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Objective: To evaluate if high-intensity interval training three times weekly for 12 weeks improves asthma control in overweight, postmenopausal women with uncontrolled, late-onset asthma., Methods: The reported study is a randomized clinical pilot study (www.clinicaltrials.gov; NCT03747211) that compared 12 weeks of high-intensity interval training (spinning) with usual care. The five-question Asthma Control Questionnaire (ACQ-5) was used as primary outcome. Secondary measures included systemic inflammation and inflammation of the airways, body composition, and cardiac function during exercise., Results: We included 12 women with asthma (mean age 65 years (SD 6); mean body mass index 30 kg/m 2 (SD 2)) from whom eight were randomized to exercise and four to control. Baseline ACQ-5 was 1.95 (SD 0.53) in the control group and 2.03 (0.54) in the exercise group. Patients had a mean blood eosinophil level of 0.16 × 10 9 cells/L (SD 0.07) and a mean fraction of exhaled nitric oxide of 23 ppb (SD 25). Mixed models showed that participants in the exercise group reduced their ACQ-5 by 0.55 points (95%CI -1.10 to -0.00; P  = 0.08) compared with the control group. The exercise group significantly reduced their mean body fat percentage (-2.7%; 95%CI -4.5 to -0.8; P  = 0.02), fat mass (-2.8 kg; 95%CI -5.1 to -0.4; P  = 0.044) and android fat mass (-0.33 kg; 95%CI -0.60- -0.06; P  = 0.038). In analyses of cardiac measures, we saw no significant effects on right ventricular function (fractional area change), diastolic function or left ventricular function., Conclusions: Although changes in ACQ-5 were slightly insignificant, these preliminary findings indicate that aerobic exercise training can be used as a means to improve asthma control in overweight, postmenopausal women with asthma., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Purpose: When first-line chronic rhinosinusitis (CRS) treatment fails, patients can either be treated with oral or injected systemic corticosteroids. Although the EPOS and international guidelines for CRS do not mention injected corticosteroids, it is commonly used by ear, nose, and throat specialists. While the risks of systemic corticosteroids, in general, are known, the pros and cons of injected and oral corticosteroids (OCS) in CRS treatment are unclear., Methods: A systematic review of studies that report the effects and/or side effects of injected and oral corticosteroids in the treatment of CRS was made according to the PRISMA guidelines., Results: Altogether, 48 studies were included, only five studies reported on injected corticosteroids, and five attended with side effects. Three studies found beneficial effects of OCS perioperatively on sinus surgery, while four articles found no effect. Nineteen articles reported that OCS resulted in an improvement in symptoms. Two articles presented a longer-lasting effect of injected corticosteroids than OCS. Three studies reported adverse side effects of systemic corticosteroids, while two studies showed no adverse side effects. One study showed less adrenal suppression after injected corticosteroids compared to OCS. The evidence is not strong but shows a positive effect of systemic corticosteroids that lasts longer with injections., Conclusion: Although systemic corticosteroids are widely used to treat CRS, there is a lack of studies comparing the OCS and injected corticosteroids. The evidence is sparse, however, injected steroids show longer effects with fewer side effects. An RCT study is needed to compare OCS and injected corticosteroids., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

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: Treatment guidelines for asthma management are derived almost exclusively from the results of controlled clinical trials undertaken in carefully selected patient populations; meaning that their outcomes may not reflect the true performance of treatments when used in general daily medical practice. The aim of this meta-analysis was to combine the results of observational studies investigating the fluticasone propionate/formoterol (FP/FORM) fixed-dose combination in real-world asthma patients., Methods: A systemic literature review was completed in March 2019 using the PubMed database. We identified 394 studies. Five studies, which included a total of 4756 patients treated with FP/FORM, were judged eligible and included in the meta-analysis., Results: The estimated severe asthma exacerbation rate was 11.47% (95% CI, 5.8 to 18.72%), calculated from the random effect model. A sensitivity analysis excluding 2 studies (one was an outlier, and the exacerbation rate for the studied treatment alone could not be determined in the other) showed a 7.04% rate of severe asthma exacerbations. The estimated relative risk of the incidence of severe asthma exacerbations was 0.323 (95% CI, 0.159 to 0.658). The estimated asthma control rate was 60.6% (95% CI, 55.7% to 65.6%). The odds of achieving asthma control significantly increased by FP/FORM compared with pre-study conditions (estimated odds ratio: 2.214 [95% CI, 1.292 to 3.795]; p  < 0.001)., Conclusions: The findings of this meta-analysis confirm the effectiveness of FP/FORM for the treatment of asthma patients in a real-world setting beyond the limitations of RCTs., Competing Interests: Mundipharma was not involved in the study design, data collection, analysis or interpretation. Mundipharma reviewed the written manuscript and was involved in the decision to submit it for publication., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

