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Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.

COPD Entities
Simple chronic bronchitis Asthmatic bronchitis/Chronic asthmatic bronchitis Chronic obstructive bronchitis small airways disease Pulmonary emphysema

Simple chronic bronchitis

Exposure to irritants without hyperreactive airways. Characterized by mucoid sputum production, decreased ciliary activity, and impaired resistance to infection.

Chronic asthmatic bronchitis or COPD with asthma

Exposure to irritants in individuals with reactive or twitchy airways. Bronchospasm is frequently accompanied by excessive mucous production and edema of bronchial walls. Episodic worsening of airway obstruction often called asthma, but there is persisting obstruction, and often productive cough, with the episodic bronchospasm.

Obstructive Chronic Bronchitis

Irreversible narrowing of airways, usually bronchioles or bronchi smaller than 2 mm., associated with increased resistance to airflow, hypoxemia, hypercapnea.

Pulmonary Emphysema
Permanent, abnormal distension of the air spaces distal to the terminal bronchiole with destruction of alveolar septae, with or without fibrosis. Reduces lung elastic recoil causing airway collapse and irreversible airway obstruction.


Pathology Chronic Bronchitis

Hypertrophy of mucous glands in submucosa of airways. Reid index (submucosa to bronchial wall). Small airways obstruction esp. with goblet cell hyperplasia, mucosal and submucosal inflammatory cells, edema, peribronchial fibrosis, mucous plugs, and increased smooth muscles. Alveolar epithelium is the target and the initiator of inflammation in CB, with neutrophils, macrophages, and CD8 lymphocytes causing epithelial cell release of IL-8 and other chemotactic and proinflammatory cytokines, and colony stimulating factors released in response to toxic, infectious, or inflammatory stimuli.

More CB Pathology
Injured epithelium may release reduced amounts of regulatory products such as ACE or neutral peptidase. Sputum production is stimulated by increased exocytosis from secretory cells, lipid mediators, and inflammatory cell products. Mucin gene expression is amplified by TNFalpha, and secretory cell hyperplasia by the neutrophil enzymes elastase and cathepsin G.

Pathology - Emphysema
Classified by pattern of involvement of the acini distal to terminal bronchiole. Centriacinar or Centrilobular limited to respiratory bronchioles primarily with little change in acinus. Normal aging is associated with this. Panacinar or Panlobular involves both central and peripheral portions of the acinus.

Causative factors
Background - Lung function over time Cigarette smoking Airway responsiveness and Allergy Air Pollution Occupational exposure to environmental dust and organic antigens Infection Antioxidant deficiency Molecular/Genetic risk factors

Cigarette Smoking
Impairs ciliary movement Inhibits alveolar macrophages Leads to hypertrophy and hyperplasia of mucus-secreting glands Probably inhibits antiprotease Acutely increases vagally mediated smooth-muscle constriction

Airway Responsiveness-Dutch Hypothesis

Increased airways responsiveness and allergy are clinical phenotypes that predict increased susceptibility to cigarette smoke. Methacholine and histamine responsiveness precedes and predicts accelerated decline in lung function, thus a risk factor for COPD.* Increased airways responsiveness noted among 1st degree relatives of patients with early onset COPD.@
*Silva, GE et al. Asthma as a risk factor for COPD in a longitudinal study.
Chest 2004; 126:59. @Celedon JC et al. Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD. Eur Respir J 1999; 14:1009.

Air Pollution
Increased incidence and higher mortality rates of COPD in industrialized urban areas. Exacerbations of CB clearly related to periods of heavy sulfur dioxide pollution and particulates. Nitrogen dioxide NOT implicated in human airways obstruction.

Occupational Exposures
Environmental dusts gold and coal miners Organic antigens COPD is most common respiratory syndrome in agricultural workers, and there is a 10% prevalence of COPD among farm workers Accelerated decline in lung function among plastics workers exposed to toluene diisocyanate and in carding room workers in cotton mills

Severe viral pneumonia in childhood may lead to small airways obstruction . Mortality, morbidity, and frequency of ARI are higher in patients with chronic bronchitis.

Antioxidant Deficiency
Oxidizing radicals derive from cigarette smoke or may be released by phagocytes in the lung. Deficiencies of antioxidants vitamins may impair host defenses against oxidative radicals and permit tissue destruction leading to COPD.

Molecular/Genetic Risk Factors

Protease/antiprotease TNF-a gene polymorphisms

Systemic Inflammation in Pathogenesis of COPD

COPD is a systemic disease. Cytokines and other inflammatory markers are a response to cigarette smoke. They circulate and may impact other diseases and symptoms, e.g. cardiac disease and cachexia. Reduced lung function associated with increased levels of systemic inflammatory markers, including CRP, fibrinogen, WBCs, and TNFalpha.*

Noxious particles and gases

Host factors

Lung inflammation


Oxidative stress


Repair mechanisms

COPD pathology

Lung Volumes and Capacities in COPD

RV increased FRC is the volume at which inward recoil of lung = outward recoil of chest wallloss of elastic recoil will increase FRC TLC increased due to loss of elastic recoil VC may be normal to decreased