Inhaled Corticosteroid Therapy Research Articles

Dyspnea and nocturnal cough due to esophageal diffuse leiomyomatosis in a girl with hematuria.

A 7-year-old girl with hematuria and clinical suspicion of Alport syndrome (AS) presented with dyspnea and nocturnal cough, initially diagnosed and treated as asthma. Despite inhaled corticosteroid therapy, her symptoms persisted, and spirometry indicated obstructive lung function without bronchodilator response. Chest CT revealed diffuse thickening of the esophageal wall, tracheal compression, with involvement of the gastric cardia, suggestive of diffuse leiomyomatosis. Subsequent genetic reanalysis confirmed the presence of a contiguous deletion of COL4A5 and COL4A6 genes, solidifying the diagnosis of AS. Diffuse leiomyomatosis, a rare benign neoplasm associated with AS, typically manifests as dysphagia, but in this case, it presented initially with asthma-like symptoms. This case emphasizes the importance of imaging when asthma treatment fails, particularly in patients with coexisting conditions of another system.

55 Post-pandemic paediatric asthma admissions: Clinical characteristics and outcomes of children hospitalized with asthma in 2022: The READAPT-Kids study cohort

Abstract Background Asthma exacerbations triggered by acute respiratory infections (ARIs) are a major cause of hospitalizations in children. There were large reductions in asthma admission during the SARS-CoV2 pandemic. Following the relaxation of public health interventions, there was a resurgence in admissions for ARIs. The effect of this rebound in ARIs on asthma management practices and outcomes is not well understood. Objectives To describe sociodemographic characteristics, etiology, management, and clinical outcomes of children and youth under the age of 18 years admitted to a tertiary care paediatric hospital with an acute asthma exacerbation from July 1, 2022 to Dec 31, 2022. Design/Methods An observational cohort study of children and youth less than 18 years, hospitalized with an acute asthma exacerbation from July 1, 2022 to Dec 31, 2022 at a single large Canadian children’s hospital. This was a subgroup analysis of the READAPT-Kids study cohort (Clinical chaRacteristics and outcomEs of hospitAlized children with Acute resPiratory infecTions.) Cases were identified using ICD-10-CA codes, then manually screened for inclusion. Detailed clinical and demographic information was extracted. Results Among 551 patients hospitalized with an ARI, 29.2% (n=161) were diagnosed with an asthma exacerbation. 99 were male (61.5%) with a median age of 3.8 years (IQR 2.2-6.3). 41.3% (n=64) had a previously documented asthma history, and of those, only 16.9% were taking any form of asthma therapy at admission. In hospital, 91.4% were given systemic corticosteroids, 86.5% had at least 1 viral pathogen identified, 72.2% had a chest x ray, 42.1% received antibiotics, and 23.7% had high flow nasal cannula oxygen outside of the paediatric intensive care (PICU). 22.4% (n=36), were admitted to the PICU, and 3.7% required invasive mechanical ventilation, there were no patient deaths. Median length of stay was 2.6 days (IQR 1.7–4.6 days). At discharge, 79.5% were prescribed regular inhaled corticosteroid therapy. Conclusion Asthma admissions accounted for a significant proportion of children hospitalized with ARIs in the post-pandemic era, with one fifth requiring transfer to PICU. CXR and antibiotic usage were high. Over 80% of those with a previous diagnosis of asthma were not taking inhaled corticosteroids at the time of admission.

Effect of continuous inhaled corticosteroids on glycated hemoglobin in asthmatic children: a pilot study

BackgroundAsthma 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.MethodsThis 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).ResultsThe 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.ConclusionThe 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.

Rapid Access Diagnostics for Asthma (RADicA): protocol for a prospective cohort study to determine the optimum series of investigations to diagnose asthma using conventional and novel tests

IntroductionThe diagnosis of asthma is often based on characteristic patterns of symptoms in the absence of an alternative explanation, resulting in over and under diagnosis. Therefore, diagnostic guidelines usually recommend...

Exploring the Impact of Inhaled Corticosteroids on Endothelial Function in Chronic Obstructive Pulmonary Disease Patients Undergoing Pulmonary Rehabilitation.

