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At least 955 records · Page 53Linked to original sources
PubMed1996

[Consecutive study on alveolar macrophage release of tumor necrosis factor-alpha and platelet-derived growth factor in bleomycin-induced pulmonary fibrosis in rats].

OBJECTIVE: Observe consecutively alveolar macrophage (AM) release of tumor necrosis factor-alpha (TNF-alpha) and platelet-derived growth factor (PDGF in bleomycin-induced pulmonary fibrosis in rats. METHODS: ELISA method for TNF-alpha quantitation; Bioassay method for PDGF assessment. RESULTS: (1) AM TNF-alpha release was elevated on 3rd day, peaked on 7th day and then remained at higher level than that in control. (2) AM PDGF release was elevated on 3rd day, also peaked on 7th day, but then decreased to a near normal level. CONCLUSION: AM might play a role in the pathogenesis of pulmonary fibrosis through release of TNF-alpha and PDGF.

Animals↗
PubMed2002

Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency and, in patients with HPS1 gene mutations, a progressive, fatal pulmonary fibrosis. We investigated the safety and efficacy of an antifibrotic agent, pirfenidone (800 mg, t.i.d.), in treating 21 adult Puerto Rican HPS patients, including 20 homozygous for the same HPS1 mutation. Patients were examined every 4 months for up to 44 months in a randomized, placebo-controlled trial, with rate of change in pulmonary function values as outcome parameters. Using the complete data set of 130 patient admissions, a repeated measures model showed that 11 pirfenidone-treated patients lost FVC at a rate 5% of predicted ( approximately 400 mL) per year slower than 10 placebo-treated patients (p=0.001). A random coefficients model showed no significant difference. However, using data restricted to patients with an initial FVC >50% of predicted, both models showed the pirfenidone group losing FVC (p<0.022), FEV(1) (p<0.0007), TLC (p<0.001), and DL(CO) (p<0.122) at a rate approximately 8%/year slower than the placebo group. Clinical and laboratory side effects were similar in the two groups. Pirfenidone appears to slow the progression of pulmonary fibrosis in HPS patients who have significant residual lung function.

Adult↗
PubMed1984

[Pulmonary fibrosis and ankylosing spondylitis].

The authors report two new cases of pulmonary fibrosis associated with ankylosing spondylitis. The clinical, radiological and histological characteristics of this fibrosis are described. Various pathogenic hypotheses which could explain the onset of this fibrosis are envisaged.

Aged↗
PubMed1994

Loss of lymphocyte modulatory control by surfactant lipid extracts from acute hypersensitivity pneumonitis: comparison with sarcoidosis and idiopathic pulmonary fibrosis.

Surfactant components are recognized to exert a regulatory control on lymphocytes in physiological conditions, as testified by in vitro studies. However, what happens following lung injury has not been established. As surfactant composition is altered in interstitial lung diseases, this work was carried out to compare the modulatory impact of normal human alveolar fluids on lymphocyte proliferation, with that from inflammatory lung diseases which are characterized by distinct patterns of immunologically-mediated alterations (i.e. sarcoidosis, acute hypersensitivity pneumonitis, idiopathic pulmonary fibrosis). Thymidine incorporation of allogeneic normal human blood lymphocytes was studied in the presence of total alveolar fluids or lipid extracts from 37 subjects, and phytohaemagglutinin (PHA) as T-cell mitogen. The results show that: 1) total alveolar fluids and lipid extracts from normal subjects share a concentration-dependent suppressive activity on T-cell proliferation; 2) total alveolar fluids from diseased patients have lost this property, either by a lack of suppressive activity (i.e. idiopathic pulmonary fibrosis) or even by enhanced activity (i.e. sarcoidosis and hypersensitivity pneumonitis); 3) lipid extracts from diseased patients still retain the suppressive activity of normal subjects, except for hypersensitivity; and 4) an imbalance in surfactant phospholipids with an increase in the inducers to suppressors ratio is more likely to explain this alteration in hypersensitivity pnuemonitis than changes in total lipid content. In conclusion, alveolar lipid extracts from acute hypersensitivity pnuemonitis have lost the modulatory control normally exerted by surfactant lipids on lymphocyte proliferation in vitro. This alteration may contribute to the invasion of the lung by lymphocytes in acute hypersensitivity pnuemonitis in vivo.

Adult↗
PubMed2000

Pulmonary fibrosis in a steel mill worker.

