PubMed Health⌕ Search

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 1,081 records · Page 60Linked to original sources
PubMed1992

Administration of alpha 1-proteinase inhibitor ameliorates bleomycin-induced pulmonary fibrosis in hamsters.

The effect of alpha 1-proteinase inhibitor (alpha 1Pi) administration on the acute lung injury and subsequent fibrosis induced by bleomycin (BLM) was examined in hamsters. Pulmonary lesions were quantitatively reduced in alpha 1Pi-administered BLM-treated (BLM-alpha 1Pi) animals compared with animals treated by BLM alone (BLM-control) at both 7 days (acute stage) and 30 days (fibrotic stage) after BLM treatment. Analysis of intraalveolar cells from bronchoalveolar lavage (BAL) fluid revealed that neutrophils and lymphocytes were significantly decreased in the BLM-alpha 1Pi animals at 7 days after BLM treatment and that 30 days after BLM treatment macrophages as well as neutrophils and lymphocytes were remarkably decreased in the BLM-alpha 1Pi animals. The elastase activity in supernatants of BAL fluid during 7 days following BLM treatment was detected, but there was no difference between the two groups. In vitro studies on neutrophil responsiveness to stimulation of BAL fluid at 3 days after BLM treatment revealed noticeable chemotaxis and generation of superoxide anion of isolated neutrophils, but alpha 1Pi did not show any inhibitory effects on neutrophil responsiveness. We suggest that alpha 1Pi administration ameliorates pulmonary fibrosis preceded by acute lung injury induced by BLM treatment in hamsters and that the inhibitory effects of alpha 1Pi on lung injury may not be brought about by altered elastase activity, chemotaxis, or superoxide generation in neutrophils. Alternative mechanisms are discussed.

Animals↗
PubMed1983

Experimental production of diffuse pulmonary fibrosis and alveolitis in cattle: the effects of repeated dosage with 3, methyl indole.

Eleven Friesian steers were given 3, methyl indole (3MI) orally at dose rates ranging from 0.1 to 0.3 g/kg. Three of these (group B) received a single oral dose of 0.2 g/kg and subsequently developed respiratory distress. Their plasma 3MI concentrations six hours after dosing were between 2.25 and 7.23 micrograms/ml. The steer with the highest six-hour plasma value died at this stage and the dominant pathological feature was severe pulmonary oedema. The other two steers survived until they were slaughtered 96 hours after dosing; the major pathological findings in them were interstitial emphysema, hyaline membranes and alveolar epithelial hyperplasia. The other eight steers (group C) each received weekly oral doses of 0.1 g 3MI/kg for 10 weeks. One animal died after developing severe respiratory distress following its third dose. Thereafter, the others developed two separate patterns of response. Three steers (subgroup C1) became progressively more tolerant to oral 3MI, even in the face of dose rates increased to 0.2 and 0.3 g/kg during the 11th to 14th weeks of the study and also in the presence of relatively high plasma 3MI concentrations after dosing. One animal was slaughtered after its 10th dose and two after their 14th dose of 3MI; post mortem examinations revealed that their lungs were macro- and microscopically normal. The other steers (subgroup C2) all continued to react after each weekly oral dose of 3MI and their post-dosing plasma 3MI concentrations consistently remained relatively low. Latterly, each of the three steers which survived to the 14th week also exhibited persistent tachypnoea and marked hyperpnoea between dosings. On post mortem examination, in addition to the signs generally associated with acute 3MI toxicity (see above), each of the subgroup C2 steers were found to have diffuse pulmonary fibrosis and an alveolitis. While certain cattle appear to become tolerant to the effects of repeated doses of 3MI, the results of this study clearly demonstrated that, in others, such treatment eventually gives rise to diffuse pulmonary fibrosis and alveolitis.

Animals↗
PubMed2006

Racial and ethnic disparities in survival in lung transplant candidates with idiopathic pulmonary fibrosis.

