Search

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-β2-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.

Study objective: To investigate the efficacy and safety of a fully human monoclonal antibody recognizing the chemokine interleukin (IL)-8 in patients with COPD. Design: Randomized, double-blind, parallel-group, placebo-controlled trial. Setting: [...]

Study objectives: The objectives of this study were as follows: (1) to compare results of the discrete and the continuous methods for measuring breathlessness; (2) to examine test-retest reliability; (3) [...]

There has been a resurgence of interest in pulmonary rehabilitation mainly because the prevalence of COPD has increased, scientific studies document consistent benefits (increased exercise endurance and reduced dyspnea), and [...]

Study objective: To investigate the ability of patients with COPD to reproduce an exercise intensity accurately on the treadmill using dyspnea ratings obtained during incremental exercise on the cycle ergometer [...]

Study objective: To investigate the short-term effects of inhaled salmeterol on the perception of dyspnea and lung function in patients with COPD Design: Double-blind, crossover, randomized trial comparing inhaled salmeterol [...]

Study objective: We tested the hypothesis that patients with COPD can use dyspnea ratings obtained from a prior graded exercise test as a target to reliably produce specific exercise intensities. [...]

Study objective: To evaluate the short-form 36-item questionnaire (SF-36) as an instrument for measuring health-related quality of life (HRQL) in patients with symptomatic COPD. Design: Observational data at a single [...]

Study Objective: To examine the relationships among clinical dyspnea ratings, physiologic pulmonary function, and general health status in symptomatic patients with chronic obstructive pulmonary disease (COPD). Design: Observational data collected [...]

Biomarkers in COPD may be clinical (prior exacerbation history), physiologic (FEV1), or blood based (eosinophil count or fibrinogen level). Recent interest in using biomarkers to predict response to therapy in clinical practice has emerged. The benefits of inhaled therapy depend on the correct use of the inhaler, including an appropriate inspiratory flow. Of the available delivery systems, dry powder inhalers are unique because they have an internal resistance, are breath actuated, and are flow dependent. Ideally, the user inhales “forcefully” to generate turbulent energy (determined by an individual’s inspiratory flow and the resistance of the device) within the device that disaggregates the powder so that the individual inhales the medication particles into the lower respiratory tract. Because of specific features of dry powder inhalers and the required optimal inspiratory flow, an unmet need exists to identify individuals who are likely or unlikely to benefit from dry powder medications. Peak inspiratory flow, defined as the maximum airflow generated during inhalation against the simulated resistance of a dry powder inhaler, is a physiologic measure that has biological plausibility, has good test characteristics (repeatability and reliability), and is generalizable. Current evidence supports peak inspiratory flow as a predictive therapeutic biomarker to optimize therapy in both outpatients with COPD as well as those hospitalized for an exacerbation before discharge. This approach is consistent with the precepts of precision medicine, which considers differences in a person’s biological features, exposure, and lifestyle to prevent and treat disease.

Peak inspiratory flow (PIF) has been proposed as a measure to assess a patient’s ability to use dry powder inhalers (DPIs). However, robust quality criteria to determine a repeatability limit for measuring PIF are lacking.

Introduction. Many patients with chronic obstructive pulmonary disease (COPD) may derive inadequate benefit from dry powder inhalers (DPIs) because of suboptimal peak inspiratory flow (sPIF). Objectives. To assess the clinical burden of COPD by characterizing the clinical characteristics of participants with sPIF against medium-low resistance DPIs versus those with optimal PIF (oPIF) from two phase 3 clinical trials. Methods. Baseline data were collected from two randomized, controlled, phase 3 trials (NCT03095456; NCT02518139) in participants with moderate-to-severe COPD. oPIF (60 L/min) against the medium-low resistance DPIs was used as the threshold for defining the PIF subgroups (<60 L/min (sPIF) vs ≥60 L/min (oPIF)). Results. Most participants included in this analysis were White (92%) and male (63%); the mean (range) age was 65 (43–87) years. Participants with sPIF had significantly greater dyspnea than those with oPIF as measured using the modified Medical Research Council scoring (mean (95% CI): 2.1 (2.0–2.2) vs 1.6 (1.4–1.7); P <0.001) and baseline dyspnea index (mean (95% CI): 5.1 (4.9–5.4) vs 6.1 (5.8–6.3); P <0.001). Based on COPD Assessment Test scores, participants with sPIF had a higher COPD symptom burden than those with oPIF (mean (95% CI): 21.5 (19.7–23.3) vs 19.5 (18.6–20.4); P=0.05). Conclusion. In these trials, participants with COPD who had sPIF against the medium-low resistance DPIs had more dyspnea and worse health status than those with oPIF. These results demonstrate that sPIF is associated with a higher clinical burden as measured by patient-reported outcomes.