We report a case of pulmonary fibrosis in a 32-year-old man, who had worked at a steel mill and who died of respiratory failure due to interstitial fibrosis despite vigorous treatment. He showed SLE-associated symptoms, such as pleural effusion, malar rashes, discoid rashes, arthritis, leukopenia, and positive antinuclear antibody and anti-histone antibody. However, he did not present anti-DNA antibody. A thoracoscopic lung biopsy showed interstitial fibrosis, chronic inflammation and a small non-caseating granuloma in lung tissues, which could be induced by external agents such as metals. The manganese concentration in the lung tissue was 4.64 microg/g compared to 0.42-0.7 microg/g in the controls. The levels of other metals, such as iron, nickel, cobalt and zinc in patient's lung tissue were higher than those in the controls. The patient was probably exposed to Si and various metal dusts, and the lung fibrosis was related to these exposures. Exposure to Si and metal dusts should be sought in the history of any patient with SLE, especially in a male with pulmonary signs, and if present, exposure should be stopped. In the meantime, steps should be taken to ensure that workers exposure to Si and metal dusts in all environments have adequate protection.

Adult↗
PubMed2003

[Potential role of cytokines in idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the expression of platelet-derived growth factor(PDGF) and transforming growth factor-beta (TGF-beta) in transbronchial lung biopsy (TBLB) from patients with idiopathic pulmonary fibrosis(IPF), and study the potential role of cytokines in the development of IPF. METHODS: The immunohistochemical methods were used to determine the expression of PDGF, TGF-beta in TBLB from patients with IPF. RESULTS: In IPF patients, TGF-beta mainly existed at tiny bronchial epithelial cells, alveolar epithelial type-II cells and alveolar macrophages, showing strong expression compared with controls (P<0.01). PDGF mainly existed at fibroblast-like cells surrounding pulmonary vessels, fibroblasts, tiny bronchial epithelial cells, alveolar epithelial type-II cells and alveolar macrophages, showing strong expression compared with controls (P<0.01). CONCLUSION: PDGF and TGF-beta, which interact with pulmonary mesenchymal cells, are involved in the formation of pulmonary fibrosis.

Adult↗
PubMed1982

Combined epidermoid and adenocarcinoma in diffuse interstitial pulmonary fibrosis.

This report documents a case of combined epidermoid and adenocarcinoma with idiopathic diffuse interstitial fibrosis developing in the lung. This type of carcinoma with diffuse interstitial fibrosis occurs only rarely in the lungs, in contrast to such carcinoma without fibrosis, which occurs less rarely. A 79-year-old man died of respiratory insufficiency three years after the was diagnosed as having diffuse interstitial pulmonary fibrosis. Six months prior to his death. a tumor shadow was noticed on a radiograph of his chest. Postmortem examination revealed diffuse interstitial pulmonary fibrosis and a primary lung tumor situated peripherally in the right lower lobe. The histologic features of the tumor closely resembled those of mucoepidermoid carcinoma of the major bronchi. However, the tumor had no relation to any bronchi or bronchial glands, and it was evident that no relation to any bronchi or bronchial glands, and it was evident that it had originated from the surface epithelium of the abnormally altered distal airspaces of the honeycomb lung. It is suggested that the malignantly transformed cells originally possessed the potential for bidirectional differentiation to epidermoid and mucous cells.

Adenocarcinoma↗
PubMed1980

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced pulmonary fibrosis.

Clinical data are presented on 14 patients undergoing BCNU therapy for a primary intracranial glioma (11 biopsied, 3 suspected) in whom pulmonary fibrosis developed as a consequence of the therapy. Pulmonary diffusion abnormalities, dry hacking cough, and chest x-ray changes herald the onset of the process. Microscopic evaluation of lung specimens revealed a wide spectrum of change including hyaline membrane formation, alveolar septal thickening, interstitial fibrosis, and granuloma formation. It is concluded that BCNU causes pulmonary fibrosis that is primarily but not necessarily dose-related and may not be reversible.

Adolescent↗
PubMed1997

Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene.

A serious limitation in the use of the DNA-cleaving, antitumoral-antibiotic, bleomycin during chemotherapy is pulmonary toxicity. Lung injury induced by bleomycin is characterized by an increased deposition of interstitial extracellular matrix proteins in the alveolar wall that compromises respiratory function. Several drugs have been tested in animal models to prevent the pulmonary toxicity of bleomycin, but have not led to a useful clinical treatment because of their adverse effects on other tissues. We have shown that transgenic mice expressing Streptoalloteichus hindustanus (Sh) ble bleomycin resistance protein in pulmonary epithelial cells in the lungs are protected against bleomycin-induced toxicity in lungs. In the present study, we used intranasal administration by adenovirus-mediated gene transfer of the bleomycin resistance Sh ble gene to mouse lung for prevention of bleomycin-induced pulmonary fibrosis. We constructed recombinant adenoviruses Ad.CMVble and Ad.RSVble harboring the bleomycin resistance Sh ble gene under the control of the cytomegalovirus early promoter and the Rous sarcoma virus early promoter, respectively. Transgene expression was detected in epithelia of conducting airways and alveolar septa by immunostaining with a rabbit polyclonal antibody directed against the bleomycin resistance protein and persisted for the duration of drug treatment; i.e., up to 17 d. No toxic effect was seen in adenovirus-treated mice. Pretreatment of mice with Ad.CMVble or Ad.RSVble completely prevented collagen deposition 42-133 d after bleomycin treatment, as measured by lung OH-proline content. Histologic studies indicated that there was little or no lung injury in the adenovirus/bleomycin-treated mice compared with the bleomycin-treated mice. These observations may lead to new approaches for the prevention of bleomycin-induced pulmonary fibrosis.

