Bronchoscopy‐guided antimicrobial therapy for cystic fibrosis
Abstract
Background
Early diagnosis and treatment of lower respiratory tract infections, particularly those with Pseudomonas aeruginosa, 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.
Objectives
To evaluate the use of bronchoscopy‐guided antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis.
Search methods
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 November 2013.
Selection criteria
We included randomized controlled studies including patients of any age with cystic fibrosis, comparing outcomes following therapies guided by the results of bronchoscopy (including bronchoalveolar lavage or protected bronchial brush sampling) with outcomes following therapies guided by the results of any other type of sampling (including cultures from sputum, throat swab and cough swab).
Data collection and analysis
Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information.
Main results
The search identified nine studies, but only one study with data from 157 participants (170 patients 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 for high‐resolution computed tomography scoring, which was graded as high.
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 patients, 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.
Authors' conclusions
This review, which only includes a single study, shows that there is 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.
PICOs
Plain language summary
Using samples obtained by bronchoscopy to decide how to treat lung infections in patients with cystic fibrosis
Respiratory problems in people with cystic fibrosis are mainly due to repeated lung infections. Culturing sputum samples often allows quick identification of the organism causing the infection and early treatment. If patients (most young children and some adults) can not provide sputum samples, swabs are taken from the upper throat to identify the organism causing the infection in the lower airways – but this may not be the most reliable method.
During a bronchoscopy, clinicians examine the lower airways using a long, thin flexible tube with a light and camera at one end; they may also collect mucus. This requires patients to be in hospital and be sedated or have a general anaesthetic. It is not certain if treatment based on bronchoscopy samples is better than that based on throat swabs.
We searched for studies of participants of any age, but this review only includes one study in young children. The study randomly assigned 170 babies under six months of age with cystic fibrosis to receive antibiotics for chest infections based on samples taken by either bronchoscopy or from the throat. Outcomes were assessed at five years of age; 157 children completed the study.
This study did not show any difference between the groups in lung function, weight, body mass index or in the score calculated by a CT scan of the lungs at five years of age. Additionally, there were no differences in how many children in each group had an infection with Pseudomonas aeruginosa at five years of age, or per year of follow up, or how often a child was unwell with respiratory symptoms. Patients in the bronchoscopy group were admitted to hospital more often than the other group, although admissions were generally shorter.
Adverse events reported during, and after bronchoscopy, were not serious and generally well tolerated; the most common was increased coughing (noted in one third of patients).
This study was limited because fewer patients were recruited than the study needed. As the treatment of initial infection with Pseudomonas aeruginosa is highly successful, larger and longer studies are needed to detect small differences between the groups. Conducting such large studies is extremely difficult.
There is currently not enough evidence to support the regular use of bronchoscopy to diagnose and treat lung infections in young patients with cystic fibrosis.
