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PubMed1992

Alveolar accumulation of fibronectin and hyaluronan precedes bleomycin-induced pulmonary fibrosis in the rat.

The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 30 days after an intratracheal instillation of bleomycin. Fibronectin was visualized in histological sections and quantified in bronchoalveolar lavage fluid (BALF) and related to simultaneous measurements of hyaluronan, collagen and albumin in BALF and/or lung tissue extracts. An increase in BALF fibronectin levels was noted after 3 days and the peak value a sixty fold increase was noted at day 7. Thereafter, the fibronectin levels declined and reached control values on day 21. A pronounced, patchily distributed staining for fibronectin appeared in the injured alveolar tissue parallel to the increased lavage fluid fibronectin levels on days 3-7. A fainter, streakily distributed fibronectin staining remained within the alveolar walls in areas with proliferating fibroblasts on days 14-30. Albumin in BALF increased to a peak level, 20 times control values, after 3 days and then rapidly declined. Thus, the ratio of fibronectin to albumin increased to a peak value of 43 times control values on day 7, indicating that plasma leakage cannot be the only source of the observed increase in lavage fibronectin. Lung tissue hydroxyproline increased between days 7 and 30, whereas extractable hyaluronan in lung tissue and bronchoalveolar lavage fluid peaked on days 3-7 and then gradually declined towards normal values on days 21-30. These data demonstrate that fibronectin accumulates in the alveolar tissue during the early inflammatory phase of the bleomycin-induced lung injury, parallelling hyaluronan accumulation and preceding the development of pulmonary fibrosis.

Animals↗

PubMed1985

Type III procollagen N-terminal peptides in experimental pulmonary fibrosis and human respiratory diseases.

In order to detect the fibrotic response in lung-tissue, concentrations of type III procollagen N-terminal peptide (P-III-P) were examined in sera and bronchoalveolar lavage fluids from rabbits with bleomycin-induced pulmonary fibrosis, and in sera from patients with various respiratory diseases, using a radioimmunoassay method. In the bleomycin-induced pulmonary fibrosis, a significant (p less than or equal to 0.05) rise in P-III-P levels was observed in the lavage fluid at 7 days, and in the sera at 21 days after bleomycin treatment, with histological confirmation of pulmonary fibrosis. Many of the patients with pulmonary fibrotic changes had significantly elevated serum P-III-P level. In lung cancer patients, most of the post-radiation serum samples were found to have P-III-P levels greater than or equal to 18 ng/ml. These results suggest that the increase in P-III-P levels is the reflection of fibrotic changes in the lungs and that the clinical assessment of serum P-III-P level could be important in the early detection of pulmonary fibrosis.

Animals↗

PubMed2005

The clinical course of patients with idiopathic pulmonary fibrosis.

BACKGROUND: Prospective data defining the clinical course in idiopathic pulmonary fibrosis (IPF) are sparse. OBJECTIVE: To analyze the clinical course of patients with mild to moderate IPF. DESIGN: Analysis of data from the placebo group of a randomized, controlled trial evaluating interferon-gamma1b. SETTING: Academic and community medical centers. PATIENTS: 168 patients in the placebo group of a trial evaluating interferon-gamma1b. MEASUREMENTS: Measures of physiology and dyspnea assessed at 12-week intervals; hospitalizations; and the pace of deterioration and cause of death over a median period of 76 weeks. RESULTS: Physiologic variables changed minimally during the study. However, 23% of patients required hospitalization for a respiratory disorder and 21% died. Idiopathic pulmonary fibrosis was the primary cause of death in 89% of patients who died, and an apparent acute clinical deterioration preceded death in 47% of these patients. LIMITATIONS: The instrument used to define the pace of deterioration and cause of death was applied retrospectively. CONCLUSIONS: Recognition of the common occurrence of acute fatal deterioration in patients with mild to moderate IPF has important implications for monitoring patients and supports early referral for lung transplantation.

Aged↗

PubMed2005

Lack of evidence for an association between neurofibromatosis and pulmonary fibrosis.

STUDY OBJECTIVES: To reassess the association between neurofibromatosis and pulmonary fibrosis. DESIGN: Retrospective single-center study with analysis of patients' chest radiographs, CT scans, and medical records. SETTING: Tertiary care, referral medical center. PATIENTS: One hundred fifty-six adult patients with neurofibromatosis seen over a 6-year period between 1997 and 2002. RESULTS: A review of chest radiographs revealed abnormal findings in 70 patients (44.9%). The most common radiographic abnormalities were extrapulmonary nodules or masses seen in 22 patients (14.1%), followed by skeletal abnormalities in 16 patients (10.3%). Bilateral interstitial infiltrates were noted in only three patients (1.9%), all of whom had potential causes other than neurofibromatosis for their lung infiltrates, including smoking-related interstitial lung disease, rheumatoid lung disease, recurrent pneumonias, and a history of ARDS. CT scans were available in two of these patients and revealed nonspecific patterns of abnormalities with no honeycombing. Six patients had bullae or cystic airspaces demonstrated on chest radiography or CT scan; all of these findings occurred in the context of smoking-related emphysema. Combined together, bilateral interstitial lung infiltrates or cystic airspaces were demonstrated in five patients (3.2%) by chest radiography, and in eight patients (5.1%) by chest radiography or CT scanning; one patient had both findings on the CT scan. CONCLUSIONS: We found little evidence to support an association between neurofibromatosis and pulmonary fibrosis or any other form of parenchymal lung disease. Interstitial lung disease and bullae described in association with neurofibromatosis in previous reports may have, in part, represented smoking-induced manifestations.

Adult↗

PubMed2006

[Lung transplantation for pulmonary fibrosis: report of 10 cases].

OBJECTIVE: To discuss the operative technique, patient selection and perioperative management of lung transplantation for pulmonary fibrosis. METHODS: From September 2002 to December 2005, 31 cases of lung transplantations were performed in our hospital. There were 10 cases receiving single lung transplantation for pulmonary fibrosis, among them 2 received right lung transplantation with cardio pulmonary bypass, and one received contralateral lung transplantation-a left donor lung implanted in the recipient's right thorax. RESULTS: The in-hospital mortality was 10.0% (1/10). Nine patients were discharged from hospital, while one patient died of severe infection on the 137th postoperative day. During follow-up, one patient died of infection 9 months and another patient died of an accident 25 months after the operation. The 7 other patients were alive with improved lung functions. CONCLUSION: Lung transplantation is effective in improving the survival of selected patients with idiopathic pulmonary fibrosis.

Adult↗

PubMed2002

Long-term survival despite early loss of graft function after single lung transplantation for pulmonary fibrosis.

We report a patient who received a single, left lung transplantation for idiopathic pulmonary fibrosis. The effect of the graft on pulmonary improvement was only temporary, because the patient developed obliterative bronchiolitis (OB), resulting in complete destruction of the graft. The patient, however, remains alive 6 years after OB was diagnosed, apparently as a consequence of native lung improvement with triple-immunosuppressive medicine. This case is of interest for several reasons: first, it shows that pulmonary fibrosis may respond to intensive immunosuppressive therapy; second, it demonstrates that ventilation scintigraphy is useful in addition to pulmonary function tests in estimating the actual function of the graft after single lung transplantation; and third, it appears that the gradation of bronchiolitis obliterans syndrome (BOS) after single lung transplantation may overestimate the true function of the transplant.

Adolescent↗

PubMed1999

Surfactant abnormalities in idiopathic pulmonary fibrosis, hypersensitivity pneumonitis and sarcoidosis.

