Impact of chronic Pseudomonas aeruginosa infection on the inflammatory response during virus-associated exacerbations of cystic fibrosis

Chronic infections with P. aeruginosa (PA) affect the course of lung disease in people with cystic fibrosis (PwCF). Experimental data have shown that PA proteases can degrade immune mediators, including IL-6. To what extent this affects heterologous infections or virus-associated pulmonary exacerbations (PEx) in PwCF is unclear. We analysed data from 28 adult PwCF, 14 of whom were chronically infected with PA and 14 PA-free individuals. During two subsequent winter seasons, participants were tested monthly for respiratory viruses and asked to provide additional samples if they experienced signs indicative of a PEx. During routine check-ups and in case of suspected PEx, blood samples were collected. Respiratory viruses were detected in 19/39 (48.7%) of all samples collected during periods of increased symptom burden, whereas only 15/307 (4.9%) of screening samples tested positive (p<0.001). Positivity rates did not differ between PwCF with chronic PA infection and PA-free participants (11.7% vs. 7.6%, p=0.4). Human rhinoviruses (38.9% of positive samples), influenza A (19.4%) and SARS-CoV2 (13.9%) were detected most frequently. Viral infections led to increased serum levels of IL-10. They moreover tended to cause higher IL-6 levels in PA-negative participants (2600 [0-6795] fg/ml vs. 0 [0-1664] fg/ml, p=0.054), but not in PwCF with chronic PA infection (0 [0-1965] vs. 0 [0-182] fg/ml, p=0.8], values given as median [IQR]). Our results emphasize the relevance of viruses as triggers of PEx in cystic fibrosis and indicate that, in line with experimental data, PA infection can modulate virus-induced IL-6 response in PwCF.