Hormonal Contraceptives Are Associated With an Increase in Incidence of Asthma in Women.

BACKGROUND: Use of exogenous female sex hormones is associated with the development of asthma, but the question of whether the effect is protective or harmful remains unresolved. OBJECTIVE: To investigate whether initiation of hormonal contraceptive (HC) treatment was associated with development of asthma. METHODS: We performed a register-based, exposure-matched cohort study including women who initiated HC treatment of any kind between 10 and 40 years of age and compared the incidence of asthma with women who did not initiate HCs. Asthma was defined as 2 redeemed prescriptions of inhaled corticosteroids within 2 years. Data were analyzed using Cox regression models adjusted for income and urbanization. RESULTS: We included 184,046 women with a mean age of 15.5 years (SD 1.5 y), in which 30,669 initiated HC treatment and 153,377 did not. We found that initiation of HCs was associated with an increased hazard ratio (HR) of developing new asthma by 1.78 (95% CI 1.58-2.00; P < .001). The cumulative risk of new asthma was 2.7% after 3 years among users of HCs compared with 1.5% in nonusers. In the different subtypes of HCs, second- and third-generation contraceptives carried significant associations (second-generation HR 1.76; 95% CI 1.52-2.03; P < .001; third-generation HR 1.62 95% CI 1.23-2.12; P < .001). The association with increased incidence was seen only in women younger than 18 years. CONCLUSIONS: In this study, first-time users of HCs had an increased incidence of asthma compared with nonusers. Clinicians prescribing HCs should be aware that airway symptoms may develop.

Assay validation for vilanterol and its metabolites in human urine with application for doping control analysis.

A bioanalytical method for detecting the ultra-long-acting beta2 -agonist (U-LABA) inhaled vilanterol and its metabolites, GSK932009 and GW630200, in urine was developed to potentially monitor permitted therapeutic versus prohibited supratherapeutic use in sport. The World Anti-Doping Agency (WADA) has established urinary concentration thresholds for the beta2 -agonists salbutamol and formoterol. Therapeutic use of vilanterol (25 µg once daily) was recently permitted by WADA; however, there is no established decision limit for adverse analytical findings due to insufficient urine concentration data. In this study, we validated an assay to detect vilanterol in urine collected from four healthy male and female athletes 0-72 h who received inhaled corticosteroid fluticasone furoate/U-LABA vilanterol (800/100 µg) combination, four times the normal therapeutic dose. After administration, subjects performed 1 h of bike ergometer exercise. The experiment was conducted again after repeat dosing for 1 week. Our method utilised liquid chromatography with tandem mass spectrometry and was validated over urine concentrations of 5-5000 (vilanterol) and 50-50,000 pg/ml (GSK932009 and GW630200). Plasma samples were analysed for vilanterol, using a previously validated assay. The peak concentration values for urine vilanterol, GSK932009 and GW630200 were 9.5, 10.4 and 0.17 ng/ml, for single dosing, and 18.6, 19.5 and 0.20 ng/ml, for repeat dosing. Urine samples from four volunteers using the final validated method are reported, demonstrating this assay has sensitivity to detect vilanterol or GSK932009 in urine for ≥72 h post single or repeat dosing with 800/100 µg fluticasone furoate/vilanterol, whereas GW630200 was quantifiable ≤4 h post dose.

Inhaled anti-asthma therapies following hormone therapy in women: a nationwide cohort study.

Research question: Does menopausal hormone therapy (HT) with exogenous oestrogens and progestogens change the use of inhaled anti-asthma medications in women with asthma? Methods: In a population-based matched cohort study using the Danish registries, we included women with asthma aged 45-65 years from 1 June 1995 to 30 June 2018. We investigated whether HT with oestrogen and/or progestogens was associated with changes in use of inhaled anti-asthma therapies in the 12 months following initiation. We used exposure density matching to match exposed subjects with unexposed subjects on age, household income and level of education. An exposed subject was defined as receiving HT. We calculated mean dose of medications and odds ratios of increases in the 12 months following HT initiation. Results: We included 139 483 women with asthma, of whom 116 014 (83.2%) were unexposed subjects and 23 469 (16.8%) exposed subjects. Mean±sd age was 53.0±5.2 years. Initiation of HT was not consistently associated with increased mean doses of inhaled corticosteroids (ICS), or long- and short-acting ß2-agonists. Women receiving systemic oestrogens had increased odds ratios of large increases (>100 µg) in ICS at 6 months (OR 1.09; 95% CI 1.04-1.13; p<0.001) and 9 months (OR 1.07; 95% CI 1.03-1.12; p<0.001). Progestogens were protective against increases in ICS at 6 and 9 months (OR 0.87; 95% CI 0.82-0.93; p<0.001; and OR 0.86; 95% CI 0.81-0.91; p<0.001). Conclusion: Initiation of HT did not change the use of inhaled medications in asthma. However, detrimental effects of oestrogen, as well as beneficial effects of progestogens, cannot be excluded.

