LABA In Patients Research Articles

LAMA improves tissue oxygenation more than LABA in patients with COPD.

The effect of bronchodilators is mainly assessed with forced expiratory volume in 1 s (FEV1) in chronic obstructive pulmonary disease (COPD). Their impact on oxygenation and lung periphery is less known. Our objective was to compare the action of long-acting β2-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD, considering their impact on proximal and peripheral ventilation as well as lung perfusion. FEV1, Helium slope (SHe) from a single-breath washout test (SHe decreases reflecting a peripheral ventilation improvement), frequency dependence of resistance (R5-R19), area under reactance (AX), lung capillary blood volume (Vc) from double diffusion (DLNO/DLCO), and transcutaneous oxygenation (TcO2) were measured before and 2 h post-LABA (day 1) and LAMA (day 3) in 30 patients with COPD (FEV1 54 ± 18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. We found that TcO2 increased more (P = 0.03) after LAMA (11 ± 12% from baseline, P < 001) compared with LABA (4 ± 11%, P = 0.06) despite a lower FEV1 increase (P = 0.03) and similar SHe (P = 0.98), AX (P = 0.63), and R5-R19 decreases (P = 0.37). TcO2 and SHe changes were negatively correlated (r = -0.47, P = 0.01) after LABA, not after LAMA (r = 0.10, P = 0.65). DLNO/DLCO decreased and Vc increased after LAMA (P = 0.04; P = 0.01, respectively) but not after LABA (P = 0.53; P = 0.24). In conclusion, LAMA significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with LABA. The mechanisms involved may differ between both drugs: LABA increased peripheral ventilation, whereas LAMA increased lung capillary blood volume. Should oxygenation differences persist over time, LAMA could arguably become the first therapeutic choice in COPD.NEW & NOTEWORTHY Long-acting muscarinic antagonists (LAMAs) significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with β2-agonists (LABAs). The mechanisms involved may differ between drugs: increased peripheral ventilation for LABA and likely lung capillary blood volume for LAMA. This could argue for LAMA as the first therapeutic choice in COPD.

Clinical experience of using formoterol/budesonide in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) today remains one of the most important problems of modern medicine. The social significance of this disease is determined by the annual health care costs for treating patients with exacerbated COPD, as well as the still high mortality and disability rates worldwide. The main goals of COPD treatment are to slow the rate of disease progression, control the symptoms, reduce the frequency of exacerbations and hospitalizations, and reduce the risk of future exacerbations. Currently, the main groups of drugs for basic therapy of COPD are inhaled prolonged bronchodilators from the groups of β2-adrenergic agonists and M-anticholinergics, as well as their combinations. Patients with COPD and bronchial asthma, as well as patients with COPD with elevated levels of eosinophils and frequent exacerbations, inhaled glucocorticosteroids (ICS) are used. It has been proven that the addition of corticosteroids to LABA in patients with moderate to severe COPD and frequent exacerbations has a more effective influence on pulmonary function and the number of exacerbations. Clinical studies have shown the relationship between the level of blood eosinophilia and the clinical effects of preventing future exacerbations when using iCS in combination with LABA. In our clinical observation, in patient with moderate COPD and blood eosinophilia &gt; 300 cells/μL, when prescribing monotherapy with long-acting agonists, frequent exacerbations of the disease were noted. The addition of corticosteroids to monotherapy with a long-acting agonist made it possible to influence the frequency of exacerbations and reduce the level of eosinophils in the blood.

Symptom Burden and GOLD Classification in Medicare Advantage Patients with COPD Initiating Umeclidinium/Vilanterol or Fluticasone Propionate/Salmeterol Therapy.

