LABA Research Articles

Leukotriene receptor antagonist (LTRA) added to regular preventive therapy: inhaled corticosteroids and longacting beta agonists (ICS/LABA) in patients with severe uncontrolled asthma

Leukotriene receptor antagonist (LTRA) added to regular preventive therapy: inhaled corticosteroids and longacting beta agonists (ICS/LABA) in patients with severe uncontrolled asthma

Medication Discontinuation in Adults With COPD Discharged From the Hospital: A Population-Based Cohort Study

Background Patients admitted to the hospital with COPD are commonly managed with inhaled short-acting bronchodilators, sometimes in lieu of the long-acting bronchodilators they take as outpatients. If held on admission, these long-acting inhalers should be re-initiated upon discharge; however, health-care transitions sometimes result in unintentional discontinuation. Research Question What is the risk of unintentional discontinuation of long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist and inhaled corticosteroid (LABA-ICS) combination medications following hospital discharge in older adults with COPD? Study Design and Methods A retrospective cohort study was conducted by using health administrative data from 2004 to 2016 from Ontario, Canada. Adults with COPD aged ≥ 66 years who had filled prescriptions for a LAMA or LABA-ICS continuously for ≥ 1 year were included. Log-binomial regression models were used to determine risk of medication discontinuation following hospitalization in each medication cohort. Results Of the 27,613 hospitalization discharges included in this study, medications were discontinued 1,466 times. Among 78,953 patients with COPD continuously taking a LAMA or LABA-ICS, those hospitalized had a higher risk of having medications being discontinued than those who remained in the community (adjusted risk ratios of 1.50 [95% CI, 1.34-1.67; P Interpretation In an observational study of highly compliant patients with COPD, hospitalization was associated with an increased risk of long-acting inhaler discontinuation. These Results suggest a likely larger discontinuation problem among less adherent patients and should be confirmed and quantified in a prospective cohort of patients with COPD and average compliance. Quality improvement efforts should focus on safe transitions and patient medication reconciliation following discharge.

IMPACT OF CHANGES IN THE 2019 GINA TREATMENT CLASSIFICATION: ASSESSMENT IN A REAL-WORLD SETTING

SESSION TITLE: Allergy and Airway Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The 2019 Global Initiative for Asthma (GINA) recommendations included major changes. For example, patients requiring high-dose inhaled corticosteroids (ICS) combined with a long-acting beta agonist (LABA) are now uniquely assigned to Step 5, whereas in previous recommendations this category included patients requiring medium- and high-dose ICS combination treatments. There are limited data available describing how these changes affect classification of patients across GINA Steps. Our objective was to characterize the impact of these 2019 changes in a real-world setting. METHODS: This retrospective analysis was based on open source patient claims data acquired from Symphony Health for the period of 10/2013-10/2018. Patients ≥18 years of age who had ≥ 2 claims indicating asthma on separate dates, 2 years of active enrollment prior to the index date, and who could be classified according to GINA 2018 and GINA 2019 criteria were included in the analysis. RESULTS: From a total sample of ∼4.2 million patients, ∼2 million met the criteria for this analysis. Five percent of the total sample did not meet predefined inclusion criteria. When patients were classified according to GINA 2018 criteria, 28%, 13%, 12%, 31%, and 5% were assigned to GINA Steps 1, 2, 3, 4, and 5, respectively. When GINA 2019 criteria were applied (still classifying patients on short-acting beta agonist only as GINA 1), 28%, 13%, 12%, 17%, and 19% were classified as GINA Steps 1, 2, 3, 4, and 5, respectively. Data were also evaluated by healthcare provider specialty; GINA Step 5 patients accounted for 6% and 23% of primary care providers’ asthma patient populations in 2018 and 2019, respectively. This change was consistent with the shift in the overall population, irrespective of provider. Similarly, among allergists and pulmonologists, the proportion of GINA Step 5 patients increased from 10% to 29%, and 14% to 33%, respectively. CONCLUSIONS: Overall, two-thirds of patients retained the same GINA Step classification across the 2018 and 2019 classifications, while one-third moved to a different step when applying GINA 2019. Most of the change occurred in GINA Steps 4 and 5; nearly half of patients classified as Step 4 according to 2018 criteria (high-dose ICS/LABA) moved to Step 5 when 2019 criteria were applied. CLINICAL IMPLICATIONS: The 2019 changes in the GINA recommendations allocated a higher proportion of patients to GINA Step 5. Early adoption of these revised recommendations may provide better understanding of the impact of ICS treatment allocation to the level of disease severity and related management across health care providers. Sponsored by GB001, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. DISCLOSURES: Consultant relationship with Novartis Please note: $5001 - $20000 Added 05/29/2020 by William Busse, source=Web Response, value=Consulting fee Consultant relationship with Sanofi Please note: $20001 - $100000 Added 05/29/2020 by William Busse, source=Web Response, value=Consulting fee Consultant relationship with GlaxoSmithKline Please note: $5001 - $20000 Added 05/29/2020 by William Busse, source=Web Response, value=Consulting fee Consultant relationship with Regeneron Please note: $1001 - $5000 Added 05/29/2020 by William Busse, source=Web Response, value=Consulting fee Consultant relationship with AstraZeneca Please note: $1-$1000 Added 05/29/2020 by William Busse, source=Web Response, value=Consulting fee No relevant relationships by Carlos Camargo, source=Web Response No relevant relationships by Harshad Chiddarwar, source=Web Response No relevant relationships by Nicola Hanania, source=Web Response No relevant relationships by Fernando Holguin, source=Web Response Employee relationship with Gossamer Bio Please note: >$100000 Added 05/29/2020 by Gina Nelson, source=Web Response, value=Salary Employee relationship with Gossamer Bio Inc. Please note: >$100000 Added 05/29/2020 by Hector Ortega, source=Web Response, value=Salary No relevant relationships by Emily Pennington, source=Web Response