Hormone Replacement Therapy and Development of New Asthma.

BACKGROUND: Hormone replacement therapy (HRT) is prescribed to millions of women worldwide. Previous studies have suggested that HRT has both protective and harmful effects in asthma. RESEARCH QUESTION: Is HRT in menopause associated with new development of asthma? STUDY DESIGN AND METHODS: We undertook a nested case-control study based on the Danish registers from June 1, 1995, through December 31, 2018. A diagnosis of asthma was defined as two redeemed prescriptions of inhaled corticosteroids within 2 years. HRT was defined as two redeemed prescriptions of female sex hormones within 6 months. Data were analyzed using a conditional logistic regression model. RESULTS: We included 34,533 women with asthma vs 345,116 women without asthma between 40 and 65 years of age. In a multivariate analysis adjusted for age, household income, and educational level, active HRT resulted in a hazard ratio (HR) of 1.63 (95% CI, 1.55-1.71; P < .001) of new asthma development. Women with asthma who terminated HRT were likely to discontinue their asthma treatment subsequently (HR, 2.12; 95% CI, 1.94-2.33; P < .001). INTERPRETATION: HRT seems to play a role in the development of asthma in mature women. Clinicians prescribing HRT and women receiving HRT should be aware that new airway symptoms can develop, and discontinuation of HRT should be considered.

Severe outcomes of COVID-19 among patients with COPD and asthma.

INTRODUCTION: Patients with obstructive lung diseases are possibly at risk of developing severe outcomes of coronavirus disease 2019 (COVID-19). Therefore, the aim of this study was to determine the risk of severe outcomes of COVID-19 among patients with asthma and COPD. METHODS: We performed a nationwide cohort study of patients with COVID-19 from 1 February to 10 July 2020. All patients with COVID-19 registered in the Danish registers were included. Using International Classification of Diseases (ICD) codes and medication history, patients were divided into asthma, COPD or no asthma or COPD. Primary outcome was a combined outcome of severe COVID-19, intensive care or death. RESULTS: Out of 5104 patients with COVID-19 (median age 54.8 years (25-75th percentile 40.5 to 72.3); women, 53.0%), 354 had asthma and 432 COPD. The standardised absolute risk of the combined end-point was 21.2% (95% CI 18.8-23.6) in patients with COPD, 18.5% (95% CI 14.3-22.7) in patients with asthma and 17.2% (95% CI 16.1-18.3) in patients with no asthma or COPD. Patients with COPD had a slightly increased risk of the combined end-point compared with patients without asthma or COPD (risk difference 4.0%; 95% CI 1.3-6.6; p=0.003). In age standardised analyses, there were no differences between the disease groups. Low blood eosinophil counts (<0.3×109 cells·L-1) were associated with increased risk of severe outcomes among patients with COPD. CONCLUSION: Patients with COPD have a slightly increased risk of developing severe outcomes of COVID-19 compared with patients without obstructive lung diseases. However, in age-standardised analysis, the risk difference disappears.

Effect of aerobic exercise training on asthma in adults: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of aerobic exercise training on asthma control, lung function and airway inflammation in adults with asthma. DESIGN: Systematic review and meta-analysis. METHODS: Randomised controlled trials investigating the effect of ≥8 weeks of aerobic exercise training on outcomes for asthma control, lung function and airway inflammation in adults with asthma were eligible for study. MEDLINE, Embase, CINAHL, PEDro and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to April 3, 2019. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: We included 11 studies with a total of 543 adults with asthma. Participants' mean (range) age was 36.5 (22-54) years; 74.8% of participants were female and the mean (range) body mass index was 27.6 (23.2-38.1) kg·m-2. Interventions had a median (range) duration of 12 (8-12) weeks and included walking, jogging, spinning, treadmill running and other unspecified exercise training programmes. Exercise training improved asthma control with a standard mean difference (SMD) of -0.48 (-0.81--0.16). Lung function slightly increased with an SMD of -0.36 (-0.72-0.00) in favour of exercise training. Exercise training had no apparent effect on markers of airway inflammation (SMD -0.03 (-0.41-0.36)). CONCLUSIONS: In adults with asthma, aerobic exercise training has potential to improve asthma control and lung function, but not airway inflammation.