Factor In Idiopathic Pulmonary Fibrosis Research Articles

Intermittent hypoxia increases ROS/HIF-1α ‘related oxidative stress and inflammation and worsens bleomycin-induced pulmonary fibrosis in adult male C57BL/6J mice

Obstructive sleep apnea (OSA) has been increasingly recognized as a risk factor for idiopathic pulmonary fibrosis (IPF). The intermittent hypoxia (IH) and re-oxygenation of OSA contribute to poor outcomes of IPF, however, the potential mechanism remains unknown. Here, C57BL/6J mice were administered intratracheal injection of Bleomycin (BLM) or saline and then exposed to IH (alternating cycles of FiO2 21% for 60S and FiO2 10% for 30 s, 40 cycles/hour, 8 h/day) to mimic OSA or intermittent air (IA) for 4 days, 8 days or 21 days. This study found that pulmonary fibrosis in BLM + IH treated mice was more severe than that in BLM + IA group at day 8 and 21, but not observed at day 4. Besides, the expression of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α),which are related to hypoxia reduced oxidative stress and inflammation, were higher in BLM + IH treated mice than BLM + IA mice, and IH increased these indexes in BLM treated mice from day 4 to day 21. Interestingly, a positive linear correlation between the HIF-1α expression and hydroxyproline (HYP) content was observed. We further found some inflammatory cells in bronchoalveolar lavage fluid were increased significantly from day 4 to 21, and there was a positive correlation between inflammation and ROS expression. Our results demonstrated that IH aggravated BLM-induced pulmonary fibrosis, and ROS/HIF-1α related oxidative stress and inflammation involved. The increase of ROS/HIF-1α related oxidative stress and inflammation may be a potential mechanism of moderate-to-severe OSA in potentiating pulmonary fibrosis of IPF, which warrants further study.

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

BackgroundThe major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. MethodsThrough an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. ResultsOut of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. ConclusionIn this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

Examining lysyl oxidase-like modulation of collagen architecture in 3D spheroid models of idiopathic pulmonary fibrosis via second-harmonic generation microscopy.

.Significance: Idiopathic pulmonary fibrosis (IPF) patients have a poor prognosis with short lifespan following diagnosis as there are limited effective treatment options. Despite matrix stiffening being the hallmark of the disease there remains a lack of knowledge surrounding the underlying collagen alterations in the disease. Specifically, while increased collagen crosslinking has been implicated, the resulting effects on collagen macro/supramolecular changes have not been explored.Aim: We sought to determine if second-harmonic generation (SHG) microscopy could characterize differences in the collagen architecture in 3D spheroid models of IPF grown under different crosslinking modulation conditions (promotion and inhibition).Approach: We used SHG metrics based on the fiber morphology, relative SHG brightness, and macro/supramolecular structure by SHG polarization analyses to compare the structure of the IPF spheroids.Results: Comparison of the fiber morphology of the spheroids showed that the control group had the longest, straightest, and thickest fibers. The spheroids with crosslink enhancement and inhibition had the highest and lowest SHG conversion efficiencies, respectively, consistent with the resulting harmonophore density. SHG polarization analyses showed that the peptide pitch angle, alignment of collagen molecules, and overall chirality were altered upon crosslink modulation and were also consistent with reduced organization relative to the control group.Conclusions: While no single SHG signature is associated with crosslinking, we show that the suite of metrics used here is effective in delineating alterations across the collagen architecture sizescales. The results largely mirror those of human tissues and demonstrate that the combination of 3D spheroid models and SHG analysis is a powerful approach for hypothesis testing the roles of operative cellular and molecular factors in IPF.

