Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149514 (bronchitis)
 6,902 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with chronic obstructive pulmonary disease (COPD) and associated bronchitis are at higher risk of exacerbations, which are a major cause of morbidity and impaired quality of life. Moreover, exacerbations are associated with more rapid disease progression and higher mortality. The typical symptoms of chronic bronchitis (chronic cough and sputum production) are correlated with inflammatory markers in COPD. Roflumilast is an anti-inflammatory drug belonging to the novel therapeutic class of phosphodiesterase-4 inhibitors and is the first drug to be developed for the treatment of a specific COPD phenotype (COPD associated with chronic bronchitis). The results of clinical trials indicate that, in patients with COPD associated with chronic bronchitis and a history of exacerbations, roflumilast improves pulmonary function and reduces the symptoms and frequency of exacerbations requiring medical intervention. This effect is maintained when regular treatment with a long-acting bronchodilator or an inhaled corticosteroid is added.
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PMID:[Clinical profile of roflumilast]. 2131 53

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, that is defined by the degree of obstruction rendered by the forced expiratory volume in the first second (FEVj). This is a good parameter to define the severity of the disease but does not account for its heterogeneity and does not provide a good comprehension of its different clinical behaviors and responses to treatment. Therefore, the classification of these patients in different clinical phenotypes has been attempted, trying to search for common clinical behaviors and responses to treatment. These phenoptypes must be validated in longitudinal studies. Some of the phenotypes detected are COPD with chronic respiratory failure and responsive to home oxygen therapy, COPD with upper lobe emphysema and responsive to volume reduction surgery, COPD with frequent exacerbation behavior, COPD resembling bronchitis and responsive to Roflumilast and possibly, COPD with systemic involvement. Historically, the phenotypes pink puffer, blue bloater, chronic bronchitis were defined. In the next years, we will know if the definitions of these phenotypes will aid in the management of patients with COPD.
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PMID:[Clinical phenotypes in chronic obstructive pulmonary disease]. 2328 8

Roflumilast is a selective phosphodiesterase 4 inhibitor (PDE4i) for the treatment of severe chronic obstructive pulmonary disease (COPD). In 2 large phase 3 trials in a broader population of COPD patients (BY217/M2-111, ClinicalTrials.gov: NCT00076089 and BY217/M2-112, ClinicalTrials.gov: NCT00430729), treatment with roflumilast reduced the rate of exacerbations; however, the reduction did not reach statistical significance. Two linked dose-response models for the primary (annualized COPD exacerbation counts) and secondary (change from baseline in forced expiratory volume in 1 second [FEV1 ]) end points were therefore developed to characterize and quantify effect sizes and the patient characteristics influencing them. The models showed that disease severity and bronchitis, particularly the severity of bronchitis expressed in cough-and-sputum scores, were good predictors of exacerbation rates and differential benefit of roflumilast in exacerbation reduction. The models were used to support the rational design of 2 phase 3 randomized, placebo-controlled clinical trials (BY217/M2-124, ClinicalTrials.gov: NCT00297102 and BY217/M2-125, ClinicalTrials.gov: NCT00297115) by identifying the most appropriate patient population using clinical trial simulations. Model predictions for both end points were found to be highly accurate - as confirmed by the results from these trials, which led to the approval of roflumilast as the first oral PDE4i for the treatment of COPD in patients associated with chronic bronchitis and a history of exacerbations.
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PMID:Modeling and Simulation of Pivotal Clinical Trials Using Linked Models for Multiple Endpoints in Chronic Obstructive Pulmonary Disease With Roflumilast. 2841 62