SEARCH · PubMed Health

Results for “PULMONARY FIBROSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed1992

Changes in distribution, morphology, and tumor necrosis factor-alpha secretion of alveolar macrophage subpopulations during the development of bleomycin-induced pulmonary fibrosis.

Previous studies indicate that heterogeneous alveolar macrophages (AM) play a pivotal role in events associated with bleomycin-induced pulmonary fibrosis. A critical role has been suggested for tumor necrosis factor-alpha (TNF-alpha), a product of activated macrophages, in this fibrotic process. The present study examined whether the characteristics and function (TNF-alpha secretion) of rat AM subpopulations were altered during the development of bleomycin-induced fibrosis. After intratracheal bleomycin treatment, AM were separated into 18 density-defined subpopulations. Bleomycin treatment altered the distribution and morphology of AM subpopulations of densities 1.017 to 1.061 g/ml at all time points studied (4, 14, and 28 days). Subpopulations of densities 1.090 to 1.141 g/ml were affected only at 4 days after bleomycin treatment. Tumor necrosis factor-alpha secretion increased with time in 14- and 28-day samples of bleomycin-treated rats, particularly in subpopulations of densities 1.075 to 1.097 g/ml. These data indicate that alterations in the distribution, morphology, and function of AM subpopulations accompany the development of bleomycin-induced pulmonary fibrosis. When coupled with previous studies suggesting that TNF-alpha plays a role in the fibrotic process in this disease model, these data indicate that AM of densities 1.075 to 1.097 g/ml are responsible for the production of TNF-alpha associated with bleomycin-induced pulmonary fibrosis.

Animals↗

PubMed1997

Detection of adenovirus E1A DNA in pulmonary fibrosis using nested polymerase chain reaction.

The history of patients with idiopathic pulmonary fibrosis (IPF) shows that the disease may be preceded by a viral-like illness. Although viruses have not been demonstrated, it is possible that viruses were not detected in culture because they do not replicate during latency. We investigated the presence of adenovirus in IPF and interstitial pneumonia associated with collagen vascular disease (CVD-IP), using the nested polymerase chain reaction (PCR) and in situ hybridization (ISH) for the E1A region of the adenovirus genome. Studies were performed on lung tissues obtained by transbronchial lung biopsy from 19 patients with IPF, 10 patients with CVD-IP and, for comparison, from 20 patients with sarcoidosis. The E1A DNA was present in 3 out of 19 (16%) cases of IPF, in 5 of 10 (50%) cases of CVD-IP, and in 2 of 20 (10%) cases of sarcoidosis. The incidence of E1A DNA in CVD-IP was significantly higher than that in sarcoidosis (p<0.05). In patients with IPF and CVD-IP, E1A DNA was more prevalent in patients treated with corticosteroids (6 out of 9 cases; 67%) than in those without it (2 out of 20 cases; 10%) (p<0.01). ISH studies showed that 1 out of 8 cases of IPF and CVD-IP, in which E1A DNA was detected by PCR, was positive for E1A DNA. We conclude that adenovirus E1A is unlikely to be aetiologically involved in the pathogenesis of idiopathic pulmonary fibrosis or interstitial pneumonia associated with collagen vascular disease. However, a latent adenovirus infection may be reactivated or may newly infect the host following corticosteroid administration.

Adenovirus Infections, Human↗

PubMed1998

[Studies on the role of colchicine in bleomycin-induced pulmonary fibrosis in rats].

