Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

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Medscape

Chronic obstructive pulmonary disease (COPD) is a common problem in the elderly. The disease is characterised by intermittent worsening of symptoms and these episodes are called acute exacerbations. The best estimate, based on several lines of evidence, is that approximately half of all exacerbations are caused by bacteria. These lines of evidence include studies of lower respiratory tract bacteriology during exacerbations, correlation of airways’ inflammation with results of sputum cultures during exacerbations, analysis of immune responses to bacterial pathogens, and the observation in randomised, prospective, placebo-controlled trials that antibacterial therapy is of benefit. The most important bacterial causes of exacerbations of COPD are nontypeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Chlamydia pneumoniae.

/pdf/chronic-obstructive-pulmonary-disease-4ipss13czj.pdf

Chronic obstructive pulmonary disease

Representatives from many countries serve as a network for the dissemination and implementation of programs for diagnosis, management, and prevention of COPD. The GOLD Board of Directors is grateful to the many GOLD National Leaders who participated in discussions of concepts that appear in GOLD reports.

Global initiative for chronic obstructive lung disease.

To examine the relation between small-airways abnormalities and specific lung functions, we performed pulmonary-function tests in 36 patients, of whom two were nonsmokers, one to three days before open-lung biopsy for localized pulmonary lesions. The primary lesion in the small airways was a progressive inflammatory reaction leading to fibrosis with connective-tissue deposition in the airway walls. Increase in disease in small airways correlated with deterioration in lung function. Lesions could be reliably detected (P<0.05) by tests for closing capacity, the volume at which air and helium flow were equal (a test of airway caliber and elastic recoil), and the slope of phase III of the single-breath washout curve (which tests evenness of ventilation). These tests showed abnormalities at a time when the pathologic changes were still potentially reversible and when other tests were not appreciably changed. (N Engl J Med 298:1277–1281, 1977)

The relations between structural changes in small airways and pulmonary-function tests.

This review is an account of how pulmonary damage caused by cigarette smoke and other environmental toxins can incite inflammatory and immunologic reactions that culminate in chronic obstructive pulmonary disease (COPD). The authors present evidence that autoimmunity has a role in the development of COPD.

/pdf/immunologic-aspects-of-chronic-obstructive-pulmonary-disease-376rvbc8f0.pdf

Immunologic Aspects of Chronic Obstructive Pulmonary Disease

The prevalent theory in the pathogenesis of emphysema proposes that increased numbers of activated neutrophils and/or alveolar macrophages produce large amounts of proteases, an activity that cannot be regulated by alpha 1-antiproteases, resulting in lung destruction. However, the cells in the lung parenchyma of smokers have not been properly identified. We characterized and quantitated the inflammatory cell load in the lungs of smokers and correlated these findings with the degree of lung destruction. Twenty-one patients, six nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes were fixed and stained for light microscopy and neutrophil identification and immunohistochemically stained for identification of lymphocytes and macrophages. By point counting, we determined the extent of emphysema by the volume density of the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01), whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = -0.78) correlated negatively with the Vvalv. The number of T-lymphocytes correlated negatively with the number of neutrophils (r = -0.58) and positively with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung. However, the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly implicated in the pathogenesis of emphysema in smokers.

Alveolar inflammation and its relation to emphysema in smokers.

The mechanisms involved in the genesis of chronic obstructive pulmonary disease (COPD) are poorly defined. This area is complicated and difficult to model because COPD consists of four separate anatomic lesions (emphysema, small airway remodeling, pulmonary hypertension, and chronic bronchitis) and a functional lesion, acute exacerbation; moreover, the disease in humans develops over decades. This review discusses the various animal models that have been used to attempt to recreate human COPD and the advantages and disadvantages of each. None of the models reproduces the exact changes seen in humans, but cigarette smoke-induced disease appears to come the closest, and genetically modified animals also, in some instances, shed light on processes that appear to play a role.

https://www.physiology.org/doi/pdf/10.1152/ajplung.90200.2008

Animal models of chronic obstructive pulmonary disease

Previously, it had been shown that T-lymphocytes are the predominant inflammatory cells found in the alveolar wall of smokers and their numbers correlated with the extent of emphysema. However, the phenotype of these cells was not defined. The aim of this study was to describe the different T-cell phenotypes and investigate the possible presence of apoptosis in the lung parenchyma of smokers. Samples from lungs were obtained at surgery from 15 patients who smoked and six who had never smoked. Samples were frozen and prepared for histological and immunocytochemical examination. Slides were stained for CD3+, CD4+, CD8+, gammadelta T-cells, CD56 natural killers ((NK) cells), and elastase (neutrophils). Anti-CD95 monoclonal antibodies and in situ end-labelling techniques were used to detect Fas expression and apoptosis. Positive staining cells were expressed as cells-mm alveolar wall-, percentage of total cells, and Fas/APO and apoptosis index. Emphysema was identified macroscopically, microscopically and reported as present or absent. All subjects had pulmonary function tests before surgery. Neutrophils were the predominant cell in the lung parenchyma of nonsmokers and smokers without emphysema. In smokers with emphysema, the CD3+ and CD8+ were the predominant cells (p<0.05) in the alveolar wall. gammadelta cells were increased in all smokers and no increased numbers of NK cells was found. The T-cell numbers x mm alveolar wall(-1) showed a bilinear relationship with the amount smoked increasing at an inflection point of 30 packs yr(-1) (R2= 0.345; p < 0.01). Apoptosis in smokers showed a bilinear relationship with the amount smoked increasing sharply in smokers with emphysema (R2=0.3613; p < 0.009). It is concluded that the pathogenesis of emphysema might be mediated by T-lymphocytes, mainly CD8+ cytolytic T-cells, and that apoptosis might be one of the mechanisms of lung destruction leading to the development of emphysema. If this is the case, it could be speculated that T-cell inflammation is a response to antigenic stimuli originating in the lung and induced by cigarette smoking.

https://erj.ersjournals.com/content/erj/17/5/946.full.pdf

Manuel G. Cosio

Papers

The relations between structural changes in small airways and pulmonary-function tests.

Immunologic Aspects of Chronic Obstructive Pulmonary Disease

Alveolar inflammation and its relation to emphysema in smokers.

Animal models of chronic obstructive pulmonary disease

Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema