Inhaled Corticosteroid Therapy Research Articles

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

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

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.

Inhaler Steroid Use Changes Oral and Airway Bacterial and Fungal Microbiome Profile in Asthma Patients

Introduction: The full spectrum of bacterial and fungal species in adult asthma and the effect of inhaled corticosteroid use is not well described. The aim was to collect mouthwash and induced sputum samples from newly diagnosed asthma patients in the pretreatment period and in chronic asthma patients while undergoing regular maintenance inhaled corticosteroid therapy, in order to demonstrate the bacterial and fungal microbiome profile. Methods: The study included 28 asthmatic patients on inhaler steroid therapy, 25 steroid-naive asthmatics, and 24 healthy controls. Genomic DNA was isolated from induced sputum and mouthwash samples. Analyses were performed using bacterial primers selected from the 16S rRNA region for the bacterial genome and “panfungal” primers selected from the 5.8S rRNA region for the fungal genome. Results: Dominant genera in mouthwash samples of steroid-naive asthmatics were Neisseria, Haemophilus, and Rothia. The oral microbiota of asthmatic patients on inhaler steroid treatment included Neisseria, Rothia, and Veillonella species. Abundant genera in induced sputum samples of steroid-naive asthma patients were Actinomyces, Granulicatella, Fusobacterium, Peptostreptococcus, and Atopobium. Sputum microbiota of asthma patients taking inhaler steroids were dominated by Prevotella and Porphyromonas. Mucor plumbeus and Malassezia restricta species were abundant in the airways of steroid-naive asthma patients. Choanephora infundibulifera and Malassezia restricta became dominant in asthma patients taking inhaled steroids. Conclusion: The oral and airway microbiota consist of different bacterial and fungal communities in healthy and asthmatic patients. Inhaler steroid use may influence the composition of the oral and airway microbiota.

Efficacy, Safety, and Systemic Exposure of Once-Daily Indacaterol Acetate in Pediatric Asthma: A Randomized, Double-Blind, Controlled Dose-Finding Study.

Indacaterol acetate (IND), a long-acting β2-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma. In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥6 to <12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler® in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV1) after two weeks of treatment. In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV1 from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV1 after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 μg group and 25% patients in IND 150 μg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile. Once-daily IND 75 μg and IND 150 μg via Breezhaler® in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 μg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma. ClinicalTrials.gov (NCT02892019; 08-Sep-2016).

Addition of long-acting beta2 agonists or long-acting muscarinic antagonists versus doubling the dose of inhaled corticosteroids (ICS) in adolescents and adults with uncontrolled asthma with medium dose ICS: a systematic review and network meta-analysis.

