Use Of Long-acting Bronchodilators Research Articles

Combined therapy of broncho-obstructive pathology: two solutions to one problem

Chronic broncho-obstructive pulmonary diseases – bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) – are a serious clinical problem and an economic burden for practical healthcare. The purpose of the scientific review is to track the evolution of views on the use of bronchodilators and inhaled corticosteroids (ICS) in these diseases and to analyze modern approaches to treatment based on domestic and international guidelines. COPD treatment is aimed at two pathogenetic components – inflammation of the bronchi and the formation of emphysema. The basis of basic therapy remains the use of long-acting bronchodilators of two classes. Treatment of asthma is directed primarily at chronic inflammation of the airways using long-acting bronchodilators. The basis of basic therapy for asthma is the use of inhaled glucocorticosteroids. Currently, the same combinations of bronchodilators and ICS are recommended for both asthma and COPD. One direction is based on the use of ICS with formoterol, a 12-hour drug with a fast onset, in which the drug can be used on demand. The second direction is based on the constant use of ICS/LABA only on a regular basis, but with the ability to use bronchodilators on demand. In this case, ICS with high affinity are more often used. An important component of treatment is adherence to medical prescriptions and the availability of different types of drugs for patients in real clinical practice. At present, conditions have been created in Russia for the implementation of both the treatment of patients with asthma and the treatment of patients with COPD with frequent exacerbations and eosinophilia based on import substitution with modern drugs.

Valoración ecográfica de la dinámica diafragmática en pacientes con enfermedad pulmonar obstructiva crónica tras tratamiento con indacaterol/glicopirronio

IntroductionAir trapping is one of the main determinants of dyspnea in patients with chronic obstructive pulmonary disease (COPD). An increase in air trapping leads to the diaphragm losing its usual configuration and thus affects its functionality; said functionality seems to improve after administering bronchodilator therapy. Chest ultrasound (CU) has been used to assess changes after the use of short-acting bronchodilators, but there are no studies that assess these changes with the use of long-acting bronchodilators. Material and methodsThis work is a prospective interventional study with 3months of follow-up that assessed diaphragm motion/thickness by means of CU before and after starting treatment with indacaterol/glycopyrronium 85/43 mcg in patients with COPD and moderate to very severe airway obstruction. ResultsThirty patients were included (56.6% men, mean age: 69.4±6.2 years). Pre- and post-treatment diaphragmatic mobility measured during resting breathing, deep breathing, and nasal sniffing were 19.9±7.1mm and 26.4±8.7mm (p < 0.0001); 42.5±14.1mm and 64.5±25.9mm (p < 0.0001); and 36.5±17.4mm and 46.7±18.5mm (p = 0.012), respectively. A significant improvement was also found in the minimum and maximum diaphragm thickness (p < 0.05), but there were no significant changes in the diaphragmatic shortening fraction after treatment (p = 0.341). ConclusionsTreatment with indacaterol/glycopyrronium 85/43 mcg every 24hours for 3months improved diaphragmatic mobility in patients with COPD with moderate to very severe airway obstruction. CU may be useful for assessing the response to treatment in these patients.

Bronchodilator therapy in patients with chronic obstructive pulmonary disease: what should be considered in clinical practice when choosing a dosing regimen?

The use of long-acting bronchodilators is central to the chronic obstructive pulmonary disease (COPD) therapy. One of the goals of bronchodilation is to reduce the morning COPD symptoms that are associated with a more severe disease and an increased risk of exacerbations.The aim of the study was to evaluate the clinical efficacy of switching COPD patients with severe morning symptoms who received combinations of long-acting bronchodilators QD to a fixed-dose combination of aclidinium bromide (AB) and formoterol fumarate (FF) BID.Methods. We examined COPD patients treated with combinations of long-acting β2-agonists and M-anticholinergics (but not AB and FF), who continued to complain of severe symptoms in the morning despite the treatment. After examination, the patients were switched to the fixed-dose combination of AB 0.4 mg and FF 0.012 mg (AB/FF) BID in the form of a metered-dose powder inhaler. The patients were examined at baseline and at 6-month follow-up.Results. Of the 115 included COPD patients, 90 completed the study. After 6 months of treatment, they showed a significant decrease in the intensity of cough, sputum amount, severity of distant wheezing, and shortness of breath in the morning (–0.88, –0.38, –0.29, –0.58 on a 4-point scale, the mean score –0.44; p &lt; 0.001). The result of the COPD Assessment test decreased from 28 (24; 34) to 24 (20; 28) (p = 0.011), the distance of a 6-minute walk increased from 319 ± 72 to 354 ± 67 m (p &lt; 0.001). The fixed-dose combination of AB/FF did not cause serious adverse events.Conclusion. The fixed-dose AB/FF combination in COPD patients resulted in a significant clinical improvement and was well tolerated. The AB/FF combination with twice daily dosing regimen is advisable for the patients with morning symptoms persisting despite therapy with other combinations of long-acting bronchodilators with once daily dosing regimen.

