Form Of Interstitial Lung Disease Research Articles

Low‐dose administration of bleomycin leads to early alterations in lung mechanics

What is the central question of this study? When do alterations in pulmonary mechanics occur following chronic low-dose administration of bleomycin? What is the main finding and its importance? Remarkably, we report changes in lung mechanics as early as day7 that corresponded to parameters determined from single-frequency forced oscillation manoeuvres and pressure-volume loops. These changes preceded substantial histological changes or changes in gene expression levels. These findings are significant to refine drug discovery in idiopathic pulmonary fibrosis, where preclinical studies using lung function parameters would enhance the translational potential of drug candidates where lung function readouts are routinely performed in the clinic. Idiopathic pulmonary fibrosis (IPF) is the most widespread form of interstitial lung disease and, currently, there are only limited treatment options available. In preclinical animal models of lung fibrosis, the effectiveness of experimental therapeutics is often deemed successful via reductions in collagen deposition and expression of profibrotic genes in the lung. However, in clinical studies, improvements in lung function are primarily used to gauge the success of therapeutics directed towards IPF. Therefore, we examined whether changes in respiratory system mechanics in the early stages of an experimental model of lung fibrosis can be used to refine drug discovery approaches for IPF. C57BL/6J mice were administered bleomycin (BLM) or a vehicle control i.p. twice a week for 4weeks. At 7, 14, 21, 28 and 33days into the BLM treatment regimen, indices of respiratory system mechanics and pressure-volume relationships were measured. Concomitant with these measurements, histological and gene analyses relevant to lung fibrosis were performed. Alterations in respiratory system mechanics and pressure-volume relationships were observed as early as 7days after the start of BLM administration. Changes in respiratory system mechanics preceded the appearance of histological and molecular indices of lung fibrosis. Administration of BLM leads to early changes in respiratory system mechanics that coincide with the appearance of representative histological and molecular indices of lung fibrosis. Consequently, these data suggest that dampening the early changes in respiratory system mechanics might be used to assess the effectiveness of experimental therapeutics in preclinical animal models of lung fibrosis.

CASE OF A GRANULOMATOUS-LYMPHOCYTIC INTERSTITIAL LUNG DISEASE IN A PATIENT WITH COMMON VARIABLE IMMUNODEFICIENCY DISORDER

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 1 SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/09/2018 03:45 PM - 04:45 PM INTRODUCTION: Common variable Immunodeficiency Disorder (CVID), is the most common primary immunodeficiency disorder. Approximately 30% of patients with CVID develop autoimmune and granulomatous disease. Interstitial lung disease (ILD) manifests in 5-15% of CVID patients and represents a diagnostic challenge. It may present with sarcoid like granulomas, organizing pneumonia, lymphocytic interstitial pneumonia and nonspecific interstitial pneumonia. We present one such case of granulomatous-lymphocytic interstitial lung disease (GL-ILD). CASE PRESENTATION: 60 year old African American non-smoking female with no significant underlying medical history presented with cough in March 2006. Family history consisted of mother with stomach cancer, aunt with bone cancer, and grandmother with liver cancer. On physical exam, she had palpable axillary and inguinal lymph nodes. She had an abnormal CT chest showing bilateral lung nodules along with mediastinal lymphadenopathy. CT abdomen/pelvis showed retroperitoneal and pelvic adenopathy. PET scan showed uptake in multiple regions in neck, chest, abdomen and pelvis. PPD and HIV tests were negative.Workup for connective tissue disease came back negative except for low IgA, low normal IgG, and reduced IgM levels. She had minimally elevated ACE level. Inguinal and left axillary lymph node biopsies were non-diagnostic, showing benign lymph nodes with reactive follicular hyperplasia. Flow cytometry was negative. Video-assisted thoracoscopic left lung biopsies showed nodular airway-centered lymphoid hyperplasia with associated scattered small non-necrotizing granulomas. Follicular bronchiolitis was present. Biopsies did not suggest sarcoidosis. Mycobacterial and fungal cultures were negative. She had serial CT chest, abdomen and pelvis for the next two years showing no progression of her disease. After 2008, she had slow progression of lymphadenopathy and was evaluated at a tertiary care center in 2012. Definitive diagnosis of GL-ILD was given at that point. She was placed on steroids for about a year with stabilization of her disease. Subsequently, she had worsening of her lymphadenopathy off steroids and has been maintained on IgG infusions. DISCUSSION: CVID is present in a considerable number of patients with a small subset presenting with cryptic ILD. Exhaustive diagnostic workup is usually needed including open lung biopsy. Patients with GL-ILD may remain stable over years after optimization of their immunoglobulin levels. Following this, steroids remain first line treatment and response may be variable. In progressive disease, immunosuppressive treatment is recommended. CONCLUSIONS: This case illustrates an example of a form of interstitial lung disease associated with CVID. When lung biopsies demonstrate lymphocytic infiltrate and/or granuloma in the lung, CVID should be considered in the differential. Reference #1: British Lung Foundation/United Kingdom PrimaryImmunodeficiency Network Consensus Statement. J Allergy Clin Immunol Pract. 2017 Jul - Aug;5(4):938-945. https://doi.org/10.1016/j.jaip.2017.01.021. Epub 2017 Mar 25. Reference #2: Granulomatous-lymphocytic interstitial lung disease as the first manifestation of common variable immunodeficiency. Clin Respir J. 2018 Jan;12(1):337-343. https://doi.org/10.1111/crj.12511. Epub 2016 Jun 22. DISCLOSURES: No relevant relationships by Riju Dasgupta, source=Web Response No relevant relationships by Asok Dasgupta, source=Web Response No relevant relationships by Chelsea Leipold, source=Web Response No relevant relationships by David Taylor, source=Web Response No relevant relationships by Paresh Timbadia, source=Web Response