Asthma and COVID-19: In Defense of Evidence-Based SABA.

There have recently been major objections to the use of short-acting beta-agonist (SABA) in episodic acute asthma culminating in a call for replacing SABA with combination of inhaled corticosteroids and long-acting beta-agonists despite little evidence supporting this point of view. It is regrettable to note that this attack on SABA occurs in the midst of an unprecedented demand for, and shortage of, SABA inhalers during the current COVID-19 pandemic, and the worldwide efforts to increase SABA supplies. In this commentary, we defend the well-established role of SABA and argue that the call for the phase out of SABA is inappropriate, since it is not solidly evidence based.

Extrafine Beclometasone Dipropionate/Formoterol Fumarate vs Double Bronchodilation Therapy in Patients with COPD: A Historical Real-World Non-Inferiority Study.

PurposeThis study aimed to evaluate the non-inferiority of initiating extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF) versus double bronchodilation (long-acting beta-agonists [LABA]/long-acting muscarinic antagonists [LAMA]) among patients with a history of chronic obstructive pulmonary disease (COPD) exacerbations.Patients and MethodsA historical cohort study was conducted using data from the UK’s Optimum Patient Care Research Database. Patients with COPD ≥40 years at diagnosis were included if they initiated extrafine BDP/FF or any LABA/LAMA double therapy as a step-up from no maintenance therapy or monotherapy with inhaled corticosteroids (ICS), LAMA, or LABA and a history of ≥2 moderate/severe exacerbations in the previous two years. The primary outcome was exacerbation rate from therapy initiation until a relevant therapy change or end of follow-up. Secondary outcomes included rate of acute respiratory events, acute oral corticosteroids (OCS) courses, and antibiotic prescriptions with lower respiratory indication, modified Medical Research Council score (mMRC) ≥2, and time to first pneumonia diagnosis. The non-inferiority boundary was set at a relative difference of 15% on the ratio scale. Five potential treatment effect modifiers were investigated.ResultsA total of 1735 patients initiated extrafine BDP/FF and 2450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV1 <80% predicted. Extrafine BDP/FF showed non-inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 1.01 [95% CI 0.94–1.09]), acute respiratory events (IRR = 0.98 [0.92–1.04]), acute OCS courses (IRR = 1.01 [0.91–1.11]), and antibiotic prescriptions (IRR = 0.99 [0.90–1.09]), but not for mMRC (OR = 0.93 [0.69–1.27]) or risk of pneumonia (HR = 0.50 [0.14–1.73]). None of the a priori defined effect modifier candidates affected the comparative effectiveness.ConclusionThis study found that stepping up to extrafine BDP/FF from no maintenance or monotherapy was not inferior to stepping up to double bronchodilation therapy in patients with a history of exacerbations.