Low income and outcome in idiopathic pulmonary fibrosis: An association to uncover

BackgroundLow income, a known prognostic indicator of various chronic respiratory diseases, has not been properly studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF. MethodsPatients were selected from the French national prospective cohort COFI. Patients’ income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to their residential address. Patients were classified in two groups as “low income” vs. “higher income” depending on whether their annual income was estimated to be < or ≥18 170 €/year (the first quartile of the income distribution in the study population). The survival and progression-free survival (PFS) of the groups were compared by a log-rank test and a Cox model in multivariate analysis. Results200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were significantly more likely to be of non-European origin (p < 0.006), and to have at least one occupational exposure (p < 0.0001), and they tended to have a higher cumulative exposure to fine particles PM2.5 (p = 0.057). After adjusting for age, gender, forced vital capacity at inclusion, geographical origin, and occupational exposure having a low-income level was a factor associated with a worse PFS (HR: 1.81; CI95%: 1.24–2.62, p = 0.001) and overall survival (HR: 1.49; CI95%: 1.0006–2.23, p = 0.049). ConclusionsLow income appears to be a prognostic factor in IPF. IPF patients with low incomes may also be exposed more frequently to occupational exposures.

Occupational and environmental risk factors of idiopathic pulmonary fibrosis: a systematic review and meta-analyses

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease of unknown cause. It has a high risk of rapid progression and mortality. We conducted a systematic review and meta-analysis to evaluate the risk factor of IPF. We searched Medline, Embase, and the Cochrane library from the earliest record to March, 2020. Case–control studies on occupational and environmental risk factors or on jobs with a risk of IPF were searched for. From 2490 relevant records, 12 studies were included. Any occupational or environmental exposure to metal dust (OR 1.83, 95% CI 1.15–2.91, I2 = 54%), wood dust (OR 1.62 5% CI 1.04–2.53, I2 = 5%) and pesticide (OR 2.07, 95% CI 1.24–3.45, I2 = 0%) were associated with an increased risk of IPF. Farming or agricultural work (OR 1.88, 95% CI 1.17–3.04, I2 = 67%) was also associated with an increased risk of IPF. Moreover, smoking increased IPF risk with an odds ratio of 1.39 (95% CI 1.01–1.91, I2 = 29%). In conclusion, metal dust, wood dust, pesticide, occupational history of farming or agriculture and ever smoking increased the risk of IPF.

The MUC5B-associated variant rs35705950 resides within an enhancer subject to lineage- and disease-dependent epigenetic remodeling.

The G/T transversion rs35705950, located approximately 3 kb upstream of the MUC5B start site, is the cardinal risk factor for idiopathic pulmonary fibrosis (IPF). Here, we investigate the function and chromatin structure of this –3 kb region and provide evidence that it functions as a classically defined enhancer subject to epigenetic programming. We use nascent transcript analysis to show that RNA polymerase II loads within 10 bp of the G/T transversion site, definitively establishing enhancer function for the region. By integrating Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analysis of fresh and cultured human airway epithelial cells with nuclease sensitivity data, we demonstrate that this region is in accessible chromatin that affects the expression of MUC5B. Through applying paired single-nucleus RNA- and ATAC-seq to frozen tissue from IPF lungs, we extend these findings directly to disease, with results indicating that epigenetic programming of the –3 kb enhancer in IPF occurs in both MUC5B-expressing and nonexpressing lineages. In aggregate, our results indicate that the MUC5B-associated variant rs35705950 resides within an enhancer that is subject to epigenetic remodeling and contributes to pathologic misexpression in IPF.

Air Pollution-An Overlooked Risk Factor for Idiopathic Pulmonary Fibrosis.

Air pollution is a major environmental risk to health and a global public health concern. In 2016, according to the World Health Organization (WHO), ambient air pollution in cities and rural areas was estimated to cause 4.2 million premature deaths. It is estimated that around 91% of the world’s population lives in places where air pollution exceeds the limits recommended by the WHO. Sources of air pollution are multiple and context-specific. Air pollution exposures are established risk factors for development and adverse health outcomes in many respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), or lung cancer. However, possible associations between air pollution and idiopathic pulmonary fibrosis (IPF) have not been adequately studied and air pollution seems to be an underrecognized risk factor for IPF. This narrative review describes potential mechanisms triggered by ambient air pollution and their possible roles in the initiation of the pathogenic process and adverse health effects in IPF. Additionally, we summarize the most current research evidence from the clinical studies supporting links between air pollution and IPF.

Telomere length across different UIP fibrotic-Interstitial Lung Diseases: a prospective Greek case-control study

IntroductionShort telomeres are recognized as risk factor for idiopathic pulmonary fibrosis (IPF). We aimed to assess the role of telomere length (TL) in fibrotic-Interstitial Lung Diseases (f-ILDs) associated with a usual interstitial pneumonia (UIP) pattern as well as in IPF acute exacerbation (IPF-AE). Aim and methodsTL was measured from peripheral white blood cells using a multiplex quantitative polymerase chain reaction in consecutive patients with f-ILDs, all presenting UIP pattern in the high-resolution chest-computed-tomography and compared to age-matched healthy controls. ResultsSeventy-nine individuals were included (mean age 69.77 ± 0.72 years); 24 stable IPF, 18 IPF-AE, 10 combined pulmonary fibrosis and emphysema, 7 Rheumatoid arthritis-UIP-ILDs and 20 controls. TL in all patients was significantly shorter compared to controls [mean T/S ratio (SE) 0.77 (±0.05) vs 2.26 (±0.36), p < 0.001] as well as separately in each one of f-ILD subgroups. IPF-AE patients presented significantly shorter TL compared to stable IPF (p = 0.029). Patients with IPF and shorter than the median TL (0−0.72) showed reduced overall survival (p = 0.004). T/S < 0.72 was associated with increased risk for IPF-AE (OR = 30.787, 95% CI: 2.153, 440.183, p = 0.012) independent of age, gender, smoking and lung function impairment. A protective effect of TL was observed, as it was inversely associated with risk of death both in UIP-f-ILDs (HR = 0.174, 95%CI: 0.036, 0.846, p = 0.030) and IPF patients (HR = 0.096, 95%CI: 0.011, 0.849, p = 0.035). ConclusionsShorter TL characterizes different UIP f-ILDs. Although no difference was observed in TL among diverse UIP subgroups, IPF-AE presented shorter TL compared to stable IPF. Reduced overall survival and higher hazard ratio of death are associated with shorter TL in IPF.

Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: a mendelian randomisation study

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease accounting for 1% of UK deaths. In the familial form of pulmonary fibrosis, causal genes have been identified in about 30% of cases, and a majority of these causal genes are associated with telomere maintenance. Prematurely shortened leukocyte telomere length is associated with IPF and chronic obstructive pulmonary disease (COPD), a disease with similar demographics and shared risk factors. Using mendelian randomisation, we investigated evidence supporting a causal role for short telomeres in IPF and COPD. Mendelian randomisation inference of telomere length causality was done for IPF (up to 1369 cases) and COPD (13 538 cases) against 435 866 controls of European ancestry in UK Biobank. Polygenic risk scores were calculated and two-sample mendelian randomisation analyses were done using seven genetic variants previously associated with telomere length, with replication analysis in an IPF cohort (2668 cases vs 8591 controls) and COPD cohort (15 256 cases vs 47 936 controls). In the UK Biobank, a genetically instrumented one-SD shorter telomere length was associated with higher odds of IPF (odds ratio [OR] 4·19, 95% CI 2·33-7·55; p=0·0031) but not COPD (1·07, 0·88-1·30; p=0·51). Similarly, an association was found in the IPF replication cohort (12·3, 5·05-30·1; p=0·0015) and not in the COPD replication cohort (1·04, 0·71-1·53; p=0·83). Meta-analysis of the two-sample mendelian randomisation results provided evidence inferring that shorter telomeres cause IPF (5·81 higher odds of IPF, 95% CI 3·56-9·50; p=2·19 × 10-12). There was no evidence to infer that telomere length caused COPD (OR 1·07, 95% CI 0·90-1·27; p=0·46). Cellular senescence is hypothesised as a major driving force in IPF and COPD; telomere shortening might be a contributory factor in IPF, suggesting divergent mechanisms in COPD. Defining a key role for telomere shortening enables greater focus in telomere-related diagnostics, treatments, and the search for a cure in IPF. Investigation of therapies that improve telomere length is warranted. Medical Research Council.

