Pulmonary talc granulomas, pulmonary fibrosis, and pulmonary hypertension resulting from intravenous injection of talc-containing drugs intended for oral use.
Explore the source record for details and available documents.
Journal Article↗
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.
Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials. The goals of this study were to determine whether serum levels of surfactant protein-A (SP-A) or surfactant protein-D (SP-D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP-A or SP-D levels predict outcome in patients with IPF. The authors found that serum SP-A and SP-D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP-D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP-A and SP-D levels were highly predictive of survival in patients with IPF. This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins-A and -D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.
Adult↗
Cytokine profile and proteome analysis in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis.
The aim of this study was to analyze the type of immune response (Th1, Th2) and protein composition of bronchoalveolar lavage (BAL) of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Flow cytometry analysis of intracellular cytokines revealed different patterns: in IPF and SSc Th2 profiles were predominant, whereas in sarcoidosis Th1 prevailed. The proteomic analysis of BAL fluid (BALF) showed that there were quantitative differences between the three diseases. These were more evident between sarcoidosis and IPF, confirming our previous observations, whereas SSc had an intermediate profile between the two, however with some peculiarities. Comparison of BALF protein maps, constructed with the same quantity of total proteins, enabled us to identify the main profiles of the three diseases: an increase in plasma protein prevalent in sarcoidosis and also present in SSc, though for fewer proteins with respect to IPF and a greater abundance of low molecular weight proteins, mainly locally produced, in IPF. These findings are in line with the different pathogenesis of these diseases: IPF is considered a prevalently fibrotic disorder limited to the lung, with intense local production of functionally different proteins, whereas sarcoidosis and SSc are systemic immunoinflammatory diseases.
Adult↗
Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is a fibrotic lung disease characterized by an increased number of mesenchymal cells in the alveolar walls. Alveolar macrophages constitutively express low levels of c-sis, the protooncogene coding for the B chain of platelet-derived growth factor, a protein with chemotactic and mitogenic activity toward mesenchymal cells. We therefore hypothesized that alveolar macrophages in patients with idiopathic pulmonary fibrosis may release increased amounts of platelet-derived growth factor, which might help to explain the accumulation of mesenchymal cells and the fibrosis of the lower respiratory tract in the disease. Evaluation of alveolar macrophages recovered from the lungs of patients with idiopathic pulmonary fibrosis demonstrated that these cells spontaneously released four times more platelet-derived growth factor than did alveolar macrophages recovered from normal persons (P less than 0.01). That the platelet-derived growth factor molecules were potentially active was shown by their chemotactic activity for smooth-muscle cells and their ability to act as a "competence" factor for fibroblast growth. These observations suggest the possibility that the accumulation of mesenchymal cells within the alveolar walls in patients with idiopathic pulmonary fibrosis may result partly from the exaggerated release of the potent mitogen platelet-derived growth factor by mononuclear phagocytes in the lower respiratory tract.
Biological Assay↗
Nitric oxide derivative in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is a chronic inflammatory disorder of unknown aetiology with a number of inflammatory cells playing a role in its pathogenesis. In this study, we have attempted to find out the possible role of nitric oxide in its pathogenesis by way of measuring the nitrite and nitrate levels in the bronchoalveolar lavage fluid. Ten patients of histologically proved idiopathic pulmonary fibrosis and 10 controls (5 with normal chest skiagrams and 5 with sarcoidosis) were included in the study Bronchoalveolar lavage was carried out in these cases. The levels of nitrates and nitrites were increased in cases of idiopathic pulmonary fibrosis (0.77+/- 0.36 and 8.93 +/- 2.63 nmol/mg of protein) compared to those in controls (0.38 +/- 0.06 and 3.80 +/- 1.11, respectively for sarcoidosis patients); (0.39 +/- 0.13 and 6.56 +/- 1.61 for subjects with normal chest skiagrams). These differences were statistically significant (p < 0.05 to 0.01). These findings suggest a possible role of nitric oxide in the pathogenesis of idiopathic pulmonary fibrosis.
