Inhaled Corticosteroids Research Articles

Budesonide/Formoterol Turbuhaler vs pMDI Salbutamol for Acute Asthma in Outpatient Emergency Department: A Prospective, Randomized, Open-Label Study

Background The Global Initiative for Asthma (GINA) has suggested the need for more studies on inhaled corticosteroid (ICS)-formoterol in the Emergency Department (ED). Objectives We aimed to compare the outcomes of budesonide/formoterol (160/4.5 mcg/inhalation) turbuhaler versus pressurized metered-dose inhaler (pMDI) salbutamol (100mcg/puff) in acute asthma in the outpatient ED. Methods This single-centre, prospective, randomized, and open-label study involved adult asthma patients with mild to moderate asthma exacerbation who attended the outpatient ED of a tertiary hospital in Malaysia. The intervention arm received budesonide/formoterol (Symbicort® 160/4.5mcg) turbuhaler, while the control arm received pMDI salbutamol with a valved holding chamber. Stratified randomization with variable baseline ICS use was employed. Direct discharge rate from outpatient ED was the primary outcome. Vital signs pre- and post-treatment between the two arms were also compared. Results Seventy-four (n = 37 for each arm) asthma patients were recruited. Baseline clinical characteristics were comparable between the two arms. Direct discharge rates from ED were comparable between the intervention (94.6%) and the control (91.9%) arms (p = 1.000). Post-treatment outcomes (respiratory rate, oxygen saturation, peak expiratory flow rate) were similar between the two arms, except for the higher increment of heart rate (p < 0.001) and lesser reduction of blood pressure in the control arm (p = 0.013). Intravenous hydrocortisone use was significantly higher in the control arm (n = 19, 51.4%) than in the budesonide/formoterol arm (n = 6, 16.2%) (p = 0.001). Conclusion Budesonide/formoterol turbuhaler is as effective as pMDI salbutamol in treating asthma exacerbation in the outpatient ED with less effect on heart rate and lower usage of intravenous corticosteroids.

Unmet needs in patients with COPD in Germany: a retrospective, cross-sectional study

BackgroundEarlier diagnosis and treatment of chronic obstructive pulmonary disease (COPD), particularly preventing exacerbations, are key to slowing disease progression and reducing mortality. This study focused on the identification of patients in Germany with unstable COPD due to suboptimal treatments.MethodsThe IQVIA™ LRx database, capturing 80% of Statutory Health Insurance prescriptions was used to identify patients with COPD using a machine learning (ML) model. Patients with unstable COPD were identified through high prescriptions of oral corticosteroid (OCS) and/or rescue inhalers during the period from April 2022 to March 2023.ResultsThe ML model identified around 2.6 million treated patients with COPD, with 77% precision. The mean age was 71 years, 48% were female and 86% were aged ≥60 years. About 14% patients (n=363k) exhibited unstable COPD due to high OCS prescriptions, while 10% patients (n=256k) had high rescue inhaler prescriptions. Among those with high OCS and high rescue inhaler prescriptions, respectively, 43% and 38% were on dual therapy, 17% and 21% were on single inhaler triple therapy, 14% and 16% were on multiple inhaler triple therapy, 11% and 9% were on monotherapy and 15% and 17% had no maintenance therapy.ConclusionsA substantial portion of unstable COPD patients were either on suboptimal maintenance therapy (monotherapy or inhaled corticosteroid-based dual therapy) or not receiving any maintenance therapy. The study highlights a substantial need in Germany for improved maintenance therapy, which could reduce disease burden, improve disease stability and reduce reliance on OCS and rescue therapies, thereby minimising side effects.

Inhalation corticosteroids for COVID-19 - a real world data analysis on guideline adherence.

The recommendation to consider prescribing inhalation corticosteroids to a subgroup of vulnerable COVID-19 patients was added to the Dutch medical guideline on November 11, 2021, and was also adopted by other countries during the pandemic. To evaluate the adherence of general practitioners to this guideline, and whether real-world data quality is sufficient to study the effect of revised guidelines on prescribing behaviour. A retrospective cohort study using Dutch primary care data from the Extramural LUMC Academic Network database, containing patient data of 129 general practices in the Leiden - The Hague area. We performed an interrupted time series analysis to measure the effect of the new guideline on the prescription rate of ICS, accounting for general trend and seasonal fluctuations. Between July 1, 2020 to August 1, 2022, 131,482 patients had 164,098 COVID-19 consultations. During this period, 1,709 patients received 2094 ICS prescriptions for COVID-19. After the guideline update, there was an instantaneous decrease in prescription rate (IRR 0.47, 95% CI 0.32-0.69). Prescription rate in the subgroup of vulnerable patients did not change significantly (IRR 0.93, 95% CI 0.66-1.32), while less vulnerable patients were significantly prescribed less (IRR 0.29, 95% CI 0.14-0.59). The revision to COVID-19 guidelines had significant impact on general practitioners' prescription behaviour soon after publication: prescription rate remained constant for vulnerable patients, while less vulnerable patient were significantly prescribed less often. Using electronic health records it is feasible to assess changes in guideline adherence using interrupted time series.

Electronic health record data analysis on the impact of rescue-triggered inhaled corticosteroids on controller therapy in Black and Latinx individuals from a pragmatic, open-label, patient-level randomised trial

ObjectiveThe Person Empowered Asthma Relief (PREPARE) study found that as-needed inhaled corticosteroid (ICS) supplementation combined with participants’ usual controller and rescue therapy reduced asthma exacerbations for Black and Hispanic/Latinx individuals....

Neuropsychiatric diagnoses after montelukast initiation in paediatric patients with asthma

BackgroundThe evidence base on montelukast-associated adverse outcomes is inconclusive in children and young persons (CYP) with asthma. We aimed to investigate 1-year incidence of neuropsychiatric diagnoses after initiation of montelukast...

Factors associated with poor asthma control in children: A prediction model.

Inhaled corticosteroids (ICS) are the first-line therapy for pediatric asthma. However, very few studies have developed simple tools for predicting treatment outcomes in pediatric asthma. This study aimed to construct a predictive model for poor asthma control in children after 6 months of ICS therapy. This retrospective study included children with asthma, aged 6-15 years, who received ICS with complete follow-up for 6 months. The potential factors associated with poor asthma control were also assessed. Poor control was considered if the child had partial or uncontrolled symptoms according to the Global Initiative for Asthma guidelines. Among the 165 eligible children, 33 (20%) had poor symptom control. The factors associated with poor control were a history of more than four exacerbations in the 12 months before ICS treatment (odds ratio [OR], 3.39 [1.06, 10.83]), the presence of moderate to severe allergic rhinitis symptoms at the 6-month follow-up visit (OR, 21.93 [2.97, 162.05]), and poor adherence to asthma medications (OR, 4.16 [1.32, 13.12]). By incorporating these factors, a model for predicting poorly controlled asthma was constructed and converted into a nomogram with a total score of 200, with prediction risk ranging from 0 to 100%. The area under the receiver operating characteristic curve of the developed model was 0.737, indicating a moderate performance level. We developed a predictive tool for poor asthma control. The model has a good discriminatory ability and is simple to use, which could facilitate the individualized management of children with asthma.

PDE4 Inhibitors and their Potential Combinations for the Treatment of Chronic Obstructive Pulmonary Disease: A Narrative Review

Chronic Obstructive Pulmonary Disease (COPD) is associated with cough, sputum production, and a reduction in lung function, quality of life, and life expectancy. Currently, bronchodilator combinations (β2-agonists and muscarinic receptor antagonists, dual therapy) and bronchodilators combined with inhaled corticosteroids (ICS), triple therapy, are the mainstays for the management of COPD. However, the use of ICS in triple therapy has been shown to increase the risk of pneumonia in some patients. These findings have laid the foundation for developing new therapies that possess both anti-inflammatory and/or bronchodilation properties. Phosphodiesterase-4 (PDE4) inhibitors have been reported as an effective therapeutic strategy for inflammatory conditions, such as asthma and COPD, but their use is limited because of class-related side effects. Efforts have been made to mitigate these side effects by targeting the PDE4B subtype of PDE4, which plays a pivotal role in the anti-inflammatory effects. Unfortunately, no selective oral PDE4B inhibitors have progressed to clinical trials. This has led to the development of inhaled PDE4 inhibitors to minimize systemic exposure and maximize the therapeutic effect. Another approach, the bronchodilation property of PDE3 inhibitors, is combined with anti-inflammatory PDE4 inhibitors to develop dual inhaled PDE4/PDE3 inhibitors. A few of these dual inhibitors have shown positive effects and are in phase 3 studies. The current review provides an overview of various PDE4 inhibitors in the treatment of COPD. The possibility of studying different selective PDE4 inhibitors and dual PDE3/4 inhibitors in combination with currently available treatments as a way forward to increase their therapeutic effectiveness is also emphasized.

A Retrospective Study Evaluating Asthma Control in Patients on Fluticasone Propionate/Salmeterol Proactive Regular Dosing with a History of Uncontrolled Asthma.

The MERIT study in Malaysia is a real-world retrospective, observational, multicenter study that evaluated asthma control in patients with uncontrolled asthma who were switched from as-needed (pro re nata [PRN]) budesonide/formoterol or inhaled corticosteroid (ICS) whenever a short-acting beta-agonist (SABA) was taken, to proactive regular dosing of fluticasone propionate/salmeterol (FP/SAL PRD). Data from the medical records of patients who were stepped up to FP/SAL PRD were extracted retrospectively at baseline and follow-up (between 3 and 6months after stepping up to FP/SAL PRD). The primary endpoint was the percentage of patients with improvement in asthma control assessed via the Asthma Control Test (ACT). Secondary endpoints included safety and the percentage of patients with moderate and severe exacerbations. Additionally, patient-reported use of reliever medication, systemic corticosteroids, emergency department visits, or hospitalization was also analyzed. One hundred twenty patients with uncontrolled asthma who were stepped up to FP/SAL PRD were enrolled in the study. Of these, 76 (63.3%) patients were on prior budesonide/formoterol PRN, and 44 (36.7%) were on prior ICS with SABA PRN treatment. After stepping up to FP/SAL PRD with a mean follow-up of 5.8months, 110 (91.7%) patients achieved asthma control at the follow-up visit (p < 0.001). Similar improvements were observed regardless of prior PRN regimen. A statistically significant improvement was observed in the mean ACT score at the follow-up visit (p < 0.0001). The proportion of patients with moderate and severe exacerbations was also reduced after stepping up to FP/SAL PRD, with no adverse events reported. Over 80% of patients reported a decrease in the use of systemic corticosteroids, visits to the emergency department, or hospitalization. This study highlights the effectiveness of the FP/SAL PRD treatment approach in patients with uncontrolled asthma on a PRN treatment regimen.

Asthma prescribing trends, inhaler adherence and outcomes: a Real-World Data analysis of a multi-ethnic Asian Asthma population

Inhaled corticosteroid (ICS) is the mainstay therapy for asthma, but general adherence is low. There is a paucity of real-world inhaler prescribing and adherence data from Asia and at the population level. To address these gaps, we performed a real-world data analysis of inhaler prescribing pattern and adherence in a multi-ethnic Asian asthma cohort and evaluated the association with asthma outcomes. We performed a retrospective analysis of adult asthma patients (aged ≥18 years) treated in the primary and specialist care settings in Singapore between 2015 to 2019. Medication adherence was measured using the medication possession ratio (MPR), and categorised into good adherence (MPR 0.75-1.2), poor adherence (MPR 0.75) or medication oversupply (MPR > 1.2). All statistical analyses were performed using R Studio. 8023 patients, mean age 57 years, were evaluated between 2015 and 2019. Most patients were receiving primary care (70.4%) and on GINA step 1–3 therapies (78.2%). ICS-long-acting beta-2 agonist (ICS-LABA) users increased over the years especially in the primary care, from 33% to 52%. Correspondingly, inpatient admission and ED visit rates decreased over the years. Between 2015 and 2019, the proportion of patients with poor adherence decreased from 12.8% to 10.5% (for ICS) and from 30.0% to 26.8% (for ICS-LABA) respectively. Factors associated with poor adherence included minority ethnic groups (Odds ratio of MPR 0.75–1.2: 0.73–0.93; compared to Chinese), presence of COPD (OR 0.75, 95% CI 0.59–0.96) and GINA step 4 treatment ladder (OR 0.71, 95% CI 0.61–0.85). Factors associated with good adherence were male gender (OR 1.14, 95% CI 1.01–1.28), single site of care (OR 1.22 for primary care and OR 1.76 for specialist care), GINA step 2 treatment ladder (OR 1.28, 95% CI 1.08–1.50). Good adherence was also associated with less frequent inpatient admission (OR 0.91, 95% CI 0.84–0.98), greater SABA overdispensing (OR 1.66, 95% CI 1.47–1.87) and oral corticosteroids use (OR 1.10, 95% CI 1.05–1.14). Inhaled corticosteroid (ICS) adherence has improved generally, however, poor adherence was observed for patients receiving asthma care in both primary and specialist care, and those from the minority ethnicities.

Association of moderate-to-vigorous physical activity with reduction of acute exacerbation in COPD patients using a dual ultra-long-acting bronchodilators

Inhaler therapy and physical activity (PA) are important methods of chronic obstructive pulmonary disease (COPD) management. This study aimed to investigate the additional benefit of moderate-to-vigorous PA (MVPA) in patients with COPD using a long-acting beta-agonists (LABA)/long-acting muscarinic antagonist (LAMA) combination. We emulated a target trial to estimate the benefit of MVPA in patients with COPD using a dual ultra-long-acting bronchodilators. We enrolled patients aged ≥ 40 who were diagnosed with COPD between 2014 and 2018, initiated a LABA/LAMA combination, and had not undergone regular MVPA. The main exposure was the initiation of MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days/week or moderate aerobic exercise > 30 min per day on ≥ 5 days/week. The main outcomes were the future usage of inhaled corticosteroids (ICS) and severe exacerbation. We identified 1,526 patients who initiated MVPA and 4,516 who did not. The median follow-up period was 3.0 years. The hazard ratio (HR) for future ICS usage in the MVPA initiation group was 0.83 (95% confidence intervals (CI): 0.72, 0.97) compared to the control group. The HR for severe exacerbation in the MVPA initiation group was 0.81 (95% CI: 0.68, 0.96) compared to the control group. Subgroup analyses by age, sex, body mass index, residence area, smoking and drinking status showed consistent benefits in these outcomes. Initiation of MVPA may offer an additional benefit for even COPD patients who use a dual ultra-long-acting bronchodilators.

Outpatient inhaled corticosteroid use in bronchopulmonary dysplasia.

In the outpatient setting, inhaled corticosteroids (ICS) are frequently given to children with bronchopulmonary dysplasia (BPD) for treatment of respiratory and asthma-associated symptoms. In this study we sought to determine if correlations existed between ICS use and ICS initiation and patient characteristics and outpatient respiratory outcomes. This study included children with the diagnosis of BPD (n = 661) who were seen in outpatient pulmonary clinics at the Children's Hospital of Philadelphia between 2016 and 2021. Chart review was used to determine patient demographics, use and timing of ICS initiation, asthma diagnosis, and acute care usage following initial hospital discharge. At the first pulmonary visit, 9.2% of children had been prescribed an ICS at NICU discharge, 13.9% had been prescribed an ICS after NICU discharge but before their first pulmonary appointment, and 6.9% were prescribed an ICS at the completion of initial pulmonary visit. Children started on an ICS as outpatientshad a higher likelihood of ER visits (adjusted odds ratio: 2.68 ± 0.7), hospitalizations (4.81 ± 1.16), and a diagnosis of asthma (3.58 ± 0.84), compared to children never on an ICS. Of those diagnosed with asthma, children prescribed an ICS in the outpatient setting received the diagnosis at an earlier age. No associations between NICU BPD severity scores and ICS use were found. This study identifies an outpatient BPD phenotype associated with ICS use and ICS initiation independent of NICU severity score. Additionally, outpatient ICS initiation correlates with a subsequent diagnosis of asthma and acute care usage in children with BPD.

Considering different Montreal Cognitive Assessment cutoff scores for older adults with asthma.

Background: There is a greater prevalence of cognitive impairment among ethnic and/or racial minorities, and cognitive impairment is a barrier to asthma self-management (SM) behaviors and outcomes in older adults. Objective: The aim of this study was to examine the relationship between cognitive impairment, assessed by using the Montreal Cognitive Assessment (MoCA), and asthma SM behaviors and outcomes in a sample of predominantly Black and Latino participants. In addition, we evaluated whether using two different MoCA cutoff scores influenced the association between cognitive impairment and asthma outcomes. Methods: Baseline cross-sectional data were extracted from a longitudinal study of older adults with asthma (N = 165) ages ≥60 years. Cognition was assessed by using the MoCA. Asthma Control Questionnaire, asthma-related quality of life (AQOL), and inhaled corticosteroid (ICS) adherence were assessed by using self-report. ICS dosing was collected through chart review and inhaler technique was observed and rated. Results: Using established MoCA cutoff scores of 23 and 26 yielded 45% and 74% cognitive impairment rates, respectively. Cognitive impairment, defined by using the cutoff score of 23, was significantly associated with worse asthma control (p = 0.04) and worse ICS adherence (p = 0.01). With a cutoff score of 26, only AQOL was significantly associated with cognitive impairment (p = 0.03). Race and/or ethnicity moderated the relationship between cognitive impairment and asthma control with a MoCA cutoff score of 23, and between cognitive impairment and AQOL with a MoCA cutoff score of 26. Conclusion: Cognitive impairment in older adults with asthma is associated with important clinical outcomes, but this relationship is influenced by the cutoff score used to define cognitive impairment.

Modification of asthma treatment efficacy by healthcare access: A reanalysis of AsthmaNet Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) clinical trial

BackgroundWhile randomized controlled trials (RCTs) in asthma management are designed to balance known and unknown variables across treatment groups, including social and environmental co-exposures, it remains important to consider how these co-exposures influence disease progression and treatment outcomes. The importance of considering socio-environmental co-exposures in the context of asthma is twofold: 1) asthma disproportionately affects low-income urban communities, where air pollution and chronic stress are pervasive; and 2) despite the wide range of asthma treatments, inadequate disease control persists. MethodsIn the present ancillary study of the Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) RCT, we investigated how socio-environmental factors, such as air pollution exposure and healthcare access, modify the effect of inhaled corticosteroid (ICS) therapy in children with asthma. The original STICS RCT evaluated the efficacy and safety of increasing the dose of inhaled glucocorticoids from a baseline daily low dose to five times the daily dose for 7 days in school-age children with mild -to-moderate persistent asthma who began to have short-term loss of asthma control (Jackson et al., 2018 Mar 8) [1]. Our study adds onto those findings by incorporating residential level particulate matter 2.5 μg/m3 (PM2.5) and geographic health provider shortage areas (HPSA) as potential modifiers. ResultsConsistent with the main trial results, we did not find a difference in the number of exacerbations between treatment arms. However, we found the effect of receiving 5xICS, as compared with 1xICS on the time to prednisone was significantly different for children living in areas a shortage of health professionals (HR: 2.09; 95 % CI: 0.74, 5.95) than for children living in no shortage areas (HR: 0.40; 95 % CI: 0.21, 0.77). ConclusionThis finding underscores the importance of considering environmental and social factors in asthma treatment. Trial registrationClinicalTrials.gov ID NCT02066129 https://clinicaltrials.gov/study/NCT02066129.

Triple inhaled therapy in asthma: Beliefs, behaviours and doubts

Long-acting muscarinic antagonists (LAMA) in association with inhaled corticosteroids (ICS) plus long-acting beta-2 agonists (LABA) are recommended by the GINA report as further option in step 4 and first choice in step 5 treatment. Despite consistent evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not largely used in patients with asthma.With the aim to explore belief and behaviours of asthma specialists, an ad hoc survey has been developed by a panel of Interasma Scientific Network (INESnet) experts and subsequently defined by two Delphi rounds among an international group of physicians. The questionnaire has been distributed through Interasma social media between June and September 2023.Besides a descriptive analysis, to assess the responses gathered from the questionnaire, Spearman's non-parametric statistical method was employed.Totally, three hundred fourteen questionnaires were completed. Clinicians' attitudes and behaviours toward timing and methodologies adopted in prescribing ITT, were analysed. 35.7 % specialists consider ITT as a relevant therapeutic option, 61.8 % that is second option after reaching high dose of ICS-LABA and 89.2 % agreed that optimization of inhaled therapy should be attempted before the use of biological drugs. Persistent flow limitation and high reversibility are considered predictive factors of response.Specialists consider ITT a resource in asthma management. Although its efficacy in decreasing exacerbation rate and improving lung function were well known, the survey revealed persistent uncertainties among clinicians in positioning it highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice.

