Idiopathic Pulmonary Fibrosis Cases Research Articles

Association of serum levels of laminin, type IV collagen, procollagen III N-terminal peptide, and hyaluronic acid with the progression of interstitial lung disease.

Noninvasive and convenient tests to assess pulmonary fibrosis and disease progression in interstitial lung diseases (ILDs) are currently unavailable. The extracellular matrix molecules, laminin (LN), type IV collagen (IVC), procollagen III N-terminal peptide (PIIINP), and hyaluronic acid (HA) are involved in ILD development and progression. This study aims to investigate the association of disease progression and serum levels of LN, IVC, PIIINP, and HA in patients with ILD. This retrospective study included 323 patients (162 cases of idiopathic pulmonary fibrosis [IPF] and 161 cases of connective tissue diseases ILD [CTD-ILD]) treated in Shanghai Pulmonary Hospital between January 2013 and January 2015 and 160 healthy controls. Serum LN, IVC, PIIINP, and HA were analyzed by radioimmunoassay. Data of the percentage of forced vital capacity in the prediction value (FVC%pred), the percentage of diffusing capacity of the lung for carbon monoxide in the prediction value (DLCO%pred), high resolution computed tomography (HRCT) score, and patient mortality were collected. Serum LN, IVC, PIIINP, and HA were significantly increased in the patients with IPF or CTD-ILD compared with the healthy controls (all P < .05) and were further elevated in the acute exacerbation cases (all P < .05). Serum LN, IVC, PIIINP, and HA positively correlated with HRCT score and negatively correlated with FVC%pred and DLCO%pred significantly in the patients (all P < .05). The survived patients had significantly lower serum LN, IVC, PIIINP, and HA than the dead patients (all P < .05). Serum levels of LN, IVC, PIIINP, and HA may reflect ILD progression and may be indicators for the severity of ILDs.

Occupational exposure and idiopathic pulmonary fibrosis: a multicentre case-control study in Korea.

Multicentred hospital-based cases and control subjects in Korea. To evaluate the association between idiopathic pulmonary fibrosis (IPF) and hazardous materials to which people are occupationally exposed. A multicentre, hospital-based, matched case-control study was performed. The ratio of IPF cases to controls was 1:1 (n = 78 in each group). IPF cases and controls were matched in terms of age group, sex and place of residence. Conditional logistic regression analysis was performed. In simple logistic regression analysis, exposure to metal dust and any exposure for >1 year in an occupational setting were significantly associated with IPF (metal dust OR 4.00, 95%CI 1.34-11.97; any exposure OR 3.67, 95%CI 1.02-13.14). After adjustment for environmental and military exposures and smoking history, the OR for metal dust exposure was 4.97 (95%CI 1.36-18.17) in multiple logistic regression analysis. Metal dust was associated with incident IPF in Seoul and Gyeonggi Provinces in Korea. This information will be used to support a tailored preventive strategy in specific industries or occupations.

Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis

Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.

Clinical characteristics in patients with asymmetric idiopathic pulmonary fibrosis

BackgroundA group of patients with idiopathic pulmonary fibrosis (IPF) presents with disease affecting one lung markedly more than the other. At this time, it is unclear how this population differs from those who present with more symmetric disease. We sought to explain the characteristics of the asymmetric group and how their disease progresses. MethodsIn this retrospective case-control study we accessed an interstitial lung disease (ILD) database and identified 14 asymmetric IPF cases via high-resolution computed tomography (HRCT) scoring of each lung lobe's disease severity. We identified 28 symmetric IPF controls from the same database using the same methods, and compared the clinical features of each group. ResultsPatients with asymmetric disease exhibited similar demographics as those in the general IPF population; they were predominantly male (64%), elderly (69 years old), and used tobacco (57%). We found a trend toward significantly increased all-cause mortality in the case population two years following diagnosis (p = 0.089). Pulmonary function tests were significantly lower in the case group at the time of diagnosis, then both groups experienced gradual decline. We found no statistically significant differences in number of IPF exacerbations (cases 43%, controls 39%, p = 0.824) and gastro-esophageal reflux (both groups 50%). ConclusionPatients with asymmetric IPF resemble patients in the general IPF population but may have a lower overall survival rate. Further systemic factors may be studied to identify reasons for disease asymmetry and clinical decline in this population.

Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients from Four European Populations.

Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94–3.06); 1.80 × 10−11]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05–1.60); 4.03 × 10−4] and combined European IPF cases [2.18 (3.16–1.50); 3.73 × 10−5]. The network analysis for these variants indicated gene–gene and gene–phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers.

Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada.

Idiopathic pulmonary fibrosis (IPF) is a rare disease, with estimates of prevalence varying considerably across countries due to paucity in data collection. The aim of this study was to investigate the prevalence and incidence of IPF in Canada using administrative data requiring minimal extrapolation.We used mandatory national administrative data from 2007-2011 to identify IPF cases of all ages with an International Classification of Diseases (Version 10, Canadian) diagnosis code of J84.1. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases, and a narrow definition that required further diagnostic testing prior to IPF diagnosis. We explored survival and quality of life.For all ages, the broad prevalence of IPF was 41.8 per 100 000 (14 259 cases) and was higher for men. The incidence rate was 18.7 per 100 000 (6390 cases) and was higher for men. The narrow prevalence was 20.0 per 100 000 (6822 cases) and incidence was 9.0 per 100 000 (3057 cases). The 4-year risk of death was 41.0% and the quality of life with IPF after 2 years was lower than for Global Initiative for Chronic Obstructive Lung Disease stage IV chronic obstructive pulmonary disease.Using comprehensive national data, the prevalence of IPF in Canada was higher than other national estimates, suggesting that either IPF may be more common in Canada or that data capture may have been previously limited.

Comparative proteomic analysis of bronchoalveolar lavage of familial and sporadic cases of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive deterioration of the alveolar integrity. Among IPF identified phenotypes, that of familial (f-)IPF is usually associated with several gene mutations which are seldom observed in sporadic (s-)IPF. This study aimed at investigating the molecular patterns and variability in f-IPF and s-IPF patients through a differential proteomic analysis. Protein patterns of bronchoalveolar lavage fluid (BALF) samples from 10 familial and 17 sporadic IPF patients were compared using 2D electrophoresis and mass spectrometry. Principal component analysis (PCA) was applied to proteomic data and an enrichment analysis was also performed to characterize specific pathogenic mechanisms and to identify potential biomarkers. BALF samples from f-IPF showed 87 protein spots differentially expressed than those from s-IPF samples; once identified, these spots revealed 22 unique proteins. The functional analysis showed that the endothelial reticulum stress probably plays a central pathogenetic role in f-IPF with an up-regulation of proteins involved in wounding and immune responses, coagulation system, and ion homeostasis. Up-regulated proteins in the s-IPF group were those involved in the oxidative stress response. PCA analysis of differentially expressed proteins clearly distinguished f-IPF from s-IPF patients, and in agreement with radiological and histological patterns, pointed out a higher heterogeneity in f-IPF than s-IPF samples. The ‘Slit/Robo signaling’, ‘clathrin-coated vesicle’ and ‘cytoskeleton remodelling’, were extrapolated by ‘pathways analysis’ and the results of ‘diseases (by biomarkers)’ highlighted a ‘connective tissue and autoimmune disease’, two aspects of increasing interest in IPF.

Could prominent airway-centered fibroblast foci in lung biopsies predict underlying chronic microaspiration in idiopathic pulmonary fibrosis patients?