Bronchoalveolar lavage fluids (BALF) from patients with idiopathic pulmonary fibrosis (IPF; n=36), hypersensitivity pneumonitis (HP; n=32) and sarcoidosis (n=44) were investigated for their surfactant properties and compared to healthy control subjects (n=29). The phospholipid (PL) and protein concentration, the PL:protein ratio, PL subclasses, and the surfactant apoproteins (SP)A and SP-B were quantified in BALF. Large surfactant aggregates (LSA) were measured by means of ultracentrifugation and assayed for surface activity using the pulsating bubble surfactometer. As compared to controls, SP-A concentrations, LSA content and PL:protein ratios were significantly decreased in all groups, whereas PL and SP-B concentrations remained unchanged. Changes in the phospholipid profile, with reduced percentages of phosphatidylcholine (not significant) and phosphatidylglycerol and increased fractions of phosphatidylinositol and sphingomyelin (p<0.05), occurred more in IPF than in HP, and not in sarcoidosis. Surface activity was found to be severely impaired in IPF (minimum surface tension (gamma min) approximately 15-20 mN x m(-1)), but only modestly affected in HP and sarcoidosis (gamma min approximately 5 mN x m(-1)) compared to controls (gamma min approximately 0 mN x m(-1)). Reconstitution of pelleted surfactant material with soluble BALF proteins further increased gamma min values. In conclusion, moderate changes in biochemical and physical surfactant properties are encountered in hypersensitivity pneumonitis and sarcoidosis, but pronounced disturbances occur in idiopathic pulmonary fibrosis.

Adolescent↗

PubMed1999

Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis.

BACKGROUND AND AIM: A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-alpha in lung tissue of patients with idiopathic pulmonary fibrosis compared to control lung tissue. METHODS: Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale. RESULTS: Eleven patients with IPF were compared to seven control subjects. TGF-alpha immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF-R, one of the receptors for TGF-alpha, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. CONCLUSIONS: TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells.

Adult↗

PubMed2004

Serum concentrations of soluble P-selectin glycoprotein ligand-1 are increased in patients with systemic sclerosis: association with lower frequency of pulmonary fibrosis.

OBJECTIVE: To determine serum concentrations of soluble P-selectin glycoprotein ligand-1 (sPSGL-1) and its clinical associations in patients with systemic sclerosis. METHODS: Serum sPSGL-1 concentrations from 65 patients with systemic sclerosis were examined by enzyme linked immunosorbent assay. In a retrospective longitudinal study, 177 sera from 35 patients with systemic sclerosis were analysed (follow up 0.3 to 6.3 years) RESULTS: Serum sPSGL-1 was raised in patients with limited cutaneous systemic sclerosis (lSSc) (n = 34) and diffuse cutaneous systemic sclerosis (dSSc) (n = 31) compared with healthy controls (n = 22) and patients with systemic lupus erythematosus (n = 20) or dermatomyositis (n = 20). Patients with systemic sclerosis who had raised sPSGL-1 concentrations less often had pulmonary fibrosis and decreased vital capacity (%VC) than those with normal sPSGL-1 levels. sPSGL-1 concentrations were positively correlated with %VC in patients with systemic sclerosis. In the longitudinal study, patients with systemic sclerosis but without pulmonary fibrosis had consistently increased sPSGL-1 concentrations in the early phase, while those with pulmonary fibrosis had decreased sPSGL-1 throughout the follow up period. CONCLUSIONS: A raised serum sPSGL-1 is associated with a lower frequency and severity of pulmonary fibrosis in systemic sclerosis. sPSGL-1 could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.

Adolescent↗

PubMed1989

Malotilate prevents accumulation of type III pN-collagen, type IV collagen, and laminin in carbon tetrachloride-induced pulmonary fibrosis in rats.