BackgroundLong-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) provide greater improvements in lung function and symptoms than inhaled corticosteroid (ICS)/LABA in patients with chronic obstructive pulmonary disease (COPD). This study evaluated symptom burden and Global Initiative for Obstructive Lung Disease (GOLD) categorization among patients who recently initiated umeclidinium/vilanterol (UMEC/VI; LAMA/LABA) or fluticasone propionate/salmeterol (FP/SAL; ICS/LABA) single-inhaler dual therapy.MethodsCOPD-diagnosed Medicare Advantage enrollees aged ≥65 years were identified from the Optum Research Database (ORD). Eligible patients had ≥1 pharmacy claim for UMEC/VI or FP/SAL in the 6-month period before sample identification, with no evidence of triple therapy (ICS/LAMA/LABA), asthma, or lung cancer. Symptom burden was assessed via cross-sectional surveys using the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Patients were classified into GOLD categories using patient-reported symptoms and claims-based exacerbation history. Treatment groups were balanced on potential confounders using inverse probability of treatment weighting (IPTW). CAT and mMRC scores were analyzed with generalized linear regression models using IPTW propensity scores.ResultsThe final analytic sample included 789 respondents (UMEC/VI: N=392; FP/SAL: N=397). Approximately 66% patients were classified as GOLD B when assessing symptoms with CAT and mMRC together, or CAT alone; more patients were classified as GOLD A (~40%) than GOLD B (~36%) using mMRC alone. Proportions of patients in each GOLD group were similar between treatment cohorts. Post-IPTW multivariable modeling showed similar symptom burden between treatment groups.ConclusionAfter controlling for baseline characteristics, symptom burden was similar between patients receiving UMEC/VI or FP/SAL. GOLD classification using mMRC produced more conservative results compared with CAT, potentially underestimating patient symptoms. Many patients receiving FP/SAL were classified as GOLD A or B, despite GOLD recommending non-ICS-containing therapy in these patients. These findings support the need for routine assessment of symptoms in patients with COPD.

Therapeutic preferences and factors determining the use of inhaled corticosteroids with long-acting β2-agonists in patients with asthma and chronic obstructive pulmonary disease.

IntroductionInhaled corticosteroids (ICS) and long-acting β2-agonists (LABA) are a part of standard therapy of bronchial asthma and chronic obstructive pulmonary disease (COPD).AimAssessment of the therapeutic preferences and factors determining the choice of polytherapy with ICS and LABA in patients with asthma and COPD in daily clinical practice.Material and methodsThis multicentre, open-label, post-marketing observational survey was performed nation-wide with the participation of 245 doctors and 13,800 patients with asthma or COPD on polytherapy with ICS and LABA. The study questionnaire included two parts: concerning doctors’ preferences in the use of ICS and LABA and their prescription in patients as well as efficacy and tolerance of inhaled drugs during two consecutive visits.ResultsThe study doctors frequently declared a choice of polytherapy with formoterol and fluticasone in patients with asthma and COPD. The most important factors supporting the choice of ICS and LABA, declared by doctors, were safety and efficacy. ICS and LABA polytherapy with formoterol and fluticasone was used in 71.0% of patients with asthma and 81.4% with COPD. The most important factors explaining the choice of this drug combination were safety (75.3% and 72.5%, respectively) and efficacy (75.2% and 71.9%, respectively).ConclusionsFormoterol and fluticasone polytherapy is frequently chosen by Polish physicians in the treatment of asthma and COPD due to its high efficacy and safety. In accordance with doctors’ declaration, in the study group this therapy was characterized by the highest effectiveness and the best tolerance.