Chronic occult aspiration of small droplets (microaspiration) due to gastroesophageal reflux disease (GERD) and/or hiatal hernia is postulated to be a contributing factor in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Usual interstitial pneumonia (UIP) is the histopathologic correlate of IPF. We hypothesized that chronic microaspiration may manifest as prominent airway-centered fibroblastic foci (FFs) in IPF. UIP cases diagnosed by wedge biopsies over a 6-year period (2006-2011) were identified and scored (1-3) for the prominence of airway-centered FFs by 2 authors blinded for clinical history. Relevant clinical information was obtained. Thirty-seven patients (22 men) were diagnosed with IPF by multidisciplinary approach. Thirteen cases (35.1%) demonstrated high airway-centered FF score (score 3). Twenty (54.1%) patients carried a clinical diagnosis of GERD, and 3 patients (8.1%) had hiatal hernia. High airway-centered FF score was significantly associated with hiatal hernia diagnosis (P=.037) but not with a diagnosis of GERD or the use of proton pump inhibitors/histamine-2 receptor antagonists. High airway-centered FF score was associated with airway-centered acute inflammation (P=.028) and peribronchiolar granulomas (P=.042). In summary, IPF cases with hiatal hernia were more likely to have a prominent airway-centered FF. Given the strong association between hiatal hernia and GERD and their risk for developing chronic microaspiration, the prominent airway-centered FF in UIP might predict the presence of chronic microaspiration, acknowledging that GERD and proton pump inhibitor/histamine-2 receptor antagonist use failed to demonstrate a significant association. Larger studies are warranted for further investigation.

Clinical Experience of the Long-term Use of Pirfenidone for Idiopathic Pulmonary Fibrosis.

Long-term effects of pirfenidone have been poorly understood to date. This study investigated the clinical efficacy and safety of long-term pirfenidone use for idiopathic pulmonary fibrosis (IPF) in clinical practice. This survey study was a retrospective observational study. A survey was used to collect clinical information on IPF cases that were treated with pirfenidone. This survey sheet came from physicians belonging to the Diffuse Lung Diseases Research Group. 502 patients at 22 institutes received pirfeidone treatment. Of the 502 cases, pirfenidone treatment was terminated in under one year in 186 cases (37.1%); adverse effect was the most frequent reason for termination. The pirfenidone treatment lasted for two years or longer in 111 cases (22.1%). The mean change in the forced vital capacity (FVC) was -30±224 (SD) mL in the first year of treatment, -158±258 mL in the second year, and -201±367 mL in the third year. FVC improved by 10% or more in the first year in 10 (14.7%) of 68 cases, and showed a change of ±10% in 47 (69.1%) cases. It showed a change of ±10% in the second and third years in 61.7% and 62.5% of the patients, respectively. The FVC improved in only a small percentage of patients who received pirfenidone treatment for a long period of time. However, a decrease in the FVC was prevented for three years in over half of the cases.

Idiopathic Pulmonary Fibrosis in United States Automated Claims. Incidence, Prevalence, and Algorithm Validation.

Estimates of idiopathic pulmonary fibrosis (IPF) incidence and prevalence from electronic databases without case validation may be inaccurate. Develop claims algorithms to identify IPF and assess their positive predictive value (PPV) to estimate incidence and prevalence in the United States. We developed three algorithms to identify IPF cases in the HealthCore Integrated Research Database. Sensitive and specific algorithms were developed based on literature review and consultation with clinical experts. PPVs were assessed using medical records. A third algorithm used logistic regression modeling to generate an IPF score and was validated using a separate set of medical records. We estimated incidence and prevalence of IPF using the sensitive algorithm corrected for the PPV. We identified 4,598 patients using the sensitive algorithm and 2,052 patients using the specific algorithm. After medical record review, the PPVs of these algorithms using the treating clinician's diagnosis were 44.4 and 61.7%, respectively. For the IPF score, the PPV was 76.2%. Using the clinical adjudicator's diagnosis, the PPVs were 54 and 57.6%, respectively, and for the IPF score, the PPV was 83.3%. The incidence and period prevalences of IPF, corrected for the PPV, were 14.6 per 100,000 person-years and 58.7 per 100,000 persons, respectively. Sensitive algorithms without correction for false positive errors overestimated incidence and prevalence of IPF. An IPF score offered the greatest PPV, but it requires further validation.

