Outcomes: Clinical Assessments

The primary outcome of this study was the FEV1 Z-score standardized for height, gender, and age (American Thoracic Society/European Respiratory Society criteria using Global Lung Initiative reference values) as a continuous variable. The FEV1 Z-score will be dichotomized to an indicator of a Z-score <−1.64 for estimating the population attributable risk.

Other clinical assessments involve the documentation of participants’ respiratory and general medical histories, medications, a clinical examination (respiratory rate, cardiovascular, and ear, nose, and throat examinations), and a Bacillus Calmette–Guérin vaccine scar presentation, clubbing severity (categorized into mild, moderate, or severe), tonsil score (according to the Brodsky and Friedman Scales [84]), and Mallampati score (a visual assessment of the space between the base of the tongue and the roof of the mouth that is an independent predictor of obstructive sleep apnea [85,86]). In addition, social behavior questions on work and sleep schedules, housing conditions, and exercise routines were asked. Participants were also asked about their caffeine, alcohol, tobacco, and drug intake.

The number of pulmonary exacerbations in the previous 12 months was documented. Symptom severity (cough, sputum color, and dyspnea) was recorded on validated 5-point scales [87,88], including (1) cough severity rated on a Likert-like symptom scale, (2) dyspnea severity rated according to the Modified Medical Research Council Dyspnea Scale [89], and (3) sputum color rated according to a Bronkotest color chart [90].

In addition, oxygen saturation (SPO₂; Medtronic, Nellcor PM10N) and spirometry pre- and postsalbutamol (EasyOne Air Spirometer, NDD Medical Technologies) were assessed. Spirometry was performed according to American Thoracic Society standards [91] with predicted values from Global Lung Initiative reference values [92]. Baseline forced expiratory measurements were performed until 3 good quality, repeatable measures were obtained (FVC and FEV1 both within 0.15 l). This was followed immediately by the administration of 400 µg of salbutamol using a meter dose inhaler through a volumetric spacer device, and reversibility was tested by using spirometry after 15 min.

Nonfasting blood tests were completed at Ascot Hospital by Labtests, a pathology laboratory service accredited by the International Accreditation New Zealand. Trained phlebotomists drew 10 mL of blood for testing the levels of Immunoglobulin E, Immunoglobulin G, Immunoglobulin A, and Immunoglobulin M, eosinophils, and C-reactive protein. A further 6 mL of serum was stored at Middlemore Hospital tissue bank for future analysis of biomarkers; a separate consent for this analysis was obtained.

Chest x-rays (posteroanterior and lateral) were performed by Ascot Radiology. The radiation dose is 0.02 millisieverts with background radiation in comparison being 3 to 4 millisieverts, which is equivalent to 3 days of usual background radiation exposure. No chest x-rays were taken if a participant was pregnant. Chest x-rays were scored by 2 scorers using the Brasfield scoring system. The Brasfield system [93] consists of scoring chest x-rays using graded responses for 5 specific aspects: air trapping (scored 0-4), linear markings (bronchial wall thickening; 0-4), nodular cystic lesions (bronchiectasis; 0-4), large lesions (atelectasis and pneumonia; 0-5), and general severity (0-5). A score of 25/25 represents normal lungs, with numbers detracted for changes seen with lower scores representing more severe disease.