Real-world phenotyping and risk assessment of childhood asthma burden using national registries.

BACKGROUND: Phenotype classification contributes to risk assessment of asthma. Previous studies have applied this concept primarily to adult populations and in the setting of research protocol assessments which may not be applicable to clinical settings. OBJECTIVE: Exploring the value of routinely collected clinical data for phenotype classification and risk assessment of childhood asthma. METHODS: Using hospital and laboratory data, 29,851 children in a Danish nationwide database aged 2-17 years with ICS-treated asthma in 2015 followed for two years (730 days) were classified to have T2 (elevated blood eosinophils (>300 cells/µL) and/or elevated total- or specific-IgE), and/or non-T2 risk factors (in utero tobacco exposure and/or severe viral infections). Logistic regression was applied to quantify associations of risk factors with asthma severity, control, and exacerbation risk. RESULTS: In a complete case analysis, 85.8 % children had at least one T2 risk factor and 29.3 % had mixed T2/non-T2 risk factors. Elevated blood eosinophils and total/specific IgE were associated with exacerbations (ORs 1.55 (1.38-1.73) and 1.41 (1.20-1.66) and higher asthma severity (1.42 (1.24-1.63) and 1.31 (1.08-1.60)), respectively. Dose-dependency was observed between blood eosinophil counts, total IgE levels, and risk of adverse outcomes. Furthermore, accumulation of risk factors demonstrated an increasing risk, with children with all four risk factors having a high risk of any adverse asthma-related outcome (OR 3.13 (2.03-4.82) CONCLUSION: Asthma phenotypic markers defined in research protocols can be reliably applied in real-world settings by utilizing data collected during routine clinical care and enable better classification of risk of adverse asthma outcomes.

Evaluating the scientific reliability of ChatGPT as a source of information on asthma.

Background: This study assessed the reliability of ChatGPT as a source of information on asthma, given the increasing use of artificial intelligence-driven models for medical information. Prior concerns about misinformation on atopic diseases in various digital platforms underline the importance of this evaluation. Objective: We aimed to evaluate the scientific reliability of ChatGPT as a source of information on asthma. Methods: The study involved analyzing ChatGPT's responses to 26 asthma-related questions, each followed by a follow-up question. These encompassed definition/risk factors, diagnosis, treatment, lifestyle factors, and specific clinical inquiries. Medical professionals specialized in allergic and respiratory diseases independently assessed the responses using a 1-to-5 accuracy scale. Results: Approximately 81% of the responses scored 4 or higher, suggesting a generally high accuracy level. However, 5 responses scored >3, indicating minor potentially harmful inaccuracies. The overall median score was 4. Fleiss multirater kappa value showed moderate agreement among raters. Conclusion: ChatGPT generally provides reliable asthma-related information, but its limitations, such as lack of depth in certain responses and inability to cite sources or update in real time, were noted. It shows promise as an educational tool, but it should not be a substitute for professional medical advice. Future studies should explore its applicability for different user demographics and compare it with newer artificial intelligence models.

Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial.

BACKGROUND: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes. METHODS: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365. RESULTS: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037. CONCLUSIONS: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.

Characteristics of Adults With Severe Asthma in Childhood: A 60-Year Follow-up Study.

BACKGROUND: Childhood asthma is a prevalent condition with potential impact on adult life. RESEARCH QUESTION: In a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood? STUDY DESIGN AND METHODS: Danish adults with a history of childhood asthma and a 4-month stay in at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was carried out through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months, with the remaining participants being classified as having current asthma. RESULTS: Among 1,394 eligible participants, 232 participants completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared with participants in remission, participants with persistent asthma showed higher total IgE (P = .03) and both lower FEV1 % predicted (P = .03) and FEV1 to FVC ratio (P < .001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count. INTERPRETATION: Our 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine of 10 participants still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared with asthma remission.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

Inhaled corticosteroids and Stenotrophomonas maltophilia in outpatients with chronic obstructive pulmonary disease: a retrospective cohort study.

OBJECTIVES: Inhaled corticosteroids (ICS) are widely used in patients with chronic obstructive pulmonary disease (COPD). However, ICS are associated with an increased risk of adverse effects.We aimed to determine whether an association between a lower respiratory tract culture with Stenotrophomonas maltophilia and increasing ICS dosing in patients with COPD exists. DESIGN: An observational cohort study of outpatients with COPD in Denmark between 2010 and 2018.ICS exposure was categorised into four groups based on average daily consumption 1 year prior to inclusion: no use, low ICS dose (≤400 µg), moderate ICS dose (400-800 µg) and high ICS dose (>800 µg). Dose-response relationship was investigated by a multivariable Cox proportional hazards regression. RESULTS: Of the total 22 689 patients, 459 had lower respiratory tract cultures positive for S. maltophilia. The HR of S. maltophilia increased with increasing daily ICS dose: low ICS dose HR 2.6 (95% CI 1.6 to 4.0), moderate ICS dose HR 3.0 (95% CI 1.9 to 4.6) and high ICS dose HR 5.7 (95% CI 3.8 to 8.5). CONCLUSIONS: We found that ICS was associated with a high, dose-dependent increased hazard of S. maltophilia in outpatients with COPD. High dose users had a nearly six times increased hazard compared with non-users of ICS. When appropriate, attempts at de-escalating ICS treatment should be made.

