title: Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis.
abstract: A thorough understanding of the early natural history of cystic fibrosis (CF) 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 through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.
authors.affiliation: Cystic Fibrosis Research Center, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA. mrosen@u.washington.edu
authors.forename: M
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: R L
authors.initials: RL
authors.lastname: Gibson
authors.forename: S
authors.initials: S
authors.lastname: McNamara
authors.forename: J
authors.initials: J
authors.lastname: Emerson
authors.forename: J L
authors.initials: JL
authors.lastname: Burns
authors.forename: R
authors.initials: R
authors.lastname: Castile
authors.forename: P
authors.initials: P
authors.lastname: Hiatt
authors.forename: K
authors.initials: K
authors.lastname: McCoy
authors.forename: C B
authors.initials: CB
authors.lastname: Wilson
authors.forename: A
authors.initials: A
authors.lastname: Inglis
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: T R
authors.initials: TR
authors.lastname: Martin
authors.forename: B W
authors.initials: BW
authors.lastname: Ramsey
mesh_terms: D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000503:physiopathology*; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha