Incidence Of Idiopathic Pulmonary Fibrosis Research Articles

Physical activity and idiopathic pulmonary fibrosis: A prospective cohort study in UK Biobank and Mendelian randomization analyses

IntroductionThe impact of physical activity on the incidence of idiopathic pulmonary fibrosis (IPF) remains less well studied. This study aimed to investigate the relationship between moderate-to-vigorous physical activity (MVPA) and the risk of developing IPF. MethodsWe analyzed data from a prospective cohort study within the UK Biobank involving 502,476 participants. Participants were categorized as meeting or not meeting the 2017 UK Physical Activity Guidelines (150 min of moderate activity or 75 min of vigorous activity per week). The cumulative incidence and hazard ratios (HRs) for IPF were analyzed using the Kaplan–Meier method, log-rank test, and Cox regression. Two-sample Mendelian randomization (MR) analyses were performed to identify potential causal links between physical activity and IPF risk. ResultsOver a median of 12.2 y follow-up, we identified 1,639 incident IPF cases and 395,172 controls. Individuals who met the physical activity guidelines had a significantly lower risk of IPF than those who did not meet the guidelines (adjusted HR = 0.843, 95 % confidence interval [CI] = 0.765–0.930).The cumulative incidence of IPF was lower in the meeting guideline group than in the nonmeeting guideline group (Log-rank P = 0.0019). Two-sample MR analysis revealed that a 1-standard deviation increase in moderate-to-vigorous physical activity was linked to a reduced IPF risk (odds ratio [OR] = 0.17, 95 % CIs = 0.04 to 0.81, P = 0.026). Moreover, an increase in the number of days per week of moderate physical activity was genetically correlated with decreased IPF risk (OR = 0.32, 95 % CIs = 0.15–0.70, P = 0.003). ConclusionHigher levels of moderate-to-vigorous physical activity are causally associated with a significant reduction in the risk of developing IPF.

Mortality trends in idiopathic pulmonary fibrosis in Europe between 2013 and 2018.

Previous research has suggested that the incidence of idiopathic pulmonary fibrosis (IPF) is increasing in the UK and elsewhere. The aim of this study is to provide contemporary estimates of IPF mortality rates across 24 European Union (EU) countries from 2013 to 2018, using death certificate data from the European Statistics Institution (EUROSTAT) database. We extracted country data for IPF (International Classification of Diseases, 10th Revision: code J84.1) mortality from the EUROSTAT dataset. We calculated country-, age- and sex-specific death registration rates between 2013 and 2018. We used direct standardisation to compare rates between countries. We calculated annual trends in mortality rate ratios using a segmented regression model. The overall standardised mortality rate in 24 EU countries during this period was 3.90 (95% CI 3.80-3.90) per 100 000 person-years, with the rate rising from 3.70 in 2013 to 4.00 in 2018 (average annual percent change 1.74%, 95% CI 0.91-2.59%). We observed substantial inter-country differences, with the highest rates detected in Ireland, the UK and Finland, the lowest rate in Bulgaria, and middle rates in Germany, Greece, Italy, the Netherlands, Portugal and Slovenia. The IPF mortality rate is increasing across Europe. There are currently more than 17 000 deaths recorded from IPF each year in Europe but the marked geographical differences we observed suggest that this figure may underestimate the true rate considerably.

The Role of Proton Pump Inhibitors in the Realm of Idiopathic Pulmonary Fibrosis and its Associated Comorbidities: A Systematic Review.

As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management ofpatients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, "Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITYand ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic reviewand meta-analysison antacid and antireflux surgery in IPFnegate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.

Gastroesophageal reflux disease and idiopathic pulmonary fibrosis risk: A mendelian randomization study

