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Introduction: Pseudomonas aeruginosa pulmonary infections are the primary cause of morbi-mortality in patients with cystic fibrosis (CF). In this cohort study, the objective was to identify candidate biomarkers of P. aeruginosa infection within the airway microbiota. Methods: A 3-year prospective multicentre study (PYOMUCO study) was conducted in Western France and included patients initially P. aeruginosa free for at least 1 year. A 16S-targeted metagenomics approach was applied on iterative sputum samples of a first set of patients (n=33). The composition of airway microbiota was compared according to their P. aeruginosa status at the end of the follow-up (colonised vs non-colonised), and biomarkers associated with P. aeruginosa were screened. In a second step, the distribution of a candidate biomarker according to the two groups of patients was verified by qPCR on a second set of patients (n=52) coming from the same cohort and its load quantified throughout the follow-up. Results: Porphyromonas (mainly P. catoniae) was found to be an enriched phylotype in patients uninfected by P. aeruginosa (p<0.001). This result was confirmed by quantitative PCR. Conversely, in patients who became P. aeruginosa-positive, P. catoniae significantly decreased before P. aeruginosa acquisition (p=0.014). Discussion: Further studies on replication cohorts are needed to validate this potential predictive biomarker, which may be relevant for the follow-up in the early years of patients with CF. The identification of infection candidate biomarkers may offer new strategies for CF precision medicine.

Introduction: Chlamydia pneumoniae respiratory tract infection has been implicated in the pathogenesis of reactive airway disease and asthma. Innate cytokine responses that are protective of infection with intracellular pathogens may be impaired in patients with asthma. Tumour necrosis factor alpha (TNF-α) is a cytokine related to functions of monocytes and may inhibit C. pneumoniae infection. We investigated TNF-α responses in C. pneumoniae-infected peripheral blood mononuclear cells (PBMCs) in patients with asthma and non-asthma, and whether ciprofloxacin, azithromycin or doxycycline affects TNF-α responses. Methods: PBMC (1.5×106) from paediatric patients with asthma (n=19) and non-asthmatic controls (n=6) were infected or mock infected for 1 hour with or without C. pneumoniae AR-39 at a multiplicity of infection=0.1, and cultured+ciprofloxacin, azithromycin or doxycycline (0.1 ug/mL) for 48 hours. TNF-α levels were measured in supernatants by ELISA. Results: When PBMC from patients with asthma were infected with C. pneumoniae, levels of TNF-α were significantly lower than in subjects without asthma (48 hours) (5.5±5.6, 38.4±53.7; p=0.0113). However, baseline responses (no infection with C. pneumoniae) were similar in asthma and non-asthma (1.0±1.7, 1.1±1.2; p=0.89). When PBMC frompatiens with asthma were infected with C. pneumoniae+ciprofloxacin, azithromycin or doxycycline, TNF-α levels increased (25%-45%); this affect was not observed in PBMC from patients without asthma. Conclusions: We identified differences in the quantity of TNF-α produced by C. pneumoniae-infected PBMC in asthma compared with non-asthma.