xRead - Nasal Obstruction (September 2024) Full Articles

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Orlandi et al.

IX.C.8 Contributing Factors for CRS: Microbiome Disturbance Because of limited data, CRSsNP and CRSwNP are com bined in this analysis. In health, the anterior nasal cavity, middle meatus, and sphenoethmoidal recess are populated by a stable microbiome that appears to be highly individualized. 732–735 Characteristic findings in health include increased bacte rial diversity, low abundance of pathogens, and limited anaerobes. 736 Particular organisms (namely Propionibacte ria , Corynebacteria ) may be more abundant in the healthy state, although precise speciation is subject to technical limitations and absent reproducibility at this time 736–738 Of interest, 20% of healthy individuals exhibit persistent Staphylococcus aureus nasal carriage, 60% are transiently colonized, and 20% almost never carry S.aureus , with broad implications for other health outcomes. 739 In contrast to the rich assemblages of bacteria that pop ulate the sinuses in the healthy state, CRS patients harbor qualitatively different microbial communities 740–743 that may be less stable over time. 744 Importantly, there is a large inter-individual personal variability, and there does not appear to be a single causative organism for CRS that is reproducibly observed across all studies. However, loss of diversity, preponderance of opportunistic pathogens over commensals, and expansion of anaerobes are routinely observed. The absence of causative organisms and differ ences in bacteria observed across studies may hint at the importance of community function, or may be in part due to intricacies of the disease process and its subtypes. In a cohort of 82 subjects, Ramakrishnan and colleagues examined microbiome alterations by phenotype and noted that the presence of polyps was not associated with micro biota alterations in CRS, but CRS patients with asthma or purulence had markedly different microbiota. 741 In this study, the authors did not find differences in alpha diversity indices (richness, evenness, complexity) of CRS patients when compared to controls but demonstrated that increased diversity was associated with improved surgi cal outcome, suggesting that a diverse microbiome may be beneficial to restoration of sinus health. Although oth ers have reported differences in CRSwNP compared to controls, 745 most publications do not observe differences in CRS populations driven by polyp status. Studying CRS phenotypes, Hoggard and colleagues did not observe dif ferences unique to CRSwNP, but reported that asthmat ics and CRS patients with CF were more likely to exhibit dysbiosis with wide variability in community structure. 746 Similarly, Mahdavinia et al. performed a cross-sectional study of 111 CRS subjects, and did not observe nasal polyps to associate with a unique surface microbiome. 747 They

were able to link comorbid AR with the lipopolysaccharide protein biosysnthesis pathway using predictive metage nomics, suggesting a functional relevance for the micro biome in atopic CRS. Chalermwatanachai and colleagues profiled the microbiota in 41 CRSwNP subjects compared to 18 controls, finding differences in microbes between the asthmatics and non-asthmatics, and demonstrating that pathogenic organisms found in CRS subjects outcompeted Propionibacterium acnes in co-cultivation experiments. 748 Cope et al. utilized sinus brushings in 59 CRS subjects and 10 controls to cluster 4 subgroups of CRS subjects accord ing to pathogenic microbiota and their predicted functions, as well as host mucosal inflammatory response. 749 The authors observed that 1 of these 4 groups had a higher inci dence of nasal polyposis, and was defined by a predom inance of Corynebacteria and increased IL-5. Hoggard et al. reported a cross-sectional analysis on 93 CRS subjects and 17 controls, evaluating microbiota alongside 10 tissue cytokines and 6 cell types. 50 The authors identified 8 clus ters of patients, strongly segregated by the presence of poly posis, asthma, cytokine profiles, and the loss of health associated groups of bacteria. In aggregate, these studies indicate microbiome differences in CRS asthmatics, and occasionally in CRSwNP although the effect appears more strongly associated with the presence of asthma in these patients. Given the common themes observed in these studies, and lack of clarity within detailed results published by various authors, Wagner Mackenzie et al. combined avail able 16S rRNA sequence data in a meta-analysis in 2017. 738 Their results demonstrated the common classes of bacteria observed across studies at a high level, but most strikingly concluded that bacterial communities in CRS are dysbiotic and ecological networks fostering colonization by healthy communities were fragmented in the diseased state. In their study, CRS was defined by loss of bacterial diversity, increased dispersion of bacterial communities, and loss of Actinobacteria and Propionibacteria that characterize the healthy state. To understand if, and how, bacteria influence host immune processes, several groups have associated micro biota surveys with host cytokine profiling or tissue func tion assays. Biswas and colleagues evaluated 23 CRS sub jects (8 CRSwNP, 8 CRSsNP, and 7 cystic fibrosis) and 8 con trols, and found 2 subgroups of CRS patients. 750 Onegroup was characterized by low bacterial diversity and domi nance of pathogens such as Pseudomonas , Haemophilus , and Achromobacter . The other group was characterized by preponderance of B cells and CRSwNP more so than its microbial signature, suggesting that integration of microbes with other clinicopathologic features may be required. In a separate report, the authors utilized pro teomics and 16S rRNA sequencing of middle meatus swabs