Risk of active tuberculosis among COPD patients treated with fixed combinations of long-acting beta2 agonists and inhaled corticosteroids

ObjectivesTo investigate the incidence of active tuberculosis (TB) among COPD patients using fluticasone/salmeterol or budesonide/formoterol, and to identify any differences between these two groups of patients.MethodsThe study enrolled COPD patients from Taiwan NHIRD who received treatment with fluticasone/salmeterol or budesonide/formoterol for > 90 days between 2004 and 2011. The incidence of active TB was the primary outcome.ResultsAmong the intention-to-treat population prior to matching, the incidence rates of active TB were 0.94 and 0.61% in the fluticasone/salmeterol and budesonide/formoterol groups, respectively. After matching, the fluticasone/salmeterol group had significantly higher rates of active TB (adjusted HR, 1.41, 95% CI, 1.17–1.70) compared with the budesonide/formoterol group. The significant difference between these two groups remained after a competing risk analysis (HR, 1.45, 95% CI, 1.21–1.74). Following propensity score matching, the fluticasone/salmeterol group had significantly higher rates of active TB compared with the budesonide/formoterol group (adjusted HR, 1.45, 95% CI, 1.14–1.85). A similar trend was observed after a competing risk analysis (HR, 1.44, 95% CI, 1.19–1.75). A higher risk of active TB was observed in the fluticasone/salmeterol group compared with the budesonide/formoterol group across all subgroups, but some differences did not reach statistical significance.ConclusionFluticasone/salmeterol carried a higher risk of active TB compared with budesonide/formoterol among COPD patients.

Inhaled Formoterol-Fluticasone Single Inhaler Therapy in Asthma: Real-World Efficacy, Budget Impact, and Potential to Improve Adherence.

Asthma is the commonest chronic disease affecting airways in humans and has an increasing global disease burden. Inhaled corticosteroids (ICS) are the first-line therapeutic option for asthma, and addition of a long-acting beta 2-agonist (LABA) has been shown to improve asthma control. A combination of the two agents in a single inhaler is beneficial with regard to ease of administration and patient compliance. Various ICS-LABA formulations are available across various countries in the world, one among them being formoterol-fluticasone. Both formoterol and fluticasone have pharmacologic peculiarities which places the combination in a uniquely advantageous position when it comes to asthma therapy. The present review focuses on some of the, hitherto, less explored aspects of this combination inhaler such as real-world efficacy, impact on budget allocation, results of switch-over therapy, and potential to improve adherence to asthma treatment. It also provides practical recommendations on positioning it in real-world asthma management.

Clinical and radiological manifestations of inhaled bronchiolitis in the process of dynamic observation

Inhaled bronchiolitis develops from exposure to gases, vapors, acids, fumes and other substances and is characterized by a progressive course. Therapy of inhaled bronchiolitis is not fully presented to date. The results of long — term follow-up of 11 patients with chronic inhaled bronchiolitis from exposure to harmful factors (3 men, 8 women 49.2±2.1 years), 18% — smokers were analyzed. A comprehensive functional study of external respiration and lung diffusion capacity (LDC) and high-resolution computed tomography (HRCT) were performed before and after 1.7±0.4 years of treatment. The diagnosis was made using a 2.6±1.2 years after the appearance of the first symptoms of bronchiolitis. Eight patients received nebulizer therapy with budesonide 1000 mcg per day for two weeks in combination with inhaled glucocorticosteroids, long-acting beta2-agonists and long-acting anticholinergic drugs in ultradisperse forms via dosed inhalers. Three patients took bronchodilators according to their needs. Against the background of therapy, all patients showed stabilization of the course of the disease. Prior to treatment, HRCT revealed a mosaic of the pulmonary pattern (75%; 6/8), centriacinar foci and bronchioloectases — the pattern “tree in the buds” (50%; 4/8), “air traps” (80%; 4/5). After therapy, positive CT dynamics was determined in the form of a decrease in the uneven density of lung tissue and the disappearance of the “tree in the buds” pattern in 5 patients (62%). In three patients who did not follow the recommendations, CT changes remained: the mosaic of the lung pattern and “air traps” were detected in 67% (2/3) of cases, the pattern “tree in the buds” — in one patient 33% (1/3). Indicators of external respiration changed according to the obstructive type. After treatment, there was a tendency to reduce hyperinflation-residual lung volume (RLV) decreased by 40.7%, although it remained elevated in 66.7% (4/6) patients. LDC increased by 6.6% and normalized in 2 patients. Conclusions . For the diagnosis of inhalation bronchiolitis is recommended to body plethysmography, LDC test and HRCT. Long-term triple therapy leads to stabilization of the course of the disease, reduction of hyperinflation, reduction of CT signs of bronchiolitis. To control the course of bronchiolitis, it is advisable to monitor the RLV and LDC, HRCT picture with the study on inhalation and exhalation.

Clinically Important Deterioration Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Treated with Nebulized Glycopyrrolate: A Post Hoc Analysis of Pooled Data from Two Randomized, Double-Blind, Placebo-Controlled Studies.

PurposeUsing a composite endpoint, pooled data from two 12-week Phase III placebo-controlled trials (GOLDEN 3, NCT02347761; GOLDEN 4, NCT02347774) were analyzed to determine whether glycopyrrolate inhalation solution (25 mcg and 50 mcg) administered twice daily (BID) via the eFlow® Closed System nebulizer (GLY) reduced the risk of clinically important deterioration (CID) in patients with moderate-to-very-severe COPD.MethodsCID was defined as ≥100-mL decrease from baseline in post-bronchodilator trough forced expiratory volume in one second (FEV1), or ≥4-unit increase in baseline St. George’s Respiratory Questionnaire (SGRQ) total score, or moderate/severe exacerbation. The relative treatment effect of GLY versus placebo on the odds of CID (any and by component endpoints) was expressed as the odds ratio (OR) and 95% confidence interval (CI). Subgroups categorized by age (<65/≥65 years), sex, smoking status (current/former), long-acting beta agonist (LABA) use, FEV1 (<50%/≥50%), and peak inspiratory flow rate (PIFR) (<60 L/min/≥60 L/min) were analyzed.ResultsCompared to placebo, GLY 25 mcg and 50 mcg BID over 12 weeks significantly reduced the risk of CID by 50% (OR: 0.50 [0.37–0.68]) and 40% (OR: 0.60 [0.44–0.80]), respectively. Subjects treated with GLY 25 mcg BID were 59% less likely to experience CID in FEV1 (OR: 0.41 [0.27–0.62]) and 48% less likely to perceive CID in health status (OR: 0.52 [0.37–0.73]). Statistically significant reductions were also observed at the higher dose. The incidence of moderate/severe exacerbations was low and comparable among the cohorts. GLY 25 mcg BID was significantly more effective than placebo (p<0.05) in preventing CID irrespective of age, smoking status, LABA use, COPD severity, or PIFR. Subjects <65 years (OR 0.45 [0.29–0.68]) and those with PIFR <60 L/min (OR 0.36 [0.20–0.67]) exhibited the largest benefit.ConclusionNebulized GLY over 12 weeks significantly reduced the risk of CID and provided greater short-term stability in patients with moderate-to-very-severe COPD.

Comparison of Two Therapies on Asthma Control in Children.

Background: Childhood asthma carries significant morbidity. Aim/Objectives: Aim of the study was to compare efficacy of 2 commonly used therapies for asthma control in children with asthma. Methods: This was a 1-year, prospective cohort study at a tertiary care children's hospital. Patients were referred by their primary care physicians (PCPs) for asthma control. All patients were on low-dose inhaled corticosteroids (ICSs) at baseline. They were either switched to medium-dose ICS (ICS group) or medium-dose ICS and long-acting beta agonist (ICS+LABA group). Results were compared over time and between both groups. Results: Our cohort included 163 children (ages 2-18 years) with mean age of 5.62 ± 3.61 years. Mean Asthma Control Test (ACT) score at baseline was 15.9 ± 5.4. Mean ACT and percent predicted forced expiratory volume in one second improved (P < 0.0001 for both) in both groups. Median emergency department visits, short courses of oral steroids, and unscheduled PCP visits for acute asthma significantly decreased (P < 0.001 for all) in both groups. Similarly, days/month with wheezing, nighttime cough, and missed school days significantly decreased in both groups (P < 0.001 for all). Patients in ICS group were more likely to fail to achieve asthma control compared to patients in ICS+LABA group. Conclusion: Our study suggests that in children with uncontrolled asthma on low-dose ICS, switching to either medium-dose ICS or medium-dose ICS+LABA resulted in better symptom control, ACT improvement, and less asthma exacerbations over time. ICS+LABA had the additional benefit of less risk of treatment failure when compared to medium-dose ICS.

Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis

ObjectivesTo integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.MethodsSystematic searches MEDLINE and Embase based...

Gender Differences in Inhaled Pharmacotherapy Utilization in Patients with Obstructive Airway Diseases (OADs): A Population-Based Study.

PurposeGender differences in the incidence, susceptibility and severity of many obstructive airway diseases (OADs) have been well recognized. However, gender differences in the inhaled pharmacotherapy profile are not well characterized.MethodsWe conducted a retrospective cohort study to investigate gender differences in new-users of inhaled corticosteroids (ICS), short-or long-acting beta2-agonist (SABA or LABA), ICS/LABA, short-or long-acting muscarinic antagonist (SAMA or LAMA) among patients with asthma, COPD or asthma-COPD overlap (ACO). We used Clinical Practice Research Datalink to identify OAD patients, 18 years and older, who were new-users (1-year washout period) from 01-January-1998 to 31-July-2018. Multivariable logistic regression was used to examine gender differences in each of the inhaled pharmacotherapies after controlling for potential confounders.ResultsA total of 242,079 new-users (asthma: 84.93%; COPD: 10.19%; ACO: 4.88%) of inhaled pharmacotherapies were identified. The multivariable analyses showed that males with COPD were more likely to be a new user of a LABA (odds ratio [OR] 1.29; 95% confidence interval [CI], 1.12–1.49), LAMA (OR 1.21; 95% CI 1.10–1.33), SAMA (OR 1.11; 95% CI 1.01–1.21) and less likely to be a new user of a SABA (OR 0.84; 95% CI, 0.80–0.89) compared to females. Similar patterns were also observed for patients with ACO; males were more likely to be prescribed with LABA (OR 1.26; 95% CI 1.03–1.55), LAMA (OR 1.28; 95% CI 1.11–1.48), SAMA (OR 1.28; 95% CI 1.11–1.48), and less likely to be a new user of a SABA (OR 0.89; 95% CI, 0.82–0.96). Also, males with asthma were more likely to be a new-user of ICS/LABA (OR 1.15; 95% CI, 1.08–1.23) and less likely to start an ICS (OR 0.97; 95% CI, 0.95–0.99) in comparison with females.ConclusionOur study showed significant gender differences in new-users of inhaled pharmacotherapies among OAD patients. Adjusting for proxies of disease severity, calendar year, smoking and socioeconomic status did not change the association by gender.

Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve.

Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated. The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence. Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca. We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups. Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations. Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS). Overall, pneumologist adherence was 79.02%. The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A. Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy. Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021). ICS overprescription was the most common type of inappropriateness (17.81%). Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004). Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved. Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important. ICS represent the most prescribed overtreatment. Further multicentric studies are needed to evaluate all factors that might influence the adherence rate.

Asthma control factors in the Gulf Cooperation Council (GCC) countries and the effectiveness of ICS/LABA fixed dose combinations: a dual rapid literature review

BackgroundAsthma control is influenced by multiple factors. These factors must be considered when appraising asthma interventions and their effectiveness in the Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates [UAE]). Based on published studies, the most prevalent asthma treatment in these countries are fixed dose combinations (FDC) of inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). This study is a rapid review of the literature on: (a) factors associated with asthma control in the GCC countries and (b) generalisability of ICS/LABA FDC effectiveness studies.MethodsTo review local factors associated with asthma control and, generalisability of published ICS/LABA FDC studies, two rapid reviews were conducted. Review 1 targeted literature pertaining to asthma control factors in GCC countries. Eligible studies were appraised, and clustering methodology used to summarise factors. Review 2 assessed ICS/LABA FDC studies in conditions close to actual clinical practice (i.e. effectiveness studies). Eligibility was determined by reviewing study characteristics. Evaluation of studies focused on randomised controlled trials (RCTs). In both reviews, initial (January 2018) and updated (November 2019) searches were conducted in EMBASE and PubMed databases. Eligible studies were appraised using the Critical Appraisal Skills Program (CASP) checklists.ResultsWe identified 51 publications reporting factors associated with asthma control. These publications reported studies conducted in Saudi Arabia (35), Qatar (5), Kuwait (5), UAE (3), Oman (1) and multiple countries (2). The most common factors associated with asthma control were: asthma-related education (13 articles), demographics (11articles), comorbidities (11 articles) and environmental exposures (11 articles). Review 2 identified 61 articles reporting ICS/LABA FDC effectiveness studies from countries outside of the GCC. Of these, six RCTs were critically appraised. The adequacy of RCTs in informing clinical practice varied when appraised against previously published criteria.ConclusionsAsthma-related education was the most recurring factor associated with asthma control in the GCC countries. Moreover, the generalisability of ICS/LABA FDC studies to this region is variable. Hence, asthma patients in the region, particularly those on ICS/LABA FDC, will continue to require physician review and oversight. While our findings provide evidence for local treatment guidelines, further research is required in GCC countries to establish the causal pathways through which asthma-related education influence asthma control for patients on ICS/LABA FDC therapy.

Stable Clinical Course of Chronic Obstructive Pulmonary Disease Patients in the Era of Double Bronchodilator Therapy: A Single Referral Center Experience.

Despite clinical benefits of long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) double bronchodilator therapy, there has been limited evidence for treatment change from LAMA/LABA to inhaled corticosteroid (ICS)-containing therapy. This study aimed to assess the rate of ICS-containing therapy from LAMA/LABA and investigate the factors associated with ICS addition. Between October 2015 and March 2019, consecutive patients prescribed with a LAMA/LABA fixed-dose combinations (FDCs) therapy without ICS were retrospectively identified from a single-referral hospital. The primary outcome was addition of ICS. During LAMA/LABA FDCs therapy (median, 12.4 months), 47 (17.7%) out of 266 patients had ICS addition. Most patients maintained bronchodilators without addition of ICS at 12 (86.5%) or 24 (76.8%) months. Patients with dyspnea (mMRC ≥ 2) at baseline, previous ICS use, and exacerbation in the previous year were at a higher risk of ICS addition. Especially, exacerbation in the previous year and dyspnea were associated with the development of frequent exacerbations during LAMA/LABA FDCs therapy, which might have led to ICS addition. Double bronchodilator therapy could be well-maintained in stable COPD patients. However, patients with exacerbation in the previous year, dyspnea, and previous ICS use should be closely approached and monitored with initiation of LAMA/LABA FDCs therapy without ICS.

Patient preferences for asthma management: a qualitative study

ObjectivePreference for asthma management and the use of medications is motivated by the interplay between lived experiences of asthma and patients’ attitudes towards medications. Many previous studies have focused on...

Fixed-dose combination of three drugs, i.e. LABA/LAMA/ICS for COPD: Results of a real-world study from India

BackgroundThe use of triple therapy with inhaled corticosteroids, long-acting beta-agonist and long-acting antimuscarinics has been shown to be beneficial in COPD patients who continue to have symptoms and exacerbations, despite receiving dual bronchodilator combinations. This study assessed the real-world effectiveness and safety of once-daily, fixed-dose combination of Tiotropium/Formoterol/Ciclesonide (TFC) (18 mcg/12 mcg/400 mcg) via dry powder inhaler (DPI) or metered dose inhaler (MDI) in patients with COPD. Patients and methodsIn this 24-week, open-label, prospective, non-comparative, multicentre, real-world study, COPD patients requiring triple therapy as judged by their physician, were enrolled. The primary endpoint was mean change from baseline in pre-dose Forced Expiratory Volume in 1 s (FEV1) at week 24. Pre and post-dose (30 min) FEV1, Forced Vital capacity (FVC), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) score and safety were also evaluated. A post-hoc analysis was conducted to evaluate the efficacy of the triple drug combination among smoker and non-smoker COPD patients. ResultsOut of the 297 patients enrolled [mean age 61 ± 10 years; 84.8% males; 55.2% smokers and post-dose FEV1 (% predicted) 39 ± 16%], 253 completed the study. Mean change in pre-dose FEV1 from baseline to week 24 increased significantly after administering the triple drug combination [580 ± 600 mL, 95% CI (510, 650 mL), p < 0.0001]. The increase in the pre-dose FEV1 was significant at all time points (p < 0.0001). Similar improvements were seen in pre-dose FVC, post-dose FEV1 and post-dose FVC across all time points. CAT scores and the proportion of patients with improved mMRC score improved at all visits. The post-hoc analysis showed that TFC significantly increased pre-dose FEV1 both among smokers [mean change 200 ± 430 mL, 95% CI (130, 270 mL), p < 0.0001] as well as non-smokers [990 ± 470 mL, 95% CI (900, 1070 mL), p < 0.0001] at week 24. This difference was significant from week 12 onwards. Mean change in pre and post-dose FEV1 and FVC was significant across all visits between the two groups. At week 24, CAT score reduced significantly from baseline (overall: -6.6 ± 6.07; smokers: -5.17 + 6.96; non-smokers: 8.06 ± 4.44; all p < 0.0001). The mean difference between the two groups was 2.88 (p < 0.0001) at week 24. TFC was well tolerated. ConclusionIn this real world, multicentre study in India, TFC significantly improved lung function, symptoms and quality of life among all patients with COPD, but the effect was more pronounced among non-smoker COPD patients.

