Risk Of Exacerbations In Patients Research Articles

Pulmonary outcomes of incretin-based therapies in COPD patients receiving single-inhaler triple therapy

IntroductionPatients with chronic obstructive pulmonary disease (COPD) on triple therapy often face exacerbations and comorbidities. Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) analogs may reduce the risk of exacerbation in patients with COPD and type 2 diabetes mellitus (T2DM). This study investigates the impact of GLP-1 analogs on pulmonary outcomes in patients with COPD on single-inhaler triple therapy (SITT) and T2DM.MethodsWe conducted a retrospective cohort study using the TriNetX database and analysed adult patients with COPD and T2DM who received SITT between April 2005 and July 2023. Patients were categorized into GLP-1 analog and dipeptidyl peptidase-4 inhibitors (DPP4i) cohorts. The primary efficacy outcome was COPD exacerbation and the secondary efficacy outcomes were pneumonia, acute respiratory distress syndrome, intubation, oxygen dependence, and all-cause mortality. The secondary outcomes were serious gastrointestinal adverse events.ResultsWe included 6898 patients, with 4184 receiving GLP-1 analogs and 2714 receiving DPP4i. After matching, 1751 GLP-1 analog users were matched with 1751 DPP4i users. GLP-1 analog users had an 18% lower risk of COPD exacerbation (hazard ratio [HR], 0.82 [95% CI: 0.71–0.94]), a 28% reduced risk of pneumonia (HR, 0.72 [95% CI: 0.61–0.85]), a 34% reduced risk of oxygen dependence (HR, 0.66 [95% CI: 0.47–0.91]), and a 40% decreased risk of all-cause mortality (HR, 0.60 [95% CI: 0.47–0.77]). No significant serious gastrointestinal adverse events were observed.ConclusionGLP-1 analogs may be associated with reduced COPD exacerbations, pulmonary comorbidities, and mortality in patients with COPD receiving SITT and T2DM, with no significant serious gastrointestinal safety concerns.

Validation of the German version of the Asthma Impairment and Risk Questionnaire (AIRQ).

The Asthma Impairment and Risk Questionnaire (AIRQ), a 10-item, equally weighted, yes/no tool assessing symptom impairment and risk of exacerbations in patients with asthma aged ≥12 years, was developed and validated in a US patient population to evaluate varying levels of asthma control. This study aimed to validate the German language version of the AIRQ in patients aged ≥12 years with different levels of asthma control. A cross-sectional, observational, multi-centre study comprising a single visit was conducted in multiple specialised asthma centres and general practices in Germany. A total of 300 patients completed the following measures: 1) Patient Sociodemographic and Clinical Questionnaire, 2) AIRQ, 3) Asthma Control Test (ACT), and 4) Asthma Control Questionnaire (ACQ-6). Logistic regression analyses were conducted to assess the AIRQ score cut points with the greatest predictive validity in discriminating between different control levels relative to a standard of ACT plus prior-year exacerbations or ACQ-6 plus prior-year exacerbations. The German version of the AIRQ demonstrated a robust capability to correctly identify well-controlled versus not well- or very poorly controlled (AUC values of 0.90 or higher) and well- or not well-controlled versus very poorly controlled asthma (AUC values of 0.89 or higher). The German version of the AIRQ is a suitable tool to identify adults with varying levels of asthma control, which in turn can help to accurately identify patients with uncontrolled asthma in clinical practice.

COPD Subtypes Are Differentially Associated With Cardiovascular Events and COPD Exacerbations