Moving the pathway goalposts: COPD as an immune-mediated inflammatory disease

Chronic obstructive pulmonary disease (COPD) encompasses a spectrum of lung disorders that cause lung function decline. The degree by which lung function has decreased is used to classify disease severity and as a guide for escalated long-acting bronchodilator use. This strategy aims to modify symptoms but does not target the inflammatory processes that drive disease progression. COPD has distinct, but non-mutually exclusive, endotypes such as chronic bronchitis and emphysema.1 These endotypes each have unique pathogeneses, and diagnosis of COPD is often not consistent between individuals in terms of immunopathology.

Explainable Machine Learning Model for Predicting First-Time Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Background: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level. Methods: We conducted a retrospective case–control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model’s decisions. Results: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745–0.921] and AUC = 0.836 [95% CI 0.757–0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was <0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD. Conclusions: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model’s decision-making process.

Long-Acting Bronchodilator Use in Chronic Obstructive Pulmonary Disease in Primary Care in New Zealand: A Retrospective Study of Treatment Patterns and Evolution Using the HealthStat Database.

PurposeLong-acting bronchodilator (LABD) use is the mainstay of pharmacologic treatment for chronic obstructive pulmonary disease (COPD). Few studies describe evolving patterns of LABD use in the setting of changing inhaler availability and updated clinical guidelines.MethodsA retrospective cohort study in New Zealand using the HealthStat general practice database (01/2014 to 04/2018). Eligible patients (aged ≥40 years) had COPD and ≥1 LABD prescription (long-acting muscarinic antagonist [LAMA] and/or long-acting β2-agonist [LABA]) during the index period (05/2015 to 04/2016). Demographics and clinical characteristics of all LABD users (overall/by treatment) were described at baseline. Patients starting LABD treatment during the index period, termed “new” users, were also described, as was their treatment evolution over 24 months of follow-up. Yearly LABD initiation rates were assessed from 2015 to 2017, covering changes to Pharmaceutical Management Agency criteria and clinical guidelines.ResultsAcross 2140 eligible patients, the most common index treatments were inhaled corticosteroid (ICS)/LABA (59.0%) and open triple therapy (LAMA+LABA+ICS; 26.7%). ICS/LABA therapy was highest in younger patients, with open triple therapy highest in older patients. Prior yearly exacerbation rates were lowest in those receiving monotherapy (LABA: 0.9/year; LAMA: 1.1/year) versus dual therapy (all 1.4/year) and open triple therapy (2.2/year). Of 312 new LABD users, ICS/LABA was the most common index treatment (69.6%), followed by LAMA monotherapy (16.0%). Continuous use with index treatment was 31.1% at 12 months and 13.5% at 24 months; mean time to treatment change was 175.5 and 244.1 days, respectively. Among patients modifying treatment at 24 months, 23.0% augmented, 7.0% switched, 45.6% re-started, and 24.4% discontinued/stepped down. Among patients initiating LABD each year from 2015 to 2017, LAMA prescription increased (17% to 46%) while ICS prescription remained stable (approximately 20%).ConclusionPredominant use of ICS/LABA (05/2015 to 04/2016) reflects available LABDs and previous restrictions on LAMA use in New Zealand.

