Use Of Long-acting Beta-agonists 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.

The efficacy and safety of additional treatment with short-acting muscarinic antagonist combined with long-acting beta-2 agonist in stable patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) is not adequately studied. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of a short-acting muscarinic antagonist (SAMA) therapy combined with a long-acting beta-2 agonist (LABA) in patients with stable COPD. Pulmonary function, dyspnea, health-related quality of life, exercise tolerance, physical activity, exacerbations of COPD, and adverse events during regular use were set as outcomes of interest. We included five controlled trials including two sets of publicly available online data without article publications for the meta-analysis. Additional use of SAMA plus LABA showed a significant improvement in the peak response in FEV1 (mean difference (MD) 98.70mL, p < .00001), transitional dyspnea index score (MD .85, p = .02), and St George's Respiratory Questionnaire score (MD -2.00, p = .008) compared to LABA treatment. There was no significant difference in the risk of exacerbation of COPD (p = .20) and only a slight trend of increased severe adverse events (OR: 2.16, p = .08) and cardiovascular events (OR: 2.38, p = .06). Additional treatment with SAMA combined with LABA could be a feasible choice due to its efficacy and safety.

A new analytic tool for assessing the impact of the US Food and Drug Administration regulatory actions.

Develop and test a flexible, scalable tool using interrupted time series (ITS) analysis to assess the impact of Food and Drug Administration (FDA) regulatory actions on drug use. We applied the tool in the Sentinel Distributed Database to assess the impact of FDA's 2010 drug safety communications (DSC) concerning the safety of long-acting beta2-agonists (LABA) in adult asthma patients. We evaluated changes in LABA use by measuring the initiation of LABA alone and concomitant use of LABA and asthma controller medications (ACM) after the DSCs. The tool generated ITS graphs and used segmented regression to estimate baseline slope, level change, slope change, and absolute and relative changes at up to two user-specified time point (s) after the intervention. We tested the tool and compared our results against prior analyses that used similar measures. Initiation of LABA alone declined among asthma patients aged 18-45 years before FDA DSCs (-0.10% per quarter; 95%CI: -0.11% to -0.09%) and the downward trend continued after. Concomitant use of LABA and ACM was stable before FDA DSCs. After FDA DSCs, there was a small trend decrease of 0.006% per quarter (95% CI, -0.008% to -0.003%). We found similar results among those aged 46-64 years and patients with poorly-controlled asthma. Our results were consistent with previous studies, confirming the performance of the new tool. We developed and tested a reusable ITS tool in real-world databases formatted to the Sentinel Common Data Model that can assess the impact of regulatory actions on drug use.

Risk Factors for Lung Function Decline in Pediatric Asthma under Treatment: A Retrospective, Multicenter, Observational Study.

Background: Childhood asthma is a major risk for low lung function in later adulthood, but what factors in asthma are associated with the poor lung function during childhood is not known. Objective: To identify clinical factors in children with asthma associated with low or declining lung function during the treatment. Methods: We enrolled children with asthma who had been treated throughout three age periods, i.e., 6–9, 10–12, and 13–15 years old, at seven specialized hospitals in Japan. Clinical information and lung function measurements were retrieved from the electronic chart systems. To characterize the lung function trajectories during each age period, we evaluated the forced expiratory volume 1 (FEV1) with % predicted values and individual changes by the slope (S) from linear regression. We defined four trajectory patterns: normal (Group N) and low (Group L), showing %FEV1 ≥80% or <80% throughout all three periods; upward (Group U) and downward (Group D), showing S ≥ 0 or S < 0%. Logistic regression analysis was performed to compare factors associated with the unfavorable (D/L) versus favorable (N/U) groups. Results: Among 273 eligible patients, 197 (72%) were classified into Group N (n = 150)/U (n = 47), while 76 (28%) were in Group D (n = 66)/L (n = 10). A history of poor asthma control, long-acting beta2 agonist use, and a lower height Z-score during 13–15 years were associated with an unfavorable outcome (Group D/L). Conversely, inhaled corticosteroid (ICS) use during 10–12 years and high-dose ICS use during 13–15 years were associated with a favorable outcome (Group N/U). Conclusion: We identified several factors that are associated with unfavorable lung function changes in pediatric asthma. Attention should be paid to the possible relationship between yearly changes in lung function and poor asthma control, use of ICS (and its dose) and use of LABA.

