Chronic Fibrosing Interstitial Pneumonia Research Articles

A cohort study of mortality predictors in patients with acute exacerbation of chronic fibrosing interstitial pneumonia

ObjectivesTo assess clinical, laboratory and radiographic findings associated with outcomes and to clarify more practical ways to predict hospital mortality in patients with acute exacerbation (AE) of chronic fibrosing interstitial...

Normativa sobre el diagnóstico y tratamiento de la fibrosis pulmonar idiopática

Idiopathic pulmonary fibrosis is defined as a chronic fibrosing interstitial pneumonia limited to the lung, of unknown cause, with poor prognosis and few treatment options. In recent years there has been an increase in their prevalence, probably due to the optimization of diagnostic methods and increased life expectancy. The ATS/ERS Consensus (2000) established the diagnostic criteria and recommendations for the assessment of the disease course and treatment. Later studies have helped to redefine diagnostic criteria and treatment options. In 2011, an international consensus was published, establishing diagnostic criteria and new treatment strategies. These guidelines have been updated with the newest aspects of diagnosis and treatment of idiopathic pulmonary fibrosis. A level of evidence has been identified for the most relevant questions, particularly with regard to treatment options.

Preventive effect of irbesartan on bleomycin-induced lung injury in mice

Idiopathic pulmonary fibrosis is a specific form of chronic fibrosing interstitial pneumonia that is limited to the lung. Angiotensin receptor blockers (ARBs) and peroxisome proliferator-activated receptor (PPAR) γ ligands have anti-inflammatory and anti-fibrotic effects. We investigated the effects of irbesartan-an ARB with PPAR γ activity-on the development of bleomycin-induced pulmonary fibrosis in mice. Lung injury was induced in imprinting control region (ICR) mice by intratracheal instillation of 2mg/kg of bleomycin. The treatment group orally received 20mg/kg of irbesartan for 5 consecutive days before instillation. The mice were sacrificed and were evaluated 14 days after bleomycin instillation. Irbesartan reduced the fluid content and hydroxyproline level in the lung and improved the pathological findings as indicated by the Ashcroft score. Total cell counts, the numbers of macrophages, neutrophils, and lymphocytes, and the levels of transforming growth factor (TGF) β1 and monocyte chemotactic protein (MCP) 1 in the bronchoalveolar lavage fluid (BALF) were decreased. Treatment with a PPARγ antagonist GW9662 reversed some of the effects of irbesartan. The results of this study indicated that irbesartan attenuated the development of bleomycin-induced pulmonary fibrosis in mice by decreasing TGF-β1 and MCP-1 via blocking of ATI, by binding to CCR2b, and by PPARγ-mediated inhibition of inflammation.

Charakteristika und Versorgung der idiopathischen Lungenfibrose

Idiopathic pulmonary fibrosis (IPF), a manifestation of chronic progressive fibrosing interstitial pneumonia, is with a prevalence of 2-29 cases per 100,000 individuals a rare disease. Current treatment options are limited, and the mean survival time of the newly diagnosed (mostly elderly) patients is only about 2-3 years. As in Europe data are limited on the characteristics and management of such patients, INSIGHTS-IPF was initiated as a new registry that documents incident and prevalent patients with confirmed IPF diagnosis prospectively. Detailed data on patient characteristics, diagnostics, management, clinical outcomes, quality of life and resource utilization are recorded. It is planned to document 500 patients in 30 centers. The registry will contribute to the optimization of the management of IPF patients in the long term.

Clinical aspects of multinodular pulmonary fibrosis in two warmblood horses

Two warmblood horses with a history of chronic weight loss and inappetence were referred to the Faculty of Veterinary Medicine, Ludwig-Maximilians University of Munich, Germany, for further examination. The clinical...