OBJECTIVE: It has well been known that cytokines and extracellular matrix protein (ECM) have played an important role in pulmonary fibrosis in animal model as well as in patients. The purpose of this study was to evaluate the suppressive effect of colchicine (Colc.) in bleomycin (BLM)-treated rats. METHOD: Consecutive changes of interleukin-6(IL-6) and interleukin-8 (IL-8) released by alveolar macrophage (AM) were measured with murine B-cell hybridoma 7TD1 cells and micro membrane filter test. ECM and lipid peroxidation were observed with radioimmunoassay and biochemical assay respectively. RESULT: (1) Colc. significantly suppressed release of IL-6 by AM from day 7 to 28 (P < 0.05). But the level of IL-6 remained higher than that of the control. On the day 1 to 3, IL-8 released by AM markedly decreased (P < 0.01) and the peak of IL-8 secretion had not appeared. (2) Colc. had no protective effects on AM lipid peroxidation injury. (3) Colc. markedly decreased the level of fibronectin (FN) by AM on day 7, 14 (P < 0.01), as well as the level of laminin (LN) in bronchoalveolar lavage fluid (BALF) on day 7 to 28. However, the level of LN remained higher than that of control. (4) Colc. lessened the collagen deposition, and the lung hydroxyproline (HYP) content decreased on day 7, 14 and 28 (P < 0.05) compared with that of the control. (5) Colc. decreased exudation of inflammatory cells in the early response, as well as the degree of fibrosis in the late stage. CONCLUSION: Lipid peroxidation of AM might be one of the mechanisms of tissue injury and of AM activation, which increases the release of cytokines (IL-6, IL-8) and deposition of extracellular matrix proteins (FN, LN). Colc. exertes somewhat inhibitory effects on the process of pulmonary fibrosis in animal model. Factors other than AM and its cytokines might also be involved in the pathogenesis of pulmonary fibrosis in experimental rats.

Animals↗

PubMed1999

Detection of anti-ADAM 10 antibody in serum of a patient with pulmonary fibrosis associated with dermatomyositis.

OBJECTIVES: It has been suggested that the humoral immune system plays a part in the pathogenesis of pulmonary fibrosis. Although circulating autoantibodies to lung protein(s) have been suggested, few lung proteins have been characterised. The purpose of this study is to determine the antigen recognised by serum of a patient with pulmonary fibrosis associated with dermatomyositis. METHODS: To accomplish this, anti-small airway epithelial cell (SAEC) antibody in a patient's serum was evaluated using a western immunoblot. RESULTS: An autoantibody against SAEC was found, and the antigen had a molecular weight of 62 kDa. Using the patient's serum, clones from the normal lung cDNA library were screened and demonstrated that anti-SAEC antibody in the patient's serum was against ADAM (A disintegrin and metalloprotease) 10. CONCLUSION: This is the first report that demonstrates the existence of anti-ADAM 10 antibody in a patient with pulmonary fibrosis associated with dermatomyositis.

ADAM Proteins↗

PubMed1983

Pulmonary fibrosis after prolonged treatment with low-dose cyclophosphamide. A case report.

Interstitial pulmonary fibrosis is described in a 26-year-old woman with malignant lymphoma after prolonged intake of cyclophosphamide. Cyclophosphamide was given over a period of 13 years in an oral daily dose of 50-100 mg. Lung biopsy revealed extensive fibrosis with no evidence of malignancy or infection. Cyclophosphamide is considered the most likely cause of pulmonary fibrosis in this patient.

Adult↗

PubMed1982

[Pulmonary fibrosis and pregnancy].

Complete pregnancy of a patient with progressive chronic interstitial pulmonary fibrosis (Hamman-Rich syndrome) is reported in this paper. One pregnancy was interrupted and the other intensively attended to up the 32nd week in which premature rupture of the membranes was followed by caesarean section and subsequent sterilisation. Reference is made to physiological and pathophysiological aspects of respiration in gravidity and in the presence of pulmonary fibrosis.

Adult↗

PubMed1993

Effective treatment of the pulmonary fibrosis elicited in mice by bleomycin or silica with anti-CD-11 antibodies.

We treated two types of experimental pulmonary fibrosis elicited in mice by the intratracheal instillation of bleomycin or silica with monoclonal antibodies (mAbs) specific for the leukocytic integrins CD-11a or CD-11b. This treatment completely prevented collagen deposition, as measured by lung hydroxyproline content on Day 15 after instillation. Furthermore, anti CD-11a mAb was also effective when given on Days 20 and 25 and the lung hydroxyproline content determined on Day 30 after instillation, i.e., in the treatment of an established pulmonary fibrosis. Histologic studies indicated that anti CD-11 mAbs attenuated the fibrosing alveolitis induced by silica or bleomycin and in addition markedly decreased the lymphoid infiltration and platelet microthrombi associated with both types of alveolitis. In contrast, these mAbs had little or no effect on the cellularity of the bronchoalveolar lavage, mainly composed of macrophages. In normal mice, anti CD-11 mAbs also decreased the number of interstitial lymphocytes and the lung collagen content. These observations may lead new to therapies for pulmonary fibrosis.

Animals↗

PubMed2006

Smad3 signaling involved in pulmonary fibrosis and emphysema.

The incidence of finding evidence of both emphysema and pulmonary fibrosis in the same patient has received increased attention. Several investigators have found on biopsy the presence of emphysema of the upper zones and diffuse parenchymal disease with fibrosis of the lower zones of the lung, especially associated with current or previous heavy smokers. Believed previously to be two different disease mechanisms, there are now data to implicate some common pathways of cell and molecular activation leading to the different morphologic and physiologic outcomes. According to a current view, emphysema may originate from a protease/antiprotease imbalance, whereas a role for antiproteases has been proposed in the modulation of fibrosis. Overexpression of transforming growth factor beta (TGF-beta) in experimental rodent models leads to progressive pulmonary fibrosis, accompanied with marked up-regulation of protease inhibitors, such as tissue inhibitor of metalloproteinases (TIMP) and plasminogen activator inhibitor-1 (PAI-1) genes, along with excessive matrix accumulation. It may be that a "matrix degrading" pulmonary microenvironment, one in which metalloproteinase activities prevail, favors the development of emphysema, whereas a "matrix nondegrading" microenvironment, with enhanced presence of TIMPs, would lead to matrix accumulation and fibrosis. Surprisingly, although Smad3 null mice, deficient in TGF-beta signal transmission, are resistant to bleomycin- and TGF-beta-mediated fibrosis, they develop spontaneous age-related airspace enlargement, consistent with emphysema, with a lack of ability to repair tissue damage appropriately. A common element is tissue damage and repair, with TGF-beta and the Smad signaling pathway playing prominent molecular roles. Both changes can be followed in experimental models with noninvasive imaging and physiologic measurements.

Animals↗

PubMed2005

Pulmonary fibrosis: searching for model answers.

Substantial challenges remain in our understanding of fibrotic lung diseases. Nowhere is this more true than in the elucidation and verification of the pathogenetic basis upon which they develop. Scientific progress, most recently in the field of experimental therapy, has relied closely on interpreting data derived from animal modeling. Such models are used to identify the cellular interactions and molecular pathways involved in lung tissue repair and fibrosis. Over the coming years, the significance of new discoveries will continue to be evaluated using the in vivo analysis of animal models substituting for patients with actual pulmonary fibrosis. The commonest strategy to induce experimental pulmonary fibrosis is by directly administering a profibrotic agent to either wild-type animals or those that bear a specific genetic modification. The creation of new models has been greatly enhanced by the availability of stem cell lines and methods for introducing genetic mutations into these cells. Despite an increasing choice of models, there are still good reasons to continue adapting and using one of its earliest examples, the bleomycin model, in post-genomic pulmonary fibrosis research. A brief review of the exacting requirements of such research will place the strengths of this particular model in perspective.

Animals↗

PubMed2004

C-type natriuretic peptide attenuates bleomycin-induced pulmonary fibrosis in mice.

