Budesonide/formoterol combination in COPD: a US perspective

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease of the lung caused primarily by exposure to cigarette smoke. Clinically, it presents with progressive cough, sputum production, dyspnea, reduced exercise capacity, and diminished quality of life. Physiologically, it is characterized by the presence of partially reversible expiratory airflow limitation and hyperinflation. Pathologically, COPD is a multicomponent disease characterized by bronchial submucosal mucous gland hypertrophy, bronchiolar mucosal hyperplasia, increased luminal inflammatory mucus, airway wall inflammation and scarring, and alveolar wall damage and destruction. Management of COPD involves both pharmacological and nonpharmacological approaches. Bronchodilators and inhaled corticosteroids are recommended medications for management of COPD especially in more severe disease. Combination therapies containing these medications are now available for the chronic management of stable COPD. The US Food and Drug Administration, recently, approved the combination of budesonide/formoterol (160/4.5 μg; Symbicort™, AstraZeneca, Sweden) delivered via a pressurized meter dose inhaler for maintenance management of stable COPD. The combination also is delivered via dry powder inhaler (Symbicort™ and Turbuhaler™, AstraZeneca, Sweden) but is not approved for use in the United States. In this review, we evaluate available data of the efficacy and safety of this combination in patients with COPD

Maintenance inhaler therapy preferences of patients with asthma or chronic obstructive pulmonary disease:a discrete choice experiment

Background A variety of maintenance inhaler therapies are available to treat asthma and COPD. Patient-centric treatment choices require understanding patient preferences for the alternative therapies. Methods A self-completed web-based discrete choice experiment was conducted to elicit patient preferences for inhaler device and medication attributes. Selection of attributes was informed by patient focus groups and literature review. Results The discrete choice experiment was completed by 810 patients with asthma and 1147 patients with COPD. Patients with asthma most valued decreasing the onset of action from 30 to 5 min, followed by reducing yearly exacerbations from 3 to 1. Patients with COPD most and equally valued decreasing the onset of action from 30 to 5 min and reducing yearly exacerbations from 3 to 1. Both patients with asthma and patients with COPD were willing to accept an additional exacerbation in exchange for a 15 min decrease in onset of action and a longer onset of action in exchange for a lower risk of adverse effects from inhaled corticosteroids. Patients with asthma and COPD valued once-daily over twice-daily dosing, pressurised inhalers over dry powder inhalers and non-capsule priming over single-use capsules, although these attributes were not valued as highly as faster onset of action or reduced exacerbations. Conclusions The most important maintenance inhaler attributes for patients with asthma and COPD were fast onset of symptom relief and a lower rate of exacerbations. Concerns about safety of inhaled corticosteroids and device convenience also affected patient preferences but were less important

Dual-combination maintenance inhaler preferences in asthma and chronic obstructive pulmonary disease:A patient-centered benefit-risk assessment

Background: A variety of dual-combination maintenance inhalers are used to treat asthma and chronic obstructive pulmonary disease (COPD). Understanding patient preferences for treatment attributes may help select an optimal treatment from the patient perspective. Methods: Patient preferences for maintenance inhaler device and medication attributes were elicited through a discrete choice experiment and used in benefit-risk assessments to calculate predicted choice probabilities (PrCPs) for 14 dual-combination maintenance inhalers in four treatment classes: lower- and higher-dose inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) inhalers for asthma, and ICS/LABA and long-acting muscarinic antagonist (LAMA)/LABA inhalers for COPD. Results: For all treatment classes, reduced exacerbations and faster onset of action were the most important attributes. For all classes, patients were willing to tolerate an extra yearly exacerbation to decrease the medication's onset of action from 30 to 5 min. For patients with asthma using lower-dose ICS/LABA (n = 497), budesonide/formoteml fumarate dihydrate (80 mu g/4.5 mu g) pressurized metered-dose inhaler (pMDI) had the highest PrCP (28.4%), and for those using a higher-dose ICS/LABA (n = 285), PrCPs were highest for mometasone furoate/formoterol fumarate dihydrate (200 mu g/5 mu g) pMDI (27.0%) and budesonide/formoterol fumarate dihydrate (160 mu g/4.5 mu g) pMDI (26.9%). For patients with COPD using an ICS/LABA (n = 574), budesonide/ formoterol fumarate dihydrate (160 mu g/4.5 mu g) pMDI had the highest PrCP (56.6%), and for those using a LAMA/LABA inhaler (n = 217), tiotropium/olodaterol (2.5 mu g/2.5 mu g) soft mist inhaler had the highest PrCP (42.3%). Conclusions: Patient preference data for maintenance inhaler attributes can be used to identify a preference order of inhalers in different treatment classes

