Implications of Cardiopulmonary Risk for the Management of COPD: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) constitutes a major global health burden and is the third leading cause of death worldwide. A high proportion of patients with COPD have cardiovascular disease, but there is also evidence that COPD is a risk factor for adverse outcomes in cardiovascular disease. Patients with COPD frequently die of respiratory and cardiovascular causes, yet the identification and management of cardiopulmonary risk remain suboptimal owing to limited awareness and clinical intervention. Acute exacerbations punctuate the progression of COPD in many patients, reducing lung function and increasing the risk of subsequent exacerbations and cardiovascular events that may lead to early death. This narrative review defines and summarises the principles of COPD-associated cardiopulmonary risk, and examines respiratory interventions currently available to modify this risk, as well as providing expert opinion on future approaches to addressing cardiopulmonary risk.

The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations.

Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting ß2-agonist (SABA) and inhaled corticosteroid (ICS) as an alternative reliever at step 2. The Food and Drug Administration approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and for reducing exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy, but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA-ICS during the window of opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that the use of albuterol-budesonide rather than albuterol as a reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the United States. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.

Use of ICS and Fast-Acting Bronchodilators in Asthma: Past, Present, and Future.

KEY TAKEAWAYS: Primary care practitioners (PCPs) play a key role in asthma management since most patients with asthma are treated in primary care settings. Despite continual advances in asthma care, important practice gaps remain, and the high burden of asthma exacerbations persists, with 43% of children with asthma and 41% of adults with asthma in the United States experiencing an asthma exacerbation in 2020. Uncontrolled asthma, incomplete assessment of exacerbation and asthma control history, reliance on systemic corticosteroids (SCS) or short-acting beta2-agonist (SABA)-only therapy, and lack of patient adherence to anti-inflammatory maintenance therapies are challenges clinicians face today with asthma care. Inhaled corticosteroids (ICS) have been thought to have slow onset of action; however, recent data indicate that ICS onset of action on bronchial tissue is seconds to minutes through nongenomic effects. A large body of evidence supports the use of ICS + fast-acting bronchodilator treatments when used as needed in response to symptoms to improve asthma control and reduce rates of exacerbations. The symptoms that occur leading up to an asthma exacerbation provide a window of opportunity to intervene with ICS + fast-acting bronchodilators, potentially preventing the exacerbation and reducing the need for SCS. Incorporating patient perspectives and preferences when designing asthma regimens will help patients be more engaged in their therapy and may contribute to improved outcomes. In January 2023, a SABA-ICS combination rescue inhaler was approved by the US Food and Drug Administration (FDA) as the first asthma rescue inhaler for as-needed use to reduce the risk of exacerbations.

The American Academy of Pediatrics Obesity Guidelines-A Critical Appraisal.

This Viewpoint discusses the American Academy of Pediatrics Obesity Guidelines.

GOLD 2023 Update: Implications for Clinical Practice.

In 2022, over 3 million people died of chronic obstructive pulmonary disease (COPD) and the global burden of the disease is expected to increase over the coming decades. Recommendations for the treatment and management of patients with COPD are published by the Global Initiative for Chronic Obstructive Lung Disease, and updated annually with scientific evidence-based recommendations. The 2023 updates, published in November 2022, contain key changes to recommendations for diagnosis and treatment of COPD that are anticipated to have a significant impact on clinical practice for patients with COPD. Updates to how COPD is defined and diagnosed, including the expansion of contributing factors beyond tobacco use, have the potential to lead to the diagnosis of more patients and to allow for the implementation of early interventions for patients during early stages of the disease. Simplification of the treatment algorithms, and placement of triple therapy within these algorithms, will support clinicians in providing appropriate, timely treatment for patients with COPD with a focus on reducing the risk of future exacerbations. Finally, recognition of mortality reduction as a treatment goal in COPD supports an increase in the use of triple therapy, the only pharmacological intervention that has been demonstrated to improve survival for patients with COPD. Although further guidance and clarification are needed in some areas, such as use of blood eosinophil counts in guiding treatment decisions and implementation of treatment protocols following hospitalizations, recent updates to the GOLD recommendations will support clinicians in addressing current gaps in patient care. Clinicians should utilize these recommendations to drive the early diagnosis of patients with COPD, the identification of exacerbations, and the selection of appropriate, timely treatments for patients.

In Honor of the Pig.

This poem describes the author's experience of open heart surgery during which he received a pig valve replacement.

Reducing the Risk of Mortality in Chronic Obstructive Pulmonary Disease With Pharmacotherapy: A Narrative Review.