The prognostic role of gender, age and physiology index and C-reactive protein/albumin ratio in idiopathic pulmonary fibrosis

Aim: We aimed to compare the gender, age, and physiology index and C-reactive protein/albumin ratio in order to evaluate the prognosis, clinical course and survival of patients with idiopathic pulmonary fibrosis.Material and Method: Forty-seven patients with idiopathic pulmonary fibrosis diagnosed by radiologically or pathologically in the 8th clinic of our hospital between January 2013 and December 2018 included to the study. Demographic characteristics, pulmonary function tests, 6-minute walk test values, echocardiography results, life span, additional diseases, treatment information, laboratory results of patients, gender, age and physiology indexes and initial C-reactive protein/albumin ratio of the patients were recorded from the patient files. Results: According to gender, age and physiology index there were 25 (53.2%) patients in stage I, 11 (23.4%) patients in stage II, and 11 (23.4%) patients in stage III. The patients were divided into 2 groups according to their life conditions. The rate of respiratory failure, the mean pulmonary arterial pressure and gender, age, and physiology stage were significantly higher (p grup 0.05) in the exitus group. The 6- minute walk test was significantly lower in the exitus group (p&amp;lt;0.05). C-reactive protein/albumin ratio results were similar in both groups and there were no significant differences according to other parameters in both groups too. There was no significant difference between the C-reactive protein/albumin ratio values of the patients in each of the three gender, age, and physiology stages.Conclusion: Gender, age, and physiology stage is easy and useful but C-reactive protein/albumin ratio isn’t convenient to predict the prognosis of idiopathic pulmonary fibrosis. The elevation of pulmonary arterial pressure, low 6 minute walk test and presence of respiratory failure are poor prognostic factors in idiopathic pulmonary fibrosis.

The European MultiPartner IPF registry (EMPIRE): validating long-term prognostic factors in idiopathic pulmonary fibrosis

BackgroundSeveral registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF.MethodsThe multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors.ResultsThe cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3–3.7) and III (HR 4.0; 95% CI: 2.8–5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8–4.0) and 5.8 (95% CI: 4.0–8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5–2.9) and lung cancer (HR 2.6; 95% CI: 1.3–4.9).ConclusionsEMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.

Cigarette smoking aggravates bleomycin-induced experimental pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that typically leads to respiratory failure and death. The cause of IPF is poorly understood. Although several environmental and occupational factors are considered as risk factors in IPF, cigarette smoking seems to be the most strongly associated risk factor. Here firstly, we treated mice with cigarette (16 mg tar, 1.0 mg nicotine in each cigarette) smoking and tried to explore the role of cigarette smoking in pulmonary fibrosis. Mice were continuously subjected to smoke for about 1 h each day (12 cigarettes per day, 5 days per week) during 40 days. Bleomycin was administrated by intraperitoneal injection at a dose of 40 mg/kg on days 1, 5, 8, 11 and 15. We found bleomycin induced pulmonary fibrosis in mice, and cigarette smoking augmented bleomycin-induced fibrosis reflected by both in fibrotic area and percentages of collagen in the lungs. Then we prepared and employed cigarette smoke extract (CSE) in cell models and found that CSE could induce the activation of p-Smad2/3 and p-Akt, as well as collagen-I synthesis and cell proliferation in lung fibroblasts and pleural mesothelial cells (PMCs). TGF-β1 signaling mediated CSE-induced PMCs migration. Moreover, in vitro studies revealed that CSE had superimposed effect on bleomycin-induced activation of TGF-β-Smad2/3 and -Akt signaling. TGF-β-Smad2/3 and -Akt signaling were further augmented by cigarette smoking in the lung of bleomycin-treated mice. Taken together, these findings represent the first evidence that cigarette smoking aggravated bleomycin-induced pulmonary fibrosis via TGF-β1 signaling.