Opportunistic screening for COPD among socially marginalized patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease associated with premature death. Tobacco exposure is the main risk factor, but lower socioeconomic status, early life insults, and occupational exposures are also important risk factors. Socially marginalized people, facing homelessness, substance use disorder, and mental illness, are likely to have a higher risk of developing COPD, and, furthermore, experience barriers to healthcare access and consequently poorer outcomes. OBJECTIVE: This study aims to assess COPD prevalence and the impact of opportunistic screening among hospitalized patients who are in contact with hospital social nurses. These patients constitute a group of patients with a high prevalence of psychiatric and somatic diseases, substance use, low life expectancy, and are socially marginalized. METHODS: The present prospective longitudinal study includes a clinical examination at baseline. Participants will have spirometry done and be interviewed regarding risk factors, socioeconomic conditions, and respiratory symptoms. The 5-year follow-up assessment incorporates data from baseline and register data over the 5 years, including information on morbidity, use of COPD medication, hospital contacts, mortality, and socioeconomic factors. ANTICIPATED RESULTS: Referral for further diagnostic work-up and management after the screening, including COPD treatment and smoking cessation support, is expected to improve survival rates. The study is still enrolling patients. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov , NCT04754308 with study status: "enrolling".

Impact of family socioeconomic position on childhood asthma outcomes, severity, and specialist referral - a Danish nationwide study.

BACKGROUND: Asthma is the most common chronic illness in children, carrying a major burden. Socioeconomic position (SEP) affects adult asthma outcomes, but its impact on childhood asthma, particularly in primary versus specialist care, has not been studied thoroughly. METHODS: In a Danish cohort consisting of all children aged 2-17 years redeeming inhaled corticosteroids in 2015, parental SEP impact on asthma outcomes was investigated. Workforce attachment, income, education, and metropolitan residence were chosen as covariates in logistic regression. Outcomes were uncontrolled (excessive use of short-acting beta2-agonists), exacerbating (oral corticosteroid use or hospitalization), and severe asthma (according to GINA 2020). RESULTS: The cohort comprised 29,851 children (median age 8.0, 59% boys). 16% had uncontrolled asthma, 8% had ≥1 exacerbation. Lower income and metropolitan residence correlated with higher odds of poor control, exacerbations, and severe asthma. Lower education correlated with worse asthma outcomes. Education and income were protective factors in primary care, but not in specialist care. Metropolitan residence was the sole factor linked to specialist care referral for severe asthma. CONCLUSION: Low parental SEP and metropolitan residence associated with poor asthma outcomes. However, specialist care often mitigated these effects, though such care was less likely for at-risk children in non-metropolitan areas.

Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register.

BACKGROUND: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. OBJECTIVE: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. METHODS: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. RESULTS: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. CONCLUSION: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

COPD: pulmonary vascular volume associated with cardiac structure and function.

BACKGROUND: Early recognition of cardiac dysfunction in patients with chronic obstructive pulmonary disease (COPD) may prevent future cardiac impairment and improve prognosis. Quantitative assessment of subsegmental and segmental vessel volume by Computed Tomographic (CT) imaging can provide a surrogate of pulmonary vascular remodeling. We aimed to examine the relationship between lung segmental- and subsegmental vessel volume, and echocardiographic measures of cardiac structure and function in patients with COPD. METHODS: We studied 205 participants with COPD, included in a large cohort study of cardiovascular disease in COPD patients. Participants had an available CT scan and echocardiogram. Artificial intelligence (AI) algorithms calculated the subsegmental vessel fraction as the vascular volume in vessels below 10 mm2 in cross-sectional area, indexed to total intrapulmonary vessel volume. Linear regressions were conducted, and standardized ß-coefficients were calculated. Scatterplots were created to visualize the continuous correlations between the vessel fractions and echocardiographic parameters. RESULTS: We found that lower subsegmental vessel fraction and higher segmental vessel volume were correlated with higher left ventricular (LV) mass, LV diastolic dysfunction, and inferior vena cava (IVC) dilatation. Subsegmental vessel fraction was correlated with right ventricular (RV) remodeling, while segmental vessel fraction was correlated with higher pulmonary pressure. Measures of LV mass and right atrial pressure displayed the strongest correlations with pulmonary vasculature measures. CONCLUSION: Pulmonary vascular remodeling in patients with COPD, may negatively affect cardiac structure and function. AI-identified remodeling in pulmonary vasculature may provide a tool for early identification of COPD patients at higher risk for cardiac impairment.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).