In 2020, chronic obstructive pulmonary disease (COPD) was the fifth leading cause of death in the United States excluding COVID-19, and its mortality burden has been rising since the 1980s. Smoking cessation, long-term oxygen therapy, noninvasive ventilation, and lung volume reduction surgery have had a beneficial effect on mortality; however, until recently, the effects of pharmacologic therapies on all-cause mortality have been unclear. Inhaled pharmacologic treatments for patients with COPD include combinations of long-acting muscarinic receptor antagonists (LAMAs), long-acting-ß2-agonists (LABAs), and inhaled corticosteroids (ICS). The recent IMPACT and ETHOS clinical trials reported mortality benefits with ICS/LAMA/LABA triple therapy compared with LAMA/LABA dual therapy. In IMPACT, fluticasone furoate/umeclidinium/vilanterol therapy significantly reduced the risk of on-/off-treatment all-cause mortality vs umeclidinium/vilanterol (hazard ratio, 0.72; 95% CI, 0.53 to 0.99; P=.042). The ETHOS trial found a reduction in the risk of on-/off-treatment all-cause mortality in patients treated with budesonide/glycopyrrolate/formoterol vs glycopyrrolate/formoterol (hazard ratio, 0.51 [0.33 to 0.80]; nominal P=.0035). Both trials included populations of patients with symptomatic COPD at high risk of future exacerbations, and a post hoc analysis of the final retrieved vital status data suggested that the observed mortality benefits are conferred by the ICS component. In conclusion, triple therapy reduces the risk of mortality in patients with symptomatic COPD characterized by moderate or severe airflow obstruction and a recent history of moderate or severe exacerbations. This benefit is likely to be driven by reductions in exacerbations. Future research efforts should focus on improving the long-term prognosis of patients living with COPD.

A Paradigm Shift for Asthma Care.

KEY TAKEAWAYS: Asthma remains a substantial health burden, despite continued treatment advances. Patients with mild or moderate asthma, even those with intermittent symptoms, are at risk for severe or fatal exacerbations. Use of short-acting beta2-agonist (SABA)-only rescue therapy is associated with an increased risk of exacerbations, beginning at about the second fill annually. Systemic corticosteroids have shortterm and long-term adverse effects, and long-term adverse effects are driven by cumulative lifetime doses starting at 0.5 to 1.0 g. Expert opinion on the use of SABA only for rescue therapy differs, but recent evidence suggests that a fast-acting bronchodilator combined with inhaled corticosteroids (ICS) is more effective at reducing the risk of exacerbations than SABA alone. There is a window of opportunity just prior to an asthma exacerbation during which use of fast-acting bronchodilator + ICS may play a significant role in mitigating the risk of exacerbation. Patients may respond better to a combination inhaler of a fast-acting bronchodilator and an ICS as needed for rescue therapy or as part of a maintenance and rescue therapy paradigm, rather than attempting to use separate inhalers. However, there is currently no fixed-dose, fast-acting bronchodilator + ICS approved in the United States for as-needed use.

COPD Population in US Primary Care: Data From the Optimum Patient Care DARTNet Research Database and the Advancing the Patient Experience in COPD Registry.

PURPOSE: To describe demographic and clinical characteristics of chronic obstructive pulmonary disease patients managed in US primary care. METHODS: This was an observational registry study using data from the Chronic Obstructive Pulmonary Disease (COPD) Optimum Patient Care DARTNet Research Database from which the Advancing the Patient Experience COPD registry is derived. Registry patients were aged ≥35 years at diagnosis. Electronic health record data were collected from both registries, supplemented with patient-reported information/outcomes from the Advancing the Patient Experience registry from 5 primary care groups in Texas, Ohio, Colorado, New York, and North Carolina (June 2019 through November 2020). RESULTS: Of 17,192 patients included, 1,354 were also in the Advancing the Patient Experience registry. Patients were predominantly female (56%; 9,689/17,192), White (64%; 9,732/15,225), current/ex-smokers (80%; 13,784/17,192), and overweight/obese (69%; 11,628/16,849). The most commonly prescribed maintenance treatments were inhaled corticosteroid with a long-acting ß2-agonist (30%) and inhaled corticosteroid with a long-acting muscarinic antagonist (27%). Although 3% (565/17,192) of patitents were untreated, 9% (1,587/17,192) were on short-acting bronchodilator monotherapy, and 4% (756/17,192) were on inhaled corticosteroid monotherapy. Despite treatment, 38% (6,579/17,192) of patients experienced 1 or more exacerbations in the last 12 months. These findings were mirrored in the Advancing Patient Experience registry with many patients reporting high or very high impact of disease on their health (43%; 580/1,322), a breathlessness score 2 or more (45%; 588/1,315), and 1 or more exacerbation in the last 12 months (50%; 646/1,294). CONCLUSIONS: Our findings highlight the high exacerbation, symptom, and treatment burdens experienced by COPD patients managed in US primary care, and the need for more real-life effectiveness trials to support decision making at the primary care level.