A Dataset of 26 Candidate Gene and Pro-Inflammatory Cytokine Variants for Association Studies in Idiopathic Pulmonary Fibrosis: Frequency Distribution in Normal Czech Population.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia with poor diagnosis and a median survival of 2–3 years from initial diagnosis (1, 2). The cellular inflammation drives the fibrotic response in lung and plays a major role in IPF pathogenesis (3). Inflammatory cells (majorly, type 2 alveolar epithelial cells) release TGF-β, the key mediator of pulmonary fibrosis, that regulates several profibrotic cytokines/chemokines, their receptors, receptor subunits, and growth factors inducing process of epithelial–mesenchymal transition (EMT) (3, 4). Among the pro-inflammatory and profibrotic cytokines involved in IPF pathogenesis, interleukin (IL)-1 (4), IL-1β (5), IL-4, IL-5 (6), IL-6Rα (4), angiogenic IL-8/CXCL-8 (7), IL-13, its receptor IL-13 Rα2 (8), and IL-33 (9) have been implicated in accelerated inflammation and irreversible damage to lung architecture with loss of alveolar-capillary barrier basal membrane leading to persistent fibrosis. Genes encoding these factors exhibit nucleotide variation that could affect the severity of immune/inflammatory reactions and extent of any subsequent dysregulated fibroproliferative activity in disease development. Furthermore, variants in mucin-encoding genes (10–13) and in genes for pathogen-associated molecular patterns (PAMPs) receptors of innate immunity known as toll-like receptors (TLRs) (14, 15) have been also implicated in IPF immunopathogenesis and related to rapid progression of the disease. Investigations of these “candidate” gene variant(s) e.g., in case-control association studies may, therefore, provide novel insight into underlying mechanism of IPF susceptibility/disease outcome and, further, may aid to develop novel diagnostic approaches and eventually therapeutic interventions based on genetic information (16). A candidate gene study typically involves genotyping 5–50 single nucleotide polymorphisms (SNPs) within gene(s) for its coding and non-coding/regulatory regions (17). Irrespective of the number of tested gene variants; for a standard conductance, data collection, and transparent reporting of a genetic association study, the recommendations of STrengthening the REporting of Genetic Association studies (STREGA) and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) should be considered (16). In case-control studies, knowledge of frequency distribution of candidate gene loci/variants among normal (healthy control) population(s) is necessary and could be useful also for genetically related population(s) to determine the gene variants associated with disease and/or its clinical course. The role of inflammatory and profibrotic mechanisms involving gene variation has been investigated in IPF and spectrum of susceptible polymorphic gene variants, including those in genes of immune reactions and signaling processes, have been recently reported from both genome-wide association studies (GWAS) and population-based case-control studies (14, 18, 19) performed mostly in US Caucasians, and also in some other ethnicities. The nominated gene variants, summarized in Table ​Table1,1, are of different functions and implicate some yet-unanticipated pathways in IPF pathogenesis, including endoplasmic reticulum stress and unfolded protein response, cellular senescence, DNA-damage response, and already known Wnt–β-catenin signaling (20). The distribution of SNPs may greatly differ with populations (ethnicities), for example, a high frequency of MUC5B rs35705950*T allele in IPF cases is observed among European-Americans (14–34%) (21, 22), while its low frequency is characteristic for Asians, such as Chinese (3.3%) (23), Japanese (3.4%) (24), and Korean (1.0%) cohorts (11). Similarly, MUC2 rs7934606*A allele exhibit frequency of 41% in Europeans and 1% in Asians (1000 Genomes Project Phase 3 allele frequencies). Furthermore, in context of participation of more than one gene in IPF pathogenesis, it will be important to analyze multiple susceptible gene variants. The approach of analyzing common and rare genetic factors in IPF susceptibility may provide novel insights into IPF and it could also be helpful in identifying population-specific rare variants, predominant panel of candidate gene variants for IPF risk and in understanding the basis of variable disease severity or progression among different populations. Table 1 List of candidate SNPs investigated in the study. No complex data have been yet reported on IPF-related variants in Slavonic populations, including Czechs. Starting our investigations of plausible multiple IPF susceptibility polymorphisms primarily in Czech and also related populations, we adopted allele-specific MALDI-TOF mass spectrometry-based SNPs genotyping assay for determination of gene variation in the relevant targets. Several IPF susceptible SNPs in genes of various functional categories were multiplexed, and in the first phase genotyped in probands from normal (healthy) Czech population using Sequenom MassARRAY platform. In the current dataset manuscript, we, besides genotyping methodology, report the genotype, allele, and phenotype (carriage rate) frequencies for plausible IPF susceptibility variants among normal population of Czech Republic of Western Slavonic (Caucasian) ancestry.