C-type natriuretic peptide (CNP) has been shown to play an important role in the regulation of vascular tone and remodeling. However, the physiological role of CNP in the lung remains unknown. Accordingly, we investigated whether CNP infusion attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. After intratracheal injection of BLM or saline, mice were randomized to receive continuous infusion of CNP or vehicle for 14 days. CNP infusion significantly reduced the total number of cells and the numbers of macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid. Interestingly, CNP markedly reduced bronchoalveolar lavage fluid IL-1beta levels. Immunohistochemical analysis demonstrated that CNP significantly inhibited infiltration of macrophages into the alveolar and interstitial regions. CNP infusion significantly attenuated BLM-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. CNP markedly decreased the number of Ki-67-positive cells in fibrotic lesions of the lung, suggesting antiproliferative effects of CNP on pulmonary fibrosis. Kaplan-Meier survival curves demonstrated that BLM mice treated with CNP had a significantly higher survival rate than those given vehicle. These results suggest that continuous infusion of CNP attenuates BLM-induced pulmonary fibrosis and improves survival in BLM mice, at least in part by inhibition of pulmonary inflammation and cell proliferation.

Animals↗

PubMedDate not supplied

Eosinophilic gastroenteritis with malabsorption, extensive villous atrophy, recurrent hemorrhage and chronic pulmonary fibrosis.

A patient with diffuse eosinophilic gastroenteritis, associated with progressive chronic interstitial pulmonary fibrosis, was followed for 29 years. His major symptoms were recurrent gastrointestinal bleeding, anemia, diarrhea, malabsorption, and increasing respiratory insufficiency. Multiple jejunal biopsies revealed eosinophilic infiltration and extensive villous atrophy. Results of a lung biopsy and pulmonary function tests were consistent with chronic interstitial pulmonary fibrosis. His gastrointestinal symptoms responded to steroid therapy, but he died of progressive respiratory insufficiency. At autopsy, villous atrophy was noted to extend throughout the whole extent of the small intestine in association with multiple "pseudopolypoidal" inflammatory lesions.

Aged↗

PubMed2006

All-trans-retinoic acid prevents radiation- or bleomycin-induced pulmonary fibrosis.

RATIONALE: Although radiotherapy is effective in treating lung cancers, resultant pulmonary injury is the main obstacle. Pulmonary fibrosis is characterized by progressive worsening in pulmonary function leading to high incidence of death. Currently, however, there has been little progress in effective preventive and therapeutic strategies. OBJECTIVES: Previously, we reported that all-trans-retinoic acid (ATRA) reduced both irradiation-induced interleukin (IL)-6 production in lung fibroblasts and IL-6-dependent cell growth, and also directly inhibited the proliferation of lung fibroblasts after irradiation. In this study, we examined the preventive effect of ATRA on the progression of lung fibrosis both in irradiated and bleomycin-treated mice. MEASUREMENTS: We performed histologic examinations and quantitative measurements of IL-6, transforming growth factor (TGF)-beta(1), and collagen type Ialpha1 (COL1A1) in irradiated and bleomycin- treated mouse lung tissues with or without the administration of ATRA. RESULTS: Lethal irradiation effect was reduced by intraperitoneal administration of ATRA, and the overall survival rate at 16 wk was 30.0% without ATRA (n = 11), whereas it was 81.8% (n = 10) in the treatment group (p = 0.04). In vitro studies disclosed that the administration of ATRA reduced (1) irradiation-induced production of IL-6, TGF-beta(1), and collagen from IMR90 cells, and (2) IL-6-dependent proliferation and TGF-beta(1)-dependent transdifferentiation of the cells, which could be the mechanism underlying the preventive effect of ATRA on lung fibrosis. Furthermore, ATRA ameliorated bleomycin-induced fibrosis in mouse lung tissues. CONCLUSIONS: These data may provide a rationale to explore clinical use of ATRA for the prevention of radiation-induced lung fibrosis and other pathologic conditions involving pulmonary fibrosis.

Animals↗

PubMed1993

[Idiopathic pulmonary fibrosis: new diagnostic and therapeutic perspectives].

