Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial

JAMA. 2011 Jul 13;306(2):163-71. doi: 10.1001/jama.2011.954.

Abstract

Context: Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking.

Objective: To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures.

Design, setting, and participants: The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009.

Interventions: BAL-directed (n = 84) or standard (n = 86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P. aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results.

Main outcome measures: Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan.

Results: Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P. aeruginosa in final BAL cultures (risk difference, -1.7% [95% confidence interval, -11.6% to 8.1%]; P = .73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95% confidence interval, -0.94% to 1.33%]; P = .74).

Conclusion: Among infants diagnosed with cystic fibrosis, BAL-directed therapy did not result in a lower prevalence of P. aeruginosa infection or lower total CF-CT score when compared with standard therapy at age 5 years.

Trial registration: anzctr.org.au Identifier: ACTRN12605000665639.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Australia / epidemiology
  • Bronchoalveolar Lavage
  • Child, Preschool
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / diagnostic imaging
  • Cystic Fibrosis / pathology*
  • Hospitalization
  • Humans
  • Infant
  • Infant, Newborn
  • Lung / physiopathology
  • Lung Injury / etiology*
  • Lung Injury / prevention & control
  • New Zealand / epidemiology
  • Prevalence
  • Pseudomonas Infections / diagnosis*
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / epidemiology
  • Respiratory Function Tests
  • Tomography, X-Ray Computed

Substances

  • Anti-Bacterial Agents