Pulmonary infection in mild variant cystic fibrosis: Implications for care

Abstract

Background Disease phenotype in cystic fibrosis (CF) shows considerable heterogeneity. Atypical or mild mutations in the CFTR gene have been linked to late-onset pulmonary disease; however, few reports document the condition of the airway in infants and young children with apparent “mild” disease. Prognosis is uncertain in this group of patients and this, in turn, has led to inconsistency in management. Our initial experience of pulmonary infection in children with mild variant CF prompted a more detailed review of clinical outcome. Methods A retrospective cohort study was carried out comparing frequency of bacterial isolates and clinical outcomes in eleven compound heterozygotes for ΔF508 and a second mild mutation, mainly R117H, with a matched group of ΔF508 homozygotes. Results Staphylococcus aureus was isolated in 8 of the 11 patients with mild variant disease and Pseudomonas aeruginosa found in 7 (64%), although the frequency of positive cultures was significantly less (2.8/year) than the ΔF508 homozygotes (6.1/year, p < 0.05). Shwachman scores (median + range) were significantly higher in patients with mild mutations — 94, 74–92 vs. 88, 77–91; p < 0.005); there was also a small but significant difference in chest radiograph (Chrispin–Norman) scores (median + range) (mild 5.1, 4–9, vs. severe 5.8, 3–10; p 0.04). There was little difference in lung function in terms of FEV 1 (median + range) between the two groups (% predicted, mild 86.5, 68–87 vs. severe 76.0, 65–88; p 0.5). Conclusions Most patients with mild variant CF will have bacterial isolates from airway cultures requiring antibiotic therapy three to four times a year. Infection with both S. aureus and P. aeruginosa is common. Anti-staphylococcal prophylaxis for the first two years should be considered.