Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 . More data on long-term safety are needed together with more efficacy data in the paediatric population.

Role of anticholinergics in asthma management: recent evidence and future needs.

PURPOSE OF REVIEW: Anticholinergic antimuscarinic bronchodilators play a major role in the treatment of chronic obstructive pulmonary disease, but their role in asthma has long been limited to acute management. More recently, the role of long-acting antimuscarinic bronchodilators (LAMAs) in chronic asthma management has been explored. This review will examine the pharmacological rationale for use of inhaled anticholinergics in the treatment of asthma, and provide an overview of the current literature supporting this use, as well as describe future research needs in this area. RECENT FINDINGS: Short-acting anticholinergic bronchodilators have a role as add-on agents in the treatment of acute asthma. Preliminary clinical studies suggest that inhaled LAMAs may be comparable to long-acting beta2-agonists (LABAs) as an add-on therapy in patients not controlled by inhaled corticosteroids (ICS) alone, and may also have added benefit in patients not controlled on combined ICS-LABA. Mechanistic studies suggest that apart from their bronchodilator activity, LAMAs may have anti-inflammatory and antiremodeling influences on the airways. Further research is needed to clarify the clinical relevance of these experimental observations. SUMMARY: Accumulating evidence supports the use of inhaled LAMAs as an add-on therapy in patients with asthma, who remain symptomatic despite guideline-based therapy with ICS with or without LABAs. Further studies are warranted to help define mechanisms of action of LAMAs, apart from their role as bronchodilators, and determine how these other actions impact asthma outcomes over time. Furthermore, future studies need to examine the long-term efficacy and safety of LAMAs in asthma and identify a subgroup of patients who would benefit from such therapies to facilitate early, personalized therapy.

Patterns of care in the management of high-risk COPD in the US (2011-2019): an observational study for the CONQUEST quality improvement program.

Background: In this study, we compare management of patients with high-risk chronic obstructive pulmonary disease (COPD) in the United States to national and international guidelines and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). Methods: Patients were identified from the DARTNet Practice Performance Registry and categorized into three high-risk cohorts in each year from 2011 to 2019: newly diagnosed (≤12 months after diagnosis), already diagnosed, and patients with potential undiagnosed COPD. Patients were considered high-risk if they had a history of exacerbations or likely exacerbations (respiratory consult with prescribed medication). Descriptive statistics for 2019 are reported, along with annual trends. Findings: In 2019, 10% (n = 16,610/167,197) of patients met high-risk criteria. Evidence of spirometry for diagnosis was low; in 2019, 81% (n = 1228/1523) of patients newly diagnosed at high-risk had no record of spirometry/peak expiratory flow in the 12 months pre- or post-diagnosis and 43% (n = 651/1523) had no record of COPD symptom review. Among those newly and already diagnosed at high-risk, 52% (n = 4830/9350) had no evidence of COPD medication. Interpretation: Findings suggest inconsistent adherence to evidence-based guidelines, and opportunities to improve identification, documentation of services, assessment, therapeutic intervention, and follow-up of patients with COPD. Funding: This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.

Managing hospitalized patients with a COPD exacerbation: the role of hospitalists and the multidisciplinary team.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with high rates of hospitalizations, costs, and morbidity. Therefore, hospitalists and the multidisciplinary team (hospital team) need to take a proactive approach to ensure patients are effectively managed from hospital admission to postdischarge. Comprehensive screening and diagnostic testing of patients at admission will enable an accurate diagnosis of COPD exacerbations, and severity, as well as other factors that may impact the length of hospital stay. Depending on the exacerbation severity and cause, pharmacotherapies may include short-acting bronchodilators, systemic corticosteroids, and antibiotics. Oxygen and/or ventilatory support may benefit patients with demonstrable hypoxemia. In preparation for discharge, the hospital team should ensure that patients receive the appropriate maintenance therapy, are counseled on their medications including inhalation devices, and proactively discuss smoking cessation and vaccinations. For follow-up, effective communication can be achieved by transferring discharge summaries to the primary care physician via an inpatient case manager. An inpatient case manager can support both the hospitalist and the patient in scheduling follow-up appointments, sending patient reminders, and confirming that a first outpatient visit has occurred. A PubMed search (prior to 26 January 2021) was conducted using terms such as: COPD, exacerbation, hospitalization. This narrative review focuses on the challenges the hospital team encounters in achieving optimal outcomes in the management of patients with COPD exacerbations. Additionally, we propose a novel simplified algorithm that may help the hospital team to be more proactive in the diagnosis and management of patients with COPD exacerbations.

Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA.

BACKGROUND: Although asthma is typically characterized by bronchodilator responsiveness (BDR), fixed airflow obstruction (FAO) occurs in ∼50% of patients with severe asthma. OBJECTIVE: Do FAO/BDR associate with efficacy of omalizumab, a monoclonal antibody that targets IgE? METHODS: In EXTRA, patients aged 12-75 years with inadequately controlled severe allergic asthma despite high-dose inhaled corticosteroids plus long-acting ß2-agonists were randomized to omalizumab (n = 427) or placebo (n = 423) for 48 weeks of treatment. In this post hoc analysis, high/low BDR were defined as ≥12%/<12% increases in baseline forced expiratory volume in 1 second (FEV1) after bronchodilator administration, respectively. FAO presence (+)/absence (-) were defined as baseline postbronchodilator FEV1/forced vital capacity <70%/≥70%, respectively. Poisson regression/analysis of covariance models were used to estimate exacerbation relative rate reductions (RRRs)/least-squares mean changes in FEV1, respectively. RESULTS: In patients with high BDR, omalizumab reduced exacerbations more than placebo over the 48-week treatment period regardless of FAO status (RRR [95% confidence interval (CI)]: FAO+, 59.8% [17.7-80.4%]; FAO-, 44.3% [16.6-62.8%]). Omalizumab improved FEV1 compared with placebo in the FAO-, high BDR subgroup (FEV1 change from baseline [95% CI] for omalizumab vs placebo, 0.065 L [-0.071 to 0.201 L] to 0.236 L [0.112-0.359 L]) across 48 weeks. This was not observed in patients with low BDR, irrespective of FAO. CONCLUSION: Omalizumab was more efficacious than placebo at reducing exacerbations in patients with high, but not low, BDR, regardless of the presence of FAO. Lung function improvement primarily occurred in FAO-, high BDR patients, suggesting that asthma with low BDR may represent a difficult-to-treat phenotype.

COPD in Primary Care: Key Considerations for Optimized Management: Anxiety and Depression in Chronic Obstructive Pulmonary Disease: Recognition and Management.

Ensuring that anxiety and depression are recognized and treated effectively in patients with chronic obstructive pulmonary disease (COPD) is essential for optimizing outcomes. Primary care practitioners are well placed to diagnose anxiety and depression, and to ensure these conditions are suitably managed alongside treatments of COPD.

How does race/ethnicity influence pharmacological response to asthma therapies?

INTRODUCTION: Our understanding of whether and/or how ethnicity influences pharmacological response to asthma therapies is still very scarce. A possible explanation for the increased asthma treatment failures observed in ethnic and racial minorities receiving asthma therapies is that some of these groups may have a pharmacogenomic predisposition to either nonresponse or to adverse response with a specific class of drugs. However, the effects of ethnicity on pharmacological response to asthma therapies are also, and mainly, determined by socioeconomic and environmental factors to a varying extent, depending on the ethnic groups. Areas covered: Genetic, socioeconomic and environmental factors that can affect the pharmacotherapeutic responses to asthma medications and their link(s) to race/ethnicity have been examined and critically discussed. Expert opinion: Differences in genetic ancestry are definitely non-modifiable factors, but socioeconomic and environmental disadvantages are all factors that can be modified. It is likely that improved outcomes may be achieved when tailored and multifaceted approaches that include home, school, and clinician-based interventions are implemented. Consequently, it is critical to determine if a clinical intervention programme combined with implementation strategies that attempt to reduce inequalities can reduce asthma disparities, including the influence of ethnicity and race on pharmacological response to asthma therapies.

Optimizing maintenance therapy for chronic obstructive pulmonary disease: strategies for improving patient-centered outcomes.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality. Published practice guidelines and treatment algorithms for COPD are designed to increase awareness of the problem and improve patient care; however, <40% of subjects diagnosed with COPD are receiving appropriate maintenance therapy. OBJECTIVE: This paper reviews the use of maintenance therapy in COPD and examines the optimal timing for initiating such therapy based on the available literature. METHODS: Relevant publications were identified through a search of MEDLINE (1995-May 2007) using the terms COPD, guidelines, treatment, maintenance therapy, bronchodilator, ipratropium, tiotropium, beta-agonist, salmeterol, and inhaled corticosteroid. English-language publications discussing pharmacologic maintenance therapy for COPD, including practice statements/guidelines, randomized controlled clinical trials, systematic reviews, and meta-analyses, with a focus on agents currently approved for use in the United States, were selected for inclusion. RESULTS: Although guidelines and algorithms agree on the importance of regularly scheduled maintenance therapy to reduce symptoms of COPD, minimize activity limitations, and improve health status, the timing of the initiation of such therapy is debatable. In most instances, maintenance medications, which include long-acting beta(2)-agonists, long-acting anticholinergics, and combination products, are prescribed late in the disease process and mainly for patients with severe disease. However, there is increasing evidence that the use of maintenance therapy early in the disease process may be associated with improvements in such outcomes as lung function, symptoms, exercise tolerance, exacerbations of COPD, and quality of life. CONCLUSION: The high burden associated with COPD highlights the need to initiate maintenance therapy before a substantial decline in lung function has occurred.

Update on the pharmacologic therapy for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is a treatable disease characterized by progressive airflow limitation. Prevention of disease progression; improvement of symptoms, exercise tolerance, and health status; and decrease in exacerbations and mortality are the goals of management. Inhaled short-acting bronchodilators are recommended for symptoms in mild disease, whereas inhaled long-acting bronchodilators are recommended for maintenance therapy of daily symptoms. When symptoms are not controlled using one bronchodilator, combining bronchodilators may be more effective. Combining a long-acting beta-agonist with an inhaled corticosteroid is more effective than either agent alone. Several novel therapies are in different stages of development.

Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline.

BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. CONCLUSIONS: This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.

Effect of a primary care continuing education program on clinical practice of chronic obstructive pulmonary disease: translating theory into practice.

OBJECTIVES: To describe the development and implementation process and assess the effect on self-reported clinical practice changes of a multidisciplinary, collaborative, interactive continuing medical education (CME)/continuing education (CE) program on chronic obstructive pulmonary disease (COPD). METHODS: Multidisciplinary subject matter experts and education specialists used a systematic instructional design approach and collaborated with the American College of Chest Physicians and American Academy of Nurse Practitioners to develop, deliver, and reproduce a 1-day interactive COPD CME/CE program for 351 primary care clinicians in 20 US cities from September 23, 2009, through November 13, 2010. RESULTS: We recorded responses to demographic, self-confidence, and knowledge/comprehension questions by using an audience response system. Before the program, 173 of 320 participants (54.1%) had never used the Global Initiative for Chronic Obstructive Lung Disease recommendations for COPD. After the program, clinician self-confidence improved in all areas measured. In addition, participant knowledge and comprehension significantly improved (mean score, 77.1%-94.7%; P<.001). We implemented the commitment-to-change strategy in courses 6 through 20. A total of 271 of 313 participants (86.6%) completed 971 commitment-to-change statements, and 132 of 271 (48.7%) completed the follow-up survey. Of the follow-up survey respondents, 92 of 132 (69.7%) reported completely implementing at least one clinical practice change, and only 8 of 132 (6.1%) reported inability to make any clinical practice change after the program. CONCLUSION: A carefully designed, interactive, flexible, dynamic, and reproducible COPD CME/CE program tailored to clinicians' needs that involves diverse instructional strategies and media can have short-term and long-term improvements in clinician self-confidence, knowledge/comprehension, and clinical practice.

Safety of chronic obstructive pulmonary disease medications: a primary care perspective.

Chronic obstructive pulmonary disease (COPD), which affects > 210 million individuals worldwide, places primary care practitioners at the forefront of diagnosing and managing COPD, and preventing adverse drug reactions (ADRs) associated with COPD medications. Therefore, it is essential that practitioners understand the safety profiles of these medications. They should also be aware of the host factors and any preexisting comorbidities in their patients that may impact the safety and efficacy of the prescribed therapy. Drug safety information obtained from randomized controlled trials, observational studies, and meta-analyses should be analyzed to assess the risk-benefit to a patient, since the majority of ADRs associated with COPD medications are predictable, and are avoidable with judicious use of these drugs. This article discusses the different medications available for COPD management and the factors affecting their safety based on current evidence.

Bronchodilator reversibility in COPD.

COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The diagnosis of COPD is based on spirometric evidence of airways obstruction following bronchodilator administration. Although it used to be commonly believed that patients with COPD have largely irreversible airflow obstruction, evidence now suggests that a considerable proportion of patients exhibit clinically significant bronchodilator reversibility. The complexity and inherent variability of a patient's acute response to a bronchodilator and the lack of a standardized procedure for assessing bronchodilator reversibility have led to significant confusion surrounding this concept. Although bronchodilator reversibility commonly is defined based on thresholds for improvement in FEV(1), lung volume-based measures of pulmonary function may be of particular importance in patients with severe COPD. The usefulness of acute reversibility to short-acting bronchodilators in predicting a patient's long-term response to bronchodilator maintenance therapy is also unclear, although most studies suggest that a lack of acute response to short-acting bronchodilators does not preclude a beneficial long-term response to maintenance bronchodilator treatment. This review outlines recent findings about the prevalence and usefulness of bronchodilator reversibility in patients with COPD based on the available literature and proposes areas of future research.

Cognitive-behavioral therapy for chronic cardiopulmonary conditions: preliminary outcomes from an open trial.

OBJECTIVE: To examine the effectiveness of tailored cognitive-behavioral therapy (CBT) for veterans with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) with comorbid symptoms of depression and/or anxiety. METHOD: Twenty-three veterans with CHF and/or COPD, identified from electronic medical records at a large Veterans Affairs medical center, with clinically significant symptoms of depression (Beck Depression Inventory-II [BDI-II] score ≥ 14) and/or anxiety (State Trait Anxiety Inventory [STAI] score ≥ 40) were enrolled in an open trial from August 2007 to August 2008. All patients received CBT delivered mostly by advanced psychology trainees that consisted of 6 weekly sessions and 3 telephone booster calls. The intervention expanded traditional CBT techniques in order to address patients' emotional and physical health difficulties using in-person and telephone-based sessions. Outcomes examined depression (BDI-II), anxiety (STAI), and disease-specific quality of life (Chronic Respiratory Questionnaire [CRQ] and Kansas City Cardiomyopathy Questionnaire [KCCQ]) postintervention and at 3-month follow-up. RESULTS: Symptoms of depression (effect size = 0.97) and anxiety (effect size = 0.57) were improved at 8 weeks and maintained at 3-month follow-up. Physical disease outcomes were also improved for COPD (CRQ mastery effect size = 0.65, CRQ fatigue effect size = 0.75) and CHF (KCCQ overall summary score effect size = 1.19). CONCLUSIONS: Modifications to traditional CBT approaches have the potential to address the emotional and physical health challenges associated with complex cardiopulmonary patients. The brief duration and use of telephone-based sessions increase the opportunity for CBT interventions to be integrated within primary care settings, but additional trials are needed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00727155.