The response variability of the asthma patients to the standard pharmacotherapy

Background. The aim of this study was to analyse the group of patients with asthma, who prefer to use short-acting anticholinergics (SAMA) for relief of asthma attacks. At the same time, these patients are prescribed inhaled glucocorticosteroids (ICS) in combination with long-acting P2-agonists (LABA) as a basic therapy according to the standards. Tha aim. To study the cause of low efficacy of LABA in patients with asthma who do not have a sufficient response to SABA, as well as the probability of reducing of bronchial obstruction with LAMA. Materials and methods. 12 non-smoking adults with moderate to severe asthma (III-IV stage of GINA), receiving medium or high doses of ICS in combination with LABA as a basic therapy without adequate control over asthma symptoms were included in the study. First group of patients showed the efficacy of salbutamol (FEV1 reversibility was more than 12% and more than 200 ml after 400 ^g of salbutamol) and ipratropium bromide (SABA+SAMA+). Second group included patients with low response to salbutamol and positive test (FEVt reversibility) with ipratropium bromide (SABA-SAMA+). Spirometry was performed at baseline point and in 5, 10, 15, 30, 60, 120 and 240 min after inhalation of bronchodilator (salmeterol 50 ^g, formoterol 12 ^g and tiotropium bromide 18 ^g in the different days). Results. It was shown that SABA-SAMA+ phenotype asthma patients demonstrated low response to LABA: FEV1 increased up to 7.64±1.67%, 156.0±16.0 ml after salmeterol inhalation and up to 9.4±5.8%, 166.7±103.1 ml after formoterol inhalation (compared with a group of SABA+SAMA+, where the response to salmeterol was 20.81±2.42%, 551.43±93.94 ml and the response to formoterol was 30.21±6.75%, 718.57±140.78 ml, p

Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma

Long-acting muscarinic antagonists (LAMAs) are a potential adjunct therapy to inhaled corticosteroids in the management of persistent asthma. To conduct a systematic review and meta-analysis of the effects associated with LAMA vs placebo or vs other controllers as an add-on therapy to inhaled corticosteroids and the use of a LAMA as add-on therapy to inhaled corticosteroids and long-acting β-agonists (LABAs; hereafter referred to as triple therapy) vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma. MEDLINE, EMBASE, Cochrane databases, and clinical trial registries (earliest date through November 28, 2017). Two reviewers selected randomized clinical trials or observational studies evaluating a LAMA vs placebo or vs another controller as an add-on therapy to inhaled corticosteroids or triple therapy vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma reporting on an outcome of interest. Meta-analyses using a random-effects model was conducted to calculate risk ratios (RRs), risk differences (RDs), and mean differences (MDs) with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength-of-evidence grading were completed by 2 independent reviewers. Asthma exacerbations. Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 [95% CI, 0.48 to 0.92]; RD, -0.02 [95% CI, -0.04 to 0.00]). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 [95% CI, 0.53 to 1.42]; RD, 0.00 [95% CI, -0.02 to 0.02]), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 [95% CI, 0.57 to 1.22]; RD, -0.01 [95% CI, -0.08 to 0.07]). In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations.

Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype

Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β2-agonist (LABA) has been shown to be beneficial in patients with symptomatic asthma. To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status. In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS+ LABA (PrimoTinA-asthma; 2 replicate trials; NCT00772538/NCT00776984; n= 912); once-daily tiotropium 5 μg or 2.5 μg, twice-daily salmeterol 50 μg, or placebo as add-on to ICS (MezzoTinA-asthma; 2 replicate trials; NCT01172808/NCT01172821; n= 2100). The prespecified efficacy outcomes of these studies have been reported previously. Here, further exploratory subgroup analyses were performed to study whether these coprimary end points were influenced by serum IgE levels, blood eosinophil counts, and clinician judgment of allergic asthma. In addition, for the continuous parameters, namely, IgE and blood eosinophils, their influence on the treatment effect was modeled over the whole range of values. Tiotropium was efficacious in improving peak FEV1 within 3 hours postdose and trough FEV1, independent of T2 status. Tiotropium significantly reduced the risk of severe asthma exacerbations and asthma worsening, independent of T2 phenotype; Cox regression modeling supported a beneficial effect of tiotropium on exacerbations, independent of IgE levels or eosinophil counts. Numerical improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder rate with tiotropium versus placebo were observed in T2high and T2low patients; logistic regression modeling provided further evidence for improvement in ACQ-7 responder rates with tiotropium, independent of IgE levels or eosinophil counts. The results of our exploratory analyses suggest that the improvements seen with tiotropium Respimat as add-on to ICS ± LABA in patients with symptomatic asthma on lung function, exacerbation risk, and symptom control are independent of T2 phenotype.

