Background: Severe asthma is associated with an accelerated lung function decline which is likely attenuated by the addition of anti-nnterleukin-5 (IL-5) therapy in patients with severe eosinophilic asthma. Objective: To study the long-term impact of add-on therapy with anti-IL-5 on FEV 1 in severe eosinophilic asthma patients. Methods: In this post-hoc analysis, we compared, through a linear mixed model, the evolution of pre-bronchodilation FEV 1 expressed in %pred in a cohort of 50 patients with severe eosinophilic asthma treated with anti-IL-5 (1576 visits) before (median follow-up: 9.2 years) and after (median follow-up: 2.1 years (up to 6.8 years) anti-IL-5 therapy start. Results: FEV 1 decline was observed before anti-IL5 start (-0.6 %pred.year -1, p<0.001). FEV 1 improved significantly after anti-IL-5 start (+1.3 %pred.year -1 p<0.001; difference pre-post: p<0.001). A sustained improvement was observed in 31 patients deemed responders (+3.1 %pred.year -1, p<0.001; difference pre-post: p<0.001) vs a continuous decline in 19 patients considered as non-responders (-0.40 %pred.year -1, p=0.087; difference pre-post: p=0.097). Non-responders exhibited a higher prevalence of nasal polyposis, better asthma control and a trend towards higher exhaled nitric oxide values. Conclusion: This post-hoc analysis shows that add-on therapy with anti-IL-5 not only stems the accelerated decline in lung function but also makes it reversible in many severe eosinophilic asthma patients, leading to an estimated improvement of 11% FEV 1 %pred after 3 years of treatment. Persistent improvement in lung function is therefore feasible in severe asthmatics and could be chosen as a lung function criterion to define remission of asthma under treatment.

Humans inhale, ingest and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom are in sharp contrast with their complex and relatively blurred taxonomy and scarce knowledge about their distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

Sensitization to shrimp and house dust mites in a Swedish population-based study: Influence on allergic disorders and lung functionIda Waern1, Magnus Molin2, Robert Movérare2,3, Jonas Lidholm2, Andrei Malinovschi4, Magnus P. Borres2,5, Christer Janson3.1Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden2Thermo Fisher Scientific, Uppsala, Sweden3Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden4Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden5Department of Maternal and Child Health, Uppsala University, Uppsala, Sweden

Introduction The IL-33 pathway involved in the development of type-2 airway inflammation is activated in allergic asthma patients. According to the “one airway, one disease” concept, the IL-33 pathway should also be activated in the airways of allergic rhinitis patients. Material and methods We compared the levels of IL-33 and its mRNA precursor, in induced sputum of patients suffering from seasonal allergic rhinitis (n=27) with those measured in patients with seasonal allergic asthma (n=23), and in healthy controls (n=17), in and out of the pollen season. Results IL-33 levels were higher in sputum supernatants of allergic rhinitis (median 9.4 pg.ml-1, range 0 – 51.1 pg.ml-1) and asthma patients (5.2 pg.ml-1, range 0 – 45.4 pg.ml-1) when compared to controls (median 0 pg.ml-1, range 0 – 13 pg.ml-1; p<0.001), and the same was observed with qPCR for IL-33. IL-33 levels were similar in patients suffering from allergic rhinitis (median 4.9 pg.ml-1 vs 7.1 pg.ml-1, p=0.256) or allergic asthma patients (median 3.6 pg.ml-1 vs 3.2 pg.ml-1, p=0.61) in and out of pollen seasons. Conclusion IL-33 is detectable in the lower airways of allergic rhinitis patients, to similar levels than in asthma patients, and appears to be independent of natural variation in allergen exposure. Those findings could reflect a silent epithelial dysfunction in the lower airways of allergic rhinitis patients without asthma, further confirming the «one airway, one disease» theory linking asthma and rhinitis.