Hematopoietic protease nexin-1 protects against lung injury by preventing thrombin signaling in mice

AbstractCoagulation and fibrinolytic system deregulation has been implicated in the development of idiopathic pulmonary fibrosis, a devastating form of interstitial lung disease. We used intratracheal instillation of bleomycin to induce pulmonary fibrosis in mice and analyzed the role of serine protease inhibitor E2 (serpinE2)/protease nexin-1 (PN-1), a tissue serpin that exhibits anticoagulant and antifibrinolytic properties. PN-1 deficiency was associated, after bleomycin challenge, with a significant increase in mortality, as well as a marked increase in active thrombin in bronchoalveolar lavage fluids, an overexpression of extracellular matrix proteins, and an accumulation of inflammatory cells in the lungs. Bone marrow transplantation experiments showed that protective PN-1 was derived from hematopoietic cell compartment. A pharmacological strategy using the direct thrombin inhibitor argatroban reversed the deleterious effects of PN-1 deficiency. Concomitant deficiency of the thrombin receptor protease-activated receptor 4 (PAR4) abolished the deleterious effects of PN-1 deficiency in hematopoietic cells. These data demonstrate that prevention of thrombin signaling by PN-1 constitutes an important endogenous mechanism of protection against lung fibrosis and associated mortality. Our findings suggest that appropriate doses of thrombin inhibitors or PAR4 antagonists may provide benefit against progressive lung fibrosis with evidence of deregulated thrombin activity.

Active epithelial Hippo signaling in idiopathic pulmonary fibrosis.

Hippo/YAP signaling plays pleiotropic roles in the regulation of cell proliferation and differentiation during organogenesis and tissue repair. Herein we demonstrate increased YAP activity in respiratory epithelial cells in lungs of patients with idiopathic pulmonary fibrosis (IPF), a common, lethal form of interstitial lung disease (ILD). Immunofluorescence staining in IPF epithelial cells demonstrated increased nuclear YAP and loss of MST1/2. Bioinformatic analyses of epithelial cell RNA profiles predicted increased activity of YAP and increased canonical mTOR/PI3K/AKT signaling in IPF. Phospho-S6 (p-S6) and p-PTEN were increased in IPF epithelial cells, consistent with activation of mTOR signaling. Expression of YAP (S127A), a constitutively active form of YAP, in human bronchial epithelial cells (HBEC3s) increased p-S6 and p-PI3K, cell proliferation and migration, processes that were inhibited by the YAP-TEAD inhibitor verteporfin. Activation of p-S6 was required for enhancing and stabilizing YAP, and the p-S6 inhibitor temsirolimus blocked nuclear YAP localization and suppressed expression of YAP target genes CTGF, AXL, and AJUBA (JUB). YAP and mTOR/p-S6 signaling pathways interact to induce cell proliferation and migration, and inhibit epithelial cell differentiation that may contribute to the pathogenesis of IPF.

