Treatment of mild chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is an epidemic in many parts of the world. Most patients with COPD demonstrate mild disease. The cornerstone of management of mild disease is smoking cessation, which is the only proven intervention to relieve symptoms, modify its natural history and reduce mortality. For asymptomatic patients, it is the only required therapy. Short-acting bronchodilators can be added on an as needed basis for those with intermittent symptoms and regularly for those with persistent symptoms. Long-acting bronchodilators can be substituted for those who remain symptomatic despite regular use of short-acting bronchodilators. Inhaled corticosteroids do not modify the natural history of COPD and as such cannot be recommended as standalone therapy for mild COPD. However, for patients with refractory and intractable symptoms, they may be used in combination with long-acting beta-2 agonists. Influenza and pneumococcal vaccination and pulmonary rehabilitation are other therapies that may be considered for select patients with mild disease. In this paper, we summarize the current standard of care for patients with mild COPD

The Importance of Early Chronic Obstructive Pulmonary Disease: A Lecture from 2022 Asian Pacific Society of Respirology

Chronic obstructive pulmonary disease (COPD) affects close to 400 million people worldwide. COPD is characterized by significant airflow limitation on spirometry. Most patients with COPD are diagnosed in their fifth or sixth decades of life. However, the disease begins much earlier. By the time airflow limitation is detected on spirometry, patients with COPD have lost close to 50% of their small airways. Thus, identification of patients with early COPD, defined as persons with preserved spirometry, who demonstrate pathologic or functional hallmarks of COPD, is essential for disease modification and ultimately disease elimination. This paper provides an up-to-date overview of the current case definition of early COPD, its importance, the novel technologies required for its detection in young adults and future directions in therapeutics for treatment

What Single Cell RNA Sequencing Has Taught Us about Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) affects close to 400 million people worldwide and is the 3rd leading cause of mortality. It is a heterogeneous disorder with multiple endophenotypes, each driven by specific molecular networks and processes. Therapeutic discovery in COPD has lagged behind other disease areas owing to a lack of understanding of its pathobiology and scarcity of biomarkers to guide therapies. Single cell RNA sequencing (scRNA-seq) is a powerful new tool to identify important cellular and molecular networks that play a crucial role in disease pathogenesis. This paper provides an overview of the scRNA-seq technology and its application in COPD and the lessons learned to date from scRNA-seq experiments in COPD

Combination of ICSs and LABAs Should Be Used in the Management of Patients with COPD -- The Pro Argument

THE EFFECTS OF INHALED CORTICOSTEROID MONOTHERAPY Airway inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD), even among ex-smokers (1), and its intensity is directly related to the severity of the underlying COPD (2). The inflammatory burden increases during periods of clinical exacerbation (3-5). Predictably, use of systemic corticosteroids during these episodes accelerates clinical recovery and improves health outcomes over several months of follow-up (6). Unfortunately, long term use of systemic corticosteroids is generally precluded by their toxic side effects. Inhaled corticosteroids, on the other hand, share much of the anti-inflammatory properties of the systemic formulations without the side effects (7). However, their effectiveness has been questioned and is a matter of heated debate among members of the scientific community (8,9)

Integrative Approach to Quality Assessment of Medical Journals Using Impact Factor, Eigenfactor, and Article Influence Scores

BACKGROUND: Impact factor (IF) is a commonly used surrogate for assessing the scientific quality of journals and articles. There is growing discontent in the medical community with the use of this quality assessment tool because of its many inherent limitations. To help address such concerns, Eigenfactor (ES) and Article Influence scores (AIS) have been devised to assess scientific impact of journals. The principal aim was to compare the temporal trends in IF, ES, and AIS on the rank order of leading medical journals over time. METHODS: The 2001 to 2008 IF, ES, AIS, and number of citable items (CI) of 35 leading medical journals were collected from the Institute of Scientific Information (ISI) and the http://www.eigenfactor.org databases. The journals were ranked based on the published 2008 ES, AIS, and IF scores. Temporal score trends and variations were analyzed. RESULTS: In general, the AIS and IF values provided similar rank orders. Using ES values resulted in large changes in the rank orders with higher ranking being assigned to journals that publish a large volume of articles. Since 2001, the IF and AIS of most journals increased significantly; however the ES increased in only 51% of the journals in the analysis. Conversely, 26% of journals experienced a downward trend in their ES, while the rest experienced no significant changes (23%). This discordance between temporal trends in IF and ES was largely driven by temporal changes in the number of CI published by the journals. CONCLUSION: The rank order of medical journals changes depending on whether IF, AIS or ES is used. All of these metrics are sensitive to the number of citable items published by journals. Consumers should thus consider all of these metrics rather than just IF alone in assessing the influence and importance of medical journals in their respective disciplines

Potential role of stem cells in management of COPD

Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic affecting over 200 million people and accounting for more than three million deaths annually. The disease is characterized by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking. Unfortunately, there are no interventions that have been unequivocally shown to prolong survival in patients with COPD. Regeneration of lung tissue by stem cells from endogenous and exogenous sources is a promising therapeutic strategy. Herein we review the current literature on the characterization of resident stem and progenitor cell niches within the lung, the contribution of mesenchymal stem cells to lung regeneration, and advances in bioengineering of lung tissue

Lung Macrophages: Pivotal Immune Effector Cells Orchestrating Acute and Chronic Lung Diseases

Macrophages are key immune cells, where they play a pivotal role in host defense and tissue homeostasis. The lungs have two major subsets, alveolar macrophages (AMs) found in airspaces and interstitial macrophages (IMs) found in lung tissues. Lung macrophages (LM) are highly heterogeneous and have high levels of plasticity. A long-lasting population of LM with self-renewal ability populate the lung during embryogenesis and monocyte-derived macrophages recruited during infection, inflammation, or tissue repair, which are more short lived. AMs have been the main focus of research due in part to their abundance, accessibility, and ease of isolation compared with IMs. With advances in multichannel flow cytometry and single-cell sequencing, the importance of IMs has been recently appreciated. LM’s functions in the lungs include maintenance of homoeostasis, immune surveillance, removal of cellular debris, tissue repair, clearance of pathogens, and the resolution of inflammation. They also activate the adaptive immune response by functioning as antigen-presenting cells. LMs are pivotal in the pathogenesis of acute and chronic inflammatory lung conditions including lung cancer. This chapter will discuss the ontology, phenotypic heterogeneity, and functions of LM’s and how these characteristics orchestrate and impact common acute and chronic lung conditions

Cigarette smoking and asthma

Globally, around half the adult asthma population are current or former cigarette smokers. Cigarette smoking and asthma interact to induce an ‘asthma-smoking phenotype(s)’, which has important implications for diagnosis, pathogenic mechanisms, and management. The lack of progress in understanding the effects of smoking on adults with asthma is due in part to their exclusion from most investigative studies and large clinical trials. In this review, we summarize the adverse clinical outcomes associated with cigarette smoking in asthma, highlight challenges in diagnosing asthma among cigarette smokers with chronic respiratory symptoms, particularly in older individuals with a long-standing smoking history, and review pathogenic mechanisms involving smoking and asthma-related airway inflammation, tissue remodeling, corticosteroid insensitivity, and low-grade systemic inflammation. We discuss key components of management including the importance of smoking cessation strategies, evidence for the effectiveness of the Global Initiative for Asthma recommendations on treatment in cigarette smokers, and the role of treatable traits such as type 2 eosinophilic airway inflammation. Lastly, we provide an algorithm to aid clinicians to manage current and former smokers with asthma. In the future, controlled and pragmatic trials in real-world populations should include cigarette smokers with asthma to provide an evidence base for treatment recommendations

The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model.

Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006-2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47-4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04-0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method

COPD: Do Imaging Measurements of Emphysema and Airway Disease Explain Symptoms and Exercise Capacity?

PURPOSE: To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease. MATERIALS AND METHODS: Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George\u27s Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT). Emphysema was estimated by using the MR imaging apparent diffusion coefficient (ADC) and the relative area of the CT attenuation histogram with attenuation of -950 HU or less (RA950). Airway disease was measured by using the CT airway wall thickness of airways with an internal perimeter of 10 mm and total airway count. Ventilation defect percentage at (3)He MR imaging was used to measure ventilation. Multivariable regression models for the 6MWD and SGRQ symptom subscore were used to evaluate the relationships between physiologic and imaging measurements. RESULTS: Multivariate modeling for the 6MWD in 80 patients with GOLD grade U-II COPD showed that ADC (β = 0.34, P = .04), diffusing capacity of the lung for carbon monoxide (β = 0.60, P = .0008), and residual volume/total lung capacity (β = -0.26, P = .02) were significant variables, while forced expiratory volume in 1 second (FEV1) and airway disease measurements were not. In 36 patients with GOLD grade III or IV disease, FEV1 (β = 0.48, P = .01) was the only significant contributor in a multivariate model for 6MWD. MR imaging emphysema measurements also made the greatest relative contribution to symptoms in patients with milder (GOLD grade U-II) COPD (ADC: β = 0.60, P = .005; RA950: β = -0.52, P = .02; FEV1: β = -0.45, P = .0002) and in grade III or IV disease (ADC: β = 0.95, P = .01; RA950: β = -0.62, P = .07; airway count: β = -0.49, P = .01). CONCLUSION: In patients with mild-to-moderate COPD, MR imaging emphysema measurements played a dominant role in the expression of exercise limitation, while both CT and MR imaging measurements of emphysema explained symptoms