COPD, treatment

Design an appropriate COPD treatment regimen based on patient-specific data. 

N-acetylcysteine has antioxidant and mucolytic activity, which makes it a promising agent for COPD treatment, but clinical trials have produced conflicting results. One of the largest trials found N-acetylcysteine to be ineffective at reducing the decline in lung function and preventing exacerbations.29 Routine use cannot be recommended at this time. 

Normally corticosteroids are used for COPD treatment. The corticosteroids bind to glucocorticoid receptors and enter the nucleus of the cells, where it recruits HDAC-2. HDAC-2 deacetylates the chromatin and represses gene expression of inflammatory genes. Thus, low levels of HDAC-2 is detrimental to the treatment of COPD. Antioxidants (for removal of superoxides) or iNOS inhibitor or theophylline/curcumin for PI3K inhibition are some of the options to restore the required HDAC-2 level. 

D Urzo AD, De Salvo MC, Ramirez-Rivera A, et al. In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium. Chest 2001 119 1347-1356. 

The powder formulation contains the active substance in the correct aerodynamic size distribution, which for most currently marketed formulations is either obtained by micronisation or by spray drying. Both techniques produce polydisperse particles and their mass median aerodynamic diameter is preferably in the range between 1 and 5 pm, depending on the precise target area. Particles within this size range are extremely cohesive, whereas the powder masses to be measured are miniscule and mostly less than 5-500 micrograms for the active substances used in asthma and COPD treatment. Such small quantities of micronised powders cannot be delivered in a reproducible way without... 

Several studies have demonstrated a direct effect of 1,8 cineole on the ciliated epithelium itself Kaspar et al. (1994) conducted a randomized, double blind three-way crossover 4 day study of the effects of 1,8-cineole (3 x 200 mg/day) or Ambroxol (3 x 30 mg/day) on mucociliary clearance in 30 patients with COPD. Treatment with the oxide resulted in a statistically signi cant increase in the ciliary beat frequency of nasal cilia, a phenomenon that did not occur with the use of Ambroxol (an increase of 8.2% and 1.1%, respectively). A decrease of saccharine time was clinically relevant and signi cant after 1,8 cineole therapy (241 s) but not after Ambroxol (48 s). Lung function parameters were signi cantly improved equally by both drugs. 

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. 

Approximately 2% of all COPD patients suffer from homozygous al-AT deficiency. Intravenous infusion of replacement protein twice weekly in patients with established al-AT deficiency is approved in the US but not in Europe. The effectiveness of this extremely expensive treatment is not yet known. 

List the treatment goals for a patient with COPD. 

Bronchodilators are the mainstay of treatment for symptomatic COPD. They reduce symptoms and improve exercise tolerance and quality of life. 

In symptomatic patients with severe COPD and frequent exacerbations, regular treatment with inhaled corticosteroids decreases the number of exacerbations per year and improves health status however, corticosteroids do not slow the longterm decline in pulmonary function. 

Upon discontinuation of inhaled corticosteroids some patients may experience deterioration in lung function and an increase in dyspnea and mild exacerbations it is reasonable to reinstitute the medication in these patients.25 Completion of ongoing clinical trials assessing mortality should help to clarify the role of corticosteroid treatment of COPD. 

The role of inhaled corticosteroids in COPD is controversial. Major clinical trials have failed to demonstrate any benefit from chronic treatment in modifying long-term decline in lung function. However, other important benefits have been observed in some patients, including a decrease in exacerbation frequency and improvements in overall health status. 

Results from clinical trials suggest that patients with acute COPD exacerbations should receive a short course of IV or oral corticosteroids. Although the optimal dose and duration of treatment are unknown, it appears that a regimen of prednisone 40 mg orally daily (or equivalent) for 10 to 14 days can be effective for most patients. 

Tetrafluoroethane has been tested in metered-dose inhalers for the treatment of respiratory diseases. Test subjects included adult and pediatric asthmatic patients as well as individuals with severe COPD. No adverse effects were reported (Smith et al. 1994 Taggart et al. 1994 Ventresca 1995 Woodcock 1995). Structurally related compounds, including 1,1,1-trichloroethane and trichlorofluoromethane, were also tested for cardiac sensitization in dogs with experimentally induced myocardial infarctions. In these experiments cardiac sensitization occurred at the same concentration as in healthy dogs (Trochimowicz et al. 1976). Thus, no sensitive or particularly susceptible populations can be identified for HFC-134a. 

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