Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate, an antifolate cytotoxic drug, is used in anticancer chemotherapy as well as an immuno suppressive in rheumatoid arthritis. It is responsible for numerous secondary effects, amongst which is a characteristic acute pneumonia known since 1969. This pneumonitis has been described in detail, up to the present time in 78 cases gathered in this review. The prevalence of this complication is estimated at around 7%. This pneumonia may occur whatever the age, indication for which methotrexate is prescribed, the route of administration of the product (including the intra-thecal route) and the dose. It includes dyspnoea, fever, (sometimes quite marked) and frequently an acute reversible respiratory failure. Radiologically the opacities are usually diffuse interstitial and symmetrical with a basal predominance with sometimes some confluence and occasionally a pleural reaction. In a small number of cases a transient mediastinal adenopathy has been described. Respiratory function tests show a rapidly developing restrictive syndrome accompanied by hypoxia and hypocapnia. Broncho-alveolar lavage is characterised by hypercellularity with a frank and apparently transitory lymphocytosis. Histologically the most frequent lesion sighted is an extensive acute granulomatous reaction with or without oedema. Most often the outcome is favourable (75% of cases). However 6 deaths due to respiratory failure have been reported. Even though there has not been any formal test, steroid therapy in high dosage seems to accelerate recovery. Progress to an irreversible pulmonary fibrosis is possible but rare. The mechanism of this drug related acute pneumonia is not known but would seem to resemble that of other granulomatosis. Besides this rapidly progressive pneumonitis, methotrexate is responsible for a very small number of cases of severe pulmonary oedema and of acute painful pleurisies.
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PMID:[Pneumopathy caused by methotrexate]. 225 35

Methotrexate may cause pulmonary side effects. Two cases of methotrexate-induced fibrosing alveolitis are reported. One of the patients died from perforated gastric ulcer, the other was successfully treated with systemic steroids. The pulmonary side effects of methotrexate are reviewed. The most common clinical manifestation is fibrosing alveolitis. Pulmonary fibrosis and acute, non-cardiogenic pulmonary oedema are rare.
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PMID:[Methotrexate induced pulmonary disease]. 226 58

Initial combination drug regimens containing Cisplatin in patients with stage III and IV head and neck cancer produce a high percentage of clinical response. We initiated the current trial to assess the role of multimodality treatment (CT plus RT) versus CT alone in eliciting tumour response rates, and the duration of tumour free survival. Patients were randomised to CT followed by RT (arm A: 36 patients) or CT alone (arm B: 44 patients). Of 96 patients entered into this study 80 are evaluable at the time of analysis. There were 13 women and 67 men with a median age of 52 years and a median performance status of 90%. All of them presented measurable stage T4N0-3M0-1 or T3N2-3M0-1 carcinomas. The chemotherapy consisted of Cisplatinum, Bleomycin and Methotrexate and was given in 2 cycles over 35 days. Local radiotherapy with 6,000 rad followed. In arm B, 3 cycles of chemotherapy were given without radiotherapy. The overall tumour responses after CT were 75% in arm B, and 70% in arm A. After RT the tumour response fell to 59%. Median tumour remission was 4 months and median survival 11 months. Toxic effects were mild mainly consisting of alopecia, nausea and vomiting. Myelotoxicity was moderate, but significant renal or ototoxic side effects did not occur. 10 cases of Bleomycin related pulmonary fibrosis were found. Our main findings show that patients receiving 2 cycles of CT do not have a statistically shorter survival compared to those who were treated by CT plus RT.
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PMID:[Chemotherapy or chemotherapy and radiotherapy in advanced head and neck tumors. A prospective, randomized study comparing the 2 therapeutic modalities]. 243 86