BACKGROUND : Although exercise and daily physical activity (PA) have long been known to benefit patients with chronic disorders, knowledge is limited regarding asthma. OBJECTIVE : In a Danish setting, our aim was to measure physical activity, sedentary behavior, and physical capacity among patients with asthma. We hypothesized that people with severe asthma would be less active and more sedentary than their mild-moderate counterparts. METHODS : Adults with asthma were recruited through respiratory outpatient clinics and subsequently examined twice, 4 weeks apart. At each visit, participants underwent a series of lung function tests, questionnaires, and maximum oxygen uptake testing (VO 2 max). Between the visits, participants wore an accelerometer continuously for 4 weeks, measuring sedentary time and daily steps. Sixty patients, 27 with mild-moderate asthma (GINA 1-3) and 33 with severe asthma (GINA 4-5), completed both visits and had valid accelerometer measurements. RESULTS : No significant differences between the two groups were found in sedentary time, number of steps or VO 2 max.   VO 2 max was significantly correlated with FeNO (r = -0.30, p < 0.05), Short Form-12 Mental Health (r = 0.37, p < 0.05), Asthma Control Questionnaire (r = -0.35, p < 0.05), and Mini Asthma Quality of Life Questionnaire (r = 0.36, p < 0.05). CONCLUSION : No differences were observed between patients with mild-moderate and severe asthma regarding sedentary behavior, daily steps or level of cardiopulmonary fitness. Furthermore, patients with the highest VO 2 max had the higher quality of life scores. Abbreviations : VO 2 max: Maximal Oxygen Uptake; CPET: Cardiopulmonary Exercise Testing; BMI: Body Mass Index; FEV1: Forced Expired Volume in the First Second; FVC: Forced Vital Capacity; PEF: Peak Expiratory Flow; EIB: Exercise-Induced Bronchoconstriction; COPD: Chronic Obstructive Pulmonary Disease; ACQ: Asthma Control Questionnaire; Mini-AQLQ: Mini Asthma Quality of Life Questionnaire; SF-12: Short Form 12 Health Survey; SNOT-22: Sino-Nasal Outcome Test 22; GINA: The Global Initiative for Asthma; CRP: C-reactive Protein; Hgb:Hemoglobin count; EOS: Eosinophil count; EVH: Eucapnic Voluntary Hyperventilation; FeNO: Fractional Exhaled Nitric Oxide; PA: Physical Activity ERS: European Respiratory Society; ATS: American Thoracic Society; CRS: Chronic Rhinosinusitis; AHR: Airway Hyperresponsiveness., Competing Interests: No potential conflict of interest was reported by the authors., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p  < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p  < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p  < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background : Listening to music as a means of relieving anxiety before and during endoscopy has been examined in several studies but results so far are contradictory and inconclusive. Aims : We aimed to determine whether listening to music could reduce anxiety prior to and during bronchoscopy, and whether it is influenced by the patient's preference in music. Methods : 300 patients undergoing bronchoscopy for suspected lung cancer were randomly assigned to: self-selected music, specially-designed music (MusiCure TM ), or control (no sound). Spielberger's State-Trait Anxiety Inventory (STAI) was administered three times: at admission, after 20 min with or without music (preceding bronchoscopy), and shortly before discharge. The primary outcome was STAI state score after 20 min, with or without exposure to music prior to bronchoscopy. Results : On average, music reduced the STAI score by 2.5 points (95% CI, 1.1 to 4.0; p < 0.001) compared with the control group. This reduction was largest in the self-selected music group (3.4; 95% CI, 1.5 to 5.3; p < 0.001). In contrast, specially designed music did not significantly reduce STAI score (1.7; 95% CI, -0.3 to 3.6; p = 0.1). Conclusion : Listening to music reduces anxiety in patients undergoing bronchoscopy, provided that the music complies with the patient's preferences.

Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma ('difficult asthma') should undergo systematic assessment, in order to differentiate between true severe asthma, and 'difficult-to-treat' patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care., Competing Interests: No potential conflict of interest was reported by the authors.