Background: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, which can be assessed non-invasively through flow-mediated dilation (FMD). In this study, we evaluated the potential impact of inhaled corticosteroid (ICS) therapy on FMD of COPD patients undergoing pulmonary rehabilitation (PR). Methods: Medical records of COPD patients undergoing FMD assessment upon admission to our Pulmonary Rehabilitation Unit were reviewed in this retrospective post hoc analysis. Results: A total of 46 patients with COPD (median age 71.5 years, 28.3% postmenopausal females) were included in the final analysis. Among these, 27 participants were currently receiving ICS therapy, while 19 were not. At baseline, the two groups showed no difference in the main clinical and functional variables. Similarly, no significant difference was observed in vascular reactivity parameters, with a median FMD of 3.12% (IQR: 2.23-4.45) in ICS users and 3.39% (IQR: 2.45-4.08) in ICS nonusers (p = 0.544). After PR, a significant improvement in the main rehabilitation and patient-reported outcomes was observed in all groups, with a significant improvement in FMD documented in both patients treated with steroids (from 3.12%; IQR: 2.23-4.45 to 4.77%; IQR: 3.25-5.63, p = 0.022) and in those who were not (from 3.39%; IQR: 2.45-4.08 to 5.04%; IQR: 3.98-6.06, p = 0.005). FMD changes were of comparable magnitude among groups. Conclusions: Our preliminary findings do not indicate a significant impact of medications containing ICS on the endothelial function of COPD patients, suggesting that the potential beneficial effect of PR on this surrogate marker of cardiovascular risk is independent of inhaled therapy.

Inhaled Medications for Maintenance Therapy in Pediatric Noncystic Fibrosis Bronchiectasis.

This review focuses on evaluating literature for the use of inhaled mucolytics (hypertonic saline, mannitol, and dornase alfa), inhaled antibiotics (tobramycin, aztreonam, colistin, and amikacin), and inhaled corticosteroids in pediatric noncystic fibrosis bronchiectasis. A literature search via PubMed was conducted using the search terms "non-cystic fibrosis bronchiectasis," "primary ciliary dyskinesia," and "bronchiectasis" in combination with each inhaled agent of interest. Studies were included if they were specific to patients with a clinical diagnosis of noncystic fibrosis bronchiectasis published from 1998 to July 2024. Several inhaled medications can be considered as maintenance therapies for pediatric patients with noncystic fibrosis bronchiectasis. Hypertonic saline could be considered for its potential airway clearance benefits and low risk of causing harm. Inhaled antipseudomonal antibiotics should be considered in patients who are colonized with Pseudomonas aeruginosa. Inhaled corticosteroid therapy should be reserved for patients with concomitant asthma. Dornase alfa has shown worse outcomes in adults with noncystic fibrosis bronchiectasis and should be used with caution. Risks and benefits should be carefully considered when evaluating these therapies for use in noncystic fibrosis bronchiectasis, and patient-specific treatment regimens should be developed. Chronic management of pediatric noncystic fibrosis bronchiectasis remains challenging due to paucity of applicable literature. Risks and benefits of different agents are discussed in this article with recommendations for application to clinical practice based on studies performed in both adult and pediatric patients with noncystic fibrosis bronchiectasis. Several inhaled medications could be considered as maintenance therapies for pediatric patients with noncystic fibrosis bronchiectasis, with more robust evidence to support use of inhaled antipseudomonal antibiotics and hypertonic saline compared with other available agents. Further investigation is needed to identify a clear place in therapy for inhaled therapies in pediatric noncystic fibrosis bronchiectasis.

Asthma diagnosis: a comparison of established diagnostic guidelines in adults with respiratory symptoms

Considerable variability exists between asthma diagnostic guidelines. We tested the performance characteristics of the European Respiratory Society (ERS), the National Institute for Health and Care Excellence (NICE) and the Global Initiative for Asthma (GINA) guidelines for the diagnosis of asthma in adults. In this prospective observational study (ISRCTN-11676160, May 2019-June 2022), participants referred from primary care with clinician-suspected asthma underwent comprehensive investigation including: spirometry, bronchodilator reversibility, fractional exhaled nitric oxide, peak expiratory flow variability, bronchial challenge testing with methacholine and mannitol, and responsiveness to inhaled corticosteroid therapy. Results were reviewed by a panel of asthma specialists to determine asthma diagnosis (reference standard) and compared to each diagnostic test and the ERS, NICE and GINA diagnostic algorithms (index tests). The sensitivity, specificity, positive predictive and negative predictive values were calculated. One hundred and forty adults were enrolled and 118 given a definitive diagnostic outcome [75 female; mean (SD) age 36 (12) years; 70 (59%) with asthma] and included in the analysis. Sensitivity of individual tests was poor (15-62%), but they provided good specificity at the most stringent thresholds (range: 88-100%). The sensitivity/specificity of ERS, NICE and GINA was 81/85%, 41/100% and 47/100%, respectively. Concordance between guidelines was only moderate (Cohen's Kappa 0.45-0.51). Current guidelines for the diagnosis of asthma in adults provide either excellent specificity but low sensitivity (GINA and NICE) or only reasonable sensitivity and specificity (ERS). All guidelines therefore have limitations with regards to their clinical application; new guidelines are needed but should be tested prospectively before roll out. This work was supported by the Manchester NIHR Biomedical Research Centre (BRC) (grant no. BRC-1215-20007, and NIHR203308), Asthma UK/Innovate (grant no. AUK-PG-2018-406), GSK ID 212474 and North West Lung Centre Charity.

Effect of long-term inhaled corticosteroids therapy on cognitive function in patients with bronchial asthma and chronic obstructive pulmonary disease.

Inhaled corticosteroids (ICS) are prominent therapies for managing both asthma and chronic obstructive pulmonary disease (COPD). It has been noted that cognitive impairment is usually linked to high levels of corticosteroids in the blood. This investigation aims to ascertain how long-term inhaled corticosteroid treatment affects individuals with bronchial asthma and COPD's cognitive performance. A total of 139 inpatients diagnosed with COPD and bronchial asthma were enrolled in the study of which 43 were newly diagnosed (group 1), 34 were taking ICS for 0.5-1 year (group 2) and 62 were on long-term ICS, that is, for >2 years (group 3). Patients with a score of at least 24 were considered to have normal cognitive function as prescribed by the Montreal Cognitive Assessment scale. It was observed that 56 patients (90.3%) were on long-term ICS treatment, 25 patients (73.5%) were on intermediate therapy and 27 patients (62.7%) who were newly diagnosed had cognitive impairment. In conclusion, the duration of ICS therapy was significantly associated with a decline in cognitive function.

Effect of Long-Term Inhaled Corticosteroid Therapy on Metabolic And Anthropometric Parameters in Pediatric Patients with Asthma

Background: The long-term impact of inhaled corticosteroids (ICSs) metabolic parameters of asthmatic children is still uncertain. Objective: This study aimed to evaluate the effects of long-term use of ICSs on metabolic and anthropometric measures in children with asthma in Iran. Methods: This case-control study was conducted among 200 pediatric asthmatic patients who were referred to Abuzar Hospital (Ahvaz, Iran) during nine months. Demographic and clinical data of the patients were recorded. The participants were categorized into two groups: Group 1 (n = 100) comprising children with moderate to severe asthma, and Group 2 (n = 100) consisting of those with mild asthma. Results: The average age of 200 patients was 8.1 ± 2.9 years. The majority of them were male. The prevalence of wasting, stunting, obesity, and overweight was higher among Group 1 compared to Group 2 (p < 0.05). Patients in Group 1 had significantly higher levels of calcium, vitamin D, lipids, and glycemic parameters than those in Group 2 (p < 0.05). In addition, the duration of ICS use was notably longer in Group 1 (p < 0.05). Conclusion: Children with moderate and severe asthma had significantly elevated lipid and glycemic parameters, as well as a higher prevalence of wasting, stunting, obesity, and overweight compared to patients with mild asthma. Further studies involving larger sample sizes and longer durations are necessary to confirm these findings.

Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine Reduces Exacerbation Rate and Risk in Patients With Moderate to Severe COPD

IntroductionExacerbations in chronic obstructive pulmonary disease (COPD) can be life-threatening and lead to irreversible declines in lung function and quality of life. Medications that reduce exacerbation burden are an unmet need, as exacerbations put patients at risk for more exacerbations and decrease quality of life. Ensifentrine is a novel, first-in-class, selective, dual inhibitor of phosphodiesterase 3/4 with demonstrated nonsteroidal anti-inflammatory activity and bronchodilatory effects. Research QuestionDoes ensifentrine reduce the rate and/or risk of COPD exacerbations? Study Design and MethodsA prespecified, pooled analysis of the phase 3 clinical trials ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) was conducted to assess the effect of ensifentrine on exacerbation rate and risk (time to first exacerbation). The trials included symptomatic patients aged 40-80 years with moderate-to-severe COPD who received 3 mg twice-daily ensifentrine over 24 weeks or placebo. Subgroup analyses and frequent exacerbator transition risk were conducted post-hoc. ResultsIn total, 975 ensifentrine-treated and 574 placebo-treated patients were included in the pooled analysis, including 62% on concomitant LAMA or LABA therapy and 18% on concomitant inhaled corticosteroid therapy. Ensifentrine was associated with significant reductions in the rate (rate ratio, 0.59; 95% CI, 0.43-0.80; P < 0.001) and risk (hazard ratio, 0.59; 95% CI, 0.44-0.81; P < 0.001) of moderate/severe exacerbations compared with placebo. Reductions in the rate and risk of exacerbations were generally consistent across patient subgroups, including age, sex, race, background maintenance medication use, chronic bronchitis, eosinophil count, COPD severity, and exacerbation history. Ensifentrine was associated with a numerical delay in transitioning from an infrequent exacerbator (GOLD B) to a frequent exacerbator (GOLD E) compared with placebo. ConclusionEnsifentrine reduced the rate of exacerbations and increased the time to first exacerbation among patients with COPD across a broad range of clinically relevant subgroups.