Abnormal expression of telomerase/apoptosis limits type II alveolar epithelial cell replication in the early remodeling of usual interstitial pneumonia/idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a distinctive, usually fatal, type of chronic fibrosing interstitial pneumonia of unknown cause that increases in prevalence with advanced age, characterized by failure of alveolar re-epithelization and progressive scar formation. Recently, limitation of the replicative capacity of tissues determined by telomerase/apoptosis balance has been implicated in pathogenesis of age-related diseases. In this study, we validated the importance of the expression of type 2 alveolar epithelial cells telomerase protein and studied the relationships between telomerase and apoptosis in early remodeling of usual interstitial pneumonia. We determined type 2 alveolar epithelial cells density, telomerase expression, and apoptosis in surgical lung biopsies from 24 patients with usual interstitial pneumonia, and in normal lung tissues from 18 subjects. We used immunohistochemistry, deoxynucleotidyl transferase method of end labeling, electron microscopy, and histomorphometry to evaluate the amount of type 2 alveolar epithelial cells staining for surfactant-A, telomerase, and in situ detection of apoptotic cells. Unaffected areas of usual interstitial pneumonia and normal lung tissue had similar densities of type 2 alveolar epithelial cells, but a significant minor subpopulation of type 2 alveolar epithelial cells was telomerase positive and a large population was telomerase negative. A significant inverse association was found between low type 2 alveolar epithelial cell telomerase expression and high apoptosis in unaffected areas of usual interstitial pneumonia. Although type 2 alveolar epithelial cell telomerase expression was higher than apoptosis in NLT group, no significant association was found between them. Electron microscopy confirmed epithelial apoptosis, alveolar collapse, and initial fibroplasia. We conclude that abnormal type 2 alveolar epithelial cells telomerase/apoptosis balance may reduce alveolar epithelial regenerative capacity, thus contributing to the early remodeling response in usual interstitial pneumonia.

Idiopatinė plaučių fibrozė ir aktualūs jos diagnostikos bei gydymo klausimai

Idiopatinė plaučių fibrozė, dar vadinama kriptogeniniu fibroziniu alveolitu, yra lėtinė, greitai progresuojanti, neaiškios kilmės intersticinė plaučių liga. Ji viena iš dviejų klasikinių intersticinių plaučių ligų – kita sarkoidozė [1]. Specifiniu požiūriu IPF yra savito tipo, kuriam būdinga savita histologinė struktūra [2].

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF; also known as cryptogenic fibrosing alveolitis) is a distinctive type of chronic fibrosing interstitial pneumonia of unknown cause associated with the histological pattern usual interstitial pneumonia (UIP). UIP is a distinct histological pattern observed in IPF but may also be found in other etiologies. The diagnosis of UIP can be established by surgical lung biopsy or by high-resolution thin-section CT scans (provided the radiographic features are classical). Historically, patients labeled as ‘IPF’ encompassed a group of disorders, including UIP, as well as other idiopathic interstitial pneumonias, which differ from UIP in prognosis and responsiveness to therapy. The term IPF should be restricted to patients with idiopathic UIP. The inciting cause(s) and pathogenesis of IPF have not been elucidated but alveolar epithelial cell injury and dysregulation or altered phenotypic expression of fibroblasts are key elements. Inflammatory cells may play minor roles in initiating or propagating the fibrotic process. The prognosis of idiopathic UIP is poor. Mean survival following diagnosis approximates at 3 years. Current medical therapies are of unproven value. Lung transplantation is a viable option for patients failing medical therapy.

Treatment of idiopathic pulmonary fibrosis: Is there anything new?

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia of unknown aetiology and is associated with the histological picture of usual interstitial pneumonia. Treatment in most cases is unsatisfactory and the prognosis remains poor. There is insufficient evidence to suggest that any treatment, apart from lung transplantation, improves survival or halts disease progression for IPF patients. Data on treatment response are limited by the paucity of clinical trails, the lack of homogenous clinical features, the small number of patients, and the absence of histological and radiological documentation in many cases. Anti-inflammatory medications such as corticosteroids, azathioprine and cyclophosphamide remain the commonly used medications. More recently, it has been proposed that IPF is a primary fibrotic disease rather than an inflammatory condition. Antifibrotic agents such as colchicine, pirfenidone and interferon-gamma (IFN-gamma) have been tried. However, a recent placebo-controlled trial has failed to demonstrate a significant effect of IFN-gamma on disease progression, lung function or quality of life in IPF patients, though a clinically significant survival benefit of the drug could not be ruled out.

