Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition

As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Pr oject, we had the unique opportunity to study the longitudinal relationship between Pseudomonas aeruginosa (Fa) acquisition and infection and developi ng lung disease in children with CF. The primary objective was to determine whether acquisition of Pa was associated with a measurable change in the p rogression of lung disease. Two outcome measures were used to study 56 pati ents who were diagnosed through newborn screening: 1) Wisconsin additive ch est radiograph score (WCXR), based on the average of scores from a pulmonol ogist and a radiologist, and 2) the highest forced expired volume in 1 sec (FEV1)/forced vital capacity (FVC) ratio. We used two measures of Fa acquis ition: 1) time of first positive protocol-determined oropharyngeal (with co ugh) culture, and 2) the magnitude of antibody titer detected by ELISA assa ys, using as antigen a crude cell lysate, purified exotaxin A, or an elasta se toxoid prepared from three Pa strains. Other predictor variables include d age, pancreatic status, height-for age, and weight-for-age-percentiles. The best regression model for predicting changes in the WCXR included time to first positive culture and antibody titer for Pa elastase. Prior to Pa a cquisition, WCXR worsened by 0.45 points/year (P > 0.26); after Pa acquisit ion, the rate of worsening increased significantly (P < 0.001) to 1.40 poin ts/year. Each antibody titer level (log base 2) increased the score by 0.48 points (P < 0.001). The best regression model for predicting change in the FEV1/FVC included only time to first positive culture. Prior to Pa acquisi tion, the FEV1/FVC ratio declined by 1.291%/year; after Pa infection, the r ate of decrease significantly accelerated to 1.81%/year (P = 0.001), Our data show that Pa acquisition is associated with declining pulmonary st atus in children with CF, and that this effect is probably gradual rather t han precipitous. Because these patients were diagnosed and treated aggressi vely, our estimates of the effects of Pa acquisition may be conservative. W e also conclude that the WCXR appears to be more sensitive than FEV1/FVC in detecting early changes in lung disease associated with CF. (C) 2001 Wiley -Liss, Inc.