Adult↗
Prognostic role of eosinophils in pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD) are chronic inflammatory lung disorders which may be characterized in various subgroups of patients by increased numbers of macrophages, neutrophils, lymphocytes, and/or eosinophils. Previous studies have suggested that the cell populations recovered with bronchoalveolar lavage (BAL) may be important in predicting disease progression and response to therapy. We evaluated this hypothesis in 27 patients by determining if the cell populations recovered with BAL differed between patients who improved, remained stable, or worsened in their pulmonary functions (as defined by at least a 15 percent change in forced vital capacity) over a six-month observation period. The findings suggested that BAL eosinophilia may be a marker of progressive lung disease in patients with IPF and PF-CVD.
Adult↗
Successful outcome of pregnancy in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is typically seen in older individuals. Occurrence of pregnancy in idiopathic pulmonary fibrosis is uncommon and ends with abortion in case it happens. Here we report a case of idiopathic pulmonary fibrosis presenting at 38 weeks of pregnancy who successfully delivered a male child without any significant complications. The disease was active at presentation and early postpartum period.
Adult↗
Carbonylated proteins in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis.
Oxygen-derived free radicals produced by phagocytes have been postulated to contribute to lung tissue damage occurring during diffuse lung diseases (DLD). The two-dimensional electrophoretic (2-DE) analysis of bronchoalveolar lavage (BAL) protein composition revealed different protein profiles in sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) with a significant increase of low molecular weight proteins in IPF. Some of these proteins are involved in antioxidant processes. The aims of this report were to analyse the oxidative stress occurring in patients with DLD through determination of BAL protein carbonyl content and to identify target proteins of oxidation by a proteomic approach (2-DE combined with immunoblotting with specific antibodies for carbonyl groups). Carbonylated proteins detected by enzyme-linked immunosorbent assay (ELISA) were increased in BAL of patients with S, IPF and SSc compared to healthy controls with a significant difference for S and IPF. The proteomic approach to the analysis of BAL revealed that protein carbonylation was a process involving specific carbonylation-sensitive proteins and that in IPF a greater number of proteins target of oxidation were present. In conclusion, to our knowledge, this is the first report providing a database of proteins target of oxidation in BAL of patients with sarcoidosis, idiopathic pulmonary fibrosis and systemic sclerosis.
Blotting, Western↗
Lung transplantation in scleroderma compared with idiopathic pulmonary fibrosis and idiopathic pulmonary arterial hypertension.
OBJECTIVE: Lung transplantation is a viable, life-saving intervention for several primary pulmonary disorders complicated by severe lung dysfunction. This study was undertaken to evaluate whether patients with systemic sclerosis (scleroderma), a systemic autoimmune rheumatic disorder, would receive similar benefit from this intervention. METHODS: Survival following lung transplantation was examined at 2 university medical centers among 29 patients with scleroderma as compared with 70 patients with idiopathic pulmonary fibrosis (IPF) and 38 with idiopathic pulmonary arterial hypertension (IPAH), the latter groups representing pathologically related primary pulmonary disorders. The end point was death from any cause. Risk of mortality in patients with scleroderma was compared with that in patients with IPF or IPAH, with adjustment for demographic and clinical parameters. RESULTS: During 2 years of followup, 11 patients with scleroderma (38%), 23 with IPF (33%), and 14 with IPAH (37%) died. Cumulative survival at 6 months posttransplantation was 69% in the scleroderma group compared with 80% in the IPF group (log-rank P = 0.21) and 79% in the IPAH group (P = 0.38). The estimated risk of mortality at 6 months was increased in patients with scleroderma compared with those with IPF (relative risk [RR] 1.70, 95% confidence interval [95% CI] 0.74-3.93) and those with IPAH (RR 1.52, 95% CI 0.59-3.96), but the differences were not statistically significant. Over the following 18 months, there was convergence in the survival rates such that cumulative survival at 2 years was comparable, at approximately 64%, among all 3 groups. CONCLUSION: Patients with scleroderma who are recipients of lung transplantation experience similar rates of survival 2 years after the procedure compared with those with IPF or IPAH. Lung transplantation may represent a viable therapeutic option to consider for patients with end-stage lung disease due to scleroderma.
Adult↗
Differential expression of elastin and alpha 1(I) collagen mRNA in mice with bleomycin-induced pulmonary fibrosis.
Interstitial pulmonary fibrosis is characterized by increased production of connective tissue components, including collagen and elastin. The role of elastin turnover in pulmonary fibrosis is not clear, and it is not known whether elastin and collagen are regulated separately or together during the inflammatory process. Mice with bleomycin-induced pulmonary fibrosis were investigated to determine the temporal and spatial changes in localization of elastin mRNA expression, as well as to compare elastin mRNA expression with that of alpha 1(I) collagen mRNA expression. In control (saline-treated) lungs, elastin mRNA was detected by in situ hybridization in arterial walls. No signal was found in alveolar or airway walls or in pleura; alpha 1(I) collagen mRNA was detected in the tissue underlying the airway epithelium. An increase in elastin mRNA expression in muscular arteries was observed 3 days after bleomycin instillation. Expression was also seen in the adventitia of terminal airways and adjacent small blood vessels. Expression of alpha 1(I) collagen mRNA increased in the tissue underlying the airway epithelium. In the pleura, alpha 1(I) collagen mRNA expression was found, although no pleural thickening was evident. The alpha 1(I) collagen mRNA expression was particularly increased in the adventitia of terminal airways and in associated small blood vessels. Obvious in areas of fibrosis, elastin mRNA expression was occasionally increased in the pleura and airway wall 7 days after bleomycin treatment; alpha 1(I) collagen mRNA expression was generally stronger than elastin mRNA expression in areas of fibrosis and was frequently intense in the adventitia of airways and associated blood vessels. The fibrotic areas showed increased elastin mRNA expression 14 and 30 days after bleomycin treatment. The arteries in fibrotic areas showed normal elastin mRNA levels. In the areas of fibrosis and in the adventitia of airways and adjacent blood vessels, alpha 1(I) collagen mRNA expression was very high. In conclusion, lung elastin biosynthesis is markedly altered by bleomycin treatment. The localization and intensity of elastin mRNA expression is different from the expression of alpha 1(I) collagen mRNA.
Animals↗
Idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is a rapidly progressive illness of unknown cause characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. Treatment at present remains largely supportive, with evidence that patients' satisfaction and survival may be improved by referral to centers specializing in the evaluation of interstitial lung diseases. Although no drug therapy has clearly been demonstrated to benefit patients with idiopathic pulmonary fibrosis, a number of novel investigational agents hold promise for future study. Given the poor prognosis associated with idiopathic pulmonary fibrosis, patients should be referred to regional centers of expertise for enrollment in therapeutic clinical trials or for lung transplantation.
Adjuvants, Immunologic↗
Viruses and idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is an increasingly recognized problem with a poor prognosis. The aetiology remains unclear. However, many patients date the onset of their disease to a recent viral infection, implying that viruses may have a potential role in disease progression. A number of studies have suggested an association between idiopathic pulmonary fibrosis and viruses including adenovirus, Epstein-Barr virus and hepatitis C. However, the molecular techniques used in identifying the viruses are extremely sensitive and may lead to erroneous associations being made. This review attempts to place into context the identification and potential role of viruses in patients with idiopathic pulmonary fibrosis.
Adenoviridae↗
Does interferon-gamma improve pulmonary function in idiopathic pulmonary fibrosis?
Idiopathic pulmonary fibrosis (IPF) is a disease with progressive and devastating deterioration of lung function and a fatal prognosis, despite aggressive therapeutic attempts, which, in the majority of cases are futile. Recently, a preliminary study of long-term treatment with interferon (IFN)-gamma1b and low-dose prednisolone in patients with IPF suggested that IFN-gamma1b treatment may improve lung function parameters of patients with IPF. Ever since, specialists in respiratory medicine who treat patients with IPF, are called by patients demanding treatment with IFN-gamma1b. Therefore, the authors here present another prospective investigation of IFN-gamma1b in five patients with IPF. According to the previously published design, patients received 200 microg IFN-gamma1b subcutaneously three-times per week and 10 mg prednisolone orally for 12 months. Two patients stopped IFN-gamma1b treatment after 4 months due to side-effects and further lung function deterioration and one patient died 3 months after commencement of therapy. In total, pulmonary function improved in only one patient during IFN-gamma1b treatment, while four patients deteriorated. To conclude, this small series of idiopathic pulmonary fibrosis cases treated with interferon-gamma1b and corticosteroids does not support previous data that this treatment improves pulmonary function or alters the natural course of idiopathic pulmonary fibrosis. Furthermore, in the authors' experience, side-effects of interferon-gamma1b treatment can significantly reduce patients' quality of life.
Aged↗
Glutathione deficiency of the lower respiratory tract in patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology. Increased oxidant burden and antioxidant, e.g. glutathione (GSH), deficiency in the lower respiratory tract have been thought to play a role in the progression of IPF. Sputum induction is a safe noninvasive tool to study inflammation in the respiratory tract. The aim of the present study was to evaluate the direct measurement of GSH in induced sputum supernatant. Sixteen IPF patients and 15 healthy, nonsmoking subjects underwent sputum induction. Total GSH in sputum, saliva and plasma was measured spectrophotometrically. Sputum GSH was decreased more then four-fold in IPF patients when compared to healthy subjects (mean GSH 1.4+/-0.34 microM versus 5.8+/-0.98 microM). Salivary GSH was generally low or undetectable in all subjects. Plasma GSH levels were lower in IPF patients (0.26+/-0.1 versus 0.74+/-0.16 microM). In IPF patients, there was a borderline correlation of sputum GSH levels with disease duration and lung-function impairment. These data confirm the established role of oxidant/antioxidant imbalance in the pathogenesis of idiopathic pulmonary fibrosis, and show the potential of induced sputum to directly study inflammatory processes and surrogate markers in interstitial lung diseases like idiopathic pulmonary fibrosis.
Adult↗
Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis.
Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, we demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, we now demonstrate the presence of transforming growth factor beta 1 (TGF-beta 1), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-beta 1 may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-beta 1 is the alveolar macrophage, and we demonstrate the expression of abundant TGF-beta 1 mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis.
Fibronectins↗
TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.
Twist-Related Protein 1↗
The timed walk test as a measure of severity and survival in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of approximately 3 yrs. Measurements of airflow and lung volumes at rest are generally used to monitor the clinical course in this disorder. This study was designed to determine if a modified version of the 6-min walk test, called the timed walk test, accurately characterises disease severity and survival in IPF. The study population consisted of 28 patients with well-characterised progressive IPF. The timed walk test and concurrent measures of disease severity were assessed at baseline. Participants were prospectively followed for > or =4 yrs to determine the relationship between parameters of the timed walk test and survival. There were strong correlations between the end-exercise saturation and walk-velocity parameters of the timed walk test and diffusing capacity, and arterial oxygen tension at rest. In univariate Cox proportional-hazards models, end-exercise saturation, change in saturation with exercise, walk distance and walk velocity were associated with survival. In unadjusted logistic regression models, odds of death at 2 yrs were associated with the same parameters. In conclusion, the timed walk test relates to disease severity and long-term outcome in progressive idiopathic pulmonary fibrosis.
Aged↗
Release of amino-terminal procollagen peptides in paraquat-induced acute pulmonary fibrosis.
Acute pulmonary fibrosis following intoxication with paraquat is characterized by increased collagen synthesis and deposition in the lungs. In the present study, a chronic lung lymph fistula preparation in sheep was used to investigate the changes in procollagen type III peptide level in the lung lymph in acute pulmonary distress associated with paraquat application. The procollagen type III peptide is supposed to be an indicator of the changing biosynthetic pattern of pulmonary collagen in lung fibrosis. All animals tested showed a progressive pulmonary distress following the application of paraquat characterized by increasing lymph flows and lymph protein flows which monitored the microvascular membrane damage. In parallel to these findings, procollagen peptide levels in the lymph fluid increased, even before manifest biochemically or histologically detectable pulmonary fibrosis occurred. The present results suggest that the release of procollagen type III peptides into lymph fluid is an early indicator of beginning fibrotic tissue disarrangement, even before completed pulmonary fibrosis can be detected by common tissue analysis.
Acute Disease↗