Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis

Background: Chronic progressive lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis (CF), but severity of lung disease and rate of lung function decline are widely variable. Accurate estimates of decline have been difficult to define and compare because the timing of measurements and duration of follow-up differ in various patient groups. Patients: Three hundred sixty-six patients with CE born from 1960 to 1974, were selected from a CF database birth cohort if they had two or more measurements of pulmonary function, at least one of which was performed before the age of 10 years. Methods: Mixed model regression analysis provided estimates of the average rate of decline of spirometry measurements in subgroups on the basis of survival age, sex, pancreatic status, and genotype. Results: Patients who died before the age of 15 years had significantly poorer pulmonary function when first tested and a more rapid decline in pulmonary function thereafter than patients who survived beyond the age of 15 years. In the latter, functional levels at the age of 5 years were normal, but average rates of decline were significantly related to survival age. Female patients had significantly steeper decline than male patients, and those with pancreatic insufficiency had much steeper decline 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, who died before age 15, appear to have had normal pulmonary function when first tested in early childhood. Pancreatic sufficiency, male gender, and some non-Delta F508 mutations are associated with a slower rate of pulmonary function decline. Mixed model analysis is a valuable tool for describing and comparing pulmonary function decline in groups of patients with CF.