Inhaled corticosteroids (ICS) are the mainstay treatment for persistent asthma. Escalating treatment is required when asthma is not controlled with ICS therapy alone, which would include, but is not limited to, adding a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA) or doubling the dose of ICS. To assess the efficacy and safety of adding a LABA or LAMA to ICS therapy versus doubling the dose of ICS in adolescents and adults whose asthma is not well controlled on medium-dose (MD)-ICS using a network meta-analysis (NMA), and to provide a ranking of these treatments according to their efficacy and safety. We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, Global Health, ClinicalTrials.gov, and the World Health Organization ICTRP for pre-registered randomised controlled trials (RCTs) from January 2008 to 19 December 2022. We searched for studies including adolescents and adults with uncontrolled asthma who had been treated with or were eligible for MD-ICS, comparing it to high-dose (HD)-ICS, ICS/LAMA, or ICS/LABA. We excluded cluster- and cross-over RCTs. Studies were of at least 12 weeks duration. We conducted a systematic review and network meta-analysis according to a previously published protocol. We used Cochrane's Screen4ME workflow to assess search results. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. The primary outcome is asthma exacerbations (moderate and severe). We included 38,276 participants from 35 studies (median duration 24 weeks (range 12 to 78); mean age 44.1; 38% male; 69% white; mean forced expiratory volume in one second 2.1 litres and 68% of predicted). MD- and HD-ICS/LABA likely reduce and MD-ICS/LAMA possibly reduces moderate to severe asthma exacerbations compared to MD-ICS (hazard ratio (HR) 0.70, 95% credible interval (CrI) 0.59 to 0.82; moderate certainty; HR 0.59, 95% CrI 0.46 to 0.76; moderate certainty; and HR 0.56, 95% CrI 0.38 to 0.82; low certainty, respectively), whereas HD-ICS probably does not (HR 0.94, 95% CrI 0.70 to 1.24; moderate certainty). There is no clear evidence to suggest that any combination therapy or HD-ICS reduces severe asthma exacerbations compared to MD-ICS (low to moderate certainty). This study suggests no clinically meaningful differences in the symptom or quality of life score between dual combinations and monotherapy (low to high certainty). MD- and HD-ICS/LABA increase or likely increase the odds of Asthma Control Questionnaire (ACQ) responders at 6 and 12 months compared to MD-ICS (odds ratio (OR) 1.47, 95% CrI 1.23 to 1.76; high certainty; and OR 1.59, 95% CrI 1.31 to 1.94; high certainty at 6 months; and OR 1.61, 95% CrI 1.22 to 2.13; moderate certainty and OR 1.55, 95% CrI 1.20 to 2.00; high certainty at 12 months, respectively). MD-ICS/LAMA probably increases the odds of ACQ responders at 6 months (OR 1.32, 95% CrI 1.11 to 1.57; moderate certainty). No data were available at 12 months. There is no clear evidence to suggest that HD-ICS increases the odds of ACQ responders or improves the symptom or qualify of life score compared to MD-ICS (very low to high certainty). There is no evidence to suggest that ICS/LABA or ICS/LAMA reduces asthma-related or all-cause serious adverse events (SAEs) compared to MD-ICS (very low to high certainty). HD-ICS results in or likely results in little or no difference in the included safety outcomes compared to MD-ICS as well as HD-ICS/LABA compared to MD-ICS/LABA. The pairwise meta-analysis shows that MD-ICS/LAMA likely reduces all-cause adverse events (AEs) and results in a slight reduction in treatment discontinuation due to AEs compared to MD-ICS (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.77 to 0.96; 4 studies, 2238 participants; moderate certainty; and RR 0.51, 95% CI 0.26 to 0.99; 4 studies, 2239 participants; absolute risk reduction 10 fewer per 1000 participants; moderate certainty, respectively). The NMA evidence is in agreement with the pairwise evidence on treatment discontinuation due to AEs, but very uncertain on all-cause AEs, due to imprecision and heterogeneity. The review findings suggest that MD- or HD-ICS/LABA and MD-ICS/LAMA reduce moderate to severe asthma exacerbations and increase the odds of ACQ responders compared to MD-ICS whereas HD-ICS probably does not. The evidence is generally stronger for MD- and HD-ICS/LABA than for MD-ICS/LAMA primarily due to a larger evidence base. There is no evidence to suggest that ICS/LABA, ICS/LAMA, or HD-ICS/LABA reduces severe asthma exacerbations or SAEs compared to MD-ICS. MD-ICS/LAMA likely reduces all-cause AEs and results in a slight reduction in treatment discontinuation due to AEs compared to MD-ICS. The above findings may assist in deciding on a treatment option during the stepwise approach of asthma management. Longer-term safety of higher than medium-dose ICS needs to be addressed in phase 4 or observational studies given that the median duration of included studies was six months.

Risk of Fracture and Osteoporosis in Patients With COPD and Inhaled Corticosteroids Treatment.

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. 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. 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. ICS use did not increase the incidence of fracture or osteoporosis in subjects with COPD.

Regular Inhaled Corticosteroids Use May Protect Against Severe COVID-19 Outcome in COPD.

