Bile Acids in Sputum and Increased Airway Inflammation in Patients With Cystic Fibrosis

doi:10.1378/chest.11-1573

Chest

Volume 141, Issue 6, June 2012, Pages 1568-1574

https://doi.org/10.1378/chest.11-1573 Get rights and content

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.

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] μg/mL vs 14.45 [7.11-27.88] μg/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 (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.

Section snippets

Study Design and Population

This was a cross-sectional study comparing patients with CF to healthy control subjects, patients with asthma, and patients with chronic cough. Healthy volunteers were recruited from the hospital personnel; subjects with prior history of any respiratory disease, typical reflux symptoms, current smoking, and abnormal spirometry were excluded. Patients with asthma and patients with chronic cough were recruited at the outpatient clinic of the University Hospital Gasthuisberg. Patients with CF were

Subjects

Fifteen healthy volunteers (two men) with mean age of 27 years (range, 21-44), 29 patients with chronic cough (13 men) with mean age of 52 years (range, 14-79), 28 patients with asthma (11 men) with mean age of 54 (range, 16-75), and 41 patients with CF (24 men) with a mean age of 24 years (range, 11-43) were recruited (Table 1). Thirty-three of 41 patients returned the reflux questionnaire; 12 (36%) had typical reflux symptoms.

BAs in Sputum

BAs were found in sputum of two of 15 healthy control subjects

Discussion

It is well established that patients with CF have a high prevalence of acid GER.2, 3, 4, 15 A major concern in CF is the risk of aspirating duodenogastric contents into the lungs, which could result in an increased bronchial inflammatory reaction. Measuring specific markers of aspiration may help to establish the potential role of GER and aspiration in CF. The gold standard in detecting aspiration would be measuring (duodeno)-gastric contents in BALF; however, this is invasive and not routinely

Acknowledgments

Author contributions: Ms Pauwels: collected the data, performed experiments, performed statistical analysis, and wrote the manuscript.

Dr Decraene: contributed to data collection, performed experiments, provided technical support, and approved the manuscript.

Dr Blondeau: contributed to the general discussion and writing and review of the manuscript and provided technical support.

Dr Mertens: contributed to data collection, provided technical support, and approved the manuscript.

Dr Farre:

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Funding/Support: This work is supported by a grant from FWO Vlaanderen (Scientific Research Fund, Flanders, Belgium).

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Chest

Original ResearchCystic FibrosisBile Acids in Sputum and Increased Airway Inflammation in Patients With Cystic Fibrosis

Background

Methods

Results

Conclusions

Section snippets

Study Design and Population

Subjects

BAs in Sputum

Discussion

Acknowledgments

Arch Pediatr

Arch Pediatr

Chest

Arch Med Res

J Pediatr Surg

J Heart Lung Transplant

Lancet

Respir Med

J Thorac Cardiovasc Surg

J Heart Lung Transplant

Chest

Letter: gastro-esophageal reflux in mucoviscidosis [in French]

Nouv Presse Med

Frequency, consequences and pharmacological treatment of gastroesophageal reflux in children with cystic fibrosis

Med Sci Monit

Prevalence and mechanisms of gastro-oesophageal reflux in adult cystic fibrosis patients

J R Soc Med

Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects

J Clin Invest

Original Research
Cystic Fibrosis
Bile Acids in Sputum and Increased Airway Inflammation in Patients With Cystic Fibrosis