Comorbid Anxiety and Depression, Though Underdiagnosed, Are Not Associated with High Rates of Low-Value Care in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) and anxiety or depression experience more symptoms and exacerbations than patients without these comorbidities. Failure to provide beneficial COPD therapies to appropriate patients (underuse) and provision of potentially harmful therapies to patients without an appropriate indication (overuse) could contribute to respiratory symptoms and exacerbations. Anxiety and depression are known to affect the provision of health services for other comorbid conditions; therefore, underuse or overuse of therapies may explain the increased risk of severe symptoms among these patients.Objectives: To determine whether diagnosed anxiety and depression, as well as significant anxiety and depression symptoms, are associated with underuse and overuse of appropriate COPD therapies.Methods: We analyzed data from a multicenter prospective cohort study of 2,376 participants (smokers and control subjects) enrolled between 2010 and 2015. We identified two subgroups of participants, one at risk for inhaled corticosteroid (ICS) overuse and one at risk for long-acting bronchodilator (LABD) underuse based on the 2011 Global Initiative for Chronic Obstructive Lung Disease statement. Our primary outcomes were self-reported overuse and underuse. Our primary exposures of interest were self-reported anxiety and depression and significant anxiety and depression symptoms. We adopted a propensity-score method with inverse probability of treatment weighting adjusting for differences in prevalence of confounders and performed inverse probability of treatment weighting logistic regression to evaluate all associations between the exposures and outcomes.Results: Among the 1,783 study participants with COPD confirmed by spirometry, 667 (37.4%) did not have an indication for ICS use, whereas 985 (55.2%) had an indication for LABD use. Twenty-five percent (n = 167) of patients reported ICS use, and 72% (n = 709) denied LABD use in each subgroup, respectively. Neither self-reported anxiety and depression nor significant anxiety and depression symptoms were associated with overuse or underuse. At least 50% of patients in both subgroups with significant symptoms of anxiety or depression did not report a preexisting mental health diagnosis.Conclusions: Underuse of LABDs and overuse of ICSs are common but are not associated with comorbid anxiety or depression diagnosis or symptoms. Approximately one-third of individuals with COPD experience anxiety or depression, and most are undiagnosed. There are significant opportunities to improve disease-specific and patient-centered treatment for individuals with COPD.

Comparative Causal Analysis of the Effects of Long-Acting Muscarinic Antagonist Versus No Long-Acting Bronchodilator Use on Readmission or Mortality After Hospitalization for Chronic Obstructive Pulmonary Disease.

BackgroundRetrospective observational studies may provide real-world evidence about long-acting muscarinic receptor antagonist (LAMA) effectiveness in reducing mortality or COPD-related readmission risk after a COPD hospitalization. Causal inference and competing risk statistical procedures aid in managing confounding and competing outcome events that complicate retrospective analyses.ObjectiveTo compare COPD-related readmission and mortality risk among patients receiving a LAMA versus patients receiving no long-acting bronchodilator (“no LABD”) within 30 days post-discharge.MethodsThis retrospective observational analysis of patients (aged ≥ 40 years) hospitalized for COPD used claims data (years 2004–2012). Events occurring during the period from 31 days through 12 months post-discharge were compared. The hazard ratio (HR) for the combined outcome of COPD-related readmission or mortality was estimated using Cox regression. Confounding was addressed using inverse probability of treatment weighting (IPTW). The competing risk of non-COPD-related readmission was considered.Results10,405 COPD patients were included (LAMA = 751, no LABD = 9654). IPTW achieved a balanced sample (10,518 LAMA, 10,405 no LABD). Unweighted HR (LAMA vs no LABD) for COPD-related readmission or death, adjusted for age, sex, comorbidities, and baseline utilization, was 1.00 [95% confidence interval (CI) 0.84, 1.20]. Weighted (IPTW) adjusted HR was 0.94 (95% CI 0.88, 1.00). Unweighted and weighted HRs further adjusted for competing risk were 0.97 (95% CI 0.82, 1.16) and 0.91 (0.86, 0.98), respectively.ConclusionsBias by indication and comorbidities make the measurement of retrospective COPD treatment effectiveness difficult. Using IPTW and additionally considering the competing event risk, LAMA use was associated with a small reduction in risk for COPD-related readmission or death over the period from 31 days to 12 months post-discharge.Electronic supplementary materialThe online version of this article (10.1007/s40801-019-00171-w) contains supplementary material, which is available to authorized users.