Cardiovascular disease in asthma patients: from mechanisms to therapeutic implications

Cardiovascular disease (CVD) is often associated with asthma, and asthma patients have an increased risk of CVD mortality. Our understanding of the bidirectional risk of CVD and asthma has been based on several observational studies. However, the specific pathogenetic mechanisms underlying the development of cardiovascular comorbidities in patients with asthma have not yet been fully determined.  Such cardiovascular complications in patients with asthma have been attributed to airway and system inflammation present in both asthma and CVD. Indeed, there is evidence that mast cells, eosinophils, inflammatory cytokines, and immunoglobulin E increase in both lungs of patients with asthma, and in injured heart and vessels of CVD patients. These findings suggest that allergic asthma and CVD may share pathogenic pathways. Understanding these pathways is critical to the choice of pharmacological interventions. Currently, the most appropriate therapeutic approach lies in using the best available evidence to optimize the management of both asthma and CVD. Therapy should be optimized to take advantage of the favorable benefits that each medication may have on both organs while minimizing the likelihood of adverse effects on the lungs and heart. It is noteworthy that inhaled β2-agonists induce benefit in patients with acute decompensated heart failure. Furthermore, ICSs may reduce the risk of atherosclerosis. On the other side, asthma is not an absolute contraindication to use cardio-selective β1-blockers, but these medications should be prescribed with caution especially if are necessary for acute cardiovascular events and alternative treatment options are unavailable. In addition, when aspirin intake causes the onset of hypersensitivity, P2Y12 inhibitors (e.g., clopidogrel, prasugrel, and ticagrelor) are effective and safe treatment alternatives

New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.</p

Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD

SummaryBackgroundCombining maintenance medications with different mechanisms of action may improve outcomes in COPD. In this study we evaluated the efficacy and safety of fluticasone/salmeterol (FSC) (250/50 mcg twice daily) when added to tiotropium (18 mcg once daily) (TIO) in subjects with symptomatic moderate to severe COPD.MethodsThis was a 24-week, randomized, double-blind, parallel group, multi-center study. Subjects 40 years or older with cigarette smoking history ≥10 pack-years and with the diagnosis of COPD and post-bronchodilator FEV1 ≥40 to ≤ 80% of predicted normal and FEV1/FVC of ≤0.70 were enrolled. Following a 4-week treatment with open-label TIO 18 mcg once daily, subjects were randomized in a double-blind fashion to either the addition of FSC 250/50 DISKUS twice daily or matching placebo. The primary efficacy endpoint was AM pre-dose FEV1 and secondary endpoints included other measures of lung function, rescue albuterol use, health status and exacerbations.ResultsThe addition of FSC to TIO significantly improved lung function indices including AM pre-dose FEV1, 2 h post-dose FEV1, AM pre-dose FVC, 2 h post-dose FVC and AM pre-dose IC compared with TIO alone. Furthermore, this combination was superior to TIO alone in reducing rescue albuterol use. However, there were no significant differences between the treatment groups in health status or COPD exacerbations. The incidence of adverse events was similar in both groups.ConclusionsThe addition of FSC to subjects with COPD treated with TIO significantly improves lung function without increasing the risk of adverse events. NCT00784550