Early Chronic Obstructive Pulmonary Disease Research Articles

New insights into early intervention of chronic obstructive pulmonary disease with mild airflow limitation.

Chronic obstructive pulmonary disease (COPD) has become one of the major public health problems worldwide due to its high morbidity and mortality. Up until now, COPD is still under-diagnosed and under-treated, especially for mild or moderate patients. It is widely accepted that the majority of patients with COPD are in the early stages, yet this subpopulation is underestimated. In recent years, growing evidence indicates that substantial physiological and clinical abnormalities exist in patients with mild COPD compared with healthy controls. Furthermore, recent studies suggest that pharmacologic intervention in early COPD has the potential to alter clinical outcomes. The main objective of this review is to summarize recent research regarding the heterogeneous pathophysiology, clinical features, and treatment of mild and moderate COPD. We also discuss promising markers of disease progression, which may contribute to the development of precision medicine in early COPD.

The Economic Effect of Early Management in Patients with Early Chronic Obstructive Pulmonary Disease: Results from a Population-Based Nationwide Survey.

The economic effect of regular follow-up and early management in patients with early chronic obstructive pulmonary disease (COPD) has not yet been clarified. Therefore, this study aimed to estimate the economic effect of regular follow-up and early management in these patients. Patients with early COPD were identified from the Korea National Health and Nutrition Examination Survey. We analyzed medical utilization and cost for 2years without any missing data by using the Korean National Health Insurance data. Patients with routine healthcare maintenance were defined as, after diagnosis, those with regular visits to the hospital and receiving early management of COPD. Among 1204 patients with early COPD, the patients who were classified as the group with routine healthcare maintenance (69/146; 47.3%) and the group with intermittent healthcare user (79/1058; 7.5%) visited to hospital for the next 2years. The patients with routine healthcare maintenance had lower cost of inpatient service and frequencies of emergency room (ER) visit and intensive care unit (ICU) admission than intermittent healthcare users (cost of inpatient service, $4595 vs. $4953 per person; ER visit, 7.2 vs. 11.5; ICU admission, 4.3 vs. 7.7). Even in patients with COPD and FEV1 ≥ 80, early intervention through follow-up reduced the cost of inpatient service because these patients could have had less severe acute exacerbations than intermittent healthcare users. Patients with early COPD, even those with FEV1 ≥ 80, need regular follow-up for early management and disease control as well as for reducing the socioeconomic burden of the disease.

Initiating drug therapy in early stage chronic obstructive pulmonary disease: does it impact the course and outcome?

Early chronic obstructive pulmonary disease (COPD) is emerging in importance for the clinical and research settings. This review will highlight a proposed definition of early COPD, examine early and midlife factors that lead to development of early COPD and review the literature pertaining to the treatment of mild COPD to gain insight into potential therapeutic approaches for early disease. Early COPD can be defined as disease occurring in patients younger than 50 years in age with a 10-pack-year or more smoking history and abnormal spirometry, imaging or lung function decline. Childhood exposures (maternal smoking and recurrent respiratory infections), childhood and adult asthma, and smoking affect middle-age lung function. Multiple studies of long-acting muscarinic antagonists (LAMAs) in mild COPD have shown improvements in lung function and symptoms scores. Smoking cessation also has a beneficial effect on longitudinal lung function. Early COPD is an important manifestation of COPD, with a newly proposed definition and associated risk factors identified. Inferring from studies on mild COPD cohorts, LAMAs and smoking cessation may have a positive effect on longitudinal lung function and symptomatic improvement.

Bronchopulmonary dysplasia: what are its links to COPD?

Emerging evidence suggests that adverse early life events can affect long-term health trajectories throughout life. Preterm birth, in particular, is a significant early life event that affects approximately 10% of live births. Worldwide, prematurity is the number one cause of death in children less than 5 years of age and has been shown to disrupt normal lung development with lasting effects into adult life. Along with impaired lung development, interventions used to support gas exchange and other sequelae of prematurity can lead to the development of bronchopulmonary dysplasia (BPD). BPD is a chronic respiratory disease of infancy characterized by alveolar simplification, small airways disease, and pulmonary vascular changes. Although many survivors of BPD improve with age, survivors of BPD often have chronic lung disease characterized by airflow obstruction and intermittent pulmonary exacerbations. Long-term lung function trajectories as measured by FEV1 can be lower in children and adults with a history BPD. In this review, we discuss the epidemiology and manifestations of BPD and its long-term consequences throughout childhood and into adulthood. Available evidence suggests that disrupted lung development, genetic susceptibility and subsequent environment and infectious events that occur in prenatal and postnatal life likely increase the predisposition of children with BPD to develop early onset chronic obstructive pulmonary disease (COPD). The reviews of this paper are available via the supplemental material section.