Major comorbidities lead to the risk of adverse cardiovascular events in chronic obstructive pulmonary disease patients using inhaled long-acting bronchodilators: a case-control study

BackgroundWhile inhaled bronchodilators reduce symptoms and acute exacerbations of chronic obstructive pulmonary disease (COPD), their use is associated with increased cardiovascular events in some studies. This study investigates the risk of adverse events associated with the use of inhaled bronchodilators in COPD patients with multimorbidity.MethodsA case-control study was conducted between January 2015 and December 2017, and patients with spirometry-confirmed diagnosis of COPD (N = 1565) using inhaled long-acting bronchodilators were enrolled. Medical records were reviewed and clinical data, including age, gender, smoking status, major comorbidities, lung function stage, history of exacerbations, bronchodilator regimens, and treatment duration were analyzed. Major adverse cardiovascular events occurring during long-acting bronchodilator use were recorded.ResultsThe most common comorbidities were cardiovascular disease (CVD) (53.6%) and chronic kidney disease (CKD) (25.8%). We observed that CVD (odds ratio [OR], 5.77), CKD (OR, 2.02) and history of frequent exacerbations (OR, 2.37) were independent risk factors for cardiovascular events, regardless of the type of bronchodilators use. Moreover, COPD patients with both CKD and CVD had higher risk (6.32-fold) of adverse cardiovascular effects than those with neither comorbidity. Eighty-seven of 1565 (5.56%) COPD patients died during this study period. Of them, 21.8% (19/87) were cardiovascular-related and 73.6% (64/87) patients were respiratory-related mortality. Among COPD patients using long-acting bronchodilators, CKD was the only risk factor to predict cardiovascular events and cardiovascular-related mortality (OR, 4.87; 95% confidence interval [CI], 1.75–13.55].ConclusionsCOPD patients had higher risk of cardiovascular events were associated with their CVD and/or CKD comorbidities and history of frequent exacerbations, rather than associated with their use of inhaled bronchodilators.

EFFICACY OF NEBULIZED ARFORMOTEROL FOR THE TREATMENT OF PATIENTS WITH COPD: A ROLE FOR LONG-ACTING BRONCHODILATORS IN TREATING LONG-TERM CARE PATIENTS WITH COPD

SESSION TITLE: Monday Electronic Posters 4 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and increased health care resource utilization in long-term care (LTC) nursing home facilities in the US. Although GOLD guidelines recommend the use of long-acting bronchodilators (LABDs) for the treatment of COPD, as they are more effective and convenient than regular treatment with short-acting bronchodilators (SABDs), a large proportion of nursing home residents with a diagnosis of COPD do not receive any respiratory medication. Arformoterol tartrate (ARF; 15 μg twice daily [BID]) is a nebulized long-acting beta2-agonist (LABA) indicated for the maintenance treatment of bronchoconstriction in patients with COPD; ARF should not be used as rescue medication. In this post-hoc analysis, the efficacy of ARF was assessed in older COPD patients and in patients with very severe COPD. METHODS: Data from two identical, 12-week, multicenter, double-dummy, randomized Phase III trials (NCT00685841 and NCT00064402) evaluating improvement in airway function with ARF treatment in patients with COPD were pooled for analysis. Patients (n=1456; mean predicted forced expiratory volume in 1 second [FEV1]=40.6% [standard deviation: 12.8]) received nebulized ARF 15 μg BID, 25 μg BID, or 50 μg once daily (QD), salmeterol 42 μg BID (via metered dose inhaler), or placebo BID for 12 weeks. In order to assess the efficacy of ARF in patients with COPD representative of an LTC population, an analysis of improvement in airway function (as measured by FEV1) was performed comparing ARF 15 ug BID with placebo (BID) in a subset of patients defined by age (≥75 years; n=160) and baseline COPD disease severity (FEV1 <30% predicted; n=410). RESULTS: In the overall study population, the median % change in FEV1 was 2.05% among patients receiving placebo and 12.72% in patients treated with ARF 15 μg BID. In patients ≥75 years of age, the median % change in FEV1 was −5.22% in patients receiving placebo compared with 18.62% improvement in patients treated with ARF 15 μg BID. In patients with severe COPD disease (<30% FEV1 % predicted), the median % change in FEV1 was 5.13% among patients receiving placebo compared with 22.58% in patients treated with ARF 15 μg BID. CONCLUSIONS: Despite the recommendations for use of LABDs by GOLD guidelines, many LTC nursing home residents with COPD do not receive any respiratory medications. In this post-hoc analysis of patients with COPD representative of nursing facility residents (≥75 years of age; severe baseline disease), treatment with ARF 15 μg BID resulted in greater improvements in lung function when compared with placebo. CLINICAL IMPLICATIONS: LABDs such as ARF should be considered as a treatment option for residents in an LTC setting with a diagnosis of COPD. DISCLOSURES: Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/11/2019 by Thomas Goodin, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/12/2019 by Ayca Ozol-Godfrey, source=Admin input, value=Salary Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/13/2019 by Barry Price, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Inc. Please note: >$100000 Added 03/14/2019 by Shahin Sanjar, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Inc. Please note: $20001 - $100000 Added 03/11/2019 by Sanjay Sharma, source=Web Response, value=Salary Removed 03/11/2019 by Sanjay Sharma, source=Web Response Employee relationship with Sunovion Pharmaceuticals, Inc. Please note: >$100000 Added 03/11/2019 by Sanjay Sharma, source=Web Response, value=Salary

Consequences of Changing the GOLD Reports (2007–2011–2017) on the Treatment Regimen of Patients with COPD

Detailed treatment regimens for patients with chronic obstructive pulmonary disease (COPD) were developed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Every few years the method of classification of COPD severity and the treatment recommendations are significantly revised. The aim of this study was to determine the clinical implications of changing GOLD reports (2007–2011–2017) and the impact that these changes would have on pharmacological treatment regimens of patients with COPD. A group of 500 randomly chosen primary care physicians in Poland each provided information on 10 consecutive patients diagnosed with COPD. This data was used to simulate the therapeutic consequences of the update of the GOLD 2007 report to GOLD 2011 and GOLD 2017. Pharmacological treatment algorithms from the GOLD 2007 report prefer the use of inhaled corticosteroids (ICS) and short-acting bronchodilators (60.2% and 50%, respectively). Compared to the GOLD 2007 report, there would be an almost eightfold reduction in the frequency of short-acting bronchodilator using the GOLD 2011 report and over fourfold decrease using the GOLD 2017 report. With each subsequent update of the GOLD report, the frequency of use of ICS would be significantly (p < 0.001) reduced. Pharmacological treatment by the GOLD 2011 and 2017 reports would be dominated by the use of long-acting bronchodilators from the group β2-agonists and muscarinic antagonist groups. Updates from the GOLD 2007 COPD report to GOLD 2011 and 2017 would have a significant impact on everyday clinical practice. Changes would result in a reduction of treatment intensity.

Respiratory medication used in COPD patients from seven Latin American countries: the LASSYC study.

BackgroundLimited information is available regarding medication use in COPD patients from Latin America. This study evaluated the type of medication used and the adherence to different inhaled treatments in stable COPD patients from the Latin American region.MethodsThis was an observational, cross-sectional, multinational, and multicenter study in COPD patients attended by specialist doctors from seven Latin American countries. Adherence to inhaled therapy was assessed using the Test of Adherence to Inhalers (TAI) questionnaire. The type of medication was assessed as: short-acting β-agonist (SABA) or short-acting muscarinic antagonist (SAMA) only, long-acting muscarinic antagonist (LAMA), long-acting β-agonist (LABA), LABA/LAMA, inhaled corticosteroid (ICS), ICS/LABA, ICS/LAMA/LABA, or other.ResultsIn total, 795 patients were included (59.6% male), with a mean age of 69.5±8.7 years and post-bronchodilator FEV1 of 50.0%±18.6%. The ICS/LAMA/LABA (32.9%) and ICS/LABA (27.7%) combinations were the most common medications used, followed by LABA/LAMA (11.3%), SABA or SAMA (7.9%), LABA (6.4%), LAMA (5.8%), and ICS (4.3%). The types of medication most commonly used in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 category were ICS/LABA (A: 32.7%; B: 19.8%; C: 25.7%; D: 28.2%) and ICS/LAMA/LABA (A: 17.3%; B: 30.2%; C: 33%; D: 41.1%). The use of long-acting bronchodilators showed the highest adherence (good or high adherence >50%) according to the TAI questionnaire.ConclusionCOPD management in specialist practice in Latin America does not follow the current guideline recommendations and there is an overuse of ICSs in patients with COPD from this region. Treatment regimens including the use of long-acting bronchodilators are associated with the highest adherence.

Clinical and economic outcomes associated with the use of fluticasone propionate 250 mcg and salmeterol 50 mcg combination versus tiotropium bromide 18 mcg as initial maintenance treatment for chronic obstructive pulmonary disease in managed care

Aims: To examine the clinical and economic outcomes associated with the use of long-acting bronchodilators for initial maintenance treatment of chronic obstructive pulmonary disease (COPD) by analyzing health insurance claims data in the US.Methods: A retrospective, observational, matched cohort study used health insurance claims data (January 2008 to June 2013) to assess COPD-related outcomes for subjects aged ≥40 years. Subjects were assigned to a study cohort according to the first observed prescription fill for a long-acting bronchodilator (fluticasone propionate 250 mcg/salmeterol 50 mcg [FSC] or tiotropium bromide 18 mcg [TIO]). The analysis period for each subject comprised a 1-year pre-index date and 1-year post-index date. Primary outcome measure was total COPD-related costs per-patient per-year (PPPY) during the follow-up period. Secondary outcome measures included COPD-related exacerbations and the components of COPD-related costs.Results: Overall, 24,040 subjects were identified; the analysis sample consisted of 19,090 subjects (9,545 per cohort) with no significant differences between cohorts. Mean COPD-related total costs PPPY were numerically lower among the FSC cohort; however, the difference was not statistically significant ($2,224 [±4,108] vs $2,352 [±3,721], p = .057). There was no difference between cohorts for COPD-related medical costs (p = .894). COPD-related pharmacy costs were significantly, yet modestly, lower in the FSC cohort compared with the TIO cohort ($1,160 [±1,106] vs 1,275 [±1,110], p < .001). There were no statistically significant differences in the rate or number of exacerbations between the matched cohorts.Limitations: While propensity scoring achieved balance in baseline characteristics, some residual confounding unobserved in the database may be present.Conclusions: Few clinical and economic differences between subjects initiating maintenance therapy with FSC or TIO were observed.

In COPD, new use of long-acting bronchodilators was linked to CV events at ≤30 days, but not >30 days.

Source Citation Wang MT, Liou JT, Lin CW, et al. Association of cardiovascular risk with inhaled long-acting bronchodilators in patients with chronic obstructive pulmonary disease: a nested case–co...

Seventeen-Year Nationwide Trends in Use of Long-acting Bronchodilators and Inhaled Corticosteroids among Adults - A Danish Drug Utilization Study.

Long-acting bronchodilators and inhaled corticosteroids (ICS) are the cornerstones in treatment of chronic obstructive and inflammatory pulmonary diseases. However, non-adherence to guidelines is widespread. Detailed information on real-life treatment patterns is needed to promote rational use. We aimed to investigate nationwide time trends in individual-level treatment patterns of long-acting bronchodilators and ICS. Using nationwide Danish health registries, we identified all Danish adults with a prescription for long-acting bronchodilators and/or ICS from 2000 to 2016. We investigated the total use of long-acting bronchodilators and ICS, the proportion of current users and the rate of new users over time. Finally, we assessed treatment persistence. We included 23,061,681 prescriptions for long-acting bronchodilators and ICS issued to 805,860 individuals from 2000 to 2016. Over this period, the total annual amount of prescribed long-acting bronchodilators and ICS increased by 39%. Similarly, the proportion of adult users increased from 2.6% to 4.5%, mainly driven by the introduction of combination therapy and long-acting muscarinic antagonist (LAMA). Although the rate of new users of fixed-dose combination drugs increased substantially over time, the overall rate of new users was stable. In general, the proportion of patients on therapy after 1 year was low (25-53%), especially among young individuals and users of ICS. We document a pronounced increase in the total use of long-acting bronchodilators and ICS over time, mainly driven by the introduction of combination drugs and LAMA. Special attention should be paid to the low level of persistence, especially among young individuals and users of ICS.

Evaluation of Inhaled Procaterol for Potential Assist Use in Patients with Stable Chronic Obstructive Pulmonary Disease

Objectives: International guidelines recommend the use of long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease (COPD), but the usefulness of short-acting bronchodilator assist use for stable COPD remains uncertain. The purpose of the present study was to objectively demonstrate the effects of assist use of procaterol, a short-acting β₂-agonist, on the respiratory mechanics of stable COPD patients treated with a long-acting bronchodilator using forced oscillation technique (FOT) and conventional spirometry. We also confirmed the length of time for which procaterol assist could significantly improve the pulmonary function. Methods: We enrolled 28 outpatients with mild to severe COPD (Global Initiative for Obstructive Lung Disease stages I–III), who had used the same long-acting bronchodilator for longer than 3 months and who were in stable condition. All measures were performed using both FOT and spirometry sequentially from 15 min to 2 h after inhalation. Results: Compared to baseline, inhaled procaterol assist use modestly but significantly improved spirometric and FOT measurements within 2 h after inhalation. These significant effects continued for at least 2 h. ­Significant correlations were found between parameters ­measured by spirometry and those measured by FOT. Conclusions: Procaterol assist use modestly but significantly improved pulmonary function determined by spirometry and respiratory mechanics in patients with stable COPD treated with long-acting bronchodilators. Thus, inhaled procaterol has the potential for assist use for COPD.

Long-Acting Bronchodilator Use in the Management of Stable COPD.

To review the management of chronic obstructive pulmonary disease (COPD), with a focus on updated information regarding the use of long-acting bronchodilators in the prevention of exacerbations and outcomes associated with this disease. A literature search of the MEDLINE databases through November 2017 was conducted. All published articles regarding use of bronchodilator therapy in the management of COPD were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of stable COPD with bronchodilator therapy in humans were reviewed; relevant clinical data were selected and included. COPD is a prevalent medical condition worldwide that results in functional impairment, and worsened quality of life and overall health status. Numerous treatment options are available; the rationale for the optimal agents to utilize in a particular patient case is dependent on a multitude of patient-specific factors and severity of disease. In this review, a discussion of the role of long-acting bronchodilators, including long-acting β agonists and long-acting muscarinic antagonists will be explored. Additionally, an update on the roles of novel delivery devices for delivering respiratory medications in this medical condition will be described. Although numerous treatment options are available, management of COPD remains a clinical challenge. Long-acting bronchodilators represent a significant class of medications that have the potential to reduce exacerbations and related hospitalizations and improve overall health outcomes.

Medication Management Patterns Among Medicare Beneficiaries With COPD Initiating Nebulized Arformoterol Treatment

SESSION TITLE: COPD: Lessons for the Real-World Management of Disease SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 02:45 PM - 04:15 PM PURPOSE: Global guidelines recommend the use of long-acting bronchodilators (LABD) as maintenance therapy for patients with COPD. However, little is known about the treatment and management patterns associated with initiating nebulized LABD therapy such as arformoterol. This study examined these treatment patterns among Medicare beneficiaries with COPD prior to and after initiating arformoterol. METHODS: Medicare administrative data from 2010-2014 were used to identify beneficiaries with ≥2 COPD outpatient visits within 30 days apart or with ≥1 COPD-related hospitalization(s) (i.e., ICD-9 codes 491.xx, 492.xx, and 496). Patients continuously enrolled in Medicare parts A, B, and D for the entire study period that initiated arformoterol were identified after excluding deaths. The use of the four following COPD medication classes 90-days prior to (pre-period) and after initiation of arformoterol (post-period) were examined: (a) LAMA/LABA: long-acting muscarinic antagonists (LAMAs) and inhaled long-acting beta2 agonists (LABAs) including fixed dose LABA+inhaled corticosteroid (ICS) combinations; (b) ICS/Neb ICS: ICS and nebulized corticosteroids (neb-CS); (c) methylxanthines, and d) other that included medications such as short-acting bronchodilators (SABD), oral corticosteroids and antibiotics. Rates of medication initiation, treatment continuation and discontinuation within these classes were determined based on refill patterns in the post-period. Sociodemographic and clinical characteristics (e.g., comorbidities) were also examined. Descriptive statistics were used to examine means, frequencies, and proportions. All analyses were preformed using SAS Enterprise Guide 7.1. RESULTS: A total of 11,886 nebulized arformoterol users were identified for the analysis. A substantial proportion of the patient cohort was 75 years or older (42%) and dually eligible for Medicaid (37%). Overall, 5,542 (46%) beneficiaries had received no LABD maintenance treatment 90 days prior to initiating arformoterol. Instead, they were being treated with a nebulized (50%) or an inhaled (37%) SABD, a systemic CS (46%), and many were on antibiotics (37%). In the post-period, 58% of beneficiaries received dual-therapy (LABA/ICS/Neb ICS [52%] or LAMA/LAMA [6%]), 21% received triple-therapy (LABA/LAMA/ICS/Neb CS), and 20% received monotherapy (only arformoterol). Nearly 41% of beneficiaries dropped ≥1 classes of medications they were taking prior to initiating arformoterol in the post-period. The largest decrease (-23%) was seen in CS use. CONCLUSIONS: The results suggest that nearly half of beneficiaries with COPD are not being treated with recommended LABD maintenance therapy. Among arformoterol users, dual therapy with a CS was highly prevalent. About 1 in 5 beneficiaries received either triple therapy or monotherapy. CLINICAL IMPLICATIONS: Evaluating the drivers associated with over reliance on SABD in lieu of recommended LABD maintenance treatment for appropriate patients, examining the triggers for initiating arformoterol, and linking arformoterol monotherapy v. combination therapy to outcomes are warranted. These analyses could help advance clinical decision-making for patients with COPD, particularly for those who have a history of exacerbations and hospitalizations. DISCLOSURE: Bartolome Celli: Consultant fee, speaker bureau, advisory committee, etc.: Advance Health Solutions, LLC, University grant monies: Astra Zeneca, Consultant fee, speaker bureau, advisory committee, etc.: Glaxo Smith Kline, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Astra Zeneca, Consultant fee, speaker bureau, advisory committee, etc.: Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Pulmonix Maryam Navaie: Consultant fee, speaker bureau, advisory committee, etc.: Sunovion Pharmaceuticals Inc., Employee: Advance Health Solutions, LLC Vaidyanathan Ganapathy: Employee: Sunovion Pharmaceuticals, Inc. Zhun Xu: Grant monies (from industry related sources): Advance Health Solutions, LLC Soojin Cho-Reyes: Consultant fee, speaker bureau, advisory committee, etc.: Advance Health Solutions, LLC Todd Gilmer: Grant monies (from industry related sources): Advance Health Solutions, LLC No Product/Research Disclosure Information