Assessment of Symptoms Control, Pulmonary Function and Related Quality of Life in Asthmatic Patients Treated with Extrafine Beclomethasone Dipropionate/Formoterol Fumarate 100/6 μg pMDI: Results of a Multicenter Observational Study in Romania (ALFRESCO Study).

IntroductionAsthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone. This is the first study done in Romania, which collected the real-world data on the effects of Foster® (extrafine beclomethasone dipropionate/formoterol fumarate BDP/FF in a pressurized metered-dose inhaler pMDI 100/6 μg formulation) in adult asthmatic population.ObjectiveWe aimed to assess the asthma symptoms control, pulmonary function and quality of life parameters in a heterogeneous Romanian asthmatic adult outpatient population, treated with extrafine BDP/FF 100/6 μg pMDI.MethodsThis was a prospective, multicenter, observational study involving 30 pulmonologists randomly selected from the Romanian healthcare system, which did not declare any competing interests. Recruitment period was Oct 2018 - Feb 2019, while the patients' observational period was 24 weeks. The study included poorly controlled and uncontrolled adult asthma outpatients treated with non-extrafine formulations medication, for which the treatment indication, according to Global Initiative for Asthma (GINA) 2018, was the use of an ICS-LABA combination. The study collected demographic data, smoking habits, comorbidities, data regarding asthma diagnosis, the evolution of asthma symptoms, spirometry, Asthma Control Questionnaire (ACQ-7) scoring test, current and concomitant treatment.ResultsOf 302 included patients, 290 completed the study. Pulmonary function parameters assessed during the trial (forced expiratory volume in one second - FEV1 and forced vital capacity - FVC) showed a significant improvement versus baseline (p<0.001). ACQ-7 score decreased significantly from 3.09±0.83 (visit 1) to 1.56±0.89 (visit 2) and to 1.09±0.81 (visit 3) (p<0.001). At the end of the study, 127 (43.79%) patients were well controlled (ACQ-7 score < 0.75).ConclusionThis observational study demonstrates the effectiveness and safety of extrafine fixed combination of BDP/FF (100/6 μg) pMDI in Romanian adult asthma patients uncontrolled with non-extrafine medication in a real-world setting, leading to clinically and statistically improvements in asthma control and pulmonary function.

Clinical and immunological evaluation of cat-allergic asthmatics living with or without a cat.

BackgroundCharacterising the clinical and immunological impact of daily cat exposure in cat‐allergic subjects with asthma who live with cats (WC) and those who do not (WoC) may provide understanding of the drivers of the allergic response.MethodsClinical and immunological characteristics (skin prick test, spirometry, symptom assessments, immunological markers) were compared between asthmatic subjects WC (n = 10) and WoC (n = 9).ResultsWC subjects had greater use of long‐acting beta agonists (p < .05) and high‐potency corticosteroids. No differences were observed in lung function, nasal and ocular symptoms, or asthma control between the groups. Cat dander‐ and Fel d 1‐specific IgG4 concentrations were higher in WC than WoC subjects (both p < .05). Total IgE and cat dander‐, Fel d 1‐ and Fel d 7‐specific IgE concentrations were similar, but Fel d 4‐sIgE was higher in WC subjects (p < .05) versus WoC. Basophil sensitivity to cat dander extract and Fel d 1 was lower in WC versus WoC subjects (p < .05) and correlated with higher IgG4 concentrations (r = 0.63; p = .009). Fel d 1‐specific CD4+ T‐cell responses polarised toward Th2A responses in WC versus WoC subjects; Fel d 1‐specific IgE correlated with surface expression of CRTH2 and CD200R (both p ≤ .05).ConclusionImmunological differences observed in WC versus WoC did not reflect clinical tolerance with natural cat exposure. The ability to live with a cat despite allergy could be driven by higher preventative medication use. This study may support design of novel therapeutics for allergy management.

Burden of illness in blood eosinophilic phenotype COPD patients in New Zealand.

