Long-Term Lung Function and Pseudomonas aeruginosa Infection in Genotyped Primary Ciliary Dyskinesia

Ann Am Thorac Soc. 2025 Feb;22(2):216-225. doi: 10.1513/AnnalsATS.202404-340OC.

Abstract

Rationale: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease and is known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives: We aimed to explore long-term lung function in PCD grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa. Methods: In this retrospective observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated forced expiratory volume in 1 second z-score trends and compared them at ages 10, 25, and 50 years, whereas generalized estimating equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Results: We included 127 genotyped patients, 6,691 spirometry measurements, and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early-onset and sustained decline in lung function, whereas DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures was on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa. Conclusions: Long-term lung function in PCD follows discrete genotype-specific profiles and appears independent of P. aeruginosa infection. We confirm and extend previous findings of CCDC39 and CCDC40 as variants associated with early-onset severe lung function impairment persisting in the long term.

Keywords: Pseudomonas aeruginosa; longitudinal lung function; primary ciliary dyskinesia.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Forced Expiratory Volume
  • Genotype*
  • Humans
  • Kartagener Syndrome* / genetics
  • Kartagener Syndrome* / microbiology
  • Kartagener Syndrome* / physiopathology
  • Lung / microbiology
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Proteins
  • Pseudomonas Infections* / complications
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa* / genetics
  • Pseudomonas aeruginosa* / isolation & purification
  • Retrospective Studies
  • Spirometry*
  • Young Adult

Substances

  • CCDC40 protein, human
  • Proteins