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Results for “PULMONARY FIBROSIS”

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PubMed1994

[The effect of IL-1 receptor antagonist on bleomycin-induced pulmonary fibrosis].

Interleukin-1 (IL-1) is a cytokine with diverse biological activities. It can serve as a fibroblast (FB) growth factor which involves in the development of pulmonary fibrosis. IL-1 receptor antagonist (IL-1ra) can compete with IL-1 for occupancy of surface receptors of target cells without agonist effect. In order to find a new method to treat pulmonary fibrosis, we investigated the effect of recombinant human IL-1ra on the development of pulmonary fibrosis by evaluating collagen content, histological change, and TGF-beta mRNA expression in the rats bleomycin-induced pulmonary fibrosis. The results indicate are that there are no significant difference between the IL-1ra treated group and the control group.

Animals↗

PubMed2005

[Effects of valsartan on bleomycin-induced pulmonary fibrosis in rats and the expression of hepatocyte growth factor in lung tissue].

OBJECTIVE: To study the effect of valsartan on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. METHODS: Sixty Wistar rats were divided into three groups. In the valsartan group and the model groups, pulmonary fibrosis was induced by intratracheal instillation of bleomycin (BLM), and then the former group received valsartan 16 mg/kg daily, but the latter group received oral normal saline. In the control group, normal saline was given both intratracheally and orally. Five rats in each group were sacrificed 7, 14, 28, and 42 days after intratracheal instillation. Collagen content of the lung tissue was assessed by hydroxyproline concentration. Histological changes of the lungs were evaluated by HE stain and Masson's trichrome stain. Lung expression of transforming growth factor-beta (TGF-beta) protein was assessed by immunohistochemistry. The mRNA of hepatocyte growth factor (HGF) was detected by in situ hybridization, and the level of HGF protein was further measured by ELISA. RESULTS: In the valsartan group, alveolitis [(0.88 +/- 0.12) points, (0.79 +/- 0.21) points, (0.75 +/- 0.17) points] decreased significantly 14 days after treatment with BLM and was significantly lower as compared with the model group [(2.05 +/- 0.25) points, (1.38 +/- 0.12) points, (1.19 +/- 0.11) points, P < 0.01]. Pulmonary fibrosis on day 7, 28, 42 [(0.28 +/- 0.03) points vs (0.45 +/- 0.10) points, (1.74 +/- 0.18) points vs (2.08 +/- 0.32) points, (1.91 +/- 0.09) points vs (2.77 +/- 0.15) points, P < 0.05], hydroxyproline concentrations on day 14, 42 [(1.08 +/- 0.13) microg/mg x pro vs (1.45 +/- 0.19) microg/mg x pro, (1.39 +/- 0.20) microg/mg x pro vs (2.19 +/- 0.37) microg/mg x pro, P < 0.01] and protein expression of TGF-beta on day 7, 42 [2.27 +/- 0.30 vs 3.99 +/- 0.43, 2.05 +/- 0.18 vs 2.71 +/- 0.46, P < 0.05] in the valsartan group all reduced significantly as compared with that of the model group. HGF mRNA [1.61 +/- 0.20 vs 1.98 +/- 0.23, 0.52 +/- 0.19 vs 0.28 +/- 0.14, P < 0.05] and its protein expression (204 +/- 18) pg/ml vs (260 +/- 21) pg/ml, (129 +/- 20) pg/ml vs (100 +/- 20) pg/ml, P < 0.05) on day 7 and day 42 in the valsartan group were increased as compared with those of the model group. CONCLUSIONS: Valsartan alleviates BLM-induced pulmonary fibrosis in rats. Inhibiting the expressions of TGF-beta and stimulating the expression of HGF in lung tissues may be one of the mechanisms.

Animals↗

PubMed2006

Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis.