Real-world data on eosinophilic chronic obstructive pulmonary disease (COPD)'s clinical burden, in exacerbating/stable states, and the stability of blood eosinophil count (BEC) measurements are limited. We described measured BEC distributions among general practice COPD patients in New Zealand (NZ). This retrospective cohort study utilized the NZ-HealthStat primary care database. Participants were aged ≥40 years, with ≥1 BEC 6 months following a COPD diagnosis code during 2011-2012. Descriptive analyses included examinations of BEC stability and association with COPD exacerbations/treatments/comorbidities. The most frequent COPD comorbidity was asthma (n=1180/2909, 40.56%). Among COPD patients: 65% had BECs >150cells/μL; 35% had BECs >300cells/μL (non-mutually exclusive threshold categories). Treatment patterns were similar, except for more frequent inhaled corticosteroid (ICS)/long-acting beta2-agonist use in COPD patients with asthma history (51%) than those without (31%). Factors associated with BECs >150cells/μL in participants without ICS treatment included Māori/Pacific ethnicity, obesity, oral corticosteroid (OCS) use, and exacerbation history. When stratified by asthma history, ICS treatment, and neutrophil count above/below 5000cells/μL, geometric mean BECs ranged from 136.70 to 398.52cells/μL. Exploratory analyses showed a fair-good COPD/BEC measurement stability over 12 months. Asthma was a common COPD comorbidity in NZ, particularly in Māori/Pacific patients. No overall relationship was observed between BEC/COPD exacerbations, which may reflect background ICS confounding. However, analyses in non-ICS treated participants suggested that Māori/Pacific patients with obesity and COPD, OCS treatment, exacerbation history, and/or elevated BECs are at the highest risk of COPD exacerbations. One BEC measurement appears a good indicator of a patient's BECs over time.

Genome‐wide association studies of exacerbations in children using long‐acting beta2‐agonists

BackgroundSome children with asthma experience exacerbations despite long‐acting beta2‐agonist (LABA) treatment. While this variability is partly caused by genetic variation, no genome‐wide study until now has investigated which genetic factors associated with risk of exacerbations despite LABA use in children with asthma. We aimed to assess whether genetic variation was associated with exacerbations in children treated with LABA from a global consortium.MethodsA meta‐analysis of genome‐wide association studies (meta‐GWAS) was performed in 1,425 children and young adults with asthma (age 6‐21 years) with reported regular use of LABA from six studies within the PiCA consortium using a random effects model. The primary outcome of each study was defined as any exacerbation within the past 6 or 12 months, including at least one of the following: 1) hospital admissions for asthma, 2) a course of oral corticosteroids or 3) emergency room visits because of asthma.ResultsGenome‐wide association results for a total of 82 996 common single nucleotide polymorphisms (SNPs, MAF ≥1%) with high imputation quality were meta‐analysed. Eight independent variants were suggestively (P‐value threshold ≤5 × 10−6) associated with exacerbations despite LABA use.ConclusionNo strong effects of single nucleotide polymorphisms (SNPs) on exacerbations during LABA use were identified. We identified two loci (TBX3 and EPHA7) that were previously implicated in the response to short‐acting beta2‐agonists (SABA). These loci merit further investigation in response to LABA and SABA use.

Effects of treatment with long-acting muscarinic antagonists (LAMA) and long-acting beta-agonists (LABA) on lung function improvement in patients with bronchiectasis: an observational study.

BackgroundPatients with bronchiectasis are often treated with bronchodilators such as long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists (LABA) for their symptoms, but empirical evidence supporting such practice is sparse. We evaluated the effect of LAMA and LABA on lung function improvement in patients with bronchiectasis.MethodsUsing the in-house patient database at a tertiary referral hospital in Seoul, South Korea, we extracted data from patients diagnosed as bronchiectasis with computed tomography (CT) scan and treated with LAMA, LABA, or both. Patients with asthma, chronic obstructive pulmonary disease (COPD) or a history of cigarette smoking were excluded, and a subgroup analysis was performed in patients who did not receive concurrent treatments such as antibiotics, mucolytics or systemic steroids that may affect lung function improvement.ResultsA total of 230 patients (males: 32.6%, median age: 60 years) were analyzed. Their mean forced expiratory volume in 1 second (FEV1) was 53.3% of the predicted value [standard deviation (SD), 15.3]. The patients received LAMA (n=95), LABA (n=36), or both (LAMA-LABA; n=99), after which their FEV1 values were increased by 0.102 liters (SD, 0.208; P<0.001), 0.133 liters (SD, 0.181; P<0.001), and 0.122 liters (SD, 0.230; P<0.001), respectively. In a subgroup of 97 patients who did not receive concurrent treatments, the FEV1 was increased by with 0.107 liters (SD, 0.167; P<0.001), 0.165 liters (SD, 0.209; P=0.005), and 0.165 liters (SD, 0.187; P<0.001) in the LAMA, LABA, and LAMA-LABA groups, respectively. Baseline FEV1 had a significant negative correlation with response to bronchodilator treatment in the total patient cohort (R=−0.242, P<0.001) and the subgroup of patients without concurrent treatments (R=−0.386, P<0.001).ConclusionsTreatment with bronchodilators such as LAMA or LABA was effective in improving lung function in patients with bronchiectasis, regardless of concurrent treatments that also improve lung function. These data may support the use of LAMA and LABA in patients with bronchiectasis.