Emerging role of long-acting anticholinergics in children with asthma.

Although the use of inhaled anticholinergics in obstructive airway disease has been established for several years, the clinical experience using these medications in treating patients with asthma is limited. Only few studies so far have included pediatric patients with asthma, but these studies demonstrate relevant therapeutic effects. This review will explore the pharmacological effects of inhaled anticholinergics, provide an overview about current adult and pediatric asthma studies using tiotropium, and describe future research needs. In a phase II study with tiotropium as add-on to maintenance treatment to inhaled corticosteroids (ICSs) in moderate persistent adolescent with asthma, significant improvement of peak and trough forced expiratory volume in 1 s (FEV1) with a good safety profile could be demonstrated. A pediatric phase II study in symptomatic patients with asthma aged 6-11with comparable study design also demonstrated significant improvement of peak FEV1 with no serious adverse events. However, both studies could not document a significant clinical improvement analyzed by standardized scores. Tiotropium might become an add-on treatment option in symptomatic pediatric and adolescent patients with asthma despite adequate therapy with ICS and long-acting β2-agonist (LABA) or as an alternative to LABA in patients with safety concerns related to LABA. For a better assessment of the clinical effect, long-term studies are needed.

Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population.

A combination of long-acting anticholinergic agents (LAACs) and long-acting β2-adrenergic receptor agonist (LABA) is effective in improving lung function in chronic obstructive pulmonary disease (COPD) compared with monotherapy. However, evidence on whether this combination increases the incidence of stroke or other cardiac events remains sparse. The objective of the present study was to investigate the incidence of stroke and other cardiovascular diseases in COPD patients treated with LAAC, LABA, or a combination of the 2.We conducted this population-based study using the Taiwan National Health Insurance Research Database (1997–2008), identifying COPD patients and their prescribed medication from the International Classification of Disease, Ninth Revision codes 490–492 or 496. A multivariate Cox proportional-hazards model was used to compare the risk of stroke and other cardiovascular diseases over the 11-year period after treatment with LAAC or LABA only or in combination.Of the 596 COPD patients (mean age 70 y), 196 were treated with LAAC, 318 with LABA, and 82 were treated with a combination. The overall incidence of stroke (8.53%) significantly increased in the combination group compared with LAAC (2.04%) or LABA (1.26%) only. In the Cox regression analysis, the adjusted hazard ratio over the 11-year survey period for stroke in patients treated with the combination compared with LABA only was 1.04 (95% confidence interval, 1.06–2.99) and for LAAC, it was 0.31 (95% confidence interval, 0.02–2.32).This cohort study using a large health insurance database showed that treating patients with COPD, with a combination of LAAC and LABA, may be associated with an increased hazard of stroke compared with treatment with either agent alone. We should be particularly cautious about comedication of LAAC and LABA in patients with COPD.

P229 Once-daily Tiotropium Respimat(R) As Add-on To At Least Medium- To High-dose Ics, With Or Without Laba, Improves Lung Function In Patients With Symptomatic Asthma, Independent Of Allergic Status

Background A substantial number of patients have symptomatic asthma despite treatment according to guidelines. Several studies have confirmed that tiotropium Respimat ® , a once-daily long-acting anticholinergic bronchodilator, improves lung function in symptomatic patients receiving at least medium-dose inhaled corticosteroids (ICS) + long-acting β 2 -agonist (LABA) (Kerstjens et al . NEJM 2012;367:1198–207; Bateman et al . JACI 2011;128:315–22). Here we examine whether the atopic and/or allergic status of patients in these trials influenced their response to tiotropium Respimat ® . Method Two 48-week trials of tiotropium Respimat ® 5 µg (PrimoTinA-asthma ® : NCT00776984, NCT00772538) in patients (n = 912) on high-dose ICS + LABA; two 24-week trials of tiotropium Respimat ® 5 µg and 2.5 µg (MezzoTinA-asthma ® : NCT01172808, NCT01172821) in patients (n = 2100) on moderate-dose ICS. Pre-planned analyses (pooled populations) were performed in two subgroups defined at baseline as total serum immunoglobulin E (IgE) ≤ or >430 μg/L or blood eosinophils ≤ or >0.6×10 9 /L or clinical judgement of allergic status (‘No’ or ‘Yes’). All tiotropium doses were delivered via the Respimat ® SoftMist™ inhaler. Results Tiotropium Respimat ® 5 µg or 2.5 µg improved peak and trough forced expiratory volume in 1 second versus placebo (Table) independent of IgE, eosinophil count and clinical judgement. Conclusion Once-daily tiotropium Respimat ® as add-on to ICS or ICS + LABA in patients with moderate to severe symptomatic asthma reduces airflow obstruction, apparently independent of their atopic and/or allergic status.

