Bronchoscopy‐guided antimicrobial therapy for cystic fibrosis

Kamini Jain, Claire Wainwright, Alan R Smyth

Early diagnosis and treatment of lower respiratory tract infections are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are unavailable, treatment relies mainly on cultures from oropharyngeal specimens; however, there are concerns regarding the sensitivity of these to identify lower respiratory organisms.Bronchoscopy and related procedures (including bronchoalveolar lavage) though invasive, allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may help in a more accurate diagnosis of lower respiratory tract infections and guide the selection of antimicrobials, which may lead to clinical benefits.This is an update of a previous review. To evaluate the use of bronchoscopy-guided antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched two registries of ongoing studies and the reference lists of relevant articles and reviews.Date of latest search: 28 August 2015. We included randomized controlled studies including people of any age with cystic fibrosis, comparing outcomes following therapies guided by the results of bronchoscopy (and related procedures) with outcomes following therapies guided by the results of any other type of sampling (including cultures from sputum, throat swab and cough swab). Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information. The search identified nine studies, but only one study with data from 157 participants (170 people were enrolled) was eligible for inclusion in the review. This study compared outcomes following therapy directed by bronchoalveolar lavage for pulmonary exacerbations during the first five years of life with standard treatment based on clinical features and oropharyngeal cultures. The study enrolled infants with CF who were under six months of age and diagnosed through newborn screening and followed them until they were five years old.We considered this study to have a low risk of bias; however, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was limited due to the prevalence (of Pseudomonas aeruginosa isolation in bronchoalveolar lavage samples at five years age) being much lower in both the groups compared to that which was expected and which was used for the power calculation. The sample size was adequate to detect a difference in high-resolution computed tomography scoring. The quality of evidence for the key parameters was graded as moderate except high-resolution computed tomography scoring and cost of care analysis, which were graded as high quality.At five years of age, there was no clear benefit of bronchoalveolar lavage-directed therapy on lung function z scores or nutritional parameters. Evaluation of total and component high-resolution computed tomography scores showed no significant difference in evidence of structural lung disease in the two groups.In addition, this study did not show any difference between the number of isolates of Pseudomonas aeruginosa per child per year diagnosed in the bronchoalveolar lavage-directed therapy group compared to the standard therapy group. The eradication rate following one or two courses of eradication treatment was comparable in the two groups, as were the number of pulmonary exacerbations. However, the number of hospitalizations was significantly higher in the bronchoalveolar lavage-directed therapy group, but the mean duration of hospitalizations was significantly less compared to the standard therapy group.Mild adverse events were reported in a proportion of participants, but these were generally well-tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of bronchoalveolar lavage in 4.8% of procedures. This review, limited to a single, well designed randomized-controlled study, shows no clear evidence to support the routine use of bronchoalveolar lavage for the diagnosis and management of pulmonary infection in pre-school children with cystic fibrosis compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence was available for adult and adolescent populations.