Risk Factors Associated with FEV1 Decline in Cystic Fibrosis (CF) Patients with Normal Pulmonary Function

Abstract 2081 Pulmonary: Cystic Fibrosis Poster Symposium, Tuesday, 5/4

Lung disease accounts for most of the morbidity and mortality in CF patients. There is wide variability among patients in the age of onset and the rate of progression of the lung disease. To evaluate the effects of CF transmembrane conductance regulator (CFTR) gene mutations, glucose tolerance abnormalities, bronchial hyperreactivity, atopy and the microbiology of respiratory secretions on the rate of decline of lung function, we are prospectively following a group of CF patients (n = 90) with normal pulmonary function at the start of the study. These patients were screened for the presence of the risk factors of interest at entry into the study, and their pulmonary function is evaluated at least quarterly. After 18 months of the planned 3 years of follow-up, interim analysis was performed using mixed linear regression. The mean age for the group at enrollment was 15.2 years (SD 8.6, median 13.7), 52% of the patients enrolled were female. Fifty-three percent of the patients had 2 copies of ΔF508, 37% had one copy, and 10% had 2 non-ΔF508 CFTR mutations. At enrollment the mean (SD) FVC was 115.4 (13)%-predicted, FEV1 was 104.77 (14.6)%-pred., FEV1/FVC was 0.89 (0.07), and FEF25-75 was 100.3 (16.8)%-pred. Nutritional status, as assessed by the ratio of weight to predicted weight-for-height was a mean of 103% (SD 16). Normal glucose tolerance was found in 56.5% of the subjects, 39.1% had impaired glucose tolerance and 4.3% showed a diabetic response. Atopy was found in 46% of the patients and bronchial hyperreactivity in 15% of the patients. Staphylococcus aureus was detected in 15.5%, Pseudomonas species (mucoid and non-mucoid) in 26.2%, both S. aureus and Pseudomonas species in 7.1%, Burkholderia cepacia in 3.6%, and other potential pathogens in 10.7%. The group has experienced an average rate of decline of -3.25%-predicted/year. No significant difference has occurred between males and females (p>0.1). Patients with no copies of ΔF508 have not experienced a change in their FEV1, and this is significantly different (p<0.01) from patients with 1 or 2 copies of ΔF508. These latter 2 CFTR genotype groups do not differ significantly in their average rates of decline (p=0.2). Bronchial hyperreactivity (p=0.01) and cultures positive for both S. aureus and Pseudomonas (p=0.001) are independently associated with a higher rate of decline. No other significant associations have been found. We conclude from this interim analysis, that of the potential risk factors examined, CFTR genotype, bronchial hyperreactivity and the presence of both S. aureus and Pseudomonas species in respiratory secretions are most strongly associated with respiratory decline over 18 months of observation of these CF patients with normal spirometry at entry into the study. However, we expect that as follow-up continues and more longitudinal data accumulates the variability for the parameters measured will decrease and other associations may become apparent.

Funded by a grant from the Cystic Fibrosis Foundation

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