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 fibrosiscomputed 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.
RCT Entities:
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.
Authors: Edith T Zemanick; Brandie D Wagner; Charles E Robertson; Richard C Ahrens; James F Chmiel; John P Clancy; Ronald L Gibson; William T Harris; Geoffrey Kurland; Theresa A Laguna; Susanna A McColley; Karen McCoy; George Retsch-Bogart; Kurtis T Sobush; Pamela L Zeitlin; Mark J Stevens; Frank J Accurso; Scott D Sagel; J Kirk Harris Journal: Eur Respir J Date: 2017-11-16 Impact factor: 16.671
Authors: Shannon B Donnola; Elliott C Dasenbrook; David Weaver; Lan Lu; Karishma Gupta; Anjali Prabhakaran; Xin Yu; James F Chmiel; Kimberly McBennett; Michael W Konstan; Mitchell L Drumm; Chris A Flask Journal: J Cyst Fibros Date: 2015-12-22 Impact factor: 5.482
Authors: J Manos; H Hu; B R Rose; C E Wainwright; I B Zablotska; J Cheney; L Turnbull; C B Whitchurch; K Grimwood; C Harmer; S N Anuj; C Harbour Journal: Eur J Clin Microbiol Infect Dis Date: 2013-07-07 Impact factor: 3.267
Authors: Lyndia C Brumback; Arthur Baines; Felix Ratjen; Stephanie D Davis; Stephen L Daniel; Alexandra L Quittner; Margaret Rosenfeld Journal: Pediatr Pulmonol Date: 2014-04-29
Authors: Felix Ratjen; Scott C Bell; Steven M Rowe; Christopher H Goss; Alexandra L Quittner; Andrew Bush Journal: Nat Rev Dis Primers Date: 2015-05-14 Impact factor: 52.329