Pulmonary Outcome in Cystic Fibrosis Is Influenced Primarily by Mucoid Pseudomonas aeruginosa Infection and Immune Status and Only Modestly by Genotype

作者：Richard B. Parad, Craig J Gerard, David Zurakowski, David P. Nichols, Gerald B. Pier · 发表于：Infection and Immunity · 年份：1999 · DOI：10.1128/iai.67.9.4744-4750.1999 · 被引用次数：144 · 研究领域：Cystic Fibrosis Research Advances、Neonatal Respiratory Health Research、Asthma and respiratory diseases

Whether allelic variants of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) independently contribute to pulmonary outcome in CF patients has not been resolved. We used both cross-sectional and mixed-model longitudinal analyses of data from CF patients that were at least 12 years old to determine the influence on pulmonary function (percent predicted forced expiratory volume [FEV(1)]) of the CFTR gene genotype, gender, mucoid Pseudomonas aeruginosa (MPA) infection status, presence of total opsonic antibody to MPA, and, separately, the opsonic antibody activity specific to the mucoid exopolysaccharide (MEP) surface antigen. Two different factors were independently associated with the lack of MPA infection: a high level of MEP-specific opsonic activity (MSOA), implicating an immunologically based mechanism of resistance to infection, and a lack of any type of opsonic antibody to MPA, indicative of no significant exposure or infection. This latter phenotype was found in a subset of CF patients who carried at least one uncommon CFTR gene allele suggestive of a genetic basis for resistance to infection in this group of older CF patients. For CF patients in whom both CFTR gene alleles were identified by screening for the 12 most common variants (75% of alleles), cross-sectional analysis showed that MPA infection was best correlated with lower percent predicted FEV(1), while genotype (two versus one DeltaF508 CFTR gene allele) and a low level of MSOA were associat...