Biomarker-guided withdrawal of inhaled corticosteroids in asthma patients with a non-T2 inflammatory phenotype - a randomized controlled trial study protocol.

BACKGROUND: Non-T2 asthma is characterized by the absence of elevated type 2 inflammatory biomarkers such as blood-eosinophils, total and allergen-specific Immunoglobulin E and Fractional exhaled Nitric Oxide (FeNO). According to guidelines, inhaled corticosteroids (ICS) are the cornerstone of asthma management. However, ICS treatment is associated with a risk of local side effects, including hoarseness and thrush, and long-term high-dose therapy may cause systemic adverse effects. Furthermore, whereas treatment with ICS is highly effective in T2 asthma, studies have shown a markedly reduced ICS efficacy in patients with a lower degree of T2 inflammation, thus posing a clinical challenge in this subgroup of patients. Hence, owing to the ICS dosage step-up approach in current clinical guidelines, patients with low T2 biomarkers are at risk of being exposed to high doses of ICS, and by that at risk of side effects. Thus, an ICS-treatment regime guided by biomarkers that reflects the inflammatory phenotype is warranted in order to reduce the corticosteroid burden in patients with non-T2 asthma. This study combines a panel of non-T2 inflammatory markers (low periostin, low blood-eosinophils, and low FeNO), to determine if this group of patients can maintain asthma control during ICS withdrawal. METHODS: This is an ongoing prospective multicenter open-label randomized, controlled trial aiming to assess if ICS can be safely tapered in patients with non-T2 asthma. The patients are randomized 1:1 to either standard of care or an ICS tapering regimen (n = 55 in each group) where the initial ICS dose is reduced by 50% for 8 weeks followed by total ICS removal. The primary endpoint is change in asthma control questionnaire (ACQ) from baseline to post-tapered ICS. The secondary endpoints are time from baseline to drop-out caused by loss of asthma control, changes in serum-periostin, blood-eosinophils, FeNO, Forced Expiratory Volume in 1 s (FEV1) and in sputum-eosinophils. DISCUSSION: This study aims to provide data on ICS tapering in non-T2 asthma patients and to contribute to a more individualized and corticosteroid-sparing treatment regime in this group of patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03141424. Registration date: May 5th, 2017.

Relationship between early life asthma and chronic airway disease in adult life - in search for disease trajectories over the life span- the RELATE study based on the Kongsberg cohort.

BACKGROUND: Chronic airway disease in adults may have its origin in early life. The purpose of this study is to investigate the long-term prognosis of severe childhood asthma in search for an association between asthma in early life and obstructive lung disease in adulthood. METHODS: This study is based on the Kongsberg cohort, which includes approximately 5000 children with severe asthma with a 4-month stay at the asthma care facility in Kongsberg, Norway during the years 1950 to 1979. An on average 60-year observational study based on a follow-up examination will be performed including questionnaires, blood samples, and tests of lung function and bronchial responsiveness. Blood samples will be stored in a biobank. In addition, we will conduct further analyses of the cohort based on nationwide register data, including socio-economic parameters and mortality. DISCUSSION: Chronic airway disease is associated with substantial burden for both the individual patient and society. Our knowledge of early life origins of chronic airway disease later in life has been increasing in recent decades but is still limited. By exploring early life risk factors for chronic airway disease in adulthood, we may gain insights paving the way for future reduction in the burden of chronic airway diseases.

Mortality and exacerbations associated with Stenotrophomonas maltophilia in chronic obstructive pulmonary disease. A regional cohort study of 22,689 outpatients.

OBJECTIVES: The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD. METHODS: An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression. RESULTS: Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1). CONCLUSIONS: A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment.

Childhood Asthma and Parental Antidepressant Use in a Nationwide Danish Cohort.

Background: Paediatric asthma is associated with caregiver depression, which in turn is associated with poor asthma control. Although sociodemographic risk factors are associated with parental depression among children with asthma, the contribution of these factors to caregiver depression in free-to-access universal healthcare settings is unknown. Methods: The association between childhood asthma and parental antidepressant use was investigated in a Danish nationwide cohort of children aged 2-17 years that redeemed inhaled corticosteroids in 2015. The odds of antidepressant use were estimated in comparison to control families that were matched 1:1 on the number of siblings, residence, income, and education. Results: Among the families of 28,595 children with actively treated asthma, 12% of mothers and 6.2% of fathers were on antidepressant therapy, compared to 9.3% and 5.3% in controls (p<0.001). Paediatric asthma was associated with increased odds of parental antidepressant use (OR 1.29 (1.23-1.35)), even after adjusting for parental asthma. Poor asthma control, but not higher asthma severity, was associated with higher odds of antidepressant use (1.43 (1.31-1.56)). Compared with the controls, families with two or more children with asthma had higher OR (1.42 (1.29-1.56)) than those with a single child (OR 1.27 (1.21-1.34)). Low socioeconomic status was associated with parental antidepressant use. Conclusion: Caregiver depression in a Danish cohort is more prevalent among mothers than among fathers and is associated with poor asthma control in children. Antidepressant use among caregivers was associated with total family asthma burden and was independent of socioeconomic status.