Background : Patients suffering from exercise-induced laryngeal obstruction (EILO) are subjected to several exhausting tests. We aimed to assess the feasibility of using a single test to obtain diagnostic measurements for maximum oxygen uptake (VO 2 max) and exercise-induced laryngeal obstruction (EILO). Methods : Patients referred to the outpatient respiratory clinic at the University Hospital of Bispebjerg, Copenhagen with exercise-induced dyspnoea were evaluated for inclusion over 13 months. Eligible patients were aged 18-43 years, had a known EILO diagnosis (moderate or severe) and were inactive (self-reported activity) with less than 3 hours activity per week. In randomised order, all participants ( n  = 11) underwent three tests: a VO 2 max test with and without concurrent laryngoscopy. VO 2 max and EILO values from the two testing methods were compared. Findings : There was no difference in VO 2 max measured by ergospirometry with and without simultaneous continuous laryngoscopy during exercise (CLE) testing (mean difference -22 ml O 2 ･min -1 ; 95% CI -125 to 81 ml O 2 ･min -1 ; P  = 0.647). EILO scores obtained during the CLE testing on the treadmill versus CLE testing on the ergometer bike revealed identical supraglottic scores in nine of the 11 participants (82%) with substantial agreement between the two types of test ( x  = 0.71). Glottic scores were identical in six of the 11 (55%), showing moderate agreement between test types ( x  = 0.38). Conclusions : Based on our findings in inactive individuals, ergospirometry with laryngoscopy is feasible and well tolerated, yielding measurements for maximal oxygen uptake comparable to those of standard bike ergospirometry. Likewise, measurements of supraglottic EILO are comparable to those of the standard treadmill CLE test., Competing Interests: No potential conflict of interest was reported by the authors.

Asthma is one of the most common chronic diseases worldwide affecting more than 300 million people. Symptoms are often non-specific and include coughing, wheezing, chest tightness, and shortness of breath. Asthma may be highly variable within the same individual over time. Although asthma results in death only in extreme cases, the disease is associated with significant morbidity, reduced quality of life, increased absenteeism, and large costs for society. Asthma can be diagnosed based on report of characteristic symptoms and/or the use of several different diagnostic tests. However, there is currently no gold standard for making a diagnosis, and some degree of misclassification and inter-observer variation can be expected. This may lead to local and regional differences in the treatment, monitoring, and follow-up of the patients. The Danish National Database for Asthma (DNDA) is slated to be established with the overall aim of collecting data on all patients treated for asthma in Denmark and systematically monitoring the treatment quality and disease management in both primary and secondary care facilities across the country. The DNDA links information from population-based disease registers in Denmark, including the National Patient Register, the National Prescription Registry, and the National Health Insurance Services register, and potentially includes all asthma patients in Denmark. The following quality indicators have been selected to monitor trends: first, conduction of annual asthma control visits, appropriate pharmacological treatment, measurement of lung function, and asthma challenge testing; second, tools used for diagnosis in new cases; and third, annual assessment of smoking status, height, and weight measurements, and the proportion of patients with acute hospital treatment. The DNDA will be launched in 2016 and will initially include patients treated in secondary care facilities in Denmark. In the nearby future, the database aims to include asthma diagnosis codes and clinical data registered by general practitioners and specialised practitioners as well., Competing Interests: and funding The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

Background: The use of music to relieve anxiety has been examined in various studies, but the results are inconclusive., Methods: From April to October 2015, 160 patients undergoing examination of pulmonary nodules were randomly assigned to MusiCure or no music. MusiCure was administered through earplugs to ensure blinding of the staff and was played from admission to the operating theatre to the end of the bronchoscopy. Spielberger's State-Trait Anxiety Inventory (STAI) was administered on admission, immediately before bronchoscopy, and on discharge. Secondary outcomes were p -cortisol, physiological variables, dosage of sedatives, movements measured by Actigraph, bronchoscopy duration, number of re-examinations, and overall perception of the sounds in the operating theatre measured by Visual analogue scale., Results: The STAI scores were similar on admission, but after a 10-min wait in the operating theatre, scores varied significantly between patients with and without music, with lower scores in the music group [median (interquartile range, IQR) 35 (18) vs. 43 (25); p= 0.03]. Post hoc multiple regression revealed treatment group as insignificant when adjusting for sex and baseline anxiety. However, there was a significantly more positive perception of the sounds in the operating theatre in the music group (median (IQR) 8.2 (1.8) vs. 5.4 (6.8); p <0.0001) and fewer re-examinations in the music group (19.2% vs. 7.7%, p< 0.032)., Conclusions: Ten minutes with MusiCure does not alter anxiety when adjusting for baseline anxiety and sex. The current study indicates that this field of research has many confounders., Competing Interests: and funding The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

