There are limited objective measures of the severity of lung disease before children are able to routinely perform spirometry, generally at age 6 years. Identifying risk factors for reduced lung function at age 6 provides opportunities to intervene and slow the progression of cystic fibrosis (CF) lung disease.

OBJECTIVES: To evaluate early childhood predictors of lung function at age 6-7 in a large U.S. CF cohort in the current era of widespread early eradication therapy for Pseudomonas aeruginosa (Pa).

METHODS: Participants were children with CF enrolled before age 4 in the Early Pseudomonas Infection Control (EPIC) Observational Study, a multicenter, longitudinal study that enrolled Pa-negative children ≤12 years. Linear regression was used to estimate the association between potential early childhood risk factors and the best FEV1 % predicted at age 6-7 years.

MEASUREMENTS AND MAIN RESULTS: 484 children (out of 1,797 enrolled in the EPIC Observational Study) met the eligibility criteria for this analysis. Mean (SD) age at enrollment was 2.0 (1.3) years. In a multivariable model adjusted for age at enrollment, the following risk factors were significantly associated with lower mean (95% Confidence Interval) FEV1 % predicted at age 6-7: weight percentile < 10% during the year of enrollment [-5.3 (-9.1, -1.5)], Pa-positive during the year of enrollment [-2.8 (-5.7, 0.0)], crackles or wheeze during the year of enrollment [-5.7 (-9.4, -1.9)], mother's education high school or less [-4.2, (-7.3, -1.2)]; and mother smoked during pregnancy [-4.4, (-8.8, 0.1)].

CONCLUSIONS: In this large U.S. cohort, we identified several early childhood risk factors for lower FEV1 at age 6-7 years, most of which are modifiable. Clinical Trial registered at clinicaltrials.gov (NCT00097773).