Population-based studies provide conflicting evidence about how inhaled corticosteroids (ICS) impact COVID-19 outcomes among COPD patients. We investigated whether regular ICS exposure affects risk, severity, or survival in SARS-CoV-2 infection, using a nationwide linked Swedish population register database. During January-December 2020, we studied two defined Swedish adult populations - Whole population [≥40 years] (N = 5243479), and COPD subpopulation [≥40 years] (N = 133372), in three study cohorts, respectively: 1. Overall cohort (index date 1 Jan 2020), 2. COVID-19 diagnosed sub-cohort (index date = diagnosis date), and 3. COVID-19 hospitalized sub-cohort (index date = admission date). Regular exposure was defined as ≥3 ICS prescriptions in the year before index. Hazard ratios (HRs) for outcomes (COVID-19 onset, hospitalization, ICU admission, or death) related to ICS exposure were estimated using Cox regression. Confounding was controlled by propensity score methods applying Average Treatment effect in the Treated (ATT) weighting. Regular ICS use was associated with only very slightly increased onset of COVID-19, hospitalization, ICU admission, and death in the overall whole population cohort and in the overall COPD subpopulation cohort, except for ICU admission (marginally non-significant HRs, up to 1.13); and no clear increase in the diagnosed sub-cohorts. However, in the COVID-19 hospitalized COPD sub-cohort, ICS therapy showed reduced risks against progression to ICU admission and death, significant for death (HR 0.82 95% CI [0.67-0.99]). For COPD patients, ICS therapy offers some protection against progression to ICU admission and death among COVID-19 hospitalized patients. Our findings alleviate concerns about increased risks of COVID-19 by ICS treatment and provide evidence supporting the continuation of ICS therapy for COPD patients.

Managing moderate-to-severe paediatric asthma: a scoping review of the efficacy and safety of fluticasone propionate/salmeterol

BackgroundFluticasone propionate/salmeterol xinafoate (FP/SAL) is an inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) combination, indicated for the regular treatment of children (aged >4 years) with asthma that is inadequately controlled...

Effectiveness and safety of bronchodilators and inhaled corticosteroids in the management of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a lung condition marked by restricted lung airflow. It is a globally prevalent condition affecting almost 300 million individuals. COPD is linked to a significant burden of morbidity and mortality thus necessitating early diagnosis and management. Rising COPD treatment options complicate care and necessitate a review of clinical data to guide treatment choices. Corticosteroids and bronchodilators are the mainstay of treatment for COPD due to their safety and efficacy. Compared to inhaled corticosteroids or long-acting β-agonist therapy alone, inhaled corticosteroids plus long-acting β-agonist lower the risk of exacerbations and enhance lung function and health status in patients with COPD. Patients who experience frequent exacerbations despite taking long-acting bronchodilators and those who have evidence of eosinophilic bronchial inflammation, as shown by high blood eosinophil levels and/or a history of asthma or asthma-COPD overlap, may both benefit greatly from inhaled corticosteroids therapy. Although not widespread, inhaled corticosteroid use is linked to an elevated risk of pneumonia and may vary depending on the particular corticosteroid utilized. Recent research on combination therapy of inhaled corticosteroids and long-acting β-agonist has shown significant advantages and supports its widespread use in COPD patients who experience frequent exacerbations however some clinical studies and trials have also demonstrated quite conflicting outcomes to this therefore necessitating the need for further clinical trials to exhibit conclusive results. The purpose of this research is to review the available information about the effectiveness and safety of bronchodilators and inhaled corticosteroids in the management of COPD.

Effect of Long-term Inhaled Corticosteroids on the Hypothalamic-Pituitary-Adrenal Axis in Children with Asthma.