Improving Detection of Early Chronic Obstructive Pulmonary Disease.

Despite being a major cause of morbidity and mortality, chronic obstructive pulmonary disease (COPD) is frequently undiagnosed. Yet the burden of disease among the undiagnosed is significant, as these individuals experience symptoms, exacerbations, and excess mortality compared to those without COPD. The U.S. Preventive Services Task Force recommends against routine screening of asymptomatic individuals with spirometry. Hence, case-finding approaches are needed. A recently developed instrument, the five-item COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk questionnaire plus peak expiratory flow, demonstrates good sensitivity and specificity for distinguishing cases from control subjects and is being studied prospectively in primary care settings to determine its impact on patient outcomes. However, finding the undiagnosed is only half the battle. Mounting evidence suggests significant COPD-like respiratory burden among individuals without airflow obstruction. Many experience dyspnea, mucus production, and exacerbation events and have emphysema and airway abnormalities on computed tomographic (CT) imaging of the chest. However, it is still unclear how to best treat these individuals and which individuals go on to develop spirometric obstruction. These challenges underline the importance of defining what constitutes "early disease." A recently proposed definition characterizes early COPD as either: 1) airflow limitation, 2) compatible CT imaging abnormalities, or 3) accelerated forced expiratory volume in 1 second decline in persons younger than 50 years and with greater than a 10 pack-year smoking history. Although it is recognized that this definition does not encompass all individuals who will develop COPD, it is an attempt to identify a group of individuals with most rapid decline to better understand mechanisms of disease development and where disease-modifying interventions are most likely to be successful. Ultimately, leveraging tools such as chest CT imaging, the electronic medical record, and machine learning algorithms may aid in the identification of such individuals.

What is early COPD and why is it important?

There is increasing interest in the origins of chronic obstructive pulmonary disease (COPD), as it is envisaged that preventive efforts and treatment can modify its clinical course. The concept of early COPD is not new, but it has recently regained interest, given new population data, recent cellular and molecular advances and insights from clinical trials. To date, many knowledge gaps in the nature of early COPD still exist, mainly because COPD has always been considered a disease of the elderly, and little attention has been paid to the pathological changes occurring in the lungs of individuals at risk before they develop clinically evident COPD. Future studies should focus on identifying early pathological manifestations of COPD in order to prevent its progression in susceptible individuals. In this review, we aim to summarise what is known on early COPD, from the epidemiological, cellular and clinical perspectives.

How to Define Early Chronic Obstructive Pulmonary Disease.

How to Define Early Chronic Obstructive Pulmonary Disease.

EARLY versus MILD Chronic Obstructive Pulmonary Disease (COPD).

Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great morbidity and mortality, disease. Since the beginning of the disease cannot be detected with precision and by using only FEV1 to monitor the evolution of the disease, the Natural History of COPD is rather obscure and sometimes controversial. Therefore, the terms EARLY COPD and MILD COPD have been used indistinguishably in the medical literature. In this review we discuss the two terms trying to clarify some of the definition issues, starting with a synopsis of the Naturel History of the disease. We recommend to use the term EARLY COPD for the pre-clinical stage of the disease (stage 0) and the term MILD COPD when the diagnosis is confirmed by spirometry and FEV1 is above 80% predicted. However, COPD is a complex disease and spirometric evaluation alone (MILD COPD, stage I), cannot fully describe the clinical status of the patient. We conclude that biomarkers to detect the starting point and been able to follow the natural history of the disease more accurately, beyond FEV, are urgently needed.

What factors influence an early COPD diagnosis in primary care?

This systematic literature review aimed to identify factors influencing late- and under-diagnosis of COPD in primary care Background: There are millions of people living with chronic obstructive pulmonary disease (COPD) who have not been diagnosed. Patients have regularly lost half of their lung function by the point of diagnosis, and therefore there are fewer interventions available. Aim: The aim of this systematic literature review was to identify factors influencing late- and under-diagnosis of COPD in primary care. This includes considering the current methods of COPD screening, and whether early screening would benefit diagnostic rates. Methods: A comprehensive, systematic literature search was undertaken using the following databases: BNI, CINAHL, Medline, NHS Evidence, PubMed, ScienceDirect, Wiley Online. Following this, a critical review of the literature was performed on 10 relevant articles. A thematic analysis followed. Results: There is a significant lack of up-to-date research on COPD screening and early detection. Generalised screening versus case-finding may be a method of identifying the undiagnosed population; however, evidence needs to improve. There is a lack of COPD education in healthcare and wider society. COPD among women is on the rise, yet they are less likely to be identified. There is a necessity for guidance and research to be provided. Screening is likely to be the future preferred method for identifying those undiagnosed, but research needs to identify the benefits of screening versus casefinding. Conclusion: The findings can be applied to primary care nursing, to combat COPD under-diagnosis.

A Novel Murine Chronic Obstructive Pulmonary Disease Model and the Pathogenic Role of MicroRNA-21

Chronic obstructive pulmonary disease (COPD) is a multi-pathogenesis chronic lung disease. The mechanisms underlying COPD have not been adequately illustrated. Many reseachers argue that microRNAs (miRs) could play a crucial role in COPD. The classic animal model of COPD is both time consuming and costly. This study proposes a novel mice COPD model and explores the role of miR-21 in COPD. A total of 50 wide-type (WT) C57BL/6 mice were separated into five euqlly-sized groups—(1) control group (CG), (2) the novel combined method group (NCM, cigarette smoke (CS) exposure for 28 days combined with cigarette smoke extract (CSE) intraperitoneal injection), (3) the short-term CS exposure group (SCSE, CS exposure for 28 days), (4) the CSE intraperitoneal injection group (CSEII, 28 days CSE intraperitoneal injection), and (5) the long-term CS exposure group (LCSE, CS exposure).The body weight gain of mice were recorded and lung function tested once the modeling was done. The pathological changes and the inflammation level by hematoxylin eosin (H&E) staining and immunohistochemical staining (IHS) on the lung tissue sections were also evaluated. The level of miR-21 in the mice lungs of the mice across all groups was detected by RT-qPCR and the effects of miR-21 knock-down in modeled mice were observed. The mice in LCSE and NCM exhibited the most severe inflammation levels and pathological and pathophysiological changes; while the changes for the mice in SCSE and CSEII were less, they remained more severe than the mice in the CG. The level of miR-21 was found to be negatively correlated with lung functions. Moreover, knocking miR-21 down from the modeled mice, ameliorated all those tested COPD-related changes. Our novel modeling method detected virtually the same changes as those detected in the classic method in WT mice, but in less time and cost. Further, it was determined that the level of miR-21 in the lungs could be an indicator of COPD severity and blocking functions of miR-21 could be a potential treatment for early stage COPD.

Plasma Proteomic Signatures in Early Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and abnormal inflammatory response of the lungs to inhaled noxious particles or gases. We used a proteomic approach with 2-DE followed by MALDI TOF-MS analyses in order to identify potential biomarkers in the early stages of the disease: global initiative for chronic obstructive pulmonary disease (GOLD) stage mild and moderate. Blood plasma was collected from 43 patients with mild and moderate COPD as well as from 43 age- and sex-matched control subjects. Proteome analysis was based on 2D-Page followed by MALDI-TOF MS identifications. Validation was made on two significant proteins by western blotting. The analyses revealed 29 between-group differences in expressed spots, belonging to 20 unique proteins. These proteins are involved in inflammation (haptoglobin, Ig alpha-1 chain C), blood coagulation and complement pathways (prothrombin, complement 4-B, ApoH), oxidative stress (ceruloplasmin, vitamin D binding protein, and serotransferrin), and lipoprotein/lipid metabolism (apolipoprotein A-I, and apolipoprotein E). These results indicate that specific proteomic signatures can be detected and useful in terms of treatment selection and in early COPD patient monitoring.

Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype

BackgroundSmoking is the main risk factor for chronic obstructive pulmonary disease (COPD). Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function. Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown. The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference.MethodWe employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18). Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest.ResultsMore pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress. Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT < −950 Hounsfield Units (HU), and regulation of actin cytoskeleton correlated with FEV1 and FEV1/FVC in female COPD patients. Alterations observed in the corresponding male cohort were minor.ConclusionThe identified molecular pathways suggest dysregulation of several phagocytosis-related pathways in BAL cells in female COPD patients, with correlation to both the level of obstruction (FEV1/FVC) and disease severity (FEV1) as well as emphysema (CT < −950 HU) in women.Trial registrationNo.: NCT02627872, retrospectively registered on December 9, 2015.

Secondary osteoporosis. Chronic obstructive pulmonary disease:COPD.

Chronic obstructive pulmonary disease(COPD), an inflammatory disease of the lung mainly caused by cigarette smoking, is a systemic disease associated with various extra-pulmonary comorbidities such as osteoporosis, ischemic heart disease and sarcopenia. Osteoporosis is one of such complications, and the prevalence of vertebral fractures in COPD is high even in early COPD stages. Loss of bone mineral density as well as deterioration of bone quality is common in COPD patients. However, the pathophysiology of bone fragility in COPD-associated osteoporosis is still incompletely understood. COPD patients are exposed to various disease-specific risk factors such as systemic inflammation, glucocorticoid use and vitamin D insufficiency/deficiency, accumulation of which leads to development of COPD-associated osteoporosis. Vitamin D repletion and timely intervention with anti-osteoporotics would be important to protect COPD patients from fracture.

At the root: Defining and halting progression of early chronic obstructive pulmonary disease

At the root: Defining and halting progression of early chronic obstructive pulmonary disease

Early detection of Chronic Obstructive Pulmonary Disease (COPD) in family practice

Background: In real practice, Chronic Obstructive Pulmonary Diseases (COPD) is often diagnosed at a late stage as its clinical manifestations pass unnoticed and spirometry is almost not utilized. Objectives: To clarify the possibility of early detection of COPD by family physicians at the primary health care level. Methods: The study was conducted during the winter season (2015) in Al-Shohadaa family health center, Al-Shohadaa city, Menoufia governorate, Egypt. All patients ≥ 40 years, smoking ≥ 20 pack-years and attending the center with respiratory symptoms were subjected after their consent to a spirometry to check for early COPD diagnosis. Results: Although based on spirometry 33 out of 192 had COPD (18 (9.4%) had GOLD I and 15 (7.8%) had ≥ GOLD II, respectively), there was no significant difference in the type and the number of respiratory symptoms between Non-COPD and early COPD patients. Conclusion: It was demonstrated that the presenting symptoms specially in early stages could not discriminate patients with COPD, so availability of spirometry in addition to training of family physicians at the family health care settings is a mandatory challenge for early COPD diagnosis.

Exhaustion of Airway Basal Progenitor Cells in Early and Established Chronic Obstructive Pulmonary Disease.

Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, prediagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired. To examine airway basal progenitor cells and lung function in smokers with and without COPD. Bronchial biopsies taken from smokers at risk for COPD and lung cancer were used to acquire airway basal progenitor cells. They were evaluated for count, self-renewal, and multipotentiality (ability to differentiate to basal, mucous, and ciliated cells), and progenitor count was examined for its relationship with lung function. Basal progenitor count, self-renewal, and multipotentiality were all reduced in COPD versus non-COPD. COPD progenitors produced an epithelium with increased basal and mucous cells and decreased ciliated cells, replicating the COPD phenotype. Progenitor depletion correlated with lung function and identified a subset of subjects without COPD with lung function that was midway between non-COPD with high progenitor counts and those with COPD. Basal progenitor dysfunction relates to the histologic and physiologic manifestations of COPD and identifies a subset that may represent an early, prediagnostic stage of COPD, indicating that progenitor exhaustion is involved in COPD pathogenesis.

Small airway disease: A different phenotype of early stage COPD associated with biomass smoke exposure.

Chronic exposure to biomass smoke (BS) can significantly compromise pulmonary function and lead to chronic obstructive pulmonary disease (COPD). To determine whether BS exposure induces a unique phenotype of COPD from an early stage, with different physiopathological features compared with COPD associated with smoking (cigarette-smoke (CS) COPD), we assessed the physiopathology of early COPD associated with BS exposure (BS COPD) by incorporating spirometry, high-resolution computed tomography (HRCT) imaging, bronchoscopy and pathological examinations. In this cross-sectional study, we recruited 29 patients with BS COPD, 31 patients with CS COPD and 22 healthy controls, including 12 BS-exposed subjects who did not smoke and 10 healthy smokers without BS exposure. Spirometry, HRCT scans, bronchoscopy and bronchial mucosa biopsies were performed to assess lung function, emphysema and air trapping, as well as the pathological characteristics and levels of inflammatory cells in bronchoalveolar lavage fluid (BALF). Among COPD patients with mild-to-moderate airflow limitation, BS exposure caused greater small airway dysfunction in BS COPD patients, although these patients had less emphysema and air trapping, as detected by HRCT (P < 0.05). We also observed significantly thicker basement membranes and greater endobronchial pigmentation in BS COPD than in CS COPD (P < 0.05). Moreover, patients with BS COPD exhibited greater macrophage and lymphocyte infiltration but reduced neutrophil infiltration in their BALF (P < 0.05). We used both radiology and pathology to document a distinct COPD phenotype associated with BS exposure. This is characterized by small airway disease.

The boundaries of mild chronic obstructive pulmonary disease (COPD): design of the searching clinical COPD onset (SOON) study

IntroductionClinical onset of chronic obstructive pulmonary disease (COPD) is the point at which the disease is first identifiable by physicians. It is a poorly defined stage which seems to include...

Ventilatory Inefficiency and Exertional Dyspnea in Early Chronic Obstructive Pulmonary Disease

Exertional dyspnea is present across the spectrum of chronic obstructive pulmonary disease (COPD) severity. However, without realizing it themselves, patients may decrease daily physical activity to avoid distressing respiratory sensations. Dyspnea also may be associated with deconditioning. Cardiopulmonary exercise testing can uncover exertional dyspnea and its physiological determinants in patients with preserved or only mildly reduced FEV1. Dyspnea in mild COPD can largely be explained by increased "wasted" ventilation in the physiological dead space, which heightens the drive to breathe and worsens the inspiratory mechanical constraints. During incremental exercise testing, this is readily identified as an excessive ventilation-to-metabolic demand, that is, a high ventilation ([Formula: see text]e) to carbon dioxide output ([Formula: see text]co2) relationship. Linking increases in [Formula: see text]e/[Formula: see text]co2 to exertional dyspnea may provide objective evidence that a patient's poor exercise tolerance is not just a consequence of deconditioning. This information should prompt a proactive therapeutic approach to increase the available ventilatory reserve by, for example, giving inhaled bronchodilators. Considering that the structural determinants of ventilatory inefficiency (early emphysema, ventilation-perfusion mismatching, and microvascular disease) may progress despite only modest changes in FEV1, serial [Formula: see text]e/[Formula: see text]co2 measurements might also prove valuable to track disease progression in these symptomatic patients.

Early Detection of Chronic Obstructive Pulmonary Disease (COPD) in Family Practice

Background: In real practice, Chronic Obstructive Pulmonary Diseases (COPD) is often diagnosed at a late stage as its clinical manifestations pass unnoticed and spirometry is almost not utilized. Objectives: To clarify the possibility of early detection of COPD by family physicians at the primary health care level. Methods: The study was conducted during the winter season (2015) in Al-Shohadaa family health center, Al-Shohadaa city, Menoufia governorate, Egypt. All patients ≥ 40 years, smoking ≥ 20 pack-years and attending the center with respiratory symptoms were subjected after their consent to a spirometry to check for early COPD diagnosis. Results: Although based on spirometry 33 out of 192 had COPD (18 (9.4%) had GOLD I and 15 (7.8%) had ≥ GOLD II, respectively), there was no significant difference in the type and the number of respiratory symptoms between Non-COPD and early COPD patients. Conclusion: It was demonstrated that the presenting symptoms specially in early stages could not discriminate the patients with COPD, so availability of spirometry in addition to training of family physicians at the family health care settings is a mandatory challenge for early diagnosis of COPD.