Acetyltransferases↗
PubMed1996

Immunohistochemical study of metalloproteinases and their tissue inhibitors in the lungs of patients with diffuse alveolar damage and idiopathic pulmonary fibrosis.

Immunohistochemical and confocal microscopic studies of the localization of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen were made in lung tissues from patients with normal pulmonary histology (n = 3), diffuse alveolar damage (n = 14), and idiopathic pulmonary fibrosis (n = 12). Pretreatment with pepsin revealed otherwise undetectable MMP- and TIMP-immunoreactive sites. In normal lung, MMP-2, MMP-9, TIMP-1, and TIMP-2 were localized in ciliated cells, endothelial cells, pneumocytes, macrophages, and smooth muscle cells; fibroblasts showed a strong reaction only for MMP-2. Only TIMP-2 showed co-localization with type IV collagen. Myofibroblasts and epithelial cells expressed increased reactivity for MMPs and TIMPs in both disorders. The reactivities for MMPs and TIMPs were stronger in diffuse alveolar damage. MMP-2 showed focal co-localization in capillary endothelial and disrupted epithelial basement membranes, suggesting activation of collagenolysis. A protective effect against this lysis was suggested by the extensive co-localization of TIMP-2 with type IV collagen and fibrillar collagens. Alveolar buds showed increased reactivity for MMPs and TIMPs in their lining epithelial cells, myofibroblasts, and their basement membranes; however, their matrices were mostly unreactive. These findings emphasize the complexity of the roles of MMPs and TIMPs in collagen turnover in diffuse alvcolar damage and idiopathic pulmonary fibrosis.

Adolescent↗
PubMed1993

Increased number of alveolar macrophages expressing surface molecules of the CD11/CD18 family in sarcoidosis and idiopathic pulmonary fibrosis is related to the production of superoxide anions by these cells.

This study was designed to investigate the expression and functional properties of leukocyte adhesion molecules (LeuCAM; CD11/CD18 family) on human alveolar macrophages (AM) from patients with sarcoidosis and idiopathic pulmonary fibrosis. Cells were obtained by bronchoalveolar lavage (BAL) from 17 patients with sarcoidosis (SA), 15 with idiopathic pulmonary fibrosis (IPF), and 14 nonsmokers (NS). Expression of LeuCAM on freshly isolated cells was studied using the peroxidase-antiperoxidase method with monoclonal antibodies (MoAb) detecting CD11a, CD11b, CD11c, and CD18. The functional properties of the adhesion molecules were studied by measuring superoxide anion production (O2-) of SA and IPF AM after blocking the CD18 molecule by an MoAb. Compared with nonsmokers, the samples from SA and IPF patients contained an increased number of AM expressing CD11a, CD11b, CD11c, and CD18 (all p < 0.008), which was correlated to the number of AM/ml BAL (p < 0.008). Spontaneous O2- secretion of AM was higher in SA (6.4 +/- 1.2 nMO2-/10(6) AM/120 min) and IPF (12.0 +/- 1.1 nMO2-/10(6) AM/120 min) compared with NS (2.5 +/- 0.2 nMO2-/10(6) AM/120 min) (both p < 0.008). Incubation of the AM with the MoAb anti-CD18 reduced the spontaneous O2- release from SA AM by 52 +/- 8% and from IPF AM by 49 +/- 3% but did not influence O2- release from NS AM (92 +/- 4%). Our data indicate that the increased expression of LeuCAM on AM in subjects with SA and IPF seems to be involved in the increased O2- production of these cells in both diseases.

Adult↗
PubMed1999

Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label Phase II study.

Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of unknown etiology and fatal outcome. Currently available therapies are ineffective and associated with significant adverse effects. Pirfenidone, a new, investigational antifibrotic agent, was evaluated for its tolerability and usefulness in terminally ill patients with advanced IPF. Consecutive patients with IPF and deterioration despite conventional therapy or who were unable to tolerate or unwilling to try conventional therapy were treated with oral pirfenidone. Treatment was administered on a compassionate basis (open-label). Fifty-four patients were followed for mortality, change in lung function, and adverse effects. Their mean age was 62, mean duration of symptoms 4.6 yr, and time since lung biopsy was 3.2 yr. Conventional therapy was discontinued in 38 of 46 patients; the other eight were able to decrease their prednisone dosage and eight had no previous conventional treatment. One- and 2-yr survival was 78% (95% CI 66%, 89%) and 63% (95% CI 50%, 76%), respectively. Patients whose lung functions had deteriorated prior to enrollment appeared to stabilize after beginning treatment. Adverse effects were relatively minor. The results of this study are encouraging. Pirfenidone is a promising new treatment for IPF that is well tolerated.

Administration, Oral↗
PubMed2004

A specific chymase inhibitor, NK3201, suppresses bleomycin-induced pulmonary fibrosis in hamsters.

We evaluated whether a chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[(3,4-dioxo-1-phenyl-7-(2-pyridyloxy))-2-heptyl]acetamide (NK3201), suppressed bleomycin-induced pulmonary fibrosis. Hamsters were orally administered NK3201 (30 mg/kg per day) or placebo, beginning 5 days before intratracheal instillation of bleomycin (10 mg/kg). Four weeks after the instillation of bleomycin, pulmonary chymase activity in placebo-treated hamsters was significantly higher than in control hamsters, whereas the activity in NK3201-treated hamsters was significantly lower than in placebo-treated hamsters. The ratio of fibrotic area to total area in NK3201-treated hamsters was significantly decreased to 54.0% of the ratio in placebo-treated hamsters. Therefore, NK3201 may be useful in the prevention of pulmonary fibrosis.

Acetamides↗
PubMed1983

The in vitro synthesis and degradation of prostaglandins during the development of bleomycin-induced pulmonary fibrosis in hamsters.

Subsequent to optimization of conditions for enzyme assay, we examined the in vitro synthesis and degradation of prostaglandins by the lung during the development of bleomycin-induced pulmonary fibrosis in hamsters. It was found that the microsomal protein content on a per lung basis was significantly increased to 144, 129, 134, and 121% of control (2.3 mg protein/lung) at 4, 7, 14 and 21 days post-treatment, respectively. The synthesis of PGD2 was significantly elevated to 10.2, 10.8, and 12.5 nmoles/lung at 7, 21 and 28 days, respectively, as compared to the control value of 5.6 nmoles/lung. Significant increases in PGF2 alpha synthesis from the control value of 3.3 nmoles/lung to 5.2, 8.2 and 5.5 nmoles/lung were found at 4, 7 and 21 days post-treatment, respectively. The synthesis of PGE2 also showed significant increases above the control value of 6.1 nmoles/lung to 10.5, 12.2 and 11.0 nmoles/lung at 7, 21 and 28 days post-treatment, respectively. Similarly, the synthesis of 6-keto-PGF1 alpha was significantly increased to 7.4, 7.5 and 8.6 nmoles/lung at 7, 21 and 28 days post-treatment, respectively, as compared to the control value of 4.4 nmoles/lung. The synthesis of TxB2 was also significantly increased from the control value of 3.9 nmoles/lung to 7.5 and 6.4 nmoles/lung at 7 and 21 days post-treatment, respectively. Accompanying the increased synthesis of prostaglandins in general, the in vitro degradation of PGF2 alpha was significantly increased from the control value of 71.1 nmoles/lung to 173.5, 131.7 and 143.3 nmoles/lung at 2, 4 and 7 days after bleomycin treatment, respectively. We conclude that bleomycin-induced pulmonary fibrosis leads to changes in prostaglandin synthesis and degradation possibly as a result of an accompanying inflammatory response and resident cellular proliferation.

6-Ketoprostaglandin F1 alpha↗
PubMed2006

Pulmonary fibrosis in hermansky-pudlak syndrome. a case report and review.

Hermansky-Pudlak syndrome (HPS) is a rare heterogeneously inherited autosomal recessive group of disorders presenting with oculocutaneous albinism, bleeding diathesis and pulmonary disease. HPS is thought to occur as a consequence of disturbed formation or trafficking of intracellular vesicles, most importantly, melanosomes, platelet dense granules and lysosomes. The latter finding, in particular, contributes much to the morbidity associated with the disease, as ceroid lipofuscin deposits in lysosomes affect many organ systems. This is especially problematic in the lungs where it is often associated with pulmonary fibrosis and premature death. Currently, there are 7 known HPS genes in humans. In the mouse, at least 16 known HPS genes produce HPS-mutant phenotypes. The HPS gene mutation is considered to be one of the most prevalent single-gene disorders in northwest Puerto Rico, home to the largest cohort of known patients. In HPS, interventions addressing the bleeding diathesis and pulmonary fibrosis are often disappointingly ineffectual. Pirfenidone, a novel compound with documented anti-inflammatory, antioxidant and antifibrotic effects, appears to hold promise in delaying or preventing fibrosis. To date, there has been one successful lung transplant performed on a patient with HPS. We present a patient with HPS and review the current literature on our understanding of this rare disorder.

Adult↗