The coronary artery calcium score (CACS) and ratio of the pulmonary artery to aorta diameters (PA:A ratio) measured from chest CT scans have been established as predictors of cardiovascular events and COPD exacerbations, respectively. However, little is known about the reciprocal relationship between these predictors and outcomes. Furthermore, the prognostic implications of COPD subtypes on clinical outcomes remain insufficiently characterized. How can these two chest CT scan-derived parameters predict subsequent cardiovascular events and COPD exacerbations in different COPD subtypes? Using COPDGene study data, we assessed prospective cardiovascular disease (CVD) and COPD exacerbation risk in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease spirometric grades 2-4), focusing on CACS and PA:A ratio at study enrollment, with logistic regression models. These outcomes were analyzed in three COPD subtypes: 1,042 patients with non-emphysema-predominant disease (NEPD) (low attenuation area at-950 Hounsfield units [LAA-950]< 5%), 1,324 patients with emphysema-predominant disease (EPD) (LAA-950≥ 10%), and 465 patients with intermediate emphysema disease (5%≤ LAA-950< 10%). Our study indicated significantly higher overall risk for cardiovascular events in patients with higher CACS (≥ median; OR, 1.61; 95%CI, 1.30-2.00) and increased COPD exacerbations in those with higher PA:A ratios (≥ 1; OR, 1.80; 95%CI, 1.46-2.23). Notably, patients with NEPD showed a stronger association between these indicators and clinical events than those with EPD (with CACS/CVD, NEPD vsEPD: OR, 2.02 vs1.41; with PA:A ratio/COPD exacerbation, NEPD vsEPD: OR, 2.50 vs1.65); the difference in ORs between COPD subtypes was statistically significant for CACS/CVD. Two chest CT scan parameters, CACS and PA:A ratio, hold distinct predictive values for cardiovascular events and COPD exacerbations that are influenced by specific COPD subtypes. ClinicalTrials.gov; No.: NCT00608764; URL: www. gov.

Treatable traits and exacerbation risk in patients with uncontrolled asthma prescribed GINA step 1-3 treatment: A nationwide asthma cohort study.

Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA). Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function. GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5. Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.

Incremental long-term benefit of drug therapies for chronic obstructive pulmonary disease in quality of life but not mortality: a network meta-analysis

IntroductionThe latest evidence revealed that dupilumab, an interleukin-4 (IL-4) and interleukin-13 (IL-13) blocker, significantly reduces the exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). The efficacy of dupilumab compared with conventional inhaled drugs remains incompletely determined. This study aimed to investigate the comparative efficacy of dupilumab and conventional inhaled drugs in patients with stable COPD.Material and methodsThis study retrieved randomised clinical trials (RCTs) with follow-up ≥ 48 weeks on long-acting β-agonists (LABAs), long-acting muscarinic receptor antagonists (LAMAs), inhaled corticosteroids (ICSs), and dupilumab in the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases. The information on eligible studies was extracted after the screening. The comparative efficacy of 4 drugs and their combinations in acute exacerbation and mortality was assessed using Bayesian network meta-analysis models.ResultsThis network meta-analysis identified 69 eligible RCTs on 7 classes of drug therapies after stepwise screening and included 125,331 COPD patients. Compared with placebo, the 7 drug interventions significantly reduced the risk of acute exacerbation, and the reduction degree increased with the incremental use of drug classes. ICS/LABA/LAMA/dupilumab was the most effective in decreasing exacerbation risk (OR = 0.561 [95% CI: 0.387–0.810]), followed by ICS/LABA/LAMA (OR = 0.717 [95% CI: 0.626–0.817]). The 7 drug therapies were not significantly associated with a lower risk of death compared to placebo. Nevertheless, ICS/LABA/LAMA/dupilumab is the most likely to be effective in decreasing mortality.ConclusionsThe incremental use of combinations of conventional and novel drugs contributed to the long-term benefits in acute exacerbation but not death in COPD. The optimal drug combination in terms of acute COPD exacerbation was ICS/LABA/LAMA/dupilumab.

Airsupra: An inhaled albuterol/budesonide combination for asthma.

The FDA has approved Airsupra (AstraZeneca), a metered-dose inhaler containing the short-acting beta2-agonist (SABA) albuterol and the inhaled corticosteroid (ICS) budesonide, for use as needed for treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients ≥18 years old with asthma. Airsupra is the first combination of a SABA and an ICS to become available in the US. It is not approved for use as maintenance therapy.

