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Casper Tidemandsen,1 Anne Vejen Hansen,1 Vibeke Backer,2 Elisabeth Juul Gade,3 Zarqa Ali,4 Charlotte Suppli Ulrik1,2 1Department of Respiratory Medicine, Hvidovre Hospital, Hvidovre, Denmark; 2Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 3Department of Gynecology and Obstetrics, Rigshospitalet, Copenhagen, Denmark; 4Department of Dermatology and Wound Healing Centre, Bispebjerg Hospital, Copenhagen, DenmarkCorrespondence: Casper TidemandsenRespiratory Research Unit Hvidovre, Department of Respiratory Medicine, Hvidovre University Hospital, Kettegård Alle 30, Hvidovre DK-2650, DenmarkTel +45 50751516Email casper.tidemandsen.01@regionh.dkBackground: Asthma has been linked with prolonged time to pregnancy compared to healthy controls, also asthma has been linked to a higher need for fertility treatment. However, knowledge of the possible association between allergy and need for fertility treatment is limited. Our aim was to explore a possible difference in having had fertility treatment in women with asthma and live births in those with perennial allergy (animals, fungi and dust mites) compared to no allergy/seasonal allergy. The primary outcome of interest was fertility treatment.Patients and Methods: Women enrolled in the Management of Asthma during Pregnancy (MAP) program at Hvidovre Hospital, DK, were included in the present analysis provided they fulfilled the following criteria: 1) diagnosed with asthma and current anti-asthma therapy and 2) first visit to the respiratory outpatient clinic within the first 18 weeks of pregnancy. Participants were divided into two groups: asthma with perennial allergy (cases) and asthma with seasonal/no allergy (controls). Logistic regression analysis was applied, and findings expressed as odds ratios (OR).Results: Among women with asthma and perennial allergy (n=544 cases), 13.8% (n=75) had fertility treatment, compared to only 10.1% (n=39) among women with asthma and seasonal/no allergy (n=388, controls) (OR 1.43, 95% CI 0.95– 2.16, p=0.087). This association remained statistically insignificant after adjusting for confounders, including BMI (OR 1.19, 95% CI 0.77– 1.84, p=0.433). In women ≥ 35 years of age, 28% (n=44) and 20% (n=19), respectively, among cases and controls had fertility treatment (OR 1.60, 95% CI 0.87– 2.94, p=0.132), and likewise, statistically insignificant after adjusting for confounders (OR 1.41, 95% CI 0.74– 2.69, p< 0.293).Conclusion: In women with asthma and live births, our study revealed a trend towards an association between perennial allergy and a higher need for fertility treatment compared to seasonal/no allergy.Keywords: asthma, allergy, pregnancy, IVF, ART, fertility, atopy

Objective: We investigate symptoms of anxiety and depression among women with asthma prior to fertility treatment., Methods: This is a cross-sectional study of women screened for eligibility to the PRO-ART study (RCT of omalizumab versus placebo in asthmatic women undergoing fertility treatment (NCT03727971)). All participants were scheduled for in vitro fertilization (IVF) treatment at four public fertility clinics in Denmark. Data on demographics and asthma control (ACQ-5) were obtained. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS-A and D, respectively) and defined as being present on both subscales if a score >7 was obtained. Spirometry, diagnostic asthma test, and measurement of fractional exhaled nitric oxide (FeNO) were conducted., Results: A total of 109 women with asthma were included (mean age 31.8 ± 4.6 and BMI 25.5 ± 4.6). Most women had male factor infertility (36.4%) or unexplained infertility (35.5%). Twenty-two percent of the patients reported uncontrolled asthma (ACQ-5 score > 1.5). The mean HADS-A and HADS-D scores were 6.0 ± 3.8 (95% CI 5.3-6.7) and 2.5 ± 2.2 (95% CI 2.1-3.0), respectively. Thirty (28.0%) women reported anxiety symptoms, and four (3.7%) had concomitant depressive symptoms. Uncontrolled asthma was significantly associated with both depressive ( p  = 0.04) and anxiety symptoms ( p  = 0.03)., Conclusions: More than 25% of women with asthma prior to fertility treatment had self-reported symptoms of anxiety, and just below 5% had self-reported depressive symptoms, possibly related to uncontrolled asthma., Competing Interests: The clinical trial PRO-ART is financed by a grant from Novartis, and the study drug omalizumab is provided by Norvartis (CIGE025ADK01T