Risk factors for hospitalization, intensive care, and mortality among patients with asthma and COVID-19

This study describes the presenting characteristics of patients with asthma and COVID-19 in a US health care system, establishing an evidence base for risk evaluation and clinical care for asthma during the COVID-19 pandemic.

Biomarkers of Type 2 Airway Inflammation as Predictors of Loss of Asthma Control During Step-Down Therapy for Well-Controlled Disease: The Long-Acting Beta-Agonist Step-Down Study (LASST)

Biomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking. To evaluate whether baseline biomarkers of type 2 airway inflammation and/or serial measurement of fractional exhaled nitric oxide (Feno) predict loss of asthma control as therapy is stepped down. In subanalyses of a multicenter randomized, double-blind, parallel 3-arm trial comparing strategies for step-down therapy in well-controlled asthma (Long-Acting Beta-Agonist Step-Down Study), we assessed whether baseline atopy as determined by serum aeroallergen allergy screening test (Phadiatop), baseline serum eosinophil peroxidase, or baseline or serial Feno measurements during follow-up predicted the time to loss of asthma control among participants. Loss of asthma control was defined in the study protocol. We analyzed these associations in adjusted models including all participants, after testing for interactions with assignment to each of the 3 treatment groups (continuation of stable dose of combination inhaled corticosteroid-long-acting beta-agonist, step-down of inhaled corticosteroid, or discontinuation of long-acting bronchodilator). Four hundred forty-seven of the 553 Long-Acting Beta-Agonist Step-Down Study participants who were randomized to 1 of 3 treatment arms and had at least 1 biomarker measurement were included in this analysis. At baseline, higher levels of Feno were significantly associated with greater levels of multiallergen IgE levels (P < .001), but not with serum eosinophil peroxidase (P= .742). Among all participants as a group, elevations in baseline biomarkers were not predictive of a higher risk of treatment failure. In addition, Feno levels measured serially at 6-week intervals demonstrated that compared with participants with low levels (<25 parts per billion), those with intermediate (25-50 parts per billion) and high (>50 parts per billion) levels did not have significantly increased likelihood of subsequent treatment failure (hazard ratios, 1.03 [95% CI, 0.59-1.78] and 1.29 [95% CI, 0.65-2.54], respectively). There were no significant interactions of treatment group and baseline biomarkers. In patients with well-controlled asthma, neither baseline levels of type 2 airway inflammatory biomarkers nor serial measures of Feno are strong predictors of treatment failure.

Clenbuterol-Induced Myocarditis: A Case Report.

We present a case of a 22-year-old bodybuilder diagnosed with myocarditis secondary to clenbuterol use. The patient was primarily managed conservatively by the discontinuation of clenbuterol and the temporary use of dual anti-platelets, beta-blockers and nitrates. Clenbuterol is a long-acting beta-2 agonist primarily used in veterinary medicine. In recent years, it has been illegally marketed as a weight loss supplement because of its anabolic properties and is popular among fitness enthusiasts. It is our aim to use this case to underscore the adverse effects of this drug with hopes that tighter regulations will be instituted to stem its illegal distribution. Clenbuterol is primarily a veterinary drug with bronchodilator and tocolytic properties.It is illegally used as a performance enhancer by athletes and bodybuilders because of its anabolic properties.Clenbuterol misuse can result in myocardial injury.