The six-minute step test can predict COPD exacerbations: a 36-month follow-up study

The six-minute step test (6MST) has been shown to be effective in assessing exercise capacity in individuals with COPD regardless of severity and, despite its easy execution, accessibility and validity, information on the prognostic power of this test remains uncertain. The aim of this study is to investigate whether the 6MST can predict the occurrence of exacerbations in patients with COPD. This is a prospective cohort study with a 36-month follow-up in patients with COPD. All patients completed a clinical assessment, followed by pulmonary function testing and a 6MST. The 6MST was performed on a 20 cm high step; heart rate, blood pressure, oxygen saturation, BORG dyspnea and fatigue were collected. Sixty-four patients were included in the study, the majority being elderly men. Performance on the 6MST demonstrated lower performance compared to normative values proposed in the literature, indicating a reduced functional capacity. Kaplan Meier analysis revealed that ≤ 59 steps climbed during the 6MST was a strong predictor of COPD exacerbation over a 36-month follow-up. We have identified a minimal threshold number of steps (≤ 59) obtained through the 6MST may be able predict the risk of exacerbations in patients with COPD.

The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations

Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting β2-agonist (SABA) and inhaled corticosteroid (ICS) as alternative reliever at Step 2. The FDA approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and to reduce exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA–ICS during the window-of-opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that use of albuterol–budesonide rather than albuterol as reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the US. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.

Impact of Body Mass Index on Risk of Exacerbation in Patients With COPD: A Systematic Review and Meta-Analysis.

The objective of this review is to synthesize current evidence of the association between body mass index (BMI) categories and the risk of exacerbation in patients with chronic obstructive pulmonary disease (COPD). A systematic search was conducted across 3 electronic databases: PubMed, Embase, and Scopus. Eligible studies must have reported on the association between BMI (either as continuous or categorical) and risk of COPD exacerbation, as defined according to recognized clinical criteria. Observational studies (cohort, case-control, cross-sectional) were eligible for inclusion. The Newcastle Ottawa Scale (NOS) was used to evaluate the methodological quality. Combined effect sizes were reported as relative risk (RR) and corresponding 95% confidence intervals (CI). A total of 11 studies were included. Of them, 4 studies were prospective, 4 were retrospective cohorts in design, 2 were cross-sectional studies, and one study was a secondary data analysis from a randomized trial. Compared to patients with a normal BMI, underweight patients had an increased risk of COPD exacerbation (RR 1.90, 95% CI: 1.03, 3.48; N=7, I2=94.2%). Overweight and obese BMI status was associated with a similar risk of exacerbation. Our findings report that underweight, but not overweight or obese patients, have an increased risk of COPD exacerbation, compared to individuals with a normal BMI. This differential association emphasizes the need for nuanced investigations into the underlying mechanisms of the impact of BMI on the course of COPD. Further research is needed to inform personalized interventions and improve COPD management strategies.

A Fully Decentralized Randomized Controlled Study of As-Needed Albuterol-Budesonide Fixed-Dose Inhaler in Mild Asthma: The BATURA Study Design.

Decentralized clinical trials, where trial-related activities occur at locations other than traditional clinical sites(eg participant homes, local healthcare facilities), have the potential to improve trial access for people for whom time and/or distance constraints may impede participation. Albuterol-budesonide 180/160 µg pressurized metered-dose inhaler (pMDI) is FDA approved for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years or older. BATURA (NCT05505734) is a fully decentralized study, investigating as-needed albuterol-budesonide in participants with mild asthma. BATURA is a fully decentralized, phase 3b, randomized, double-blind, event-driven exacerbation study conducted in the United States. Participants aged ≥12 years using as-needed short-acting β2-agonist (SABA), alone or with low-dose inhaled corticosteroid or leukotriene receptor antagonist maintenance, are randomized 1:1 to as-needed albuterol-budesonide 180/160 µg or albuterol 180 µg pMDI for up to 52 weeks (minimum 12 weeks). Participants continue their current maintenance therapy, if applicable. Participants must have used SABA for ≥2 days in the 2 weeks pre-enrollment and have an Asthma Impairment Risk Questionnaire score ≥2 at screening and randomization. All trial-related visits, including screening and consent, are conducted virtually, with study medication shipped directly to each participant's residence. The primary objective is to evaluate the efficacy of as-needed albuterol-budesonide versus albuterol on severe asthma exacerbation risk, measured by time-to-first severe asthma exacerbation (primary endpoint). Secondary endpoints include annualized rate of severe asthma exacerbation and total systemic corticosteroid exposure. Study medication use is captured via a Hailie sensor attached to the study medication pMDI. The intended sample size is 2500 participants. BATURA evaluates as-needed albuterol-budesonide in participants with mild asthma. The decentralized study model enables the trial to move out of research sites into participant homes, reducing participant burden and improving access.

Exploring the impact of comorbid dementia on exacerbation occurrence in general practice patients with chronic obstructive pulmonary disease.

Previous studies have shown an increased risk of dementia in patient with COPD, but whether comorbid dementia modifies the risk of exacerbations in patients with COPD is unknown. We explored exacerbation occurrence in patients with COPD with comorbid dementia and compared this to patients with COPD without comorbid dementia. We performed a retrospective cohort study based on medical record data from 88 Dutch general practices. Patients diagnosed with COPD and comorbid dementia (n = 244, index group) were matched 1:1 to patients with COPD without comorbid dementia (n = 244, controls). Exacerbations were assessed 1year before and 1year after the dementia diagnosis (or corresponding date in controls) and compared between index and control groups by calculating Rate Ratios (RRs). Average number of COPD exacerbations after dementia diagnosis increased from 5 to 14 per 100 patient years in the index group (RR = 2.70, 95%CI 1.42-5.09; p = 0.02) and from 17 to 30 per 100 patient years in the control group (RR = 1.74, 1.19-2.54; p = 0.04). These RRs did not significantly differ between the index and control groups (RR ratio = 1.55, 0.74-3.25; p = 0.25). We conclude that although the risk of exacerbation increased after patients with COPD were diagnosed with dementia, their change in exacerbation risk did not seem to differ from the change observed in patients with COPD without comorbid dementia. However, as our study was hypothesis-generating in nature, further investigations on the subject matter are needed.

Interaction effect of chronic cough and ageing on increased risk of exacerbation in patients with asthma: a prospective cohort study in a real-world setting.

Older adults with asthma have the greatest burden and worst outcomes, and there is increasing evidence that chronic cough (CC) is associated with asthma severity and poor prognosis. However, the clinical characteristics of older adult patients with both asthma and CC remain largely unknown. Participants with stable asthma underwent two cough assessments within 3 months to define the presence of CC. Patients were divided into four groups based on CC and age (cut-off ≥60 years). Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to investigate asthma exacerbations. Logistic regression models were used to explore the interaction effect of CC and age on asthma control and exacerbations. In total, 310 adult patients were prospectively recruited and divided into four groups: older CC group (n=46), older non-CC group (n=20), younger CC group (n=112) and younger non-CC group (n=132). Compared with the younger non-CC group, the older CC group had worse asthma control and quality of life and increased airflow obstruction. The older CC group showed an increase in moderate-to-severe exacerbations during the 12-month follow-up. There was a significant interaction effect of CC and ageing on the increased moderate-to-severe exacerbations (adjusted risk ratio 2.36, 95% CI 1.47-3.30). Older asthma patients with CC have worse clinical outcomes, including worse asthma control and quality of life, increased airway obstruction and more frequent moderate-to-severe exacerbations, which can be partly explained by the interaction between CC and ageing.

Calcium Channel Blockers and the Risk of Exacerbation in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Study of 48,488 Outpatients.

Patients with chronic obstructive pulmonary disease (COPD) are prone to developing arterial hypertension, and many patients are treated with the calcium channel blocker amlodipine. However, it remains unclear whether using this drug potentially affects the risk of acute severe exacerbations (AECOPD) and all-cause mortality in these patients. The data were collected from Danish national registries, containing complete information on health, prescriptions, hospital admissions, and outpatient clinic visits. The COPD patients (n = 48,488) were matched via propensity score on known predictors of the primary outcome in an active comparator design. One group was exposed to amlodipine treatment, and the other was exposed to bendroflumethiazide, since both of these drugs are considered to be the first choice for the treatment of arterial hypertension according to Danish guidelines. The use of amlodipine was associated with a reduced risk of death from all causes at the 1-year follow-up (hazard ratio 0.69, 95% confidence interval: 0.62-0.76) compared with the use of bendroflumethiazide in the matched patients. No difference in the risk of severe AECOPD was found. In the COPD patients, amlodipine use was associated with a lower risk of death from all causes compared with the use of bendroflumethiazide. Amlodipine seems to be a safe first choice for the treatment of arterial hypertension in COPD patients.

Modelling ASthma TrEatment Responses (MASTER): Effect of individual patient characteristics on the risk of exacerbation in moderate or severe asthma: A time-to-event analysis of randomized clinical trials.

There is limited understanding of how clinical and demographic characteristics are associated with exacerbation risk in patients with moderate-to-severe asthma, and how these factors correlate with symptom control and treatment response. Here we assess the relationship between baseline characteristics and exacerbation risk during regular dosing with inhaled corticosteroids (ICS) monotherapy or in combination with long-acting beta2-agonists (ICS/LABA) in clinical trial patients with varying levels of symptom control, as assessed by the asthma control questionnaire (ACQ-5). A time-to-event model was developed using pooled patient data (N = 16 282) from nine clinical studies [Correction added on 26 July 2023, after first online publication: The N value in the preceding sentence has been corrected in this version.]. A parametric hazard function was used to describe the time-to-first exacerbation. Covariate analysis included the assessment of the effect of seasonal variation, clinical and demographic baseline characteristics on baseline hazard. Predictive performance was evaluated by standard graphical and statistical methods. An exponential hazard model best described the time-to-first exacerbation in moderate-to-severe asthma patients. Body mass index, smoking status, sex, ACQ-5, % predicted forced expiratory volume over 1 s (FEV1 p) and season were identified as statistically significant covariates affecting baseline hazard irrespective of ICS or ICS/LABA use. Fluticasone propionate/salmeterol (FP/SAL) combination therapy resulted in a significant reduction in the baseline hazard (30.8%) relative to FP monotherapy. Interindividual differences at baseline and seasonal variation affect the exacerbation risk independently from drug treatment. Moreover, it appears that even when a comparable level of symptom control is achieved in a group of patients, each individual may have a different exacerbation risk, depending on their baseline characteristics and time of the year. These findings highlight the importance of personalized interventions in moderate-to-severe asthma patients.

Comparison of treatment persistence, adherence, and risk of exacerbation in patients with COPD treated with single-inhaler versus multiple-inhaler triple therapy: A prospective observational study in China.

Aim: This study sought to compare treatment persistence, adherence, and risk of exacerbation among patients with COPD treated with single-inhaler triple therapy (SITT) and multiple-inhaler triple therapy (MITT) in the Chinese population. Methods: This was a multicenter, prospective observational study. Patients with COPD from ten hospitals in Hunan and Guangxi provinces in China were recruited from 1 January 2020 to 31 November 2021 for the study and were followed up for oneyear. Treatment persistence, adherence, and exacerbation rates during the 12-month follow-up were analyzed in COPD patients treated with SITT and MITT. Results: A total of 1,328 patients were enrolled for final analysis, including 535 (40.3%) patients treated with SITT and 793 (59.7%) treated with MITT. Of these patients, the mean age was 64.9years and most patients were men. The mean CAT score was 15.2 ± 7.1, and the median (IQR) FEV1% was 54.4 (31.2). The SITT group had a higher mean CAT score, more patients with mMRC >1, and lower mean FEV1% and FEV1/FVC than the MITT patients. Moreover, the proportion of patients with ≥1 exacerbation in the previous year was higher in the SITT cohort. SITT patients had, compared to MITT patients, a higher proportion of adherence (proportion of days covered, PDC) ≥0.8 (86.5% vs. 79.8%; p = 0.006), higher treatment persistence [HR: 1.676 (1.356-2.071), p < 0.001], lower risk of moderate-to-severe exacerbation [HR: 0.729 (0.593-0.898), p = 0.003], and severe exacerbation [HR: 0.675 (0.515-0.875), p = 0.003], as well as reduced all-cause mortality risk [HR: 0.475 (0.237-0.952), p = 0.036] during the 12-month follow-up. Persistence was related to fewer future exacerbations and mortality than non-persistence in the SITT and MITT groups. Conclusion: Patients with COPD treated with SITT showed improved treatment persistence and adherence, as well as a reduction in the risk of moderate-to-severe exacerbation, severe exacerbation, and mortality compared to patients treated with MITT in the Chinese population. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR-POC-17010431.

