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ABSTRACTToday, more than 90% of people with cystic fibrosis (pwCF) are eligible for the highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy called elexacaftor/tezacaftor/ivacaftor (ETI) and its use is widespread. Given the drastic respiratory symptom improvement experienced by many post-ETI, clinical studies are already underway to reduce the number of respiratory therapies, including antibiotic regimens, that pwCF historically relied on to combat lung disease progression. Early studies suggest that bacterial burden in the lungs is reduced post-ETI, yet it is unknown how chronic Pseudomonas aeruginosa populations are impacted by ETI. We found that pwCF remain infected throughout their upper and lower respiratory tract with their same strain of P. aeruginosa post-ETI, and these strains continue to evolve in response to the newly CFTR-corrected airway. Our work underscores the continued importance of CF airway microbiology in the new era of highly effective CFTR modulator therapy.IMPORTANCEThe highly effective cystic fibrosis transmembrane conductance regulator modulator therapy Elexakaftor/Tezacaftor/Ivacaftor (ETI) has changed cystic fibrosis (CF) disease for many people with cystic fibrosis. While respiratory symptoms are improved by ETI, we found that people with CF remain infected with Pseudomonas aeruginosa. How these persistent and evolving bacterial populations will impact the clinical manifestations of CF in the coming years remains to be seen, but the role and potentially changing face of infection in CF should not be discounted in the era of highly effective modulator therapy.

ABSTRACT Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard of care guidelines for the management of CF CRS suggest treatment of upper airway disease may ameliorate lower airway disease. We sought to determine whether changes to sinus microbial community diversity and specific taxa known to cause CF lung disease are associated with increased respiratory disease and inflammation. We performed 16S rRNA gene sequencing, supplemented with cytokine analyses, microscopy, and bacterial culturing, on samples from the sinuses of 27 adults with CF CRS. At each study visit, participants underwent endoscopic paranasal sinus sampling and clinical evaluation. We identified key drivers of microbial community composition and evaluated relationships between diversity and taxa with disease outcomes and inflammation. Sinus community diversity was low, and the composition was unstable, with many participants exhibiting alternating dominance between Pseudomonas aeruginosa and staphylococci over time. Despite a tendency for dominance by these two taxa, communities were highly individualized and shifted composition during exacerbation of sinus disease symptoms. Exacerbations were also associated with communities dominated by Staphylococcus spp. Reduced microbial community diversity was linked to worse sinus disease and the inflammatory status of the sinuses (including increased interleukin-1β [IL-1β]). Increased IL-1β was also linked to worse sinus endoscopic appearance, and other cytokines were linked to microbial community dynamics. Our work revealed previously unknown instability of sinus microbial communities and a link between inflammation, lack of microbial community diversity, and worse sinus disease. IMPORTANCE Together with prior sinus microbiota studies of adults with CF chronic rhinosinusitis, our study underscores similarities between sinus and lower respiratory tract microbial community structures in CF. We show how community structure tracks with inflammation and several disease measures. This work strongly suggests that clinical management of CRS could be leveraged to improve overall respiratory health in CF. Our work implicates elevated IL-1β in reduced microbiota diversity and worse sinus disease in CF CRS, suggesting applications for existing therapies targeting IL-1β. Finally, the widespread use of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to less frequent availability of spontaneous expectorated sputum for microbiological surveillance of lung infections. A better understanding of CF sinus microbiology could provide a much-needed alternative site for monitoring respiratory infection status by important CF pathogens.

Background: Hospitalisation is an ideal time to implement smoking cessation interventions. However, little is known about the extent to which inpatients receive such advice, or the impact it has on motivation to quit and quitting behaviours post-hospitalisation. Aims: This study aimed to determine the prevalence of smoking and cessation advice received by inpatients in two teaching hospitals in Ireland, and the impact of cessation advice on smoking at 3 months post discharge. Methods: We surveyed 1001 inpatients across two hospital sites, over a six-month period. Demographic details, clinical history, smoking history, motivation to quit, cigarette dependence, and recent quitting history were assessed. Results: Prevalence of smoking within the sample was 23.4% (235/1001). Only 32% (75/235) of smokers reported that smoking cessation was discussed during admission. Smokers’ mean Fagerström nicotine-dependence score was 3.7 (SD = 2.7), indicating low dependence levels. At 3 months, 17% (25/146) of smokers reported smoking cessation. Provision of smoking cessation advice during hospitalisation was associated with higher motivation to quit (OR = 2.79, 95% CI 2.12–3.68), and successful quit behaviour for confirmed (OR = 1.98, 95% CI 1.55–2.53) and self-reported quitters (OR = 1.47, 95% CI 1.3–1.66) Conclusions: This observational study finds that provision of brief cessation advice and smoking status documentation was suboptimal. Where advice was given, it was associated with enhanced motivation to quit and increased quit rates. These findings, along with low dependence scores, suggest that systematic provision of low-intensity cessation interventions could significantly enhance quit rates in hospitalised smokers.