β2-Adrenergic Receptor Haplotype may be Associated with Susceptibility to Desensitization to Long-Acting β2-Agonists in COPD Patients

Τhat β2-adrenergic receptor (β2AR) haplotypes may play a key role in clinical response to β2-agonists and haplotype Cys-19Gly16Gln27 (CysGlyGln) is reported to be associated with desensitization of β2AR to β-agonists in lymphocytes isolated from patients with asthma and septic shock. We sought to determine whether haplotypic variation of the β2AR affects the functional outcomes of long-acting β2-agonist (LABA) treatment for chronic obstructive pulmonary disease (COPD) when used as monotherapy. Treatment-naïve patients with COPD (n = 36) were prospectively treated with two kinds of LABA--inhaled salmeterol and transdermal tulobuterol patch--for 12 weeks in crossover study, and changes in pulmonary function data and 6-minute walk distance (6 MWD) were compared between groups stratified by the CysGlyGln. Frequencies of haplotype and diplotype for the CysGlyGln were 0.51 and 0.36, respectively. The individuals homozygous for CysGlyGln showed less improvement in FEV(1), %FEF(25-75 %), and IC/TLC than those with 0 or 1 copy of CysGlyGln after treatment with both LABAs despite initial bronchodilator responses to albuterol being similar in these groups. The response in these parameters was not significantly different between two types of LABA. Overall changes in 6 MWD in individuals with 2 copies of CysGlyGln versus 0 or 1 copy for salmeterol were 2.8 and 11 m, and for tulobuterol were -1.3 and 16 m, respectively. Homozygous haplotype for the CysGlyGln of β2AR may be associated with susceptibility to desensitization to LABA in patients with COPD.

LABA in patients with stage I COPD and mild sleep apnea syndrome: a pilot study

Abstract Patients suffering from both sleep apnea-hypopnea syndrome (SAHS) and chronic obstructive pulmonary disease (COPD) have a more severe form of sleep apnea. Knowing all pathophysiological aspects that mutually interact in sleep disorders and COPD, we aimed to investigate if the introduction of long-acting β2 agonists (LABA) during the night could improve overnight oxygenation and the ability to perform daily activities in stage I COPD patients with mild SAHS. We conducted a prospective study of 22 patients with stage I COPD and SAHS confirmed by overnight polygraph screening, without nocturnal CPAP treatment. During twelve weeks, all patients used LABA (salmeterol 50 mcg) with a metered dose inhaler before bedtime. The levels of apnea hypopnea index, oxygen saturation, heart rate, and Epworth daytime sleepiness scale (ESS) were recorded before and after the treatment. There was a significant improvement of lowest and average overnight oxygenation compared to baseline (mean difference 2.1±0.42, p&lt;0.0001; 1.7±0.3, p&lt;0.0001, respectively). In addition, patients reported reduction in daytime sleepiness according to ESS (mean difference 1.23±0.51; p=0.03). Fewer patients exhibited tachycardia when on salmeterol (68 vs. 41%; p=0.01). Use of inhaled salmeterol improves overnight oxygenation in patients with stage I COPD and SAHS. Future prospective studies are warranted to confirm this potentially beneficial effect of long-acting β2 agonists.