To assess the effect of the long-term use of inhaled corticosteroids (ICS) on the hypothalamic-pituitary-adrenal (HPA) axis. Children (5-18 y) diagnosed with asthma and on ICS therapy for ≥6 mo were included. In the first step, screening with fasting at 8 AM, cortisol level was measured; a value <15 mcg/dl was considered low. Children with low fasting cortisol levels were subjected to adreno-corticotropic hormone (ACTH) stimulation test in the second step. Post-ACTH stimulation, cortisol level <18 mcg/dl was considered to have HPA axis suppression. A total of 78 children (males 55, 70.5%) diagnosed with asthma, with a median age of 11.5 (8, 14) y, were enrolled. The median duration of ICS use was 12 (12-24) mo. The median value of post-ACTH stimulation cortisol level was 22.5 (20.6, 25.5) mcg/dl, and a value <18 mcg/dl was observed in 4 (5.1%; 95% CI 0.2-10%) children. There was statistically no significant correlation between low post-ACTH stimulation cortisol level with ICS dose (p = 0.23) and asthma control (p = 0.67). None of the children had clinical features of adrenal insufficiency. In this study, a few children had low post-ACTH stimulation cortisol values; however, none had clinical evidence of HPA axis suppression. Therefore, ICS is a safe drug in children for treating asthma, even for long-term use.

Controller therapy attenuates asthma exacerbations associated with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children

Controller therapy attenuates asthma exacerbations associated with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children

Impact of Post-Visit Outreach on Inhaled Corticosteroid Refill Persistence in Children and Young Adults With Asthma.

Inhaled corticosteroids (ICSs) are a fundamental pillar of most regimens for long-term control of persistent asthma. Poor adherence to ICS medication is a common problem in the asthma population that can lead to poor asthma control. We hypothesized that conducting a follow-up telephone call after general pediatric clinic visits for asthma would improve refill persistence. We conducted a prospective cohort analysis of pediatric and young adult subjects followed in our pediatric primary care clinic for asthma on ICS medication found to have poor ICS refill persistence. This cohort received a follow-up telephone outreach call 5-8 weeks after the clinic visit. The primary outcome measure was refill persistence with regard to ICS therapy. There were 289 subjects who met the inclusion criteria and did not meet any exclusion criteria for the study (n = 131 in the primary cohort, n = 158 in the post-COVID cohort). The mean ICS refill persistence increased significantly for subjects in the primary cohort (39.4 ± 30.8% post intervention vs 32.4 ± 19.7% pre intervention) (P = .02) but not in the post-COVID cohort (36.4 ± 25.6% post intervention vs 38.9 ± 21.0% pre intervention) (P = .26). There was not a statistically significant change in hospitalizations after the intervention in either the primary or the post-COVID cohorts (P = .08 and .07, respectively). Systemic corticosteroid courses and emergency department visits decreased significantly post intervention (P = .01 and P = .004, respectively) in the primary group but not in the post-COVID group (P = .75 and P = .16, respectively). These results suggest that telephone outreach after out-patient clinic visits for asthma may have short-term benefit in ICS refill persistence; however, the effect size was small.

Based on what parameters is safe to discontinuate inhaled corticosteroids in children with asthma?

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.

COPD - what has changed in GOLD 2023 and is relevant for clinical practice?

The annual report of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) is one of the most relevant documents covering prevention, diagnosis and treatment of chronic obstructive pulmonary disease (COPD). The 2023 edition contains a number of changes with impact on clinical practice. For assessment and categorization, a new patient group termed E based on individual exacerbation history has been introduced. The basis of pharmacological management for most patients is the use of combinations containing a long acting β2-agonist (LABA) and a long-acting anticholinergic (LAMA). Combinations of LABA and inhaled corticosteroids (ICS) are no longer recommended. When there is an indication for ICS therapy, a combination of LABA, LAMA and ICS should be used. For these triple combinations, a significant reduction of mortality could be demonstrated in selected patient populations. GOLD proposes a new definition and assessment of COPD exacerbations focussing on objectively assessible parameters and relevant differential diagnoses.

The Impact of Inhaled Corticosteroids on the Prognosis of Chronic Obstructive Pulmonary Disease.

A comprehensive analysis of the effects of inhaled corticosteroids (ICS) on COPD in a real-world setting is required due to safety concerns regarding ICS in COPD. This study aimed to explore the impact of ICS on the prognosis of Asian COPD patients in the real-life world. We examined 978 COPD patients registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database and with their data linked to Health Insurance and Review Assessment (HIRA) data. The outcome measures were ascertained by HIRA from January 1, 2009, to December 31, 2012. This study enrolled two arms; ICS users (N = 85, mean age = 66.7 ± 8.9 years) and non-ICS users (N = 893, mean age = 63.7 ± 9.7 years). Compared to the non-ICS users, the ICS users had a higher rate of pneumonia, tuberculosis, and acute exacerbations (P<0.05). Hospitalization due to respiratory causes was also higher among ICS users (P<0.05). Multivariate analysis showed that acute exacerbation was independently associated with the development of pneumonia (P<0.05), whereas ICS therapy had a tendency to be associated with pneumonia. Another multivariate analysis demonstrated that old age, FEV1, ICS therapy, and pneumonia were independently associated with the occurrence of acute exacerbation (P<0.05). The concomitant pneumonia (HR = 3.353, P = 0.004) was independently associated with higher mortality (P<0.05). Our data demonstrated that the ICS users had a higher rate of pneumonia and tuberculosis and the concomitant pneumonia was independently associated with higher mortality, highlighting the importance of cautious and targeted administration of ICS in COPD.

Risk of Pneumonia with Inhaled Corticosteroid/ Long-Acting β2 Agonist Therapy in Chronic Obstructive Pulmonary Disease

Aim: To determine the pneumonia risk in COPD patients, which treatment is more effective to prevent patients to develop more complex situation. Method: This randomized study design was conducted from September 2022 to December 2022 and approval by the ethical committee of the Hospital was obtained. All the participants were 45 to 65 years old. Patients were receiving a combination of medicine whereas the first group had 51 patients receiving low-dose fluticasone propionate 250 µg and salmeterol 50 µg twice in a day. The second group was receiving high-dose treatment of fluticasone propionate 500 µg and salmeterol 100 µg twice a day. Clinical follow-up proceeded for complete assessment and for safety measures. It also includes vital sign measurements such as heart rate, pneumonia, bone fracture, and hematological measurement. In the case of suspected pneumonia, moderate to severe exacerbation event chest radiography was performed. For statistical analysis two software are used one is statistics 8.1 and the other is Pad prism version 5. One Way ANOVA is applied. Results: A total 110 number of patients aged 45-65 were recruited for this study. From the total of 110, eight persons are excluded due to cystic fibrosis, pulmonary fibrosis, and bronchiectasis. 102 patients are part of this study out of which 33(32.35%) were females and 70(67.64%) were males. Patients with smoking history were 40(39.21%), history of moderate and severe exacerbations were 20(19.60%) and 8(7.84%). Patients of group one who were receiving low doses of fluticasone propionate 250µg and salmeterol 50µg shows improvement in the patient condition and at the eight week of treatment dose the results are, moderate exacerbation was found in 12(23.52%) patients with 95% Cl=1.89-2.30, severe exacerbation in 6(11.76%) with 95% confidence intervals, and pneumonia in 6(11.76%) with 95% Cl=1.71-1.67.Group two follow-up also shows improvement in patients’ health status but it also increases the chances of pneumonia development. At eight week moderate exacerbation was found in 7(13.72%) patients with 95% Cl=3.00-0.34, severe exacerbation in 4(7.84%) with 95% confidence intervals 3.06-0.56, and pneumonia in 9(17.64%) with 95% Cl= 3.08-0.66. All the factor's p-value was statistically significant. As the number of pneumonia, patients was higher in group two patients as compared to group one. Practical implication: Pneumonia is more likely to occur in patients with chronic obstructive pulmonary disease (COPD). The frequency of acute episodes of symptom exacerbation is decreased by inhaled corticosteroids. Low dose therapy is more effective than the high doses effective in patients. This research article helps to aware the society about the risk factors and their treatment. Conclusion: we concluded that COPD patients are more vulnerable to developing pneumonia even if we used the ICS therapy in combination with long-acting β2 agonist therapy. Low dose therapy is more effective than the high doses effective in our study Keywords: chronic obstructive pulmonary disease COPD, Inhaled corticosteroids (ICS), Long-acting bronchodilators