Resp_22_3_mayjun2015.indbDiagnosis and management of asthma in
preschoolers: A Canadian Thoracic Society and
Canadian Paediatric Society position paper
Francine M Ducharme MD MSc1, Sharon D Dell MD2, Dhenuka Radhakrishnan MD MSc3, Roland M Grad MDCM MSc FCFP4, Wade TA Watson MD MEd5, Connie L Yang MD MSc6, Mitchell Zelman MDCM7 FM Ducharme, SD Dell, D Radhakrishnan, et al. Diagnosis and
Le diagnostic et la prise en charge de l'asthme chez les
management of asthma in preschoolers: A Canadian Thoracic
enfants d'âge préscolaire : document de principes de la
Society and Canadian Paediatric Society position paper. Can Respir J
Société canadienne de thoracologie et de la Société
canadienne de pédiatrie
Asthma often starts before six years of age. However, there remains uncer- L'asthme fait souvent son apparition avant l'âge de six ans. Cependant, il tainty as to when and how a preschool-age child with symptoms suggestive subsiste des incertitudes relativement à quand et comment un enfant d'âge of asthma can be diagnosed with this condition. This delays treatment and préscolaire ayant des symptômes de type asthmatique peut être diagnostiqué contributes to both short- and long-term morbidity. Members of the avec cette condition. Ceci retarde le traitement et contribue à la morbidité à Canadian Thoracic Society Asthma Clinical Assembly partnered with the court et à long terme. L'Assemblée clinique sur l'asthme de la Société cana- Canadian Paediatric Society to develop a joint working group with the dienne de thoracologie s'est associée à la Société canadienne de pédiatrie mandate to develop a position paper on the diagnosis and management of pour créer un groupe de travail conjoint afin de préparer un document de asthma in preschoolers. principes sur le diagnostic et la prise en charge de l'asthme chez les enfants In the absence of lung function tests, the diagnosis of asthma should be con- d'âge préscolaire. sidered in children one to five years of age with frequent (≥8 days/month) En l'absence de mesures de la fonction pulmonaire, le diagnostic d'asthme asthma-like symptoms or recurrent (≥2) exacerbations (episodes with devrait être envisagé chez les enfants de un à cinq ans ayant des symptômes de asthma-like signs). The diagnosis requires the objective document of signs type asthmatique fréquents (≥8 jours/mois) ou des exacerbations récurrentes or convincing parent-reported symptoms of airflow obstruction (improve- (≥2) (épisodes accompagnés de signes compatibles). Le diagnostic nécessite une ment in these signs or symptoms with asthma therapy), and no clinical documentation objective des signes cliniques ou un compte rendu parental suspicion of an alternative diagnosis. The characteristic feature of airflow convaincant de symptômes d'obstruction des voies respiratoires et de révers- obstruction is wheezing, commonly accompanied by difficulty breathing ibilité de l' obstruction (amélioration suite à un traitement pour l'asthme), ainsi que l'absence de suspicion clinique de tout autre diagnostic. La respiration sif- and cough. Reversibility with asthma medications is defined as direct flante, souvent accompagnée de difficultés respiratoires et de toux, est le signe observation of improvement with short-acting ß2-agonists (SABA) (with cardinal de l'obstruction des voies respiratoires. La réversibilité à la suite de la or without oral corticosteroids) by a trained health care practitioner during prise de médicaments pour l'asthme se définie par l'observation directe par un an acute exacerbation (preferred method). However, in children with no professionnel de la santé compétent, d'une amélioration après l'administration wheezing (or other signs of airflow obstruction) on presentation, revers- ibility may be determined by convincing parental report of a symptomatic 2-agonistes à courte durée d'action (BACA) (accompagnés ou non de cor- ticostéroïdes par voie orale) pendant une exacerbation aigue (méthode diagnos- response to a three-month therapeutic trial of a medium dose of inhaled tique privilégiée). Cependant, chez les enfants qui n'ont pas à l'examen une corticosteroids with as-needed SABA (alternative method), or as-needed respiration sifflante (ni d'autres signes d'obstruction des voies respiratoires), la SABA alone (weaker alternative method). The authors provide key mes- réversibilité peut être déterminée par un compte rendu parental convaincant sages regarding in whom to consider the diagnosis, terms to be abandoned, d'une réponse symptomatique à un essai thérapeutique de trois mois de cortico- when to refer to an asthma specialist and the initial management strategy. stéroïdes inhalés, à dose moyenne, avec un BACA au besoin (méthode diagnos- Finally, dissemination plans and priority areas for research are identified.
tique alternative), ou avec seulement un BACA au besoin (méthode diagnostique alternative moins certaine) est recommandé. Les auteurs présen-tent des messages clés quant aux enfants chez lesquels on doit envisager le Key Words: Asthma; Child; Criteria; Diagnosis; Disease management;
diagnostic, quant aux termes désuets à abandonner, quant aux situations pour Preschool; Therapeutic trial lesquelles on doit orienter l'enfant vers un spécialiste de l'asthme et quant à la stratégie de prise en charge initiale. Enfin, ils décrivent la stratégie de diffusion de ces messages et identifient les domaines de recherche prioritaires. POSITION STATEMENT DEVELOPMENT PROCESS
literature review was conducted and key messages were agreed on by A joint working group was formed with the mandate to develop a unanimous consensus through extensive discussions based on review position paper on the diagnosis and management of asthma in pre- of the evidence and existing guidelines. The completed document was schoolers. The group included academic and community-based pedia- subsequently sent for external review to four experts, as well as the tricians, pediatric respirologists, a pediatric allergist and a family CTS Canadian Respiratory Guidelines Committee, and the Canadian physician with combined expertise in pediatric acute and chronic Pediatric Society Community Paediatrics Committee and Respiratory asthma care, as well as knowledge translation. Health Section Executive. The final document was then approved for The document was developed in accordance with Canadian publication by the CTS Executive and the Canadian Paediatric Thoracic Society (CTS) requirements for a position paper. A scientific Society Board of Directors.
1Departments of Pediatrics and of Social and Preventive Medicine, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec; 2Department of Pediatrics and IHPME, The Hospital for Sick Children, University of Toronto, Toronto; 3Department of Pediatrics, Children's Hospital, London Health Sciences, Western University, London, Ontario; 4Department of Family Medicine, Jewish General Hospital, McGill University, Montreal, Quebec; 5Department of Pediatrics, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia; 6Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia; 7Department of Pediatrics, Queen Elizabeth Hospital, Charlottetown, Prince Edward Island, Dalhousie University, Halifax, Nova Scotia Correspondence and reprints: Dr Francine M Ducharme, Canadian Thoracic Society, Lung Association – National Office, 300-1750 Courtwood Crescent, Ottawa, Ontario K2C 2B5. Telephone 613-569-6411, fax 613-569-8860, e-mail email@example.com Can Respir J Vol 22 No 3 May/June 2015 2015 Pulsus Group Inc. All rights reserved Ducharme et al
Uncertainty exists as to how and when a preschool-age child with symptoms suggestive of asthma can be diagnosed with the condition. 1. Terms such as ‘bronchospasm', ‘reactive airway disease', ‘wheezy The wide spectrum of labels commonly used in preschoolers, denoting bronchitis' and ‘happy wheezer' should be abandoned. either a suggestive pathophysiology (eg, ‘bronchospasm' or ‘reactive 2. Recurrent preschool wheezing can be associated with substantial airway disease'), symptoms (eg, ‘wheeze' or ‘chronic cough'), vague morbidity and may impact long-term health. diagnoses (‘wheezy bronchitis' or ‘happy wheezer') or, possibly, inappropriate diagnoses (eg, repeated ‘bronchiolitis' or ‘recurrent bronchitis or pneumonia') (1), attests to the need for clarity. KEY CRITERIA FOR THE DIAGNOSIS OF ASTHMA
In school-age children and adults, guidelines recommend the use of lung function tests, primarily spirometry, to confirm the diagnosis Asthma is an inflammatory disorder of the airways characterized by (2,3). In children <6 years of age, the forced expiratory manoeuvre episodic or persistent symptoms such as dyspnea, chest tightness, required for spirometry is difficult to perform, and alternative lung wheezing, sputum production and cough, associated with variable air- function tests for preschoolers are limited to a few pediatric academic flow limitation and airway hyper-responsiveness to endogenous or settings or are insufficiently specific. Consequently, there is contro- exogenous stimuli (2). These features, well documented in school-age versy as to when the diagnostic label of ‘asthma' should be applied to children and adults, are presumed to also apply to preschoolers. We preschool-age children. Some experts prefer reserving the diagnosis of propose that the diagnosis of asthma in preschoolers – in whom spi- asthma for children with persistent or atopic symptoms and refer to rometry cannot be readily measured – requires the objective documen- those who have asthma symptoms only with upper respiratory tract tation of signs (or convincingly reported symptoms) of airflow infections (URTIs) as having ‘viral-induced wheezing' (4). Other spe- obstruction and reversibility of airflow obstruction (ie, improvement cialists recommend considering children with either pattern of asthma of signs and symptoms with asthma medication), in the absence of symptoms as having asthma. clinical factors suggestive of an alternative diagnosis (Table 1). Given these issues, we offer a pragmatic approach to confirm the Personal atopy (eg, eczema, food allergy, etc) and family history of diagnosis of asthma in children one to five years of age, and refer read- asthma heighten the suspicion of, but are not necessary for, the diag- ers to the 2012 CTS guideline update (2) for the management of nosis. These diagnostic criteria apply to children with recurrent (≥2) children ≥6 years of age. The target audience for the present position asthma-like symptoms or exacerbations (episodes with asthma-like statement includes family physicians, pediatricians, respirologists, signs), even when only triggered by viral respiratory infections.
allergists, emergency physicians and other health care practitioners. Three main approaches have historically been proposed to make a Airflow obstruction
presumptive diagnosis of asthma in preschoolers: a list of suggestive Wheezing is the most specific sign of airflow obstruction. Occurring symptoms; the exclusion of alternative diagnoses; and a set of features predominantly during expiration, with increasing airflow obstruction, that predict asthma at six years of age (ie, when old enough to perform wheezing can be heard during inspiration until it becomes absent with spirometry). Lists of nonprioritized criteria, with an unspecified num- severely diminished airflow. It is most reliably documented by a trained ber required for the diagnosis, have led to implementation difficulties. health care practitioner using a stethoscope (preferred diagnostic Exclusion of alternative conditions, resulting in unnecessary testing method), but can be audible without a stethoscope. When parents and parental anxiety, has reassured physicians on the absence of com- report ‘wheezing', it is important to verify what is meant because the orbidities without confirming the diagnosis of asthma. Several features term is often used nonspecifically to describe nasal or otherwise noisy are associated with the persistence of asthma at school age, such as the or troubled breathing sounds unrelated to asthma (14) (alternative number of wheezing episodes and personal or family history of atopy dignostic method).
