DIAGNOSTIC PITFALLS IN PEDIATRIC BRONCHIAL ASTHMA Ibrahim A. Janahi, MD, FCCP, FRCPCH Professor of Clinical Pediatrics, Weill Cornell Medicine- Qatar Division Chief, Pediatric Pulmomnology

Learning points What is asthma/Differential diagnosis of wheezy chest Asthma diagnosis Definition and overarching principles Predictive index of asthma Approach to establish asthma diagnosis Organization of diagnostic services Wheezing in pre-school children and persistent asthma Pitfalls in asthma diagnosis Pitfalls/Remedies Take home message

WHAT IS ASTHMA / DIFFERENTIAL DIAGNOSIS

Asthma….? A heterogeneous disease, usually characterized by chronic airway inflammation. Recurrent episodes of: wheezing Shortness of breath Chest tightness/pain Coughing This happens as a response to a trigger. It varies over time and in intensity, together with variable expiratory airflow limitation

Asthma Phenotypes

Causes of wheezing in children and infants

DEFINITION AND OVERARCHING PRINCIPLES

Definition Diagnosis is defined as the presence of symptoms (more than one of wheeze, breathlessness, chest tightness, cough) and of variable airflow obstruction on chronic and recurrent basis (more than 6-8 weeks) More recent descriptions of asthma have included airway hyper-responsiveness airway inflammation as components of the disease reflecting a developing understanding of the diverse subtypes (phenotypes and endotypes) of asthma. Wheezy chest has many differential diagnosis which might be confusing to clinicians if not following a diagnostic algorithm to confirm the diagnosis.

Overarching Principles of Asthma Diagnosis Asthma diagnosis is based on clinical assessment + supported by objective tests. In patients with a very high probability of asthma prior to testing, the results of a diagnostic test with a substantial false negative rate will have minimal influence on the diagnosis. In patients with an intermediate or low probability of asthma, a positive diagnostic test may significantly shift the probability towards an asthma diagnosis. Tests influence the probability of asthma but do not prove the diagnosis:

Overarching Principles Asthma status and the outcome of diagnostic tests for asthma vary over time Patients who have not received prescriptions for a year are considered to be ‘inactive’, some patients may shift from ‘inactive’ to ‘active’ status (and vice versa) over time. Objective tests performed when patients are asymptomatic or during an ‘inactive’ period may result in false negatives. Golden Rule Compare the results of diagnostic tests undertaken whilst a patient is asymptomatic with those undertaken when a patient is symptomatic to detect variation over time.

Predictive Value (symptoms, signs and diagnostic tests)

Asthma Predictive Index It is a guide to determining which individual will develop asthma in later years. Children younger than 3 years who have had four or more significant wheezing episodes over the past year are much more likely to have persistent asthma after the age of five.

Predictive values i. Test of Variability in lung functions ii. Spirometry and bronchodilator reversibility Combination of symptoms and signs will be more helpful to accurately diagnose rather than isolated ones. Only “Quarter” of children who have asthma signs were proven to be asthmatic. Episodic nature of symptoms as opposed to current symptoms may improve the predictive value. Wheezy chest should be well distinguished from noisy breathing or stridor. Carry out quality-assured spirometry using the lower limit of normal to demonstrate airway obstruction, provide a baseline for assessing response to initiation of treatment and exclude alternative diagnoses. Obstructive spirometry with positive bronchodilator reversibility increases the probability of asthma. Normal spirometry in an asymptomatic patient does not rule out the diagnosis of asthma.

iii. Tests of variability in lung function iv. Tests to detect eosinophilic airway inflammation or atopy Direct challenge tests: (highly predictive) A negative test in a child, makes a diagnosis of asthma improbable. Indirect challenge tests (highly predictive) A positive response as a fall in FEV1of greater than 15%, is a specific marker of asthma In children, a positive challenge test is highly predictive of asthma with a false positive rate of less than 10%, while the negative excludes it. Peak expiratory flow monitoring There is no evidence to support the routine use of peak flow monitoring in the diagnosis of asthma in children. Fractional exhaled nitric oxide (FeNO) Use measurement of FeNO (if available) to find evidence of eosinophilic inflammation. A positive test increases the probability of asthma but a negative test does not exclude asthma. Tests of atopic status Use a previous record of skin-prick tests, blood eosinophilia of 4% or more, or a raised allergen-specific IgE to corroborate a history of atopic status, but do not offer these tests routinely as a diagnostic test for asthma. Sputum eosinophils Induced sputum in school age children is more of a research than a diagnostic tool.

Approach to Establish Asthma Diagnosis

Initial Structured Clinical Assessment Undertake a structured clinical assessment to assess the initial probability of asthma. This should be based on: History of recurrent episodes (attacks) of symptoms, ideally corroborated by variable peak flows when symptomatic and asymptomatic. Symptoms of wheeze, cough, breathlessness and chest tightness that vary over time. Recorded observation of wheeze heard by a healthcare professional. Personal/family history of other atopic conditions. No symptoms/signs to suggest alternative diagnoses.

Approach to Establish Asthma Diagnosis Initial structured clinical assessment. High probability of asthma based on initial structured clinical assessment. Low probability of asthma based on initial structured clinical assessment. Intermediate probability of asthma based on initial structured clinical assessment.

