Management of Chronic Cough in Children

➡️Introduction

Chronic cough is defined as the presence of daily cough of more than 4 weeks duration in children aged <14 years old (4). It has been divided into specific and nonspecific cough. Specific cough is usually associated with an underlying disease and non-specific cough indicates prolonged cough in the absence of any symptoms, signs, history, or laboratory findings indicating a specific diagnosis (specific cough pointers) (5).

➡️Scope

This guideline focuses on prevention and management of Chronic Cough in Children

➡️Guideline development process and methods

After reviewing all the inclusion and exclusion criteria and quality appraisal results, the GDG/ GAG recommended using the following source original clinical practice guidelines (CPGs):

1- Chronic cough guidelines ACCP (2006-2020)

2- Chronic cough guidelines (ERS 2019)

3- Chronic cough guidelines (KAAACI 2018)

We conducted Adolopment for these guidelines: (Adoption, Adaptation, and Development)

         -  Adoption for most of the guideline recommendations.

         -   Adaptation for 2 recommendations according to GRADE criteria to be suitable to our Economic implications (Evidence-to-Decision (EtD) table was done)

         -   Development of Good Practice Statements

➡️Recommendations and Good Practice Statements (GPS)

This version of the CPG includes recommendations and good practice statements on the Management of Chronic Cough in Children

The guideline covers children up to 14 years of age

➡️We can summarize the guidelines’ recommendations in the following:

▪️  For patients seeking medical care complaining of cough, clinician suggest that estimating the duration of cough is the first step in narrowing the list of potential diagnoses. (Low quality evidence, Weak (conditional) recommendation).

▪️  We recommend that history should include cough characteristics and the associated clinical history such as using specific cough pointers like presence of productive/wet cough. (High qulaity evidence, strong recommandation).

▪️ We suggest that history should include symptoms of red flags or other potential life-threatening symptoms and if present, they should be immediately addressed and evaluated. (good practice statement).

▪️  We suggest that exposure to airborne irritants (e.g. tobacco exposure, combustions, traffic related exposure etc.), allergens or infection may be a reason for dry chronic cough. (Very low quality evidence, weak (conditional) recommendation).

▪️We suggest that in unexplained or unresponsive chronic cough, obstructive sleep apnea should be included in the differential diagnosis. (Very low quality evidence, weak (conditional) recommendation).

▪️  We suggest that detailed history of drug intake is needed including ACEI and other drugs such as bisphosphonates or calcium channel antagonists and prostanoid eye drops. (Very low quality evidence, weak (conditional) recommendation).

▪️ We recommend basing the management on the etiology of the cough. An empirical approach aimed at treating upper airway cough syndrome due to a rhinosinus condition, gastroesophageal reflux disease and/or asthma should not be used unless other features consistent with these conditions are present. (high evidence, strong recommendation).

▪️ We suggest that diagnosis of asthma is suggested by presence of risk factors and/or response to a short (2-4 weeks) therapeutic trial of 400 ug/day of beclomethasone equivalent may be warranted, and these children should be evaluated in 2-4 weeks. (Very low quality evidence, weak (conditional) recommendation).

▪️  We suggest that cough variant asthma (CVA) was originally described as asthma with cough as the sole symptom and where treatment with bronchodilators improved coughing. (Very low quality evidence, weak (conditional) recommendation).

▪️ We suggest that patients with cough with or without fever, night sweats, hemoptysis, weight loss and/or contact with TB case and -who are at risk of pulmonary TB in community high in TB prevalence. (Very low quality evidence, weak (conditional) recommendation).

▪️  We recommend that the clinician should recommend chest radiography. (Intermediate quality evidence, strong recommendation).

▪️We suggest that the clinician should not routinely perform a chest CT scan in patients who have normal physical examination and chest X-ray. (Very low quality evidence, weak (conditional) recommendation).

▪️  We recommend that the clinician should recommend spirometry (pre and post β2 agonist) when age is appropriate. (Intermediate evidence, strong recommendation).

▪️ We suggest that the clinician should suggest a test for airway hyper-responsiveness (mannitol or methacholine inhalation). (low quality evidence, weak (conditional) recommendation).

▪️  We suggest that this recommendation places relatively higher value on predictability for the treatment response and the impact on the treatment decision. (Very low quality evidence, weak (conditional) recommendation).

▪️   We recommend that clinicians should not routinely perform additional tests. These should be individualized and undertaken according to the child’s clinical symptoms and signs. (Intermediate quality evidence, strong recommendation).

▪️  We suggest that the clinician should suggest undertaking tests for evaluating recent Bordetella pertussis infection when pertussis is clinically suspected (if there is post-tussive vomiting, paroxysmal cough or inspiratory whoop). (Very low quality evidence, weak (conditional) recommendation).