Efficacy of montelukast sodium in the treatment of stable chronic obstructive pulmonary disease

Objective To investigate the application value of montelukast in patients with stable chronic obstructive pulmonary disease (COPD). Methods 64 patients with stable COPD in Jinqiu Hospital of Liaoning Province from December 2015 to December 2016 were randomly divided into observation group and control group according to the digital table, 32 cases in each group.The two groups were given routine treatment, including cough, phlegm, oxygen therapy, smoking cessation, rehabilitation treatment, regular use of long-acting bronchodilators, on this basis, the observation group was treated with montelukast sodium.After 12 weeks of treatment, the patients were assessed for airway improvement and quality of life before and after treatment, and recorded the two groups of acute exacerbation and adverse drug reactions. Results The two groups had improved lung function and quality of life after treatment, but after treatment, the FEV1, FVC and FEV1 actual/FEV1 prediction of the observation group were significantly higher than those of the control group, the differences were statistically significant (t=2.49, 1.77, 1.85 all P<0.05). After treatment, the 6 minutes walking distance of the observation group was longer than that of the control group, Borg score of the observation group was lower than that of the control group, the differences were statistically significant (t=1.83, 6.66, all P<0.05). After treatment, the SGRQ score in the observation group was lower than that of the control group, the difference was statistically significant[(51.15±3.14)points vs.(54.83±4.03)points, t=3.94, P<0.01]. Conclusion Montelukast can effectively improve the stability of COPD pulmonary function and quality of life, and with high safety. Key words: Pulmonary disease, chronic obstructive; Montelukast sodium; Clinical observation

Concurrent use of long-acting bronchodilators in COPD and the risk of adverse cardiovascular events.

The cardiovascular risk of concurrently using long-acting β2-agonists (LABAs) and anticholinergics (LAMAs) in COPD is uncertain. We assessed the comparative cardiovascular and cerebrovascular safety of adding a second long-acting bronchodilator in patients with COPD.We identified a cohort of COPD patients, new users of LABA or the LAMA tiotropium during 2002-2012, from the UK Clinical Practice Research Datalink. Using high-dimensional propensity scores, each patient adding a second bronchodilator was matched with a patient who remained on monotherapy. Patients were followed for 1 year for the occurrence of acute myocardial infarction (AMI), stroke, heart failure and arrhythmia.The cohorts included up to 31 174 patients adding a bronchodilator matched to 31 174 patients remaining on bronchodilator monotherapy. Adding a long-acting bronchodilator, compared to remaining on monotherapy, was not associated with an increased risk of AMI (hazard ratio (HR) 1.12, 95% CI 0.92-1.36), stroke (HR 0.87, 95% CI 0.69-1.10) or arrhythmia (HR 1.05, 95% CI 0.81-1.36), but the risk was elevated for heart failure (HR 1.16, 95% CI 1.03-1.30).Adding a second long-acting bronchodilator in the real-world-setting treatment of COPD does not increase the risk of most cardiovascular events. The modest increase for heart failure warrants further investigation.