Chest

Chest

Volume 130, Issue 4, October 2006, Pages 995-1002
Journal home page for Chest

Original Research
Prospective Analysis of Cystic Fibrosis Transmembrane Regulator Mutations in Adults With Bronchiectasis or Pulmonary Nontuberculous Mycobacterial Infection

https://doi.org/10.1378/chest.130.4.995Get rights and content

Background

Bronchiectasis and pulmonary infection with nontuberculous mycobacteria (NTM) may be associated with disease-causing mutations in the cystic fibrosis transmembrane regulator (CFTR).

Methods

Fifty adult patients at Stanford University Medical Center with a diagnosis of bronchiectasis and/or pulmonary NTM infection were prospectively characterized by sweat chloride measurement, comprehensive mutational analysis of CFTR, and sputum culture results.

Results

A de novo diagnosis of cystic fibrosis (CF) was established in 10 patients (20%). Patients with CF were more likely than those without CF to have mucus plugging seen on chest high-resolution CT, and women with a CF diagnosis were thinner, with a significantly lower mean body mass index than the non-CF subjects. Thirty CFTR mutations were identified in 24 patients (50% prevalence). Sweat chloride concentration was elevated > 60 mEq/dL (diagnostic of CF) in seven patients (14%), and from 40 to 60 mEq/dL in eight patients (16%). The frequency of CFTR mutations was elevated above that expected in the general population: heterozygous ΔF508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T (17% vs 5 to 10%). Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I. Three novel CFTR mutations were identified: A394V, F650L, and C1344S.

Conclusions

Mutations in CFTR that alter RNA splicing and/or functional chloride conductance are common in this population, and are likely to contribute to the susceptibility and pathogenesis of adult bronchiectasis and pulmonary NTM infection. Careful clinical evaluation for disease cause should be undertaken in this clinical context.

Section snippets

Patient Population

The study was approved by the Stanford University Institutional Review Board, and all subjects provided written informed consent to participate. Fifty patients with bronchiectasis and/or symptomatic NTM infection were prospectively enrolled through the Stanford University Medical Center adult pulmonary medicine clinic from January 2003 through April 2004. Some of these patients (n = 7) had been seen previously at Stanford University Medical Center but had not undergone evaluation for the cause

Results

Fifty subjects (42 women and 8 men) aged 28 to 82 years (mean, 61.4 years) were enrolled. Thirty subjects (60%) had both bronchiectasis and pulmonary NTM, while 17 subjects (34%) had bronchiectasis alone without NTM infection. Three subjects (6%) had a pulmonary NTM infection without evidence of bronchiectasis on HRCT studies. There was no apparent association between specific pulmonary pathogens recovered and particular CFTR mutations or sweat chloride measurements.

Mean BMI was 22.1 ± 3.40 for

Discussion

This prospective study revealed that 20% of patients presenting to an adult pulmonary clinic with bronchiectasis and/or pulmonary NTM infection were conferred a de novo diagnosis of CF based on sweat chloride concentration or identification of two CFTR gene mutations. The study illuminates a number of important clinical points. First, the presence of bronchiectasis and/or pulmonary NTM infection in adults can be associated with a significant risk for the presence of occult CF. Second, a

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    The authors have no conflicts of interest with respect to this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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    Copyright © 2006 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.