▪️  We recommend that the clinician should suggest further investigations (e.g. flexible bronchoscopy with quantitative culture and sensitivity with or without chest CT assessment for aspiration) to be undertaken. (Intermediate quality evidence, strong recommendation).

▪️ We recommend that the clinician should recommend evaluation of the immunologic competence in presence of criteria suspicious of immunodeficiency (appendix) to assess for an underlying disease. (Intermediate quality evidence, strong recommendation).

▪️ We recommend that in patients with suspected bronchiectasis without a characteristic chest radiograph finding, a high-resolution CT (HRCT) scan of the chest should be ordered because it is the diagnostic procedure of choice to confirm the diagnosis. (low quality evidence, strong recommendation).

▪️   We recommend that A 24-h esophageal pH monitoring test is the most sensitive and specific test.  ( low quality evidence, strong recommendation).

▪️  We recommend that barium esophagography may be beneficial. It can be considered if it is the only available test to reveal that GERD is of potential pathologic significance. (quality evidence, strong recommendation).

▪️   We recommend that a normal esophagoscopy finding does not rule out GERD as the cause of cough. (low quality evidence, strong recommendation0.

▪️  We recommend that the clinician should suggest screening for TB regardless of cough duration. (low quality evidence, stromg recommendation).

▪️  We suggest that the clinician should suggest Xpert MTB/RIF test, when available, to replace sputum microscopy as an initial diagnostic test. (Very low quality evidence, weak (conditional) recommendation).

▪️ We suggest that in patients who report upper airway symptoms laryngoscopy, rhinoscopy or CT sinuses may be performed but not routinely. (good practice statement).

▪️For children with non-specific cough, we suggest that if cough does not resolve within 2 to 4 weeks, the child should be re-evaluated for emergence of specific etiological pointers. (Very low quality evidence, weak (conditional) recommendation).

▪️ We recommend that when risk factors for asthma are present, a short (2-4 weeks) trial of 400 microgram/day of beclomethasone equivalent, and re-evaluated. (Intermediate quality evidence, strong recommendation).

▪️ We suggest that asthma medications should not be used for cough unless other evidence of asthma is present. (Very low quality evidence, weak (conditional) recommendation).

▪️ We recommend that an empirical approach should not be used unless other features consistent with these conditions are present. (High quality evidence, strong recommendation).

▪️ We suggest that if an empirical trial is used, the trial should be of a defined limited duration in order to confirm or refute the hypothesized diagnosis. (Very low quality evidence, weak (conditional) recommendation).

▪️ For wet or productive cough unrelated to an underlying disease and without any other specific cough pointers we recommend that Two weeks of antibiotics targeting the common respiratory bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and depending on the local antibiotic sensitivities. (High quality evidence, strong recommendation).

▪️  We recommend that the diagnosis of PBB be made when the wet cough persists after2 weeks of appropriate antibiotics, consider treatment with an additional 2 weeks of the appropriate antibiotic(s). (low quality evidence, strong recommendation).

▪️  We recommend that when the wet cough persists after 4 weeks of appropriate antibiotics, further investigations as flexible bronchoscopy with quantitative cultures and sensitivities with or without chest CT) can be undertaken. (Intermediate quality evidence, strong recommendation).

▪️In children without an underlying lung disease who have symptoms and signs or tests consistent with gastroesophageal pathological reflux we recommend that they can be treated for GERD according to evidence-based GERD-specific guidelines (intermediate quality evidence, strong recommendation( & acid suppressive therapy should not be used solely for their chronic cough (low quality evidence, strong recommendation).

▪️For a child diagnosed as somatic cough disorder we recommend that non-pharmacological trials of hypnosis or suggestion therapy or reassurance and counseling or referral to a psychologist or psychiatrist. ( low quality evidence, strong recommendation).

▪️  For children suspected for having OSA we suggest that they are managed in according to sleep guidelines. (Very low quality evidence, weak (conditional) recommendation).

▪️ We suggest that the use of H1RAs in children with non-specific cough must be balanced against the well-known adverse events, especially in very young children, (Low quality evidence, weak (conditional) recommendation). ACCP recommended against the empirical use of H1RAs in children with chronic cough, unless other features consistent with upper airways cough syndrome due to rhinosinusitis are present. (Good practice statement)

▪️We suggest that careful considerations of cost, risk and benefits are needed until there is sufficient data to determine the efficacy of LTRAs in these children. (Very low quality evidence, weak (conditional) recommendation).

▪️   We suggest that cough neuromodulators, are not used in children due to reported adverse events, possible toxicity and lack of clinical trials. (Good practice statement).

➡️Guideline Registration

PREPARE (Practice guideline REgistration for transPAREncy), WHO Collaborating Center for Guideline Implementation and Knowledge Translation, EBM Center, University of Lanzhou, Lanzhou, China. Registration Number: ((submitted and in process)). Link: http://www.guidelines-registry.org/