Bile Acids in Sputum and Increased Airway Inflammation

Background: Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux and aspiration of duodenogastric contents into the lungs. We aimed to assess aspiration in patients with CF by measuring duodenogastric components in induced sputum and to investigate whether the presence of bile acids (BAs) in sputum was correlated with disease severity and markers of inflammation.

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Methods: In 41 patients with CF, 15 healthy volunteers, 29 patients with asthma, and 28 patients with chronic cough, sputum was obtained after inhalation of hypertonic saline. Sputum supernatant was tested for BA and neutrophil elastase. Spirometry and BMI were assessed on the day of sputum collection.

Results: Two of 15 healthy patients (13%), eight of 29 patients (28%) with asthma, four of 28 patients (14%) with chronic cough, and 23 of 41 patients (56%) with CF had BA in sputum. BA concentrations were similar in patients who are positive for BA with genotype F508del homozygote, F508del heterozygote, and other CF mutations and were not related with BMI and age. Patients with CF with BA in sputum had a higher concentration of neutrophil elastase compared with patients without BA in sputum (31.25 [20.33-54.78] mg/mL vs 14.45 [7.11-27.88] mg/mL, P < .05). There was a significant correlation between BA concentrations and dynamic lung volumes (FEV₁ % predicted [r = —0.53, P< .01], FVC% [r = —0.59, P< .01]) as well as with number of days of antibiotic IV treatment Asthma (r = 0.58, P < .01).

Conclusions: BAs are present in the sputum of more than one-half of patients with CF, suggesting aspiration of duodenogastric contents. Aspiration of BA was associated with increased airway inflammation. In patients with BA aspiration, the levels of BA were clearly associated with the degree of lung function impairment as well as the need for IV antibiotic treatment.

Abbreviations: AZM = azithromycin; BA = bile acid; BALF = BAL fluid; CF = cystic fibrosis; GER = gastroesophageal reflux; NADH = nicotinamide adenine dinucleotide hydrogen; NSE = neutrophil elastase; PPI = proton pump inhibitor