies of immunotherapy for asthma have been per- assessment of asthma control have not been developed for young children, it is recommended that both current impair- PY formed in this age group. Therefore, immunotherapy is not ment (day and night symptoms, activity level impairment, children 5 years and younger (Evidence D). recommended for the treatment or prophylaxis of asthma in RI need for rescue medications) and future risk (likelihood of GH (Table 2) (Evidence B). acute exacerbation in the future) be assessed and controlled Comparisons Between Controller Medications TE In older children and adults, regular treatment with inhaled D Who Should be Treated glucocorticosteroids has been well documented to be clini- Regular controller treatment is normally recommended for MA cally more effective than other controller treatments for asthma. Moreover, they attenuate the decline in lung func- children 5 years and younger whose frequency and severity TE asthma is not controlled (Table 2). tion seen in association with severe exacerbations85. Fewer of asthma symptoms without treatment indicates that their RI comparative studies have been conducted in children 5 years AL and younger. However, two studies of nearly 1,000 chil- dren in this age group86,87 confirmed the superiority of in- Selecting Initial Therapy , points assessing asthma control (Evidence A). haled glucocorticosteroids over cromones for almost all end- DO A low-dose inhaled glucocorticosteroid is recommended as years and younger57,70,88 (Table 4) (Evidence A). the preferred initial treatment to control asthma in children 5 NO Two additional studies compared inhaled glucocorticos- TA teroids with leukotriene modifiers. A one-year, randomized, Table 4: Low Daily Doses* of Inhaled open study compared montelukast with nebulized budes- Glucocorticosteriods for Children 5 Years and Younger LT onide in 400 children; overall measures favored budes- ER onide88. In the second, a blinded, placebo-controlled study Drug µ Low Daily Dose (µ g) of 63 children, only the fluticasone propionate treatment sig- OR Beclomethasone dipropionate 100 nificantly improved symptoms over placebo, whereas mon- lung function after three months89 (Evidence B). telukast did not, and fluticasone propionate also improved RE Budesonide MDI+spacer 200 Budesonide nebulized 500 PR Rapid-acting inhaled β2-agonists are the most effective bron- Reliever Medications OD Ciclesonide † NS chodilators available and therefore the preferred reliever U treatment for asthma in children 5 years and younger. An Fluticasone propionate 100 CE ering reliever therapy62,90 (Evidence A). When delivery is not MDI with spacer is, in most cases, an effective way for deliv- . optimal because of lack of cooperation or distress, or when † Mometasone furoate NS the child is hypoxic, nebulizer therapy is also an option. Triamcinolone acetonide NS Oral therapy is not recommended due to its slower onset of † action and its tendency to produce more side effects. * A low daily dose is defined as the dose which has not been associated There is no evidence that inhaled ipratropium has an impor- with clinically adverse effects in trials including measures of safety. years and younger91 (Evidence A). tant role in the daily management of asthma in children 5 This is not a table of clinical equivalence. †NS = Not studied in this age group. 8 FOR PERSONAL USE ONLY - DO NOT ALTER OR REPRODUCE!

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