Orally administered malotilate was studied as a protective antifibrotic agent with respect to experimentally induced pulmonary fibrosis in rats using immunohistochemical methods. Specific antibodies raised in rabbits against the aminoterminal propeptide of human type III procollagen and against two basement membrane proteins, the 7S domain of human type IV collagen and the P1 fragment of human laminin, were used for the immunohistochemical analysis, and the result was confirmed by morphometry. Intraperitoneally injected carbon tetrachloride significantly increased the volume densities of reticulin fibers, type III pN-collagen, type IV collagen, and laminin, whereas treatment with malotilate completely normalized these. Binding of the antibodies to rat antigens was also demonstrated by immunoelectron microscopy in which the collagen fibers with a typical periodic pattern were labeled positively with rabbit antitype III procollagen, whereas the amorphous basement membrane material reacted positively with rabbit antitype IV collagen and antilaminin, indicating good, specific cross-reactivity between these antibodies and the rat antigens. It is concluded that malotilate prevents the accumulation of type III pN-collagen and two basement membrane proteins, type IV collagen and laminin, in experimental pulmonary fibrosis, and can potentially be developed to provide a useful drug for preventing pulmonary fibrosis in humans.

Animals↗

PubMed1993

Expression and localization of tumor necrosis factor-alpha and its mRNA in idiopathic pulmonary fibrosis.

The expression of tumor necrosis factor alpha and its mRNA was investigated in surgical biopsies from idiopathic pulmonary fibrosis by immunohistochemistry, in situ hybridization, and Northern blotting. Normal areas of lungs resected for cancer were used as controls. Tumor necrosis factor alpha mRNA levels were higher in idiopathic pulmonary fibrosis than in normal lungs as determined by Northern blots. In normal lungs, tumor necrosis factor alpha and its mRNA were identified in alveolar and interstitial macrophages. In fibrotic lungs, tumor necrosis factor alpha was detected in macrophages and, to a greater extent, in epithelial cells (presumably type II cells) lining the thickened septae. Tumor necrosis factor alpha mRNA was found only in some interstitial cells and some of the cells lining the alveolar septae. An elevated concentration of tumor necrosis factor = alpha, particularly within the alveolar epithelium, might contribute to the alveolar damage and proliferation of interstitial cells in idiopathic pulmonary fibrosis.

Adult↗

PubMed2001

[Role of fibronectin in rat pulmonary fibrosis].

OBJECTIVE: To study the roles of fibronectin (FN) played in rat pulmonary fibrosis. METHODS: The dynamic change of FN was observed in bleomycin-induced rat pulmonary fibrosis using immunohistochemical technique. Northern blot analysis and immunocytochemistry techniques were performed to detect the expression of type I, III procollagen mRNA and their relevant proteins in cultured rat pulmonary fibroblasts (PFbs) after FN treatment. RESULTS: (1) The pulmonary tissue of rats which received bleomycin showed continuously strong positive reaction with anti-FN. (2) The expression of type I, III procollagen mRNA in rat PFbs enhanced at 2 h after FN treatment, and reached their peaks at 6 h, 12 h respectively. The expression of type I, III procollagen proteins detected by immunocytochemistry was also increased after the FN treatment (P < 0.01). Anti-integrin alpha(5) monoclonal antibody could partially inhibit the effect of FN on enhancing the expression of type I, III procollagen in PFbs (P < 0.05). CONCLUSIONS: FN could up-regulate the synthesis of type I, III procollagen mainly by enhancing the transcriptions of procollagen genes.

Animals↗

PubMed2003

[Chronic hypersensitivity pneumonitis or idiopathic pulmonary fibrosis? Diagnostic role of high resolution Computed Tomography (HRCT)].