TRAIL-Dependent Resolution of Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) was key to the resolution of bleomycin-induced pulmonary fibrosis. Both in vivo and in vitro studies demonstrated that Gr-1+TRAIL+ bone marrow-derived myeloid cells blocked the activation of lung myofibroblasts. Although soluble TRAIL was increased in plasma from IPF patients, the presence of TRAIL+ myeloid cells was markedly reduced in IPF lung biopsies, and primary lung fibroblasts from this patient group expressed little of the TRAIL receptor-2 (DR5) when compared with appropriate normal samples. IL-13 was a potent inhibitor of DR5 expression in normal fibroblasts. Together, these results identified TRAIL+ myeloid cells as a critical mechanism in the resolution of pulmonary fibrosis, and strategies directed at promoting its function might have therapeutic potential in IPF.

Role of MicroRNAs in TGF-β Signaling Pathway-Mediated Pulmonary Fibrosis.

Pulmonary fibrosis is the most common form of interstitial lung disease. The transforming growth factor-β (TGF-β) signaling pathway is extensively involved in the development of pulmonary fibrosis by inducing cell differentiation, migration, invasion, or hyperplastic changes. Accumulating evidence indicates that microRNAs (miRNAs) are dysregulated during the initiation of pulmonary fibrosis. miRNAs are small noncoding RNAs functioning as negative regulators of gene expression at the post-transcriptional level. A number of miRNAs have been reported to regulate the TGF-β signaling pathway and consequently affect the process of pulmonary fibrosis. A better understanding of the pro-fibrotic role of the TGF-β signaling pathway and relevant miRNA regulation will shed light on biomedical research of pulmonary fibrosis. This review summarizes the current knowledge of miRNAs regulating the TGF-β signaling pathway with relevance to pulmonary fibrosis.

HRCT findings of childhood follicular bronchiolitis.

Follicular bronchiolitis is a lymphoproliferative form of interstitial lung disease (ILD) defined by the presence of peribronchial lymphoid follicles. Follicular bronchiolitis has been associated with viral infection, autoimmune disease and immunodeficiency. The most common clinical manifestation is respiratory distress in infancy followed by a prolonged course with gradual improvement. We found no reports of systematic review of high-resolution computed tomography (HRCT) findings in pediatric follicular bronchiolitis. The purpose of this study was to describe the HRCT findings of follicular bronchiolitis in children and correlate these imaging findings with histopathology. A 5-year retrospective review of all pathology-proven cases of follicular bronchiolitis was performed. Inclusion criteria were age <18years and an HRCT within 6months of lung biopsy. HRCTs were reviewed by three observers and scored using the system previously described by Brody et al. Six patients met the inclusion criteria with age range at HRCT of 7-82months (median: 39.5months). Pulmonary nodules (n=6) were the most common HRCT finding followed by focal consolidation (n=5), bronchiectasis (n=4) and lymphadenopathy (n=3). Tree and bud opacities and nodules on CT correlated with interstitial lymphocytic infiltrates and discrete lymphoid follicles on pathology. The salient HRCT findings of childhood follicular bronchiolitis are bilateral, lower lung zone predominant pulmonary nodules and bronchiectasis with infantile onset of symptoms. These characteristic HRCT findings help differentiate follicular bronchiolitis from other forms of infantile onset ILD.

Heterogeneity of Fibroblasts and Myofibroblasts in Pulmonary Fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is the most common form of interstitial lung diseases of unknown eathiopathogenesis, mean survival of 3-5 years and limited therapeutics. Characterized by a loss of alveolar type II epithelial cells and aberrant activation of stromal cells, considerable effort was undertaken to characterize the origin and activation mechanisms of fibroblasts and myofibroblasts in IPF lungs. In this review, the origin and contribution of fibroblast and myofibroblasts in lung fibrosis will be summarized. Lineage tracing experiments suggested that interstitial lung fibroblasts and lipofibroblasts, pericytes and mesothelial cells differentiate into myofibroblasts. However, epithelial and bone marrow derived cells may give rise to collagen expressing fibroblasts but do not differentiate into myofibroblasts. There is great heterogeneity in fibroblasts and myofibroblasts in fibrotic lungs. Further, there is evidence for the expansion of pericyte derived myofibroblasts and loss of lipofibroblasts and lipofibroblast derived myofibroblasts in IPF.

Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis.

The receptor for advanced glycation end products (RAGE) is underexpressed in idiopathic pulmonary fibrosis (IPF) lung, but the role of RAGE in human lung fibrosis remains uncertain. To examine (1) the association between IPF risk and variation at rs2070600, a functional missense variant in AGER (the gene that codes for RAGE), and (2) the associations between plasma-soluble RAGE (sRAGE) levels with disease severity and time to death or lung transplant in IPF. We genotyped the rs2070600 single-nucleotide polymorphism in 108 adults with IPF and 324 race-/ethnicity-matched control subjects. We measured plasma sRAGE by ELISA in 103 adults with IPF. We used generalized linear and additive models as well as Cox models to control for potential confounders. We repeated our analyses in 168 (genetic analyses) and 177 (sRAGE analyses) adults with other forms of interstitial lung disease (ILD). There was no association between rs2070600 variation among adults with IPF (P = 0.31). Plasma sRAGE levels were lower among adults with IPF and other forms of ILD than in control subjects (P < 0.001). The rs2070600 allele A was associated with a 49% lower sRAGE level (95% confidence interval [CI], 11 to 71%; P = 0.02) among adults with IPF. In adjusted analyses, lower sRAGE levels were associated with greater disease severity (14% sRAGE decrement per 10% FVC decrement; 95% CI, 5 to 22%) and a higher rate of death or lung transplant at 1 year (adjusted hazard ratio, 1.9 per logarithmic unit of sRAGE decrement; 95% CI, 1.2-3.3) in IPF. Similar findings were observed in a heterogeneous group of adults with other forms of ILD. Lower plasma sRAGE levels may be a biological measure of disease severity in IPF. Variation at the rs2070600 single-nucleotide polymorphism was not associated with IPF risk.

MDA5 autoantibody-another indicator of clinical diversity in dermatomyositis.

Allenbach and colleagues have recently reported for the first time the results of an intriguing study of the histopathologic, immunopathologic and gene expression differences in muscle biopsy tissue from adult dermatomyositis (DM) patients who do and do not have circulating MDA5 autoantibodies (anti-MDA5). Anti-MDA5 were originally identified in a clinically-defined subset of DM patients whose disease was expressed predominately in the skin for unusually long periods of time without accompanying muscle weakness [i.e., "clinically-amyopathic DM" (CADM)] and were at risk for acute, rapidly-progressive form of interstitial lung disease (ILD). As an academic dermatologist in the United States of America (USA) having a career-long interest in the CADM subset, I would like to share my perspective on the results of the work by Allenbach and colleagues and offer some suggestions for additional study in this area. But to do so most effectively, I first would like to review the clinical concept of CADM and its association with anti-MDA5 antibody production and a potentially-fatal form of (ILD).

Role of pirfenidone in the management of pulmonary fibrosis.

Pulmonary fibrosis is associated with a number of specific forms of interstitial lung disease (ILD) and can lead to progressive decline in lung function, poor quality of life, and, ultimately, early death. Idiopathic pulmonary fibrosis (IPF), the most common fibrotic ILD, affects up to 1 in 200 elderly individuals and has a median survival that ranges from 3 to 5 years following initial diagnosis. IPF has not been shown to respond to immunomodulatory therapies, but recent trials with novel antifibrotic agents have demonstrated lessening of lung function decline over time. Pirfenidone has been shown to significantly slow decline in forced vital capacity (FVC) over time and prolong progression-free survival, which led to its licensing by the United States Food and Drug Administration (FDA) in 2014 for the treatment of patients with IPF. However, pirfenidone has been associated with significant side effects, and patients treated with pirfenidone must be carefully monitored. We review recent and ongoing clinical research and experience with pirfenidone as a pharmacologic therapy for patients with IPF, provide a suggested approach to incorporate pirfenidone into a treatment algorithm for patients with IPF, and examine the potential of pirfenidone as a treatment for non-IPF forms of ILD accompanied by progressive pulmonary fibrosis.

DIFFUSE PULMONARY OSSIFICATION

Diffuse pulmonary ossification is a rare form of interstitial lung disease. Specific symptoms are often lacking. The present article describes a case of diffuse pulmonary ossification in an elderly person.

Autoantibodies in children with juvenile dermatomyositis: A single centre experience from North-West India.

The objective of this study is to determine autoantibody profile in children with juvenile dermatomyositis (JDM). Children who were diagnosed with JDM (either recently diagnosed during the study period or follow-up patients) were included in the study. Autoantibodies were detected with commercially available Immunodot kit. Thirty patients were included in the study. Nine out of thirty patients (30%) were positive for one of the 12 autoantibodies tested. Anti-SRP antibody was most common antibody detected in 3 patients followed by anti-MDA-5 antibody in 2 patients; while anti-Jo1 antibody, anti-TIF1-γ antibody, anti-Mi-2 antibody, and anti-PM-Scl antibody were positive in 1 patient each. A different disease phenotype was observed with each autoantibody. The patient with anti-Jo1 antibody had a severe systemic disease in the form of interstitial lung disease; patients with anti-MDA-5 antibody and anti-Mi2 antibody had more severe skin disease with mild muscle disease and patients with anti-SRP antibody had significant skin and muscle disease. Anti-TIF1-γ and anti-PM-Scl antibodies were seen in patients with features of overlap syndrome (myositis-scleroderma). Estimation of autoantibodies may serve as an adjunct tool in delineating and defining distinct clinical phenotypes in children diagnosed with juvenile dermatomyositis. They may also help in prognostication.

Desquamative Interstitial Pneumonia Complicated with IgG4-related Lung Disease.

As an idiopathic interstitial pneumonia, desquamative interstitial pneumonia (DIP) is an uncommon form of interstitial lung disease and is considered to be a smoking- or dust inhalation-related interstitial pneumonia in the majority of cases. However, the details regarding immunoglobulin G4 (IgG4)-related lung disease remain unclear and controversial. We herein report the first case of DIP complicated with IgG4-related lung disease. Even if a patient has a smoking history, we emphasize the importance of exploring the association between DIP and IgG4-related lung disease to clarify the pathogenesis of these two disorders.

Managing interstitial lung disease detected on CT during lung cancer screening.

As long-term smokers undergo computed tomography (CT) to screen for lung cancer, cases of interstitial lung disease are being discovered incidentally. This article explains how to distinguish among the most common forms of interstitial lung disease in this situation and the role of primary care physicians in managing them.

Idiopathic Interstitial Pneumonias (IIPs): Review of Clinical, Radiographic and High-Resolution Computed Tomography (HRCT)

Making a confident diagnosis is a complex task for a specific form of interstitial lung disease and providing appropriate management in an attempt to achieve normalization of the disease can put up an alarming process for the clinicians. A set of diffuse and restrictive lung diseases incorporate with idiopathic interstitial pneumonias, showing inflammation and fibrosis of the interstitium due to parenchymal damage. High-resolution computed tomography (HRCT) has magnified the diagnostic standpoint in stepwise identification and classified various patterns in the evaluation of interstitial lung disease. The aim of our review is to elaborate clinical, radiographic and typical and atypical HRCT findings of idiopathic interstitial pneumonias by correlating with its differential diagnosis. Idiopathic pulmonary fibrosis is the most predominant idiopathic interstitial pneumonias and its diagnosis needs to omit all other well-known causes of interstitial lung diseases. According to the 2011 evidence-based guidelines, usual interstitial pneumonia can be diagnosed by HRCT when all criteria are fulfilled. Non-specific interstitial pneumonia is distinguished by bilateral patchy ground-glass opacities and irregular linear/reticular opacities. Respiratory bronchiolitis associated-interstitial lung disease and desquamative interstitial pneumonia show centrolobular nodules and ground-glass opacities as imaging patterns. Cryptogenic organizing pneumonia consists of patchy peripheral or peribronchial consolidations, while ground-glass opacities with tendency for migration, which is evolving to fibrosis, in acute interstitial pneumonia. Lymphoid interstitial pneumonia and idiopathic pleuro-parenchymal fibroelastosis are classified under rare idiopathic interstitial pneumonias. HRCT images help radiologists in diagnosis and mapping specific patterns of idiopathic interstitial pneumonias. This article reviews the stages of evolution in HRCT features for idiopathic interstitial pneumonias.

