LABA Research Articles

Frequency and characteristics of asthma in smokers attending smoking cessation units in Spain

Introduction The interaction between smoking and asthma impairs lung function and increases airflow obstruction severity. The identification of smoking patterns in smokers with and without asthma is crucial to provide the best care strategies. The aims of this study are to estimate asthma frequency, describe asthma features, and characterize smoking in smokers attending smoking cessation units. Material and methods We carried out a cross-sectional study in five smoking cessation units with different geographical distribution to estimate asthma frequency in smokers, characterize asthma features in smokers, as well as smoking in asthmatic smokers. Results Asthma frequency among smokers was 18.6%. Asthmatic smokers presented high passive exposure, low smoking self-efficacy and will to quit smoking, as well as a high exacerbation frequency, severe symptoms, and frequent use of long-acting beta agonists, inhaled steroids, and short-acting beta agonists. Discussion Smokers with asthma constitute a high-risk group with worsened evolution of pulmonary involvement. All smokers should be regularly screened for asthma. Effective smoking cessation strategies should be proposed to smokers with asthma in order to reverse the harmful effects of smoking on the airway, together with a comprehensive and integral approach.

Inhaled medications for chronic obstructive pulmonary disease predict surgical complications and survival in stage I non-small cell lung cancer.

Lung function is routinely assessed prior to surgical resection for non-small cell lung cancer (NSCLC). Further assessment of chronic obstructive pulmonary disease (COPD) using inhaled COPD medications to determine disease severity, a readily available metric of disease burden, may predict postoperative outcomes and overall survival (OS) in lung cancer patients undergoing surgery. We retrospectively evaluated clinical stage I NSCLC patients receiving surgical treatment within the Veterans Health Administration from 2006-2016 to determine the relationship between number and type of inhaled COPD medications (short- and long-acting beta2-agonists, muscarinic antagonists, or corticosteroids prescribed within 1 year before surgery) and postoperative outcomes including OS using multivariable models. We also assessed the relationship between inhaled COPD medications, disease severity [measured by forced expiratory volume in 1 second (FEV1)], and diagnosis of COPD. Among 9,741 veterans undergoing surgery for clinical stage I NSCLC, patients with COPD were more likely to be prescribed inhaled medications than those without COPD [odds ratio (OR) =5.367, 95% confidence interval (CI): 4.886-5.896]. Increased severity of COPD was associated with increased number of prescribed inhaled COPD medications (P<0.0001). The number of inhaled COPD medications was associated with prolonged hospital stay [adjusted OR (aOR) =1.119, 95% CI: 1.076-1.165), more major complications (aOR =1.117, 95% CI: 1.074-1.163), increased 90-day mortality (aOR =1.088, 95% CI: 1.013-1.170), and decreased OS [adjusted hazard ratio (aHR) =1.061, 95% CI: 1.042-1.080]. In patients with FEV1 ≥80% predicted, greater number of prescribed inhaled COPD medications was associated with increased 30-day mortality (aOR =1.265, 95% CI: 1.062-1.505), prolonged hospital stay (aOR =1.130, 95% CI: 1.051-1.216), more major complications (aOR =1.147, 95% CI: 1.064-1.235), and decreased OS (aHR =1.058, 95% CI: 1.022-1.095). When adjusting for other drug classes and covariables, short-acting beta2-agonists were associated with increased 90-day mortality (aOR =1.527, 95% CI: 1.120-2.083) and decreased OS (aHR =1.087, 95% CI: 1.005-1.177). In patients with early-stage NSCLC, inhaled COPD medications prescribed prior to surgery were associated with both short- and long-term outcomes, including in patients with FEV1 ≥80% predicted. Routine assessment of COPD medications may be a simple method to quantify operative risk in early-stage NSCLC patients.

