Complexity, Temporal Stability, and Clinical Correlates of Airway Bacterial Community Composition in Primary Ciliary Dyskinesia

Abstract

g Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary function, leading to compromised airway clearance and chronic bacterial infection of the upper and lower airways. The compositions of these infections and the relationships between their characteristics and disease presentation are poorly defined. We describe here the first systematic culture-independent evaluation of lower airway bacteriology in PCD. Thirty-three airway samples (26 from sputum, 7 from bronchoalveolar lavage [BAL] fluid) were collected from 24 PCD patients aged 4 to 73 years. 16S rRNA quantitative PCR and pyrosequencing were used to determine the bacterial loads and community compositions of the samples. Bacterial loads, which ranged from 1.3 ؋ 10 4 to 5.2 ؋ 10 9 CFU/ml, were positively correlated with age (P ‫؍‬ 0.002) but not lung function. An analysis of ϳ7,000 16S rRNA sequences per sample identified bacterial species belonging to 128 genera. The concurrently collected paired samples showed high bacterial community similarity. The mean relative abundance of the dominant genera was 64.5% (standard deviation [SD], 24.5), including taxa reported through standard diagnostic microbiology (members of the genera Pseudomonas, Haemophilus, and Streptococcus) and those requiring specific ex vivo growth conditions (members of the genera Prevotella and Porphyromonas). The significant correlations observed included a positive relationship between Pseudomonas aeruginosa relative abundance and age and a negative relationship between P. aeruginosa relative abundance and lung function. Members of the genus Ralstonia were also found to contribute substantially to the bacterial communities in a number of patients. Follow-up samples from a subset of patients revealed high levels of bacterial community temporal stability. The detailed microbiological characterization presented here provides a basis for the reassessment of the clinical management of PCD airway infections.

Diagnosis and management of primary ciliary dyskinesia

“…A prolonged course of high-dose oral antibiotics can be prescribed in the settings of worsening respiratory symptoms, a deterioration in lung function or a positive culture. Culture-independent analysis of PCD respiratory samples has shown the bacteria present in PCD patient's airways to be plentiful and varied 37. The most commonly cultured pathogens are Haemophilus influenzae , Staphylococcus aureus and Streptococcus pneumonia.…”

“…The most commonly cultured pathogens are Haemophilus influenzae , Staphylococcus aureus and Streptococcus pneumonia. Pseudomonas aeruginosa and non-tuberculous mycobacteria have also been reported, although predominantly in adults 1 37. Intravenous antibiotics can be used if there is no response to oral antibiotics.…”

Bronchiectasis: Treatment decisions for pulmonary exacerbations and their prevention

“…Sequencing the 16S ribosomal RNA genes in adults revealed greater bacterial diversity within sputum than detected by culture. 56,57 In a study of the respiratory microbiome in children, the profile of those with CF, protracted bacterial bronchitis or bronchiectasis had more similarity between these groups than when compared to adults with CF or bronchiectasis. 58 However, at this stage, airway microbiota determination is a research rather than a clinical tool.…”

Cephalosporin-3′-Diazeniumdiolate NO Donor Prodrug PYRRO-C3D Enhances Azithromycin Susceptibility of Nontypeable Haemophilus influenzae Biofilms

“…NTHi is also the predominant early colonizer in primary ciliary dyskinesia (PCD), another genetic chronic lung disease characterized by a lack of mucociliary clearance, chronic lung infection, and lung function decline (3,4).…”