High Probability of Asthma Based on Initial Structured Clinical Assessment Record the patient as likely to have asthma and commence a carefully monitored initiation of treatment (typically six weeks of inhaled corticosteroids). Assess the patient’s status with a validated symptom questionnaire, ideally corroborated by lung function tests. With a good symptomatic and objective response to treatment, confirm the diagnosis of asthma and record the basis on which the diagnosis was made. If the response is poor or equivocal, check inhaler technique and adherence, arrange further tests and consider alternative diagnoses.

Low Probability of Asthma Based on Initial Structured Clinical Assessment If there is a low probability of asthma and/or an alternative diagnosis is more likely, investigate for the alternative diagnosis and/or undertake or refer for further tests of asthma.

Intermediate Probability of Asthma Based on Initial Structured Clinical Assessment Spirometry, with bronchodilator reversibility, is the preferred initial test for investigating intermediate probability of asthma in adults, and in children old enough to undertake a reliable test. In children with an intermediate probability of asthma and airways obstruction identified through spirometry; undertake reversibility tests and/or a monitored initiation of treatment assessing the response to treatment by repeating lung function tests and objective measures of asthma control. In children with an intermediate probability of asthma and normal spirometry results; undertake challenge tests and/or measurement of FeNO to identify eosinophilic inflammation.

In children with an intermediate probability of asthma who cannot perform spirometry: Consider watchful waiting if the child is asymptomatic Offer a carefully monitored initiation of treatment if the child is symptomatic.

Diagnostic Algorithm

Indications for Referral

Organization of Diagnostic Services

Diagnostic Services … Streamline referral pathways should be developed for tests not available or appropriate in primary care. Simple tests as spirometer and bronchodilator reversibility mostly will be available in primary care centers. FENO and skin prick test are available in secondary care. Challenge test will require referral to a diagnostic center (tertiary care).

Wheezing in Preschool Children and Future Risk of Persistent Asthma

Factors Associated with High / low Risk of Persistent Asthma Development Age at presentation Sex Severity and frequency of previous wheezing episode Coexistence of atopic disease Family history of atopy Abnormal lung function

Pitfalls in Asthma Diagnosis

Most common Pitfalls in Asthma Diagnosis Under-diagnosis of Asthma. Ineffective inhalation therapy. Ignoring concomitant disorder. Ignoring common risk factors/triggers. Failure to deliver asthma education.

1. Under-diagnosed Asthma

2. Ineffective Inhalation Therapy

3. Ignoring Concomitant Disorder

4. Ignoring Common Risk Factors / Triggers

5- Failure to Deliver Asthma Education

Take home message

Take home message

Case (1) 14 year old girl presents with history of recurrent attacks of shortness of breath associated with wheezing for the last 2 years. These attacks occur when she is exposed to certain perfumes but she can’t pinpoint which ones. They occurred 4 times in the last 2 years each one of them lasting few hours and responding fairly well upon taking salbutemol inhalers that she borrows from her elder brother who has asthma. She reports annoying dry nocturnal cough that has not gone away since it started few months ago. The cough some times wakes her up from sleep early morning; at one stage she tried taking salbutemol inhaler for this cough and she noticed improvement and thus decided to use the inhaler whenever the cough is “very bad” Her physical examination in normal apart from slight increase in the AP diameter of her thorax.

Case (1) Questions What is the most likely diagnosis? How would you confirm the diagnosis? How would you treat this girl?

Case (2) 2 year old boy is brought to your clinic because he has been having recurrent episodes of wheezing and shortness of breath for the last 2 years. These episodes occur on monthly basis, mainly with URTIs but some times without a trigger that the mother could pinpoint He first started to have these episodes when he was 10 months old when he was admitted to the PEC for a day to treat a “bad” episode of “chest infection”. You noted form the EMR that he was then positive for Rhino Virus infection These episodes respond quite dramatically to salbutemol nebulizations but some times he has to continue using the nebs for 3-4 days till he gets “completely clear” He is followed at the dermatology clinic for a “stubborn” eczema His elder brother (12 year) used to have “asthma” when he was younger but he “outgrew it” His physical examination today is completely normal

Case (2) Questions What is your diagnosis? Can you confirm the diagnosis? And how? How would you treat this child?

References The Diagnosis of Wheezing in Children LISA NOBLE WEISS, MD, MEd, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Forum Health Family Practice Center, Youngstown, OhioAm Fam Physician. 2008 Apr 15;77(8):1109-1114. Asthma: tips and pitfalls in diagnosis and treatment.Volume 21, Issue 15-16, Version of Record online: 27 AUG 2010 m http://onlinelibrary.wiley.com/doi/10.1002/psb.658/pdf Pitfalls in the Management of Bronchial Asthma Medicine Update 2008 Vol. 18 http://citeseerx.ist.psu.edu/viewdoc download;jsessionid=1B70F5B10EB971F24D66B7D163410FBE?doi=10.1.1.689.3978&re p=rep1&type=pdf. British guidelines on the management of asthma; a national clinical guideline. SIGN 153-September 2016 http://www.sign.ac.uk/pdf/SIGN153.pdf

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