Anti-inflammatory effects of tiotropium in copd: a randomized double-blind trial

IntroductionChronic Obstructive Pulmonary Disease (COPD) is a major global health issue characterized by respiratory symptoms and exacerbations, significantly impacting mortality and quality of life. Muscarinic antagonists are known to prevent exacerbations, possibly by mitigating airway inflammation. This study evaluated the anti-inflammatory effects of tiotropium in patients with COPD by examining inflammatory protein profiles in sputum and blood, and genome-wide expression in sputum.MethodsWe conducted the prospective, double-blind, randomized-controlled ANTIOFLAM trial. Patients with COPD GOLD II and worse, aged≥40 years and with≥10 smoking pack years were included. After a 4-week wash-out period of inhaled corticosteroids (ICS) and anticholinergics, participants were randomized to 6 weeks of treatment with placebo or tiotropium (soft mist inhaler, 5 µg daily). Our primary endpoint was a decrease of sputum interleukin-6 and interleukin-8 levels in the tiotropium group when compared to the placebo group.ResultsWe evaluated samples of 33 participants (n=17 placebo and n=16 tiotropium). Changes in sputum proteins interleukin-6 and interleukin-8 were significantly higher after treatment with tiotropium when compared to placebo (p&lt;0.05). Differential expression analysis did not reveal gene expression differences including interleukin-6 and −8.ConclusionWe did not find tiotropium to have anti-inflammatory effects in sputum or blood of patients with COPD. In contrast, we found 6 weeks of treatment with tiotropium to increase the concentration of almost all tested sputum inflammatory proteins when compared to placebo, while RNA expression levels did not change.

Inhaled Reliever Therapies for Asthma

The optimal inhaled reliever therapy for asthma remains unclear. To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma. The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], -10.3% [95% CI, -11.8% to -8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, -4.7% [95% CI, -8.0% to -1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, -5.5% [95% CI, -8.4% to -2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, -0.6% [95% CI, -1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, -1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

Detection of chronic obstructive pulmonary disease and frequency of cardiopulmonary events in patients with a significant smoking history hospitalised for acute myocardial infarction

Abstract Background Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and also myocardial infarction (MI). Patients with COPD are more likely to have MI than those without and adequately treating COPD might improve cardiovascular outcomes. Reliable diagnosis is important for appropriate treatment. Prevalence of COPD in those hospitalised for MI has not been accurately established. Blood eosinophil count is an important guide to the benefit of inhaled corticosteroid (ICS) treatment in COPD. We aimed to accurately characterise lung function, symptom burden, eosinophil count and cardiopulmonary events in those with a significant smoking history hospitalised for acute MI. Methods Participants (n=216) with a smoking history of ≥10 pack-years currently hospitalised for acute MI were recruited at a single UK centre. Microspirometry and completion of the COPD Assessment Test (CAT) questionnaire were performed at enrolment. Presence and severity of COPD was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. A high burden of COPD symptoms was defined as a CAT score of &amp;gt;10. Repeat CAT and assessment for relevant cardiopulmonary events was undertaken at 3 months and 1 year after enrolment. Results In the enrolled cohort, median age was 60 years (IQR 53-67), 26% were female, 57% were current smokers and median pack-year history was 32 (23-45). 41 of 216 (19 %, [95% CI 14-25]) had evidence of COPD, defined as FEV1/FEV6 &amp;lt;0.7 on best-attempt microspirometry, with 39 (95%) being GOLD2 or greater. Of the 41 with detected COPD, only 15 (37%, [22-53]) had a prior diagnosis. In those with evidence of COPD, a high burden of COPD symptoms was present in 63% of participants at enrolment, 40% at 3 months and 45% at 1 year. 20% [9-35] were receiving inhaled corticosteroids at enrolment. 63% [47-78] had eosinophil count ≥100 cells/mm3 and 17% [7-32] ≥300 cells/mm3. Among those with detected COPD, after 1 year 19.5% (95% CI 9-35%) had suffered a respiratory illness requiring prescription of medication, which was numerically but not statistically significantly higher than those without detected COPD (14.3% [10-20%]). In the COPD cohort, death, infection requiring hospitalisation, MI or unplanned coronary revascularisation, and bleeding requiring hospitalisation each occurred on two occasions (4.9%). Conclusions Based on these data, the prevalence of microspirometry-diagnosed COPD of any severity in patients with significant smoking history hospitalised for MI is around 19%. There is a high rate of undiagnosed and untreated disease, a significant burden of symptoms, including during convalescence, and around a 20% incidence of respiratory illness requiring medical treatment at 1 year. Gathering accurate data from this group is helpful in planning research and service improvement. Increasing detection of COPD in patients with MI would lead to improved cardiopulmonary outcomes.

