Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Avoidance of irritants such as tobacco smoke slows the progression of severe chronic obstructive pulmonary disease (COPD). Drugs have only a modest, purely symptomatic effect; a bronchodilator is combined with an inhaled corticosteroid when exacerbations are frequent. Oxygen therapy prolongs survival in very severe disease. Roflumilast, a nonsteroidal antiinflammatory drug that inhibits type 4 phosphodiesterase, has been authorised in the European Union for the treatment of severe COPD. Roflumilast has not been compared with an inhaled corticosteroid. Its evaluation is primarily based on 8 double-blind, randomised, placebo-controlled trials lasting from 24 to 52 weeks, in a total of approximately 9000 patients. In four trials, the average frequency of exacerbations fell by about 0.2 episodes per patient per year, but the statistical significance of the difference was variable. Even in the most favourable trials, roflumilast did not reduce the frequency of hospitalisation for exacerbations. In six trials (including the four previous trials), roflumilast led to a statistically significant increase in forced expiratory volume in one second, by about 50 ml on average, but the clinical relevance of this improvement is questionable. An inherently unreliable indirect comparison suggests that roflumilast is less effective than an inhaled corticosteroid. Treatment was stopped because of adverse reactions in 14% of patients taking roflumilast, versus 8.5% in the placebo groups. The most common adverse effects were gastrointestinal disorders (diarrhoea, nausea), weight loss, and neuropsychiatric disorders (insomnia, anxiety, depression). Concerns have been raised about the carcinogenic potential of roflumilast. Roflumilast is metabolised by cytochrome P450 isoenzymes CYP 3A4 and CYP 1A2, creating a high potential for pharmacokinetic interactions. In practice, it is better not to use roflumilast. For patients with severe COPD and repeated exacerbations, the standard treatment remains an inhaled bronchodilator combined with an inhaled corticosteroid, or oxygen therapy in some cases.
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PMID:Roflumilast: doubtful efficacy but clear harms in COPD. 2336 74

COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation. COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity. The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia. COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode. Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations. Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD. Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis. Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity. Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease. Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations.
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PMID:Roflumilast: a review of its use in the treatment of COPD. 2679 88