(as identified in the Asthma Predictive Index ), or the age of onset and Other less-specific signs of airflow obstruction are often associated trajectory of symptoms over time (6); these criteria have slowly with wheezing, but may occur in the absence of wheezing. On auscul- become synonymous with the diagnosis of asthma in toddlers, even if tation, breath sounds may be normal with mild obstruction. With this was not the original intention. Moreover, the prediction tools are increasing airflow obstruction, breath sounds will be decreased initially far from perfect (7,8) and a future trajectory of symptoms cannot be at the lung bases, progressing to a widespread decrease and even used to make a diagnosis at any age. becoming inaudible in very severe asthma. With increasing airflow Most children with asthma experience onset of symptoms in the obstruction, tachypnea, prolonged expiration, signs of accessory preschool years. Preschoolers have the highest rate of emergency muscle use (eg, chest indrawing), hypoxemia and, in severe cases, department visits and hospital admissions for asthma symptoms, com- altered level of consciousness (eg, agitation or apathy) can be pared with other age groups (9,10). Wheezing in early life has been observed. Cough is the most commonly observed sign and reported associated with reduced lung function at six years of age that generally symptom, but it is not specific to asthma. Apart from viral respiratory persists until adulthood (11); the magnitude of the reduction is infections, a chronic cough that occurs during sleep or is triggered by approximately a 10% lower predicted forced expiratory volume in 1 s allergen exposures, exertion, laughing or crying increases the likeli- (FEV1), compared with healthy peers (11). Airway remodelling (ie, hood of asthma (15). irreversible damage to the airways) has been documented in toddlers and may explain the altered lung function trajectory (12). Although Reversibility of airflow obstruction
up to 60% of children become asymptomatic by six years of age, pre- A hallmark of asthma is the reversibility of airflow obstruction (ie, school wheeze is frequently associated with persistence until, or recur- a clear and timely response to asthma therapy). More specifically, rence in, adulthood (6). Importantly, evidence indicates that recurrent reversibility is best defined as a documented response to short-acting preschool wheezing responds to inhaled corticosteroid (ICS) therapy, ß2-agonists (SABA) (with or without oral corticosteroids) by health similar to older children and adults (13). Early diagnosis is, therefore, care professionals during an acute exacerbation (preferred diagnostic important to avoid treatment delay, reduce morbidity and, potentially, method). In children with no objective signs of airflow obstruction maximize lung growth and function. Our proposed operational criteria (ie, symptoms only), reversibility may be determined by convin- aim to standardize the diagnosis of asthma in the absence of lung func- cing parental report of symptomatic response to a three-month tion tests. As with all clinical diagnostic approaches, there is a risk for therapeutic trial of a medium dose of inhaled corticosteroids with misclassification. We acknowledge that these diagnostic criteria may as-needed SABA (alternative diagnostic method), or convincingly lead to a slight overdiagnosis of asthma, which, in our view, outweighs reported and repeatedly observed response to as-needed SABA alone the greater negative impact of underdiagnosis. by parents (weaker, alternative diagnostic method) (Table 1).
Can Respir J Vol 22 No 3 May/June 2015 Diagnosis and management of asthma in preschoolers
Operational diagnostic criteria for asthma in children one
Signs/symptoms* (red flags) suggesting an alternative
to five years of age
diagnosis to asthma
1. Documentation of airflow obstruction
Signs and/or symptoms
Documented wheezing and other signs of airflow obstruction Persistent nasal discharge by physician or trained health care practitioner Stridor; noisy breathing worse when Upper airway narrowing: Convincing parental report of wheezing or other symptoms crying, eating, supine or with (i) Infection: croup, tracheitis of airflow obstruction respiratory infection (ii) Intrinsic: laryngomalacia, 2. Documentation of reversibility of airflow obstruction
tracheal stenosis Documented improvement in signs of airflow obstruction to (iii) Extrinsic: vascular ring, SABA ± oral corticosteroids* by physician or trained health care practitioner Acute onset of cough, wheeze or Foreign-body inhalation Alternative† Convincing parental report of symptomatic response to a stridor during eating or playing; history Aspiration of food/gastric contents 3-month trial of a medium dose of ICS (with as-needed SABA)* of choking, recurrent pneumonia in Alternative‡ Convincing parental report of symptomatic response to SABA 3. No clinical evidence of an alternative diagnosis
First episode wheeze in child <1 year *See Table 3 for further details regarding the recommended therapy or thera- Sick contacts, focal signs on chest Pneumonia†, atelectasis†, peutic trial; †In children with frequent symptoms and/or one or more exacerba- tuberculosis, pertussis tion requiring rescue oral corticosteroids or a hospital admission; ‡In children Severe, paroxysms of cough, possibly with mild intermittent symptoms and exacerbations, the diagnosis is only sug- initially associated with a ‛whoop', gested because the accuracy of parental report of a short-term response to Premature birth, needed prolonged inhaled short-acting β -agonists (SABA) may be unreliable due to mispercep- supplemental oxygen ± mechanical tion and spontaneous improvement of another condition. Because this is a weaker alternative diagnostic method, confirmation by direct observation when Symptoms since infancy, recurrent Congenital pulmonary airway symptomatic is preferred. ICS Inhaled corticosteroids pneumonia, focal signs on chest Chronic wet cough, clubbing, failure to Bronchiectasis, cystic fibrosis thrive, recurrent pneumonia, onset in No alternative diagnosis
infancy, ± steatorrhea A thorough medical history and physical examination must be con- Neonatal respiratory distress, early Primary ciliary dyskinesia ducted, and medical conditions with similar presentations must be onset year-round daily cough and carefully considered to ensure that there is no alternative diagnosis. nasal congestion ± situs inversus (Table 2). Additional investigations are not required for the diagnosis Cough when supine, when feeding; Gastroesophageal reflux disease† of asthma unless there is suspicion of an alternative diagnosis. A chest vomiting after feeding, abdominal x-ray may be indicated in specific instances to rule out other causes of wheezing or comorbidities. Dysphagia, cough triggered by Eosinophilic esophagitis Recurrent URTIs with postnasal drip is the most frequent cause of recurrent cough; it is not associated with wheeze or difficulty breath- Feeding intolerance, wet cough or Swallowing problem ± aspiration ing. Croup presents with airflow obstruction in the upper airways with noisy breathing after eating barking cough and inspiratory stridor; it is more common in children Recurrent, persistent, severe Immune dysfunction with asthma (and vice versa) (16). It may be difficult to distinguish or unusual infections asthma from bronchiolitis in young toddlers because they present with Cardiac murmur, cardiac failure, Pulmonary edema due to: similar signs of airflow obstruction and viral respiratory illness. cyanosis when eating, failure to (i) Acute myocarditis/pericarditis Although there is no definite age cut-off, bronchiolitis usually presents thrive, tachypnea, hepatomegaly as the first episode of cough, wheezing and respiratory difficulty in an (ii) Congenital heart disease infant (<12 months of age) (17) and is best treated with supportive *Nonexhaustive list of signs and symptoms suggestive of possible alternative care (18). Asthma usually starts in toddlers (one to three years of age). diagnoses, prompting additional investigations and/or a different management However, repeated (≥2) wheezing episodes occurring before one year in the preschool child. Symptoms and signs listed may overlap among different of age should raise the suspicion of asthma and prompt the considera- diseases; †Indicates the most frequent alternative diagnoses to, or comorbidities tion of a referral to a specialist for evaluation. In children ≥1 year(s) of associated with, asthma age, the best way to distinguish bronchiolitis from asthma is probably by the response to asthma medications. DIAGNOSIS IN A CHILD PRESENTING WITH SIGNS
OF AIRFLOW OBSTRUCTION (FIGURE 1)
3. Asthma can be diagnosed in children one to five years of age.
When a child exhibits wheezing or other signs of airflow obstruction 4. The diagnosis of asthma requires documentation of signs or on presentation (as expected in the acute care setting), the documen- symptoms of airflow obstruction, reversibility of obstruction tation by a physician (or other trained health care practitioner) of (improvement in these signs or symptoms with asthma therapy) signs of airflow obstruction and improvement in these signs with and no clinical suspicion of an alternative diagnosis. asthma therapy, in the absence of clinical suspicion of an alternative 5. Bronchiolitis usually presents as the first episode of wheezing in diagnosis, is the preferred diagnostic approach. The diagnosis of a child <1 year of age.
asthma is based on recurrent (≥2) asthma-like exacerbations (episodes 6. The diagnosis of asthma should be considered in children one to with documented signs) or symptoms (reported). In case of a first five years of age with recurrent asthma-like symptoms or asthma-like exacerbation, the diagnosis of asthma is suspected, and exacerbations, even if triggered by viral infections. can be confirmed with recurrence of asthma-like signs or symptoms and response to asthma therapy.
Can Respir J Vol 22 No 3 May/June 2015 Ducharme et al
age 1-5 years presenting with: Current signs of airflow obstruction no current signs of airflow obstruction • ≥1 documented* asthma-like exacerbation† • ≥ 2 reported episodes of asthma-like symptoms • no red flags for an alternative diagnosis (Table 2) • no previously documented* signs of airflow obstruction OR• no previously documented* improvement to asthma therapy • no red flags for an alternative diagnosis (Table 2) Frequent symptoms‡‡ or ≥1 moderate to severe§§ asthma-like exacerbation† ?
Mild exacerbation‡ Moderate or severe Monitor and reassess when
therapeutic trial§ of medium
dose ICS for 3 months with ± 3-month therapeutic trial§
as needed SaBa with as-needed SaBa Reassess when symptomatic Reassess at 6 weeks and/or at 3 months Clear improvement¶ no/unclear improvement** • Documented* signs of airflow obstruction anD • Convincing response to SaBa¶¶ 1st episode → Suspected asthma††
≥ 2 episodes → asthma
Consider co-morbidity or an alternative diagnosis Watchful observation Referral to an asthma specialist if persistent symptoms and/or moderate to severe exacerbations Figure 1) Diagnosis algorithm for children one to five years of age. *Documentation by a physician or trained health care practitioner; †Episodes of wheezing
with/without difficulty breathing; ‡Severity of an exacerbation documented by clinical assessment of signs of airflow obstruction, preferably with the addition of
objective measures such oxygen saturation and respiratory rate, and/or validated score such as the Pediatric Respiratory Assessment Measure (PRAM) score;
§See Table 3 for dosing; ¶Based on marked improvement in signs of airflow obstruction before and after therapy or a reduction of ≥3 points on the PRAM score, recognizing the expected time response to therapy; **A conclusive therapeutic trial hinges on adequate dose of asthma medication, adequate inhalation technique, diligent documentation of the signs and/or symptoms, and timely medical reassessment; if these conditions are not met, consider repeating the treatment or therapeutic trial; ††The diagnosis of asthma is based on recurrent (≥2) episodes of asthma-like exacerbations (documented signs) and/or symptoms. In case of a first occurrence of exacerbation with no previous asthma-like symptoms, the diagnostic of asthma is suspected and can be confirmed with re-occurrence of asthma-like symptoms or exacerbations with response to asthma therapy ; ‡‡≥8 days/month with asthma-like symptoms; §§Episodes requiring rescue oral corti-costeroids (OCS) or a hospital admission; ¶¶In this age group, the diagnostic accuracy of parental report of a short-term response to as-needed short-acting β2-agonist (SABA) may be unreliable due to misperception and/or spontaneous improvement of another condition. Documentation of airflow obstruction and reversibility when symptomatic, by a physician or trained health care practitioner, is preferred; ***Based on 50% fewer moderate/severe exacerbations, shorter and milder exacerbations, and fewer, milder symptoms between episodes. ICS Inhaled corticosteroid Clinical improvement