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)

The majority of patients with non-small cell lung cancer (NSCLC) present with advanced disease, which is associated with a poor prognosis and symptoms such as pain, coughing, and shortness of breath. In patients who present at an earlier stage, the progressive nature of NSCLC and its resistance to treatment often result in recurrence, with the associated symptoms of advanced disease. These symptoms negatively affect patient quality of life and performance status rating, both of which are predictive of treatment response and survival. There is increasing interest in using assessments of improvements in symptoms and quality of life as outcomes in clinical trials for patients with advanced NSCLC. Patients with NSCLC have limited therapeutic options. Even those patients who are able to tolerate chemotherapy can expect median survival increases of only 2 to 4 months. The new targeted therapies for lung cancer, in contrast, are relatively nontoxic and may provide benefits for symptoms and quality of life in addition to tumor responses. The Functional Assessment of Cancer Therapy-Lung (FACT-L) scale is a validated, sensitive, and reliable patient questionnaire that evaluates and quantifies quality of life across several dimensions, including lung cancer-related symptoms (Lung Cancer Subscale). The Lung Cancer Subscale ranges from 0 (severe debilitation) to 28 (asymptomatic). A change of two points reflects a clinically significant change in NSCLC-related symptoms and quality of life. In phase I studies and also in the Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL)-1 and IDEAL-2 phase II monotherapy trials, treatment of patients with advanced NSCLC with the epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals LP, Wilmington, DE) has shown tumor responses as well as rapid improvements in NSCLC-related symptoms and quality of life. In IDEAL-1 and IDEAL-2, improvements in NSCLC-related symptoms and quality of life, as measured by FACT-L, correlated with tumor response, and improvements in symptoms also correlated with progression-free and overall survival. Although symptom response is correlated with tumor response, it is also uniquely predictive of progression-free and overall survival. The FACT-L questionnaire has also been included in phase III trials of ZD1839 treatment in combination with chemotherapy regimens.
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PMID:Impact of ZD1839 on non-small cell lung cancer-related symptoms as measured by the functional assessment of cancer therapy-lung scale. 1264 83

Gefitinib is a newly developed molecular-target drug with selective inhibitory activity for tyrosine kinase of the epidermal growth factor receptor and has an encouraging effect on non-small cell lung cancer in an advanced stage. The adverse drug reactions including diarrhea, skin eruptions and liver dysfunction have been considered mild. However, cases of severe acute lung injuries were reported after approval of the drug in Japan in July, 2002. We report a case of recurrent large cell carcinoma of the lung in a 73-year-old man who suffered from radiation recall pneumonitis induced by Gefitinib. Two months after radiation therapy to the mediastinal and right hilar lesions was completed, he started to take Gefitinib at a dose of 250 mg/day. Six weeks later, he complained acutely of a dry cough, slight fever and effort dyspnea, and his chest CT demonstrated ground-glass opacity corresponding to the previous radiation field. In administering Gefitinib, as well as other cytotoxic drugs, meticulous monitoring for acute lung injury and radiation recall reaction is required.
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PMID:[Radiation recall pneumonitis induced by Gefitinib (Iressa): a case report]. 1450 45

Lung cancer often develops in individuals with pre-existing pulmonary and cardiac pathology. Many of these individuals with pre-existing pathology are also at risk of occupational lung disease. New and worsening symptoms can be secondary to pre-existing pathology, progressive cancer or treatment. Pulmonary toxicity, including interstitial lung disease, following radiotherapy and conventional cytotoxic chemotherapy (e.g. cyclophosphamide, bleomycin), has been recognised for many years. Pulmonary toxicity also occurs with the newer classes of cytotoxic agents, including the deoxycytidine analogue gemcitabine. A small percentage (0.88%) of patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib have developed interstitial lung disease. This complication has been reported at a higher frequency in Japanese patients than in US patients (1.9% vs 0.34%, respectively) and in those with pre-existing pulmonary fibrosis. This review discusses the difficulties in both recognition and treatment of gefitinib-associated interstitial lung disease. Symptoms are vague, such as dyspnoea, cough and fever and can be difficult to differentiate from progressive disease, co-existing morbidity and new pulmonary pathology. Diagnosis is, therefore, by rigorous investigation to exclude all other differential diagnoses. Treatment, at present, is supportive and includes discontinuation of gefitinib, oxygen supplementation, high-dose corticosteroids and antibacterials.
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PMID:Interstitial lung disease in lung cancer: separating disease progression from treatment effects. 1569 Dec 21