Clinical Management of COPD in a Real-World Setting. A Big Data Analysis

ObjectiveThe aim of this study was to evaluate the quality of diagnosis and treatment of COPD using Big Data methodology on the Savana Manager 2.1 clinical platform. Materials and methodsA total of 59,369 patients with a diagnosis of COPD were included from a population of 1,219,749 adults over 40 years of age. ResultsIn total, 78% were men. Spirometry data were available for only 26,453 (43.5%) subjects. Disease severity was classified in 18,172 patients: 4396 mild, 7100 moderate, and 6676 severe, although only 27%, 34%, and 28%, respectively, presented obstructive spirometry. The clinical management of COPD is mainly the responsibility of the primary care and pulmonology departments, while internal medicine and, to a lesser extent, geriatrics also participate. Drug treatment was based on bronchodilators and inhaled corticosteroids (ICS). A marked decline in the use of long-acting beta-2 agonists (LABA) in monotherapy and a slight reduction in ICS/LABA combinations, associated with a long-acting anticholinergic (LAMA) in 74% of cases, were observed. All-cause in-hospital mortality among the overall population was 5.6% compared to 1% of the general population older than 40 years. In total, 35% were admitted to hospital, with an average stay of 6.6 days and an in-hospital mortality rate in this group of 10.74%. DiscussionThis study identifies the main features of an unselected COPD population and the main errors made in the management of the disease.

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.

Gastroesophageal Reflux Disease Is Not Associated With Jackhammer Esophagus: A Case-control Study.

Background/AimsThe pathophysiology of jackhammer esophagus (JE) remains unknown but may be related to gastroesophageal reflux disease or medication use. We aim to determine if pathologic acid exposure or the use of specific classes of medications (based on the mechanism of action) is associated with JE.MethodsHigh-resolution manometry (HRM) studies from November 2013 to March 2019 with a diagnosis of JE were identified and compared to symptomatic control patients with normal HRM. Esophageal acid exposure and medication use were compared between groups. Multivariate regression analysis was performed to look for predictors of mean distal contractile integral.ResultsForty-two JE and 127 control patients were included in the study. Twenty-two (52%) JE and 82 (65%) control patients underwent both HRM and ambulatory pH monitoring. Two (9%) JE patients and 14 (17%) of controls had evidence of abnormal acid exposure (DeMeester score > 14.7); this difference was not significant (P = 0.290). Thirty-six (86%) JE and 127 (100%) control patients had complete medication lists. Significantly more JE patients were on long-acting beta agonists (LABA) (JE = 5, control = 4; P = 0.026) and calcium channel blockers (CCB) (JE = 5, control = 3; P = 0.014). Regular opioids (β = 0.298, P = 0.042), CCB (β = 0.308, P = 0.035), and inhaled anticholinergics (β = 0.361, P = 0.049) predicted mean distal contractile integral (R2 = 0.082, F = 4.8; P = 0.003).ConclusionsPathologic acid exposure does not appear to be associated with JE. JE patients had increased CCB and LABA use. The unexpected finding of increased LABA use warrants more investigation and may provide support for a cholinergic etiology of JE.

Manejo clínico de la EPOC en situación de vida real. Análisis a partir de big data

ObjectiveThe aim of this study was to evaluate the quality of diagnosis and treatment of COPD using Big Data methodology on the Savana Manager 2.1 clinical platform. Materials and methodsA total of 59,369 patients with a diagnosis of COPD were included from a population of 1,219,749 adults over 40 years of age. ResultsIn total, 78% were men. Spirometry data were available for only 26,453 (43.5%) subjects. Disease severity was classified in 18,172 patients: 4,396 mild, 7,100 moderate, and 6,676 severe, although only 27%, 34%, and 28%, respectively, presented obstructive spirometry.The clinical management of COPD is mainly the responsibility of the primary care and pulmonology departments, while internal medicine and, to a lesser extent, geriatrics also participate. Drug treatment was based on bronchodilators and inhaled corticosteroids (ICS). A marked decline in the use of long-acting beta-2 agonists (LABA) in monotherapy and a slight reduction in ICS/LABA combinations, associated with a LAMA in 74% of cases, was observed.All-cause in-hospital mortality among the overall population was 5.6% compared to 1% of the general population older than 40 years. In total, 35% were admitted to hospital, with an average stay of 6.6 days and a rate of hospital mortality in this group of 10.74%. DiscussionThis study identifies the main features of an unselected COPD population and the major errors made in the management of the disease.

