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Purpose: Exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) are the two disorders commonly considered when athletes complain of exertional dyspnea. They are highly different but often confused. We aimed to address this diagnostic challenge and its consequences in elite athletes. Methods: We included all athletes competing at national or international level, referred to our institution for workup for EILO during 2013–2016. We diagnosed EILO from video-recorded laryngoscopy performed during maximal cardiopulmonary treadmill exercise (CLE test). Symptoms and previous diagnostic evaluations were obtained from referral letters and chart reviews. Results: Exercise-induced laryngeal obstruction was diagnosed in 73/101 referred athletes, of whom 70/73 had moderate/severe supraglottic obstruction and 3/73 had primarily glottic obstruction with only minor supraglottic involvement. Of the 73 athletes with EILO, we were able to identify objective tests for asthma in 55 participants, of whom 22 had findings supporting asthma. However, 58/73 had used asthma therapy at some time previously, with current use in 28. Only three reported that asthma medication had improved their exercise-related breathing problems, two of whom with tests confirming asthma. Treatment for EILO improved breathing problems in all but four. Conclusions: Objective testing verified EILO in most of the referred athletes. EILO coexisting with asthma was common, and large proportions had used asthma medication; however, few reported effect on exercise-related breathing problems. Unexplained persistent exertional dyspnea must not lead to indiscriminate escalation of asthma treatment, but instead incite investigation for EILO, either as a co-morbidity or as a differential diagnosis. publishedVersion

The secretion of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were compared when freshly isolated autologous monocytes or monocytederived macrophages (MDMs) were co-cultured in vitro with autologous fragment (F)-spheroids established from a series of head and neck squamous cell carcinoma (HNSCC) patients. F-spheroids were generated from the malignant tumour (M-spheroids) or from benign mucosa (B-spheroids) from which the tumour originated control. If monocytes maturated towards MDMs before co-culture, the IL-6 secretion declined dependent on the extent of the MDM maturation by both M- and B-spheroid stimulation. When MDMs maturated in continuous co-culture, a steady-state secretion of IL-6 continued for several days but diminished when the culture medium was changed every 24 h. No co-culture-induced IL-1β or TNF-α was determined. Both the cytokine secretion and the mRNA gene expression revealed a different monocyte/MDM activation when co-culture and lipopolysaccharide (LPS)-stimulation were compared. Addition of anti-CD14 (10 µg/ml) decreased monocyte LPS-stimulated, but increased monocyte co-culture stimulated IL-6 secretion. In conclusion, M- and B-spheroids similarly stimulated monocytes and to a lesser extent MDMs. MDMs that maturated with F-spheroids present, retained responsiveness at the monocyte level. Co-culture-induced monocyte stimulation, as measured by IL-6 secretion, was not dependent on activation via the CD14 molecule.