Pulmonary infection in mild variant cystic fibrosis: implications for care.
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 DeltaF508 and a second mild mutation, mainly R117H, with a matched group of DeltaF508 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 DeltaF508 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 FEV1 (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.
Lording
A
A
Academic Unit of Child Health, Stephenson Unit, Sheffield Children's Hospital, Western Bank, Sheffield S10 2 TH, United Kingdom.
McGaw
J
J
Dalton
A
A
Beal
G
G
Everard
M
M
Taylor
C J
CJ
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013183:Sputum / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator