This was a prospective study performed with consecutively selected patients over a period of 4 years. The standard workup for all patients included chest radiography, bronchoscopy (for anatomy, and bronchial wash for bacterial culture and lipid-laden macrophages), pulmonary function testing with methacholine challenge tests (for bronchial hyperreactivity, especially in the absence of wheezing to make a diagnosis of cough-variant asthma), sweat chloride testing, extended (20 to 24 h) esophageal pH/impedance monitoring, allergy skin testing, and measuring of Ig levels (IgA, IgE, IgM, and IgG subclasses). In select cases, esophagogastroduodenoscopy (for anatomy, esophagitis, and eosinophilia), barium swallow/esophagogram (for anatomy, swallowing function, and aspiration), antibodies to childhood vaccines, CT scans of the paranasal sinuses, CT scans of the chest, skin tests for tuberculosis, and α1-antitrypsin phenotypes were performed. An ear, nose, and throat evaluation including laryngoscopy was also performed in select cases for all but those children who tested positive for allergy. For the extended pH study monitoring, the position of the distal probe was confirmed radiologically in the distal esophagus about 2.5 cm proximal to the lower esophageal sphincter. The study finding was regarded as being abnormal if the pH in the distal esophagus was < 4 for > 5% of the duration. For the bronchial provocation test, methacholine was administered by using the five-breath dosimeter method, in which concentrations of 0.025, 0.25, 2.5, 10, and 25 mg/mL were given to the patients.11,12 After a baseline spirometry test was performed, patients were instructed to inhale from the nebulizer for five slow inhalations. The FEV1 was measured about 1 min after the fifth inhalation. If the FEV1 fell < 20% from the baseline, the procedure was continued by using the next higher dosage; however, if it fell ≥ 20% from the baseline, testing was discontinued. The results were interpreted by analyzing the changes in the FEV1. A negative methacholine challenge result indicated that the patient was not responsive to the provocative concentration of > 10 to 25 mg/mL; a positive methacholine challenge result was identified as a provocative concentration of < 10 mg/mL, causing a fall in FEV1 of > 20% from the baseline.