The most common cause of COPD in the developed world is exposure to tobacco smoke. Data have shown that, over time, 50% of chronic smokers develop COPD. The development of COPD is a complex process that is not completely understood. Inflammation, oxidant-antioxidant imbalance, protease-antiprotease imbalance, and several additional processes including recurrent infection, immunosenescence, autoimmunity, altered tissue healing, and other mechanisms are all implicated in the pathogenesis of COPD. While tobacco smoking is a well-recognised cause of COPD, the risk for developing COPD may also depend on gender, genetic and socioeconomic factors, as well as exposures to dusts, chemicals, or pollutants, and early childhood severe respiratory infection. Acute exacerbations of COPD occur intermittently throughout the course of the disease over the patient’s lifetime. Exacerbations vary in severity and are thought to be triggered primarily by infections (both viral and bacterial) and airborne pollutants. In approximately one third of COPD exacerbations, no clear cause can be identified. A careful search for other causes of respiratory decompensation (e.g., congestive heart failure or pulmonary embolus) should be considered in such cases.
During an episode, decreases in the FEV1, forced vital capacity, and peak expiratory flow may be identified and are due at least in part to airway inflammation. However, exacerbations are diagnosed by the identification of typical signs and symptoms rather than by spirometry.
Bacterial pathogens are thought to be responsible for triggering 50% to 70% of exacerbations. The most common bacterial pathogens include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Atypical bacterial pathogens such as Mycoplasma and Chlamydia pneumoniae are also thought to trigger exacerbations, as are respiratory viruses such as rhinovirus, influenza, respiratory syncytial virus, parainfluenza virus, and human metapneumovirus. The severity of baseline lung function impairment influences the profile of pathogens most likely to be present.
Smoking, or other significant exposure to smoke, is noted in most people with COPD. Components of smoke lead to impaired integrity of the tight junctions between lung epithelial cells, stimulate inflammation, and have been shown to decrease respiratory tract mucociliary clearance, increasing the likelihood of microbial pathogens penetrating the normally sterile lower respiratory tract. The presence of microbial flora leads to antigen presentation and stimulation of the innate and then the adaptive immune response. Over time, chronic irritation by smoke and the inflammatory response leads to emphysema, hypertrophy of airway mucous glands, small airway fibrosis, and a decrease in the elastic recoil of the lung. The decrease in elastic recoil (due to emphysema) and/or obstruction of the small airways due to inflammation, oedema, and hypersecretion of mucus leads to decreased FEV1 and FEV1/FVC. Hyperinflation that results from airflow limitation is a main cause of dyspnoea. Unlike asthma, airflow limitation in COPD is not fully reversible with medical therapy. Furthermore, while the pathogenesis of both asthma and COPD is rooted in inflammation, the specific inflammatory process differs between these disorders. However, a substantial number of patients with COPD do have a component of airflow obstruction that is reversible with bronchodilator therapy. Indeed, inhaled bronchodilators (beta-2-agonists and anticholinergics) are one of the primary forms of therapy for all patients with COPD, because, in addition to bronchodilation, they have also been shown to decrease dynamic hyperinflation.
Acute exacerbations of COPD may be defined as an acute worsening of respiratory symptoms (e.g., dyspnoea, cough, sputum production) that results in additional therapy. This worsening appears to result from increases in airway inflammatory cells and proteins that are triggered by an infection, airborne pollutants, and/or other factors. The acute on chronic inflammatory response and/or concurrent bronchoconstriction leads to worsening in expiratory airflow limitation. Worsening of expiratory airflow limitation leads to increased resistive work of breathing, increased ventilation/perfusion mismatch, and gas exchange disturbances. It also results in increased hyperinflation, which then further worsens lung mechanics and can lead to impaired function and fatigue of the respiratory muscles. Due to the difficulty in obtaining specimens from people with exacerbations of COPD, further complicated by heterogeneous triggers, knowledge of the inflammatory response during an episode is incomplete.
Acute exacerbations have significant impact on activity level, functional status, and quality of life experienced by people with COPD. Moreover, recovery from exacerbations may be prolonged, and some patients never regain their prior level of lung function and/or functional status. There is evidence to suggest that exacerbations not only tend to be more frequent and more severe as COPD progresses, but may themselves accelerate the decline in lung function in COPD. Indeed, some patients may also be at increased risk for COPD exacerbations (i.e., have a phenotype of increased susceptibility) independent of disease severity. Currently recommended assessment of COPD patients includes determination of the severity of the airflow obstruction, assessment of symptoms, as well as assessment of the risk of exacerbations. People with severe or very severe airflow obstruction, those with a history of two or more exacerbations in the preceding year, or those with history of hospitalisation due to exacerbation in the previous year are considered at high risk of subsequent exacerbations. Several additional factors are also associated with exacerbations and/or hospitalisations for COPD. COPD exacerbations, particularly those requiring hospitalisation, are associated with increased mortality, as well as significant healthcare costs.
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