Lower Airway Inflammation in Infants with Cystic Fibrosis Detected by Newborn Screening

Abstract

Controversy exists over whether the lower airway inflammation that characterizes cystic fibrosis (CF) is initiated primarily by the genetic defect. To determine if inflammation precedes infection, we examined bronchoalveolar lavage (BAL) fluid cytology, cytokines (interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-α), and free neutrophil elastase activity from 70 CF (aged 1.5–71 months) children detected by newborn screening and 19 (aged 2.0–48 months) controls with chronic stridor. CF subjects were selected and categorized as pristine (13 aged ≤ 6 months, lacking prior respiratory symptoms and exposure to antibiotics, and without respiratory pathogens on BAL), infected (42 with viruses or ≥ 10⁵ colony-forming units/ml of pathogenic bacteria in BAL), and uninfected (15 aged > 6 months, asymptomatic, not taking antibiotics at bronchoscopy, and free of pathogens in their BAL). To further resolve if inflammation develops without infection, inflammatory mediators in paired annual BAL samples from 38 CF subjects were measured, and results were grouped according to whether BAL showed persistence (n = 6), acquisition (n = 8), clearance (n = 13), or absence (n = 11) of infection. While pristine, uninfected, and control subjects had similar BAL profiles, infected patients showed elevated inflammatory indices, including increased IL-10 (P < 0.001). Pristine subjects had the fewest signs of inflammation. Analysis of BAL pairs found differences between the four infection groups for changes in neutrophil percentages, IL-8 (P < 0.001), and free neutrophil elastase (P = 0.009). Infection was associated with elevated inflammatory mediators in BAL fluid. In contrast, minimal or reduced signs of inflammation accompanied absence of eradication of infection from BAL fluid. We conclude that in CF, infection initiates and sustains airway inflammation. Pediatr Pulmonol.