Дисфункція дрібних дихальних шляхів та можливості її корекції при астмі

Abstract. Background. Although randomized controlled trials have shown that asthma control is an achievable goal, real-life studies over the past 20 years have shown that asthma remains poorly controlled in a significant proportion of patients, even among those receiving treatment at asthma specialist, and in patients with mild asthma who regularly take inhaled corticosteroids. Even when asthma control is achieved, it is not optimal on all GINA steps. The small airways have been recognized as the primary site of airflow limitation in asthma. The aim of the work: to study, according to the literature, the peculiarities of the dysfunction of the small airways in asthma and to evaluate the possibilities of its treatment. Materials and methods. Scientific articles that covered the pathophysiology of small airways disorders, their impact on asthma control, diagnostic methods, and pharmacological treatment methods were analyzed. The results. Airways with an internal diameter &lt; 2 mm, which do not contain cartilage in their walls and extend from the 8th generation of the airways to the periphery of the lung, are collectively called “small airways”. They are called the QUIET ZONE because they are difficult to assess and treat in patients with asthma who are not optimally controlled but have relatively normal FEV1 and disproportionate small airways dysfunction (SAD). Predominant in patients at all stages of treatment, associated with poor disease control. The ATLANTIS study showed that up to 91 % of patients with asthma have. The small airways have a high density of corticosteroid and β2-adrenoceptors, which means that they can be influenced. The main task is that the drugs should reach these small airways. Conventional inhalers that generate particles larger than 2 μm do not address the problem of SAD in patients with asthma. Inhaler devices that produce ultrafine particles of inhaled corticosteroids alone or in combination with long-acting β-agonists with a diameter of less than 2 μm have the potential to improve long-term asthma control along with a corresponding improvement in small airway function. The fixed combination of beclomethasone dipropionate with formoterol has optimal deposition in the respiratory tract — central pulmonary deposition accounts for 66 %, and peripheral — 34 % of the dose, thus the drug is delivered to both the central and peripheral respiratory tracts and affects inflammation and bronchoconstriction throughout the lungs. This is facilitated by MODULITE technology. The effectiveness and safety of the use of the BDP/F combination (Foster) in MART regimen is confirmed by a significant evidence base, which guaranteed its place in the Track1 treatment of asthma. Conclusions: Patients with asthma have a serious inflammatory process in the peripheral airways, which makes them the main site of obstruction in asthma; SAD predominates in patients at all stages of asthma, is associated with poor disease control, is responsible for air trapping, correlates with poor asthma control1, and predicts an increased risk of exacerbations in patients. The fixed combination of beclamethasone/formoterol in one inhaler (Foster) is the only extrafinely dispersed fixed combination of ICS/LABA that reaches the small airways; the fixed combination of BDP/Formoterol in the MART regimen provides a significant reduction in the frequency of severe complications, hospitalizations, emergency calls, and reduces the number of courses of systemic corticosteroids.

Clinically relevant effects of Mindfulness-Based Stress Reduction in individuals with asthma

BackgroundPsychological distress and comorbid psychopathology contribute to exacerbation risk in patients with asthma. Thus, interventions designed to reduce stress and improve emotion regulation, such as Mindfulness-Based Stress Reduction (MBSR), may augment standard care. Few studies have addressed this question and a paucity of data exists to determine the ability of MBSR to impact clinical outcomes in asthma. MethodsThis randomized controlled trial investigated effects of MBSR training on asthma control and airway inflammation, in relation to psychological symptoms, in adults with asthma. Participants were randomized to an 8-week MBSR training (n = 35) or wait-list control group (n = 34). Clinically relevant asthma assessments, including Asthma Control Questionnaire and inflammatory biomarkers, were collected at baseline and six approximately-monthly follow-ups. Self-reported mindfulness, distress, depression, and anxiety symptoms were assessed at baseline, post-intervention, and study completion. Chronic stress level was determined at baseline only. ResultsAsthma control improved significantly in individuals randomized to MBSR, relative to wait-list controls (p = .01; effect size d = 0.76), which was maintained at 4mo post-intervention. 32% of MBSR participants achieved a clinically significant improvement, based on the ACQ6 Minimally Important Difference, relative to 12% of wait-list participants. Moreover, MBSR-related improvement in asthma control was associated with a reduction in distress (p = .043) and the intervention was most efficacious for those with the highest baseline depressive symptoms (p = .023). Importantly, MBSR also reduced levels of exhaled nitric oxide, a biomarker of airway inflammation, relative to wait-list controls (p < .05). ConclusionSupporting and extending extant evidence of mind-body relationships in asthma and the benefits of stress reduction for these patients, this is, to the best of our knowledge, the first RCT to demonstrate that training in MBSR improves clinically relevant asthma outcomes. MBSR may thus be a valuable addition to optimal asthma management, particularly for those with comorbid psychopathology. Clinical trial registrationNCT02157766.

Lack of Association between Inhaled Corticosteroid Use and the Risk of Future Exacerbation in Patients with GOLD Group A Chronic Obstructive Pulmonary Disease.

Background: As most clinical trials have been performed in more symptomatic and higher-risk patients, evidence regarding treatment in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A chronic obstructive pulmonary disease (COPD) is limited. We assessed the distribution of inhaler treatment and sought to investigate the association between inhaled corticosteroid (ICS) use and future exacerbation in GOLD group A COPD patients. Methods: Patients with GOLD group A COPD who received maintenance inhalers were identified from a multicentre, prospective cohort in South Korea. Patients were categorized as group A when they had fewer symptoms and did not experience severe exacerbation in the previous year. Development of moderate or severe exacerbation during the 1-year follow-up was analysed according to baseline inhaler treatment. Results: In 286 patients with GOLD group A COPD, mono-bronchodilator (37.8%), dual-bronchodilator (29.0%), triple therapy (17.5%), and ICS/long-acting beta-2 agonist (15.4%) were used. Compared to patients without ICS-containing inhalers (N = 191), those using ICS (N = 95) were more dyspnoeic, and more likely to have asthma history, lower lung function, and bronchodilator response. During the 1-year follow-up, moderate or severe exacerbations occurred in 66 of 286 (23.1%) patients. In the multivariable logistic regression analysis, ICS-containing inhaler use was not associated with the development of exacerbation, even in the subgroup with a high probability of asthma–COPD overlap. Conclusion: Although about one-third of patients with GOLD group A COPD were using ICS-containing inhalers, use of ICS was not associated with a reduction in the future development of exacerbation.

Effect of timing of bronchodilator therapy initiation on exacerbations in patients with chronic obstructive pulmonary disease: a retrospective cohort study

BackgroundThe benefit of prompt vs delayed treatment initiation with inhaled long-acting bronchodilators in reducing exacerbations in chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate if long-acting bronchodilator therapy initiation within 30 days of COPD diagnosis reduces exacerbation risk in patients with COPD.MethodsThis was a retrospective cohort study of patients with COPD based on claims and electronic medical records data extracted from the Real World Data database. The index date (day 0) was the date of the first confirmed inpatient or outpatient COPD diagnosis between January 1, 2005, and December 31, 2018. Patients with COPD without an asthma diagnosis and aged ≥ 40 years at the index date were included. Patients who initiated inhaled long-acting bronchodilator therapy within the first 30 days (day 0 to day 29) were categorized into the “prompt therapy” group and the rest into the “delayed therapy” group. Time from day 30 post-diagnosis to the first exacerbation and annual exacerbation rate (AER) were evaluated for the overall population and those stratified by COPD phenotype, including chronic bronchitis (CB) and emphysema.ResultsCompared with the delayed therapy group (n = 1516), time to first exacerbation was prolonged (hazard ratio 0.78; 95% confidence interval [CI] [0.70, 0.87]) and annual rates of moderate or severe exacerbations were lower (rate ratio 0.74; 95% CI [0.65, 0.84]) in the prompt therapy group (n = 1466). Similarly, time to first exacerbation was prolonged and AERs were lower in the prompt therapy group in the subgroups of patients with CB or emphysema.ConclusionsThis is the first study to demonstrate a prolonged time to first exacerbation upon initiation of long-acting bronchodilators within 30 days of COPD diagnosis. A beneficial effect was also observed in patients with CB and emphysema. Our data support advising patients to initiate long-acting bronchodilators soon after COPD diagnosis.

