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Impact of Burkholderia dolosa on Lung Function and Survival in Cystic Fibrosis

Clinical Research Program; Divisions of Respiratory Diseases and Infectious Disease; Infection Control Program; Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts; and Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan

Correspondence and requests for reprints should be addressed to Donald Goldmann, M.D., Infectious Diseases Division, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. E-mail: don.goldmann{at}childrens.harvard.edu

Rationale: Chronic infection with Burkholderia cepacia complex bacteria in cystic fibrosis is associated with accelerated decline in pulmonary function and increased mortality. Clinical implications of the recently characterized genomovar VI, B. dolosa, are unknown.

Objectives: Characterization of impact of B. dolosa on pulmonary function and mortality in cystic fibrosis.

Methods: We compared patients chronically infected with B. dolosa (n = 31) with unmatched patients with B. multivorans (n = 24) and with age- and sex-matched control subjects without Burkholderia species (n = 58). We analyzed rates of pulmonary function decline (% predicted FEV₁) using a random effects model assuming segmented linear trends. All available FEV₁ measurements from 5 yr (median, 4.8) before until 2.5 yr (median, 1.5) after the first positive culture for Burkholderia (reference date) were analyzed. Survival was compared using the Kaplan-Meier method and proportional hazards model.

Measurements and Main Results: Baseline FEV₁ and rate of decline were similar in the cohorts. Decline in FEV₁ after the reference date accelerated in patients with B. dolosa (–2.3 percentage points/yr pre vs. –7.1 post, p = 0.002), but was unchanged in the B. multivorans and control patients (–2.3 vs. –0.8 post, p = 0.38, and –2.1 pre vs. –0.5 post, p = 0.20, respectively). The probability of dying within 18 mo of the reference date was 13, 7, and 3% for B. dolosa, B. multivorans, and control patients, respectively (B. dolosa vs. control hazard ratio, 10.8; 95% confidence interval, 1.3–92.8; p = 0.03).

Conclusions: B. dolosa chronic infection in cystic fibrosis is associated with accelerated loss of lung function and decreased survival.

Key Words: Burkholderia cepacia complex • Burkholderia multivorans • infection control

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