Longitudinal analysis of sinus microbiota post endoscopic surgery in patients with cystic fibrosis and chronic rhinosinusitis: a pilot study

Abstract

Background Cystic fibrosis is a debilitating, autosomal recessive disease which results in chronic upper and lower airway infection and inflammation. In this study, four adult patients presenting with cystic fibrosis and chronic rhinosinusitis were recruited. Culture and molecular techniques were employed to evaluate changes in microbial profiles, host gene expression and antimicrobial resistance (AMR) in the upper respiratory tract over time. Methods Swab samples from the sinonasal cavity were collected at the time of surgery and at follow-up clinics at regular time intervals for up to 18 months. Nucleic acids were extracted, and DNA amplicon sequencing was applied to describe bacterial and fungal composition. In parallel, RNA was used to evaluate the expression of 17 AMR genes and two inflammatory markers (interleukins 6 and 8) using custom qPCR array cards. Molecular results were compared with routine sinus and sputum culture reports within each patient. Results Bacterial amplicon sequencing and swab culture reports from the sinonasal cavity were mostly congruent and relatively stable for each patient across time. The predominant species detected in patients P02 and P04 were Pseudomonas aeruginosa, Staphylococcus aureus in patient P03, and a mixture of Enterobacter and S. aureus in patient P01. Fungal profiles were variable and less subject specific than bacterial communities. Increased expressions of interleukins 6 and 8 were observed in all patients throughout the sampling period compared with other measured genes. The most prevalent AMR gene detected was ampC. However, the prevalence of AMR gene expression was low in all patient samples across varying time-points. Conclusions We observed a surprising degree of stability of sinonasal microbial composition, and inflammatory and AMR gene expression across all patients post sinus surgery.

Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis

“…Our findings share similarities and build upon prior microbiota studies of CF CRS and CF sputum examining diversity and taxonomic drivers of community structure. Consistent with previous adult CF CRS and sputum studies, microbial community diversity was low ( 4 , 5 , 19 , 32 – 35 ), and communities were frequently dominated by P. aeruginosa or staphylococci ( 4 – 6 , 35 – 38 ). Lucas et al recently showed that low diversity was associated with dominance by Pseudomonas spp.…”

“…can drive low community diversity and that low diversity is associated with worse sinus disease as measured by mLK score. Additionally, a recent longitudinal study of four adults with CF CRS reported marked stability in sinus communities over time ( 38 ), whereas approximately half of our cohort exhibited instability. These inconsistencies between studies could be due to differences in study design (e.g., cohort sizes or cross-sectional versus longitudinal), methodological differences in sequencing or analysis approaches, or potentially differences in the cohorts themselves, all of which were recruited at single, distinct study centers.…”

Is there a role for antibiotics in the treatment of chronic rhinosinusitis?

“…[100][101][102] Given the strong correlation between upper and lower airway microbial populations, it could be inferred from these observations that the CF CRS bacterial population is also resistant to change. 103 There is little consensus on the optimal use of antibiotics in CF-related CRS. 104 Nebulized tobramycin 105 and oral What is the effect of long-term systemic antibiotics, particularly nonmacrolides, on CRS outcomes?…”

“…( 101 – 103 ) Given the strong correlation between upper and lower airway microbial populations, it could be inferred from these observations that the CF CRS bacterial population is also resistant to change. ( 104 )…”

Evaluating Sinus Microbiology by Transplant Status in Persons With Cystic Fibrosis: A Matched Cohort Study

“…6,7 Culture-independent methods studying the microbiome have demonstrated that the sinuses mirror the lower respiratory tract with polymicrobial communities that progressively become dominated by classical CF pathogens with advancing disease. [8][9][10][11][12] PwCF who have undergone lung transplantation are a unique subgroup in whom the airway microbiome is even less understood. Concordance between the pre-and posttransplant sputum microbiome of PwCF suggests the sinuses are a persistent nidus of airways infection.…”