TREATMENT PATTERNS FOR PATIENTS HOSPITALIZED WITH THE DIAGNOSIS OF ASTHMA OR COPD EXACERBATION

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: The use of long-acting beta agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy in hospitalized patients with COPD and asthma may prove beneficial due to flatter peak/trough variation in lung function, fewer PRN rescue treatments and easier transition of care for patients. However, the cost of such inhalers has caused hospitals to substitute scheduled short-acting combination (SABD) bronchodilators in place of longer acting medications. COPD guidelines do not address the use of LABA/LAMA in hospitalized patients. Because of conflicting views (efficacy vs cost) we sought to understand our unique hospital's practice habits by determining the difference in scheduled PRN SABD treatments when LABA and/or LAMA was added. METHODS: Patients with the diagnosis of COPD or asthma for at least 12 months and who were hospitalized for an exacerbation were selected for this retrospective chart review. Sixty charts were randomly selected to review respiratory therapy treatments prescribed and administered. The first treatment counted began in the Emergency Department and ended at discharge or at the end of 7 days. The scheduled use of routine, separate or combination, SABA and/or SAMA treatment times given during waking hours, night time hours, and any as needed treatments were collected. LABA and/or LAMA and SABD, scheduled or PRN was recorded. Charts were also reviewed for comorbid conditions. RESULTS: Twenty-five (43%) of the 60 participants were men and the average age was 66 years (58.5,76). The most prevalent diagnosis was COPD (90%), followed by asthma (7%), and asthma + COPD (3%). Comorbidities included heart failure (20%), diabetes mellitus (15%), pneumonia (16%), and hypoxemia (7%). The rates of therapy were SABD (30%), LABA (70%), LAMA (42%). Overall, patients who received both LABA and LAMA had fewer short-acting treatments than those who did not receive either LABA or LAMA. Patients who received both LABA and LAMA had numerically fewer short-acting treatments than patients who did not receive LABA and LAMA; combination LABA/LAMA therapy was associated with a statistically significant reduction in SABD treatments (p=0.03). CONCLUSIONS: Prescribing practices for hospitalized COPD and asthma patients in a large, urban, academic, hospital are heterogeneous. At our hospital, the prescription of LABA/LAMA decreased the number of PRN SABD significantly. From a purely financial perspective, the auto-substitution of scheduled SABD is driven by labor and medication costs. From a health outcome perspective, a larger head-to-head trial is critically needed to help adjudicate questions of real financial cost, length of stay, and hospital readmissions as well as patient safety. CLINICAL IMPLICATIONS: This study implies that LABA/LAMA treatments prescribed for patients hospitalized with the diagnosis of COPD or asthma exacerbation may reduce the number of PRN SABD treatments. DISCLOSURES: Speaker/Speaker's Bureau relationship with Monaghan Medical Corporation Please note: $1-$1000 Added 11/19/2018 by Mary Hart, source=Web Response, value=travel Removed 03/11/2019 by Mary Hart, source=Web Response Advisory Committee Member relationship with AstraZeneca Please note: $1001 - $5000 Added 11/19/2018 by Mary Hart, source=Web Response, value=travel Speaker/Speaker's Bureau relationship with AstraZeneca Please note: $20001 - $100000 Added 03/13/2019 by Mark Millard, source=Web Response, value=Honoraria Research relationship with AstraZeneca Please note: >$100000 Added 03/13/2019 by Mark Millard, source=Web Response, value=Grant/Research Support Speaker/Speaker's Bureau relationship with Boerhinger Ingleheim Please note: $5001 - $20000 Added 03/13/2019 by Mark Millard, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 Added 03/13/2019 by Mark Millard, source=Web Response, value=Honoraria No relevant relationships by Kristen Tecson, source=Web Response

Medication management patterns among Medicare beneficiaries with chronic obstructive pulmonary disease who initiate nebulized arformoterol treatment.

Purpose: Global evidence-based treatment strategies for chronic obstructive pulmonary disease (COPD) recommend using long-acting bronchodilators (LABDs) as maintenance therapy. However, COPD patients are often undertreated. We examined COPD treatment patterns among Medicare beneficiaries who initiated arformoterol tartrate, a nebulized long-acting beta2 agonist (LABA), and identified the predictors of initiation.Methods: Using a 100% sample of Medicare administrative data, we identified beneficiaries with a COPD diagnosis (ICD-9 490–492.xx, 494.xx, 496.xx) between 2010 and 2014 who had ≥1 year of continuous enrollment in Parts A, B, and D, and ≥2 COPD-related outpatient visits within 30 days or ≥1 hospitalization(s). After applying inclusion/exclusion criteria, three cohorts were identified: (1) study group beneficiaries who received nebulized arformoterol (n=11,886), (2) a subset of the study group with no LABD use 90 days prior to initiating arformoterol (n=5,542), and (3) control group beneficiaries with no nebulized LABA use (n=220,429). Logistic regression was used to evaluate predictors of arformoterol initiation. Odds ratios (ORs), 95% confidence intervals (CIs), and p values were computed.Results: Among arformoterol users, 47% (n=5,542) had received no LABDs 90 days prior to initiating arformoterol. These beneficiaries were being treated with a nebulized (50%) or inhaled (37%) short-acting bronchodilator or a systemic corticosteroid (46%), and many received antibiotics (37%). Compared to controls, beneficiaries who initiated arformoterol were significantly more likely to have had an exacerbation, a COPD-related hospitalization, and a pulmonologist or respiratory therapist visit prior to initiation (all p<0.05). Beneficiaries with moderate/severe psychiatric comorbidity or dual-eligible status were significantly less likely to initiate arformoterol, as compared to controls (all p<0.05).Conclusion: Medicare beneficiaries who initiated nebulized arformoterol therapy had more exacerbations and hospitalizations than controls 90 days prior to initiation. Findings revealed inadequate use of maintenance medications, suggesting a lack of compliance with evidence-based treatment guidelines.

IMPROVEMENT IN MORNING PEAK EXPIRATORY FLOW WITHIN THE FIRST WEEK OF TREATMENT WITH IV RESLIZUMAB

Introduction In duplicate 52-week placebo (PBO)-controlled Phase 3 trials, patients with inadequately controlled eosinophilic asthma (blood eosinophils ≥400 cells/µL) who received reslizumab (RES; 3mg/kg IV Q4W) achieved significant improvements in FEV1, FVC and FEF25-75% 4 weeks after the first dose. The objective of this post-hoc analysis was to assess earlier improvements in lung function based on ambulatory morning peak expiratory flow (PEF). Methods Patients used a PEF meter and recorded their pre-dose (prior to use of long-acting beta agonists and inhaled corticosteroids) PEF daily throughout the trials (Study 1 and Study 2). PEF technique was reviewed at scheduled clinic visits. Weekly averages of daily morning PEF measurements are reported. Results Study 1 included 489 patients (PBO 244, RES 245) and Study 2 included 464 patients (PBO 232, RES 232). Patients receiving RES demonstrated increases in mean morning PEF (L/min) versus placebo of 22.66±7.85 and 18.90±9.28 (p=0.004; p=0.042) at 52 weeks in Study 1 and Study 2, respectively. Improvement compared with placebo was evident within the first week (RES vs PBO, Study 1: 1.18±4.78 vs -8.22±4.02; Study 2: 0.850±6.03 vs -8.18±4.55). Between-treatment differences increased through week 7 (RES vs PBO, Study 1: 15.82±6.29 vs -10.98±5.41; Study 2: 27.33±8.06 vs -6.97±6.01) and were sustained through the 52-week treatment period. PEF improvements corresponded with FEV1 improvements at Week 4. Conclusions Treatment with IV RES was associated with rapid and sustained improvement in lung function as assessed by morning PEF in patients with severe eosinophilic asthma, confirming earlier FEV1 data. Overall change from baseline over 52 weeks of treatment in Studies 1 and 2, weekly average AM Peak Expiratory Flow Rate (PEFR) (L/min) In duplicate 52-week placebo (PBO)-controlled Phase 3 trials, patients with inadequately controlled eosinophilic asthma (blood eosinophils ≥400 cells/µL) who received reslizumab (RES; 3mg/kg IV Q4W) achieved significant improvements in FEV1, FVC and FEF25-75% 4 weeks after the first dose. The objective of this post-hoc analysis was to assess earlier improvements in lung function based on ambulatory morning peak expiratory flow (PEF). Patients used a PEF meter and recorded their pre-dose (prior to use of long-acting beta agonists and inhaled corticosteroids) PEF daily throughout the trials (Study 1 and Study 2). PEF technique was reviewed at scheduled clinic visits. Weekly averages of daily morning PEF measurements are reported. Study 1 included 489 patients (PBO 244, RES 245) and Study 2 included 464 patients (PBO 232, RES 232). Patients receiving RES demonstrated increases in mean morning PEF (L/min) versus placebo of 22.66±7.85 and 18.90±9.28 (p=0.004; p=0.042) at 52 weeks in Study 1 and Study 2, respectively. Improvement compared with placebo was evident within the first week (RES vs PBO, Study 1: 1.18±4.78 vs -8.22±4.02; Study 2: 0.850±6.03 vs -8.18±4.55). Between-treatment differences increased through week 7 (RES vs PBO, Study 1: 15.82±6.29 vs -10.98±5.41; Study 2: 27.33±8.06 vs -6.97±6.01) and were sustained through the 52-week treatment period. PEF improvements corresponded with FEV1 improvements at Week 4. Treatment with IV RES was associated with rapid and sustained improvement in lung function as assessed by morning PEF in patients with severe eosinophilic asthma, confirming earlier FEV1 data.

Long‐Acting Beta‐Agonist Use is Associated with Lower Carotid Artery Stiffness and Greater Carotid Artery Compliance in Individuals with Chronic Obstructive Pulmonary Disease

BackgroundCardiovascular disease (CVD) is the most prevalent comorbidity in individuals with chronic obstructive pulmonary disease (COPD). Elevated large elastic artery stiffness (i.e. carotid and aorta) is a robust predictor of CVD events and mortality and is associated with airway obstruction in COPD patients, suggesting that large artery stiffness may contribute, at least in part, to the high CVD risk in COPD. Previous studies demonstrate that in COPD patients, bronchodilator therapy improves respiratory symptoms, lowers the risk of exacerbations and reduces aortic stiffness, as measured by carotid‐femoral pulse wave velocity (CFPWV), in COPD patients with a very high CFPWV (≥ 11 m/s). However, the long‐term benefits of bronchodilator therapy on cardiovascular risk remain controversial. We hypothesized that individuals with COPD who reported using a long‐acting beta‐agonist (LABA) or an inhaled corticosteroid (ICS) would have lower carotid artery stiffness/greater compliance compared with COPD patients not on LABAs or ICSs.MethodsSixty‐three adults with COPD (age 70 ± 7 yrs; 23M/40F; GOLD stage 1–4; 6% stage 1, 47% stage 2, 24% stage 3, 23% stage 4) completed measurements of common carotid artery stiffness and compliance (carotid artery ultrasound and tonometry) and were retrospectively stratified by self‐report of LABA and ICS use.ResultsThirty‐two (49%) participants reported using a LABA/ICS combination bronchodilator. Seven (11%) of patients reported using a LABA alone and 7 (11%) of patients reported using an ICS alone. COPD patients using a LABA/ICS combination bronchodilator had significantly lower carotid β‐stiffness (8.7 ± 0.5 vs. 10.9 ± 0.9 U, P=0.04) and greater carotid compliance (0.11 ± 0.01 vs. 0.08 ± 0.01 mm/mmHg, P=0.01) compared with patients not using a LABA/ICS. This difference remained significant after adjusting for age, gender, BMI, oxygen use and smoking pack‐years (carotid β‐stiffness P=0.04; carotid compliance P=0.05). BP, heart rate and oxygen saturation did not differ between COPD patients using vs. not using a LABA/ICS. Furthermore, patients that reported using a LABA alone, and not in combination with an ICS, had significantly lower carotid β‐stiffness (6.9 ± 0.6 vs. 10.1 ± 0.6 U, P&lt;0.01), but not greater carotid compliance (0.11 ± 0.01 vs. 0.09 ± 0.01 mm/mmHg, P=0.2) compared with those not using a LABA. In contrast, there was no difference in carotid β‐stiffness (9.0 ± 1.2 vs. 9.9 ± 0.6 U, P=0.60) or carotid compliance (0.10 ± 0.01 vs. 0.10 ± 0.01 mm/mmHg, P=0.93) between COPD patients that reported using vs. not using an ICS.ConclusionThese data indicate that COPD patients who are taking a LABA, either in combination with an ICS or alone, have lower carotid artery stiffness than those not taking a LABA. This finding raises the possibility that LABAs may be beneficial in reducing the CVD risk observed in COPD, however randomized, controlled clinical trials are needed to test whether LABAs impact CVD risk.Support or Funding InformationNIH K23 HL095658, R01 HL089897, NIH/NCATS CTSI UL1 TR001082This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Patterns of use of long-acting bronchodilators in patients with COPD: A nationwide follow-up study of new users in New Zealand.

