Table 1.

Prospective Studies That Have Described Various Etiologies of Chronic Cough in Children (Key Questions 1 and 2)

Study/Year	Country	Setting	Method of Assessment	Inclusion Criteria, Exclusion	No. Enrolled/ No. Completed/ Age	Primary Outcome Used	Diagnoses Defined A Priori; Length of Follow-Up	Period Effect Considereda	Top 3 Most Common Diagnoses	Age or Setting Influence (or Both) Described
Asilsoy et al22/2008	Turkey	Single center, pediatric outpatients	ACCP guideline14	> 4 wk cough Exclusion: none reported	108/108 Mean = 8.4 y Range = 6-14 y	Cough, unspecified	Partial; Follow-up not reported	Not specified	Asthma/asthma-like n = 27 (25%) PBB = 25 (23%) UACS = 22 (20%)	No
Chang et al1/2012	Australia	Multicenter, Respiratory outpatients	Modified ACCP14 and TSANZ23 guidelines	Age < 18 y cough > 4 wk duration, newly referred Exclusion: chronic respiratory illness	346/346 Mean = 4.5 y, SD, 3	Cough resolution by cough diary,24,c PC-QOL25	Yes; Follow-up maximum 12 mo for diagnosis and 6 mo after diagnosis	Yes, 2 wk of treatment	PBB = 142 (41%) Asthma = 55 (16%) Resolved without specific diagnosis = 48 (14%)	Common diagnoses differed in age groups and settings (rural vs cities)
Dani et al26/2002	India	Single center, pediatric outpatients	Sequential routine investigations: full blood count, erythrocyte sedimentation rate, Mantoux test, sputum, throat swab, chest radiograph Further investigations (eg, HIV, CT imaging, bronchoscopy, barium swallow) when indicated	Consecutive, immune-competent, age 1-12 y Chronic cough > 3 wk, unknown etiology Exclusion: heart disease	94 Age NR	Diagnosis by history and physical examination and routine investigations	NR Follow-up NR	No	Asthma = 35 (37%) Tuberculosis = 21 (22.3%) Pulmonary eosinophilia = 9 (9.5%) Sinusitis = 9 (9.5%)	No
Gedik et al34/2015	Turkey	Single center, pediatric or allergy outpatients	ACCP guideline14	Age < 17 y, persistent cough > 4 wk Exclusion: known chronic respiratory, neuromuscular, growth, cardiac problems; genetic syndromes; prematurity	563/563 Follow-up: NR Mean age = 5.4 y, SD, 3.8	Verbal category score	Yes Follow-up: 2 mo after cough resolution	Yes	Asthma = 140 (25%) Asthma-like = 107 (19%) PBB = 67 (12%)	Yes for age: asthma most common in all ages; second most common diagnosis: PBB in young children, psychogenic cough in older children
Karabel et al5/2014	Turkey	Single center, respiratory outpatients	ACCP guideline14	> 4 wk cough Exclusion: neuromuscular, cardiac, syndromes, respiratory tract infection last 4 wk	270/270 Mean = 6.5 y range = 7 mo-17 y	Not described	Partial; Follow-up: 12 mo	Not specified	Asthma = 73 (27%) Asthma-like = 42 (15.5%) GERD = 27 (10%)	No
Khoshoo et al27/2009	USA	Single center, pediatric outpatients	Chest radiograph, bronchoscopy, PFT with methacholine, sweat test, pH- or impedence-metry, skin testing, Ig levels Ohers also had: Barium meal or swallow, CT chest/sinus, laryngoscopy, Mantoux test	> 8 wk cough, born full term, neurodevelopmentally normal, no smoke exposure, no history of febrile or respiratory illness, no cardiac illness Exclusion: asthma, RAD, cystic fibrosis (unless able to do PFT/airway hyperreactivity)	40/40 Mean age = 7.8 y (range = 5-12 y)	Visual analogue scale score but success of treatment undefined Only 1 group (infection) had visual analogue scale improvement of ≥ 70%	Yes, Follow-up: none	No	GERD = 11 (27.5%) Asthma/cough variant asthma = 11 (27.5%) Allergy = 9 (22.5%)	No Note: comparison was made using mean and SD, although group size ranged from 1-11
Marchant et al28/2006	Australia	Single center, respiratory outpatients	Modified ACCP 199829 guideline	> 3 wk cough, age < 18 y, newly referred Exclusion: NR	108/103 Median = 2.6 y IQR = 1.2-6.9	Cough diary24	Yes Follow-up: maximum 12 mo for diagnosis, after diagnosis NR	Yes, 2 wk of treatment	PBB = 43 (40%) Resolved without specific diagnosis = 24 (22%) Bronchiectasis = 6 (5.6%)	No
Rehman et al30/2009	Pakistan	Single center, pediatric outpatients	Locally designed algorithm with Mantoux test	Age 6-59 mo > 4 wk cough Exclusion: use of ACE inhibitors	172/161 Summary NR	Parents reporting—unspecified	NR Follow-up: until cough resolved (maximum 18 mo)	No	Asthma = 61 (38%) Postviral = 21 (13%) Tuberculosis = 14 (9%)	No
Usta et al31/2014	Turkey	Single center, pediatric allergy outpatients	British Thoracic Society guideline	Inclusion: NR Exclusionb	156/156 Mean = 8.4 y SD, 2.6	Cough, unspecified	Partial; Follow-up: maximum 18 mo for diagnosis, After diagnosis, NR	Not specified	Postnasal drip + asthma = 30 (19%) Postnasal drip = 29 (19%) Asthma = 19 (12%) PBB = 19 (12%)	No
Yilmaz et al32/2014	Turkey	Single center, pediatric asthma, allergy outpatients	CHEST guidelines but evaluated by allergists skin prick test (house dust mites, pollen, alternaria, animal dander, latex), full blood count	Age < 18 y, chronic cough > 4 wk (nonspecific isolated dry cough) Exclusion: specific cough pointer present, wet cough, chest radiograph or PFT results abnormal, characteristic cough pattern, chronic respiratory illness, use of ICS, LTRA, ACE inhibitor	119/109 Median = 5 y IQR, 3.5-9	Cough diary card	Yes, Follow-up: mean 21 mo (SD, 5)	No	Resolved without prescription = 23 (21%) Rest were treated with ICS for 2 wk: 24 (22%) responded, 62 (57%) partially responded	No

ACE = angiotensin-converting enzyme; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroid; IQR = interquartile range; LTRA = leukotriene receptor antagonist; NR = not reported; PBB = protracted bacterial bronchitis; PC-QOL = parent cough-specific quality of life; PFT = pulmonary function test; RAD = reactive airway disease; TSANZ = Thoracic Society of Australia and New Zealand; UACS = upper airway cough syndrome. (Modified with permission from Chang et al²¹ and Chang et al.⁶)

^aPeriod effect considered, that is, use of “time to response”: the temporal relationship between use of medication and outcome was defined a priori.

^b”Premature birth, neuromotor development retardation, developmental growth retardation, chest wall deformity, smoking habit, clubbing, cardiac disease, any known chronic disease or pulmonary disease, or both, and those who could not cooperate in pulmonary function testing.”³¹

^cImprovement of ≥ 75% or total resolution according to parental reports and cough diary data for ≥ 3 d.