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Background: Cold exposure is associated with increased morbidity and mortality. Elite cross-country skiers are regularly exposed to cold, dry air and have a high prevalence of asthma compared to the Swedish population. However, evidence is limited regarding how a combination of sub-zero temperatures and physical activity affects the airways of healthy individuals.

Aims: The aims of this thesis were to study the prevalence of self-reported asthma, age at asthma onset, and predictors of asthma in Swedish endurance athletes, with a focus on cross-country skiers. This thesis also aimed to assess the effects of subzero temperature and physical activity on healthy human airways.

Methods: Study 1 (papers I-II) consisted of an annual postal questionnaire investigating asthma prevalence and predictors of asthma that was sent to invited athletes in 2011–2015. Invited athletes were Swedish elite cross-country skiers, biathletes, ski orienteers, and orienteers from Swedish National Elite Sport Schools, national teams, and Swedish Ski Universities, or top orienteers according to national ranking. Former Swedish Olympic skiers and an adolescent reference group were invited in 2013. Paper I included cross-sectional data from 2011 for adolescents/adults and from 2013 for former skiers (n=491). Paper II included adolescent elite skiers (n=253) from the Swedish National Elite Sport Schools invited during 2011-2013, as well as a reference group (n=500) aged 16-20 years that was matched for school municipalities and invited in 2013. Study 2 (papers III-IV) comprised whole-body experimental exposure of healthy adults to sub-zero temperatures and exercise in an environmental chamber. Lung function and biochemical markers in plasma and urine were measured before and after exposure. Symptoms were investigated before, during, and after exposure. In both trials, study subjects were exposed for 50 min on two separate occasions in randomized order. Paper III comprised 31 subjects and moderate-intensity exercise (30 min running at 62-78% of VO2max), at 10°C vs. -10°C. Paper IV included 29 subjects and hard-intensity exercise (30 min of running at 85% of VO2max) vs. rest, both at a temperature of -15°C.

Results: In paper I, the overall response rate was 82%. Athletes reporting asthma in the different age categories were: 29% of skiers (38% of the female skiers) and 17% of orienteers (p=0.071) among 15 to 19-year-olds; 35% of skiers and 16% of orienteers (p=0.029) among 20 to 34-year-olds; and 22% of the skiers aged 40–94 years. Asthma onset occurred in adolescence among the active athletes. Increasing age, female sex, allergy, family history of allergy/asthma, and being a skier were predictors of self-reported physician-diagnosed asthma. In paper II, the response rate was 96% for skiers and 48% for the reference group. Skiers reported a higher prevalence of self-reported physician-diagnosed asthma than the reference population (27% vs. 19%, p=0.046). Physician-diagnosed asthma was more frequently reported by female skiers than male skiers (34% vs. 20%, p=0.021). Median age at asthma onset was higher among skiers than in the reference population (12.0 vs. 8.0 years; p<0.001). Female sex, family history of asthma, nasal allergy, and being a skier were risk factors associated with self-reported physician-diagnosed asthma. In paper III, exercise at -10°C decreased FEV1 (p=0.002) and FEV1/FVC (p<0.001) and increased resistance at 20 Hz (p=0.016) to similar magnitudes as exercise at 10°C. Exercise at 10°C increased reactance (p=0.005), which differed (p=0.042) from a less pronounced response after exercise at -10°C. Plasma CC16 increased similarly after both exposures, without significant differences. More intense symptoms from the upper airways were reported after exercise at -10°C than at 10°C. Symptoms from the lower airways were few and mild. In paper IV, FEV1 decreased from baseline after both rest (p<0.001) and exercise (p=0.012) at -15°C, with no differences between exposures. Compared to rest, exercise at -15°C induced greater increases in reactance (p=0.023), plasma CC16 (p<0.001), and plasma IL-8 (p<0.001). Exercise gave rise to more intense symptoms from the lower airways, whereas rest induced more general symptoms.

Conclusions: In the 1990s, a high prevalence of physician-diagnosed asthma was reported among Swedish elite cross-country skiers, and our studies show that this has not changed. Asthma onset commonly occurs in early adolescence among skiers, in the beginning of their career. Being an elite skier is an independent risk factor associated with asthma. Targeted preventive measures should be introduced at an early age to avoid the development of asthma in endurance athletes. Healthy individuals performing short-duration moderate- and hard-intensity exercise in sub-zero temperatures responded with lung function changes and an increased airway permeability. These findings warrant further research on airway responses to sub-zero temperatures in vulnerable individuals such as elite endurance athletes.