STUDY OBJECTIVES: The development of pulmonary arterial hypertension (PAH) can complicate many interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). We sought to characterize the prevalence of PAH and its impact on survival in patients with advanced IPF. DESIGN: Retrospective analysis of consecutive IPF patients undergoing pretransplantation right heart catheterization. SETTING: Lung transplant and IPF referral center. METHODS: PAH was defined as a mean pulmonary artery pressure (mPAP) of > 25 mm Hg. We compared demographic, spirometric, 6-min walk test (6MWT) results, and survival outcomes between those with PAH and those without PAH. MEASUREMENTS AND RESULTS: Seventy-nine patients were included in the study. PAH was present in 31.6% of patients (mean [+/- SD] mPAP, 29.5 +/- 3.3 vs 19.1 +/- 3.7 mm Hg, respectively). Those patients with PAH had a lower mean diffusing capacity of the lung for carbon monoxide (Dlco) (37.6 +/- 11.3% vs 31.1 +/- 10.1%, respectively; p = 0.04) and were more likely to require supplemental oxygen (66.7% vs 17.6%, respectively; p < 0.0001). Mean distance walked (143.5 +/- 65.5 vs 365.9 +/- 81.8 m, respectively; p < 0.001) and mean pulse oximetric saturation nadir (80.1 +/- 3.7% vs 88.0 +/- 3.5%, respectively; p < 0.001) during the 6MWT were also lower among those with PAH. PAH was associated with a greater risk of death during the study period (mortality rate, 60.0% vs 29.9%, respectively; odds ratio, 2.6; 95% confidence interval [CI], 2.3 to 3.1; p = 0.001). One-year mortality rates were higher in those with PAH (28.0% vs 5.5%, respectively; p = 0.002). As a predictor of mortality, PAH had a sensitivity, specificity, and accuracy of 57.1%, 79.3%, and 73.4%, respectively. There was a linear correlation between mPAP and outcomes with higher pressures associated with a greater risk of mortality (hazard ratio, 1.09; 95% CI, 1.02 to 1.16). FVC and Dlco did not predict outcomes. CONCLUSIONS: PAH is common in advanced cases of IPF and significantly impacts survival. A reduced Dlco, supplemental oxygen requirement, or poor 6-min walk performance should raise suspicion of the presence of underlying PAH. Identifying PAH might be an important adjunct in monitoring disease progression, triaging for transplantation, and guiding therapy.

Comorbidity↗

PubMed1997

Azelastine hydrochloride (Azeptin) inhibits peplomycin (PLM)-induced pulmonary fibrosis by contradicting the up-regulation of signal transduction.

Inhibition of peplomycin (PLM)-induced pulmonary fibrosis by azelastine hydrochloride (Azeptin) was examined using ICR mice, and the effects of both drugs on signal transduction were investigated. Microscopically, Azeptin (a total of 56 mg/kg for 28 days) suppressed pulmonary fibrosis in mice which received an i.p. injection of a total of 60 or 75 mg/kg PLM. In parallel with the microscopic findings, smaller amounts of collagen were synthesized in the lungs of Azeptin-injected mice. PLM enhanced the expression of interleukin-1 beta- and transforming growth factor-beta-mRNA in lungs. In contrast, Azeptin suppressed the expression. Compatible with these in vivo results, Azeptin and PLM contradictively regulated protein tyrosine phosphorylation and c-myc mRNA expression in human gingival and mouse pulmonary fibroblasts. In addition, NF-kappa B was activated by fibroblast treatment with 5 micrograms/ml PLM for 1 h, but intranuclear NF-kappa B was decreased by cell treatment with 10(-5) M Azeptin. From these results, it is concluded that Azeptin inhibits PLM-induced pulmonary fibrosis by antagonizing the up-regulation of signal transduction.

Animals↗

PubMed1997

Expression of bcl-2 protein and APO-1 (Fas antigen) in the lung tissue from patients with idiopathic pulmonary fibrosis.

The fibrotic process of idiopathic pulmonary fibrosis (IPF) is considered to be the consequence of an exaggerated response to an inflammatory lung injury. In a previous report, except for the response to PG-E2, we found no difference in the proliferative profiles of lung fibroblasts between IPF patients and healthy subjects [Mio et al. (1992) Chest, 102:832-837]. In the present study, we hypothesized that lung fibroblasts from IPF patients would not undergo apoptosis as observed in the normal repair process. Additionally, we focused on the protooncogene bcl-2 which prevents apoptosis and the APO-1 (Fas antigen) which induces apoptosis. In order to explore this question, we used immunohistochemical staining to investigate whether apoptotic markers are expressed on lung parenchymal cells of IPF patients obtained by open lung biopsy. Bcl-2 protein was expressed on mononuclear cells in the mantle zone of lymphoid follicules and smooth muscle cells, but it was not expressed on other parenchymal cells. Apo-1 was expressed on epithelial cells, some germinal center cells, and many parenchymal cells including smooth muscle cells, fibrocytes, and myofibroblasts in patients with IPF, findings of which are fundamentally the same as those in normal subjects. Although we could not find any abnormality of lung fibroblasts in IPF patients, the positive staining with anti-Bcl-2 monoclonal antibody and anti-Fas (anti-APO-1) monoclonal antibody in lung lymphoid follicules suggests the continuous activation of B lymphocytes localized in the lung parenchyma in patients with IPF. The role of apoptosis in fibrosis should be further examined.

Aged↗

PubMed2000

Expression of transforming growth factor-beta type I and type II receptors is altered in rat lungs undergoing bleomycin-induced pulmonary fibrosis.

Transforming growth factor-beta (TGF-beta) is a family of autocrine/paracrine/endocrine cytokines involved in controlling cell growth and extracellular matrix metabolism. TGF-beta exerts its biological effects via binding to type I (TbetaRI) and type II (TbetaRII) receptors. To gain insight into the possible role of TGF-beta receptors in the pathogenesis of pulmonary fibrosis, we investigated the expression of TGF-beta receptors and their ligands in a bleomycin-induced model of pulmonary fibrosis. We found that the expression of both TbetaRI and TbetaRII was altered in rat lungs during pulmonary fibrosis induced by bleomycin. The increase in TbetaRI mRNA level was evident after 3 days of bleomycin administration, and TbetaRI mRNA continually increased for over 12 days after bleomycin instillation, whereas TbetaRII mRNA declined at day 3 post bleomycin instillation and then increased during the reparative phase of lung injury (days 8 and 12). The immunoreactivity for both TbetaRI and TbetaRII was detected in the cells of the interstitium, the epithelium, and the blood vessels of normal rat lungs. In bleomycin-induced pulmonary fibrosis, an extensive immunostaining for TbetaRI and TbetaRII was present in the cells at the sites of injury and active fibrosis. These results demonstrate that the expression of TGF-beta type I and type II receptors was altered during pulmonary fibrosis, suggesting that the TGF-beta signal transduction pathway may be involved in the pathogenesis of lung fibrosis.

Activin Receptors, Type I↗

PubMed1995

Correlation of structure and function in idiopathic pulmonary fibrosis.

The early stage of idiopathic pulmonary fibrosis (IPF) is thought to involve a smaller number of alveoli and to be characterized predominantly by cellularity and minimal fibrosis, whereas advanced disease involves a large number of alveoli and is characterized predominantly by fibrosis with minimal cellularity. In addition, correlative studies have indicated that prognosis and response to therapy is determined in part by the extent of fibrosis and cellularity. This study was undertaken to determine whether pulmonary function assessment would help distinguish between the cellular and fibrotic phases of this disorder, as determined by a semiquantitative pathology scoring system that comprised four factor scores: fibrosis, cellularity, granulation/connective tissue, and desquamation. Ninety-six untreated patients with biopsy-confirmed IPF (27 never smokers, 32 current smokers, and 37 ex-smokers) were evaluated. In the group as a whole, there was no significant relationship between the fibrosis or the connective/granulation tissue factor scores and any of the physiologic parameters. The DLCO correlated with the "desquamation" and the total pathology scores, whereas the TLC and FVC correlated with the cellularity factor score. In the current smokers, the coefficient of elastic retraction, DLCO/VA, and FEV1/FVC ratio were significantly lower than in never smokers and ex-smokers, and TLC and FVC were higher than in never smokers. Also, the mean cellularity and granulation/connective tissue factor scores were significantly lower, and the desquamation factor score was significantly higher than those in never smokers and ex-smokers. Both age and smoking status were significant for the cellularity factor score, whereas for the connective/granulation tissue factor score, age was not significant but smoking status was.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.

Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p < 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis.

Adult↗

PubMed2001

[The research of pancadherin and beta-catenin expression in pulmonary tissue of mice with bleomycin-induced pulmonary fibrosis].

OBJECTIVE: To investigate the changes of pancadherin(Pan-cd) and beta-catenin(beta-cat) expression in pulmonary tissue of mice with bleomycin (BLM)-induced pulmonary injury and explore the relation between the Pan-cd/beta-cat expression and pulmonary fibrosis. METHOD: A single dose of BLM was intratracheally injected to induce pulmonary fibrosis of mice. Animals were killed and immunohistochemical methods were used with polyclonal anti-Pan-cd and anti-beta-cat antiserum. RESULTS: The expression of Pan-cd in type I alveolar cells was down-regulation. The expression of Pan-cd in type II alveolar cells was induced. The expression of Pan-cd and beta-cat in small airway epithelial cells were all down-regulation and were repeated with the way of down-regulation-reparation-down-regulation. The expression of Pan-cd on membrane in small airway epithelial cells decreased, whereas the cytoplasmic expression increased and was repeatedly alternated between cytoplasma with membrane. The expression of Pan-cd in alveolar macrophage and interstitial cells increased. CONCLUSION: The abnormal expression of cadherin and beta-cat may play a role in the pathogenesis of pulmonary fibrosis after pulmonary injury.

Animals↗

PubMed2025

Rare variants and survival of patients with idiopathic pulmonary fibrosis: analysis of a multicentre, observational cohort study with independent validation.

BACKGROUND: Rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in idiopathic pulmonary fibrosis (IPF). We aimed to assess whether rare qualifying variants in monogenic adult-onset pulmonary fibrosis genes are associated with IPF survival. Using polygenic risk scores (PRS), we also evaluated the influence of common IPF risk variants in patients carrying the qualifying variants. METHODS: We identified qualifying variants in telomere and non-telomere genes using whole-genome sequences from individuals clinically diagnosed with IPF and enrolled in the Pulmonary Fibrosis Foundation Patient Registry (PFFPR), a large multicentre, observational cohort study (March 29, 2016 to June 15, 2018, n=888). We also derived a PRS for IPF (PRS-IPF) from known common sentinel IPF variants. The primary outcome was the association between qualifying variants and survival. The secondary outcome was the association between qualifying variants and PRS-IPF. We used logistic regression models adjusted for sex, age at diagnosis, and principal components of genetic heterogeneity to examine the mutual relationship of qualifying variants and PRS-IPF. The association between qualifying variants and PRS-IPF with survival was tested using Cox proportional hazard models adjusted for baseline confounders. Validation of the results was sought in data from an independent multicentre, prospective, observational cohort study of IPF in the UK (PROFILE, May 17, 2010 to Sept 5, 2017, n=472), and results were meta-analysed under a fixed-effects model. FINDINGS: We included 888 patients from PFFPR and 472 from PROFILE, totalling 1360 participants. In the PFFPR, carriers of qualifying variants in monogenic adult-onset pulmonary fibrosis genes were associated with lower PRS-IPF (odds ratio 1·79 [95% CI 1·15-2·81]; p=0·010) and shorter survival (hazard ratio 1·53 [1·12-2·10]; p=7·33 × 10-3). Individuals with the lowest PRS-IPF also had worse survival (1·61 [1·25-2·07]; p=1·87 × 10-4). These findings were validated in PROFILE and the meta-analysis of the results showed a consistent direction of effect across both cohorts. INTERPRETATION: We found non-additive effects between qualifying variants and common risk variants in IPF survival, suggesting distinct disease subtypes and raising the possibility of using PRS to guide sequencing prioritisation. Assessing the carrier status for qualifying variants and modelling PRS-IPF promises to further contribute to predicting disease progression among patients with IPF. FUNDING: Instituto de Salud Carlos III; Instituto Tecnológico y de Eenergías Renovables; Cabildo Insular de Tenerife; Fundación DISA; National Heart, Lung, and Blood Institute of the US National Institutes of Health; and UK Medical Research Council.

Humans↗

PubMed1997

CT findings during phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis.

OBJECTIVE: Most patients with idiopathic pulmonary fibrosis (IPF) show slowly progressive deterioration. However, accelerated deterioration also occurs in patient with IPF who have previously shown slowly progressive deterioration. The purpose of this study was to evaluate the CT findings of accelerated deterioration in patients with IPF. MATERIALS AND METHODS: We evaluated the CT findings of 17 patients with IPF who fulfilled all the following criteria for accelerated deterioration of IPF: exacerbation of dyspnea within 1 month, new diffuse pulmonary opacities on chest radiography, a decrease in arterial oxygen tension (PaO2) of more than 10 mm Hg under similar conditions, and absence of apparent infectious agents and heart failure. Seven patients underwent sequential CT examination. Pathologic specimens were obtained from nine patients. RESULTS: CT findings were classified as peripheral parenchymal opacification (n = 6), multifocal parenchymal opacification (n = 6), and diffuse parenchymal opacification (n = 5). Multifocal lesions developed diffusely in two of the seven patients who underwent sequential CT. These two patients both died. Three of the six patients with a multifocal pattern responded to corticosteroid therapy. All patients with a peripheral pattern showed various degrees of improvement following corticosteroid therapy. Multifocal and diffuse parenchymal opacification corresponded pathologically to acute diffuse alveolar damage. Peripheral parenchymal opacification corresponded pathologically to active fibroblastic foci. CONCLUSION: CT patterns seen during periods of rapid deterioration in patients with IPF may allow predictions of prognosis and of response to treatment.

Aged↗

PubMed2006

Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease despite the available treatment regimes. Increased acid gastroesophageal reflux (GER) occurs in IPF patients. OBJECTIVES: To follow the course of IPF in patients while being treated for acid GER alone. METHODS: A retrospective review of the clinical outcomes of four patients with newly diagnosed IPF and increased acid GER who chose to be treated solely with anti-acid GER therapy were followed up regularly with pulmonary function tests (PFTs) [measuring FVC and the diffusing capacity of the lung for carbon monoxide] over a period of 2 to 6 years. Anti-acid GER therapy was administered using proton-pump inhibitors and fundoplication, if needed. Adequate suppression of acid GER was ascertained by 24-h esophageal pH monitoring. MAIN RESULTS: PFT results in all four patients stabilized or improved while their conditions were maintained with adequate treatment for acid GER. All patients were alive at the last follow-up, and none manifested an acute exacerbation of IPF or needed treatment for respiratory problems during this period. After maintaining 4 years of improved status (based on PFT and exercise testing findings) while adhering to treatment for acid GER, one patient's deterioration correlated with poor compliance to daily treatment during the fifth year, although the PFT results at the sixth year showed stabilization compared to baseline values. The condition of another patient was stabilized by adhering to anti-acid GER treatment after an initial period of deterioration that was associated with nonadherence CONCLUSIONS: Future clinical studies are indicated to clarify the role of acid GER in IPF and to determine whether adequate treatment for increased acid GER in part improves the outcome of patients with IPF.

Aged↗

PubMed2000

GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism.

To characterize the role of GM-CSF in pulmonary fibrosis, we have studied bleomycin-induced fibrosis in wild-type mice vs mice with a targeted deletion of the GM-CSF gene (GM-CSF-/- mice). Without GM-CSF, pulmonary fibrosis was worse both histologically and quantitatively. These changes were not related to enhanced recruitment of inflammatory cells because wild-type and GM-CSF-/- mice recruited equivalent numbers of cells to the lung following bleomycin. Interestingly, recruitment of eosinophils was absent in GM-CSF-/- mice. We investigated whether the enhanced fibrotic response in GM-CSF-/- animals was due to a deficiency in an endogenous down-regulator of fibrogenesis. Analysis of whole lung homogenates from saline- or bleomycin-treated mice revealed that GM-CSF-/- animals had reduced levels of PGE2. Additionally, alveolar macrophages were harvested from wild-type and GM-CSF-/- mice that had been exposed to bleomycin. Although bleomycin treatment impaired the ability of alveolar macrophages from wild-type mice to synthesize PGE2, alveolar macrophages from GM-CSF-/- mice exhibited a significantly greater defect in PGE2 synthesis than did wild-type cells. Exogenous addition of GM-CSF to alveolar macrophages reversed the PGE2 synthesis defect in vitro. Administration of the PG synthesis inhibitor, indomethacin, to wild-type mice during the fibrogenic phase postbleomycin worsened the severity of fibrosis, implying a causal role for PGE2 deficiency in the evolution of the fibrotic lesion. These data demonstrate that GM-CSF deficiency results in enhanced fibrogenesis in bleomycin-induced pulmonary fibrosis and indicate that one mechanism for this effect is impaired production of the potent antifibrotic eicosanoid, PGE2.

Animals↗

PubMed2006

[Inhibition of pulmonary fibrosis by doxycycline: an experiment with mice].

OBJECTIVE: To investigate the effect of doxycycline, an antimicrobial antibiotic inhibiting type IV collagenase, on the development of pulmonary fibrosis induced by bleomycin (BLM) in mice. METHODS: Gelatin zymography assay was used to detect the secretion of 72,000 and 92,000 type IV collagenase in HT-1080 cells and the activity of these enzymes in vitro. Experimental pulmonary fibrosis was induced by intra-tracheal administration of BLM in anesthetized mice. Total lung collagen content was determined by hydroxyproline assay. The histopathological changes of pulmonary fibrosis were evaluated by image analysis. RESULTS: The secretion of 72,000 and 92,000 type IV collagenase in HT-1080 cell was markedly inhibited by doxycycline at concentrations of 0.1 mg/ml and 0.05 mg/ml. The activity of type IV collagenase in vitro was also suppressed by doxycycline. The hydroxyproline level in the lung was decreased in mice treated with doxycycline at the dose of 100 mg/kg, down to 34.7% of that of the BLM model group. As shown by image analysis, the extensiveness of fibrotic lesions, the thickness of interalveolar septa, and the accumulation of nucleated cells were decreased in doxycycline treated group in comparison with BLM model group. CONCLUSION: This study provides evidence that doxycycline shows inhibitory effect on BLM induced pulmonary fibrosis.

Animals↗

PubMed1979

Methotrexate-induced diffuse interstitial pulmonary fibrosis.

Three patients received respectively 190 mg, 175 mg, and 196 mg of methotrexate and developed bilateral pulmonary infiltrates without evidence of peripheral blood eosinophilia. Sputum in the three cases failed to reveal acid-fast bacilli, pathogenic fungi, or opportunistic organisms by cultures and appropriate stains. Despite discontinuance of the drug and/or institution of corticosteroid therapy, progressive respiratory failure led to death. In all three cases, autopsy revealed gross and microscopic features indistinguishable from those seen in the Hamman-Rich syndrome, and methotrexate hepatotoxicity was present in one. Pulmonary eosinophilia or granulomas, classically seen in previously reported cases of methotrexate pneumonitis, were not observed. It is suggested therefore that methotrexate be added to the list of agents capable of inducing diffuse interstitial pulmonary fibrosis. Conversely, diffuse interstitial pulmonary fibrosis should be considered in the differential diagnosis of patients receiving methotrexate who develop bilateral pulmonary infiltrates seen on chest roentgenograms.

Aged↗

PubMedDate not supplied

Rapidly progressive pulmonary fibrosis in a patient treated with danazol for idiopathic thrombocytopenic purpura.

The case of a patient that developed pulmonary fibrosis two months after initiation of danazol for treatment of idiopathic thrombocytopenic purpura is described. Bilateral pneumothoraxes and pneumomediastinum complicated the rapidly fatal pulmonary fibrosis. An association between danazol therapy and the development of pulmonary fibrosis is suspected. There is only one other case report with this connection in the literature.

Aged↗

PubMed2006

Clinical review: idiopathic pulmonary fibrosis--past, present and future.

Idiopathic pulmonary fibrosis (IPF) is an important, and devastating, interstitial lung disease. It has a median mortality of only 3 years, worse than many cancers, and its incidence continues to rise. In this article, an overview of key developments in our understanding and clinical management of IPF will be provided.

Administration, Oral↗

PubMed2004

Pulmonary fibrosis: thinking outside of the lung.

Pulmonary fibrosis is a devastating condition that leads to progressive lung destruction and scarring. Previous mechanistic research has focused on the local fibroproliferative process in the lung. However, emerging evidence suggests that circulating cells of hematopoietic origin play a crucial role in the pathogenesis of this disease.

Animals↗