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology affecting alveolo-interstitial structures. It is clinically characterized by progressive dyspnea and dry cough. In the physical exploration, crakles at the pulmonary bases and acropachies are usually detected. Its diagnosis has been a major clinical problem. Currently, a definitive diagnosis can be established with high resolution computerized axial tomography, bronchoalveolar lavage and open pulmonary biopsy. The next clinical problem is the assessment of activity, since it allows to differentiate subsidiary patients for receiving treatment. The description of new therapeutical alternatives has brought new perspectives in the management of these patients. Corticotherapy associated to immunosuppressors has allowed to reduce side effects and to obtain dramatic improvements. Lung transplantation, currently under study, will be the therapy of the future.

Female↗

PubMed2003

Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis.

There is significant heterogeneity in survival time among patients with idiopathic pulmonary fibrosis. Studies of baseline clinical and physiologic variables as predictors of survival time have reported inconsistent results. We evaluated the predictive value of changes in clinical and physiologic variables over time for survival time in 81 patients with biopsy-proven idiopathic pulmonary fibrosis. Six-month changes in dyspnea score, total lung capacity, thoracic gas volume, FVC, FEV1, diffusing capacity of carbon monoxide, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time even after adjustment for baseline values. Analyses were repeated on 51 patients with 12-month change data. Twelve-month changes in dyspnea score, total lung capacity, FVC, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time after adjustment for baseline values. Evaluation of changes in clinical and physiological variables over 6 and 12 months may provide clinicians with more accurate prognostic information than baseline values alone.

Aged↗

PubMed2002

Protection from pulmonary fibrosis in leukotriene-deficient mice.

Although overproduction of proinflammatory 5-lipoxygenase (5-LO)-derived leukotrienes (LTs) has been demonstrated in the lungs of patients with pulmonary fibrosis, their causal involvement in this condition has not been established. Bleomycin-induced pulmonary fibrosis was studied in mice rendered LT deficient by knockout of the 5-LO gene (KO) and in wild-type (WT) control mice. Following administration of bleomycin, lung lavage fluid of WT mice demonstrated an approximately 5-fold increase in levels of cysteinyl-LTs over baseline levels at Day 1, with persistent elevation up to Day 21. As compared with WT mice, 5-LO KO mice demonstrated reduced amounts of histologically evident collagen as well as an approximately 60% reduction in lung hydroxyproline levels postbleomycin. Unlike WT mice, KO mice showed no increases in the numbers of lung inflammatory cells postbleomycin. Furthermore, in situ expression and stimulated production by mixed lung leukocytes of the antifibrotic cytokine interferon-gamma were significantly greater in cells from the 5-LO KO mice. Finally, lavage levels of the antiinflammatory and antifibrotic molecule, prostaglandin E(2), were significantly greater in the KO animals. These results provide strong evidence that LTs may participate in the pathogenesis of pulmonary fibrosis, and they may do so by direct effects as well as indirect effects occurring via their modulation of the synthesis of other inflammatory mediators.

Animals↗

PubMedDate not supplied

Noninvasive estimation of clinically asymptomatic pulmonary hypertension in idiopathic pulmonary fibrosis.

OBJECTIVES: To determine the prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis (IPF) by noninvasive methods. PATIENTS AND METHODS: Twenty seven patients with IPF attending the Chest Clinic over a period of one-and-a-half-years underwent echocardiography for evidence of pulmonary hypertension, which was defined as pulmonary artery systolic pressure > or = 40 mmHg by Doppler echocardiography, or pulmonary acceleration time < or = 100 milliseconds or two-dimensional echocardiographic findings of right ventricular hypertrophy or overload. RESULTS: Two patients with clinical evidence of pulmonary hypertension were excluded from analysis. Their mean age (n = 25) was 53.8 years. The mean duration of symptoms before presentation was 2.1 years. Pulmonary hypertension was diagnosed by echocardiography in nine of the 25 patients (36%). There was a statistically significant difference between the duration of illness, arterial oxygen tension (PaO2) levels and forced vital capacity in patients with pulmonary hypertension than in those without pulmonary hypertension. Logistic regression analysis showed a significant association between the duration of illness, decreasing forced vital capacity and hypoxemia with the development of pulmonary hypertension. CONCLUSIONS: Echocardiography detects pulmonary hypertension in clinically asymptomatic individuals, and should be used routinely for the diagnosis of pulmonary hypertension in patients with IPF.

