Natural pollen exposure increases in a dose-dependent way Fraction of exhaled Nitric Oxide (FeNO) levels in patients sensitized to one or more pollen species

Background: Co-exposures and polysensitization to several pollen species are very common in real life practice. However, little information exists on allergic symptoms and airway inflammation related to natural pollen exposure in large general population samples. Objective: To assess the combined effect of sensitization and/or exposure to one or more pollen species on Fraction of exhaled Nitric Oxide (FeNO) levels. Methods: Within Gene Environment Interactions in Respiratory Diseases (GEIRD) multicase-control study, 1070 adults from the general population of Verona, Italy, underwent a clinical evaluation including standardized interview, spirometry, skin prick test to inhalants and FeNO measurement. Pollen exposure was assumed, when the mean pollen concentration in the previous week was above the cutoff established by the Italian Aerobiological Monitoring Network. Results: Subjects sensitized to one or more pollen species were respectively 15.5% and 29.6%. FeNO levels were directly related to the number of both pollen species around and pollen-related sensitizations. Median FeNO levels were directly related to number of pollen species around and pollen sensitization. FeNO levels increased from 15.4 ppb (p. 25-p. 75 = 9.9-21.0) outside the pollen season to 17.5 ppb (11.2-30.5) when there were ≥3 pollen species around. Likewise FeNO levels rose from 14.8 ppb (10.0-22.3) in not sensitized subjects, to 16.7 (10.1-25.0) in monosensitized and further to 20.4 (12.3-40.6) in poly-sensitized. According to multivariable quantile regression, median FeNO was 17.9 ppb higher (p. 25-p. 75 = 12.5-23.3) for subjects sensitized and exposed to more than one pollen species, compared to subjects who were neither sensitized nor exposed. Differences in FEV1/FVC between groups were less pronounced (-2.0%, -4.1 to 0.1). Median FeNO level was 15.1 ppb (p. 25-p. 75 = 10.0-23.2) in subjects without pollen-related symptoms, 17.8 ppb (12.1-40.2) in those with nasal symptoms only, and 22.7 ppb (14.7-43.0) in those with asthma-like symptoms (p < 0.001). Conclusion and clinical relevance: Airways inflammation, evaluated by FeNO, increases in dose-dependent manner from subjects monosensitized to pollen species to those poly-sensitized, especially when asthma-like symptoms on pollen exposure are also reported. This should be considered by allergists during natural pollen seasons when evaluating both pulmonary function and airways inflammation.