Clinical efficacy of a triple combination of budesonide/ glycopyrronium bromide/formoterol in the treatment of chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterized by persistent airflow limitation, caused by chronic inflammation in response to exposure to inhaled damaging particles or gases. Exacerbations of COPD lead to the progression of symptoms, worsening lung function, reduced physical tolerance, and, as a result, contribute to an increase mortality. Therefore, the prevention of exacerbations is a primary objective in the management of COPD. The foundation of COPD therapy involves prescribing long-acting bronchodilators, and for some patients, the use of anti-inflammatory agents, such as inhaled corticosteroids (ICS). ICS are used in combination with long-acting beta2-agonists (LABA) or as part of triple therapy (ICS/LABA/ LAMA). The choice of triple therapy depends on the patient’s exacerbation history, severity of symptom, level of peripheral blood eosinophilia, risk of infectious complications, and the presence of a concomitant diagnosis of bronchial asthma. Triple therapy offers advantages in terms of improving lung function, disease symptoms, reducing exacerbation frequency, and significantly decreasing mortality compared to other inhaled therapy options for COPD. A significant advantage of this therapy has been shown in patients with eosinophilic COPD. Currently, three combined inhalation medications containing ICS/LABA/LAMA are available for COPD treatment in our country. This review provides basic information on the clinical efficacy and safety profile of one of them, budesonide/glycopyrronium bromide/formoterol, in patients with various COPD phenotypes.

Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort.

Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). Nomograms built from these models can assist clinicians in the decision-making process of COPD care.

Characteristics and outcomes of adult patients with asthma presenting with COVID-19: A comparative cohort study.

Bronchial asthma affects about 20% of Qatar's population. The impact of asthma on COVID-19 outcomes is controversial. The aim of this study was to explore the impact of asthma on COVID-19 outcomes and the predictors of COVID-19-related morbidity and mortality in a cohort of asthma patients infected by COVID-19. This is a retrospective cohort study of adult patients with asthma infected with COVID-19, who were recruited from Hamad Medical Corporation (HMC), the main healthcare system in Qatar. Patients were matched to a control group of non-asthmatic COVID-19 patients (1:2) based on sex, age, and other comorbidities. Between March and August 2020, 616 patients with asthma met the inclusion criteria. The need for hospitalization among patients with asthma was independently associated with older age (adjusted odds ratio [aOR] for 10 years, 1.32; 95% confidence interval [CI], 1.13-1.54; p = 0.001) and hypertension (aOR, 2.4; 95% CI, 1.43-3.93; p = 0.001) but not with the use of inhaled corticosteroids (ICS), long-acting beta2 agonists, montelukast, or tiotropium. Patients with asthma required less hospitalization for COVID-19 than non-asthmatic patients (28.2% vs. 37.3%, respectively; aOR, 0.59; 95% CI, 0.77-0.90; p < 0.001). However, admission to the intensive care unit (ICU) was comparable between both groups (3.3% vs. 2.2%; aOR, 1.64; 95% CI, 0.78-3.43; p = 0.193). No difference in mortality rate was observed between the two groups. In Qatar, adult patients with asthma do not appear to be at higher risk of COVID-19-related hospitalization or ICU admission compared to the general adult COVID-19-infected population. Older age and hypertension were the only significant predictors of COVID-19-related hospitalization among patients with asthma. Further larger studies are required to confirm such an association.

Association between use of transdermal tulobuterol and short-term outcomes in patients with stroke and underlying chronic obstructive pulmonary disease: A retrospective cohort study.

Transdermal tulobuterol, a long-acting beta agonist in a transdermal form, is available in some countries, including Japan, Korea, and China. It may provide an alternative treatment option for the management of chronic obstructive pulmonary disease (COPD) in patients who are unable to effectively use inhalers, such as those with acute stroke. This study examined the short-term outcomes of transdermal tulobuterol in patients hospitalized with acute stroke and underlying COPD. Using the Diagnosis Procedure Combination database, a national inpatient database in Japan, we identified patients with stroke and underlying COPD who were hospitalized between July 2010 and March 2021. We performed propensity-score overlap weighting to compare in-hospital death, COPD exacerbation, pneumonia, and cardiac complications between patients who initiated transdermal tulobuterol within 2 days of admission and those who did not use it during hospitalization. Of the 1878 eligible patients, 189 received transdermal tulobuterol within 2 days of admission. After adjusting for baseline variables, transdermal tulobuterol was not associated with a reduction in in-hospital death (18.3% vs 16.1%; odds ratio, 1.17; 95% confidence interval, 0.72-1.90). Additionally, we observed no significant difference in COPD exacerbation, pneumonia, and cardiac complications between both groups. Transdermal tulobuterol was not associated with improving short-term outcomes in patients with acute stroke and underlying COPD. Our study does not support the routine use of transdermal tulobuterol in this patient group. However, further research investigating the long-term efficacy of transdermal tulobuterol in patients with stroke and underlying COPD could help establish its role for the management of these patients.