Magnesium sulfate treatment for acute severe asthma in adults-a systematic review and meta-analysis.

Introduction: Add-on magnesium sulfate (MgSO4) for refractory asthma exacerbation has been much debated. The aim of this review and meta-analysis is, therefore, to provide an update on the current evidence for the efficacy of MgSO4 in exacerbations of asthma in adults refractory to standard of care treatment. Methods: A systematic review was performed in accordance with the PRISMA guidelines. The search was performed in the PubMed database (updated April 2023). For the meta-analysis, a random-effects model was applied using the metaphor package for RStudio (RStudio, Inc.). Results: A total of 17 randomized controlled trials were included. Three of the nine studies addressing treatment with intravenous (IV) MgSO4 found a significant effect on lung function compared to placebo. Of the eight studies investigating hospital admission rate, only two found a significant effect of MgSO4. Six of the nine studies investigating treatment with nebulized MgSO4 compared to placebo found a favorable effect on forced expiratory volume in 1. second (FEV1) and peak expiratory flow rate (PEF). Only two of the five studies investigating the effect on hospital admission rate found an effect of MgSO4. Comparing effect sizes in a meta-analysis revealed a greater effect on PEF in asthma patients treated with nebulized MgSO4 (MD, 23.57; 95% CI, -2.48 to 49.62, p < 0.01) compared to placebo. The analysis of patients treated with i.v. MgSO4 compared to placebo showed no statistically significant difference (MD, 5.49; 95% CI, -18.67 to 29.65, p = 0.10). Conclusion: Up to two out of three studies revealed an effect of MgSO4 treatment for asthma exacerbation when assessed by FEV1/PEF, but fewer studies were positive for the outcome of hospital admissions.

Pulmonary telerehabilitation vs. conventional pulmonary rehabilitation - a secondary responder analysis.

Home-based pulmonary telerehabilitation (PTR) has been proposed to be equivalent to supervised outpatient pulmonary rehabilitation (PR) but available randomised trials have failed to reach the minimal important changes (MIC). The purpose of this study was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total and between groups in 134 patients with COPD randomised (1:1) to either home-based PTR or traditional hospital-based outpatient PR. Difference between PTR and PR on 6MWD response proportion could not be shown at 10 (OR=0.72, CI=0.34 to 1.51, p=0.381) or 62 weeks (OR=1.12, CI=0.40 to 3.14, p=0.834). While the evidence and knowledge of PTR accumulate, outpatient supervised PR for now remains the standard of care, with home-based PTR as a strong secondary option for those unable to attend out-patient programmes.

Effect of 10-Day Treatment with 50 mg Prednisolone Once-Daily on Haemostasis in Healthy Men-A Randomised Placebo-Controlled Trial.

Synthetic corticosteroids are widely used due to their anti-inflammatory and immunosuppressant effects. Their use has been associated with venous thromboembolism, but it is unknown whether thromboembolism has a causal relationship with corticosteroid treatment. In a randomised, double-blind, placebo-controlled trial in normal to overweight healthy men, the effect of the corticosteroid prednisolone on haemostasis using either 50 mg prednisolone or matching placebo once daily for ten days was investigated. The primary outcome was a change from baseline in the viscoelastic measurement maximal amplitude of clot in kaolin-activated thromboelastography (TEG). Changes from baseline in other TEG measurements, D-dimer, von Willebrand factor (VWF) antigen, and ristocetin cofactor activity (RCo), antithrombin, protein C, prothrombin, fibrinogen, INR, APTT, and platelet count were secondary outcomes. Thirty-four men participated in this study. Compared to placebo, prednisolone treatment did not affect maximal amplitude of clot (difference -0.77 (95% confidence interval (CI) -2.48, 0.94) mm, p = 0.37, missing: n = 2), but it altered VWF antigen (28%, p = 0.0004), VWF:RCo (19%, p = 0.0006), prothrombin (5%, p = 0.05), protein C (31%, p < 0.0001), antithrombin (5%, p = 0.013), and fibrinogen (-15%, p = 0.004). Thus, prednisolone treatment did not alter TEG-assessed maximal amplitude of clot, despite that it affected prothrombotic markers (increased prothrombin, VWF antigen, VWF:RCo, prothrombin, and decreased fibrinogen) and increased antithrombotic markers (protein C and antithrombin).