Hedgehog signaling pathway regulates Th17 cell differentiation in asthma via IL-6/STAT3 signaling

Asthma is the most prevalent chronic inflammatory disease of the airways in children. The most prevalent phenotype of asthma is eosinophilic asthma, which is driven by a Th2 immune response and can be effectively managed by inhaled corticosteroid therapy. However, there are phenotypes of asthma with Th17 immune response that are insensitive to corticosteroid therapy and manifest a more severe phenotype. The treatment of this corticosteroid-insensitive asthma is currently immature and requires further attention. The objective of this study is to elucidate the regulation of the Hedgehog signaling pathway in Th17 cell differentiation in asthma. The study demonstrated that both Smo and Gli3, key components of the Hedgehog signaling pathway, were upregulated in Th17 polarization in vitro and in a Th17-dominant asthma model in vivo. Inhibiting Smo with a small molecule inhibitor or genetically knocking down Gli3 was found to suppress Th17 polarization. Smo was found to increase in Th1, Th2, Th17 and Treg polarization, while Gli3 specifically increased in Th17 polarization. ChIP-qPCR analyses indicated that Gli3 can directly interact with IL-6 in T cells, inducing STAT3 phosphorylation and promoting Th17 cell differentiation. Furthermore, the study demonstrated a correlation between elevated Gli3 expression and IL-17A and IL-6 expression in children with asthma. In conclusion, the study demonstrated that the Hedgehog signaling pathway plays an important role in the pathogenesis of asthma, as it regulates the differentiation of Th17 cells through the IL-6/STAT3 signaling. This may provide a potential therapeutic target for corticosteroid-insensitive asthma driven by Th17 cells.

Asthma control among teenagers attending the respiratory outpatient clinic of an academic hospital in Pretoria, South Africa

Objectives: Bronchial asthma is characteristically a diverse illness that results from chronically inflamed bronchi. Adolescents are a particularly vulnerable group to asthma, and both its prevalence and death rate have increased in this patient population. Asthma care creates a particular set of difficulties for adolescents who are at a stage where there is a search for greater autonomy and changing social and emotional dynamics. The aim of this study was to describe the clinical characteristics of teenage asthmatics in an academic hospital. Materials and Methods: This was a cross-sectional study of patients between the ages of 13 and 18 who had consented to participate. The study consisted of face-to-face interviews and a review of their clinical and laboratory records. Data were analyzed using descriptive statistics and comparisons between groups made using Fisher’s test of exactness. Results: Eighty-seven teenagers were studied. The mean age was 15.5 ± 1.5 years. The majority (59%) were male. Ten study subjects (11.5%) were current smokers. A positive family history of asthma was found in 31% (n = 27) of the patients. All patients were on inhaled corticosteroid therapy. The majority of the study subjects (60.9%) had satisfactory asthma control as evidenced by a mean asthma control test score (ACT) of 19.2 ± 2.29. Fifteen patients (26.7%) had had an acute flare-up of the disease requiring hospitalization in the preceding 12 months, and 5.8% had had a previous intensive care unit admission. Conclusion: The majority of the teenagers studied had overall satisfactory asthma control, as determined by their ACT scores. The use of inhaled corticosteroids was standard, but the inhaler technique was largely unsatisfactory. The prevalence of tobacco use is a cause for concern.

Assessing the impact of long-term inhaled corticosteroid therapy on patients with COVID-19 and coexisting chronic lung disease: A multicenter retrospective cohort study

Background Patients with chronic lung disease (CLD), such as asthma or chronic obstructive pulmonary disease, were expected to have an increased risk of clinical manifestations and severity of COVID-19. However, these comorbidities have been reported less frequently than expected. Chronic treatment with inhaled corticosteroids (ICS) may impact the clinical course of COVID-19. The main objective of this study is to know the influence of chronic treatment with ICS on the prognosis of COVID-19 hospitalized patients with CLD. Methods A multicenter retrospective cohort study was designed, including patients hospitalized with COVID-19. Epidemiological and clinical data were collected at admission and at seven days, and clinical outcomes were collected. Patients with CLD with and without chronic treatment with ICS were compared. Results Two thousand five hundred ninety-eight patients were included, of which 1,171 patients had a diagnosis of asthma and 1,427 of COPD (53.37% and 41.41% with ICS, respectively). No differences were found in mortality, transfer to ICU, or development of moderate-severe ARDS. Patients with chronic ICS had a longer hospital stay in both asthma and COPD patients (9 vs. 8 days, p = 0.031 in asthma patients), (11 vs. 9 days, p = 0.018 in COPD patients); although they also had more comorbidity burden. Conclusions Patients with chronic inhaled corticosteroids had longer hospital stays and more chronic comorbidities, measured by the Charlson comorbidity index, but they did not have more severe disease at admission, evaluated with qSOFA and PSI scores. Chronic treatment with inhaled corticosteroids had no influence on the prognosis of patients with chronic lung disease and COVID-19.

Eosinophilic Inflammation in COPD: Mechanisms, Diagnostic Markers, Clinical Features and Therapy Guidance

Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality worldwide. Eosinophilia, which may have a significant role in the inflammation process and obstruction of airways, is present in about one third patients suffering from COPD. The significance of eosinophil counts in COPD is currently debated, but they can potentially serve as biomarkers for treatment selection. Blood eosinophil counts can assist in determining the patients who can benefit from inhaled corticosteroid therapy to prevent or eliminate exacerbations.&lt;br /&gt; The aim of this review is to demonstrate the significance of eosinophilic inflammation COPD and the use of eosinophilic inflammation biomarkers to guide therapy decisions.&lt;br /&gt; To reach this goal, a search of relevant literature on the subject was conducted. Articles were searched in electronic sources: PubMed and Google Scholar. The keywords "COPD and eosinophilia", "COPD exacerbations and eosinophilia", "inhaled corticosteroids, COPD and eosinophilia" were used. One hundred and twenty sources were found, of which 66 were selected.&lt;br /&gt; Results of the review showed high frequency of eosinophilic phenotype detection in COPD. Blood eosinophilia becomes a potential universal marker of eosinophilic COPD. Blood eosinophils level can predict response to inhaled corticosteroids treatment patients with COPD, but increases the likelihood of pneumonia. Overall, the role of eosinophilia in COPD has not been obtained to date, which suggests it needs further study.

Differences in the effectiveness of single, dual, and triple inhaled corticosteroid therapy for reducing future risk of severe asthma exacerbation: A systematic review and network meta-analysis

ImportanceThe effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear. ObjectiveThis 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 sourcesA systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA. Study selectionUsing the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified. Data extraction and synthesisA 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 measuresThe main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations. ResultsThis 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. ConclusionAND 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.

The effects of inhaled corticosteroids on healthy airways.

The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. 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. 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. 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. 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.

Clinical Characteristics and 2-Year Outcomes of Chronic Obstructive Pulmonary Disease Patients With High Blood Eosinophil Counts: A Population-based Prospective Cohort Study in China

BackgroundHigh blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. MethodsWe obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/μL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. ResultsOf the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09–1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. ConclusionsCOPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

Participant Perspectives on the Implementation of a School-Linked Text-Message Intervention to Improve Pediatric Asthma Medication Adherence.