Twenty-two patients with locally advanced or metastatic head and neck tumors received a total of 84 courses of a combination of cisplatin, bleomycin, and Methotrexate (PBM) for a median of four courses per patient (range, 1-7). Among these 22 patients there were four patients (18%) who achieved complete remission (CR) and 13 patients (60%) who had a partial remission (PR). The overall remission rate (CR + PR) thus reached 78%; five patients (22%) progressed while on therapy. The mean duration of objective response (CR + PR) was 8 months; CR lasted a median of 18 months (range, 2-48). Survival was not influenced by tumor histology or by previous surgery. The presence of locoregional disease did adversely affect survival from the onset of chemotherapy (P = 0.1). The rate of survival was also affected by primary tumor site; patients with nasopharyngeal primaries survived longer than all other patients (22 vs. 11 months, P = 0.06). Toxicity to chemotherapy consisted mainly of nausea and vomiting and stomatitis. Three patients developed fever while leukopenic. One patient experienced irreversible renal damage, and another suffered from bleomycin-induced pulmonary fibrosis. The high response rate obtained in our group of patients did not have a substantial impact on overall survival. Aggressive, multimodality approaches should be considered in the treatment of these patients when possible.
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PMID:Cisplatin, bleomycin, and methotrexate (PBM) chemotherapy in locally advanced and metastatic head and neck cancer. 248 Apr 93

A 71-year-old man with a long-standing history of rheumatoid arthritis required methotrexate treatment since 1986, with a total dose of 210 mg. In April 1987, before arthroplastic surgery, methotrexate was discontinued. Four weeks later a syndrome of fever, dry cough, shortness of breath, and diffuse air-space consolidations on the chest radiograph evolved. An antibiotic therapy had no beneficial effect, and a bronchoscopy yielded no pathogens. An open lung biopsy led to the diagnosis of methotrexate-induced pneumonitis. This is the first report of a case where methotrexate-induced pneumonitis developed several weeks after cessation of the treatment. Methotrexate can cause four types of pulmonary adverse reactions: pneumonitis, pulmonary edema, pulmonary fibrosis, and pleuritis. Possible pathogenetic mechanisms, symptoms, treatment, and prognosis are discussed.
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PMID:Methotrexate-induced pneumonitis: appearance four weeks after discontinuation of treatment. 280 69

Methotrexate is frequently used in the treatment of severe psoriasis, and its hepatotoxicity has long been recognized by dermatologists. Pulmonary complications resulting from use of the drug are uncommon but should be considered in any patient on methotrexate who develops pulmonary symptoms in the absence of infection. We describe two patients, one who developed an acute pneumonitis and one with progressive pulmonary fibrosis following long-term, low-dose methotrexate for psoriasis. Early recognition of these complications by lung function testing and withdrawal of the drug, when necessary, may arrest or reverse methotrexate-induced lung disease.
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PMID:Pulmonary complications following methotrexate therapy. 381 74

We have developed a new combination intravenous chemotherapy regimen called COMPA (IV-COMPA). The clinical value of IV-COMPA chemotherapy was evaluated based on the results of 24 patients with urothelial cancers. From October 1989 through October 1993, a total of 24 patients (20 males and 4 females) received IV-COMPA chemotherapy at Tokyo Medical College Hospital and Tokyo Medical College Hachioji Medical Center. All patients had advanced transitional cell carcinoma or adenocarcinoma of the urothelial tract (renal pelvis, ureter or bladder). One course of IV-COMPA was delivered at 2-week intervals and consisted of 30 mg/m2 CDDP on day 4 and 5, 0.6 mg/m2 VCR (Oncovin) on day 1 and 2, 5 mg/m2 MTX on day 2 and 3, 5 mg/m2 PEP on day 1, 2 and 3, 20 mg/m2 ADM on day 4. A few patients received the same regimen without peplomycin called IV-COMA to avoid pulmonary fibrosis. Fifteen patients with surgically confirmed invasive carcinoma were defined by at least 1 of the following criteria: multiple tumors or size greater than 5 cm, grade 3, stage P3 or P4, pN+, pR1, pL1, pV1, or secondary carcinoma in situ. These patients were treated with 2 or 3 corpses of postoperative IV-COMPA chemotherapy to improve prognosis. In this group, 14 of 15 (93%) are alive at a median follow-up of 22 months (range, 8-57 months) and actuarial survival rates of 1 and 3 years were 100%, 90.9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical results of IV-compa (cisplatin, vincristine, methotrexate, peplomycin and adriamycin) chemotherapy for advanced urothelial cancer]. 760 60

Pulmonary involvement is one of the extra-articular manifestations of rheumatoid arthritis (RA) and includes pleurisy, parenchymal nodules, interstitial involvement, and airway disease. Rheumatoid pulmonary vasculitis is rare. Pulmonary disease also may be observed as a toxic event consequent to treatment for RA. Although RA is more common in women, rheumatoid lung disease occurs more frequently in men who have long-standing rheumatoid disease, positive rheumatoid factor and subcutaneous nodules. Pleural involvement, usually asymptomatic, is the most common manifestation of lung disease in RA and may occur concurrently with pulmonary nodulosis or interstitial disease. The clinical features and course of pulmonary fibrosis in RA are similar to those of idiopathic pulmonary fibrosis. Bronchiolitis obliterans organizing pneumonia (BOOP), which has been recently described in RA patients, has nonspecific clinical features. The histological patterns correspond to proliferative bronchiolitis in the airway and organizing pneumonia in the alveoli. Obstructive lung disease in RA includes obliterative bronchiolitis (OB) and bronchiectasis. OB is an acute illness characterized histologically by a constrictive bronchiolitis. It may be idiopathic or induced by D-penicillamine or intramuscular gold compounds. Methotrexate (MTX)-pneumonitis is an uncommon complication of MTX treatment. Its clinical presentation is not specific, and diagnosis must be made after exclusion of other causes of pulmonary diseases. It is uncertain if preexisting lung disease predisposes RA patients to MTX-pneumonitis. Treatment of lung disease in RA is empirical. Corticosteroids are usually administered and immunosuppressive drugs are often added when pulmonary disease progresses and/or steroid side-effects appear.
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PMID:Pulmonary involvement in rheumatoid arthritis. 774 Mar 4

Methotrexate is known to induce pulmonary fibrosis. The present study was undertaken to assess pulmonary toxicity, if any, in psoriasis patients on methotrexate therapy and correlate the dose and duration of the treatment with any changes in pulmonary function. Ten patients who had taken methotrexate for one year and ten patients receiving methotrexate were included in the present study. Detailed lung function studies including arterial blood gas analysis were carried out. In both groups, the only pulmonary function abnormalities detected were FEF200-1200, FEF25-75%, residual volume (RV), and RV/TLC%, which showed a decline after six months of treatment. However, this was not significant. No changes were detected in the arterial blood gas values following methotrexate therapy. Therefore, the present study did not find any significant deterioration of lung functions in psoriasis patients on methotrexate therapy.
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PMID:Pulmonary function changes in patients with psoriasis on methotrexate therapy. 1045 81

The rational treatment of systemic sclerosis can be based on a model of its pathogenesis. This model posits a genetic background upon which external stimulae act, resulting in immune activation, vascular injury, fibroblast proliferation, and collagen deposition. The collagen, in turn, increases immune activation, thus resulting in perpetuation of the activation/injury cycle. If this pathogenetic model holds true, intervention can occur at the level of vascular damage, prevention of fibrosis or immunosuppression. Prevention of vascular damage and improvement of oxygenation has been attempted with prostacyclin derivatives, with mixed results. Prevention of fibrosis with interferon-gamma shows some hopeful results in pulmonary fibrosis. Relaxin, too, seems to hold hope for efficacy, whereas the results of therapy with D-penicillamine have been disappointing. Immunosuppression with chlorambucil has not been effective, but the study design was flawed in that trial. Methotrexate may work, but results are mixed. 5-Fluorouracil seems effective, but may be toxic. Cyclophosphamide is effective in open trials, and well-controlled trials are just starting. Finally, stem cell transplantation, a very aggressive form of immunosuppression, is showing some apparent efficacy, but its use is only in the pilot stages.
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PMID:Rational therapy in the treatment of systemic sclerosis. 1109 5


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