Two Japanese females complained of cough and bronchorrhea for which chest radiographs showed infiltrate in the lungs. The patients were subsequently diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy. After receiving systemic chemotherapy, their symptoms were slightly improved. A few months later, their bronchorrhea and dyspnea worsened, and they were then treated with gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor. Bronchorrhea and dyspnea were improved within 24 h after treatment with gefitinib where the improvement was evident after 6 h for one patient and 24 h for the other patient. Thereafter, their radiological findings showed gradual improvement. Rapid relief of bronchorrhea preceded the improvement seen by the radiological findings. These observations suggest that gefitinib may inhibit mucin production as well as exert anti-proliferative activity against bronchioloalveolar carcinoma.
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PMID:Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma; two case reports. 1594 98

Hypertrophic osteoarthropathy is an important manifestation of lung carcinoma, particularly in a non-small cell tumor, and hampers quality of life. Although removal of the primary tumor usually resolves this syndrome, effective treatment in patients with advanced lung carcinoma has not been established. Recently, an orally active, selective epidermal growth factor receptor tyrosine kinase (EGFR) inhibitor ("Gefitinib") provided clinical anti-tumor activity. We describe a 71-year-old male smoker with cough, who presented with clubbed fingers. A transbronchial lung biopsy (stage T2N3M1-IV) on a cavity lesion in the left lower lobe showed the features of adenocarcinoma, while bone scintigram revealed bilaterally symmetrical abnormal uptakes in the lower extremities, suggesting secondary hypertrophic osteoarthropathy. The serum level of growth hormone was increased to 1.42 ng/ml. Chemotherapy (cisplatin, vinorelbine) was not effective. Gefitinib, as a second-line therapy, induced disappearance of the abnormal accumulation on bone scintigraphy and decrease of the cavity in the lung and of serum growth hormone. The presented case suggests that the EGFR inhibitor might be a promising option for the treatment of hypertrophic osteoarthropathy with advanced lung adenocarcinoma.
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PMID:Successful treatment of hypertrophic osteoarthropathy by gefitinib in a case with lung adenocarcinoma. 1608 Apr 71

Eosinophil-associated conditions, such as asthma and eosinophilic bronchitis, have been associated with chronic persistent cough, usually responding to corticosteroid therapy. This case study reports a case of persistent cough associated with gastro-oesophageal reflux (GOR) and hypereosinophilia. Treatment of GOR with proton pump inhibitors and fundoplication did not control the cough. However, high dose prednisolone, but not inhaled corticosteroids, did. The presence of the FIP1L1-PDGFRA fusion gene in myeloid cells was confirmed by fluorescence in situ hybridisation analysis using CHIC2 deletion as a surrogate marker. The cough and other disease features were subsequently suppressed by the tyrosine kinase inhibitor, imatinib. This is the first case of persistent cough caused by hypereosinophilic syndrome characterised by FIP1L1-PDGFRA fusion gene and aberrant tyrosine kinase activity.
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PMID:Cough and hypereosinophilia due to FIP1L1-PDGFRA fusion gene with tyrosine kinase activity. 1638 54

