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The varied treatment response to inhaled corticosteroids (ICS) in patients with COPD and the associated increased risk of pneumonia necessitate a personalized ICS therapeutic approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. However, BEC appears to change in response to ICS treatment. Does (1) BEC measured on ICS treatment (2) BEC measured off ICS treatment, or (3) the change in BEC during ICS treatment best predict treatment response to ICS in COPD? The Fluticasone Salmeterol on COPD Exacerbations Trial (FLAME), a 52-week, double-blind randomized controlled trial compared long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs) with LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing BEC before and after the run-in period to represent BEC on and off ICS, respectively. In this post hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS-containing regimen. Our study showed that LABA/LAMA combination was superior, or at least noninferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off ICS, higher BEC on ICS, and significant BEC suppression during ICS treatment corresponded to superior response to LABA/ICS in terms of exacerbation rate, time to first exacerbation, and time to first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment (≥ 200 cells/μL), and higher BEC on ICS did not predict ICS treatment response. For these patients, BEC off ICS and BEC change proved more predictive. Excess pneumonia risk associated with ICS appeared to be confined to patients who do not benefit from this treatment. BEC was not predictive of treatment effects on lung function and health status. This exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response. ClinicalTrials.gov; No.: NCT01782326 ; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Background: Asthma is a prevalent chronic disease with significant impact on patients, families, and communities. Inhaled corticosteroids (ICS) are the mainstay of treatment for persistent and uncontrolled asthma. However, concerns remain about the potential adverse effects of ICS, including HbA1c level. This study aims to evaluate the influence of ICS on Hemoglobin A1c (HbA1c) levels in children with bronchial asthma. Methods: This prospective cohort study included 48 pediatric asthma patients aged 2 to 15 years who had been using ICS for at least 6 months. Comprehensive clinical assessments and measurements of HbA1c levels were conducted at the start of recruitment and after 6 months of ICS use. The types and doses of ICS used followed the guidelines provided by the Global Initiative for Asthma (GINA). Results: The initial HbA1c levels ranged from 4.46 to 6.11, with a mean of 5.32 ± 0.35. Three patients (6.3%) had persistent prediabetes status after 6 months. There was no significant relationship between glycemic status and the characteristics of ICS. The duration of ICS therapy and the doses used did not significantly affect HbA1c levels. A weak positive correlation was observed between initial and subsequent HbA1c levels. Conclusion: The study found no significant difference in HbA1c levels among asthmatic children using ICS after six months of treatment. Additionally, there was no significant difference in HbA1c levels between patients using different types of ICS. Regular monitoring of HbA1c levels is recommended, particularly for children on high doses or prolonged use of inhaled Fluticasone. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroids (ICS) are effective in managing asthma and chronic obstructive pulmonary disease (COPD) but increase the risk of pneumonia. Benzodiazepines (BZD), commonly prescribed for comorbid psychiatric disorders in asthma or COPD patients, are also associated with pneumonia. This study investigates the risk of pneumonia associated with the concomitant use of ICS and BZD. Methods: Data from the FDA Adverse Event Reporting System from Q4 2013 to Q3 2023 were extracted. Reports involving asthma or COPD patients were included. Disproportionality analysis and logistic regression analysis were performed to assess the risk of pneumonia associated with the combined use of ICS and BZD. Additive and multiplicative models were used to further confirm the results. Additionally, subgroup analyses were conducted based on gender, age, and disease type. Results: A total of 238,411 reports were included. The combined use of ICS and BZD was associated with a higher reporting of pneumonia (ROR: 2.41, 95% CI 2.25–2.58). Using additive and multiplicative methods, the results remained significant. The strongest risk signals were observed in specific drug combinations, such as mometasone with clonazepam, budesonide with temazepam, and mometasone with zopiclone. Subgroup analyses showed higher pneumonia risks in females, patients over 60 years old, and those with asthma. Conclusion: Our findings identified a significantly elevated pneumonia risk with the combined use of ICS and BZD. These results highlighted the necessity for cautious co-prescription of ICS and BZD and suggested the need for more comprehensive clinical studies to assess this interaction. [ABSTRACT FROM AUTHOR]

Introduction: COPD is a leading cause of global mortality, particularly under-recognized and under-diagnosed. In 2020, it was the sixth leading cause of death in the US and has contributed to 4.72% of all-cause mortality (ACM) according to the Global Burden of Disease Study 2017. Factors influencing COPD-related mortality include smoking, aging populations, comorbidities, sarcopenia, physical capacity, and lack of effective treatments. Areas Covered: This review discusses various factors influencing COPD-related mortality and analyzes observational studies and pivotal RCTs evaluating the impact of different therapies on ACM. Expert Opinion: COPD significantly impacts ACM, necessitating effective management strategies. Smoking cessation is crucial in reducing mortality risk. Exacerbation management and comorbidity treatment are essential to improve patient outcomes. Various therapeutic interventions, such as smoking cessation, vaccination, long-term oxygen therapy, and lung volume reduction surgery, have shown benefits in reducing mortality. Pharmacotherapies might reduce the risk of mortality, although the current scientific evidences remain inconclusive. Advances in pharmacological interventions, tailored treatment plans, and physical activity programs are vital. More robust and long-term studies, focusing on real-world data and addressing biases in treatment allocation, are needed to conclusively determine the efficacy of different therapies in reducing ACM in COPD patients. [ABSTRACT FROM AUTHOR]

In this study, a new and straightforward process for the preparation of budesonide 21-phosphate (Bud-21P) and its disodium salt (Bud-21P-Na2) is described. The method results in a yield comparable to those obtained by diphosphoryl chloride, but it is more manageable, less expensive, and safer. The new compounds are characterized by better water solubility compared to the parent compound. Moreover, they have been evaluated for their anti-inflammatory activity and the obtained results clearly evidence that Bud-21P and Bud-21P-Na2 retained anti-inflammatory activity like the parent compound budesonide (Bud) in mice with cutaneous induced edema. [ABSTRACT FROM AUTHOR]

Objective: Analyze the duration of symptom‐free intervals following laser wedge excision (LWE) for recurrent idiopathic subglottic stenosis (iSGS). Secondary aim includes evaluating the influence of patient‐related or disease factors. Study Design: Retrospective review. Setting: Tertiary center. Methods: Review of iSGS patients who underwent LWE between 2002 and 2021. LWE patients without prior airway surgery were labeled LWE primary (LWEP) and those with prior history of dilation were labeled LWE secondary (LWES). A conditional frailty repeated events model was used to analyze the median time to recurrence (MTR) for each nth recurrence. Secondary analysis included stratification by use of medical therapy and initial preoperative characteristics of scar (Myer‐Cotton grade, distance between the glottis and superior‐most aspect of scar, DGS; length of scar, DL). Results: Two hundred and ten iSGS patients underwent LWE (131 LWEP, 79 LWES). The proportion of patients experiencing at least 1, 3, 6, and 12 recurrences, respectively, was 68.0% (n = 143), 40.7% (n = 85), 20.0% (n = 42), and 5.2% (n = 11). There was exponential time‐shortening from the 1st to 12th recurrence (P <.0001). While MTR was 4.1 years after the first LWE, this fell to 2.8, 1.7, 1.0, and 0.7 years for the 2nd, 3rd, 6th, and 12th recurrences. Furthermore, LWEP patients experienced longer MTR than LWES counterparts within the first 6 recurrences (P <.01). There was no significant relationship between intersurgical interval and medication adherence, DL, DGS, or grade for recurrences beyond the first (P =.207, P =.20, P =.43, P =.16). Conclusion: Symptom‐free intervals in iSGS shorten with each subsequent recurrence and LWE. The difference in MTR between LWEP and LWES groups was significant within the first 6 recurrences with LWEP having longer MTR. Level of Evidence: 3. [ABSTRACT FROM AUTHOR]

Abstract Background Asthma is a prevalent chronic disease with significant impact on patients, families, and communities. Inhaled corticosteroids (ICS) are the mainstay of treatment for persistent and uncontrolled asthma. However, concerns remain about the potential adverse effects of ICS, including HbA1c level. This study aims to evaluate the influence of ICS on Hemoglobin A1c (HbA1c) levels in children with bronchial asthma. Methods This prospective cohort study included 48 pediatric asthma patients aged 2 to 15 years who had been using ICS for at least 6 months. Comprehensive clinical assessments and measurements of HbA1c levels were conducted at the start of recruitment and after 6 months of ICS use. The types and doses of ICS used followed the guidelines provided by the Global Initiative for Asthma (GINA). Results The initial HbA1c levels ranged from 4.46 to 6.11, with a mean of 5.32 ± 0.35. Three patients (6.3%) had persistent prediabetes status after 6 months. There was no significant relationship between glycemic status and the characteristics of ICS. The duration of ICS therapy and the doses used did not significantly affect HbA1c levels. A weak positive correlation was observed between initial and subsequent HbA1c levels. Conclusion The study found no significant difference in HbA1c levels among asthmatic children using ICS after six months of treatment. Additionally, there was no significant difference in HbA1c levels between patients using different types of ICS. Regular monitoring of HbA1c levels is recommended, particularly for children on high doses or prolonged use of inhaled Fluticasone.

Christian Kjer Heerfordt,1 Christian Rønn,1 Josefin Eklöf,1 Pradeesh Sivapalan,1 Zitta Barrella Harboe,2,3 Charlotte Hyldgaard,4 Andreas Fløe,5 Alexander G Mathioudakis,6,7 Mats Christian Højbjerg Lassen,8 Tor Biering-Sørensen,8,9 Jens-Ulrik Stæhr Jensen1,3,10 1Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark; 2 Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital, North Zealand, Hillerød, Denmark; 3Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 4Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark; 5Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; 6Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, UK; 7North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; 9Faculty of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark; 10PERSIMUNE & CHIP: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Jens-Ulrik Stæhr Jensen, Email jens.ulrik.jensen@regionh.dkBackground: Extra-fine particle inhaled corticosteroids (ICS) improve peripheral airway distribution, but their effect on risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD) is unclear.Methods: This observational cohort study compares patients with COPD who received extra-fine particle ICS to those who received standard particle size ICS from 2010 to 2017 while followed in outpatient clinics. The primary outcome was the time to a COPD exacerbation that required hospitalization, with all-cause mortality as a secondary outcome. Data were analyzed using an adjusted Cox proportional hazards model and a competing risk analysis. Two predefined subgroup analyses of patients treated with pressurised metered dose inhalers (pMDIs) and patients with a previous exacerbation history, was carried out. Lastly, we created a propensity score matched cohort as a sensitivity analysis.Results: Of the 40,489 patients included, 38,802 (95.8%) received stand particle size ICS and 1,687 (4.2%) received extra-fine particle ICS. In total 7,058 were hospitalized with a COPD exacerbation, and 4,346 died. No significant protective effect of extra-fine particle ICS against hospitalization due to COPD exacerbations (HR 0.93, 95% CI 0.82– 1.05, p=0.23) or all-cause mortality (HR 1.00, 95% CI 0.85– 1.17, p=0.99) was found when compared to standard particle size ICS. However, in the subgroup analysis of patients treated with pMDIs, extra-fine particle ICS was associated with reduction in risk of exacerbations (HR 0.72, 95% CI 0.63– 0.82, p< 0.001) and all-cause mortality (HR 0.72, 95% CI 0.61– 0.86, p< 0.001).Conclusion: The administration of extra-fine particle ICS was not associated with reduced risk of exacerbations or all-cause mortality in our primary analysis. A subgroup consisting of patients treated with pMDIs suggested potential protective benefits.Keywords: COPD, Inhaled Corticosteroids, Particle size, COPD exacerbations

BackgroundThe upper-airway microbiome is involved in asthma exacerbations despite inhaled corticosteroid (ICS) treatment. Although human genetics regulates microbiome composition, its influence on asthma-related airway bacteria remains unknown.ObjectiveWe sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma exacerbations and ICS response.MethodsSaliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association of 6,296,951 genetic variants with exacerbation-related microbiome traits despite ICS treatment was tested through microbiome genome-wide association studies. Variants with 1 × 10-4 -6 were examined in gene-set enrichment analyses. Significant results were sought for replication in 114 African American and 158 Latino children with and without asthma. ICS-response-associated single nucleotide polymorphisms reported in the literature were evaluated as microbiome quantitative trait loci. Multiple comparisons were adjusted by the false discovery rate.ResultsGenes associated with exacerbation-related airway-microbiome traits were enriched in asthma comorbidities development (ie, reflux esophagitis, obesity, and smoking), and were likely regulated by trichostatin A and the nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein transcription factors (7.8 × 10-13 ≤ false discovery rate ≤ 0.022). Enrichment in smoking, trichostatin A, nuclear factor-κB, and glucocorticosteroid receptor were replicated in the saliva samples from diverse populations (4.42 × 10-9 ≤ P ≤ .008). The ICS-response-associated single nucleotide polymorphisms rs5995653 (APOBEC3B-APOBEC3C), rs6467778 (TRIM24), and rs5752429 (TPST2) were identified as microbiome quantitative trait loci of Streptococcus, Tannerella, and Campylobacter in the upper airway (0.027 ≤ false discovery rate ≤ 0.050).ConclusionsGenes associated with asthma exacerbation-related microbiome traits might influence asthma comorbidities. We reinforced the therapeutic interest of trichostatin A, nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein in asthma exacerbations.

Abstract Background Glucocorticoids are widely used in inhalation aerosol therapy for wheezing diseases. This study aims to explore guardians’ knowledge and attitude towards inhaled corticosteroids (ICS) aerosol therapy and the medication compliance of children with wheezing diseases in China. Methods This cross-sectional study enrolled guardians of children with wheezing diseases at the First Hospital Affiliated to Shaoyang College between October 2022 and February 2023. A self-administered questionnaire was developed to collect demographic information of the participants and evaluate their knowledge and attitude towards ICS aerosol therapy. The 8-item Morisky Medication Adherence Scale was used to assess the medication compliance of children. Results A total of 506 valid questionnaires were collected. 260 (51.38%) participants were guardians of a ≤ 3-year-old child and 327 (64.62%) were children’s mothers. The knowledge, attitude, and medication compliance scores of all participants were 12.61 ± 5.78, 20.95 ± 2.37, and 4.69 ± 2.18, respectively. Multivariate logistic regression showed that knowledge scores [OR = 1.053, 95% CI (confidence interval): 1.017–1.090, P = 0.003], attitude scores (OR = 1.121, 95% CI: 1.030–1.219, P = 0.008), guardians of children aged 4–6 years (OR = 0.385, 95% CI: 0.242–0.612, P

Background: Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab. Methods: Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit. Results: Three of the patients were men, median age was 52.5 years (range 79–53), median length of asthma before mepolizumab start was 67.5 months (range 24–240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/μL at baseline. The median follow-up was 73.5 months (range 71–74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12–39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3–6) to 0; p=0.0286). Conclusions: Mepolizumab could be a ‘disease-modifying’ agent, with high tolerability and a good efficacy profile in the long term.

Kwang Yong Choi,1 Hwan Il Kim,1 Chin Kook Rhee,2 Kwang Ha Yoo,3 Yong Bum Park,4 Youlim Kim,3 So Eun Lee,5 Jung-Ae Kim,6 Yong Il Hwang1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 5Respiratory, Medical Affairs, Boehringer-Ingelheim Korea, Seoul, Republic of Korea; 6Real-World Solutions, IQVIA Korea, Seoul, Republic of KoreaCorrespondence: Yong Il Hwang, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14068, Republic of Korea, Email hyicyk@hallym.or.kr; hyicyk@gmail.comBackground: COPD causes substantial economic burden on healthcare. Alternative treatment strategies for COPD can be associated with different costs dependent upon their relative safety and effectiveness. We compared costs and healthcare resource utilization (HCRU) associated with LAMA or LABA/ICS initiation.Methods: Using the Korean National Health Insurance Service database, we enrolled COPD patients initiating treatment with LAMA or LABA/ICS between January 2005 and April 2015. Propensity score matched individuals were compared on all-cause and COPD-related medical costs and HCRU over a three-year follow-up period.Results: A total of 2444 patients were enrolled in each treatment group. LAMA group was associated with significantly lower costs than LABA/ICS group, both in all-cause (403.08 vs 474.50 USD per patient per month [PPPM], cost ratio 1.18, 95% confidence interval [CI]=1.10– 1.26, p< 0.0001) and COPD-related (216.37 vs 267.32 USD PPPM, cost ratio 1.24, 95% CI=1.13– 1.35, p< 0.0001) medical costs. All-cause HCRU was not significantly different between groups, while COPD-related HRCU was higher in LAMA group (0.66 vs 0.60 medical visits PPPM, p< 0.0001).Conclusion: COPD patients initiating treatment with LAMA were associated with lower all-cause and COPD-related medical costs than those starting with LABA/ICS despite the similar all-cause HCRU and higher COPD-related HCRU. Initiation with LAMA is a cost-efficient option for the treatment of COPD.Keywords: chronic obstructive pulmonary disease, inhaled corticosteroids, long-acting beta-2 agonists, long-acting muscarinic receptor antagonists, medical cost

Abstract Background The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. Methods A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. Results Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660–0·909) and 0·770 (95% CI: 0·662–0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. Conclusions We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated.

Andrea Georgiou, Reshma Ramesh, Peter Schofield, Patrick White, Timothy H Harries School of Population Health & Environmental Sciences, King’s College London, London, UKCorrespondence: Timothy H Harries, King’s College London, Department of Population Health Sciences, School of Life Course & Population Sciences, King’s College London, 3rd Floor Addison House, Guys Campus, London, SE1 1UL, UK, Tel +44 20 7836 5454, Email timothy.harries@kcl.ac.ukBackground: Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately controlled by dual long-acting bronchodilator therapy and who have ≥ 2 exacerbations per year and a blood eosinophil count ≥ 300cells/μL. ICS therapy is widely prescribed outside guidelines to COPD patients, making ICS withdrawal an important consideration. This systematic review aims to provide an up-to-date analysis of the effect of ICS withdrawal on exacerbation frequency, change in lung function (FEV1) and to determine the proportion of COPD patients who resume ICS therapy following withdrawal.Methods: Randomised controlled trials (RCTs) and observational studies which compared ICS withdrawal with ICS continuation treatment were included. Cochrane Central, Web of Science, CINHAL, Embase and OVID Medline were searched. Risk of bias was assessed using the Cochrane RoB2 tool and the Newcastle-Ottawa Scale. Quality assessment of RCTs was conducted using GRADE. Meta-analysis of post-hoc analyses of RCTs of ICS withdrawal, stratified by blood eosinophil count (BEC), was undertaken.Results: Ten RCTs (6642 patients randomised) and 6 observational studies (160,029 patients) were included in the results. When ICS was withdrawn and long-acting bronchodilator therapy was maintained, there was no consistent difference in exacerbation frequency or lung function change between the ICS withdrawal and continuation trial arms. The evidence for these effects was of moderate quality. There was insufficient evidence to draw a firm conclusion on the proportion of patients who resumed ICS therapy following withdrawal (estimated range 12– 93% of the participants).Discussion: Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes.Keywords: COPD, inhaled corticosteroid, drug withdrawal, exacerbations, randomised controlled trials, observational studies

Topical corticosteroids are a mainstay in the treatment of many pediatric disorders. While they have proven beneficial therapeutic effects and are generally considered safe, systemic adverse events may occur. This study presents four cases of children who experienced systemic adverse events after using inhaled and intranasal topical corticosteroids, as well as topical corticosteroids in other forms. A comprehensive literature review was performed to explore the existing evidence on this topic. The aim of this study is to raise awareness among healthcare providers about the possibility of systemic adverse events associated with the use of locally administered corticosteroids in pediatric patients. This information underscores the importance of careful monitoring, individualized treatment plans, and further research to better understand and mitigate the risks associated with corticosteroids, even those not given systemically. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to determine the efficacy of inhaled corticosteroids (ICS) on mortality in patients with coronavirus disease-2019 (COVID-19). A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on the treatment of COVID-19 with ICS were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). Eleven RCTs (enrolling 5832 participants) met the inclusion criteria. There was no statistically significant difference in COVID-19-related death (RR 0.88, 95% CI 0.38–2.04), all-cause death (RR 1.05, 95% CI 0.49–2.23), and invasive ventilation (RR 1.26, 95% CI 0.60–2.62) between the two groups. ICS was not associated with reduced mortality and invasive ventilation in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids are widely used in inhalation aerosol therapy for wheezing diseases. This study aims to explore guardians' knowledge and attitude towards inhaled corticosteroids (ICS) aerosol therapy and the medication compliance of children with wheezing diseases in China. Methods: This cross-sectional study enrolled guardians of children with wheezing diseases at the First Hospital Affiliated to Shaoyang College between October 2022 and February 2023. A self-administered questionnaire was developed to collect demographic information of the participants and evaluate their knowledge and attitude towards ICS aerosol therapy. The 8-item Morisky Medication Adherence Scale was used to assess the medication compliance of children. Results: A total of 506 valid questionnaires were collected. 260 (51.38%) participants were guardians of a ≤ 3-year-old child and 327 (64.62%) were children's mothers. The knowledge, attitude, and medication compliance scores of all participants were 12.61 ± 5.78, 20.95 ± 2.37, and 4.69 ± 2.18, respectively. Multivariate logistic regression showed that knowledge scores [OR = 1.053, 95% CI (confidence interval): 1.017–1.090, P = 0.003], attitude scores (OR = 1.121, 95% CI: 1.030–1.219, P = 0.008), guardians of children aged 4–6 years (OR = 0.385, 95% CI: 0.242–0.612, P < 0.001), and grandparents of children (OR = 2.633, 95% CI: 1.104–6.275, P = 0.029) were independently associated with children's medication compliance. Conclusions: In conclusion, guardians of children with wheezing diseases in China had insufficient knowledge, unsatisfactory attitude, and poor medication compliance towards ICS aerosol therapy. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. Methods: A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. Results: Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660–0·909) and 0·770 (95% CI: 0·662–0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. Conclusions: We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated. [ABSTRACT FROM AUTHOR]

All patients with Chronic Obstructive Pulmonary Disease (COPD), a multifactorial illness, have decreased post-bronchodilator lung function. While it was once believed that hyperresponsiveness and acute bronchodilator reversibility were characteristics of asthma, it is now generally acknowledged that these clinical features also occur in COPD. The current review provides an overview of corticosteroids' role in treating COPD signs. Both localized and systemic inflammations are key components of the pathophysiology of COPD. Inflammation occurs during an exacerbation and has been linked to a quicker course of COPD. Both systemic and local inflammations have been linked to COPD and using both Inhaled and Systemic Corticosteroids (ICS) has been found to be important when treating COPD. According to several current international documents on the management and therapy of COPD, patients at high risk of exacerbations-those with a Forced Expiratory Volume in one second (FEV1) of a fifty percent probability of exacerbation or more than one exacerbation per year-should receive ICS in addition to long-acting bronchodilators as maintenance treatment. In summary, systemic corticosteroids are the gold standard for treating Acute Exacerbations of COPD (AECOPD). Research has shown that using these drugs can improve lung function in the short term while reducing the likelihood of treatment failure, 30-day recurrence rates and length of hospital stay. [ABSTRACT FROM AUTHOR]

Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS). Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps. Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses. Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9. [ABSTRACT FROM AUTHOR]

Background: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease‐related genes and disease‐related alterations in ICS responsiveness. Methods: Randomized open‐label bronchoscopy study of high‐dose ICS therapy in 30 healthy adult volunteers randomized 2:1 to (i) fluticasone propionate 500 mcg bd daily or (ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics. Results: ICS induced small between‐group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type‐2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell‐mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA‐DQB2, CD96, PTPN7), B‐cell immunity (CD20, immunoglobulin heavy and light chains) and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL‐17‐dependent gene signature was not upregulated by ICS. Conclusions: In healthy airways, 4‐week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type‐2 inflammation. This implies that homeostasis in health involves tonic type‐2 signalling in the airway mucosa, which is exquisitely sensitive to ICS. [ABSTRACT FROM AUTHOR]

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Objective: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD) patients as a treatment option. However, ICS may also increase the risk of pneumonia and alter the composition of airway microbiota. In clinical application, the overuse of ICS exists pervasively and may potentially lead to adverse effects. Whether the long-term use of ICS confers enough benefit to COPD patients to justify its use so far remains unknown. Therefore, this study employed a single-center retrospective cohort study to compare alterations in airway function and the sputum microbial community structure between COPD patients who had undergone either long-term or short-term treatment with ICS. Methods: Sixty stable COPD patients who had used ICS were recruited and classified into the long-term use group (more than 3 months) and short-term use group (less than 3 months). The demographic features and clinical information of the subjects were investigated and their sputum samples were collected and subjected to metagenomic next-generation sequencing (mNGS). Results: The study found that compared with short-term ICS use, long-term ICS use did not further improve the clinical airway function, decrease the number of acute exacerbations, or decrease hospital readmission. In terms of sputum microbiota, the long-term use of ICS significantly altered the beta diversity of the microbial community structure (p < 0.05) and the top three phyla differed between the two groups. At the genus level, long-term ICS induced higher relative abundances of Abiotrophia, Schaalia, Granulicatella, Mogibacterium, Sphingobium, and Paraeggerthella compared to short-term ICS use. Additionally, alpha diversity was positively associated with clinical airway indicators (pre-bronchodilatory FEV1 and pre-bronchodilatory FVC) in the long-term ICS group. The relative abundances of Rothia, Granulicatella, Schaalia, and Mogibacterium genera had positive correlations with the eosinophil % (of all white blood cells). Conclusion: This study reveals the effect of long-term and short-term ICS use on sputum microbiota among COPD patients and provides a reference for the appropriate application of clinical ICS treatment in COPD patients. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of clinical pharmacist practitioner (CPP) management on potentially inappropriate use of inhaled corticosteroids (ICS) in the ambulatory care setting. Design: Multicenter, prospective quality assurance/improvement (QA/QI) project. Setting: Erie Veterans Affairs Medical Center (VAMC) and surrounding Ashtabula, Crawford, and Venango County Community-Based Outpatient Clinics (CBOCs). Participants: Thirty-five participants with chronic obstructive pulmonary disease (COPD) who met inclusion criteria were included in the project. Interventions: Participants were contacted to schedule an initial sixty-minute telephone visit with a CPP. Exacerbation history, rescue inhaler use, and symptom burden were assessed using the COPD Assessment Test (CAT) and Modified Medical Research Counsel Breathlessness Scale (mMRC) scales. Medication regimens were optimized based on guideline recommendations with an emphasis on appropriate use of ICS. Participants were scheduled for follow-up telephone visits with the CPP every 4 weeks. Main Outcome Measures: The primary project outcome was potentially inappropriate use of ICS without a long-acting muscarinic antagonist (LAMA)/long-acting beta agonist (LABA). Secondary project outcomes included ICS de-escalation, vaccinations, and smoking cessation. Results: The primary outcome of reducing use of ICS without a LAMA/LABA was achieved in thirty-one (88.6%) participants. ICS de-escalation was achieved in twenty-three (65.7%) participants. Rates of recommended vaccinations and smoking cessation with nicotine replacement therapy increased as a result of pharmacist intervention. Conclusion: Pharmacist management of COPD in the ambulatory care setting was associated with a decrease in potentially inappropriate use of ICS and an increase in preventative care measures. [ABSTRACT FROM AUTHOR]

This research letter discusses the potential for enhancing asthma pharmacogenetics through subtype-specific associations. The study focuses on the relationship between genetic variants and the response to inhaled corticosteroids (ICS) in asthma patients with different levels of eosinophilia. The findings suggest that certain genetic variants are associated with a greater improvement in lung function following ICS treatment in patients with high eosinophil counts, while there is no significant association in patients with low eosinophil counts. The study highlights the importance of considering specific asthma endotypes in personalized medicine approaches. [Extracted from the article]

Erdostein is a mucoactive agent belonging to the group of thiol drugs with antioxidant, anti-inflammatory and antibacterial activity against a number of major respiratory pathogens. After transformation in the liver, erdostein is metabolized to a compound with an open ring M1 (MET-1) having unique properties. In the RESTORE study (2022), it was confirmed that erdostein significantly reduces the risks of severe exacerbations in patients with chronic obstructive pulmonary disease (COPD), reduces their duration, and reduces the number of hospitalizations with acute respiratory failure (ARF). The unique preventive properties of erdostein do not depend on the administration of inhaled (ICS) or systemic (SCS) corticosteroids to COPD patients, as well as on the level of eosinophilia in the blood. The results obtained contrast with the available therapy strategy, where thiol mucolytics are indicated in patients who do not use ICS-therapy and/or SCS-therapy. Moreover, this confirms the assumption about the use of erdostein in COPD patients as a drug for the phased withdrawal of ICS-therapy.

Abstract Background High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. Methods COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. Results 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83–0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. Conclusions Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

Abstract Background A significant update was made to both the Global Initiative for Asthma (GINA) in 2019 and the National Heart Lung and Blood Institute (NHLBI) asthma guidelines in 2020 for mild asthma. These groups no longer recommend short-acting beta-agonists (SABA) as monotherapy for mild (GINA) or mild-persistent (NHLBI) asthma. With the lag that can occur between guideline or evidence updates and changes in practice, this study sought to evaluate whether guideline adoption had occurred. Methods In this retrospective chart review, patient electronic medical records from a large healthcare system were evaluated from July 1 of 2021 to July 1 of 2022 to determine how many patients with mild asthma were prescribed as needed or daily inhaled corticosteroids (ICS) in addition to as needed SABA. The secondary outcome was to evaluate the incidence of exacerbations in patients with mild asthma, comparing those on guideline-directed therapy or not. In addition, we evaluated other patient factors increasing exacerbation risk in mild asthma. Results For the primary outcome, of the 1,107 patients meeting inclusion criteria, 284 patients (26%) did not have documentation of guideline-directed therapy for mild asthma during the study period, while 823 (74%) were on guideline-directed therapy (Diff:48.7%; 95% CI:45.1 to 52.3%, p

Background A decreasing use of inhaled corticosteroids (ICS) in patients with a hospital-registered diagnosis of chronic obstructive pulmonary disease (COPD) has recently been documented in Denmark. ICS treatment is not recommended in patients with high pneumonia risk, and we aimed to assess the development of ICS treatment in relation to pneumonia occurrence.Methods Annual nationwide register-based cross-sectional studies from 1998 to 2018 including all patients ≥40 years of age with a hospital-registered ICD-10 diagnosis of COPD on the 31st of December each year. We calculated the annual proportion of patients with at least one outpatient pneumonia (redeemed prescription of relevant antibiotics) or pneumonia hospitalization (hospitalization or ER visit), and stratified by ICS dose (No ICS, low dose, medium dose, or high dose).Results The study population increased from 35,656 patients in 1998 to 99,057 patients in 2018. The annual proportion of patients experiencing a pneumonia decreased from 69.4% to 55.2%. The proportion of patients with at least one outpatient pneumonia, but no hospitalization, decreased (59.2% to 46.2%). The overall proportion of patients with at least one pneumonia hospitalization remained unchanged (10.2% to 9.0%), but this proportion increased in patients in high dose ICS (9.9% to 14.6%). The overall proportion of patients in high dose treatment decreased (12.7% to 5.7%), but not in patients with pneumonia hospitalization (16.5% to 15.1).Conclusions Our study demonstrates a nationwide decrease from 1998 to 2018 in the proportion of patients who redeemed a prescription for antibiotics used mainly for respiratory tract infections, which may reflect a decrease in the number of outpatient pneumonias. This decrease was largely caused by an increase in the number of patients without pneumonia. No differences over time were seen regarding hospitalization-requiring pneumonia. High dose ICS treatment was unchanged in patients with hospitalization-requiring pneumonia.

Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting β2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment. Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression. Maintenance treatment with ICS together with long-acting β2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1–18.9%, p < 0.001), while SABA use decreased (46.4– 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2–57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use. The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains. [ABSTRACT FROM AUTHOR]

The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic "skin" CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways. The subsequent ICS development, with resulting clinical landmarks, is exemplified here with budesonide (BUD), showing that a similar efficacy/safety relationship is achievable by partly alternative mechanisms. BUD is much less lipophilic, giving it a 100-fold higher water solubility than BDP and later developed ICSs, leading to its more rapid intraluminal dissolution and faster airway and systemic uptake rates. In airway tissue, a BUD fraction is reversibly esterified to intracellular fatty acids, a lipophilic conjugate, which prolongs airway efficacy. Another mechanism is that the rapidly absorbed bulk fraction, via short plasma peaks, adds anti-inflammatory activity at the blood and bone marrow levels. Importantly, these plasma peaks are too short to provoke systemic adverse actions. Controlled clinical trials with BUD changed the use of ICS from a last resort to first-line treatment. Starting ICS treatment immediately after diagnosis ("early intervention") became a landmark for BUD. An established dose response made BUD suitable for the treatment of patients with all degrees of asthma severity. With the development of the budesonide/formoterol combination inhaler (BUD/FORM), BUD contributed to the widely used BUD/FORM maintenance and reliever therapy (MART). Recent studies demonstrated the value of BUD/FORM as a generally recommended as-needed therapy for asthma ("anti-inflammatory reliever", AIR). These abovementioned qualities have all influenced international asthma management and treatment guidelines. [ABSTRACT FROM AUTHOR]

Background: A significant update was made to both the Global Initiative for Asthma (GINA) in 2019 and the National Heart Lung and Blood Institute (NHLBI) asthma guidelines in 2020 for mild asthma. These groups no longer recommend short-acting beta-agonists (SABA) as monotherapy for mild (GINA) or mild-persistent (NHLBI) asthma. With the lag that can occur between guideline or evidence updates and changes in practice, this study sought to evaluate whether guideline adoption had occurred. Methods: In this retrospective chart review, patient electronic medical records from a large healthcare system were evaluated from July 1 of 2021 to July 1 of 2022 to determine how many patients with mild asthma were prescribed as needed or daily inhaled corticosteroids (ICS) in addition to as needed SABA. The secondary outcome was to evaluate the incidence of exacerbations in patients with mild asthma, comparing those on guideline-directed therapy or not. In addition, we evaluated other patient factors increasing exacerbation risk in mild asthma. Results: For the primary outcome, of the 1,107 patients meeting inclusion criteria, 284 patients (26%) did not have documentation of guideline-directed therapy for mild asthma during the study period, while 823 (74%) were on guideline-directed therapy (Diff:48.7%; 95% CI:45.1 to 52.3%, p < 0.001). For the secondary objective, 161 patients had an exacerbation (12% on guideline-directed therapy, 15.4% not on guideline-directed therapy). This difference in incidence of exacerbation between the two treatment groups was not statistically significant (Diff: -3.4%; 95% CI: -8 to 1.1%; p = 0.133). In addition, being female, having GERD, and being obese were all statistically significant factors associated with having asthma exacerbations among our patient population. Conclusions: Nearly one-fourth of patients with mild persistent asthma were not on guideline-directed therapy, despite updates in asthma guidelines (GINA 2019, NHLBI 2020). Factors such as being female, having GERD, and being obese were all statistically significant factors associated with having asthma exacerbations among patients with mild persistent asthma. [ABSTRACT FROM AUTHOR]

Background: Although inhaled corticosteroids (ICS) are the first-line therapy for patients with persistent asthma, many patients continue to have exacerbations. We developed machine learning models to predict the ICS response in patients with asthma. Methods: The subjects included asthma patients of European ancestry (n = 1371; 448 children; 916 adults). A genome-wide association study was performed to identify the SNPs associated with ICS response. Using the SNPs identified, two machine learning models were developed to predict ICS response: (1) least absolute shrinkage and selection operator (LASSO) regression and (2) random forest. Results: The LASSO regression model achieved an AUC of 0.71 (95% CI 0.67–0.76; sensitivity: 0.57; specificity: 0.75) in an independent test cohort, and the random forest model achieved an AUC of 0.74 (95% CI 0.70–0.78; sensitivity: 0.70; specificity: 0.68). The genes contributing to the prediction of ICS response included those associated with ICS responses in asthma (TPSAB1, FBXL16), asthma symptoms and severity (ABCA7, CNN2, PTRN3, and BSG/CD147), airway remodeling (ELANE, FSTL3), mucin production (GAL3ST), leukotriene synthesis (GPX4), allergic asthma (ZFPM1, SBNO2), and others. Conclusions: An accurate risk prediction of ICS response can be obtained using machine learning methods, with the potential to inform personalized treatment decisions. Further studies are needed to examine if the integration of richer phenotype data could improve risk prediction. [ABSTRACT FROM AUTHOR]

Introduction: Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). Methods: A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. Results: The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50 μg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5 μg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. Conclusions: The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy. Plain Language Summary: In this study, we tried to understand how patients with moderate to severe asthma use their quick-relief inhalers (like albuterol), how it relates to their symptoms and the risk of having asthma attacks. To evaluate whether differences in reliever inhaler use between patients are associated with factors like smoking or their asthma symptoms at the beginning of treatment, we gathered data from five clinical studies (n = 6212 patients). These data allowed us to create a model that predicts how often patients use their reliever inhalers (expressed as number of puffs in 24 h) during maintenance therapy with inhaled corticosteroids alone or in combination with long-acting beta agonists. The final model showed that reliever inhaler use is higher in patients who have been diagnosed with asthma for > 10 years, are smokers, have higher asthma symptom scores, and are obese or extremely obese. Patients who had asthma attacks also used their reliever inhalers more often. In addition, to understand how relief inhalers are used in real-life situations, we also created heatmaps that include a wide range of patient characteristics. By using individual patient data together with this model, we have learned that smoking, asthma control, BMI, long history of asthma and previous asthma attacks significantly influence reliever use. This information can help physicians and healthcare professionals understand know how well someone's asthma is managed. A patient who uses their reliever inhaler often is likely not to have their asthma well controlled by their regular medications. [ABSTRACT FROM AUTHOR]

Importance: The effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear. Objective: This network meta-analysis (NMA) extensively evaluated the treatment effects of single ICS; dual ICS i.e., ICS/long-acting β2-adrenergic agonists (LABA); ICS/LABA as single maintenance and reliever therapy (SMART); and triple ICS, i.e., ICS/LABA/long-acting muscarinic antagonists (LAMA) in preventing severe asthma exacerbations. Data sources: A systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA. Study selection: Using the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified. Data extraction and synthesis: A pairwise meta-analysis was used to select trials based on the criteria for minimizing heterogeneity (I2). Subsequently, the “BUGSnet” package of R software was used to perform a Bayesian network meta-analysis. Main outcome measures: The main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations. Results: This review included 56 randomized control trials (RCTs; n = 78,171 patients). As the pairwise meta-analysis demonstrated that the annualized rate ratio of severe asthma exacerbation had moderate heterogeneity, we analyzed the risk rate of severe asthma exacerbation using a network meta-analysis. In terms of direct/indirect comparisons with non-ICS, single ICS, dual ICS, SMART, and triple ICS reduced severe asthma exacerbations by 34 %, 47 %, 58 %, and 57 %, respectively. SMART and triple ICS showed high effectiveness in reducing severe exacerbations. Conclusion: AND RELEVANCE: SMART and triple ICS were ranked higher in effectiveness in reducing severe asthma exacerbations in comparison with other therapies, indicating that these are the most effective treatments for reducing the future risk of severe asthma exacerbations.

David Price,1,2 William Henley,1,3 José Eduardo Delfini Cançado,4 Leonardo M Fabbri,5 Huib AM Kerstjens,6 Alberto Papi,7 Nicolas Roche,8 Elif &Scedil;en,9 Dave Singh,10 Claus F Vogelmeier,11 Elena Nudo,12 Victoria Carter,1 Derek Skinner,1 Rebecca Vella,1 Joan B Soriano,13 Maxim Kots,12 George Georges14 1Observational and Pragmatic Research Institute, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Health Statistics Group, Department of Health and Community Sciences, University of Exeter Medical School, Exeter, UK; 4Santa Casa de São Paulo Medical School, São Paulo, Brazil; 5Respiratory Medicine, Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy; 6Department of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, and Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands; 7Respiratory Medicine, University of Ferrara, Ferrara, Italy; 8Department of Respiratory Medicine, APHP-Centre University of Paris, Cochin Hospital and Institute (UMR1016), Paris, France; 9Department of Pulmonary Medicine, Ankara University School of Medicine, Ankara, Turkey; 10Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Global Medical Affairs, Chiesi Farmaceutici, S.p.A, Parma, Italy; 13Respiratory Department, Hospital Universitario de La Princesa and Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; 14Global Clinical Development, Chiesi Farmaceutici, S.p.A, Parma, ItalyCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Combined ICS and long-acting bronchodilators (LABD) more effectively reduce COPD exacerbations than LABD therapy alone. Corticosteroid-related adverse effects, including pneumonia, limit ICS use. Previous data suggest this risk is lower for extrafine beclometasone (ef-BDP). We compared pneumonia risk among new users of fixed dose ICS/LABD formulations containing ef-BDP, versus patients initiating LABD without any ICS.Methods: A propensity-matched historical cohort study design used data from OPCRD. COPD patients with ≥ 1 year of continuous data who initiated LABD or ICS/LABD formulations containing ef-BDP were matched. Primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions, with non-inferiority boundary of 15%.Results: 23,898 COPD patients were matched, who were 68± 11 years, 54.3% male and 56% current-smokers, while 43% were former-smokers. Initiation of ef-BDP/LABD was not associated with an increased risk of pneumonia versus LABD, for either a sensitive 0.89 (0.78– 1.02), P = 0.08 or a specific 0.91 (0.78– 1.05), P = 0.18 definition of pneumonia. The probability of remaining pneumonia free 1-year after ef-BDP/LABD was 98.4%, which was comparable to LABD at 97.7%, and was sustained up to 6 years of observation; non-inferiority criterion was met for both definitions. Initiation of ef-BDP/LABD was also associated with a reduced risk of developing LRTIs in the propensity matched cohort.Conclusion: Risk of pneumonia when using ICS for the management of COPD reported in several randomised controlled trials may not be relevant with ef-BDP in a diverse real-world clinical population.Keywords: inhaled corticosteroids, pneumonia, COPD, extrafine beclometasone, long-acting bronchodilators

Exercise-induced bronchoconstriction (EIB) is a common condition in athletes, both with and without asthma. It involves the narrowing of the airways during intense exercise and is prevalent among elite athletes. Identifying and monitoring EIB is crucial for determining the best treatment. Inhaled corticosteroids (ICS) can effectively control EIB when taken daily for at least three months. Achieving remission in athletes with severe asthma through targeted treatments that inhibit eosinophils and mast cells is discussed, with the loss of airway hyperresponsiveness to mannitol proposed as a marker for documenting remission. Preventing and managing EIB in athletes, especially during the Olympics, is emphasized, and the use of inhaled corticosteroids is suggested as a potential treatment to reduce the risk of EIB. [Extracted from the article]

Abstract Asthma is a polygenic disease that may onset during childhood. Inhaled corticosteroids (ICS) are the main therapy in asthma, although their efficacy varies among individuals. Nuclear factor κB (NF-κB) is an important target of ICS treatment of asthma. Recent research has reported that GRB2 associated binding protein 1 (GAB1) gene may participate in the pathogenesis of asthma by regulating the NF-κB pathway. Therefore, we used the technique of an improved multiplex ligation detection reaction to sequence GAB1 gene and investigated the involvement of Single-nucleotide variants (SNVs) in GAB1 gene in asthma and ICS efficacy in asthmatic children. We found no differences between asthma cases and controls in allele or genotype frequencies of GAB1. Haplotype analysis showed an increased tendency for AGGAGC frequency in asthma patients compared with controls (OR = 2.69, p = 0.018). The percentage of EOS and genotype distribution of rs1397527 were associated (p = 0.007). The EOS percentage was higher in GT genotype when compared to the GG genotype (5.50 vs 3.00, Bonferroni adjusted p = 0.005). After 12-weeks ICS treatment, GAB1 rs1397527 TT and GT genotype carriers had a smaller change in forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) than GG carriers (p = 0.009), and rs3805236 GG and AG genotype carriers also had a smaller change in FEV1/FVC than AA carriers (p = 0.025). For ICS response, the frequency of GG genotype of rs1397527 was significantly higher in good responders (p = 0.038). The generalized multifactor dimensionality reduction (GMDR) analysis showed a best significant four-order model (rs1397527, allergen exposure, environmental tobacco smoke exposure, and pet exposure) involving gene-environment interactions (p = 0.001). In summary, we found that GAB1 SNVs were not associated with asthma susceptibility. Haplotype AGGAGC was a risk factor for asthma. GAB1 variants were associated with eosinophils and ICS response in asthmatics. Furthermore, gene-environment interaction was observed.

In this study, a new and straightforward process for the preparation of budesonide 21-phosphate (Bud-21P) and its disodium salt (Bud-21P-Na2) is described. The method results in a yield comparable to those obtained by diphosphoryl chloride, but it is more manageable, less expensive, and safer. The new compounds are characterized by better water solubility compared to the parent compound. Moreover, they have been evaluated for their anti-inflammatory activity and the obtained results clearly evidence that Bud-21P and Bud-21P-Na2 retained anti-inflammatory activity like the parent compound budesonide (Bud) in mice with cutaneous induced edema.

Asthma is a common condition affecting millions of children globally. The main goal of this study is to assess factors related to asthma management, particularly atopy level and the impact of genetic variants of the vitamin D receptor (VDR) gene. Asthmatic children were enrolled in an outpatient respiratory clinic. Information on patients' medication adherence, medical and medication factors, and sociodemographic were gathered. Spirometry FEV1% and FVC% measurements, and the asthma control test were used to evaluate the severity of asthma, and genotyping of the VDR gene and radioallergosorbent test (RAST) were conducted. Regression analyses were conducted to evaluate variables associated with asthma control and spirometry measures. A total of 313 participants (67.4% males) were recruited in the current study. The mean age was 9.37 (±3.45) years. The mean score for adherence was 4.26 (±2.52), and only 46% of the participants had controlled asthma. Forward conditional stepwise binary regression showed that low and moderate Inhaled corticosteroids (ICS) dose (OR= 0.42 (95% CI 0.20–0.90), p = 0.026; OR = 0.371 (95% CI 0.2–0.72), p = 0.003, respectively) decreased the odds of being in the controlled asthma group, while higher inhaler score (OR = 2.75 (95% CI 2.17–3.49, p < 0.001)) increased the odds of being in the controlled asthma group. However, results found no association between VDR genotype and asthma control, spirometry values or hospitalization due to asthma. The results indicated that many of the asthma patients had poorly controlled asthma. Factors that were associated with poor asthma control included poor inhaler technique. [ABSTRACT FROM AUTHOR]

We aimed to examine the effects of framed mobile messages (messages emphasizing losses or gains because of a behavior) on young adults' beliefs about their daily Inhaled Corticosteroids (ICS), intentions to take their ICS, adherence, and asthma control. College students (18–29 years) who owned a mobile phone and had a diagnosis of asthma with a prescription for an ICS were recruited. Participants (n = 43) were randomized to receive either gain- or loss-framed mobile messages three times per week for eight weeks. Engagement rates with messages were calculated. Outcomes included beliefs, intentions, adherence, and asthma control. Data collection was performed at baseline, week 4, and week 8. Mixed-design ANOVA assessed whether outcomes improved differentially from baseline to week eight between gain- and loss-framed groups. Twenty-two participants were randomly assigned to the gain-framed group and 21 to the loss-framed group. There was a 100% retention rate. The engagement rate with the text messages was 85.9%. There was a significant difference in participants' intentions to take medication and asthma control from baseline. There were no significant changes in other outcomes from baseline. There was no difference in changes in all outcomes between participants receiving gain- versus loss-framed messages. Framed mobile messages improved young adults' asthma control and intentions to take their medication as prescribed. [ABSTRACT FROM AUTHOR]

Recommendations for the treatment of chronic obstructive pulmonary disease (COPD) have shifted towards a more restrictive use of inhaled corticosteroids (ICS). We aimed to identify the nationwide development over time in the use of ICS treatment in COPD. We conducted a register-based repeated cross-sectional study using Danish nationwide registers. On a yearly basis from 1998 to 2018, we included all patients in Denmark ≥ 40 years of age with an ICD-10 diagnosis of COPD (J44). Accumulated ICS use was calculated for each year based on redeemed prescriptions. Patients were divided into the following groups: No ICS, low-dose ICS, medium-dose ICS, or high-dose ICS. From 1998 to 2018, the yearly proportion of patients without ICS treatment increased (from 50.6% to 57.6%), the proportion of patients on low-dose ICS treatment increased (from 11.3% to 14.9%), and the proportion of patients on high-dose ICS treatment decreased (from 17.0% to 9.4%). We demonstrated a national reduction in the use of ICS treatment in COPD from 1998 to 2018, with an increase in the proportion of patients without ICS and on low-dose ICS treatment and a decrease in the proportion of patients on high-dose ICS treatment. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) in bronchiectasis. A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81–1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84–1.33) for acute exacerbation, and 1.06 (95% CI 0.66–1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43–0.81; BUD/FOR HR 0.68, 95% CI 0.50–0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26–0.86) and all-cause hospitalization (HR 0.55, 95% 0.37–0.80) compared to FLU/SAL. Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL. [ABSTRACT FROM AUTHOR]

