Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pirfenidone, an antifibrotic drug with anti-inflammatory and antioxidant effects, delays fibrosis in idiopathic pulmonary fibrosis (IPF). Patients with IPF have a greater cough reflex sensitivity to inhaled capsaicin than healthy people, and cough is an independent predictor of IPF disease progression; however, the effects of pirfenidone on cough reflex sensitivity are unknown. After challenge with an aerosolized antigen in actively sensitized guinea pigs, pirfenidone was administered intraperitoneally, and the cough reflex sensitivity was measured at 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed, and the tracheal tissue was collected. Pirfenidone suppressed the capsaicin-induced increase in cough reflex sensitivity in a dose-dependent manner. Additionally, increased levels of prostaglandin E2, substance P, and leukotriene B4, but not histamine, in the BAL fluid were dose dependently suppressed by pirfenidone. The decrease in neutral endopeptidase activity in the tracheal tissue was also alleviated by pirfenidone treatment. The total number of cells and components in the BAL fluid was not influenced. These results suggest that pirfenidone ameliorates isolated cough based on increased cough reflex sensitivity associated with allergic airway diseases, and potentially relieve chronic cough in IPF patients who often have increased cough reflex sensitivity. Prospective studies on cough-relieving effects of pirfenidone in patients with IPF are therefore warranted.
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PMID:Effects of pirfenidone on increased cough reflex sensitivity in guinea pigs. 2381 7

Idiopathic pulmonary fibrosis is a rare disorder due to progressive, widespread fibrotic damage of the lung parenchyma. It usually occurs after the age of 50, and its cause is unknown. Symptoms include progressive shortness of breath and nonproductive cough. The course of the disease is marked by exacerbations. Death from respiratory failure occurs about 2 to 5 years after diagnosis. There are currently no drugs that can control or slow the fibrotic process. Pirfenidone, an immunosuppressant, has been authorised in the European Union for the treatment of mild to moderate idiopathic pulmonary fibrosis. Clinical evaluation is based on two double-blind randomised placebo-controlled trials lasting 72 weeks in a total of 779 patients. Mortality, the frequency of exacerbations and the number of lung transplants did not differ significantly between the pirfenidone and placebo groups in either trial. Decline in forced vital capacity was smaller with pirfenidone than with placebo, but the difference was statistically significant in only one of the trials. The small difference in this surrogate endpoint is of questionable clinical relevance. 14.8% of the patients taking pirfenidone 2403 mg/day (maintenance dose according to the marketing authorisation) discontinued treatment because of adverse events, versus 8.6% of patients in the placebo groups. Serious adverse effects included 3 cases of bladder cancer in the pirfenidone groups versus 1 case in the placebo groups. Photosensitivity and skin rash, cardiac arrhythmias and coronary artery disease were more frequent with pirfenidone 2403 mg/day than with placebo. Abnormal transaminase elevation occurred in 4.1% of patients on pirfenidone 2403 mg/day versus 0.6% of patients on placebo. A few cases of acute renal failure were also observed. In practice, there is no evidence that pirfenidone improves quality of life in patients with mild to moderate idiopathic pulmonary fibrosis, or that it slows the progression of pulmonary fibrosis. The adverse effect profile is already burdensome. Pending real therapeutic advance, it is best to avoid pirfenidone altogether and to focus on symptomatic treatment.
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PMID:Pirfenidone. First, do no harm. 2381 68

Idiopathic pulmonary fibrosis (IPF) is a severe and progressive fibrosing interstitial lung disease, which ultimately results in respiratory failure and death. The median age at diagnosis is 66 years, and the incidence increases with age, making this a disease that predominantly affects the elderly population. IPF can often be difficult to diagnose, as its symptoms--cough, dyspnoea and fatigue--are non-specific and can often be attributed to co-morbidities such as heart failure and chronic obstructive pulmonary disease. Making an accurate diagnosis of IPF is imperative, as new treatments that appear to slow the progression of IPF have recently become available. Pirfenidone and nintedanib are two such treatments, which have shown efficacy in randomised controlled trials. As with all new treatments, caution must be advocated in the elderly, as these patients often lie outside the narrow clinical trial cohorts that are studied, and the benefits of therapy must be weighed against potential toxicities. Both medications, while relatively safe, have been associated with adverse effects, particularly gastrointestinal symptoms such as nausea, diarrhoea and anorexia. In this review, we highlight measures to improve recognition and accurate diagnosis of IPF, as well as co-morbidities that often affect the diagnosis and disease course. The gold standard for IPF diagnosis is a multidisciplinary meeting whereby clinicians, radiologists and histopathologists reach a consensus after interactive discussion. In many cases, a lung biopsy may not be available because of high risk or patient choice, particularly in the elderly. In these cases, there is debate as to whether a biopsy is required, given the high rates of IPF in patients over the age of 70 years with interstitial changes on computed tomography. We also discuss the management of IPF, drawing particular attention to specific issues affecting the elderly population, especially with regard to polypharmacy and end-of-life care. Through this article, we endeavour to improve awareness of this devastating disease and thus improve recognition of the disease and its outcomes in elderly patients.
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PMID:Idiopathic Pulmonary Fibrosis and the Elderly: Diagnosis and Management Considerations. 2708 34

Systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) has become the leading SSc-related cause of death. Although various types of immunosuppressive therapy have been attempted for patients with SSc-ILD, no curative or effective treatment strategies for SSc-ILD have been developed. Therefore, management of patients with SSc-ILD remains a challenge. Here, we report a Chinese, female, SSc-ILD patient who was negative for Scl-70 and showed an excellent response to pirfenidone without obvious adverse effects. She had been suffered from dry cough and exertional dyspnea for 2 months. The chest computed tomography manifestation was consistent with a pattern of fibrotic nonspecific interstitial pneumonia. The pulmonary function test showed isolated impaired diffusion. After 11 weeks of administration of pirfenidone, the dry cough and dyspnea had disappeared. Both of the lung shadows and the pulmonary diffusion function were improved. Pirfenidone might be an effective option for early SSc-ILD treatment. A well-controlled clinical trial is expected in the future.
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PMID:A case report: The efficacy of pirfenidone in a Chinese patient with progressive systemic sclerosis-associated interstitial lung disease: A CARE-compliant article. 2739 14

Patients with idiopathic pulmonary fibrosis, an incurable, progressive fibrotic interstitial lung disease, suffer an impaired quality of life due to symptoms, resultant functional limitations, and the constraints of supplemental oxygen. Two antifibrotic medications, nintedanib and pirfenidone, are approved for the treatment of idiopathic pulmonary fibrosis. Both medications slow the rate of decline of lung function, but their effect on patient-reported outcomes is not yet fully understood. Nintedanib may slow the decline in health-related quality of life for treated patients. Pirfenidone may slow the progression of dyspnea and improve cough. Patients and providers should participate in shared decision-making when starting antifibrotic therapy, taking into consideration the benefits of treatment in addition to drug-related side effects and dosing schedules. Although antifibrotic therapy may have an impact on health-related quality of life, providers should also focus on comprehensive care of the patient to improve health-related outcomes. This includes a multidisciplinary evaluation, diagnosis and treatment of comorbid medical conditions, and referral to and participation in a pulmonary rehabilitation program.
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PMID:Impact of novel antifibrotic therapy on patient outcomes in idiopathic pulmonary fibrosis: patient selection and perspectives. 3028 34