Minority patients have worse outcomes than nonminority patients in a variety of pulmonary diseases. We aimed to compare the survival of Black and Hispanic patients to that of others with idiopathic pulmonary fibrosis (IPF). We performed a retrospective cohort study of patients with IPF who were evaluated for lung transplantation at our center. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare survival between groups. Black and Hispanic patients had spirometry, lung volumes and diffusion capacity that were similar to others, but had worse exercise capacity. Minority patients had a significantly increased risk of death compared to others independent of transplantation status (hazard ratio = 3.3, 95% CI 1.2-8.9, p = 0.02). Differences in exercise capacity, pulmonary hemodynamics and socioeconomic factors appeared to account for some of the differences in survival. Black and Hispanic patients with IPF had an increased risk of death following referral for lung transplantation. This finding may be due to differences in disease progression and/or differences in access to medical care among minority patients. Future studies should confirm our findings in a larger cohort. The elimination of racial and ethnic disparities in outcome should be a priority for clinicians and researchers in this field.

Aged↗
PubMed2006

Serum levels of monocyte chemotactic protein-3/CCL7 are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis.

OBJECTIVE: To determine serum levels of monocyte chemotactic protein-3 (MCP-3) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum MCP-3 levels from 69 patients with SSc were examined by ELISA. RESULTS: Serum MCP-3 levels were raised in patients with SSc (n = 69) compared with healthy controls (n = 28). Patients with diffuse cutaneous SSc (n = 36) had higher levels of serum MCP-3 than those with limited cutaneous SSc (n = 33). Patients with raised MCP-3 levels had pulmonary fibrosis and decreased vital capacity (VC) more often than those with normal MCP-3 levels. MCP-3 levels correlated positively with the extent of skin fibrosis, and inversely with %VC and carbon monoxide transfer factor (Tlco) in patients with SSc. CONCLUSION: MCP-3 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. These results suggest that MCP-3 may have a role in the development of fibrosis in SSc.

Adolescent↗
PubMed2004

Characterization of fibroblast-specific protein 1 in pulmonary fibrosis.

Because fibroblasts produce collagen and other extracellular matrix components that are deposited during tissue fibrosis, defining the behavior of these cells is critical to understanding the pathogenesis of fibrotic diseases. We investigated the utility of fibroblast-specific protein 1 (FSP1), a member of the calmodulin S100 troponin C superfamily, for identifying lung fibroblasts in a murine model of pulmonary fibrosis induced by intratracheal administration of bleomycin. Protein and mRNA expression of FSP1 was minimal in untreated lungs, but increased by 1 week after bleomycin administration and remained increased at 2 and 3 weeks after treatment. By immunohistochemistry, the number of FSP1(+) cells increased in a dose-dependent manner in the lungs after bleomycin treatment. Colocalization of alpha1 procollagen and FSP1 in interstitial cells demonstrated that FSP1(+) fibroblasts contribute to the deposition of collagen after bleomycin administration. In primary lung cell cultures, lung fibroblasts, but not macrophages or type II alveolar epithelial cells, expressed FSP1. FSP1 also identified fibroblasts in lung biopsy specimens from patients with documented usual interstitial pneumonitis. Therefore, FSP1 is an improved marker for lung fibroblasts that could be useful for investigating the pathogenesis of pulmonary fibrosis.

Animals↗
PubMed2004

Surgical treatment of tracheoesophageal fistula in a patient with severe acute respiratory syndrome complicated with extensive pulmonary fibrosis.

Tracheoesophageal fistula is an uncommon complication usually associated with chronic usage of ventilator and pressure necrosis of the tracheoesophageal wall. A 56-year-old female patient with severe acute respiratory syndrome (SARS) with tracheoesophageal fistula is reported. She was intubated for ventilatory support 3 days after admission because of progressive respiratory distress. Methylprednisolone pulse therapy followed by a maintenance dosage was given due to persistence of bilateral pulmonary fibrosis. Thirty three days after admission, she underwent tracheostomy because of difficulty in weaning from the ventilator. Ten days after tracheostomy, she developed tracheoesophageal fistula, which was confirmed by bronchoscopy and panendoscopy. Tracheal resection and primary repair for the esophageal defect was performed via a cervical incision combined with partial sternotomy. She was weaned from the ventilator soon after the surgery and discharged 34 days after the operation. In SARS patients with persistent pulmonary fibrosis and under prolonged corticosteroid treatment, special care should be given to avoid intubation-related tracheal injury during the period of ventilatory support. The tracheoesophageal fistula, once developed, can be repaired in a single stage after improvement of the nutritional status.

Female↗
PubMed1999

Collagen accumulation is decreased in SPARC-null mice with bleomycin-induced pulmonary fibrosis.

Secreted protein acidic and rich in cysteine (SPARC) has been shown to be coexpressed with type I collagen in tissues undergoing remodeling and wound repair. We speculated that SPARC is required for the accumulation of collagen in lung injury and that its absence would attenuate collagen accumulation. Accordingly, we have assessed levels of collagen in SPARC-null mice in an intratracheal bleomycin-injury model of pulmonary fibrosis. Eight- to ten-week-old SPARC-null and wild-type (WT) mice received bleomycin (0.0035 U/g) or saline intratracheally and were subsequently killed after 14 days. Relative levels of SPARC mRNA were increased 2.7-fold (P < 0.001) in bleomycin-treated WT lungs in comparison with saline-treated lungs. Protein from bleomycin-treated WT lung contained significantly more hydroxyproline (191.9 microg/lung) than protein from either bleomycin-treated SPARC-null lungs or saline-treated WT and SPARC-null lungs (147.4 microg/lung, 125.4 microg/lung, and 113. 0 microg/lung, respectively; P < 0.03). These results indicate that SPARC is increased in response to lung injury and that accumulation of collagen, as indicated by hydroxyproline content, is attenuated in the absence of SPARC. The properties of SPARC as a matricellular protein associated with cell proliferation and matrix turnover are consistent with its participation in the development of pulmonary fibrosis.

Animals↗
PubMed1988

[New methods in the early detection of pulmonary fibrosis in asbestosis and silicosis].

Much recent work in thoracic medicine has been slanted towards the early detection of respiratory disease and the prevention of disabling sequelae. In the field of pneumoconioses associated with inhalation of mineral dust the interest of research workers has been largely orientated towards the objectives of early detection and the prevention of fibrotic scarring. To achieve real progress the research workers have used new investigational techniques such as axial tomography of the thorax, quantitative scintigraphy using Gallium-67 and analyses of bronchiolar lavage in parallel with a traditional approach, namely: a clinical examination of the patient, a pulmonary radiograph and respiratory function tests. These studies have enabled further clarification of the specific value of each of these new methods of investigation, whether at the level of early detection, the early recognition of pulmonary fibrosis, the characterisation of the current state of the disease and the prediction of fibrogenic power. Several different forms of intervention on the fibrotic process are currently under trial and may contribute to the prevention of pulmonary fibrosis.

Asbestosis↗
PubMed1993

Ultrastructural study on human lung in alveolitis versus pulmonary fibrosis.

Lung specimens of 21 patients with diffuse interstitial lung disease were examined. The present ultrastructural study outlines the topography and distribution of inflammatory changes in the interstitium, endothelium, and in pneumocytes and phagocytes. Alveolitis is characterized by marked regenerative activity of type II pneumocytes (cuboid metaplasia), intraluminal macrophage accumulation, endothelial swelling, multilamination of the endothelial basement membrane, pericapillary edema, and primarily by cellular infiltrates in the interstitial space. The most prominent feature of the interstitium in pulmonary fibrosis is the lack of immunoinflammatory cells. In some areas there is a marked absence of alveolar lumen while only a small number of macrophages are present in the remaining alveolar lumen. Most of the capillaries in the fibrous septum have been destroyed. Ultrastructural studies of lung biopsies in patients with diffuse interstitial lung disease allow the differentiation between alveolitis and pulmonary fibrosis and thus contribute to a therapeutic decision.

Adult↗
PubMed2003

Quantitative CT indexes in idiopathic pulmonary fibrosis: relationship with physiologic impairment.

PURPOSE: To determine whether measurements of skewness, kurtosis, and mean lung attenuation on thin-section computed tomographic (CT) histograms in patients with idiopathic pulmonary fibrosis (IPF) correlate with pulmonary physiologic abnormality in a nonspirometrically controlled multicenter study. MATERIALS AND METHODS: The authors analyzed baseline digital thin-section CT data from 144 patients with IPF who enrolled in a double-blind placebo-controlled clinical effectiveness trial of interferon beta 1a in the treatment of IPF. All patients underwent thin-section CT in the supine position at full inspiration. The lungs were isolated by using a semiautomated thresholding technique, with an upper threshold of -200 HU. An attenuation correction algorithm was used. Pulmonary function tests (PFTs) included forced vital capacity, total lung capacity, forced expiratory volume in 1 second, and diffusing lung capacity. Univariate and multiple correlation and regression statistical analyses were used to determine relationships between histogram features and results of PFTs. RESULTS: Moderate correlations existed between histogram features and PFT results. Kurtosis showed the greatest degree of correlation with physiologic abnormality (r = 0.53, P <.01). Strength of correlation increased with exclusion of suboptimal scans but did not change significantly after application of an attenuation correction algorithm. Attenuations for lungs, gas, and soft tissue varied considerably between scanner manufacturers. Kurtosis alone provided predictions of pulmonary function that were virtually as good as those from all histogram features combined. CONCLUSION: Thin-section CT histograms of the lungs were found to correlate with results of PFTs in patients with IPF, which supports the claim that histogram features can be used as valid indexes of IPF in a multiinstitutional nonspirometrically controlled study.

Algorithms↗
PubMed2005

Health-related quality of life in patients with idiopathic pulmonary fibrosis. What is the main contributing factor?

The prognosis of patients with idiopathic pulmonary fibrosis (IPF) is generally considered to be poor. As the disease progresses, patients invariably become severely limited in their activities. Therefore, evaluating the health-related quality of life (HRQoL) in IPF patients is considered to be important. However, there have been few studies of this kind to date. We applied the St. George's Respiratory Questionnaire (SGRQ) to 41 consecutive IPF patients and examined various physiological variables to identify factors that were correlated with the HRQoL. Total lung capacity, transfer factor, arterial partial pressure of oxygen at rest, the lowest oxygen saturation during exercise test, and the baseline dyspnoea index (BDI) score were significantly correlated with the total SGRQ score. A similar tendency was observed in each component. Conversely, peak oxygen uptake, known as one of the important factors that determines HRQoL in chronic obstructive pulmonary disease (COPD), did not correlate with any SGRQ scores. In stepwise multiple regression analysis, the BDI score was selected as the only factor significantly contributing to the total SGRQ score. Dyspnoea was the most important factor determining HRQoL in IPF. The types of other variables that correlated with the HRQoL in IPF patients were different from those in COPD.

Carbon Dioxide↗
PubMed1976

Interstitial associations of cells lining air spaces in human pulmonary fibrosis.

An ultrastructural study of the cells that line air spaces in human pulmonary fibrosis is reported. Intimate associations between these cells and cellular elements in the interstitium were consistently found in biopsies from 25 cases. Cytoplasmic extensions of cuboidal pneumocytes protruded through discontinuities in the subjacent basement membrane. Attenuated cells having structural properties of fibroblasts were situated on connective tissue that formed the walls of numerous air spaces. In this situation, a basement membrane was not demonstrable. These heretofore undescribed features suggest a dynamic interaction between certain mesenchymal and epithelial elements in the fibrotic lung.

Adult↗
PubMed2004

Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitides.

OBJECTIVE: The association of pulmonary fibrosis (PF) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitides has not been well documented. The aim of this study was to assess the clinicopathological characteristics of PF in patients who tested positive for MPO-ANCA. METHODOLOGY: In this study, 31 patients (17 males and 14 females; mean age, 69 years) diagnosed as having PF with positive MPO-ANCA levels ranging from 10 to 840 EU with a mean of 112.5 EU, were evaluated clinicopathologically. RESULTS: Among 31 patients with PF, 22 had underlying systemic diseases such as collagen vascular diseases, while nine had unknown aetiology. Evidence of glomerulonephritis was demonstrated in 14 patients. The clinical features were a history of dry cough and/or fine crackles in all 31 patients. Chest CT scans showed honeycombing in the lung bases in 26 patients. The histopathological features of the diseased lung tissues in all 11 autopsied cases were compatible with the usual interstitial pneumonia (UIP) pattern. Vasculitis was confirmed in bronchial arteries and/or pulmonary arterioles in five patients. The mortality was as high as 13 of the 31 patients. The causes of death were: deterioration of PF in five (two of whom were associated with pulmonary haemorrhage), lung cancer in two, pneumonia in four, and digestive tract bleeding in two. The survival rates in PF with MPO-ANCA-negative collagen vascular diseases, cryptogenic fibrosing alveolitis (CFA), and PF with positive MPO-ANCA, were compared. The 5-year survival rate in PF with positive MPO-ANCA was worse than in PF with MPO-ANCA-negative collagen vascular diseases and was the same for CFA. CONCLUSION: Although there was no correlation between MPO-ANCA titres and the activity of PF, this study demonstrated that the presence of positive MPO-ANCA was an unfavorable prognostic factor in patients with PF.

Aged↗
PubMed1995

Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during idiopathic pulmonary fibrosis. Possible role of transforming growth factor beta and tumor necrosis factor alpha.

Pulmonary biopsy specimens from ten cases of idiopathic pulmonary fibrosis (IPF) were examined using routine histological stains, including toluidine blue, and immunohistochemistry by means of specific antibodies against alpha-smooth muscle (alpha-SM) actin, desmin, keratin, TGF beta 1, and TNF alpha. The sections were compared with two cases of normal lung. As shown previously, normal alveolar interstitium did not contain alpha-SM actin positive myofibroblasts nor did the alveolar lining contain any significant number of TGF beta 1 or TNF alpha laden epithelial cells. In IPF, during the inflammatory stage, the alveolar myofibroblasts expressed alpha-SM actin and the regenerating type II alveolar epithelium staining strongly with TGF beta 1 and TNF alpha antibodies. The former cytokine was also detected in the interstitial matrix and fibroblastic cells as well as in the wall of vessels. At this stage, a manifest mast cell infiltration was noted. In very fibrotic and cystic alveolar tissue, i.e., at end stage fibrosis, the number of alpha-SM actin positive myofibroblasts as well as that of TNF alpha laden type II epithelial cells diminished, while TGF beta 1 positive cells persisted. Our findings demonstrate that during IPF alveolar type II epithelium constitutes, if not the site of synthesis, at least the main reservoir for TGF beta 1 and TNF alpha. These cytokines, besides their involvement in fibrogenesis, play probably an important role in the expression of alpha-SM actin by alveolar myofibroblasts. Our study suggests the possibility of an interaction between interstitial cells and alveolar epithelium, during IPF.

Actins↗
PubMed2006

Migratory marker expression in fibroblast foci of idiopathic pulmonary fibrosis.

BACKGROUND: Fibroblast foci (FF) are considered a relevant morphologic marker of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), and are recognised as sites where fibrotic responses are initiated and/or perpetuated in this severe disease. Despite their relevance, the cellular and molecular mechanisms responsible for the formation of FF and their role in tissue remodelling are poorly defined. In previous studies we have provided evidence of abnormal activation of the wnt-signaling-pathway in IPF/UIP that is centred on FF and the overlying epithelium. This important morphogenetic pathway is able to trigger epithelial-mesenchymal-transition (EMT), a mechanism involved in developmental and metastatic processes, which is also potentially involved in pulmonary fibrosis. METHODS: Since EMT is characterised by enhancement of migratory potential of cells, we investigated the molecular profile of FF in 30 biopsies of IPF/UIP and a variety of control samples, focussing on the immunohistochemical expression of three molecules involved in cell motility and invasiveness, namely laminin-5-gamma2-chain, fascin, and heat-shock-protein-27. RESULTS: We provide evidence that in UIP these three molecules are abnormally expressed in discrete clusters of bronchiolar basal cells precisely localised in FF. These cellular clusters expressed laminin-5-gamma2-chain and heat-shock-protein-27 at very high levels, forming characteristic three-layered lesions defined as "sandwich-foci" (SW-FF). Upon quantitative analysis SW-FF were present in 28/30 UIP samples, representing more than 50% of recognisable FF in 21/30, but were exceedingly rare in a wide variety of lung pathologies examined as controls. In UIP, SW-FF were often observed in areas of microscopic honeycombing, and were also found at the interface between normal lung tissue and areas of dense scarring. CONCLUSION: These molecular abnormalities strongly suggest that SW-FF represent the leading edge of pulmonary remodelling, where abnormal migration and re-epithelialisation take place, and that abnormal proliferation and migration of bronchiolar basal cells have a major role in the remodelling process characterising IPF/UIP. Further investigations will assess their possible use as reliable markers for better defining the UIP-pattern in difficult cases.

Biomarkers↗