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Background: A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARIs) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0·92 [95% CI 0·86 to 0·99]). Since then, six eligible RCTs have been completed, including one large trial (n=15 804). We aimed to re-examine the link between vitamin D supplementation and prevention of ARIs., Methods: Updated systematic review and meta-analysis of data from RCTs of vitamin D for ARI prevention using a random effects model. Subgroup analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, dosing regimen, or age. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov between May 1, 2020 (end-date of search of our previous meta-analysis) and April 30, 2024. No language restrictions were imposed. Double-blind RCTs supplementing vitamin D for any duration, with placebo or lower-dose vitamin D control, were eligible if approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. The study was registered with PROSPERO (no. CRD42024527191)., Findings: We identified six new RCTs (19 337 participants). Data were obtained for 16 085 (83·2%) participants in three new RCTs and combined with data from 48 488 participants in 43 RCTs identified in our previous meta-analysis. For the primary comparison of any vitamin D versus placebo, the intervention did not statistically significantly affect overall ARI risk (OR 0·94 [95% CI 0·88-1·00], p=0·057; 40 studies; 61 589 participants; I 2 =26·4%). Pre-specified subgroup analysis did not reveal evidence of effect modification by age, baseline vitamin D status, dosing frequency, or dose size. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0·96 [95% CI 0·90-1·04]; 38 studies; I 2 =0·0%). A funnel plot showed left-sided asymmetry (p=0·0020, Egger's test)., Interpretation: This updated meta-analysis yielded a similar point estimate for the overall effect of vitamin D supplementation on ARI risk to that obtained previously, but the 95% CI for this effect estimate now includes 1·00, indicating no statistically significant protection., Funding: None., Competing Interests: Declaration of interests ARM reports grants from the Fischer Family Trust, Pharma Nord, DSM Nutritional Products, the AIM Foundation, Cytoplan, and Thornton & Ross outside the submitted work. CG reports grants from the Health Technology Assessment Program of the UK National Institute of Health Research during conduct of the study and is supported by the National Institute for Health and Care Research ARC North Thames. The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health and Care Research or the Department of Health and Social Care. WJ reports grants from Chiesi and AstraZeneca outside the submitted work. REN reports grants from the Australian National Health and Medical Research Council during the conduct of the study. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Diagnosing asthma typically relies on clinical history, physical examination, and objective lung function test results. Spirometry, the gold standard for assessing lung function, is universally recommended for the diagnostic, assessment, and monitoring of asthma. It requires maximal respiratory effort that limits cooperation in certain populations and has limitations in detecting small airway dysfunction. Oscillometry requires minimal patient effort, is noninvasive, and provides valuable information on both large and small airways. Recent task force reports have suggested oscillometry as an alternative or a complementary lung function test to spirometry in the management of individuals with asthma. This review explores the scientific evidence and psychometric properties regarding oscillometry in the main purposes served by lung function testing in asthma, namely diagnosis, assessment of control and future risk, as well as longitudinal monitoring, including clinical utility. Furthermore, it addressed challenges and facilitators to implementation and future directions regarding its positioning as lung function testing in individuals with asthma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The small airways comprise generations 8 to 23 of the bronchial tree, consist of airways with an internal diameter < 2 mm, and are classically difficult to assess and treat in persistent asthma. Small airways dysfunction (SAD) is integral to the asthma management paradigm because it is associated with poorer symptom control and greater levels of type 2 inflammation, and it has been proposed as a potentially treatable asthma trait. Although identification of SAD based on oscillometry has been found to be clinically useful in managing asthma, very few physicians, including specialists, use this technique as part of standard or adjunct evaluation of lung function to diagnose asthma, grade severity of airway obstruction, ascertain disease control or the risk for future exacerbations, or to make management decisions. To rectify the unrecognized value of oscillometry in the asthma community, a consortium of authors who are investigators with knowledge and experience of oscillometry wished to address the most important clinical questions raised by our colleagues who are considering using this technique, including its clinical utility. In this article, we discuss integral concepts, including applicability of oscillometry as a predictive tool for asthma exacerbations and disease control, adequacy of spirometry and oscillometry in assessing SAD, potential limitations of oscillometry, and treatment options for SAD., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: R. C. reports institutional grants from Chiesi; advisory boards for AstraZeneca; personal fees (talks) from AstraZeneca, Chiesi, and Thorasys; support for attending meetings from AstraZeneca, Chiesi, NIOX, and Sanofi-Regeneron; and honoraria (drafting educational material) from AstraZeneca and Vitalograph. L. G.-R. reports personal fees for conferences from GlaxoSmithKline, Chiesi, and Thorasys; and support for attending ERS from Chiesi. E. A. G. has received institutional grants from Gilead, Circassia, Chiesi, Propeller Health, Helicon Health, Adherium Ltd, and AstraZeneca; and personal fees from Circassia and Sanofi. F. M. D. has received unrestricted research funds from AstraZeneca, Covis Pharma, GlaxoSmithKline, Merck Canada, Novartis, Teva, Trudell Medical, GlaxoSmithKline, and MEDTEQ in partnership with Thorasys Inc; honoraria for consultancy work from AstraZeneca, Covis Pharma, Sanofi, Teva, and Thorasys Inc; and honoraria as an invited speaker from Covis Pharma, Jean-Coutu Pharmacy, and Brunet Pharmacy. None declared (M. C., P. C., S. P. G.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Numerous studies indicate an association between vitamin D status and inflammatory biomarkers in patients with asthma, but findings are inconsistent. This review aims to summarize the relationship between serum vitamin D status, assessed by 25-hydroxyvitamin D (25(OH)D) level, and inflammatory biomarkers in children and adults with asthma., Methods: A literature search of interventional and observational studies on 25(OH)D up to November 2022 was conducted across six electronic databases. Outcomes of interest included a range of inflammatory biomarkers classified in four categories: T helper 2 (Th2) pro-inflammatory, non-Th2 pro-inflammatory, anti-inflammatory, and non-specific biomarkers. Study characteristics were extracted and risk of bias was evaluated using the American Academy of Nutrition and Dietetics tool. Meta-analysis was conducted on studies with a low risk of bias, while narrative reporting was used to present the direction of associations (positive, no association, or negative) for each biomarker, overall and within the low-risk studies., Results: We included 71 studies (3 interventional, 68 observational) involving asthma patients. These studies investigated the association between serum 25(OH)D and Th2 pro-inflammatory biomarkers (N = 58), non-Th2 pro-inflammatory biomarkers (N = 18), anti-inflammatory biomarkers (N = 16), and non-specific biomarkers (N = 10). Thirteen (18.3%) studies, 50 (70.4%), and 8 (11.3%) were at high, moderate, and low risk of bias, respectively. In all studies, irrespective of risk of bias, the most frequently reported finding was no significant association, followed by a negative association between 25(OH)D and pro-inflammatory biomarkers and a positive association with anti-inflammatory biomarkers. In low-risk studies, one biomarker could be meta-analysed. The pooled estimate for 25(OH)D and serum IgE showed a negative association (β (95% CI)= - 0.33 (-0.65 to - 0.01); I 2  = 88%; N = 4 studies). A negative association between 25(OH)D and blood eosinophils was also observed in the largest of three studies, as well as with cathelicidin (LL-37) in the only study reporting it. For other biomarkers, most low-risk studies revealed no significant association with 25(OH)D., Conclusion: Serum 25(OH)D is negatively associated with serum IgE and possibly with blood eosinophils and LL-37, supporting an in vivo immunomodulatory effect of 25(OH)D. Future research should employ rigorous methodologies and standardized reporting for meta-analysis aggregation to further elucidate these associations., (© 2024. The Author(s).)

Background: Home blood self-collection devices can enable remote monitoring, but their implementation requires validation. Our objectives were to explore (i) the impact of sampling sites and topical analgesia on capillary blood volume and pain perception and (ii) the safety, acceptability, and failure of capillary self-collection among adults and children using the Tasso-SST device., Methods: We conducted a two-phase study. The investigational phase consisted of two on-site cross-sectional studies in healthy adult participants (≥ 12 years) and children (1-17 years) with their accompanying parent. Adults received 4 capillary samplings, where puncture sites and topical analgesia were randomized in a factorial design, and a venipuncture; children (and one parent) had one capillary sampling. The two co-primary outcomes were blood volume and pain. The implementation phase was conducted in two multicentre trials in participants choosing remote visits; blood volume, collection failure, adverse events, and satisfaction were documented., Results: In the investigational phase, 90 participants and 9 children with 7 parents were enrolled; 15 adults and 2 preschoolers participated in the implementation phase. In the adult investigational study, the device collected a median (25%, 75%) of 450 (250, 550) μl of blood with no significant difference between the puncture site, topical analgesia, and its interaction. Using topical analgesia reduced pain perception by 0.61 (95% CI: 0.97, 0.24; P <0.01) points on the 11-point scale; the pain reduction varied by puncture site, with the lower back showing the most significant decrease. Overall, combining all studies and phases, the median volume collected was 425 (250, 500) μl, and the device failure rate was 4.4%; minor adverse effects were reported in 8.9% of the participants, all were willing to use the device again., Conclusion: Capillary blood self-collection, yielding slightly less than 500 μl, proves to be a safe and relatively painless method for adults and children, with high satisfaction and low failure rates. The puncture site and topical analgesia do not affect blood volume, but topical analgesia on the lower back could reduce pain., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Francine M. Ducharme has received unrestricted research funds from AstraZeneca, Covis Pharma, GlaxoSmithKline, Merck Canada, Novartis, Teva, Trudell Medical; GlaxoSmithKline and MEDteq in partnership with Thorasys Inc., as well as honorariums for consultancy work from AstraZeneca, Covis Pharma, Sanofi, Teva, and Thorasys Inc. and honorariums as an invited speaker from Covis Pharma, Jean-Coutu Pharmacy and Brunet Pharmacy. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Dasari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: While the association between vitamin D and several inflammatory biomarkers in asthma patients has been extensively reported, it remains unclear whether supplementation modifies these biomarkers. This review aims to evaluate the impact of vitamin D supplementation on inflammatory biomarkers measured in vivo in individuals with asthma., Methods: We conducted a systematic review of randomized controlled trials (RCTs) published until November 2022 in six electronic databases evaluating the impact of vitamin D supplementation (any dose, form, administration route, frequency, or duration) compared to placebo in children or adults. The two co-primary outcomes were serum IgE and blood eosinophils reported at the endpoint. Secondary outcomes included other markers of type 2 inflammation (e.g., sputum eosinophils, fractional exhaled nitric oxide, etc.), anti-inflammatory biomarkers (e.g., interleukin (IL)-10, etc.), markers of non-type 2 inflammation (e.g., high-sensitivity C-reactive protein, etc.), and non-specific biomarkers (e.g., macrophages, etc.). Data were aggregated using fixed or random effect models., Results: Thirteen RCTs (5 in adults, 5 in pediatric patients, and 3 in mixed age groups) testing doses of vitamin D supplementation ranging from 800 to 400,000 IU over periods of 6 weeks to 12 months were included. Eight studies provided data on serum IgE and four on blood eosinophils. As secondary outcomes, three studies reported on sputum eosinophils, four on FeNO, five on serum IL-10, and two on airway IL-10. Compared to placebo, vitamin D supplementation had no significant effect on serum IgE (Mean difference [MD] [95% CI]: 0.06 [-0.13, 0.26] IU/mL), blood eosinophils (MD [95% CI]: - 0.02 [-0.11, 0.07] 10 3 /μL), or FeNO (MD [95% CI]: -4.10 [-10.95, 2.75] ppb) at the endpoint. However, the vitamin D supplementation group showed higher serum IL-10 levels compared to placebo (MD [95% CI]: 18.85 [1.11, 36.59] pg/ml) at the endpoint. Although data could not be aggregated, narrative synthesis suggested no significant effect of supplementation on sputum eosinophils and IL-10 in both sputum and exhaled breath condensate, at the endpoint., Conclusion: Vitamin D supplementation in individuals with asthma was not associated with lower inflammatory biomarkers related to type 2 inflammation. However, it was significantly associated with higher serum IL-10 compared to placebo., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022365666., Competing Interests: FMD has received unrestricted research funds from Jamieson and GSK, as well as investigator initiated research funds from Covis Pharma, Banque Scotia Foundation, GlaxoSmithKline, and MEDteq in partnership with Thorasys Inc. FMD has received an honorarium for consultancy work from INESSS, Astra Zeneca, Covis Pharma, Ontario Lung Association, Sanofi, and Teva. FMD has also been on the advisory board for Sanofi and has received honoraria as an invited speaker from the Association des Médecins omnipraticiens du Richelieu Saint-Laurent, Covis Pharma, Réseau québécois d’éducation en santé respiratoire (RQESR), Sanofi-Regeneron, Thorasys Inc., and Trudell Medical International. HT reported receiving occasional lecture fees from Merck and unrestricted grants form ViiV Healthcare. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 El Abd, Dasari, Dodin, Trottier and Ducharme.)

Increasingly, clinical practice guidelines advocate a precision medicine-based approach to care for asthma. This focus requires knowledge of not only different asthma phenotypes and their associated biomarkers but also sex and gender differences through the lifespan. Evidence continues to build in favor of different lifetime prevalence, clinical presentations, responses to management, and long-term prognosis of asthma. Women transition through many biological and psychosocial phases in their lives, all of which may interact with, and influence, their health and well-being. Historically, explanations have focused on hormonal effects on asthma in reproductive life, but a greater understanding of mechanisms starting before birth and changing over a lifetime is now possible, with immunologic, inflammatory, and hormonal factors playing a role. This article describes the evidence for the differences in asthma and rhinitis between men and women at different stages of life, the potential underlying mechanisms that contribute to this, and the implications for management and research. Future research studies should systematically report sex differences in asthma so that this knowledge can be used to develop a personalized approach to care, to achieve best possible outcomes for all., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Competing Interests: Declaration of interests MLL has received payments from publishers Taylor Francis and from Class Publishing; consulting fees from Smart Respiratory, Respiri, Imperial College, AstraZeneca, Novartis, and Teva; speaker or writing fees from Chiesi, AstraZeneca, and Teva; honoraria for manuscript writing and educational events from Consorzio Futuro in Ricerca; fees for expert testimony from HM Coroner, Waltham Forrest, London; support to attend meetings from Teva; and has held leadership roles (unpaid) in GINA, NHS England, and UK All Party Parliamentary Advisory Group (Asthma). EDB has received consulting fees from AstraZeneca, Regeneron, and Sanofi; speaker fees from AstraZeneca, Boehringer Ingelheim, Cipla, Novartis, Regeneron, Orion, and Sanofi Aventis; support to attend meetings from Orion, Sanofi, AstraZeneca, and GINA; and has participated (unpaid) in a board for DSMB for PACE study in COPD. KA declares no competing interests. LBB has received grants from the National Heart, Lung, and Blood Institute and National Institute of Allergy and Infectious Diseases; book royalties from Elsevier; consulting fees from Sanofi, Regeneron, Genentech, GlaxoSmithKline, DBV technologies, Teva, Medscape, Kinaset, OM Pharma, AstraZeneca, and Recludix; speaker fees from Sanofi, Regeneron, and GlaxoSmithKline; payment for advisory board participation from DBV Technologies, AstraZeneca, and Vertex; has participated in American Academy of Allergy Asthma & Immunology (unpaid) and American Board of Allergy and Immunology (paid); and has received medical writing services from Sanofi/Regeneron. MB has received grants from AstraZeneca and from GlaxoSmithKline; consulting fees from AstraZeneca, GlaxoSmithKline, and Sanofi; and speaker fees from AstraZeneca, Boehringer, Chiesi, GlaxoSmithKline, Menarini, Novartis, and Sanofi. L-PB has received grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Sanofi-Regeneron; royalties for texts published by UptoDate and by Taylor and Francis; consulting fees from Astra Zeneca, Novartis, GlaxoSmithKline, Merck, and Sanofi-Regeneron; speaker fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck, and Sanofi; and has participated (unpaid) in GINA as Chair of Board of Directors, Global Asthma Organisation (Interasma) as President, Canadian Thoracic Society Respiratory Guidelines Committee, and in Laval University as Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. AB has received grants, consulting fees and speaker fees from AstraZeneca, Boehringer Ingelheim, Sanofi, Novartis, GlaxoSmithKline, and AB science; support to attend meetings from AstraZeneca, Boehringer Ingelheim, Sanofi, Novartis, GlaxoSmithKline, AB science, and Chiesi; and has participated in an advisory board for AB science. CB has received grants (paid to institution) from GlaxoSmithKline, AstraZeneca, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, and Mologic; and has received consulting fees (paid to institution) from GlaxoSmithKline, AstraZeneca, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, Mologic, and Areteia. GB has received speaker fees from AstraZeneca Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MSD, Novartis, and Sanofi. RB has received grants (paid to institution) from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche; speaker fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Sanofi, Roche, and Teva; and has received payment for advisory board participation from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Sanofi, Roche, and Teva. AAC has received speaker fees from Chiesi, GlaxoSmithKline, Boehringer Ingelheim, Eurofarma, Abdi Ibrahim, Novartis, Sanofi, and AstraZeneca. JD has received editing fees from Cecil's Textbook of Medicine-Pulmonary and Critical Care, and has been a pro-bono board member of the Nantucket Cottage Hospital. FMD has received grants from Canadian Institutes of Health Research, Thorasys-Medteq, GlaxoSmithKline, Covis Pharma, Breathe, Canadian Lung Association, Children's Hospital Academic Medical Organisation, and Bank Scotia Foundation; consulting fees from Sanofi Regeneron, Ontario Lung Association, Covis Pharma, GlaxoSmithKline, FMSQ, AstraZeneca, Institut national d'excellence en santé et services sociaux, Quebec, and Canadian Thoracic Society; and speaker fees from Federation des Mds specialists du Québec, Jean-Coutu, Réseau Quebecois de l'enseignement en santé respiratoire, Teva, Thorasys, Association des Mds Omnipraticiens du Richelieu St-Laurent, Sanofi/Regeneron, and Covis Pharma. LD has received speaker fees (paid to institution) from AstraZeneca and British Thoracic Society; opponent's fees from Karolinska Institutet, University of Copenhagen, Barcelona Institute for Global Health; and grants (paid to institution) for CoKids Study (ZonMW, number 10150062010006, Stichting Vrienden van Sophia, and HZ2020: EUCAN-Connect grant agreement number 824989; ATHLETE, grant agreement number 874583; LIFECYCLE, grant agreement number 733206). LF has received grants from Asthma UK, National Institute of Health Research, and Asthma and Lung UK; consulting fees (paid to institution) from Sanofi, Regeneron, and AstraZeneca; and speaker fees (paid to institution) from Novartis and AstraZeneca. HI has received grants (paid to institution) from Boehringer Ingelheim, GlaxoSmithKline, Kyorin, Omron, Ono, and Teijin-Pharma; speaker fees from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Kyorin, Novartis, Ono, and Sanofi; and payment for advisory board participation from AstraZeneca, GlaxoSmithKline, Omron, and Sanofi. FWSK has received grants (paid to institution) from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Novartis; and support to attend meetings from Novartis and from Boehringer Ingelheim. JAK has received grants (paid to institution) from the National Heart, Lung, and Blood Institute, COPD Foundation, Regeneron, Sergey Brin Family Foundation, US Patient Centered Outcomes Research Institute, and American Lung Association; consulting fees from GlaxoSmithKline, AstraZeneca, CereVu Medical, Propeller and ResMed, and BData; speaker fees from University of Chicago, and from American Academy of Asthma, Allergy, and Immunology; support to attend meetings from Global Initiative for Asthma and from American Thoracic Society; and has participated in Respiratory Health Association, Global Initiative for Asthma, and COPD Foundation. RM has received speaker fees from AstraZeneca and Organon; payment for advisory board participation from AstraZeneca and Organon; and has participated (unpaid) in leadership roles within Global Asthma Network. KM has received payment for advisory board participation from AstraZeneca and GlaxoSmithKline. PP has received consulting fees from AstraZeneca, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, and Novartis; support to attend meetings from AstraZeneca and Boehringer Ingelheim; payment for advisory board participation from AstraZeneca; and is an unpaid member of the Board of Directors for the Brazilian Severe Asthma Group. SS has received consulting fees (paid to institution) and speaker fees (paid to institution) from Cipla, India. AS has received support to attend meetings from GINA. HKR has received grants from AstraZeneca, GlaxoSmithKline, Novartis, and Perpetual Philanthropy; consulting fees from Novartis, AstraZeneca, and GlaxoSmithKline; speaker fees from Alkem, AstraZeneca, GlaxoSmithKline, Teva, Boehringer-Ingelheim, Sanofi, Getz, and Chiesi; payment for advisory board participation from AstraZeneca, GlaxoSmithKline, Novartis, Chiesi, and Sanofi; and has participated (unpaid) in Global Initiative for Asthma as Chair of Science Committee, and in National Asthma Council Australia's Guidelines Committee. AY has received consulting fees (paid to institution) from GSK, AstraZeneca, and Chiesi; speaker fees (paid to institution) from GlaxoSmithKline, AstraZeneca, Bilim, and Abdi Ibrahim; and support to attend meetings from GINA. MJC declares no competing interests.

Background: Preventing poor childhood asthma control is crucial for short-term and long-term respiratory health. This study evaluated associations between perinatal and early-life factors and early childhood asthma control., Methods: This retrospective study used administrative health data from mothers and children born 2010-2012 with a diagnosis of asthma before age 5 years, in Alberta, Canada. The outcome was asthma control within 2 years after diagnosis. Associations between perinatal and early-life factors and risk of partly and uncontrolled asthma were evaluated by multinomial logistic regression., Results: Of 7206 preschoolers with asthma, 52% had controlled, 37% partly controlled and 12% uncontrolled asthma 2 years after diagnosis. Compared with controlled asthma, prenatal antibiotics (adjusted risk ratio (aRR): 1.19; 95% CI 1.06 to 1.33) and smoking (aRR: 1.18; 95% CI 1.02 to 1.37), C-section delivery (aRR: 1.11; 95% CI 1.00 to 1.25), summer birth (aRR: 1.16; 95% CI 1.00 to 1.34) and early-life hospitalisation for respiratory illness (aRR: 2.24; 95% CI 1.81 to 2.76) increased the risk of partly controlled asthma. Gestational diabetes (aRR: 1.41; 95% CI 1.06 to 1.87), C-section delivery (aRR: 1.18; 95% CI 1.00 to 1.39), antibiotics (aRR: 1.32; 95% CI 1.08 to 1.61) and hospitalisation for early-life respiratory illness (aRR: 1.65; 95% CI 1.19 to 2.27) were associated with uncontrolled asthma., Conclusion: Maternal perinatal and early-life factors including antibiotics in pregnancy and childhood, gestational diabetes, prenatal smoking, C-section and summertime birth, and hospitalisations for respiratory illness are associated with partly or uncontrolled childhood asthma. These results underline the significance of perinatal health and the lasting effects of early-life experiences on lung development and disease programming., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 has led to a significant increase in demand for remote blood sampling in clinical trials. This study aims to ascertain the concordance between venous versus capillary samples, processed immediately or exposed to various pre-analytical conditions., Methods: Participants (≥12 years old) provided a venous blood sample (processed immediately) and capillary samples allocated to one of the following conditions: processed immediately or exposed to 12-, 24-, or 36-h delays at room temperature or 36-h delays with a freeze-thaw cycle. The analytes of interest included SARS-CoV-2 IgG, 25-hydroxy vitamin D (25(OH)D), alkaline phosphate (ALP), calcium (Ca), phosphate (Ph), and c-reactive protein (CRP). Paired samples were considered interchangeable if they met three criteria: minimal within-subject mean difference, 95% of values within desirable total errors, and inter-class correlation (ICC) > 0.90., Results: 90 participants (44.1% male) were enrolled. When comparing rapidly processed venous with capillary samples, 25(OH)D, ALP, and CRP met all three criteria; SARS-CoV-2 IgG met two criteria (mean difference and ICC); and Ca and Ph met one criterion (mean difference). When considering all three criteria, concentrations of 25(OH)D, CRP, and ALP remained unchanged after delays of up to 36 h; SARS-CoV-2 IgG met two criteria (mean difference and ICC); Ca and Ph met one criterion (mean difference)., Conclusion: These findings suggest that remote blood collection devices can be used to measure anti-SARS-CoV-2 IgG, 25(OH)D, CRP, and ALP. Further analysis is required to evaluate the interchangeability between venous and capillary testing in Ca and Ph levels, which are more sensitive to pre-analytical conditions.

Introduction: In the COVID-19 pandemic, healthcare workers (HCWs) were at high risk of infection due to their exposure to COVID infections. HCWs were the backbone of our healthcare response to this pandemic; every HCW withdrawn or lost due to infection had a substantial impact on our capacity to deliver care. Primary prevention was a key approach to reduce infection. Vitamin D insufficiency is highly prevalent in Canadians and worldwide. Vitamin D supplementation has been shown to significantly decrease the risk of respiratory infections. Whether this risk reduction would apply to COVID-19 infections remained to be determined. This study aimed to determine the impact of high-dose vitamin D supplementation on incidence of laboratory-confirmed COVID-19 infection rate and severity in HCWs working in high COVID incidence areas., Methods and Analysis: PROTECT was a triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D supplementation in HCWs. Participants were randomly allocated in a 1:1 ratio in variable block size to intervention (one oral loading dose of 100 000 IU vitamin D 3 +10 000 IU weekly vitamin D 3 ) or control (identical placebo loading dose+weekly placebo). The primary outcome was the incidence of laboratory-confirmed COVID-19 infection, documented by RT-qPCR on salivary (or nasopharyngeal) specimens obtained for screening or diagnostic purposes, as well as self-obtained salivary specimens and COVID-19 seroconversion at endpoint. Secondary outcomes included disease severity; duration of COVID-19-related symptoms; COVID-19 seroconversion documented at endpoint; duration of work absenteeism; duration of unemployment support; and adverse health events. The trial was terminated prematurely, due to recruitment difficulty., Ethics and Dissemination: This study involves human participants and was approved by the Research Ethics Board (REB) of the Centre hospitalier universitaire (CHU) Sainte-Justine serving as central committee for participating institutions (#MP-21-2021-3044). Participants provided written informed consent to participate in the study before taking part. Results are being disseminated to the medical community via national/international conferences and publications in peer-reviewed journals., Trial Registration Number: https://clinicaltrials.gov/ct2/show/NCT04483635., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In preschoolers, asthma control is assessed clinically using history and physical examination. In certain centres, oscillometry is used to support clinical assessment; yet its clinical utility for asthma management remains to be quantified. The objectives were to determine if oscillometry, as adjunct to clinical assessment, influences asthma assessment, management and control, compared to clinical assessment alone in preschoolers. We conducted a cross-sectional study in children aged 3-5 years with a confirmed asthma diagnosis. Oscillometry-tested preschoolers were matched by propensity score to untested children. The co-primary outcomes, the likelihood of a persistent asthma phenotype and a maintenance therapy prescription at the index visit, were examined by multivariable logistic regression. Asthma control over the next year was examined by cumulative logistic regression in the nested retrospective cohort with available drug claim data. The cohort comprised 726 (249 oscillometry-tested; 477 untested) children with 57.4% male (median age: 4.6 years). Propensity score matching resulted in comparable groups. Compared to controls, oscillometry-tested children were more frequently labelled with a persistent phenotype (67% vs. 50%; adjusted OR [95% CI]: 2.34 [1.66-3.34]) with no significant difference in maintenance therapy prescription (65% vs. 58%; 1.37 [0.98-1.92]); but experienced a lower likelihood of poor control over the next year (adjusted OR [95% CI]: 0.24 [0.08-0.74]). The association between the addition of oscillometry to clinical assessment with more persistent phenotype labelling and better asthma control supports its clinical utility; no significant impact on maintenance therapy prescription was observed at the index visit., Competing Interests: Declaration of competing interest Bennet Desormeau and Anna Smyrnova declare no conflicts of interest. Francine Monique Ducharme has received unrestricted research funds from Astra Zeneca, Covis Pharma, GlaxoSmithKline, Merck Canada, Novartis, Teva, Trudell Medical; research funds from Covis Pharma, GlaxoSmithKline, and MEDteq in partnership with Thorasys Inc.; honorarium for consultancy work from Astra Zeneca, Covis Pharma, Teva, and Thorasys Inc.; and honorarium as an invited speaker from Covis Pharma, Jean Jean-Coutu Pharmacy and Brunet Pharmacy. Olivier Drouin has received funding from Fonds de la Recherche du Québec en Santé and research funds from Covis Pharma., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Asthma is one of the most prevalent chronic diseases of childhood and disproportionately affects children with lower socioeconomic status. Controller medications such as inhaled corticosteroids significantly reduce asthma exacerbations and improve symptoms. However, a large proportion of children still have poor asthma control, in part owing to suboptimal adherence. Financial barriers contribute to hindering adherence, as do behavioral factors related to low income. For example, unmet social needs for food, lodging, and childcare may create stress and worry in parents, negatively influencing medication adherence. These needs are also cognitively taxing and force families to focus on immediate needs, leading to scarcity and heightening future discounting; thus, there is the tendency to attribute greater value to the present than to the future in making decisions., Objective: In this project, we will investigate the relationship between unmet social needs, scarcity, and future discounting as well as their predictive power over time on medication adherence in children with asthma., Methods: This 12-month prospective observational cohort study will recruit 200 families of children aged 2 to 17 years at the Asthma Clinic of the Centre Hospitalier Universitaire Sainte-Justine, a tertiary care pediatric hospital in Montreal, Canada. The primary outcome will be adherence to controller medication, measured using the proportion of prescribed days covered during follow-up. Exploratory outcomes will include health care use. The main independent variables will be unmet social needs, scarcity, and future discounting, measured using validated instruments. These variables will be measured at recruitment as well as at 6- and 12-month follow-ups. Covariates will include sociodemographics, disease and treatment characteristics, and parental stress. Primary analysis will compare adherence to controller medication, measured using the proportion of prescribed days covered, between families with versus those without unmet social needs during the study period using multivariate linear regression., Results: The research activities of this study began in December 2021. Participant enrollment and data collection began in August 2022 and are expected to continue until September 2024., Conclusions: This project will allow the documentation of the impact of unmet social needs, scarcity, and future discounting on adherence in children with asthma using robust metrics of adherence and validated measures of scarcity and future discounting. If the relationship between unmet social needs, behavioral factors, and adherence is supported by our findings, this will suggest the potential for novel targets for integrated social care interventions to improve adherence to controller medication and reduce risk across the life course for vulnerable children with asthma., Trial Registration: ClinicalTrials.gov NCT05278000; https://clinicaltrials.gov/ct2/show/NCT05278000., International Registered Report Identifier (irrid): PRR1-10.2196/37318., (©Olivier Drouin, Tamara Perez, Tracie A Barnett, Francine M Ducharme, Eric Fleegler, Arvin Garg, Kim Lavoie, Patricia Li, Marie-Élaine Métras, Serge Sultan, Sze Man Tse, Jiaying Zhao. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 07.03.2023.)

We thank Drs. Leong et al. for their comments [...].

Background: The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial., Methods: In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vitamin D 3 or placebo. The co-primary outcomes were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75 nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented., Results: Thirty-four (19 intervention, 15 control) subjects were randomized, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95% CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95% CI:1.6, 22.9). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported., Conclusion: The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation., Trial Registration: This trial was registered at https://clinicaltrials.gov on July 23, 2020 (# NCT04483635 )., (© 2022. The Author(s).)

Background: New oscillometry devices allowing quantification of respiratory function using tidal breathing are commercially available, but reference equations are lacking for the multiethnic Canadian pediatric population., Methods: We conducted a prospective cross-sectional study of healthy children carefully selected for absence of asthma, atopy, tobacco smoke, obesity, prematurity, and recent respiratory infection. Triplicate measures were obtained of respiratory system resistance (Rrs) and reactance (Xrs), area under the reactance curve (AX) and resonant frequency (Fres) on four signals, whose testing order was randomized: two signals on the Resmon Pro Full (8 Hz and 5-11-19 Hz) and two signals on the tremoflo C-100 (5-37 Hz and 7-41 Hz). Feasibility was defined as the ability to obtain valid reproducible results. Prediction equations and 95% confidence intervals were derived for whole- and within-breath Rrs and Xrs and for AX and Fres, using linear regression or Generalized Additive Models for Location, Scale and Shape., Results: Of 306 children randomized, valid and reproducible results on ≥1 signal were obtained in 299 (98%) multiethnic (69% Caucasians: 8% Black: 23% Others) children aged 3-17 years, 91-189 cm tall. Standing height was the strongest predictor with no significant effect of sex, age, body mass index or ethnicity. Significant within-patient differences were observed between Resmon Pro and tremoflo C-100 measurements, justifying the derivation of device-specific reference equations., Conclusion: Valid reproducible oscillometry measurements are highly feasible in children aged 3 years and older. Device-specific reference equations, valid for our multiethnic population, are derived., (© 2022 Wiley Periodicals LLC.)

Introduction: Asthma guided self-management enhances patients' control of their condition under the guidance of the treating physician. The aim of the present study was to understand how physicians perceive, endorse, uptake, and support asthma guided self-management., Methods: We conducted a secondary supplementary analysis of data originally collected as part of a multicenter collective case study in which physicians treating patients with asthma were interviewed. Using reflective thematic analysis, we aimed to explore physicians' understanding of guided asthma self-management as related to four ideas, namely: (a) understanding of the disease management and treatment goals; (b) defining medical frame and guidance; (c) describing the importance of patient-physician relationship; and (d) implementing asthma guided self-management., Results: Evidence indicates that physicians perceived optimal guided self-management as related to patients' adherence to physician's instructions and recommendations, supported by the adjustment of prescribed pharmaceutical therapy contingent upon patient's symptoms. Some physicians also perceived behavior change and environmental control along with the medical recommendations. While physicians' perception of asthma and its treatment were aligned with the recommended guidelines-i.e., patient-centered care approach based on guided self-management, the actual guidance offered to patients remained primarily directive and paternalistic. Non-pharmacological approaches, such as exercise, smoking cessation, patient self-monitoring, and self-management supported by education and written self-management plans, were given little consideration in the context of the recommended treatment plan.

The COVID-19 outbreak has rapidly expanded to a global pandemic; however, our knowledge is limited with regards to the protective factors against this infection. The aim of this systematic literature review and meta-analysis was to evaluate the impact of vitamin D supplementation on COVID-19 related outcomes. A systematic search of relevant papers published until January 2022 was conducted to identify randomized controlled trials (RCTs) and non-randomized studies of intervention (NRISs). The primary outcomes included the risk of COVID-19 infection (primary prevention studies on uninfected individuals), hospital admission (secondary prevention studies on mild COVID-19 cases), and ICU admission and mortality rate (tertiary prevention studies on hospitalized COVID-19 patients). We identified five studies (one RCT, four NRISs) on primary prevention, with five (two RCTs, three NRISs) on secondary prevention, and 13 (six RCTs, seven NRISs) on tertiary prevention. Pooled analysis showed no significant effect on the risk of COVID-19 infection. No meta-analysis was possible on hospitalization risk due to paucity of data. Vitamin D supplementation was significantly associated with a reduced risk of ICU admission (RR = 0.35, 95% CI: 0.20, 0.62) and mortality (RR = 0.46, 95% CI: 0.30, 0.70). Vitamin D supplementation had no significant impact on the risk of COVID-19 infection, whereas it showed protective effects against mortality and ICU admission in COVID-19 patients.

Background: The potential influence of asthma control in early life on long-term outcomes in childhood remains largely unknown., Objective: To examine whether asthma control trajectories in the 2 years after diagnosis in preschoolers are associated with long-term unsatisfactory asthma control., Methods: We conducted a multicenter population-based retrospective cohort study, including four Canadian provincial birth cohorts derived from administrative databases. We included preschoolers (aged <5 years) with a diagnosis of asthma, defined as having one hospitalization or two physician visits for asthma within 2 years. Asthma control trajectories, ascertained over four 6-month periods after diagnosis using a validated index, were classified as controlled throughout, improving control, fluctuating control, worsening control, and out of control throughout. Long-term unsatisfactory control was defined as four or more short-acting β 2 -agonist average doses per week or an exacerbation, measured within 6 months before index ages 6, 8, 10, 12, 14, and 16 years. Average risk ratios for long-term unsatisfactory control across all index ages were estimated using a robust Poisson model by province and meta-analyzed with a random effects model., Results: In 50,188 preschoolers with asthma, the pooled average risk of having unsatisfactory control at any index age was 42% (95% confidence interval, 34.6-49.4). Compared with children who were controlled throughout, incrementally higher average risk ratios (95% confidence interval) of long-term unsatisfactory control were observed in each trajectory: improving control, 1.38 (1.28-1.49); fluctuating control, 1.54 (1.40-1.68); worsening control, 1.70 (1.55-1.86) and out of control throughout, 2.00 (1.80-2.21)., Conclusions: Suboptimal asthma control trajectories shortly after a preschool diagnosis were associated with long-term unsatisfactory asthma control. Early control trajectories appear to be promising for predicting the risk for long-term adverse outcomes., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Suboptimal adherence to inhaled corticosteroids (ICS) is associated with poor asthma control. Adult studies suggest that simplification of ICS regimen leads to better adherence., Objective: We aimed to determine whether once-daily, compared with twice-daily, ICS dosing was associated with better adherence among children with asthma., Methods: We conducted a retrospective observational study of children with asthma prescribed with either once-daily or twice-daily ICS monotherapy between 2011 and 2019. Our primary adherence outcome was the proportion of prescribed days covered (PPDC)-that is, the number of days for which the drug was dispensed by the pharmacy divided by the number of days for which it was prescribed. The impact of once-daily vs twice-daily ICS regimen on adherence was evaluated using linear multivariable regression analysis adjusting for covariates. Secondary outcomes included the proportion of patients with greater than or equal to 75% adherence analyzed using logistic regression models., Results: A total of 232 children (61% boys; mean age of 5.8 [3.6] years) were included; 120 children were prescribed once-daily, and 112 twice-daily, ICS. The median PPDC was 66.8% for the once-daily and 57.9% for the twice-daily group (P = .03). Children prescribed once-daily ICS had a 7.2% (95% confidence interval, 1.3-13.1) greater mean PPDC compared with the twice-daily group and greater odds of having PPDC greater than or equal to 75% (71.4% vs 45.5%; odds ratio, 1.80; 95% confidence interval, 1.01-3.26)., Conclusion: Our findings suggest that once-daily dosing of ICS is associated with better medication adherence than twice-daily dosing. Whether the gain in adherence leads to better asthma control and health outcomes remains to be evaluated., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)