The transient receptor potential vanilloid 1 (TRPV1) is an excitatory cation channel, rather selectively expressed in a subpopulation of nociceptive, primary sensory neurons that promote neurogenic inflammation via neuropeptide release. TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid derivatives, and is uniquely sensitive to vanilloid molecules, including capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide sensitize/activate TRPV1. In the airways, TRPV1 agonists cause cough, bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion. Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. TRPV1 antagonists may be useful in the treatment of these diseases.
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PMID:The transient receptor potential vanilloid 1: role in airway inflammation and disease. 1646 49

Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia and are increasingly used for other indications. Fluid retention, however, including pleural effusions, are a significant side effect of imatinib, the first-line treatment for chronic myeloid leukemia. We investigated pleural and pulmonary complications in patients treated with dasatinib, a novel multitargeted tyrosine kinase inhibitor, as part of clinical trial protocols. Of 40 patients who received dasatinib (70 mg twice daily) for imatinib resistance or intolerance, 9 (22.5%) developed dyspnea, cough, and chest pain. Of these nine patients, six had pleural effusions (all were exudates) and seven had lung parenchyma changes with either ground-glass or alveolar opacities and septal thickening (four patients had both pleural effusions and lung parenchyma changes). Lymphocytic accumulations were detected in pleural and bronchoalveolar lavage fluids in all patients except for one who presented with neutrophilic alveolitis. Pleural biopsies revealed lymphocytic infiltration in one patient and myeloid infiltration in another. After dasatinib interruption, lung manifestations resolved in all cases and did not recur in three of four patients when dasatinib was reintroduced at a lower dose (40 mg twice daily). Thus, lung physicians should be aware that lung manifestations, presumably related to an immune-mediated mechanism rather than fluid retention, may occur with dasatinib treatment.
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PMID:Lung abnormalities after dasatinib treatment for chronic myeloid leukemia: a case series. 1760 Feb 77

The transient receptor potential (TRP) family of channels is represented by at least six members in primary sensory neurons. These include the TRP vanilloid subtypes 1 (TRPV1), 2, 3, and 4, the cold and menthol receptor TRPM8, and TRPA1. Much interest has been directed to the study of the TRPV1, because capsaicin has been instrumental in discovering the unique role of a subset of primary sensory neurons in causing nociceptive responses, in activating reflex pathways including cough, and in producing neurogenic inflammation. TRPV1 is now regarded as an integrator of diverse sensory modalities because it undergoes marked plasticity and sensitization through a variety of mechanisms, including activation of G-protein-coupled or tyrosine kinase receptors. Evidence in experimental animals and in patients with airway diseases indicates a marked hypersensitivity to cough induced by TRPV1 agonists. Recent studies with newly developed high-affinity and selective TRPV1 antagonists have revealed that TRPV1 inhibition reduces cough induced by citric acid or antigen challenge.
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PMID:Cough sensors. II. Transient receptor potential membrane receptors on cough sensors. 1882 35

Pulmonary toxicity is a known complication of erlotinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors. It consists of diverse entities such as interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia and pulmonary fibrosis. In our report, an unusual case of an asymmetric interstitial lung disease was described. A 68-year-old female presented with resistant cough, hemoptysis and a right lung atelectasis on chest X-ray. She underwent selective bronchial artery embolization successfully after pharmaceutical therapy failed to stop hemoptysis. Flexible bronchoscope revealed that the opening of the right main bronchus was blocked completely by a neoplasm with a distance <2 cm to the carina and the sample of bronchoscopic biopsy confirmed the diagnosis of lung adenocarcinoma (cT3N2M0). Dyspnea and asymmetric interstitial lung disease in the nontumorous lung were noted on the 6th day of erlotinib therapy (150 mg daily) which had been efficacious in its anticancer effect. Discontinuing erlotinib use and treatment with corticosteroids could not relieve her symptoms. The patient deteriorated rapidly and died of progressive respiratory failure. We explored the mechanisms of asymmetric interstitial lung disease.
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PMID:Fatal asymmetric interstitial lung disease after erlotinib for lung cancer. 2288 62


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