Profile of Idiopathic Pulmonary Fibrosis Cases at a Tertiary Care Institute

Objective: Idiopathic pulmonary fibrosis is characterized by acute or chronic diffuse involvement of pulmonary parenchyma leading to a variable degree of lung fibrosis. Study was planned to asses clinical profile of patients with idiopathic pulmonary fibrosis (IPF) and methods used for diagnosis. Material and methods: It was a retrospective analysis of symptoms, signs, radiological findings and lung biopsy of patients diagnosed to have IPF over a 16-month period. Results: During the study period, 185 patients (85 men) with a mean age of 44.63 ± 10.4 years were diagnosed to have IPF. Breathlessness (100%) and dry cough (53.4%) were the most common presenting symptoms. Patients were diagnosed based on clinical features and high resolution chest tomography (HRCT) findings. HRCT was performed in all patients; 90% had features suggestive of diffuse interstitial fibrosis. Transbronchial lung biopsy (TBLB) was performed in 20 (10%) patients. Conclusion: IPF is diagnosed more commonly now than in the past. Indian patients may be developing the disease a decade earlier than their counterparts in the West. TBLB and HRCT are useful in establishing diagnosis. IPF should be considered a distinct clinical entity rather than a diagnosis of exclusion.

Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction

Idiopathic pulmonary fibrosis (IPF) is a degenerative disease of the lungs with an average survival post-diagnosis of 2-3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protection are found in both familial and sporadic IPF cases. However, the lack of mouse models that faithfully recapitulate the human disease has hampered new advances. Here, we generate two independent mouse models that develop IPF owing to either critically short telomeres (telomerase-deficient mice) or severe telomere dysfunction in the absence of telomere shortening (mice with Trf1 deletion in type II alveolar cells). We show that both mouse models develop pulmonary fibrosis through induction of telomere damage, thus providing proof of principle of the causal role of DNA damage stemming from dysfunctional telomeres in IPF development and identifying telomeres as promising targets for new treatments.

Serum levels of matrix metalloproteinases in patients with idiopathic pulmonary fibrosis and their clinical value

Objective To investigate serum levels of matrix metalloproteinase (MMP)-1, -2 and -9 in patients with idiopathic pulmonary fibrosis (IPF), and to assess their clinical value. Methods 39 clinically confirmed IPF cases and 36 healthy controls were recruited. A sample of 5 ml peripheral blood was collected from each individual and serum levels of MMP-1, -2 and -9 were detected by the enzyme-linked immunosorbent assay.Forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO) were measured in IPF patients. Serum levels of MMP-1, -2 and -9 were compared between the groups. The correlations between serum levels of MMPs and lung function indicators were analyzed. Results The median serum levels of MMP-1, MMP-2 and MMP-9 were higher in the IPF group than in the control group〔906.30 (613.50-1139.23) μg/L vs. 808.38 (596.59-1249.36) μg/L, 9.13 (5.95-11.92) μg/L vs. 7.72 (5.28-10.35) μg/L, 14.56 (8.24-18.96) μg/L vs. 11.38 (8.07-17.14) μg/L, Z=-2.397, -3.564, -4.152, respectively, P=0.017, 0.000, 0.000〕. In patients with IPF, the serum level of MMP-2 was negatively correlated with DLCO% (r=-0.53, P=0.011) and the serum level of MMP-9 had a negative correlation with FVC% (r=-0.49, P=0.020) and DLCO% (r=-0.58, P=0.005). Conclusions Taken together, serum MMP-1 , MMP-2 and MMP-9 levels may help in the clinical diagnosis of IPF. MMP-2 and MMP-9 may be important biomarkers to predict the prognosis of IPF. Key words: Pulmonary fibrosis; Matrix metalloproteinases

The evaluation of clinical usefulness of transbrochoscopic lung biopsy in undefined interstitial lung diseases: a retrospective study.