Nicotine Modulates Growth Factors and MicroRNA to Promote Inflammatory and Fibrotic Processes.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that destroys the structure and function of the lungs. Risk factors include advanced age and genetic predisposition. However, tobacco use is the chief modifiable risk factor. The prevalence of tobacco use in IPF reaches up to 80%. Although tobacco smoke contains over 5000 chemicals, nicotine is a major component. Nicotine is a bioactive molecule that acts upon nicotinic acetylcholine receptors expressed on neuronal and non-neuronal cells including endothelial cells. Accordingly, it has a pleiotropic effect on cell proliferation and angiogenesis. The angiogenic effect is partly mediated by stimulation of growth factors including fibroblast, platelet-derived, and vascular endothelial growth factors. Nintedanib, a Food and Drug Administration-approved drug for IPF, works by inhibiting receptors for these growth factors, suggesting a pathobiologic role of the growth factors in IPF and a potential mechanism by which tobacco use may exacerbate the disease process; additionally, nicotine downregulates anti-inflammatory microRNAs (miRs) in lung cells. Here, we profiled the expression of miRs in lung tissues explanted from a lung injury model and examined the effect of nicotine on one of the identified miRs (miR-24) and its downstream targets. Our data show that miR-24 is downregulated during lung injury and is suppressed by nicotine. We also found that nicotine upregulates the expression of inflammatory cytokines targeted by miR-24. Finally, nicotine stimulated growth factors, fibroblast proliferation, collagen release, and expression of myofibroblast markers. Taken together, nicotine, alone or as a component of tobacco smoke, may accelerate the disease process in IPF through stimulation of growth factors and downregulation of anti-inflammatory miRs.

Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a severe lung disease characterised by extensive pathological changes. The objective for this study was to identify the gene network and regulators underlying disease pathology...

A PROMISING PREDICTIVE FACTOR OF MORTALITY IN INTERSTITIAL LUNG DISEASE

SESSION TITLE: Diffuse Lung Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 pm - 02:00 pm PURPOSE: Many predictive risk factors of idiopathic pulmonary fibrosis (IPF/ UIP) such as FVC, DLCO, and 6-MWT showed low accuracy in recent clinical trials... Aims: to evaluate the prognostic value of the New York Heart Association index (NYHA) compared to high resolution CT, somatostatin receptor scintigraphy (octreoscan), and echocardiography METHODS: A prospective study population of 128 patients, IPF = 59, NSIP = 19, granulomatous diseases, such as sarcoidosis, Wegener granulomatosis, alveolitis, = 50 were enrolled respectively. The diagnosis of all patients was confirmed histologically. RESULTS: Median survival was 89.3 months (7.4 years) and 79.4 percent of patients were alive at 3 years after diagnosis with a poorer survival rate among UIP patients. Strong correlation was found with age (p<0.001), CT-score, octreoscan between all UIP patients with respect to NSIP and granulomatous diseases. No deaths were observed among patients with NYHA index and prognosis was progressively worse with increased index (LRT p-value <0.001). Among patients with UIP, NYHA was confirmed to be a performing prognostic factor, as survival of patients with moderate levels was lower than that observed in lower NYHA levels (p<0.01) Indeed, age and NYHA were independent prognostic factors (LLR test p-value <0.001) . CONCLUSIONS: The NYHA index is confirmed to be a reliable and important prognostic factor when observing the significant difference in survival rates among the different NYHA levels, and when confirming for the histological pattern of UIP. CLINICAL IMPLICATIONS: Following our findings we strongly recommend the use of NYHA as prognostic factor of IPF including graulomatous lung diseases. DISCLOSURES: no disclosure on file for Giovanni Bottino; No relevant relationships by Roberto CARBONE, source=Web Response no disclosure on file for Assaf Monselise; no disclosure on file for Paolo Paredi

EMPIRE Registry, Czech Part: Impact of demographics, pulmonary function and HRCT on survival and clinical course in idiopathic pulmonary fibrosis.

