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- Study of the etiopathogenesis of Chronic Rhinosinusitis with Nasal Polyps: Focus on the host-environment interationPublication . Teles, Rafaela da Cruz Vieira Veloso; Farinha, Rosa Maria Barreiro da Cruz Ventura Roque; Buchwald, Christian vonIntroduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease, with high morbidity and chronicity, but its exact etiology is still unclear and remains a difficult to treat condition. Considering the emerging consensus that chronic rhinosinusitis (CRS) results from a dysfunctional host-environment interaction, this study pretends to clarify exogenous and endogenous factors, which can contribute to the occurrence and perpetuation of sinonasal mucosa inflammation observed in CRSwNP. The aims of this study are: 1) To evaluate endoscopic sinus surgery (ESS) efficacy in CRSwNP treatment and to establish prognostic factors for disease recurrence; 2) To compare the prevalence of nasal polyps (NP) in a group of workers with occupational dust exposure and in a control group; 3) To characterize systemic immunological alterations that occur in patients with CRSwNP compared to controls; 4) To clarify the role of food allergy in CRSwNP disease, comparing serum levels of food specific IgE and IgG antibodies in cases and controls. Material and Methods 1) Retrospective observational study in 85 patients with CRSwNP submitted to ESS and a minimum follow-up of 9 months. Patients’ demographics, occupational exposure, comorbidities, previous nasal surgeries, pre and postoperative symptoms and ENT examination findings, CT results, medical and surgical treatment information were collected from medical records. 2) Cross-sectional study with a random sample of textile (n=215) and retail store employees (n=101). Clinical data was gathered through a systematic interview, which included RhinoQOL-pv and CATTM questionnaires. A systematic endoscopic nasal examination was performed using a 0º rigid endoscope and Lund-Kennedy endoscopic score was determined for each participant. 3) Case-control study with 37 CRSwNP patients and 34 controls without CRS. Clinical data was gathered through a systematic interview. CT scan, skin prick test, spirometry, immunological parameters (leukocyte differential count, immunoglobulin classes and IgG subclasses) and 25-hydroxyvitamin D (25-HOD), alpha1-antitrypsin (A1AT) and C-reactive protein (CRP) dosage in serum specimens were obtained. 4) Case-control study with 33 patients with CRSwNP and 31 controls without CRS. Clinical data was gathered through a systematic interview (including the application of Food Frequency Questionnaire (QFA)). ELISA tests using OmegaDiagnostics® kit with 40 food allergens for detection of specific IgG antibodies were performed and food specific IgE antibodies were determined by immunoassay using ImmunoCAP™ against 11 food antigens. Statistical analysis was performed using SPSS v.23. Results 1) All rhinologic symptoms improved after ESS. The major and minor complications prevalences were 1.2% and 15.3%, respectively. Disease recurrence occurred in 31% of cases, but only 7% required surgical reintervention. Multivariate logistic regression analysis identified occupational dust exposure (p=0.001) and non-atopic asthma (p=0.012) as independent predictive variables in CRSwNP recurrence, unlike the other tested variables: age, sex, atopic asthma, allergic rhinitis, smoking habits, nasal polyps endoscopic grade, Lund-Mackay score and postoperative topical corticoid use. The adjusted logistic model had a ROC area under curve of 0.82 (p<0.001; CI95%: [0.73; 0.91]). 2) 316 participants were included in the study, i.e. 215 textile workers and 101 retail store workers. NP were found in 19 subjects (8.8%) among textile workers and none in the control group (p=0.001). The prevalence of NP increased by age strata (p=0.03) and by years of dust exposition (p=0.017). Polypoid degeneration of the middle turbinate was more prevalent in the exposed group (p=0.001) with Lund-Kennedy scoring also higher (p<0.001). RhinoQOL-pv and CATTM questionnaires had both significantly higher scores among textile employees. 3) A significantly higher eosinophil (p<0.001) and basophil relative count (p=0.022) and a lower relative neutrophil count (p=0.013) were found among CRSwNP group. Patients with CRSwNP had higher IgG1 (p=0.022), but lower IgG2 (p=0.014) and IgG3 (p=0.018) serum levels compared to controls. IgG4, total IgG, IgA, IgM and IgE serum levels did not differ between groups, as well as the prevalence of immunoglobulin classes or IgG subclasses deficiency; 25-HOD, A1AT and CRP dosage had also no significant difference. 4) The overall sum of food IgG antibodies was significantly lower in CRSwNP compared to control group (p=0.012), and this difference was also observed for different specific IgG antibodies (corn, soya, grain legumes, pear and apple, berries, citric fruit). In controls a positive correlation between IgG1 and the sum of food IgG antibodies was seen (p=0.049) but in CRSwNP group a negative correlation was found (p=0.048). Significant higher level of IgG1 was found among CRSwNP patients (p=0.041). Levels of serum specific IgE antibodies against the different studied food allergens, as well as the sum of food IgE antibodies, did not differ significantly between the groups. Conclusions Endoscopic sinus surgery proved to be an effective treatment in CRSwNP, but with a considerable disease recurrence. The first study of this investigation demonstrated that occupational dust exposure and non-atopic asthma are independent predictive factors of disease recurrence risk. The epidemiologic study performed, based on endoscopy, was pioneer in the evaluation of occupational exposure to dust impact on NP prevalence and the results pointed to an important association between them by demonstrating a significantly higher prevalence of the disease among textile workers. This investigation also showed a distinct systemic immunologic profile in CRSwNP patients compared to controls, and the variation observed in peripheral relative leukocyte count and the systemic IgG1 subclass shift are similar to what is known to happen in nasal polyp tissue. Concerning food allergy, it does not seem to have an important role in CRSwNP etiopathogenesis, whether if it is IgG or IgE-mediated. Moreover, the observed suppression of specific IgG antibodies against food allergens, its negative correlation with IgG1 and the raised IgG1 serum levels in CRSwNP, can be related to deviated IgG responses against other targets (e.g. airborne particles) and warrants future investigation.