PROART). CSU has outside the submitted work received personal fees from AZ, TEVA, Novartis, Pfizer, GSK, Takeda, BI, Berlin Chemie, Sanofi, Covis Pharma and Orion Pharma. The authors (EYH, AVH, CT, NLF, HSN & VB) declare that they also have no conflict of interests in relation to this manuscript., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Women with asthma appear to have an increased risk of pregnancy loss (PL). The impact of asthma on recurrent pregnancy loss (RPL), defined as 3 consecutive losses, is, however, unknown., Objective: The aim of this study was to investigate whether having asthma before or during the fertile age is associated with PL and RPL., Methods: Based on Danish national health registers, we identified all women aged 6 to 45 years with at least 2 filled prescriptions of an antiasthma drug during the period 1977 to 2019. Women with asthma were compared with women without asthma. Pregnancy outcomes were retrieved for both groups from national health registers. Logistic regression with adjustment for the year of birth and educational level provided odds ratios (ORs) for the number of PLs. Subgroup analyses were conducted for early-onset (age 6-15 years), adult-onset (age 16-39 years), and late-onset (age 40-45 years) asthma. Lastly, we compared uncontrolled asthma (defined as ≥ 400 doses of a short-acting beta-2 agonist in a year) to controlled asthma (defined as < 400 doses of a short-acting beta-2 agonist in a year)., Results: In a population of 1,309,786 women, we identified 128,553 women with asthma and 1,297,233 women without asthma. Compared with nonasthmatic women, women with asthma had ORs for 1, 2, and 3 or more PLs of 1.05 (95% CI 1.03-1.07), 1.09 (95% CI 1.05-1.13), and 1.18 (95% CI1.11-1.24), respectively, and for RPL of 1.19 (95% CI 1.12-1.27). In women with early-onset asthma, the OR of 3 or more PLs was 1.47 (95% CI 1.24-1.72). For women classified as having uncontrolled asthma compared with controlled asthma, we found a significant OR of 1.60 (95% CI 1.16-2.16) for 3 or more PLs., Conclusions: We found a significant positive association between asthma and number of PLs and RPLs. Early-onset asthma and uncontrolled asthma were more strongly associated with PL than adult-onset and late-onset asthma and controlled asthma., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Asthma and infertility are the most common disorders among women of reproductive age. Time to pregnancy is prolonged in women with asthma, and importantly, age seems to be a more important risk factor regarding fertility in women with asthma compared to women without asthma. Some data have shown a higher frequency of miscarriages in women with asthma, although the data are conflicting on this issue as studies have observed no association between asthma and pregnancy loss. Furthermore, studies have shown no negative effect of asthma on the total number of offspring. Pregnancy may, thus, have a significant impact on women with asthma, as well as on their offspring. The age of the women has an important impact on ability to conceive, but also for the pregnancy itself, with higher risk of uncontrolled asthma as well as asthma exacerbations with increasing age. Well-controlled asthma decreases the risk of maternal and fetal complications, while poorly controlled and undertreated asthma is associated with a range of risks for both mother and fetus. Asthma treatment should follow the general guidelines for asthma therapy, irrespective of pregnancy status, including treatment with inhaled corticosteroids, β 2 -agonists and muscarinic antagonists. Targeted treatment with biologics for severe asthma seems to be without important adverse effects. The use of systemic corticosteroids may be associated with adverse events during the first trimester; however, an exacerbation with the associated risk of hypoxaemia is worse for the fetus. Best possible asthma control may be achieved using repeated measurements of fractional exhaled nitric oxide ( F ENO ), as the use of F ENO compared with symptoms registration only has been shown to reduce exacerbation rate. In conclusion, women with asthma should be encouraged to conceive at an early age, might experience miscarriages, but the number of offspring are the same as in women without asthma. Well treated asthma is important for the well-being of both the mother and the unborn fetus., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©ERS 2022.)

