COPD anti-inflammatories

O Inflammation plays a key role in the pathophysiology of COPD, but it differs from that seen in asthma therefore, the use of and response to anti-inflammatory medications are different. 

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. 

This xanthine derivative is an only a modest bron-chodilator in COPD, and because of its narrow therapeutic range, frequently seen adverse effect and drug interactions, it is becoming less frequently used, some patients experience side effects even within the therapeutic range. The non-bronchodilator effects of theophylline such as systemic and pulmonary vascular dilatation, central nervous system stimulation, improvement of the strength and effectiveness of respiratory muscles and possibly anti-inflammatory effects are of disputed clinical significance at usual therapeutic levels. 

There is no role for other anti-inflammatory drugs such as sodium cromoglycate, nedocromil, keto-tifen, leukotriene antagonists or antihistamines in COPD. 

Evidence also suggests that leukotriene inhibitors can be combined with other drugs (glucocorticoids, beta agonists) to provide optimal management in specific patients with asthma and COPD.11,60 In particular, it appears that these drugs may enhance the anti-inflammatory effects of glucocorticoids, and may therefore provide therapeutic effects at a relatively... 

Aspirin is a non-steroidal anti-inflammatory drug (NSAID) which is used to treat pain and, in low dosage, for the prophylaxis of coronary heart disease. It must be used with caution in asthmatic patients because of possible bronchoconstriction, and in large doses aspirin can adversely affect respiration by depressing the respiratory centre, leading to CO2 retention. Therefore it is not useful in COPD. 

Practicing physicians face daily the economic hardships faced by patients who must pay for medications from limited incomes. Patients with chronic diseases in particular are especially vulnerable. Patients with asthma and COPD often carry several metered-dose inhalers and also take oral anti-inflammatory medications as well. In addition, many have other problems, such as diabetes or... 

It is helpful to differentiate inflammation occnrring in COPD from that present in asthma because the response to anti-inflammatory therapy differs. The inflammatory cells that predominate differ between the two conditions, with neutrophils playing a major role in COPD and eosinophils and mast cells in asthma. Mediators of inflammation also differ with LTB4, IL-8, and TNF-a predominating in COPD, compared with LTD4, IL-4, and IL-5 among the nnmer-ous mediators modulating inflammation in asthma. Characteristics of inflammation for the two diseases are summarized in Table 27-2. 

The anti-inflammatory mechanisms whereby corticosteroids exert their beneficial effect in COPD include (1) reduction in capillary permeability to decrease mucus, (2) inhibition of release of proteolytic enzymes from leukocytes, and (3) inhibition of prostaglandins. Unfortunately, the clinical benefits of systemic corticosteroid therapy in the chronic management of COPD are often not evident, and the risk of toxicity is extensive and far-reaching. Currently, the appropriate situations to consider corticosteroids in COPD include (1) short-term systemic use for acute exacerbations and (2) inhalation therapy for chronic stable COPD. 

ACE angiotensin-converting enzyme CNS central nervous system COPD chronic obstructive pulmonary disease DPIs dry-powder inhalers EDTA ethylenediamine tetraacetic acid EDA Eood and Drug Administration EEVi forced expiratory volume in 1 second HIV human immunodeficiency virus IPS idiopathic pneumonia syndrome NSAIDs nonsteroidal anti-inflammatory drugs... 

More importantly, the effects of theophylline are not limited to bronchodila-tion, bnt also include immunomodulatory, anti-inflammatory, and bronchoprotec-tive activity that substantially contribute to its usefulness as a prophylactic drug in asthma and other respiratory diseases. Additional effects include an increase in mucociliary clearance, a decrease of microvascular leakage into the airways, and an improvement of respiratory mnscle fatigue, especially that of the diaphragm. Theophylline fnrthermore acts centrally, blocking the decrease in ventilation that occurs with sustained hypoxia. While some of these effects are the rationale for its use in asthma, others form the basis for its effectiveness in chronic obstructive pulmonary disease (COPD) or in the treatment of apnea in premature newborns. 

Steroidal and nonsteroidal anti-inflammatory drugs such as corticosteroids, sodium cromoglycate, and nedocromil sodium, respectively, are used to treat asthma and COPD. In the sections below, we present potential targets for these... 

Pulmonary administration of active substances is common in the treatment of lung diseases such as asthma and COPD and infectious lung diseases. For these indications different levels of the airways are targeted with different medicines. For the beta-agonists such as formoterol the higher airways (generation 4 to 11, see Fig. 16.2) are the primary target, whereas for the anti-inflammatory... 

In a randomized, double-blind, placebo-controlled study of 51 patients with COPD, 1,8-cineole (3 X 200 mg/day) was given for 8 weeks. For the objective lung functions of airway resistance and specific airway resistance, there was a clinically significant reduction of 21% and 26%, respectively. The improvement was attributed to a positive influence on disturbed breathing patterns, mucociliary clearance, and anti-inflammatory effects (Habich and Repges, 1994). 

Worth et al. [123] investigated whether 1,8-cineole can, due to its mucolytic, bronchodilating, and anti-inflammatory activity, reduce the exacerbation rate and improve the health status when applied as a concomitant therapy in COPD patients. The substance possesses positive effects on the beat frequency of the cilia in the mucus. 1,8-Cineole reduced the exacerbation rate and improved lung function by improving the airflow obstmction and reducing severity of dyspnoea. Due to its positive effect on the health status, lack of side effects, and relative low cost, concomitant therapy can be recommended with therapy of the rather costly COPD, in the opinion of the authors. 

Corticosteroids are effective through their anti-inflammatory properties and the more acute the exacerbation, the more they are of benefit. There is general agreement that short course of corticosteroids increases the rate of recovery from acute exacerbations (8-10). They may be started intravenously, if necessary, and then continued orally as soon as the patient is able to swallow safely. A short course of corticosteroids may also be of benefit in chronically obstructed COPD patients. The optimum duration is not known, although 10-14 days of therapy is commonly prescribed. Dosage is usually tapered over this time, the exact schedule varying with the clinician s experience and practice location. 

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