Variation in Demographic and Clinical Characteristics of Patients with COPD Receiving Care in US Primary Care: Data from the Advancing the Patient EXperience (APEX) in COPD Registry.

Introduction: Little is known about the variability in chronic obstructive pulmonary disease (COPD) management and how it may be affected by patient characteristics across different healthcare systems in the US. This study aims to describe demographic and clinical characteristics of people with COPD and compare management across five primary care medical groups in the US. Methods: This is a retrospective observational registry study utilizing electronic health records stored in the Advancing the Patient Experience (APEX) COPD registry. The APEX registry contains data from five US healthcare organizations located in Texas, Ohio, Colorado, New York, and North Carolina. Data on demographic and clinical characteristics of primary care patients with COPD between December 2019 and January 2020 were extracted and compared. Results: A total of 17,192 patients with COPD were included in analysis: Texas (n = 811), Ohio (n = 8722), Colorado (n = 472), New York (n = 1149) and North Carolina (n = 6038). The majority of patients at each location were female (>54%) and overweight/obese (>60%). Inter-location variabilities were noted in terms of age, race/ethnicity, exacerbation frequency, treatment pattern, and prevalence of comorbid conditions. Patients from the Colorado site experienced the lowest number of exacerbations per year while those from the New York site reported the highest number. Hypertension was the most common co-morbidity at 4 of 5 sites with the highest prevalence in New York. Depression was the most common co-morbidity in Ohio. Treatment patterns also varied by site; Colorado had the highest proportion of patients not on any treatment. ICS/LABA was the most commonly prescribed treatment except in Ohio, where ICS/LABA/LAMA was most common. Conclusions and Relevance: Our data show heterogeneity in demographic, clinical, and treatment characteristics of patients diagnosed with COPD who are managed in primary care across different healthcare organizations in the US.

Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan-O randomized trial.

AIMS: To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol). MATERIALS AND METHODS: The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening. RESULTS: The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2-hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c -1.9% vs. -1.6% or -1.0% [-20 vs. -17 or -10 mmol/mol; 2-hour PPG -7.2 vs. -4.6 or -5.5 mmol/L). Greater proportions of participants achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi versus iGlar or Lixi (67% vs. 51% or 18%), and the composite endpoints of HbA1c <7% (<53 mmol/mol) with no body weight gain (36% vs. 19% or 16%), and HbA1c <7% (<53 mmol/mol) with no body weight gain and no documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L; 28% vs. 15% or 15%). The incidence rates of documented symptomatic hypoglycaemia were 29.0%, 27.9% and 12.1% for iGlarLixi, iGlar and Lixi, respectively. CONCLUSIONS: Adults with T2D and HbA1c ≥64 mmol/mol (≥8%) despite two OADs at screening achieved better glycaemic control with iGlarLixi versus iGlar or Lixi, without increased risk of hypoglycaemia versus iGlar.

Integrating semaglutide into obesity management - a primary care perspective.

This final article in the supplement aims to summarize a clinical approach for weight management geared toward primary care practitioners, offering practical advice about how to integrate weight management into day-to-day practice. To achieve long-term successful weight loss, a comprehensive multimodal approach is recommended, focusing on both lifestyle modification and appropriate use of therapy. Once-weekly subcutaneous semaglutide 2.4 mg is a novel treatment that can be used as an adjunct to lifestyle modification for the management of overweight and obesity. Key considerations are presented to support its optimal administration in conjunction with lifestyle modification, with a focus on assessing suitability and the importance of dose escalation and monitoring.

Cardiometabolic risk factors efficacy of semaglutide in the STEP program.

People with overweight or obesity often suffer from associated cardiometabolic diseases and comorbidities. Current therapies for obesity include lifestyle intervention, bariatric surgery, and pharmacotherapy. The magnitude of weight loss achieved with these therapies can determine the level of improvement in various comorbidities. Once-weekly subcutaneous semaglutide 2.4 mg is a glucagon-like peptide-1 receptor agonist recently approved by the US Food and Drug Administration for the treatment of obesity. This article reviews data from the global phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program, comparing the efficacy of once-weekly subcutaneous semaglutide 2.4 mg versus placebo for weight loss and improvements in cardiometabolic parameters across the STEP 1 to 5 trials. In STEP 1 to 3 and STEP 5, semaglutide led to greater reductions from baseline versus placebo in body weight, waist circumference, body mass index, systolic blood pressure (SBP), and diastolic blood pressure, as well as positive changes in glycated hemoglobin (HbA1c), C-reactive protein, and lipid levels. In STEP 4, all participants had a 20-week run-in period on semaglutide before either continuing on semaglutide or switching to placebo at week 20 in a 2:1 ratio for 48 weeks. At week 68, continued semaglutide led to further reductions from week 20 in HbA1c, improvements in lipid profile, and stabilization of SBP. Overall, across the STEP trials, treatment with semaglutide 2.4 mg versus placebo improved cardiometabolic risk factors associated with obesity, illustrating an effective treatment option for people with overweight (and associated comorbidities) or obesity.

Importance of diabetes management during the COVID-19 pandemic.

Uncontrolled diabetes and/or hyperglycemia is associated with severe COVID-19 disease and increased mortality. It is now known that poor glucose control before hospital admission can be associated with a high risk of in-hospital death. By achieving and maintaining glycemic control, primary care physicians (PCPs) play a critical role in limiting this potentially devastating outcome. Further, despite the hope that mass vaccination will help control the pandemic, genetic variants of the virus are causing surges in some countries. As such, PCPs will treat an increasing number of patients with diabetes who have symptoms of post-COVID-19 infection, or even have new-onset type 2 diabetes as a result of COVID-19 infection. However, much of the literature published focuses on the effects of COVID-19 in hospitalized patients, with few publications providing information and advice to those caring for people with diabetes in the primary care setting. This manuscript reviews the current knowledge of the risk and outcomes of individuals with diabetes who are infected with COVID-19 and provides information for PCPs on the importance of glucose control, appropriate treatment, and use of telemedicine and online prescription delivery systems to limit the potentially devastating effects of COVID-19 in people with hyperglycemia.

Importance of Early Screening and Diagnosis of Chronic Kidney Disease in Patients with Type 2 Diabetes.

It is estimated that one in ten people in the USA have diabetes. Approximately 40% of those with diabetes also develop chronic kidney disease (CKD), which in turn increases their risk of developing cardiovascular disease. Evidence-based recommendations for the treatment of patients with type 2 diabetes (T2D) and concomitant CKD are provided by several medical societies, including the American Diabetes Association (ADA), but in real life are only carried out in fewer than 50% of individuals for whom they are recommended. Screening for CKD is recommended using the spot urine albumin-to-creatinine ratio and estimated glomerular filtration rate in all patients with T2D at the time of diagnosis, and at least annually thereafter. Screening enables early CKD diagnosis, counseling, pharmacologic intervention and, when appropriate, referral to a nephrologist. The ADA guidelines recommend good glycemic and blood pressure control and the use of medications that are kidney protective. Medications shown to slow progression of CKD include renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists and, more recently, non-steroidal mineralocorticoid receptor antagonists. Novel agents with different mechanisms of action are also in development that have the potential to further slow or prevent disease progression when used with currently recommended therapies.

Translating iGlarLixi Evidence for the Management of Frequent Clinical Scenarios in Type 2 Diabetes.

Treatment of type 2 diabetes (T2D) requires progressive therapy intensification to reach and maintain individualized glycemic targets. iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide (Lixi), has been shown to provide robust HbA1c reductions allowing more people to reach HbA1c targets compared with separate administration of iGlar or Lixi. The purpose of this review is to help clinicians understand treatment intensification using iGlarLixi by presenting typical clinical scenarios supported by research evidence. These cases will focus on individuals with T2D inadequately controlled by oral antihyperglycemic drugs, basal insulin, or glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and take into consideration T2D duration, body mass index, incidence of adverse events, and regimen simplicity. Clinical evidence on the efficacy, effectiveness, and safety of iGlarLixi from randomized controlled trials and real-world studies will be discussed in the context of these cases.

Advancing the Patient EXperience (APEX) in COPD Registry: Study Design and Strengths.

The Advancing the Patient Experience (APEX) in Chronic Obstructive Pulmonary Disease (COPD) registry (https://www.apexcopd.org/) is the first primary care health system-based COPD registry in the United States. While its ultimate goal is to improve the care of patients diagnosed with COPD, the registry is also designed to describe real-life experiences of people with COPD, track key outcomes longitudinally, and assess the effectiveness of interventions. It will retrospectively and prospectively collect information from 3000 patients enrolled in 5 health care organizations. Information will be obtained from electronic health records, and from extended annual and brief questionnaires completed by patients before clinic visits. Core variables to be collected into the APEX COPD registry were agreed on by Delphi consensus and fall into 3 domains: demographics, COPD monitoring, and treatment. Main strengths of the registry include: 1) its size and scope (in terms of patient numbers, geographic spread and use of multiple information sources including patient-reported information); 2) collection of variables which are clinically relevant and practical to collect within primary care; 3) use of electronic data capture systems to ensure high-quality data and minimization of data-entry requirements; 4) inclusion of clinical, database development, management and communication experts; 5) regular sharing of key findings, both at international/national congresses and in peer-reviewed publications; and 6) a robust organizational structure to ensure continuance of the registry, and that research outputs are ethical, relevant and continue to bring value to both patients and physicians.