Immunomodulatory agents for idiopathic pulmonary fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) or Usual Interstitial Pneumonia (UIP) is a form of chronic fibrosing interstitial pneumonia of unknown aetiology, with progressively deteriorating respiratory function and ultimately death from respiratory failure. Most treatments are intended to suppress inflammation but none has been proven to alter this process. The most widespread approach uses oral corticosteroids; others use immunosuppressive, immunomodulatory or anti-fibrotic agents, alone or with corticosteroids. A Cochrane review of corticosteroids in IPF has found no evidence that they are of benefit. To determine the effect of non-corticosteroid immunosuppressive, anti-fibrotic and immunomodulatory agents in the treatment of IPF(UIP). We searched the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, Issue 2 2003), MEDLINE (January 1966 to April 2003), EMBASE (January 1985 to April 2003) and with additional handsearching. RCTs/CCTs utilising non-corticosteroid immunosuppressive, anti-fibrotic or immunomodulatory agents versus either placebo or corticosteroids alone in adult patients with histological evidence of IPF(UIP) or with a diagnosis consistent with published American Thoracic Society guidelines were included. We retrieved abstracts of identified articles and reviewed those possibly fulfilling inclusion criteria and included or excluded. Two reviewers assessed the studies for inclusion in the review. Where doubt existed a third reviewer re-assessed the article and consensus was obtained. Methodological quality was assessed using the Jadad scale and the Cochrane assessment of allocation of concealment. 59 studies were identified. Quality was generally poor. Only three RCT/CCTs were suitable for meta-analysis, two lesser quality RCTs were included in discussion only, 52 studies were excluded and two ongoing trials were identified. Each high quality trial used a different agent (azathioprine, colchicine, interferon-gamma 1b) and meaningful comparisons are not possible. Azathioprine and Interferon were studied as additional therapy, whilst colchicine was compared with oral corticosteroids. Only interferon was shown to produce any significant improvement in pulmonary function and arterial oxygenation. There may be a small (but undefined) long term survival advantage for azathioprine. One of the lower quality studies showed a marginal benefit for cyclophosphamide and prednisone over prednisone alone; the other showed no benefit for azathioprine and prednisone over prednisone alone. There are no high quality studies utilising cyclophosphamide. There is little good quality information regarding the efficacy of non-corticosteroid agents in IPF(UIP). The older agents have generally not been well evaluated. A number of new agents require further evaluation. Currently there is little to justify the routine use of any non-corticosteroid agent in the management of IPF(UIP).

Antifibrotic Therapy for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia characterized by a poor response to therapy and a dismal prognosis. Historically, the fibrotic process in IPF has been thought to be preceded by a chronic inflammatory process that injures the lung and causes irreversible fibrosis. This notion has led to an emphasis on antiinflammatory therapy with corticosteroids and immunosuppressive agents (azathioprine or cyclophosphamide). However, several studies have shown little or no benefit with these drugs in addition to potentially harmful side effects. A search for additional therapies has focused on strategies to abrogate fibroblast proliferation and collagen deposition. Unfortunately, certain antifibrotic agents such as colchicine and D-penicillamine, which showed initial promise in preclinical studies, were not shown to be efficacious in patients with IPF. In a recent open-label study, pirfenidone appeared to stabilize pulmonary function and impact favorably on survival in patients with IPF. However, a more definitive study is required to confirm these findings. Exciting research has further defined the fibrotic process as one involving cytokine mediators, alveolar epithelial cell injury, and fibroblast apoptosis. In a preliminary study, interferon gamma was shown to improve or stabilize lung function in steroid-recalcitrant IPF, findings that warrant confirmation in a larger clinical trial. Furthermore, a phase II clinical trial evaluating the efficacy of interferon beta was recently completed with results soon to be available. Agents widely used in clinical practice may have a role in the treatment of IPF. For example, angiotensin-converting enzyme inhibitors, such as captopril, may protect the alveolar epithelium, whereas lovastatin, a cholesterol-lowering agent, may induce fibroblast apoptosis. With new understanding of the regulation of injury, repair, and fibrogenesis, novel therapies will continue to be discovered.