Prognostic factors of idiopathic pulmonary fibrosis (IPF) currently recognized include changes in vital capacity and radiologic findings. However, most of the prognostic studies in IPF are based on clinical studies with preselected IPF populations. Therefore, we decided to analyze the factors influencing IPF prognosis based on the real-practice data from our IPF registry. Data of 514 subjects consecutively entered since 2012 into Czech EMPIRE IPF registry were analyzed. Median age of our patient cohort was 67 years (50-82). Median overall survival (OS) of the cohort was 63.1 months. The clinical course of IPF according to FVC (forced vital capacity) changes was stabilized in 32.8% of patients (29.7% according to DLCO [diffuse lung capacity] changes), slowly progressive in 39.5% (45%), rapidly progressive in 23.5% (20.7%); and 1.7% patients had at least one acute exacerbation during follow-up. Deterioration in FVC of ≥10% at month 12 and in DLCO of ≥15% at months 12, 18, and 24 influenced the OS significantly. The fast progressors defined by the DLCO decline rate had higher risk of death compared to those defined by the FVC change over time. In multivariate analysis, age ≥70 years, interstitial HRCT scores ≥3, and change in DLCO of ≥15% at month 12 were confirmed as factors negatively influencing OS. DLCO changes over time were shown as a better predictor of mortality compared with FVC changes in our study. In our opinion it is necessary to implement the DLCO analysis into clinical trials and routine practice.

Antacid Therapy and Disease Progression in Patients with Idiopathic Pulmonary Fibrosis Who Received Pirfenidone

Background: Gastroesophageal reflux disease is a potential risk factor for idiopathic pulmonary fibrosis (IPF) progression; however, the impact of antacid therapy (AAT) is under debate. Objective: To evaluate the effect of AAT on IPF progression in pirfenidone-treated patients. Methods: This post hoc analysis included patients with IPF who received pirfenidone in 3 trials (CAPACITY [PIPF-004/PIPF-006] and ASCEND [PIPF-016]). Pulmonary function, exercise tolerance, survival, hospitalizations, and adverse events (AEs) over 52 weeks were analyzed by baseline AAT use. Disease progression was defined as a decrease in forced vital capacity (FVC) of ≥10%, a decrease in 6-min walking distance of ≥50 m, or death over 1 year. Results: Of 623 patients, 44% received AAT. No significant differences were found at 52 weeks (AAT versus non-AAT, respectively) in disease progression (24.9 vs. 30.6%; p = 0.12), all-cause mortality rate (2.9 vs. 4.0%; p = 0.47), IPF-related mortality rate (1.1 vs. 2.0%; p = 0.37), all-cause hospitalization rate (16.1 vs. 18.3%; p = 0.48), or mean change in percent FVC (-2.7 vs. -3.1%; p = 0.44). A relative, but not absolute, FVC decline of ≥10% favored AAT (15 vs. 22%; p = 0.03). Severe gastrointestinal AEs (3.7 vs. 0.9%; p = 0.015) and severe pulmonary infections (3.7 vs. 1.1%; p = 0.035) were more frequent with AAT. Conclusions: AAT and pirfenidone had outcomes comparable to those of pirfenidone alone in patients with IPF, underscoring the need for prospective trials to elucidate the role of AAT with or without antifibrotic drugs as a treatment for IPF.