While several studies have found that prescribing practices do not conform to chronic obstructive pulmonary disease (COPD) treatment guidelines, none have examined longitudinal patterns of use of long-acting beta2 -agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy across an entire country. We undertook a nationwide follow-up study to describe treatment patterns in new users of long-acting bronchodilators. National health and pharmaceutical dispensing data were used to identify patients aged ≥45 years who initiated LABA and/or LAMA therapy for COPD between 1 February 2006 and 31 December 2013. Dispensings of LABAs, LAMAs and inhaled corticosteroids (ICSs) were aggregated into episodes of use of therapeutic regimens. Kaplan-Meier curves, sunburst plots and sequence index plots were generated to summarize, respectively, the duration of the first regimen, the sequences in which unique regimens were used and the patterns of use and non-use during follow-up. The study cohort included 83 435 patients with 290 400 person-years of follow-up. The most commonly initiated regimen was a LABA with an ICS. ICS use was inconsistent with international guidelines: over- and under-treatment occurred in patients with infrequent and frequent exacerbations, respectively, and ICS monotherapy was common. The median duration of the first regimen was 46 days. Many patients used multiple regimens over time and periods of non-use were common. In this nationwide study, patterns of use of LABAs, LAMAs and ICSs were complex and often did not comply with treatment guidelines. Further work is required to address the discrepancy between guidelines and prescribing practices.

A review of the efficacy and safety of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with asthma.

Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of, unresponsive to, or uncontrolled by long-acting beta 2-agonists (LABAs). Tiotropium bromide, delivered through the Respimat soft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged ≥6 years. An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varying degrees of asthma severity. The role of the parasympathetic nervous system in the pathophysiology of asthma, the development of tiotropium for respiratory disease, and the value of the Respimat inhaler are also discussed. A literature search of all phase II and phase III trials of once-daily tiotropium Respimat 2.5 micrograms. Once-daily tiotropium Respimat 2.5 micrograms was studied in five phase III studies: three studies in adults and two in adolescents aged 12-17 years. Tiotropium Respimat 2.5 micrograms demonstrated efficacy in adults and adolescents with mild, moderate, or severe asthma, showing significant improvements in lung function and asthma control in patients with uncontrolled asthma despite inhaled corticosteroids (ICS) or ICS plus LABA use. The adverse event profile of tiotropium was very acceptable, with safety similar to placebo. Once-daily tiotropium Respimat 2.5 micrograms has positive attributes that include efficacy, a safety profile similar to placebo, once-daily dosing, administration by inhalation, and delivery in the easy-to-use and consistent-dosing Respimat device. However, more data are needed on the effects of tiotropium on clinical outcomes, patients' day-to-day lives, and real-world effectiveness.

Long-Acting β2-Agonists and Risk of Hypertensive Disorders of Pregnancy: A Cohort Study

Maternal asthma has been found to be associated with an increased risk of hypertensive disorders of pregnancy (HDP), that is, gestational hypertension, preeclampsia, and eclampsia. There is limited data, however, regarding the relationship between the use of long-acting beta-agonists (LABAs) during pregnancy and these outcomes. To investigate whether exposure to a LABA in addition to an inhaled corticosteroid increases the risk of HDP or preeclampsia/eclampsia, as compared with nonexposure to LABAs, in pregnant women with asthma. A cohort of 8,936 pregnancies in women with asthma who delivered between 1998 and 2010 was reconstructed using Quebec (Canada) health administrative databases. Cox proportional hazard regression models, adjusted for potential confounders, were used for statistical analyses. The primary exposure was LABA use (yes/no) measured on the first day of the 20th week of pregnancy. HDP were identified on the basis of recorded diagnoses and on prescriptions of antihypertensive drugs filled on or after the first day of week 20 of gestation. There were 567 (6.3%) cases of HDP and 256 (2.9%) cases of preeclampsia/eclampsia in the cohort, and the rates of both disorders were similar in women exposed or not exposed to LABAs. LABA use was not associated with increased risks of HDP (adjusted hazard ratio, 0.96; 95% CI, 0.69-1.33) or preeclampsia/eclampsia (adjusted hazard ratio, 0.89; 95% CI, 0.53-1.50). The results of this study provide evidence suggesting the safety of LABAs for the treatment of asthma in pregnancy, in terms of the risks of HDP and preeclampsia/eclampsia.