NetWorks

Beta-blockers in COPD


 

 

Airway disorders

Beta-blockers in COPD: A settled debate?

Beta-blockers are the cornerstone in the management of patients with heart failure and myocardial infarction where they have shown to improve morbidity and mortality. Cardiovascular disease is common in patients with COPD. A 2014 meta-analysis of retrospective studies involving patients with COPD using a beta-blocker has shown lower death and lower exacerbation rate (Du Q, et al. PLoS One. 2014;9[11]:e113048). More recent studies continue to note underutilization of beta-blockers in patients with COPD due to concerns for adverse effects on pulmonary function (Lipworth B, et al. Heart. 2016;102[23]:1909).

Dr. Muhammad Adrish

Dr. Muhammad Adrish

To further study these concerns, Dransfield and colleagues conducted a randomized controlled trial (BLOCK COPD) of 532 randomly assigned patients to receive either metoprolol or placebo (Dransfield, et al. N Engl J Med. 2019;381[24]:2304). Primary outcome was time to first COPD exacerbation whereas secondary outcomes included rate of exacerbation, mortality, hospitalization, symptoms, and spirometry data. Median time to exacerbation was similar between the two groups; however, metoprolol was associated with higher incidence of severe exacerbation requiring hospitalization (HR 1.91, 95% CI 1.29-2.83). There was nonstatistical increase in deaths in metoprolol group, mainly contributed by fatal COPD events (seven in metoprolol vs one in placebo). The study results validated some of the concerns of worsening pulmonary function with beta-blocker use; however, in order to better understand the study results, we must pay attention to the study cohort.

 

Dr. Navitha Ramesh

Dr. Navitha Ramesh

In summary, patients did not have significant cardiac disease and, therefore, did not have an overt indication for beta-blocker use. Patients with COPD in this study were sicker than average patients. Lastly, there were more patients in the metoprolol group who had COPD exacerbations requiring ED visit or hospitalization in 12 months prior to study enrollment. For the above-mentioned reasons, the conclusion of this study should not discourage the use of beta-blockers in patients with COPD when underlying cardiac disease warrants their use, after careful consideration of benefits and risks.

Muhammad Adrish, MD, FCCP, Steering Committee Member

Navitha Ramesh, MD, FCCP, Steering Committee Member

Clinical research

Nintedanib in progressive fibrosing interstitial lung diseases: Does one size really fit all?

Interstitial lung diseases (ILDs) include a variety of lung disorders, such as idiopathic interstitial pneumonias (IIPs), autoimmune diseases, granulomatous lung disease, and environmental diseases. They all have one thing in common—a progressive fibrosing phenotype that is almost universally fatal. It has been suggested that such diseases have a shared pathophysiologic mechanism irrespective of the cause and, hence, could respond to similar therapy. Nintedanib acts intracellularly by inhibiting multiple tyrosine kinases. Previous clinical trials have suggested that nintedanib inhibits the progression of lung fibrosis in patients with idiopathic pulmonary fibrosis (Richeldi, et al. N Engl J Med. 2014;370[22]:2071) and systemic sclerosis-associated ILD (Distler, et al. N Engl J Med. 2019;380[26]:2518). The INBUILD trial was conducted to study the efficacy and safety of nintedanib in patients with fibrosing interstitial lung diseases (Flaherty, et al. N Engl J Med. 2019;381[18]:1718).

Dr. Mohsin Ijaz, Bronx (N.Y.) Lebanon Hospital Center

Dr. Mohsin Ijaz

Patients with a wide spectrum of progressive fibrosing ILD were enrolled in the INBUILD trial. This gave the phenotypic approach needed to study the effects of nintedanib in fibrosing ILDs. The authors reported an absolute difference of 107 mL in the annual rate of decline in forced vital capacity in the overall population, 128.2 mL (95% CI 65.4 to 148.5; P less than .001) in patients with UIP-like fibrotic pattern and 75.3 mL in patients with other fibrotic patterns, between patients who received nintedanib and those who received placebo. Earlier studies have shown similar results in patients with IPF. The most frequent adverse event was diarrhea (66.9% in the nintedanib group and 23.9% in placebo group). Liver enzymes derangement was more common in the nintedanib group. Nausea, vomiting, abdominal pain, decreased appetite, and weight decrease were also more frequent in the nintedanib group than in those in the placebo group. In conclusion, this study not only explored the effects of nintedanib on progressive fibrosing ILDs but also helped to enhance the understanding of their natural history, suggesting a final common pathway toward lung fibrosis.


Mohsin Ijaz, MD, FCCP, Steering Committee Member

Critical care

Vaping-related acute lung injury: Where there’s smoke, there’s fire

E-cigarette or vaping product use–associated lung injury (EVALI) is a burgeoning public health problem in the United States. There have been more than 2,506 hospitalizations and 54 deaths from EVALI (cdc.gov). Unfortunately, the diagnosis is one of exclusion at present. The CDC defines EVALI as lung disease associated with e-cigarette or vaping exposure within 90 days, infiltrates, and absence of other causes (Layden, et al. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614). As critical care providers, we are uniquely poised to detect and treat this illness, given that roughly 1 in 3 patients with EVALI require mechanical ventilation. Moreover, one-quarter of rehospitalizations and deaths occur 2 days after discharge from initial hospitalization (Mikosz, et al. MMWR 2020;68[5152]:1183). .
 

To better identify EVALI, the Centers for Disease Control and Prevention (CDC) recommends that health-care providers ask e-cigarette or vaping product users about respiratory, gastrointestinal, and constitutional symptoms, obtain chest imaging in those suspected of EVALI, consider outpatient management of stable patients, test for influenza, and use caution when prescribing steroids in the outpatient setting. Emphasizing cessation and advocating for annual influenza vaccination is also recommended (Update: Interim Guidance for Health Care Providers for Managing Patients with Suspected E-cigarette, or Vaping, Product Use–Associated Lung Injury. (MMWR. 2019;68[46]:1081).