Background: Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for coronavirus disease 2019 (COVID-19)., Methods: Placebo-controlled double-blind randomised multicentre trial. Patients aged ≥18 years, admitted to hospital for ≤48 h (not intensive care) with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR test were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice-daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (DAOH14)., Results: After randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on 1 February 2021. 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median (interquartile range) 9.0 (3-11) DAOH14 versus 9.0 (7-10) DAOH14 in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for one patient in the intervention group versus two patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for nine patients in the intervention group versus six patients receiving placebo (p=0.57)., Conclusions: The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19., Competing Interests: Conflict of interest: P. Sivapalan reports fees from Boehringer Ingelheim, outside the submitted work. C.S. Ulrik reports fees from Boehringer Ingelheim, AZ, GSK, TEVA, Novartis, ALK-Abello, Mundipharma, Sanofi Genzyme, Orion Pharma and Actelion, outside the submitted work. K.E.J. Håkansson reports personal fees from AstraZeneca, Chiesi and TEVA, outside the submitted work. T. Biering-Sørensen has received research grants from GE Healthcare and Sanofi Pasteur, as well as personal fees from Sanofi Pasteur, Novartis and Amgen, outside the submitted work. None of the other authors have any conflicts of interest., (Copyright ©The authors 2022.)

There are many unique aspects of asthma in women. Compared with men, women go through several hormonal stages over the life span-childhood, menarche, reproductive years, pregnancy, menopause, and postmenopause-and each affects asthma. Onset of asthma in women differs from men. Asthma in women is more often associated with obesity and women are over-represented among patients with severe asthma, including those being prescribed biologic therapies. Asthma affects fertility and pregnancy, and female hormone replacement therapy has been found to affect asthma onset as well as asthma severity. We explore the unique aspects of asthma in women., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Hydroxychloroquine has been proposed as a primary prophylactic agent against coronavirus disease 2019 (COVID-19). This study aimed to investigate if patients treated with hydroxychloroquine for a non-COVID-19 indication had a lower risk of verified infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with matched controls., Methods: A cohort comprising all persons in Denmark collecting hydroxychloroquine prescriptions in 2020 and 2019 (i.e., both during and before SARS-CoV-2 was confirmed in Denmark), matched by age and sex with controls, was studied. Data were collected using the Danish national registries, which contain complete information on patient health data, prescriptions and microbiological test results. The main outcome was microbiologically verified SARS-CoV-2 infection., Results: In total, 5488 hydroxychloroquine users were matched with 54,486 non-users. At baseline, the groups differed in terms of diagnoses of pulmonary disease, cardiovascular disease, renal disease, gastrointestinal/metabolic disease and dementia, as well as treatment with antirheumatic drugs. The final model was adjusted for these potential confounders. Use of hydroxychloroquine for non-COVID-19 indications was not associated with any change in confirmed SARS-CoV-2 (hazard ratio 0.90, 95% confidence interval 0.76-1.07). This result was robust in the propensity-score-matched sensitivity analysis., Conclusion: This study, which is the largest to date to investigate the primary prophylactic effect of hydroxychloroquine against SARS-CoV-2, does not support any prophylactic benefit of hydroxychloroquine in the prevention of infection with SARS-CoV-2., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Asthma is associated with prolonged time to pregnancy and a higher need for fertility treatment. However, the mechanism underlying this association remains incompletely understood. Previous research points to asthma-driven systemic inflammation also affecting the reproductive organs and thereby fertility. The aim of this study was to determine if treatment with omalizumab prior to fertility treatment will increase pregnancy rate among women with asthma by decreasing the systemic asthma-related inflammation and, by that, to provide insight into the underlying mechanisms., Methods and Analysis: This is an ongoing prospective multicentre randomised controlled trial planned to enrol 180 women with asthma recruited from fertility clinics in Denmark. The patients are randomised 1:1 to either omalizumab or placebo. The primary endpoint is the difference in pregnancy rate confirmed with ultrasound at gestational week 7 of pregnancy. The secondary endpoints are change in sputum and blood eosinophil cell count, change in biomarkers, change in microbiota, together with rate of pregnancy loss, frequency of malformations, pre-eclampsia, preterm birth, birth weight, small for gestational age and perinatal death between groups., Ethics and Dissemination: The methods used in this study are of low risk, but if successful, our findings will have a large impact on a large group of patients as infertility and asthma are the most common chronic diseases among the young population. The study has been approved by the Ethics Committee-Danish national research ethics committee (H-18016605) and the Danish Medicines Agency (EudraCT no: 2018-001137-41) and the Danish Data Protection Agency (journal number: VD-2018486 and I-Suite number 6745). The test results will be published regardless of whether they are positive, negative or inconclusive. Publication in international peer-reviewed scientific journals is planned., Trial Registration Number: NCT03727971., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)