in the signs of airflow obstruction after controlled asthma. Response to oral corticosteroids is expected to inhaled SABA and/or oral corticosteroids observed by a health care begin within 4 h of administration (21), although the maximal effect practitioner provides direct evidence of reversibility (19) (Table 3). may be documented after several days of therapy (22,23), which may With a peak SABA effect at 20 min, one would observe a rapid be difficult to distinguish from spontaneous improvement over time. response to a single appropriate dose of SABA in children with mild clinical findings and to repeated (two to three) doses of SABA admin- Documenting objective response to therapy
istered over a 60 min period in those with moderate and severe airflow Improvement with asthma therapy can be assessed by noting changes obstruction (20). A suboptimal response to SABA is anticipated if in signs of airflow obstruction before and after therapy, recognizing most of the airflow obstruction is not due to bronchospasm (but rather the expected time response to therapy (Table 3) (20,21,23,24). Use of inflammation), particularly in a child with long-standing, poorly objective measures (ie, oxygen saturation in room air, respiratory rate) Can Respir J Vol 22 No 3 May/June 2015 Diagnosis and management of asthma in preschoolers
Therapeutic trial for documenting reversibility of airflow obstruction
Signs of airflow obstruction (preferred)
Mild clinical findings* Inhaled salbutamol Moderate or severe exacerbation* Inhaled salbutamol Oral corticosteroids‡ Prednisone/prednisolone (oral) 1–2 mg/kg (maximum 50 mg)‡ 0.15–0.60 mg/kg (maximum 10 mg)‡ 1st dose No signs of airflow obstruction (alternative)
Mild intermittent symptoms or exacerbations§ Inhaled salbutamol 2 puffs every 4 h to 6 h Frequent symptoms or moderate or severe exacerbations¶ Inhaled salbutamol 2 puffs every 4 h to 6 h Daily inhaled corticosteroids Fluticasone propionate Unless indicated otherwise, all medications are administered by metered-dose inhaler (MDI) with an age-appropriate valved spacer under health care professional super- vision (top panel) or by parents (bottom panel); doses are reported ex-valve. Medications listed in shaded area are not approved for use in this age group by Healh Canada with the exception of beclomethasone dipropionate approved for use in children ≥5 years of age. Because delivery by MDI is preferred, budesonide is not included in this table because it is only available for use by nebulization in this age group in Canada. *Severity of signs may be based on national guidelines for severity assessment (19) or on the Pediatric Respiratory Assessment Measure (PRAM, mild: PRAM 0–3; moderate: PRAM 4–7; severe: PRAM 8–12) (25,26); †Dosage according to age- or weight- specific emergency treatment protocol (19); ‡Oral prednisone (or prednisolone) may be given at a dose of 1 mg/kg or 2 mg/kg of three- to five-day course. Oral dexa- methasone may be given either at a dose of 0.15 mg/kg to 0.3 mg/kg as the first dose of a subsequent two- to four-day course of prednisone or at a dose of 0.6 mg/kg as part of a one- or two-day course (21-24); §Refers to asthma-like symptoms of mild severity occurring <8 days/month and mild exacerbations requiring no rescue oral corticosteroids or admission and lasting hours to a few days; ¶Frequent asthma-like symptoms occurring ≥8 days/month; moderate or severe exacerbations refer to epi-sodes with asthma-like signs requiring rescue oral corticosteroids or hospital admission; **As monitored by parents for subsequent reporting at the medical reassessment; ††With medical reassessment (or another health care practitioner contact) at 6 weeks to ensure adherence to asthma medication and diary completion and/or a standardized clinical score such as the Pediatric Respiratory In children with frequent symptoms (≥2 days/week  or ≥8 days/ Assessment Measure (PRAM), in which a change of 3 points is con- month) or ≥1 moderate or severe asthma-like exacerbation (ie, treated sidered to be clinically important (25,26), reduces the subjectivity of with oral corticosteroids or a hospital admission), a therapeutic trial the assessment (Table 4). Recurrence of signs of obstruction after the with a medium (200 μg to 250 μg) daily dose of ICS and as-needed effects of SABA have lapsed is confirmatory.
SABA, administered by metered-dose inhaler, is suggested (Table 3).