So how can critical care providers assist in the understanding and treatment of EVALI? Critical care physicians treating patients with EVALI face unique challenges moving forward. We need to develop a better understanding of the triggers and pathophysiology of EVALI and learn to improve our recognition of the disease. We should study interventions that may improve outcomes such as corticosteroids. We know little about the long-term outcomes and sequalae of EVALI.

Dr. Daniel R. Ouellette

Dr. Daniel R. Ouellette

The best treatment for EVALI is prevention. Critical care physicians are experts at identifying and treating life-threatening conditions but as a community have less experience in the public health arena. If as physicians we are called upon to advocate for our patients, then perhaps there is a role for critical care physicians to advocate for a ban on vaping.
 

Matthew K. Hensley, MD, MPH, Fellow-in-Training

Daniel R. Ouellette, MD, MS, FCCP, NetWork Vice-Chair

Home-based mechanical ventilation and neuromuscular disease

Keeping up with the times: incorporating home mechanical ventilation education into pulmonary and critical care fellowship and clinical practice

Home mechanical ventilation (HMV) utilization for patients with chronic respiratory conditions is rapidly increasing in both pediatric and adult populations. By 2016, the estimated prevalence of HMV was 2.9-12.9/100,000 (3.1-18% via tracheotomy) (Rose, et al. Respir Care. 2015;60[5]:695; Valko, et al. BMC Pulm Med. 2018;18[1]:190). In 2012 limited regional U.S. data were extrapolated to approximate a prevalence of 4.7-6.4/100,000 children utilizing HMV (King, A. Respir Care. 2012;57[6]921), but there is currently no comprehensive registry of HMV use in the United States. A U.S. Department of Health and Human Services report in 2016 described an 85-fold increase in Medicare claims for home ventilators in 2015 compared with 2009 (OEI-12-15-00370; 9/22/2016).

Dr. Bethany L. Lussier

Dr. Bethany L. Lussier

With increasing demand, educating clinicians responsible for providing and managing HMV is paramount. Education specific to longitudinal management of the HMV is noticeably overlooked. The ACGME core competencies for PCCM fellowships include principles inherent to HMV, including modes/principles of ventilation, modalities/principles of oxygen supplementation, tracheostomy tube management, as well as the use of “masks for delivery of supplemental oxygen, humidifiers, nebulizers, and incentive spirometry” (ACGME Common Program Requirements 7/1/2019). However, training programs are not required to provide skills essential in HMV management, including: (1) appropriate patient selection for long-term HMV, (2) selection of well-matched home ventilators suited to patients’ chronic conditions, (3) assessment/timing of transition to invasive ventilation, or (4) adjustments necessary to maintain optimal ventilator support. Life-sustaining ventilators used in ICUs differ from life-supporting HMV systems in modes, interface, cost, algorithms, circuitry, and available adjuncts.

 

Dr. Won Y. Lee

Dr. Won Y. Lee

There is an opportunity (and responsibility) to improve current training guidelines to meet growing needs of the population and anticipate needs of trainees as they enter unsupervised practice. Although simulation initiatives at national CHEST meetings attempt to bridge education gaps, it is incumbent upon fellowship training programs to prepare pulmonologists with skills to manage HMV in order to maintain high standards of care in a safe, financially responsible and evidence-based manner.

Bethany L. Lussier, MD, FCCP, NetWork Member

Won Y. Lee, MD, FCCP. Steering Committee Member

Interstitial and diffuse lung disease

Granulomatous lymphocytic interstitial lung disease (GL-ILD)

Among the granulomatous lung diseases, Gl-ILD is hardly a new discovery, but for many reasons, it often goes undiagnosed for years. The relative rareness of the disease itself and, hence, the lack of awareness makes it an uncommon differential for granulomatous ILD. Patients with GL-ILD are often misdiagnosed with sarcoidosis, unspecified ILD, or lymphoid interstitial pneumonia, etc, before receiving a diagnosis of GL-ILD.

Dr. Avanthika Thanushi Wynn

Dr. A. Thanushi Wynn

GL-ILD is seen in 5% to 22% of patients with common variable immunoglobulin deficiency (CVID). There are instances where patients are diagnosed with CVID based on a radiologic or histologic diagnosis of GL-ILD. Although GL-ILD suggests a pulmonary process, it actually encompasses a multisystemic granulomatous inflammatory disease that may affect the liver, spleen, bowels, lymphoid tissue, and conceivably any other organ system (Hartono, et al. Ann Allergy Asthma Immunol. 2017;118[5]:614. Pathogenesis of GL-ILD in CVID includes dysfunctional antigen handling (due to impaired T cell function) and aberrant immune response to viruses (Hurst, et al. J Allergy Clin Immunol Pract. 2017;5[4]:938).

Patients with GL-ILD often present with progressive shortness of breath, restrictive lung functions with a background of CVID. Imaging findings are 5-30 mm lower lobe-predominant, nodules, ground glass opacities, and splenomegaly. Histopathology varies with predominant granulomas vs lymphocytic infiltrates. The process can be treated and often reversed with use of high dose immunoglobulin replacement, immunomodulatory therapy with agents like azathioprine, and rituximab. However, steroids are not helpful. Due to the lymphocytic dysregulation in GL-ILD, patients are at high risk of death from lymphoma. Part of the management is surveillance for malignancy and involvement of other organ systems.

A. Thanushi Wynn, MD, Fellow-in-Training

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