Heart transplantation from a dermatomyositis donor: Case report and review

Dermatomyositis is known to have sequelae outside of dermatological and musculoskeletal findings. These can also include pulmonary manifestations in the form of interstitial lung disease (ILD). Cardiac manifestations can include: myopericarditis, dysrhythmias and congestive heart failure. There are even patients with dermatomyositis who have required ventricular assist devices, pacemakers, implantable cardiac devices and even cardiac transplantation. However, we report the case of a patient with dermatomyositis with associated ILD who required lung transplantation who subsequently became a cardiac donor himself after a catastrophic neurological event during his pulmonary deterioration and cardiac work-up. With no prior literature, to our knowledge, this is the first published description of usage of a dermatomyositis donor in with successful cardiac transplantation without post-operative sequelae of dermatomyosits cardiac manifestations.

Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM)-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

CYFRA 21.1 in bronchoalveolar lavage of idiopathic pulmonary fibrosis patients

ABSTRACTAim: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases, however, clinically relevant biomarkers of diagnosis or prognosis are lacking. In this study, we investigated the levels of a fragment of Cytokeratin 19 (CYFRA 21.1) in bronchoalveolar lavage (BAL) of IPF patients at time of diagnosis. We further evaluated associations between CYFRA 21.1, pulmonary function evolution, mortality, and BAL cell count. Materials and Methods: Using the Lumipulse® G1200, CYFRA 21.1 was measured in BAL samples of 81 IPF patients and 9 controls. Based upon the median detected level (1.2 ng/mL) of CYFRA 21.1 in IPF patients, they were subdivided into an IPF CYFRA 21.1 low group (≤ 1.2 ng/mL) and IPF CYFRA 21.1 high group (> 1.2 ng/mL). Results: The CYFRA 21.1 levels were significantly higher in BAL of IPF patients compared to controls (P = .0015).Worse survival was observed, but no changes in pulmonary function, for IPF patients with high CYFRA 21.1 levels versus patients with low CYFRA 21.1 levels [P = .030, HR: 0.41, (0.18-0.92)[. The CYFRA 21.1 level correlated with both neutrophils (%: R = 0.60, P < .0001; #: R = 0.47, P < .0001) and eosinophils (%: R = 0.38, P = .0005; #: R = 0.30, P < .0072). Conclusions: CYFRA 21.1 is increased in BAL of IPF patients. IPF patients with a high CYFRA 21.1 concentration have a worse survival. CYFRA 21.1 levels correlate with eosinophils and neutrophils. Further studies are warranted in using CYFRA 21.1 as a biomarker for IPF prognosis.

Idiopathic Pulmonary Fibrosis: A Study of 46 Patients from Western India: Clinical Presentations and Survival.

Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease (ILD) diagnosed all over the world as well as in India. The objective was to study the clinical presentations, treatment options, and survival of patients diagnosed with IPF. This was a 6-year retrospective observational study. All patients diagnosed with ILD underwent a comprehensive evaluation to confirm the diagnosis of IPF and were subsequently included in the study. Clinical data and laboratory data were recorded. Patients were treated as per current guidelines. Out of the total number of patients (n=123) diagnosed with ILD, 46 (37.4%) patients were included in the study [Males, n=19 (41%) and females, n=27 (59%)]. Sixty-seven percent (n=31) of the patients were in the age group of 61-80 years. The mean age of males and females was 68.36 and 66.25 years, respectively. Clubbing was observed in 67% (n=29) of the patients. The mean forced vital capacity (FVC) was 52%. High-resolution computed tomography (HRCT) of the chest showed a definite usual interstitial pneumonia (UIP) pattern of honeycombing in 60% (n=28) of the patients. Desaturation on a 6 min walk distance was noted in 60% (n=28) of the patients. Ten patients wrongly received-anti tuberculosis treatment (21%) before they were diagnosed with IPF. The median delay in diagnosis was 20 months. The 5-year survival rate was 25%; the average survival was 39 months. Patients receiving pirfenidone showed a survival benefit compared with those having received triple therapy. Survival in IPF was significantly low compared with that in other ILDs. Twenty-four (52%) patients died during the study. IPF is a disease which affects the fourth to seventh decade of the Indian population with low survival.