LONGITUDINAL ANALYSIS OF PULMONARY-FUNCTION DECLINE IN PATIENTS WITH CYSTIC-FIBROSIS

Background: Chronic progressive lung disease is the most prominent cau se of morbidity and death in patients with cystic fibrosis (CF), but s everity of lung disease and rate of lung function decline are widely v ariable. Accurate estimates of decline have been difficult to define a nd compare because the timing of measurements and duration of follow-u p differ in various patient groups. Patients: Three hundred sixty-six patients with CE born from 1960 to 1974, were selected from a CF datab ase birth cohort if they had two or more measurements of pulmonary fun ction, at least one of which was performed before the age of 10 years. Methods: Mixed model regression analysis provided estimates of the av erage rate of decline of spirometry measurements in subgroups on the b asis of survival age, sex, pancreatic status, and genotype. Results: P atients who died before the age of 15 years had significantly poorer p ulmonary function when first tested and a more rapid decline in pulmon ary function thereafter than patients who survived beyond the age of 1 5 years. In the latter, functional levels at the age of 5 years were n ormal, but average rates of decline were significantly related to surv ival age. Female patients had significantly steeper decline than male patients, and those with pancreatic insufficiency had much steeper dec line than those with pancreatic sufficiency. In the subset of 197 who survived to 1990 and were subsequently genotyped, rate of decline was greater in those homozygous for the Delta F508 mutation, compared with those who were heterozygous for Delta F508 or those who had two other mutations. Discussion: All but the most severely affected patients, w ho died before age 15, appear to have had normal pulmonary function wh en first tested in early childhood. Pancreatic sufficiency, male gende r, and some non-Delta F508 mutations are associated with a slower rate of pulmonary function decline. Mixed model analysis is a valuable too l for describing and comparing pulmonary function decline in groups of patients with CF.