Asthma and obesity are inflammatory diseases that have a considerable impact on the development of oral diseases. The purpose of this study was to establish the link between asthma induced inflammation, obesity and their impact on the development of periodontal disease. This is a cross-sectional study concerning 130 Algerians aged between 18 and 86 years old. 70 of the subjects were atopic asthmatics and 60 were control cases. The functional assessment of asthma was performed by spirometry. The C-reactive protein, (CRP) Erythrocyte Sedimentation Rate (ESR) and eosinophil count confirmed the inflammation state. Our study revealed that women are more likely to develop asthma than men. Statistical evidence from the study indicated that snacking played a significant role in weight gain. Treatment and more especially inhaled corticosteroids have a direct effect on obesity and on the aggravation of the quality of oral cavity. This study also confirms the high correlation between the control of asthma, the ESR and the CRP in obese asthmatics. A very high correlation was observed between eosinophil levels and the control of asthma in obese people compared to lean ones. This study has highlighted and strengthened the link between asthma and obesity and their effect on oral health. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Often we call the patient's pharmacy to obtain a refill history to assess inhaled corticosteroid (ICS) adherence. The purpose of this project was to determine the accuracy of refill histories for ICS (with or without long-acting beta agonist) listed in Epic's Medication Dispense History. METHODS: We evaluated 61 patients and used data from 38 who met the following criteria: 1) under the care of the UF Pediatric Severe Asthma Clinic; 2) taking the same dose of the same ICS product for 6 months before the patient's last clinic visit; and 3) having data available from the pharmacy where the last ICS prescription was electronically sent. We called the pharmacies to obtain a verbal report of their refill record. Then, we compared the number of refills reported to the number listed in Epic's records using a Wilcoxon matched-pairs signed-ranks test. RESULTS: Of the 293 refill dates listed in Epic, 157 were duplicates, giving a 54% error. After deleting duplicates, the mean (SD) number of refills listed in Epic was 3.6 (2.0) compared with 3.3 (2.0) in pharmacies over a period of 6 months (p < 0.0001). After removing duplicates Epic correctly reported the total number of refills for 30 of the 38 patients (78.9%). Seven of the remaining patients had more refills listed in Epic while 1 patient had more refills dispensed. CONCLUSION: This study indicates that our version of Epic over-reports refills thus limiting assessment of adherence. In contrast, absence of refills in Epic is a clear indication of poor adherence. [ABSTRACT FROM AUTHOR]

Asthma is a polygenic disease that may onset during childhood. Inhaled corticosteroids (ICS) are the main therapy in asthma, although their efficacy varies among individuals. Nuclear factor κB (NF-κB) is an important target of ICS treatment of asthma. Recent research has reported that GRB2 associated binding protein 1 (GAB1) gene may participate in the pathogenesis of asthma by regulating the NF-κB pathway. Therefore, we used the technique of an improved multiplex ligation detection reaction to sequence GAB1 gene and investigated the involvement of Single-nucleotide variants (SNVs) in GAB1 gene in asthma and ICS efficacy in asthmatic children. We found no differences between asthma cases and controls in allele or genotype frequencies of GAB1. Haplotype analysis showed an increased tendency for AGGAGC frequency in asthma patients compared with controls (OR = 2.69, p = 0.018). The percentage of EOS and genotype distribution of rs1397527 were associated (p = 0.007). The EOS percentage was higher in GT genotype when compared to the GG genotype (5.50 vs 3.00, Bonferroni adjusted p = 0.005). After 12-weeks ICS treatment, GAB1 rs1397527 TT and GT genotype carriers had a smaller change in forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) than GG carriers (p = 0.009), and rs3805236 GG and AG genotype carriers also had a smaller change in FEV1/FVC than AA carriers (p = 0.025). For ICS response, the frequency of GG genotype of rs1397527 was significantly higher in good responders (p = 0.038). The generalized multifactor dimensionality reduction (GMDR) analysis showed a best significant four-order model (rs1397527, allergen exposure, environmental tobacco smoke exposure, and pet exposure) involving gene-environment interactions (p = 0.001). In summary, we found that GAB1 SNVs were not associated with asthma susceptibility. Haplotype AGGAGC was a risk factor for asthma. GAB1 variants were associated with eosinophils and ICS response in asthmatics. Furthermore, gene-environment interaction was observed. [ABSTRACT FROM AUTHOR]

Objective: Short-acting β2-agonist (SABA) overuse is associated with poor asthma outcomes; however, the extent of SABA use in Thailand is largely unknown. As part of the SABA use IN Asthma (SABINA) III study, we describe asthma treatment patterns, including SABA prescriptions, in patients treated by specialists in Thailand. Methods: In this observational, cross-sectional study, patients (aged ≥12 years) with an asthma diagnosis were recruited by specialists from three Thai tertiary care centers using purposive sampling. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma [GINA] recommendations). Data on sociodemographics, disease characteristics, and asthma treatment prescriptions were collected from existing medical records by healthcare providers and transcribed onto electronic case report forms. Analyses were descriptive. Results: All 385 analyzed patients (mean age: 57.6 years; 69.6% female) were treated by specialists. Almost all (91.2%) patients were classified with moderate-to-severe asthma (GINA treatment steps 3-5), 69.1% were overweight/obese, and 99.7% reported partially/fully reimbursed healthcare. Asthma was partly controlled/uncontrolled in 24.2% of patients; 23.1% experienced ≥1 severe asthma exacerbation in the preceding 12 months. Overall, SABAs were over-prescribed (≥3 canisters/year) in 28.3% of patients. Inhaled corticosteroids (ICS), ICS/ long-acting β2-agonists, oral corticosteroid (OCS) burst treatment, and long-term OCS were prescribed to 7.0, 93.2, 19.2, and 6.2% of patients, respectively. Additionally, 4.2% of patients reported purchasing SABA over the counter. Conclusions: Despite receiving specialist treatment, 28.3% of patients were over-prescribed to SABA in the previous 12 months, highlighting a public health concern and the need to align clinical practices with current evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Objective: Remission of childhood asthma has not been widely studied. Patients in clinical remission continue to have some degree of bronchial hyperresponsiveness (BHR). The aim of this study was to investigate whether clinical parameters and lung function test are good parameters for discontinuation of inhaled corticosteroids (ICS) in asthmatic children, including patients with persistent BHR, as measured by the methacholine challenge test (MCT). Methods: One year after discontinuation of inhaled corticosteroids (ICS), MCT was performed in a group of 40 asthmatic children to confirm or exclude BHR. In all patients, ICS treatment was discontinued based on the same parameters: symptoms, spirometry, daily PEF, and negative bronchodilator test. After achieving complete asthma control for at least 6 to 12 months, ICS treatment was stepped down and discontinued. Clinical course and spirometry were followed up after ICS discontinuation. Results: Positive MCT was found in 50% of the patients. There was no statistically significant difference between the positive and negative MCT groups in age at initiation and discontinuation of ICS therapy, duration of ICS therapy, duration of stepping down period, FEV1, and PEF at the time of withdrawal of ICS and one year later. ICS treatment had to be restarted in two patients from the positive MCT group, due to recurrence of asthma symptoms. Conclusion: Clinical parameters, normal spirometry, daily PEF values, and a negative bronchodilator test are good parameters for discontinuing ICS treatment in asthmatic children, even in patients with persistent BHR. Children should continue to be monitored, as symptoms may recur. [ABSTRACT FROM AUTHOR]

Background: There are disputes whether inhaled corticosteroids (ICS) increase the incidence of fracture or osteoporosis among patients with COPD. The aim of this meta-analysis was to assess the effect of ICS treatment on the risk of fracture and osteoporosis in subjects with COPD. Methods: This study included parallel-group randomized controlled trials (RCTs) comparing ICS and control (non-ICS) therapy for subjects with COPD that reported adverse events including fractures or osteoporosis. Studies were found using MEDLINE/PubMed, Embase, and Cochrane Library databases between 1998-September 2022. Pooled risk ratios (RRs) and 95% CIs were calculated for primary outcomes. Results: A total of 61,380 participants from 26 RCTs were included in the meta-analysis. Exposure to ICS did not increase the risk of fracture (RR 1.10 [95% CI 0.98-1.23], P = .10) or osteoporosis risk (RR 0.93 [95% CI 0.49-1.79], P = .84) in subjects with COPD. Conclusions: ICS use did not increase the incidence of fracture or osteoporosis in subjects with COPD. [ABSTRACT FROM AUTHOR]