The St. George\u2019s Respiratory Questionnaire as a prognostic factor in IPF

BackgroundIt is unclear whether health related quality of life (HRQL) may have a predictive value for mortality in idiopathic pulmonary fibrosis (IPF).We investigated the relationship between HRQL assessed using the St. George’s Respiratory Questionnaire (SGRQ) and survival time in patients with IPF, and tried to determine a clinical meaningful cut off value to predict poorer survival rates.MethodsWe retrospectively analyzed consecutive patients with IPF who underwent an initial evaluation from May 2007 to December 2012. The diagnosis of IPF was made according to the 2011 international consensus guidelines. We used Cox proportional hazard models to identify independent predictors for mortality rate in patients with IPF.ResultsWe examined 182 eligible cases, average age was 66 years old, and 86% were male. Mean levels of percent predicted FVC, DLco, six-minute-walk test distance, and the SGRQ total score were around 80%, 58%, 580 m, and 34 points. On multivariate analysis, the SGRQ total score (hazard ratio [HR], 1.012; 95% confidence interval [CI] 1.001–1.023; P = .029) and percent predicted FVC (HR, 0.957; 95% CI 0.944–0.971, P < .001) were independent predictors for mortality rate. Moreover, a score higher than 30 points in the SGRQ total score showed higher mortality rate (HR, 2.047; 95% CI, 1.329–3.153; P = .001).ConclusionsThe SGRQ total score was one of independent prognostic factors in patients with IPF. Total scores higher than 30 points were associated with higher mortality rates.Trial registrationThis study was retrospective, observational study, so it is not applicable.

P102 &lt;break /&gt; Building A Better Mousetrap: Expression of Surfactant Protein C (SFTPC) Mutations Induces Dose-Dependent Fibrotic Parenchymal Lung Remodeling In Vivo

Epithelial cell dysfunction has emerged as an important factor in Idiopathic Pulmonary Fibrosis (IPF) pathogenesis. Mutations in the Surfactant Protein C [SP-C] gene [SFTPC], an alveolar type 2 cell [AT2] restricted protein, have been linked to sporadic and familial forms of diffuse parenchymal lung disease [DPLD] including IPF. The …

Serial Measurements of Tricuspid Regurgitation Pressure Gradient by Echocardiography Predict Prognosis In Idiopathic Pulmonary Fibrosis

Background and Objectives: Idiopathic Pulmonary Fibrosis (IPF), especially with emphysema, reportedly involved with Pulmonary Hypertension (PH). However, it is not elucidated whether pulmonary arterial pressure changes serially during the course and influence on prognosis in IPF. We examined whether serial measurements of Tricuspid Regurgitation Pressure Gradient (TRPG) by echocardiography were meaningful predictors of IPF patient survival. Methods: We retrospectively investigated 83 IPF patients. The echocardiographic TRPG cutoff was set at 30 mmHg, and the subjects were divided into two groups: high TRPG and normal TRPG. We also evaluated the relationship between serial TRPG changes during follow-up. Results: A total of 28 patients were included in the high TRPG group. The high TRPG group showed significantly lower %FVC and %DLco, higher A-aDO 2 , shorter 6-minute walk test distance, and more frequent emphysema than the normal TRPG group. The high TRPG group also had poorer survival than the normal TRPG group. A multivariate Cox proportional hazard model demonstrated that TRPG, %FVC, and A-aDO 2 significantly affected patient survival. Thirty-six patients underwent echocardiography twice. At the time of the second echocardiog- raphy, 7 patients with normal TRPG at baseline (n=22) increased to a TRPG of more than 30 mmHg. These patients had significantly showed poorer survival. Conclusions: TRPG is an independent prognostic factor in IPF. Emphysema involvement, de- creased DLco, and decreased FVC were associated with an increase in TRPG. Serial measure- ments of TRPG are recommended for the early detection of PH and predict prognosis in IPF patients.