A trial of a medium-dose ICS (Table 5) for determination of DIAGNOSIS IN A CHILD PRESENTING WITHOUT
reversibility of airflow obstruction is suggested because daily ICS are SIGNS OF AIRFLOW OBSTRUCTION (FIGURE 1)
the preferred asthma controller medications for the management of Many children presenting in ambulatory care are not acutely ill and both recurrent episodic exacerbations and persistent asthma symp- their physical examination is typically normal. On occasion, convin- toms, with an efficacy that has been well demonstrated in systematic cing signs of airflow obstruction can be provoked after a deep inspira- reviews of randomized controlled trials (13,27). Because ICS have an tion or exercise. However, the physical examination remains relatively onset of action within one to four weeks (28), and most trials demon- insensitive to identifying airflow obstruction, particularly if the strated ICS efficacy within three to six months (13,27), a minimum obstruction is long standing. In this case, previous documentation of therapeutic trial of three months is recommended. In this age group, wheezing or other signs of airflow obstruction by a trained health care budesonide and fluticasone have been studied the most extensively and practitioner, and improvement with SABA and/or oral corticosteroid have been found to be clinically effective (19,27), with fluticasone when acutely ill, acceptably replaces one's own evaluation. showing less effect on growth than beclomethasone dipropionate and In children presenting with no signs of airflow obstruction, a diag- budesonide at equivalent doses (29). Because delivery by metered-dose nosis of asthma is suspected if they experienced recurrent (≥2) epi- inhaler is preferred, budesonide is not recommended because it is only sodes with asthma-like symptoms and no previously documented signs available for use by nebulization in Canada in children <6 years of age. of airflow obstruction or reversibility, and no suspicion of an alterna- There is only one published trial of ciclesonide (30) and none with tive diagnosis. Asthma is also suspected if there has been a single epi- mometasone in preschoolers. Because of weaker evidence compared sode of airflow obstruction with reversibility documented by a trained with ICS (27), montelukast is not recommended for a therapeutic trial. health care practitioner with no previous or subsequent episodes with asthma-like signs or symptoms. Confirmation of diagnosis may be Documenting symptomatic response to therapy
obtained by a therapeutic trial. A conclusive therapeutic trial hinges on adherence to asthma medica- Children who experience mild and infrequent symptoms (<8 days/ tion, adequate inhalation technique, diligent documentation of signs month) and only mild exacerbations (lasting hours to a few days, with- and/or symptoms, and timely medical reassessment. Because it is easier out rescue oral corticosteroids or hospital admission), convincing par- to interpret, the therapeutic trial should preferably be conducted dur- ental report of a rapid and repeatedly observed symptomatic response ing the season when the child is most symptomatic. To document a to as-needed SABA alone is suggestive of asthma, but is a weaker change in the frequency and severity of symptoms between and during alternative diagnostic method (Table 3). For increased diagnostic cer- asthma-like exacerbations, we encourage prospective parental mon- tainty, these children should be monitored and reassessed by a trained itoring of key elements of asthma control, including daytime and health care practitioner for signs of airflow obstruction and reversibility nighttime symptoms, rescue SABA use, effort limitation, absenteeism when symptomatic. from usual activities, and exacerbations requiring unscheduled medical Can Respir J Vol 22 No 3 May/June 2015 Ducharme et al
Pediatric Respiratory assessment Measure (PRaM)
Inhaled corticosteroid (ICS) dosing categories* in children
one to five years of age
Oxygen saturation Daily ICS dose, micrograms (mcg)†
Corticosteroid (trade name)
Beclomethasone (QVAR®) Suprasternal retraction Fluticasone (Flovent®) Scalene muscle contraction *Proposed dosing categories are based on a combination of approximate dose equivalency as well as safety and efficacy data rather than the available prod- uct formulations. Shaded area indicates that these medications are not approved for use in this age group by Health Canada with the exception of ↓ At the apex and the Beclomethasone (QVAR), which is approved for use in children ≥5 years of age. Because delivery by metered-dose inhaler is preferred, budesonide is not included in this table because it is only available for use by nebulization in Minimal or absent Canada in children <6 years of age. High doses of ICS are not recommended in this age group and referral to an asthma specialist is suggested if asthma is not controlled on a medium dose of ICS; †The ICS doses are reported ex-valve as the total daily dose; they should be divided in half for twice-daily administra- tion, except where indicated otherwise. ICS are to be administered by metered-dose inhaler with an age-appropriate valved spacer; ‡Licensed for stethoscope or silent once daily dosing in Canada; §Fluticasone is not licensed for once-daily dosing chest (minimal or in Canada but 125 μg once daily is sometimes used to improve adherence over twice-daily use of 50 μg PRaM score (maximum 12)
(34) and adults (35) with respect to bronchodilator response may be unreliable, and short-term improvement may be spontaneous or due to Adapted from Ducharme FM, Chalut D, Plotnick L, et al. The Pediatric Respiratory the natural course of an alternative condition. If a satisfactorily con- Assessment Measure: A valid clinical score for assessing acute asthma severity ducted trial remains inconclusive, the presence of a comorbidity and/ from toddlers to teenagers. J Pediatr 2008;152(4):476-80, 480.e1. This tool is or an alternative diagnosis should be reconsidered.
available at <www.chu-sainte-justine.org/childasthmatools>. *In case of asym- metry, the most severely affected (apex-base) lung field (right or left, anterior or Dechallenge
posterior) will determine the rating of the criterion; †In case of asymmetry, the two In children with mild infrequent symptoms and mild episodes with most severely affected auscultation zones, irrespectively of their location (right asthma-like signs in whom improvement with a therapeutic trial is upper lobe, right middle lobe, right lower lobe, left upper lobe, left lower lobe), will unclear, a period of observation after stopping therapy for three to six determine the rating of the criterion. ↓ Decreased months or until recurrence of symptoms, whichever occurs first, is sug-gested. Parental report of aggravation of symptoms on withdrawal of therapy is suggestive of the diagnosis of asthma.
visits, oral corticosteroids and/or hospital admission. Recording in a KEY MESSAGES
diary is suggested to avoid inaccurate recall (31), although it may be 7. In children one to five years of age with recurrent (≥2) episodes of subject to missing or falsified data (32,33). The reliability of parental asthma-like symptoms and wheezing on presentation, direct
report of treatment response to ICS has not been formally examined observation of improvement with inhaled bronchodilator (with or nor has the ability of this approach been formally tested to accurately without oral corticosteroids) by a physician or trained health care distinguish children with asthma from those without asthma in the practitioner confirms the diagnosis (preferred diagnostic method).
