Corticosteroids COPD

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. 

Corticosteroids have been evaluated in several types of cerebral injury, including cerebral infarction. Corticosteroids reduce vasogenic edema, such as that associated with neoplasms, but not cytotoxic edema, the type associated with ischemic stroke. A large meta-analysis found no benefit to the use of corticosteroids in ischemic stroke (or intracerebral hemorrhage), and their use is not recommended, except to treat concomitant conditions that mandate it (e.g., COPD flare). 

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 antiinflammatory mechanisms whereby corticosteroids exert their beneficial effect in COPD include reduction in capillary permeability to decrease mucus, inhibition of release of proteolytic enzymes from leukocytes, and inhibition of prostaglandins. 

The clinical benefits of systemic corticosteroid therapy in the chronic management of COPD are often not evident, and there is a high risk of toxicity. Consequently, chronic, systemic corticosteroids should be avoided if possible. 

Appropriate situations to consider corticosteroids in COPD include (1) shortterm systemic use for acute exacerbations and (2) inhalation therapy for chronic stable 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. 

The first commercially available DPI system appeared on the market in 1949, developed and marketed by Abbott under the name Aerohaler. Like all early pulmonary drug-delivery devices, it delivered small-molecule compoimds (bronchodilators or inhaled corticosteroids) to the airways (not necessarily the deep limg) for the treatment of asthma or chronic obstructive pulmonary disease. Table 6 lists some of the early DPI systems used for asthma and COPD the energy somces in these devices were mechanical and patient inspiration. 

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. 

The majority of the marketed products are used for asthma and COPD. Typical agents that are used for these indications are fl2-agonists such as salbutamol (albuterol), Terbutalin or formoterol, corticosteroids such as budesonide, FUxotide or beclomethasone and mast-cell stabilizers such as sodium cromoglycate or nedocromil. 

Reversibility tests to bronchodilators are recommended at all stages of obstructive airways diseases. They are helpful in differentiating patients with COPD with those of asthma. Many patients with COPD and even those with severe airflow obstruction can demonstrate (partial) reversibility. Patients with a positive bronchodilator response i.e. reversibility are more likely to respond to a trial of oral or inhaled corticosteroids. 

Although a variety of interpretations have been issued, reversibility to bronchodilators is considered to be present when the FEV i increases by 200 ml and 12% of the pre-bronchodilator value. Although in the latest GINA guidelines this issue is no longer addressed, the same criteria have been used for evaluation of the response to corticosteroids. A corticosteroid trial compared spirometric tests before and at the end of oral prednisolone (e.g. 30 mg/d) taken for two weeks or a course of inhaled steroid (e.g. beclomethasone 500 pg twice daily or equivalent) taken for six weeks. A positive response to corticosteroids justified prescription of regular inhaled steroid. Subjective improvement as a single efficacy parameter is not considered to be a satisfactory end point. Objective improvement is seen in 10-20% of patients with COPD. 

Presently, inhaled steroids (up to the equivalent of BDP 1000 pg/d, budesonide 800 pg/d, fluticasone 500 pg/d) should be given to patients who show an objective response to either oral or inhaled steroids (s. corticosteroid reversibility testing). For those patients who experience no symptomatic relief, the currently available evidence does not support the use of ICS for alteration of the natural history of the disease. Nevertheless, corticosteroids are effective in treating acute exacerbations in COPD and taking patients of off their ICS regimen may lead to deterioration. Oral corticosteroids (e.g. 40 mg prednisolone for ten days) are recommended for exacerbations, if... 

Table 5. Randomized placebo controlled trials on inhaled corticosteroids in COPD ...

Renkema TE, Schouten JP, Koeter GH, Postma DS. Effects of long-term treatment with corticosteroids in COPD. Chest 1996 109 1156-62. 

Larj MJ, Bleecker ER. Therapeutic responses in asthma and COPD. Corticosteroids. Chest. 2004 126 (suppl 2) 138S—149S. 

Inhaled corticosteroids do have a role in COPD. They should be prescribed for patients with an FEV, <50% predicted, with two or more exacerbations in 12 months that require antibiotics or oral corticosteroids. These patients are still breathless despite monotherapy with a long-acting beta2-agonist. Maintenance use of oral corticosteroids is not recommended, but some patients with advanced COPD may require them. Oral corticosteroids should be used in all patients admitted to hospital with an exacerbation of COPD. There is insufficient evidence to establish the minimum dose of inhaled corticosteroids to obtain benefit (NICE, 2004). 

Inhaled corticosteroids should be prescribed for patients with an FEVi of 50% predicted or less, who have two or more exacerbations needing treatment with antibiotics or oral corticosteroids a year. Warn patients about the possible risk of osteoporosis and other side effects of high-dose inhaled corticosteroids. None of the inhaled corticosteroids currently available is licensed alone for use in COPD. 

Q12 It is recommended that a trial of a short-acting beta-2-agonist (/S)-agonist) inhaler be made for a few weeks as some COPD patients do benefit from bronchodilation. Although his doctor has prescribed a bronchodilator previously, it may be useful for Bill to try this again. There should also be a trial of a corticosteroid inhaler, as this diminishes the inflammatory component of COPD. If there is no appreciable benefit after four weeks, the steroid should be discontinued. 

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