EFFECTIVENESS OF COPD MAINTENANCE THERAPY WITH LAMA/LABA VS LAMA/LABA/ICS IN A UNITED STATES CLAIMS DATABASE

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: This retrospective cohort study compared time to a) first hospitalization for community-acquired pneumonia and b) first COPD exacerbation in patients initiating maintenance therapy with the long-acting dual bronchodilator therapy tiotropium/olodaterol (T/O) vs triple therapy (TT) with long-acting muscarinic antagonist (LAMA)/long-acting beta agonist (LABA)/inhaled corticosteroids (ICS). METHODS: Administrative data from the US HealthCore Integrated Research Database (Jan 2013–Mar 2019) were used to compare patients for up to 1 year. Eligible patients were aged ≥40 years, diagnosed with COPD (not asthma), and had ≥1 inhaler prescription of fixed-dose T/O, or fixed or free TT (first prescription=index date). Propensity scores were calculated. Within the area of overlap, fine stratification and reweighting were used to balance measured covariates between the cohorts. Residual imbalances (standardized difference >0.10 [10%]) in the reweighted pseudo-population were adjusted for in the outcome models. A sensitivity analysis excluded patients with an exacerbation ≤30 days pre-index to minimize confounding e.g. due to higher TT prescription in frequent exacerbators. Further sensitivity analyses excluded patients with any prior use of maintenance therapy, and substituted the propensity score fine stratification/reweighting method with a 1:1 greedy match (propensity score caliper: 0.05). In all analyses, a Cox proportional hazard regression model was used to assess outcomes (as-treated analysis). RESULTS: The study population had 2,864 T/O and 24,326 TT users (after reweighting: 2,785 T/O and 15,465 TT users; mean age, 65.6 years; female, 47.1% [T/O] vs 49.7% [TT]). There were no differences in baseline characteristics, except for calendar year and season of cohort entry. No difference in prior exacerbations (any) was observed (std diff: <0.1); however, a higher proportion of TT users had severe exacerbations ≤1 year pre-index (32.7% vs 17.3%) and any exacerbations ≤30 days pre-index (25.8% vs 10.8%) vs T/O users. For T/O vs TT, adjusted hazard ratio (aHR) for exacerbation was 0.85 (95% CI: 0.76–0.96) (adjusted for calendar year, season of cohort entry). Excluding exacerbators ≤30 days pre-index balanced the cohorts (std diff: <0.1) in terms of prior exacerbations (any, moderate or severe). In this population, the aHR for exacerbation was 1.04 (95% CI: 0.91–1.19) (adjusted for calendar year, LABA/ICS use, season of cohort entry). Results were similar when applying 1:1 matching (aHR 1.02; 95% CI 0.84–1.24) and when restricting to treatment-naïve patients (no LABA, LAMA, ICS use prior to T/O or TT) (aHR 1.08; 95% CI 0.81–1.44). T/O users had a numerically lower risk of pneumonia than TT users (aHR 0.83; 95% CI 0.64–1.07). CONCLUSIONS: This study showed no benefit of TT vs T/O in reducing exacerbation risk in patients with no recent exacerbations, including treatment-naïve patients. In line with previous data, T/O was associated with a numerically lower risk of pneumonia vs TT. CLINICAL IMPLICATIONS: In an infrequently exacerbating population, prescribing T/O in place of TT appears not to increase exacerbation risk and could reduce pneumonia risk. DISCLOSURES: Employee relationship with Boehringer Ingelheim Please note: $20001 - $100000 by Alberto de la Hoz, source=Web Response, value=Salary Consultant relationship with HealthCore, Inc Please note: 2010-2018 Added 05/04/2021 by Daina Esposito, source=Web Response, value=Consulting fee Employee relationship with Moderna Please note: Since Feb 2021 Added 05/04/2021 by Daina Esposito, source=Web Response, value=Salary Owner/Founder relationship with Ciconia Inc Please note: 2018-2021 Added 05/04/2021 by Daina Esposito, source=Web Response, value=Ownership interest Employee relationship with Anthem Inc (HealthCore Inc) Please note: April 2019-present Added 05/04/2021 by Xintong He, source=Web Response, value=Salary Employee relationship with Boehringer-Ingelheim Please note: 2016- Added 05/03/2021 by Jukka Montonen, source=Web Response, value=Salary Advisory Committee Member relationship with GlaxoSmithKline Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria Advisory Committee Member relationship with AstraZeneca Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria Advisory Committee Member relationship with Bayer Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria