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

Abstract

As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Project, we had the unique opportunity to study the longitudinal relationship between Pseudomonas aeruginosa (Pa) acquisition and infection and developing lung disease in children with CF. The primary objective was to determine whether acquisition of Pa was associated with a measurable change in the progression of lung disease. Two outcome measures were used to study 56 patients who were diagnosed through newborn screening: 1) Wisconsin additive chest radiograph score (WCXR), based on the average of scores from a pulmonologist and a radiologist, and 2) the highest forced expired volume in 1 sec (FEV(1))/forced vital capacity (FVC) ratio. We used two measures of Pa acquisition: 1) time of first positive protocol-determined oropharyngeal (with cough) culture, and 2) the magnitude of antibody titer detected by ELISA assays, using as antigen a crude cell lysate, purified exotoxin A, or an elastase toxoid prepared from three Pa strains. Other predictor variables included 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 acquisition, WCXR worsened by 0.45 points/year (P > 0.25); after Pa acquisition, the rate of worsening increased significantly (P < 0.001) to 1.40 points/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 FEV(1)/FVC included only time to first positive culture. Prior to Pa acquisition, the FEV(1)/FVC ratio declined by 1.29%/year; after Pa infection, the rate of decrease significantly accelerated to 1.81%/year (P = 0.001). Our data show that Pa acquisition is associated with declining pulmonary status in children with CF, and that this effect is probably gradual rather than precipitous. Because these patients were diagnosed and treated aggressively, our estimates of the effects of Pa acquisition may be conservative. We also conclude that the WCXR appears to be more sensitive than FEV(1)/FVC in detecting early changes in lung disease associated with CF.

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

“…However, we speculate that changes in ASL pH might contribute, in part, to variations in the species of bacteria that infect CF airways. For example, S. aureus is commonly cultured early and P. aeruginosa is cultured later in the course of CF airway disease in humans and pigs (46,47,75). Interestingly, a reduced pH impaired hBD-3 killing of S. aureus, but had minor effects on killing of P. aeruginosa.…”

Early Childhood Risk Factors for Decreased FEV1at Age 6-7 Years in Young Children with Cystic Fibrosis

“…Several studies have demonstrated that young age at initial P. aeruginosa acquisition is an important risk factor for the development of more severe CF lung disease (6,(31)(32)(33). It is likely that the earlier acquisition of P. aeruginosa allows more time for phenotypes to develop that are associated with pulmonary exacerbations and/or lower FEV 1 % predicted, for example, mucoidy (34,35).…”

Reducing bias in bacterial community analysis of lower respiratory infections

“…The aim of this study was to determine the effects of PMA treatment on bacterial community characteristics (abundance, diversity, composition and structure), as analysed by 16S rRNA gene pyrosequencing, total bacterial Q-PCR enumeration and species-specific Q-PCR enumeration of Pseudomonas aeruginosa, a clinically important pathogen in CF airway disease (Ballmann et al, 1998;Kosorok et al, 2001). Comparisons were made first between paired PMA-treated and non-PMA-treated samples (that is, the local community level), before focusing on core and satellite groups of bacterial taxa within the entire collection of PMA-and non-PMA-treated samples (that is, the metacommunity).…”