PURPOSE: In the diagnosis of extrinsic allergic alveolitis, high-resolution computed tomography (HRCT) is more sensitive and more specific than radiography; however, the accuracy of HRCT is not absolute. The role of HRCT in this field has scarcely been investigated in the literature. The purpose of this paper is to explore the possibilities of HRCT in this field and to analyse the correlations between HRCT and functional parameters. MATERIALS AND METHODS: We performed a retrospective blind evaluation the HRCT scans of 24 patients (19 males and 5 females). Twelve were affected by idiopathic pulmonary fibrosis (IPF); 12 had chronic extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. The HRCT findings were studied by two radiologists, who were not aware of the diagnoses. The possible differences in evaluation were subsequently resolved by consensus. In the presence of interstitial fibrosis, we recorded the prevailing site and the anatomical extension (with the method of the visual percentage score, described in the literature). In all the cases, we recorded the blood gas values (PaO2, PaCO2, and pH), total lung capacity (TLC), forced expiratory volume in 1 second (FEV1), Vital Capacity (VC), Tiffeneau index (FEV1/VC) and monoxide carbon diffusion (DLCO). The statistical significance of the correlations was investigated using the Mann-Whitney and Wilcoxon tests. Student "t"-test and Pearson's chi squared were used to compare the variables of the different groups. A value of p< or =0.05 was considered significant. RESULTS: Overall, the diagnosis was formulated with a high degree of confidence in 13 of 24 cases (54.1%); in these patients, the result was correct in 84.6% of cases (11 of 13). In the diagnosis of EAA, HRCT sensitivity was 50%, with 91.6% specificity, 70.8% accuracy. In the diagnosis of IPF, HRCT sensitivity was 75%, with 83.3% specificity, 79.1% accuracy. The HRCT signs of interstitial fibrosis were visible in 11 cases of IPF (91.6%) and in 4 cases of EAA (33.3%), with significant statistical difference (p<0.005). In the analysis of the whole series (24 patients) we found a significant inverse correlation between the HRCT score of fibrosis and the extension of the areas with air-trapping (p<0.003). There was no significant difference between IPF and EAA considering age, FEV1, PaO2, PaCO2 and pH. We found inverse correlation (p<0.001) between HRCT extension of the fibrosis and DLCO. There was a significant difference between pulmonary fibrosis and extrinsic allergic alveolitis considering TLC (in average, respectively: 65% and 84.3%; p<0.02), and DLCO (respectively 40.4% and 74.7%; p<0.03). DISCUSSION AND CONCLUSIONS: HRCT is a reliable and strong method to be used in particularly complex fields. We found signs of interstitial fibrosis more frequently in IPF than in EAA (91.6% versus 33.3%). In IPF cases, the extension of the fibrosis--evaluated with the visual score method--was higher then in EAA (34.7% versus 6%). The presence of fibrosis with basal and peripheral distribution was characteristic of idiopathic pulmonary fibrosis, with good sensitivity and specificity (75%), whereas in chronic extrinsic allergic alveolitis the areas of fibrosis often presented an irregular and heterogeneous distribution, in 91.6% of cases. However, 25% of extrinsic allergic alveolitis cases had a distribution mimicking idiopathic pulmonary fibrosis. The presence of areas with increased ground-glass opacity is more common in EAA than in IPF (66.6% versus 33.3%). Areas of mosaic attenuation, visible in inspiratory CT scans, are not rare in IPF (41.6% of cases), and generally have a basal distribution. The presence of hyperlucent lobules inside the fibrotic areas does not exclude the diagnosis of IPF. The finding of the expiratory air-trapping is more common in chronic EAA than in IPF, and the extension of this areas is greater in EAA (17.3% versus 6.5%). We found an inverse correlation between the extension of the fibrosis and the expiratory trapping. Signs of emphysema were observed in 25% of cases, wiema were observed in 25% of cases, with equal prevalence and the same extension in IPF and in EAA. All patients were smokers or ex-smokers. Smoking has not been demonstrated to have a protective effect against EAA. The areas of mosaic perfusion during inspiration do not represent a sound criterion for the differential diagnosis between IPF and chronic EAA. In fact, they can also be frequently found in IPF. HRCT can be employed in clinical practice for the differential diagnosis between IPF and chronic EAA with good (but not absolute) accuracy.

Alveolitis, Extrinsic Allergic↗

PubMed1998

[Expressions of TNF alpha, PDGF in alveolar type II epithelial cells of rats with bleomycin-induced pulmonary fibrosis].

OBJECTIVE: The expressions of TNF alpha and PDGF in alveolar type II epithelial cells of rats with bleomycin(BLM)-induced pulmonary fibrosis were studied. METHOD: A single intratracheal injection of BLM was administrated to induce pulmonary fibrosis of rats. Animals were killed at day 3,7,14 and 28 after BLM-administration. The immunohistochemical methods were used to analyze the expressions of TNF alpha and PDGF proteins in alveolar epithelium of rats. The total RNA was extracted from the alveolar type II epithelial cells of rats and the expressions of TNF alpha and PDGF mRNA were analyzed with Northern blot. RESULT: TNF alpha and PDGF were expressed in the alveolar type II epithelial cells of BLM-administrated rats. The expression of TNF alpha elevated in median and late-stage of the process and reached the peak at day 28. While the expression of PDGF elevated in early-stage and reached the peak at day 7. By contrast, TNF alpha and PDGF weren't expressed in the alveolar type II epithelial cells of normal controls. CONCLUSION: The results show that the alveolar type II epithelial cell from rats with pulmonary fibrosis overexpresses TNF alpha and PDGF and they may play roles in the pathogenesis of lung fibrosis.

Animals↗

PubMed2004

Idiopathic pulmonary fibrosis: pathogenesis and therapeutic approaches.

Idiopathic pulmonary fibrosis (IPF), also termed cryptogenic fibrosing alveolitis, is a clinicopathological syndrome characterised by cough, exertional dyspneoa, basilar crackles, a restrictive defect on pulmonary function tests, honeycombing on high-resolution, thin-section computed tomographic scans and the histological diagnosis of usual interstitial pneumonia on lung biopsy. The course is usually indolent but inexorable. Most patients die of progressive respiratory failure within 3-8 years of the onset of symptoms. Current therapies are of unproven benefit. Although the pathogenesis of IPF has not been elucidated, early concepts focused on lung injury leading to a cycle of chronic alveolar inflammation eventuating in fibrosis and destruction of the lung architecture. Anti-inflammatory therapies employing corticosteroids or immunosuppressive or cytotoxic agents have been disappointing. More recent hypotheses acknowledge that sequential alveolar epithelial cell injury is likely to be a key event in the pathogenesis of IPF, but the cardinal event is an aberrant host response to wound healing. In this context, abnormal epithelial-mesenchymal interactions, altered fibroblast phenotypes, exaggerated fibroblast proliferation, and excessive deposition of collagen and extracellular matrix are pivotal to the fibrotic process. Several clinical trials are currently underway or in the planning stages, and include drugs such as interferon-gamma 1b, pirfenidone, acetylcysteine, etanercept (a tumor necrosis factor-alpha antagonist), bosentan (an endothelin-1 receptor antagonist) and zileuton (a 5-lypoxygenase inhibitor). Future therapeutic strategies should be focused on alveolar epithelial cells aimed at enhancing re-epithelialisation and on fibroblastic/myofibroblastic foci, which play an essential role in the development of IPF. Stem cell progenitors of the alveolar epithelial cells and genetic and epigenetic therapies are attractive future approaches for this and other fibrotic lung disorders.

Clinical Trials as Topic↗

PubMed2006

A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18.

RATIONALE: Recently, models of macrophage activation have been revised. Macrophages stimulated with Th2 cytokines have been classified as alternatively activated. OBJECTIVES: This article examines the expression and regulation of CC chemokine ligand 18 (CCL18), a marker of alternative activation, by human alveolar macrophages (AMs). METHODS: AM were obtained from bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis, sarcoidosis, or hypersensitivity pneumonitis (n = 69) and healthy volunteers (n = 22). Expression of CCL18 was determined by quantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, flow cytometry, and immunohistochemistry, respectively. MEASUREMENTS AND MAIN RESULTS: Spontaneous CCL18 production by BAL-derived cells was markedly increased in patients with pulmonary fibrosis and correlated negatively with pulmonary function test parameters. CCL18 gene expression and protein production were up-regulated in normal AMs after Th2 cytokine stimulation and/or coculture with human lung fibroblasts. Native collagen significantly up-regulated CCL18 expression in normal AMs activated with Th2 cytokines via a mechanism mediated by beta2-integrin/ scavenger receptor(s). Culture supernatants of AMs from patients with idiopathic pulmonary fibrosis increased collagen production by normal lung fibroblasts partly mediated via CCL18. CONCLUSIONS: Our findings suggest that AMs from patients with pulmonary fibrosis disclose a phenotype of alternative activation and might be a part of a positive feedback loop with lung fibroblasts perpetuating fibrotic processes.

Biopsy↗

PubMed1999

[In vitro studies on the bioactive materials released by lung fibroblasts in experimental pulmonary fibrosis].

OBJECTIVES: The purpose of the present study was to clarify the consecutive changes and roles of hyaluronan (HA), interleukin-8 (IL-8) and collagen production by lung fibroblasts in the course of pulmonary fibrosis. METHODS: Quantitative and comparative assessments of the HA, IL-8 and collagen (presented by hydroproline; HYP) levels in lung fibroblast-conditioned media were made at various stages during the development of bleomycin-induced pulmonary fibrosis in rats. RESULTS: In lung fibroblast-conditioned media of bleomycin-treated animals: (1) The HA levels increased significantly on day 1, peaked on day 3, and then gradually declined and returned to control values on days 14 - 28. (2) The IL-8 levels strikingly increased on day 1, reached the peak values on day 7, thereafter, gradually decreased, regained control values by day 28. (3) The collagen levels increased significantly on day 7, peaked on day 14, and then gradually declined, However, remained significantly above normal values on day 28. (4) In bleomycin group, the HA and IL-8 levels both significantly correlated to cell components in BALF. CONCLUSIONS: The lung fibroblasts were activated, produced increased HA and IL-8, and were the main source of HA and IL-8 within the lung in the early stage of pulmonary fibrosis; increased HA and IL-8 synthesis of lung fibroblasts might reflect the intensity of alveolitis and the disease activity; The excessive collagen deposition within the lung primarily occurred at the middle stage of pulmonary fibrosis.

Animals↗

PubMed2005

Susceptibility to oxygen desaturation during bronchoscopy in elderly patients with pulmonary fibrosis.

BACKGROUND: Fiber-optic flexible bronchoscopy (FFB) is a frequently performed procedure for the diagnosis and treatment of pulmonary disorders. However, hypoxemia occasionally occurs during FFB. OBJECTIVES: We attempted to examine the causes of arterial oxygen desaturation during FFB. METHODS: We studied 336 patients who underwent FFB without intervention between June 1, 2001 and September 30, 2002. Arterial oxygen saturation (SpO2) was continuously monitored using oximetry with a recording system. We analyzed the relationship between a reduction in SpO2 during FFB and various clinical parameters or background lung diseases. RESULTS: Of the 336 patients, 73 (22%) had an episode of oxygen desaturation (SpO2 <90% over 10 s). Of patients over 80 years old, 55% had an episode of oxygen desaturation, which was significantly higher than 27% observed in the patients of 80 and less than 80 years old (p < 0.05). Patients with pulmonary fibrosis had a higher risk of desaturation (55%) compared to patients with other complications or patients without any complication (p < 0.05). Multivariable analysis revealed that both age and pulmonary fibrosis were independent predictors of oxygen desaturation. However, the majority of the patients (94%) did not require routine oxygen supplementation. CONCLUSION: Although FFB is safe and does not require oxygen supplementation in most cases, age over 80 years and pulmonary fibrosis are high risk factors for significant oxygen desaturation during FFB.

Adult↗