Echocardiography↗

PubMed1984

Inhibition of bleomycin-induced pulmonary fibrosis by lipopolysaccharide.

Current evidence suggests that bleomycin toxicity may be attributable to its DNA degradative activity possibly via generation of free radicals and O2 metabolites as mediators. Since lipopolysaccharide (LPS) has been known to provide protection against O2 toxicity, which is correlated with increased activity of O2 metabolite-detoxifying enzymes, the effect of this agent on bleomycin-induced pulmonary fibrosis was examined. Endotracheal bleomycin administration caused increased lung collagen synthesis. A single intraperitoneal injection of LPS (500 micrograms/kg) at day zero significantly decreased these increases. Total bleomycin-induced lung collagen increase was also significantly reduced. LPS alone had no significant effect on total lung catalase activity. Glutathiione peroxidase activity, however, was significantly decreased by 15.8% compared to untreated animals at 2 days after LPS treatment and remained unchanged at other time points. In addition, superoxide dismutase activity was significantly elevated by 30% above untreated animals only at 14 days after LPS administration and remained unchanged at other time points. Endotracheal bleomycin administration alone caused significant reductions in catalase activity at 2 days and 2 weeks after treatment, whereas glutathione peroxidase activity increased above control untreated animals at 2 and 4 weeks, respectively. Superoxide dismutase activity was unaffected by bleomycin treatment. Pretreatment with LPS before bleomycin prevented these reductions or caused increases in the activities of these enzymes at 2 days. Glutathione peroxidase was increased and was significantly greater than those animals treated with bleomycin alone. Catalase also was higher in the LPS plus bleomycin group (by 22.2%, p less than 0.05) than the bleomycin group alone. Compared to the effects on lung collagen synthesis and content, LPS treatment resulted in much less dramatic changes in total lung antioxidant enzyme activities. This discrepancy between the intensity of LPS effects on lung O2 metabolite-detoxifying enzymes and that on pulmonary fibrosis implies that the LPS-ameliorating effect on pulmonary fibrosis could not be totally explained by increased ability to detoxify O2 metabolites. Rather, the data would favor the possibility that LPS inhibits bleomycin-induced pulmonary fibrosis either by its known immunosuppressive effects or some other unknown mechanism. The former would be in agreement with previous data which suggest that an intact immune response is necessary for complete expression of the fibrogenic response to bleomycin.

Animals↗

PubMed2005

Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy.

Idiopathic ulmonary fibrosis (histopathology of usual interstitial pneumonia) is a progressive lung disease of unknown etiology. No treatment has been shown to improve the prognosis of the patients with this disease. Recent evidence, including the observations that the patients with idiopathic pulmonary fibrosis have higher levels of oxidant stress than control patients, and a recent multicenter European study examining the effect of the antioxidant N-acetylcysteine on the progression of idiopathic pulmonary fibrosis suggest that the cellular redox state may play a significant role in the progression of this disease. These complex mechanisms include activation of growth factors as well as regulation of matrix metalloproteinases and protease inhibitors. Potential future approaches for the therapy of interstitial pulmonary fibrosis may involve synthetic agents able to modulate cellular redox state. Investigation into therapeutic approaches to inhibit oxidant-mediated reactions in the initiation and progression of pulmonary fibrosis may provide hope for the future treatment of this disease.

Animals↗