Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis

A thorough understanding of the early natural history of cystic fibrosis (C F) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period th rough annual bronchoalveolar lavage (BAL) for culture and measurements of p ro- and anti-inflammatory cytokines, semiannual infant pulmonary function t esting, and quarterly clinical evaluations. Both the prevalence of CIF pathogens and their density in BAL fluid increas ed with age. Infants had neutrophilic lower airway inflammation and elevate d IL-8 concentrations independent of whether CF pathogens were recovered. T otal leukocyte and neutrophil densities and IL-8 concentrations increased w ith density of CIF pathogens in BAL fluid, whether the isolated organism wa s P. aeruginosa or another pathogen. IL-10 concentrations were similar in C F subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (d ecreased expiratory flows and air trapping). Subjects from whom CF pathogen s were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Bra sfield chest X-ray scores. Our findings provide a foundation for future stu dies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy. (C) 2001 Wiley-Liss, Inc.