community setting; however, parental report is widely used in clin- 8. Children one to five years of age with recurrent (≥2) episodes of ical trials of ICS showing efficacy in preschoolers. Recognizing that asthma-like symptoms, no wheezing on presentation, frequent
parental adherence to daily controller and diary completion drops symptoms or any moderate or severe exacerbation warrant a
significantly over time, an initial follow-up is recommended approxi- three-month therapeutic trial with a medium daily dose of ICS mately half way (six weeks) through the trial. (with as-needed SABA). Clear consistent improvement in the A clear and consistent improvement in the frequency and sever- frequency and severity of symptoms and/or exacerbations confirms ity of symptoms and/or exacerbations during a therapeutic trial of the diagnosis (alternative diagnostic method). asthma controller medication is required to confirm reversibility of 9. Children one to five years of age with recurrent (≥2) episodes of airflow obstruction (ie, response to therapy). The magnitude of change asthma-like symptoms, no wheezing on presentation, infrequent
required to meet the definition of a satisfactory clinical response has symptoms, and mild exacerbations can be monitored and
not been formally examined. However, based on trials of medium re-assessed by a health care practitioner when symptomatic. doses of daily ICS, a reduction of approximately 50% in the number Alternatively, a therapeutic trial with as-needed SABA is of exacerbations requiring oral corticosteroids (RR 0.57 [95% CI suggested. Convincing parental report of a rapid and repeatedly 0.40 to 0.80]) is expected, with a shorter duration and severity of observed response to SABA suggests the diagnosis (weaker exacerbations (27) and fewer symptoms between exacerbations. We alternative diagnostic method) acknowledge that reversibility could also be suggested by the convin- 10. To adequately interpret a therapeutic trial, clinicians should cingly reported and repeatedly observed by parents of a rapid short- ascertain adherence to asthma therapy, inhalation technique term response to SABA when symptomatic (Table 3); this has been and parental report of monitored symptoms, at an appropriately included as a weaker alternative diagnostic criterion for reversibility timed medical reassessment.
(Table 1). Clinicians should be aware that the perception of children Can Respir J Vol 22 No 3 May/June 2015 Diagnosis and management of asthma in preschoolers
WHEN TO REFER TO A SPECIALIST
Recommendations for specialty referral are summarized in Table 6 children one to five years of age with diagnosis of asthma
(3,36-40). Preschool lung function testing, available in some pediatric academic centres, can be helpful to confirm the diagnosis (41-44). Allergy testing is suggested in a child with persistent symptoms to assess the possible role of environmental allergens and provide advice about implementation of avoidance strategies (39,45).
Persistent symptoms* Mild intermittent or moderate or severe KEY MESSAGE
11. Referral to an asthma specialist is recommended in children one to five years of age with diagnostic uncertainty, suspicion of comorbidity, poor symptom and exacerbation control despite Daily low-dose ICS§ ICS at daily doses of 200 μg to 250 μg, a life-threatening event as-needed SaBa and with as-needed SaBa (requiring intensive care admission and/or intubation) and/or asthma education‡ for allergy testing to assess the possible role of environmental APPROACH TO MANAGEMENT
Once a diagnosis of asthma has been confirmed, families and care-
givers should receive asthma education that includes a written self-management plan emphasizing adherence to asthma medication, and Referral to an asthma specialist appropriate inhaler with spacer technique instructions (2). For chil-dren one to three years of age, a spacer with a correctly sized facemask Figure 2) Treatment algorithm for preschoolers with asthma. *Symptoms
is preferred. For children four to five years of age, consideration to use occurring ≥8 days/month, ≥8 days/month with use of inhaled short-acting a spacer with a mouthpiece is encouraged if the child can form a good β2-agonists (SABA), ≥1 night awakening due to symptoms/month, any seal around the mouthpiece and breathe in through the mouth as exercise limitation/month or any absence from usual activities to asthma observed by a trained health care professional. Avoidance of irritants, symptoms; †Episodes requiring rescue oral corticosteroids or hospital admis- such as cigarette smoke, is important as well as environmental sion; ‡Asthma education including environmental control and a written aeroallergens if the child is sensitized. self-management plan; §Inhaled corticosteroids (ICS) are more effective than leukotriene receptor antagonists (LTRA) Pharmacological
Once the diagnosis is confirmed, ICS taken every day at the lowest
effective dose (Table 5) is the preferred first-line management for
children presenting with persistent symptoms (>8 days/month) and/or
be given to incrementally stepping down their medication to the low- moderate or severe exacerbations (ie, requiring rescue oral cortico- est effective dose. Given the high rate of symptom resolution in this steroids or hospital admission) (13,27). If the patient has received a age group, a trial off medication can be attempted when symptoms are therapeutic trial with a medium dose of ICS, this entails downward minimal on a low dose of ICS during the season when the child is usu- titrating to the lowest effective dose after control has been achieved ally most symptomatic.
(Figure 2). Until more evidence supporting their effectiveness is avail-able, the following three commonly used strategies are not advocated KEY MESSAGE
and/or should be avoided: daily leukotriene receptor antagonists, 12. Daily ICS at the lowest effective dose is the preferred first-line which are less effective than ICS and should remain a second-line management for asthma once the diagnosis is confirmed and option (46); stepping-up the daily dose of ICS during URTI, which control has been achieved.
remains untested in preschoolers; and the intermittent use of asthma controller medications at the onset of symptoms (eg, montelukast or low or medium doses of ICS) that has not been convincingly shown to KNOWLEDGE TRANSFER AND TOOLS
reduce the number or severity of asthma exacerbations (27,47,48). In FOR PRACTICE
contrast, use of pre-emptive high-dose ICS at the onset of symptoms • The present document is available for download at is effective in reducing the severity and duration of exacerbations in preschoolers with moderate or severe viral-induced asthma; however, • A slide deck for teaching and self-learning as well as a brochure for due to the risk for overuse and potential side effects, this treatment health care professionals and students is available at should be reserved for asthma specialists and only if daily ICS fails <www.respiratoryguidelines.ca> under the ‘Tools and Resources' tab.
