CHEST Guidelines-Lung-Function-Longitudinal-Study-by-Phenotype-and- (1)

Lung-Function-Longitudinal-Study-by-Phenotype-and- (1)

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This study examined the progression of lung function in individuals with primary ciliary dyskinesia (PCD), focusing on associations with ultrastructural defects, genetic mutations, body mass index (BMI), and bacterial infections. Conducted over 10 years, it involved 135 pediatric and adult participants diagnosed with PCD, whose lung function and respiratory infections were regularly monitored.<br /><br />Key findings reveal variability in lung function decline based on ciliary ultrastructure and genetic mutations. Participants with inner dynein arm, central apparatus, and microtubular disorganization (IDA/CA/MTD) defects showed poorer spirometry results compared to others. Similarly, those with biallelic mutations in the genes CCDC39 and CCDC40 had more significant spirometric declines compared to DNAH5 and DNAH11 mutations. This suggests these ultrastructural and genetic factors contribute to a worse lung prognosis in PCD patients.<br /><br />The study also highlighted the impact of bacterial infections. While the prevalence of Haemophilus influenzae and Staphylococcus aureus decreased with age, Pseudomonas aeruginosa (PsA) infections became more common in older cohorts and were associated with more severe declines in lung function. Children infected with PsA at the start of the study had worse lung function, indicating that PsA may signal a pre-existing severe condition.<br /><br />Furthermore, the study found a significant correlation between BMI and lung function in children, suggesting that nutritional status may play a role in disease progression.<br /><br />The study's limitations include small genetic subgroup sizes and the use of only a 35-gene panel, potentially missing other relevant mutations. However, the findings underscore the need for tailored treatment approaches based on individual PCD phenotypes and genotypes, and emphasize the importance of early intervention, especially against PsA infections.

Keywords

primary ciliary dyskinesia

lung function

ultrastructural defects

genetic mutations

bacterial infections

CCDC39

CCDC40

Pseudomonas aeruginosa

body mass index

spirometry