Guideline-discordant inhaler regimens after COPD hospitalization: associations with rurality, drive time to care, and fragmented care – a United States cohort study

Many patients receive guideline-discordant inhaler regimens after chronic obstructive pulmonary disease (COPD) hospitalization. Geography and fragmented care across multiple providers likely influence prescription of guideline-discordant inhaler regimens, but these have not been comprehensively studied. We assessed patient-level differences in guideline-discordant inhaler regimens by rurality, drive time to pulmonary specialty care, and fragmented care. Retrospective cohort analysis using national Veterans Health Administration (VA) data among patients who received primary care and prescriptions from the VA. Patients hospitalized for COPD exacerbation between 2017 and 2020 were assessed for guideline-discordant inhaler regimens in the subsequent 3 months. Guideline-discordant inhaler regimens were defined as short-acting inhaler/s only, inhaled corticosteroid (ICS) monotherapy, long-acting beta-agonist (LABA) monotherapy, ICS+LABA, long-acting muscarinic antagonist (LAMA) monotherapy, or LAMA+ICS. Rural residence and drive time to the closest pulmonary specialty care were obtained from geocoded addresses. Fragmented care was defined as hospitalization outside the VA. We used multivariable logistic regression models to assess associations between rurality, drive time, fragmentated care, and guideline-discordant inhaler regimens. Models were adjusted for age, sex, race/ethnicity, Charlson Comorbidity Index, Area Deprivation Index, and region. Of 33,785 patients, 16,398 (48.6%) received guideline-discordant inhaler regimens 3 months after hospitalization. Rural residents had higher odds of guideline-discordant inhalers regimens compared to their urban counterparts (adjusted odds ratio [aOR] 1.18 [95% CI: 1.12-1.23]). The odds of receiving guideline-discordant inhaler regimens increased with longer drive time to pulmonary specialty care (aOR 1.38 [95% CI: 1.30-1.46] for drive time >90min compared to <30min). Fragmented care was also associated with higher odds of guideline-discordant inhaler regimens (aOR 1.56 [95% CI: 1.48-1.63]). Rurality, long drive time to care, and fragmented care were associated with greater prescription of guideline-discordant inhaler regimens after COPD hospitalization. These findings highlight the need to understand challenges in delivering evidence-based care. NIHNCATS grants KL2TR002492 and UL1TR002494.

Study protocol: A comparison of mobile and clinic-based spirometry for capturing the treatment effect in moderate asthma.

Several inefficiencies in drug development trial implementation may be improved by moving data collection from the clinic to mobile, allowing for more frequent measurements and therefore increased statistical power while aligning to a patient-centric approach to trial design. Sensor-based digital health technologies such as mobile spirometry (mSpirometry) are comparable to clinic spirometry for capturing outcomes, such as forced expiratory volume in 1 s (FEV1); however, the impact of remote spirometry measurements on the detection of treatment effect has not been investigated. A protocol for a multicenter, single-arm, open-label interventional trial of long-acting beta agonist (LABA) therapy among 60 participants with uncontrolled moderate asthma is described. Participants will complete twice-daily mSpirometry at home and clinic spirometry during weekly visits, alongside continuous use of a wrist-worn wearable and regular completion of several diaries capturing asthma symptoms as well as participant- and site-reported satisfaction and ease of use of mSpirometry. The co-primary objectives of this study are (A) to quantify the treatment effect of LABA therapy among participants with moderate asthma, using both clinical spirometry (FEV1c ) and mSpirometry (FEV1m ); and (B) to investigate whether FEV1m is as accurate as FEV1c in detecting the treatment effect using a mixed-effect model for repeated measures. Study results will help inform whether the deployment of mSpirometry and a wrist-worn wearable for remote data collection are feasible in a multicenter setting among participants with moderate asthma, which may then be generalizable to other populations with respiratory disease.

PRevalence of the Eosinophilic Phenotype Among SeveRE asthma patients in Lebanon: results of the PREPARE study

BackgroundThe prevalence of eosinophilic asthma in Lebanon, one of the most severe phenotypes among severe asthma, is not known. This study aimed at determining the prevalence of the eosinophilic phenotype defined as an eosinophil count ≥ 300 cells/mm3 among severe asthma patients in Lebanon.MethodsThe Lebanese Chapter of the PREPARE study was a national, multicenter, cross-sectional observational study. Patients aged ≥ 12 years with severe asthma were identified and prospectively enrolled during clinic visits and completed the Global Initiative for Asthma (GINA) assessment of asthma control questionnaire. Patients’ health characteristics were collected from medical records and blood samples were obtained for measurement of serum IgE levels and blood eosinophils count.ResultsOverall, 101 patients (with mean age of 46.3 ± 17.0 years and 73.27% females) with severe asthma were included and, among them, 37% had eosinophilic phenotype, 67.3% had atopic phenotype with IgE > 100 IU/mL and 25.7% patients had overlapping atopic and eosinophilic phenotypes. Close to 80% had late-onset asthma, beyond 12 years of age, and around 85% had at least one severe exacerbation in the 12 months prior to study enrolment. The majority of participants [64.4%] had uncontrolled asthma, 24.7% had partially controlled symptoms and 10.9% had controlled symptoms. 19.8% of participants were on chronic oral corticosteroids, 78.2% had short course treatment of corticosteroids and all were prescribed a combination of inhaled corticosteroids and long-acting beta-agonist.ConclusionsThe majority of patients with severe asthma were uncontrolled of which 37% present with an eosinophilic phenotype, which should be taken into consideration for better management of these patients in view of the novel phenotype-specific therapeutic options.

Guideline Alignment and Medication Concordance in COPD

Provider adherence to clinical treatment guidelines in COPD is low. However, for patients to receive guideline-aligned care, providers not only must prescribe guideline-aligned care, but also must communicate that regimen successfully to patients to ensure medication concordance. The rate of medication concordance between patients and providers and its impact on clinical management is unknown in COPD. To examine rates of guideline alignment and medication concordance and to identify patient-level factors that place patients at risk for these types of poor disease management outcomes. This study was a secondary data analysis of the Medication Adherence Research in COPD study (2017-2023). Participants were categorized into 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Medication regimens were classified as aligned or nonaligned with 2017 GOLD guidelines. Nonaligned regimens were stratified further into overuse and underuse categories. Medication concordance between provider-reported and participant-reported regimens was determined. Factors associated with guideline alignment and medication concordance were evaluated using logistic regression. Of 191 participants, 51% of provider-reported regimens were guideline aligned, with 86% of nonaligned regimens reflecting overuse with an inhaled corticosteroid (ICS). Thirty-eight percent of participants reported different regimens than their providers, of which > 80% reflected participants not reporting medications their providers reported prescribing. Participants did not report long-acting muscarinic antagonists and long-acting beta-agonists at similar rates as ICSs. Greater symptom burden and absence of a pulmonologist on the care team were associated with both guideline misalignment and medication discordance. Cognitive impairment and Black race additionally were associated with medication discordance. Guideline misalignment and medication discordance were common and were driven by overuse of ICSs and unreported medications, respectively. The patient-level factors associated with medication discordance highlight the importance of improving patient-provider communication to improve clinical management in COPD.

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.

How does long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) compare with LABA plus inhaled corticosteroid (ICS) for people with stable chronic obstructive pulmonary disease (COPD)?

How does long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) compare with LABA plus inhaled corticosteroid (ICS) for people with stable chronic obstructive pulmonary disease (COPD)?

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis

IntroductionBronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung...

Treatable traits, combination inhaler therapy and the future of asthma management.

The landscape of asthma has considerably changed in the last decade. Effective medications and inhaler devices have been developed and integrated into the asthma pharmacopoeia, but unfortunately, the proportion of uncontrolled patients remains unacceptably high. This is now recognized to be mainly due to the inappropriate use of medications or inhaler devices, heterogeneity of the disease or other factors contributing to the disease. Currently, inhaled corticosteroids (ICS), with or without long-acting beta agonists (LABA), are the cornerstone of asthma management, and recently international guidelines recognized the importance of combination inhaler therapy (ICS/LABA) even in mild asthma. In future, ultra-long-acting personalized medications and smart inhalers will complement combination inhaler therapy in order to effectively addresses issues such as adherence, inhaler technique and polypharmacy (both of drugs and devices). Asthma is now acknowledged as a multifaceted cluster of disorders and the treatment model has evolved from one-size-fits-all to precision medicine approaches such as treatable traits (TTs, defined as measurable and treatable clinically important factors) which encourages the quality use of medications and identification and management of all underlying behavioural and biological treatable risk factors. TT requires research and validation in a clinical context and the implementation strategies and efficacy in various settings (primary/secondary/tertiary care, low-middle income countries) and populations (mild/moderate/severe asthma) are currently evolving. Combination inhaler therapy and the TTs approach are complementary treatment approaches. This review examines the current status of personalized medicine and combination inhaler therapy, and describes futuristic views for these two strategies.

Asthma and COPD: Comparison with International Guidelines and Medication Adherence in Belgium.

Asthma and chronic obstructive pulmonary disease (COPD) are major chronic conditions. It is possible to limit their impact by controlling symptoms, which limits exacerbations and worsening of the disease, by choosing the appropriate treatment and ensuring that the patient adheres to it. The main purpose of this study was to assess medication adherence and persistence with inhaled medications for chronic treatment of asthma and COPD, as well as to evaluate the factors influencing this adherence. Medication adherence was measured from January 2013 to December 2016 using continuous multiple-interval measures of medication availability (CMA). Persistence was evaluated by treatment episodes (TE). We analyzed the influence of different factors on CMA such as sex, age, type of device, and the realization of the "new medicines service" (NMS), introduced in Belgium in October 2013 to support patients in adhering to their treatment. We also analyzed the consumption of these inhaled medications within the Belgian population and compared them with the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations. Medication adherence varied greatly between the different pharmacological classes: inhaled corticosteroids (ICS) alone or in combination with long-acting beta agonists (LABA) had the lowest medication adherence and persistence, while adherence was highest for the long-acting muscarinic antagonists (LAMA) and LABA/LAMA associations. The NMS seemed to have a positive impact on medication adherence, although few patients completed the two guidance interviews offered by the service. In addition, only a minority of the targeted patients took advantage of this new service.

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.

A population-based study of the burden of severe asthma in Alberta, Canada

RATIONALE A comprehensive understanding of the burden of illness and management strategies for severe asthma (SA), especially by disease control, is lacking in Canada. OBJECTIVES The objectives of this study were to describe treatments, exacerbation outcomes and healthcare resource utilization (HCRU) for patients with controlled and uncontrolled SA in Alberta, Canada. METHODS A retrospective cohort of SA patients 12+ years (April 1, 2011 to March 31, 2020) was identified from administrative health data, based on medication dispensed for controlling asthma symptoms, stratified by disease control at index. Treatment patterns were analyzed for incident SA patients. Annualized exacerbation incidence rate ratios (IRR) were estimated throughout follow-up and stratified by disease control at index. Asthma-specific HCRU and direct costs were calculated. RESULTS The study cohort included 74,134 patients (12.4% of eligible asthma patients) of whom 71,099 (95.5%) were classified as controlled and 3,035 (4.1%) as uncontrolled at index. Inhaled corticosteroid + long-acting beta agonist (ICS + LABA) was the most frequent first-line therapy among incident SA patients (n = 53,084), received by 42.7% of patients. A minority received >2 lines of therapy; few received triple therapy. The uncontrolled (at index) versus controlled (at index) cohort had a 5.5 times higher exacerbation rate (IRR: 5.5, 95% CI: 5.1–5.8; p < 0.001), higher HCRU, and higher associated annual costs (mean [SD]: $3,799 [$6,668] uncontrolled vs $1,339 [$2,515] controlled). CONCLUSIONS SA, whether controlled or uncontrolled at index, was associated with ongoing exacerbations and HCRU despite treatment intensification that identified patients as having SA. Some treatment patterns appeared misaligned with guidelines, suggesting potential need for better recognition of asthma severity and escalating therapies.

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach.

Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade2) versus severe and very severe COPD (GOLD grades3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD. The modelling approach used data on decline in forced expiratory volume in 1s (FEV1) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV1 and annual exacerbation rates from age 40 to 75years in COPD with initiation of long-acting anti-muscarinic antagonist(LAMA)/long-acting beta2-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65years of age. Model-predicted decline in FEV1 showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65years preserved an additional 469.7mL or 236.0mL, 327.5mL or 203.3mL, or 213.5mL or 137.5mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65years of age, respectively. This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA.

Clinical Characteristics and Economic Burden of Asthma in China: A Multicenter Retrospective Study.

Asthma is a common chronic airway inflammation that produces a healthcare burden on the economy. We aim to obtain a better understanding of the clinical status and disease burden of patients with asthma in China. A retrospective study was carried out based on the computerized medical records in the Jinan Health Medical Big Data Platform between 2011 and 2019 (available data from 38 hospitals). The asthma severity of each patient was assessed retrospectively and categorized as mild, moderate, or severe according to Global Initiative for Asthma 2020 (GINA 2020). The results revealed that the majority (75.0%) of patients suffered from mild asthma. Patients treated with inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) at emergency department visits had lower frequencies of exacerbations compared with non-ICS/LABA-treated patients. The incidence rates for 1, 2, 3, and 4 exacerbation of the patients treated with ICS/LABA are lower than those treated without ICS/LABA (14.49 vs. 15.01%, 11.94% vs. 19.12%, 6.51% vs.12.92% and 4.10% vs. 9.35%). The difference got a statistical significance Chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), two comorbidities related to asthma, were risk factors for asthma exacerbation. Finally, patients who suffered from exacerbations produced a heavier economic burden compared to the patients who never suffered exacerbations (mean costs are ￥3,339.67 vs. ￥968.45 separately). These results provide a reference for clinicians and patients to obtain a better treatment and therapy strategy management for people living with asthma.

American College of Allergy, Asthma and Immunology members' preferred steps 1 to 3 asthma maintenance and reliever therapy and incomplete insurance coverage indicated as main practice hurdle

BackgroundNew asthma guidelines (GINA, 2022; NAEPP EPR-4, 2020) include considerable changes in treatment recommendations, specifically regarding anti-inflammatory rescue and Single MAintenance and Reliever Therapy (SMART). ObjectiveTo explore American College of Allergy, Asthma and Immunology members’ preferred treatment and perceived hurdles. MethodsA survey (SurveyMonkey) regarding steps 1 to 3 asthma therapy was e-mailed to American College of Allergy, Asthma and Immunology members. ResultsThe allergists completed 147 surveys (46% with >20 years of experience; 98% from United States; 29% academic, 75% [also] private practice). In addition, 69% follow the National Asthma Education and Prevention Program and 81% the Global Initiative for Asthma recommendations. Of 147 allergists, 117 (80%) indicated correctly what SMART strategy is; 21%/36%/50%/39% would use SMART in step 3 treatment of a below 5-year-old/5- to 11-year-old/12- to 65-year-old/above 65-year-old patient, respectively. In this group, 11% to 14% incorrectly chose inhaled corticosteroid (ICS) plus salmeterol and 9% ICS plus vilanterol for SMART. In a 4-year-old needing step 1 therapy (N = 129), 55% of the respondents would add anti-inflammatory therapy; for step 2 treatment, most would prescribe ICS 100 to 200 µg budesonide equivalent daily; in step 3, 49% would prescribe ICS plus long-acting beta-agonist (LABA). In a 7-year-old needing step 1 treatment (N = 134), 40% would prescribe only short-acting beta-agonist; in step 3, 45% would institute SMART strategy, but only 8 of 135 (6%) chose very-low dose ICS plus formoterol (as recommended in Global Initiative for Asthma); most (39%) use low-dose ICS plus formoterol. As for rescue therapy, 59% is now instituting some form of anti-inflammatory rescue. Finally, in a 25-year-old patient (N = 144): in step 1, 39% would prescribe exclusively short-acting beta-agonist; in step 2, 4% only anti-inflammatory rescue and the rest prescribes ICS maintenance; one-third begins SMART strategy at step 2 and 50% in step 3.Major hurdles for prescribing one's preferred strategy included incomplete insurance coverage, insurance not approving more than one canister of ICS-formoterol per month, and cost. ConclusionAsthma therapy varies among physicians, with respondents suggesting underutilization of the recommended anti-inflammatory rescue and SMART therapy. A major hurdle is lack of insurance coverage of medication in line with the guidelines.