Previous studies mostly focused on the diagnostic accuracy of transbronchoscopic lung biopsy (TBLB) in the diagnosis of interstitial lung diseases (ILDs). We aimed to explore the clinical usefulness of TBLB results in the diagnostic procedure of undefined ILDs. The retrospective analysis included patients undergoing TBLB for the diagnosis of undefined ILDs from January 2007 to December 2010. The clinically useful TBLB was defined as that lead to a specific histopathological diagnosis or that was consistent with the working diagnosis based on existing clinical and radiological data. A total of 664 patients were included in the study. TBLB failed to obtain lung parenchyma in 155 cases (23.3%). TBLB was considered clinically helpful in 202 procedures (30.4%), including 114 cases that provided definitive histopathological diagnoses and 88 cases that were consistent with working diagnoses. Among 202 cases of clinically useful TBLBs, the majority were diagnosed as pulmonary alveolar proteinosis (PAP) (67 cases, 33.2%), connective tissue disease-related ILDs (CTD-ILDs) (65, 32.2%) and idiopathic pulmonary fibrosis (IPF) (33, 16.3%). Although TBLB could provide definitive histopathological diagnoses in all cases diagnosed as PAP, only few cases of IPF (7, 21.2% of IPF diagnoses) and CTD-ILDs (9, 13.8% of CTD-ILD diagnoses) could be identified by TBLBs. The clinical usefulness of TBLB, in conjunction with thorough clinical and radiological data, in the diagnosis of ILDs may be varied depending on different subtypes. The use of histopathological analysis and the type of biopsy employed should therefore be considered on a case-by-case basis.

The genetic basis of idiopathic pulmonary fibrosis.

Throughout the past decade, there have been substantial advances in understanding the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recently, several large genome-wide association and linkage studies have identified common genetic variants in more than a dozen loci that appear to contribute to IPF risk. In addition, family-based studies have led to the identification of rare genetic variants in genes related to surfactant function and telomere biology, and mechanistic studies suggest pathophysiological derangements associated with these rare genetic variants are also found in sporadic cases of IPF. Current evidence suggests that rather than existing as distinct syndromes, sporadic and familial cases of IPF (familial interstitial pneumonia) probably reflect a continuum of genetic risk. Rapidly evolving bioinformatic and molecular biology techniques, combined with next-generation sequencing technologies, hold great promise for developing a comprehensive, integrated approach to defining the fundamental molecular mechanisms that underlie IPF pathogenesis.

THE EFFECT OF SELENIUM SUPPLEMENTATION ON LUNG FUNCTIONS IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS

Idiopathic pulmonary fibrosis (IPF) is a common aggressive form of the idiopathic interstitial pneumonias of unknown cause. It is chronic, progressive, irreversible, fibrosing and lethal lung disease with a poor prognosis. The cardinal symptom of IPF is dyspnea; however, other pulmonary and extra-pulmonary symptoms are often present. The study aims to implement a novel pharmaceutical approach by administration of selenium accompanied with prednisone in an attempt to improve clinical outcome of IPF patients to decrease other medications toxicities and improve patients’ quality of life. This study was conducted at Kasr El-Ainy Chest Hospitals, from April 2012 to March 2014.The work included forty clinically and radiologically diagnosed cases of IPF and twenty healthy controls, they were subdivided into Group I: twenty IPF patients received; N-acetyl cysteine (NAC) 600 mg/3 times (for 3 months).Group II: twenty IPF patients received: Selenium 200 mcg/day (for 3 months). All cases subjected to medical history, clinical examination, plain X-ray chest, and High resolution computed tomography (HRCT), 6-minute walk test, and spirometry. All patients signed informed consents. The comparison of Selenium group with NAC revealed a significant increase in both of forced vital capacity (FVC) and Forced expiratory volume in the first second (FEV1) (p= 0.008, 0.016, respectively), using a Mann-Whitney test. There was no remarkable adverse drug reactions observed in both groups, and no serious drug interactions. This study showed that selenium supplementation in IPF patients’ significantly improved pulmonary functions, which reflect an antioxidant capacity. In addition patients’ clinical presentation shown as significant decrease of coughing and dyspnea on exertion.

Risk Factors for Cardiovascular Disease in People With Idiopathic Pulmonary Fibrosis

People with idiopathic pulmonary fibrosis (IPF) have been shown to be at an increased risk for cardiovascular (CV) disease, but reasons for this are unknown. The aim of this study was to compare the prevalence of common CV risk factors in people with IPF and the general population and establish the incidence of ischemic heart disease (IHD) and stroke after the diagnosis of IPF, controlling for these risk factors. We used data from a large, UK primary care database to identify incident cases of IPF and matched general-population control subjects. We compared the prevalence of risk factors for CV disease and prescription of CV medications in people with IPF (before diagnosis) with control subjects from the general population and assessed the incidence of IHD and stroke in people with IPF (after diagnosis) compared with control subjects. We identified 3,211 cases of IPF and 12,307 control subjects. Patients with IPF were more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with control subjects; they were also more likely to have been prescribed several CV drugs. The rate of first-time IHD events was more than twice as high in patients than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P < .001), but the incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and stroke were not altered substantially after adjusting for CV risk factors. Several CV risk factors were more prevalent in people with IPF; however, this did not account for the increased rate of IHD in this group of patients.

Serum Torque Teno Virus DNA Titer in Idiopathic Pulmonary Fibrosis Patients with Acute Respiratory Worsening

Acute respiratory worsening is defined as the unexpected rapid deterioration of idiopathic pulmonary fibrosis (IPF), and idiopathic acute respiratory worsening is known as an acute exacerbation of IPF. Torque teno virus (TTV) is a circular single-stranded DNA virus whose pathological significance remains unclear. The aim of the present study was to investigate the prevalence and titer of TTV DNA in IPF patients with acute respiratory worsening. The serum TTV DNA titer was measured using real-time PCR in nine IPF patients (two treated with steroids and immunosuppressants; seven treated without steroids or immunosuppressants) who developed acute worsening, including five patients with acute exacerbation. The serum TTV DNA titer was also measured in eight stable IPF cases and four IPF cases of lung cancer. In addition, in order to examine time course changes in the TTV DNA titer, the titer was measured more than once, with an interval of four weeks or longer, in eight patients. Among the nine IPF patients with acute worsening, the TTV DNA titer was above 1×10(6) copies/mL in two subjects without acute exacerbation who had been continuously treated with steroids and immunosuppressants. Meanwhile, the mean TTV DNA titer was 2.4±2.6 (×10(4) copies/mL) in the five patients with acute exacerbation and 3.1±3.4 (×10(4) copies/mL) in the eight patients with stable IPF. Moreover, the TTV DNA titers were increased in all three IPF patients who started treatment with steroids and immunosuppressants. Our results suggest that it is unlikely that TTV is directly involved in the onset of acute exacerbation of IPF and that the serum TTV DNA titer potentially reflects the immunosuppressive state of the host due to treatment.

The Impact of Lung Cancer on Survival of Idiopathic Pulmonary Fibrosis

Lung cancer (LC) is frequently associated with idiopathic pulmonary fibrosis (IPF). Despite this well-known association, the outcome of LC in patients with IPF is unclear. The objective of this study was to evaluate the impact of LC on survival of patients with associated IPF. A total of 260 patients with IPF were reviewed, and 186 IPF cases had complete clinical and follow-up data. Among these, five cases were excluded because LC was radiologically suspected but not histologically proven. The remaining 181 cases were categorized in two groups: 23 patients with biopsy-proven LC and IPF (LC-IPF) and 158 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared. Prevalence of histologically proven LC was 13%, and among those with LC-IPF cumulative incidence at 1 and 3 years was 41% and 82%. Patients with LC were more frequently smokers (91.3% vs 71.6%, P = .001), with combined pulmonary fibrosis and emphysema (52% vs 32%, P = .052). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC (median survival, 38.7 months vs 63.9 months; hazard ratio = 5.0; 95% CI, 2.91-8.57; P < .001). Causes of death in the study group were respiratory failure in 43% of patients, LC progression in 13%, and LC treatment-related complications in 17%. In patients with IPF, LC has a significant adverse impact on survival. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the cancer itself.