Rhinosinusitis beyond the upper airways. Epidemiological aspects

Sammanfattning: Rhinosinusitis (RS) is a prevalent, multi-factorial disease, including several subgroups of disease with different characteristics and pathophysiology. RS symptoms for more than 12 weeks are defined as chronic rhinosinusitis (CRS). The underlying mechanisms likely involve multiple and distinct physiological processes that ultimately result in the inflammation of the sino-nasal mucosa. The potential relationship between upper- and lower-airway diseases would justify the concept of “global airway disease” – a field of increasing interest in research during the last decade. However, there is still much to uncover and a need systematically to investigate the natural history of CRS and the impact of risk factors and comorbidities. This thesis is based on four large, population-based studies from randomly selected population cohorts investigating CRS and the wider definition of non-infections rhinitis (NIR) and their relationship with the lower airways and the esophagus. Methods and results: Papers I, III and IV are single-center cohorts from Sweden and Norway. Paper II is a multi-center study from 26 centers in Europe and Australia. In Paper I (n=3,612 participants, age 25-75), we found an increased risk of developing NIR among subjects with COPD based on spirometry (OR 1.44, 95% CI 1.05-1.97). Smoking, atopy and occupational exposure to gas, fumes and dust were also risk factors for developing NIR. In Paper II (n=5,901), NIR was strongly associated with COPD at early follow-up (mean age 43) and weaker at later follow-up (mean age 54). Age was a protective factor and female gender was associated with an increased risk of NIR. Paper III is a five-year follow-up in a cohort from Telemark, Norway (n=7,393, age 16-50 at baseline). CRS was associated with an increased risk of developing chronic bronchitis (CB) (OR 3.8, 95% CI 2.65-5.40). Smoking and asthma were also more common among subjects with CRS. Paper IV investigates nocturnal gastroesophageal reflux (nGER) as a potential extra-respiratory comorbidity in CRS. Here, CRS was associated with nGER and the frequency of CRS increased stepwise with increasing numbers of nGER events. Conclusion: There are several links between chronic upper- and lower-airway diseases. In this thesis, the odds ratio for developing NIR increased among subjects with COPD. The association between NIR and COPD was shown to be age dependent, where the association was more robust at a younger age. Furthermore, the risk of developing CB increased among subjects with CRS and CRS was also associated with nGER in a dose-dependent manner. The results of this thesis emphasize CRS as a potential systemic disease and highlight the need to evaluate concomitant inflammatory diseases as comorbidities in CRS.