Comparative Study of Inhaled Corticosteroids and Leukotriene Receptor Antagonists As Controller Options for Mildly to Moderately Persistent, Stable Asthma.

Asthma is a chronic inflammatory disease of the airways characterized by bronchoconstriction, airway hyperresponsiveness, and variable airflow limitation. This results in symptoms such as wheezing, difficulty breathing, chest tightness, chest pain, and coughing. The primary objective of the study is to compare the efficacy of inhaled corticosteroids (ICS) versus leukotriene receptor antagonists (LTRA) in improving asthma control, lung function, and quality of life in patients with mild to moderate persistent asthma. This prospective comparative study was conducted at Khyber Teaching Hospital and Dow University Hospital from January 2018 to July 2021. 210 patients suffering from asthma were included in the study. Patients aged 18 years and older, diagnosed with mild to moderate persistent asthma as per Global Initiative for Asthma (GINA) guidelines, and requiring pharmacological intervention were included in the study. Participants were randomly allocated into two groups.Treatment efficacy was compared based on asthma control (Asthma Control Test (ACT) score), lung function (forced expiratory volume in one second (FEV1),peak expiratory flow rate (PEFR)), and quality of life using validated questionnaires. In this study involving 210 patients with asthma, Group A (ICS) had a mean age of 36.23 ± 7.09 years, while Group B (LTRA) had a mean age of 35.23 ± 8.01 years. Both groups exhibited similar baseline asthma control, as indicated by ACT scores of 17.2 ± 3.5 for Group A and 16.8 ± 3.2 for Group B. Significant improvements were observed in both groups at the end of the study, with ACT scores rising to 21.8 ± 2.1 (p < 0.001) for Group A and 20.5 ± 2.5 (p < 0.001) for Group B. Additionally, lung function, measured by FEV1 and PEFR, showed similar enhancements; Group A improved from a baseline FEV1 of 2.5 ± 0.8 L to 3.2 ± 0.6 L (p < 0.01), while Group B improved from 2.4 ± 0.7 L to 3.0 ± 0.5 L. The PEFR values also increased significantly from 300 ± 50 L/min to 380 ± 40 L/min (p < 0.001) for Group A and from 290 ± 45 L/min to 360 ± 30 L/min (p < 0.001) for Group B. Both treatments were well-tolerated, with adverse events being low and comparable between the groups. This study reveals that both ICSand LTRAsignificantly improve asthma control, lung function, and quality of life in patients with mild to moderate persistent asthma, with ICS showing superior efficacy. ICS led to greater improvements in ACT scores and lung function parameters, supporting its use as a more effective treatment option in this patient population.

Achieving clinical remission in asthma with mepolizumab: a subanalysis on vitamin D as a predictor of response

Objective Mepolizumab, an anti-IL-5 monoclonal antibody, has shown promise in reducing exacerbations and steroid dependency in severe eosinophilic asthma. This study aims to evaluate the effectiveness of mepolizumab in achieving clinical remission in asthma over 12 months and explore Vitamin D levels as a predictor of response. Method We assessed Asthma Control Questionnaire (ACQ) scores, spirometry, number of exacerbations, oral corticosteroid (OCS) use, and inhaled corticosteroid (ICS) use in 32 patients, observing significant clinical improvements. Data were collected 1 year prior to starting mepolizumab and one year after starting mepolizumab. Nasal polyps were not seen in all the patients, and computed tomography of para-nasal sinuses are not available for all the patients, so nasal polyps status are not evaluated to avoid any bias. Result Our results indicate that 12 patients achieved clinical remission after starting mepolizumab, with a strong correlation between higher Vitamin D levels and positive treatment outcomes. This suggests that optimizing Vitamin D levels could enhance the response to mepolizumab in asthma patients, and help in achieving better asthma control. Conclusion Mepolizumab is an effective treatment for severe eosinophilic asthma, significantly improving clinical outcomes and reducing corticosteroid use. This study highlights the importance of Vitamin D as a predictor of response to mepolizumab, suggesting that higher Vitamin D levels may enhance treatment efficacy.

Triple Therapy De-Escalation and Withdrawal of Inhaled Corticosteroids to Dual Bronchodilator Therapy in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80-1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00-1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy.