In COPD

One intensively investigated feature of the inflammatory process in COPD is the release of proteases from neutrophils and monocytic cells that destroy elastin and other components of the interstitial matrix (Table 1). The best studied protease is neutrophil elastase. Independent of its elastolytic activity, neutrophil elastase is a potent secretagogue. More recently matrix metalloproteases (MMP) have received increasing attention, in particular MMP 12 (macrophages elastase). To which extent and how exactly these proteases become activated is not clear at present. 

Usually, it takes years of toxin exposure to cause the pathological alterations seen in COPD. In most cases, the disease is already well-progressed when COPD is diagnosed. Reversal of established chronic inflammatory disease is always extremely difficult to achieve and at present healing of COPD is impossible. Smoking cessation is the single most effective and cost-effective... 

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

The use of antibiotics is not recommended, except for the treatment of infectious exacerbations of COPD and other bacterial infections. Influenza vaccines decrease illness and death in COPD patients. Pneumococcal vaccination is also recommended. 

Inflammation is present in the lungs of all smokers. It is unclear why only 15% to 20% of smokers develop COPD, but susceptible individuals appear to have an exaggerated inflammatory response.5 O The inflammation of COPD differs from that seen in asthma, so the use of anti-inflammatory medications and the response to those medications are different. The inflammation of asthma is mainly mediated through eosinophils and mast cells. In COPD the primary inflammatory cells include neutrophils, macrophages, and CD8+ T lymphocytes. 

Proteinases and antiproteinases are part of the normal protective and repair mechanisms in the lungs. The imbalance of proteinase-antiproteinase activity in COPD is a result of either increased production or activity of destructive proteinases or inactivation or reduced production of protective antiproteinases. AAT (an antiproteinase) inhibits trypsin, elastase, and several other proteolytic enzymes. Deficiency of AAT results in unopposed proteinase activity, which promotes destruction of alveolar walls and lung parenchyma, leading to emphysema. 

In advanced COPD, airflow obstruction, damaged bronchioles and alveoli, and pulmonary vascular abnormalities lead to impaired gas exchange. This results in hypoxemia and eventually hypercapnia. Hypoxemia is initially present only during exercise but occurs at rest as the disease progresses. Inequality in the ventilation/perfusion ratio (VAQ) is the major mechanism behind hypoxemia in COPD. 

Serious illness and death in COPD patients can be reduced by about 50% with annual influenza vaccination. The optimal time for vaccination is usually from early October through mid-November. All patients with COPD should also receive a one-time vaccination with the pneumococcal polysaccharide vaccine, even though sufficient data supporting its use in COPD patients are lacking.1,2 Patients over 65 years of age should be revacdnated if it has been more than 5 years since initial vaccination and they were less than 65 years of age at the time. 

Leukotriene modifiers (e.g., zafirlukast and montelukast) have not been adequately evaluated in COPD patients and are not recommended for routine use. Small, short-term studies showed improvement in pulmonary function, dyspnea, and quality of life when leukotriene modifiers were added on to inhaled bronchodilator therapy.27,28 Additional long-term studies are needed to clarify their role. 

Nedocromil, a mast cell stabilizer, has not been adequately tested in COPD patients and is not included in the GOLD recommendations. 

The role of bacterial infections in COPD exacerbations is controversial, and there are limited data on the efficacy of antibiotics in treating COPD exacerbations. Recent studies suggest that bacteria cause 40% to 50% of acute exacerbations.31 Antibiotics should be used in patients with COPD exacerbations who have either of the following characteristics (1) at least two of three cardinal symptoms increased dyspnea, sputum volume, or sputum purulence or (2) a severe exacerbation requiring mechanical ventilation.2... 

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