The responsiveness of a new computerized method for patients to provide continuous ratings of dyspnea during exercise in patients with chronic obstructive pulmonary disease (COPD) is examined. Results reveal that continuous ratings of dyspnea were responsive to inhaled bronchodilator therapy during both incremental and constant work exercise tests in patients with symptomatic COPD.

Research indicates that patients with chronic obstructive pulmonary disease can use the same dyspnea ratings after their participation in pulmonary rehabilitation to monitor exercise training at the same relative intensity regardless of the physiologic response.

Background: Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use [...]

Richard Casaburi, PhD, MD(*); Donald A Mahler, MD; Paul W Jones, PhD; Charles W Serby, MD; Shailendra S Menjoge, PhD and Theodore J Witek, Dr, PH. Division of Respiratory Medicine, [...]

Study objectives: We tested the hypothesis that descriptors of breathlessness represent distinct and separable cognitive constructs, and predicted that the use of descriptors of breathlessness by healthy individuals is the [...]

The traditional approach of caring for patients with chronic respiratory disease has been to rely on pulmonary function tests to quantify the severity and to assess response to therapy. However, [...]

Flaws and Guffaws To the Editor: A recent article by Mahler et al (April 1999)[1] that compared the effectiveness of a highly potent inhaled Β-agonist with an established and effective [...]

To the Editor: When we read the article in CHEST (September 2004) (1) by Mahler et al, we may think that placebo-controlled trials are difficult to perform. The overall results [...]

[Editor's note: Dyspnea is an extremely common symptom in patients with respiratory or cardiac disorders. Over the years, advances have been made in quantifying this symptom. Dr Mahler has been [...]

Dyspnea is due to an imbalance between the demand to breatheand the ability to breathe. The prevalence is ∼30% for those 65 years or older with walking on a level surface or up an incline. Dyspnea is a strong predictor of mortality in elderly individuals. Anemia, cardiovascular disease, deconditioning, psychological disorders, and respiratory diseases are common causes of dyspnea. Initial treatments to relieve breathing discomfort should be directed toward improving the pathophysiology of the underlying disease. Simple and inexpensive strategies to relieve dyspnea are available. This article provides an update on the evaluation of chronic dyspnea in elderly individuals.

Training of patients with moderate to severe chronic obstructive pulmonary disease to strengthen their respiratory muscles was shown to improve the functional capacity of the respiratory muscles and to reduce dyspnea, or breathlessness. a study was conducted in which 19 patients trained for 15 minutes, twice a day with a device which provided resistance when the patients breathed in. The device provided feedback to the patients, as it showed how strong each breath was, which allowed the patients to tell if they were training properly on a breath-to-breath basis. Patients who were in a control group trained at a constantly low resistance level, while those in an experimental group trained at increased levels of resistance. The patients who trained at increased levels of resistance showed a significant increase in the strength of their inspiratory muscles. There was, however, no significant increase in the maximum inspiratory pressure that could be achieved in the trained group compared with the control group. The trained patients had decreased dyspnea after eight weeks of training. There was no change in either lung function or strength of the expiratory muscles of the patients after training. Therefore, patients with chronic obstructive pulmonary disease may have reduced dyspnea, if they strengthen their respiratory muscles through a training program. Further study is needed to determine the optimum conditions of the training, such as the frequency, duration and intensity. (Consumer Summary produced by Reliance Medical Information, Inc.)

To evaluate measurements of respiratory sensation in ILD, we compared ratings of breathlessness from three clinical scales with the perceived magnitude of added elastic loads in 20 symptomatic ILD patients. [...]

Nebulizers are commonly employed for inhaled drug delivery. As they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The coronavirus disease 2019 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could negatively impact outcomes, especially for patients who may not derive full treatment benefit from hand-held inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that may also be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this Expert Guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting, and one for the home environment. Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient-care situations and to evaluate the effectiveness of mitigation strategies.

As guidelines and strategies for pharmacologic treatment of COPD focus on specific classes of inhaled medications, there is an unmet need for information to guide health care professionals (HCPs) for selecting an inhaled medication delivery system that matches the unique characteristics of individual patients. In this Special Feature article, we provide guidance for selecting an inhaled medication delivery system based on three “key” patient factors – cognitive function, manual dexterity/strength, and peak inspiratory flow (PIF). Additionally, information is provided about specific tests to assess these patient factors. Cognitive impairment with an estimated prevalence of 25% among patients with COPD adversely affects patients’ ability to use a handheld device correctly. To our knowledge, the prevalence of impaired manual dexterity/strength has not been reported in those with COPD. However, 79% of patients with COPD have reported one or more physical impediments that could impact their ability to manipulate an inhaler device. The measurement of PIF against the simulated resistance (r) of a dry powder inhaler (DPI) establishes whether the patient has the inhalation ability for creating optimal turbulent energy within the device. A suboptimal PIFr for low to medium-high resistance DPIs has been reported in 19% to 84% of stable out-patients with COPD. HCPs should consider cognitive function, manual dexterity/strength, and PIFr in their patients with COPD when prescribing inhaled pharmacotherapy. Impairments in these patient factors are common among those with COPD and can affect the individual’s competency and effectiveness of using inhaled medications delivered by handheld devices.

AbstractEffective treatment of dyspnea, or breathing difficulty, for patients with chronic obstructive pulmonary disease is a major unmet need. Five of six published randomized controlled trials show that acupuncture and/or applying transcutaneous electrical nerve stimulation over acupuncture points improves breathing difficulty in patients with chronic obstructive pulmonary disease. Acupuncture techniques may relieve the perception of dyspnea by three possible mechanisms: (1) activation of areas in the central nervous system where afferent signals are processed and integrated; (2) relaxation of bronchial smooth muscle; and (3) the release of neurotransmitters, such as endorphins, that modulate breathlessness. Adverse events of acupuncture reported in a national database in the United Kingdom include retained needles, dizziness, loss of consciousness/unresponsiveness, falls, bruising at the needle site, and pneumothorax. Caution is advised before needles are placed into the chest of an individual who has chronic obstructive pulmonary disease because lung hyperinflation and low chest wall fat may increase the risk of a pneumothorax. Transcutaneous electrical nerve stimulation at acupuncture points is an alternative noninvasive approach to insertion of needles into the chest. Clinical uncertainties need to be addressed in prospective clinical trials to further understand the potential role of acupuncture techniques in relieving the distressing symptom of dyspnea.

(Chest 1992; 102:1875-76) A 65-year-old woman was referred because of a 2-month history of progressive dyspnea on exertion, a 5.5-kg weight loss, and muscle weakness. She had stopped doing her [...]

Although patients may find it difficult to describe their breathing discomfort, most are able to select statements among a list to describe their experience. The primary objective of this study was to examine sensitivity and specificity of descriptors of breathing discomfort prospectively in patients with common respiratory conditions as well as those patients who had refractory dyspnea.

Dyspnea is the most prevalent symptom among patients with cardiac and respiratory diseases. It is an independent predictor of mortality in patients with heart disease, COPD, and the elderly. Studies using naloxone to block opioid-receptor signaling demonstrate that endogenous opioids modulate dyspnea in patients with COPD. Neuroimaging studies support a cortical-limbic network for dyspnea perception. A 2012 American Thoracic Society statement recommended that dyspnea be considered across three different constructs: sensory (intensity), affective (distress), and impact on daily activities. The 2013 GOLD (Global Initiative for Chronic Obstructive Lung Disease) executive summary recommended a treatment paradigm for patients with COPD based on the modified Medical Research Council dyspnea score. The intensity and quality of dyspnea during exercise in patients with COPD is influenced by the time to onset of critical mechanical volume constraints that are ultimately dictated by the magnitude of resting inspiratory capacity. Long-acting bronchodilators, either singly or in combination, provide sustained bronchodilation and lung deflation that contribute to relief of dyspnea in those with COPD. Opioid medications reduce breathing discomfort by decreasing respiratory drive (and associated corollary discharge), altering central perception, and/or decreasing anxiety. For individuals suffering from refractory dyspnea, a low dose of an opioid is recommended initially, and then titrated to achieve the lowest effective dose based on patient ratings. Acupuncture, bronchoscopic volume reduction, and noninvasive open ventilation are experimental approaches shown to ameliorate dyspnea in patients with COPD, but require confirmatory evidence before clinical use.

BACKGROUND:Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD.

PURPOSE: To examine and compare the component and total scores of the self-administered computerized (SAC) versions of the Baseline (BDI) and the Transition (TDI) Dyspnea Indexes with scores from the [...]

The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However, the risks of other respiratory infections, such as TB and influenza, remain unclear.

Study objectives: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled [Β.sub.2]-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. Design: [...]

Whether the combination of a once-daily inhaled corticosteroid with a once-daily longacting β2agonist is more protective than a once-daily longacting β2agonist alone against exacerbations of chronic obstructive pulmonary disease (COPD) is unknown. We hypothesised that fluticasone furoate and vilanterol would prevent more exacerbations than would vilanterol alone.

Although opioid receptors are expressed broadly in the CNS and in peripheral sensory nerve endings including bronchioles and alveolar walls of the respiratory tract, it is unknown whether the modulatory effect of endogenous opioids on breathlessness occurs in the CNS or in the peripheral nervous system. The purpose of this investigation was to examine whether increased blood levels of β-endorphin modify breathlessness by a putative effect of binding to peripheral opioid receptors in the respiratory tract.

Patients with COPD exhibit greater oxyhemoglobin desaturation during walking than with cycling. The purpose of this investigation was to investigate differences in ventilatory responses and gas exchange as proposed mechanisms for this observation.