Background: Several studies have shown that the use of pulmonary medication is widespread and often initiated without initial spirometry. Early detection of chronic obstructive pulmonary disease (COPD) by spirometry in General Practice is essential for an early and correct implementation of medical treatment., Aim: The aim of the present study was to evaluate the use of regular therapy following diagnostic spirometry for COPD in General Practice from February 2008 to February 2009., Method: Spirometry data and results were linked through Statistics Denmark with information from the Register of Medicinal Product Statistics using the unique personal identification code. Data were analysed to evaluate the impact of screening on use of regular COPD therapy. Primary outcome was initiation of regular therapy following COPD diagnosis with spirometry., Results: In a population of 3,376 individuals at risk, 1,458 underwent spirometric assessment with 631 being diagnosed with COPD; 110 of those received regular therapy before assessment with this figure increasing to 161 after spirometry. Of 827 participants not receiving a COPD diagnosis, 36 received regular therapy prior to assessment and 42 received regular therapy after spirometry despite no established COPD diagnosis., Conclusion: There is a significant chance of receiving regular therapy after being diagnosed with COPD. However, a large proportion of subjects diagnosed with COPD did not receive regular therapy following diagnosis. Efforts should be made to ensure correct diagnosis and correct medical treatment according to guidelines in individuals with COPD.

Background: Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (-131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40, and SNP (-131 C/G, rs4950928)., Methods: In this study, 1,137 patients with asthma, 415 with rhinitis only, and 275 non-asthmatic controls were included. Assessment included a clinical interview concerning the diagnosis of asthma, severity of asthma, and asthma treatment as well as clinical tests to assess asthma and rhinitis. Serum YKL-40 was measured, and genotyping for the SNP (-131 C/G) was conducted., Results: No significant difference in the serum concentration of YKL-40 was found between patients with asthma, patients with rhinitis, and non-asthmatic controls; however, YKL-40 was increased in patients with severe asthma. No association was found between the SNP (-131 C/G rs4950982) and the risk of having asthma (odds ratio = 0.90, p=0.4). Higher levels of serum YKL-40 were found in all subjects when comparing CC genotype to CG and GG genotypes (45 µg/L vs. 32 µg/L and 19 µg/L, p<0.0001)., Conclusion: There was no association between polymorphisms of SNP (-131 C/G) and asthma. The highest serum YKL-40 concentrations were seen in severe asthmatics. Individuals with less severe asthma showed a smaller difference against controls, limiting its clinical usefulness. More research is needed to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1.

Objective: The best strategy for diagnosing asthma remains unclear. Accordingly, the aim of this study was to evaluate diagnostic strategies in individuals with possible asthma referred to a respiratory outpatient clinic at a university hospital., Methods: All individuals with symptoms suggestive of asthma referred over 12 months underwent spirometry, bronchodilator reversibility test, Peak expiratory flow rate (PEF) registration, and bronchial challenge test with methacholine and mannitol on three separate days. The results of these tests were compared against an asthma diagnosis based on symptoms, presence of atopy and baseline spirometry made by a panel of three independent respiratory specialists., Results: Of the 190 individuals examined, 63% (n=122) were classified as having asthma. Reversibility to β2-agonist had the lowest sensitivity of 13%, whereas airway hyperresponsiveness to methacholine had the highest (69%). In contrast, specificity was the highest for reversibility testing (93%), whereas methacholine had the lowest specificity (57%). The combination of reversibility, peak-flow variability, and methacholine yielded a cumulative sensitivity of 78%, albeit a specificity of 41%. In comparison, a combination of reversibility and mannitol resulted in a specificity of 82% and a sensitivity of 42%., Conclusion: In this real-life population, different diagnostic test combinations were required to achieve a high specificity for diagnosing asthma and a high sensitivity, respectively: Our findings suggest that the diagnostic test approach should be based on whether the aim is to exclude asthma (high sensitivity required) or confirm a diagnosis of asthma (high specificity required).

Background: Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in accumulation of glycosphingolipids in multiple organs, primarily heart, kidneys, skin, CNS, and lungs., Materials and Method: A systematic literature search was performed using the PubMed database, leading to a total number of 154 hits. Due to language restriction, this number was reduced to 135; 53 papers did not concern Fabry disease, 19 were either animal studies or gene therapy studies, and 36 papers did not have lung involvement in Fabry disease as a topic. The remaining 27 articles were relevant for this review., Results: The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory examinations are seldom performed. Pulmonary function tests primarily show obstructive airway limitation, but a few articles also report of patients with restrictive limitation and a mixture of both. No significant association has been found between smoking and the development of symptoms or spirometry abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed by high-resolution CT has not been significantly correlated with lung spirometry., Conclusion: Consistent findings have not been shown in the current literature. Pulmonary function tests and registration of symptoms showed various results; however, there is a trend towards obstructive airway limitation in patients with Fabry disease. Further studies are needed to evaluate pathogenesis, progression, and the effects of treatment.