BAL Inflammatory Markers Can Predict Pulmonary Exacerbations in Children With Cystic Fibrosis.

BACKGROUND: Pulmonary exacerbations in cystic fibrosis are characterized by airway inflammation and may cause irreversible lung damage. Early identification of such exacerbations may facilitate early initiation of treatment, thereby potentially reducing long-term morbidity. RESEARCH QUESTION: Is it possible to predict pulmonary exacerbations in children with cystic fibrosis, using inflammatory markers obtained from BAL fluid? STUDY DESIGN AND METHODS: A longitudinal analysis was conducted of children aged 0 to 7 years included in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) study between 2005 and 2015. The association between inflammatory markers from annual BAL fluid and time to pulmonary exacerbation requiring hospital admission in the 6-month period post-BAL was analyzed using Kaplan-Meier curves and Weibull regression, adjusting for annually repeated measurements. Admissions for Pseudomonas eradication were excluded in the main analysis, because of the standard policy in participating centers to treat Pseudomonas in-hospital. RESULTS: Nine hundred seventy-six BAL samples from 308 children were analyzed. After exclusion of admissions for Pseudomonas eradication (n = 43), there were 145 pulmonary exacerbations recorded within 6 months of BAL; median time to exacerbation was 31 days (interquartile range, 9-100). In univariate analyses, high IL-8 (hazard ratio [HR], 2.25 for 75th vs 25th percentile; 95% CI, 1.87-2.72), neutrophil elastase (HR, 3.00; 95% CI, 2.03-4.42), and high neutrophil percentage (HR, 1.80 for 75th vs 25th percentile; 95% CI, 1.56-2.04) were all significantly associated with risk for a pulmonary exacerbation (P < .001). The inflammatory markers remained significant predictors after adjustment for clinical predictive variables. INTERPRETATION: Inflammatory markers in BAL fluid are significant predictors of pulmonary exacerbations in young children with cystic fibrosis. The development of noninvasive measures of lung inflammation may facilitate routine surveillance of cystic fibrosis.

Persistent and Recurrent Bacterial Bronchitis-A Paradigm Shift in Our Understanding of Chronic Respiratory Disease.

The recent recognition that the conducting airways are not "sterile" and that they have their own dynamic microbiome, together with the rapid advances in our understanding of microbial biofilms and their roles in the causation of respiratory diseases (such as chronic bronchitis, sinusitis, and chronic otitis media), permit us to update the "vicious circle" hypothesis of the causation of bronchiectasis. This proposes that chronic inflammation driven by persistent bacterial bronchitis (PBB) causes damage to both the epithelium, resulting in impaired mucociliary clearance, and to the airway wall, which eventually manifests as bronchiectasis. The link between a "chronic bronchitis" and a persistence of bacterial pathogens, such as non-typable Haemophilus influenzae, was first made more than 100 years ago, and its probable role in the causation of bronchiectasis was proposed soon afterward. The recognition that the "usual suspects" are adept at forming biofilms and hence are able to persist and dominate the normal dynamically changing "healthy microbiome" of the conducting airways provides an explanation for the chronic colonization of the bronchi and for the associated chronic neutrophil-dominated inflammation characteristic of a PBB. Understanding the complex interaction between the host and the microbial communities of the conducting airways in health and disease will be a key component in optimizing pulmonary health in the future.