Background: Poor adherence to inhaled corticosteroids (ICS) is a significant challenge in pediatric asthma, contributing to health inequities. Text-message reminders for ICS therapy are an evidence-based approach that improves pediatric asthma medication adherence, yet has not been widely adopted into practice, partly due to lack of (1) participant input on design and implementation and (2) use of sustainable community linkages. Remote Asthma Link™ (RAL) seeks to fill this gap as a school-linked text-message intervention wherein parents of children with poorly controlled asthma received daily, 2-way text-message reminders for preventive inhaler use. Responses were shared with school nurses who conducted remote check-ins with families. Enrolled children, largely from underserved backgrounds, experienced improvements in medication adherence and asthma health outcomes. While initial results were promising, we have yet to elicit participant input to refine the protocol for more widespread implementation. Objective: Examine participant perspectives on barriers and facilitators of RAL implementation. Methods: Semistructured interviews were conducted May-June 2022 with intervention participants: 10 parents, 7 school nurses, and 4 pediatric providers (n = 21) until thematic saturation was reached. Interview transcripts were coded using thematic analysis. Results: Several facilitators for RAL implementation were identified, including ease of use and accessibility, personal connection to the school nurse, and receipt of a visual notification for habit formation. Barriers included challenges with school nurses reaching parents, poor understanding of program expectations, and lack of reimbursement structure. Participant-proposed solutions to barriers included utilizing alternate communication methods (eg, social media), educational sessions, and meeting with payors to consider reimbursement models. Conclusion: RAL is a school-linked text-message intervention demonstrating promise in improving outcomes and equity in asthma care. Key implementation facilitators, barriers, and proposed solutions will inform protocol adaptations to promote successful implementation of this and other text-message interventions into clinical practice.

Advanced Diagnostics of Respiratory Distress Syndrome in Premature Infants Treated with Surfactant and Budesonide through Computer-Assisted Chest X-ray Analysis.

This research addresses the respiratory distress syndrome (RDS) in preterm newborns caused by insufficient surfactant synthesis, which can lead to serious complications, including pneumothorax, pulmonary hypertension, and pulmonary hemorrhage, increasing the risk of a fatal outcome. By analyzing chest radiographs and blood gases, we specifically focus on the significant contributions of these parameters to the diagnosis and analysis of the recovery of patients with RDS. The study involved 32 preterm newborns, and the analysis of gas parameters before and after the administration of surfactants and inhalation corticosteroid therapy revealed statistically significant changes in values of parameters such as FiO2, pH, pCO2, HCO3, and BE (Sig. < 0.05), while the pO2 parameter showed a potential change (Sig. = 0.061). Parallel to this, the research emphasizes the development of a lung segmentation algorithm implemented in the MATLAB programming environment. The key steps of the algorithm include preprocessing, segmentation, and visualization for a more detailed understanding of the recovery dynamics after RDS. These algorithms have achieved promising results, with a global accuracy of 0.93 ± 0.06, precision of 0.81 ± 0.16, and an F-score of 0.82 ± 0.14. These results highlight the potential application of algorithms in the analysis and monitoring of recovery in newborns with RDS, also underscoring the need for further development of software solutions in medicine, particularly in neonatology, to enhance the diagnosis and treatment of preterm newborns with respiratory distress syndrome.

Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study

Stepwise intensification of inhaled corticosteroids (ICS) is routine for severe eosinophilic asthma, despite some poor responses to high-dose ICS. Dose reductions are recommended in patients responding to biologics, but little supporting safety evidence exists. SHAMAL was a phase 4, randomised, open-label, active-controlled study done at 22 study sites in four countries. Eligible participants were adults (aged ≥18 years) with severe eosinophilic asthma and a five-item Asthma Control Questionnaire score below 1·5 and who received at least three consecutive doses of benralizumab before screening. We randomly assigned patients (3:1) to taper their high-dose ICS to a medium-dose, low-dose, and as-needed dose (reduction group) or continue (reference group) their ICS-formoterol therapy for 32 weeks, followed by a 16-week maintenance period. The primary endpoint was the proportion of patients reducing their ICS-formoterol dose by week 32. The primary outcome was assessed in the reduction group, and safety analyses included all randomly assigned patients receiving study treatment. This study is registered at ClinicalTrials.gov, NCT04159519. Between Nov 12, 2019, and Feb 16, 2023, we screened and enrolled in the run-in period 208 patients. We randomly assigned 168 (81%) to the reduction (n=125 [74%]) and reference arms (n=43 [26%]). Overall, 110 (92%) patients reduced their ICS-formoterol dose: 18 (15%) to medium-dose, 20 (17%) to low-dose, and 72 (61%) to as-needed only. In 113 (96%) patients, reductions were maintained to week 48; 114 (91%) of patients in the reduction group had zero exacerbations during tapering. Rates of adverse events were similar between groups. 91 (73%) patients had adverse events in the reduction group and 35 (83%) in the reference group. 17 patients had serious adverse events in the study: 12 (10%) in the reduction group and five (12%) in the reference group. No deaths occurred during the study. These findings show that patients controlled on benralizumab can have meaningful reductions in ICS therapy while maintaining asthma control. AstraZeneca.