(49). Children with mild infrequent symptoms (≤8 days/month) and • The CTS plans to develop, in collaboration with McGill University no or mild exacerbation (ie, no rescue oral corticosteroids or admission (Montreal, Quebec), a mobile application to raise awareness of and lasting hours to a few days), as-needed SABA may be sufficient to our 12 key messages and other guidelines' recommendations, for maintain control. clinical practice. Monitoring
• Several forms of patient diaries, for use in the context of a Asthma control should be assessed every three to four months using therapeutic trial, are available to document response.
the same criteria as for school-age children and adults (2). An exacer- • For the acute care setting, an online teaching module on PRAM is bation requiring rescue systemic corticosteroids or hospitalization is an available at www.chu-sainte-justine.org/pram. indication of suboptimal management and should prompt reassess- The CTS Asthma Clinical Assembly welcomes the opportunity to ment. Once adequate control has been sustained over the three partner with other organizations and stakeholders in the development months before reassessment, despite exposure to the child's typical of educational tools and resources that support implementation and unavoidable asthma triggers (eg, URTI, cold air), consideration should uptake of these key messages with various targeted groups.
Can Respir J Vol 22 No 3 May/June 2015 Ducharme et al
obstruction, evidence-based grading of the severity of airflow Reasons for referral to an asthma specialist for consultation
obstruction, and identification of the magnitude of between-visit improvement indicating a significant treatment response.
Diagnostic uncertainty or suspicion of comorbidity • Exploring the impact of portable preschool lung function testing in Repeated (≥2) exacerbations requiring rescue oral corticosteroids or ambulatory care on asthma control, risk of future exacerbations hospitalization or frequent symptoms (≥8 days/month) despite moderate and lung function trajectories of preschool-age children who (200 μg to 250 μg) daily doses of inhaled corticosteroids experience asthma-like exacerbations. Life-threatening event such as an admission to the intensive care unit Need for allergy testing to assess the possible role of environmental allergens ACKOWLEDGEMENTS: The authors acknowledge the support pro-
Other considerations (parental anxiety, need for reassurance, additional vided by the Canadian Thoracic Society and the Canadian Paediatric Society for this initiative. The authors sincerely thank Drs Paul Brand, Tom Kovesi, Rod Lim, Tim O'Callahan, Catherine Lemière, Diane Lougheed, Richard Leigh, Chris Licskai and Samir Gupta for their constructive com- ments in reviewing this manuscript. They are indebted to Meriem Bougrassa Asthma is diagnosed in children one to five years of age with recurrent for coordinating this initiative, Annie Théoret for assistance in the manu- asthma-like episodes, using signs (or convincingly-reported symptoms) script preparation and Risa Shorr for the literature search.
of airflow obstruction and reversibility of obstruction with asthma therapy, in the absence of clinical evidence of an alternative diagnosis. EDITORIAL INDEPENDENCE: The CTS Asthma Clinical Assembly
Objective documentation of airflow obstruction and reversibility by a is accountable to the CTS Respiratory Guidelines Committee and the CTS physician or other trained health care practitioner is preferred. We Board of Directors, and is functionally and editorially independent from any offer a pragmatic diagnostic algorithm, depending on the presence or funding sources of the CTS. No funders played a role in the collection, absence of signs of airflow obstruction on presentation to children into review analysis or interpretation of the literature, or in any decisions regard- asthma, suspected asthma or unclear diagnosis (Figure 1). Once the ing the key messages presented in this document.
diagnosis is confirmed, daily low-dose ICS (100 μg/day to 125 μg/day) with as-needed SABA, is the preferred management strategy in pre- DISCLOSURES: Members of the working group declared potential con-
schoolers with persistent symptoms and/or moderate or severe exacer- flicts of interest at the time of appointment, which were updated throughout bations and as-needed SABA alone for those with mild intermittent the development process in accordance with CTS Conflict of Interest symptoms and exacerbations (Figure 2).
Disclosure Policy. Individual member conflict of interest statements are posted at www.respiratoryguidelines.ca/guideline/asthma MONITORING ADHERENCE TO KEY MESSAGES
The following parameters may be used to monitor or audit adherence KNOWLEDGE TRANSFER AND TOOLS FOR PRACTICE
with some of the key recommendations contained in the present position statement: • Decreased use of terms such as ‘bronchospasm', ‘reactive airway disease', ‘wheezy bronchitis' and ‘happy wheezer' in medical records.
• Clear documentation in the medical charts of preschoolers with asthma-like exacerbations of the presence or absence of: signs and 1. Hughes D. Recurrent pneumonia. Not! Paediatr Child Health symptoms of airflow obstruction; improvement with therapy; and clinical suspicion of another condition.
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• Documenting the frequency of the adequate medical documentation 9. Lougheed MD, Garvey N, Chapman KR, et al. Variations and gaps of the three asthma criteria by health care professionals in various in management of acute asthma in Ontario emergency departments. 10. Lougheed MD, Garvey N, Chapman KR, et al. The Ontario Asthma • Improving the ability and documenting the reliability of parental Regional Variation Study: Emergency department visit rates and the documentation of symptoms in written and/or electronic diaries or relation to hospitalization rates. Chest 2006;129:909-17.
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CIHR Institute of Nutrition, Metabolism and Diabetes Internal Assessment for 2011 International Review Table of Contents CIHR Institute of Nutrition, Metabolism and Diabetes List of Figures and Tables CIHR Institute of Nutrition, Metabolism and Diabetes Mandate and ContextMandateThe Institute of Nutrition, Metabolism and Diabetes (INMD) is mandated to support
International Journal of Technical Research(IJTR) Vol. 2, Issue 1, Mar-Apr 2013 COMBINED STUDY OF ATENOLOL AND ESCITALOPRAM ON ANXIETY AND Gulshan Sindhwani ABSTRACT of people who commit suicide have Major depressive disorder is a depression or another mood disorder. DRUG PROFILE encompassingaccompanied by 1. Escitalopram