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with unknown etiology and treatment options for it were limited. Whether Gastroesophageal reflux disease (GERD) could affect the occurrence of IPF remains unclear. Methods: Using available data from FINNGEN and IEU OpenGWAS, we performed Two-sample mendelian randomization (MR) to explore the causal relationship between GERD and IPF. Results: Using 65 GERD-related SNPs, we found the association between GERD and the risk of IPF was not statistically significant with IVW approach (OR = 1.20, 95% CI = 0.84-1.70, p = .32), MR-Egger regression (OR = 1.65, 95% CI = 0.19-14.43, p = .65) and weighted median approaches (OR = 1.44, 95% CI = 0.94-2.23, p = .09). However, heterogeneity was observed with MR-Egger ( p = .001) and IVW ( p = .001) analysis. Similar results were obtained with MR-PRESSO (global heterogeneity test p value <.01). After removing one outlier (rs9636202), with weighted median method, we found GERD increased the risk of IPF (OR 1.55, 95% CI: 1.01-2.36, p = .045) while not with the IVW (OR: 1.27, 95% CI: 0.91-1.78, p = .16) and MR-Egger method (OR: 2.01, 95% CI: 0.26-15.8, p = .51). Hence, we set a stricter instrument p value threshold to a level of <1 × 10−8, there was no statistical significance with MR estimates. Additionally, there was no directional pleiotropy observed (intercept = −0.01; SE = 0.036. p = .772). To validate causal effect of GERD on IPF, we identified three SNPs (rs79348626, rs12759463 and rs4269485) from another GWAS data that were significantly associated with GERD independently. The analysis showed no evidence of causality between GERD and IPF using the IVW method (OR = 0.91, 95% CI = 0.42-1.97, p = .814), MR-Egger regression (OR = 0.43, 95% CI = 0.06-3.07, p = .553) and weighted median approaches (OR = 0.90, 95% CI = 0.36-2.27, p = 0 0.819). Conclusions: Our analysis using MR does not support GERD could significantly increase the incidence of IPF, which suggests that treating GERD cannot reduce the risk of developing IPF.

Low-level ambient sulfur dioxide exposure and genetic susceptibility associated with incidence of idiopathic pulmonary fibrosis: A national prospective cohort study

BackgroundThe association between long-term air pollution exposure and the development of idiopathic pulmonary fibrosis (IPF) has been established, but the evidence regarding the effect of low levels of air pollution, especially ambient sulfur dioxide (SO2), is limited. Besides, the combined effect and interaction between genetic susceptibility and ambient SO2 on IPF remain uncertain. MethodsThis study retrieved data from 402,042 participants who were free of IPF at baseline in the UK Biobank. The annual mean concentration of ambient SO2 was estimated for each participant based on their residential addresses using a bilinear interpolation method. Cox proportional hazard models were used to examine the relationship between ambient SO2 and incident IPF. We further generated a polygenic risk score (PRS) for IPF and estimated the combined effects of genetic susceptibility and ambient SO2 on incident IPF. ResultsAfter a median follow-up of 11.78 years, 2562 cases of IPF were identified. The results indicated that each 1 μg/m3 increase in ambient SO2 was associated with a hazard ratio (HR) (95% confidence interval [CI]) of 1.67 (1.58, 1.76) for incident IPF. The study found statistically significant synergistic additive interaction between genetic susceptibility and ambient SO2. Individuals with high genetic risk and high ambient SO2 exposure had a higher risk of developing IPF (HR = 7.48, 95% CI:5.66, 9.90). ConclusionThe study suggests that long-term exposure to ambient SO2, even at concentrations lower than current air quality guidelines set by the Word Health Organization and European Union, may be an important risk factor for IPF. This risk is more pronounced among people with a high genetic risk. Therefore, these findings emphasize the need to consider the potential health effects of SO2 exposure and the necessity for stricter air quality standards.

Trends and Outcomes in Lung Transplantation in Patients with and without Idiopathic Pulmonary Fibrosis in Spain during the Period 2016-2020.

(1) Background: This paper aims to assess temporal trends (2016-2020) in incidence, patient's characteristics, complications, length of hospital stay (LOHS) and in-hospital mortality (IHM) among patients with and without idiopathic pulmonary fibrosis (IPF) undergoing lung transplantation (LTx). We also analyse the effect of the COVID-19 pandemic on LTx in these populations. (2) Methods: A retrospective, population-based observational study was conducted using the Spanish National Hospital Discharge Database. Multivariable adjustment was conducted with logistic regression to analyse the IHM. (3) Results: We identified 1777 admissions for LTx during the study period, of which 573 (32.2%) were performed in patients with IPF. The number of hospital admissions for LTx rose from 2016 to 2020, both in patients with and without IPF, but a marked reduction was observed from year 2019 to year 2020. Over time, the proportion of single LTx decreased and bilateral LTx increased significantly in both groups. The incidence of LTx complications increased significantly over time along with the increase in the incidence of IPF. No significant differences in the incidence of complications or in the IHM between patients with and without IPF were found. Suffering any complication of the LTx and pulmonary hypertension were conditions positively associated with IHM in patients with and without IPF. The IHM remained stable from 2016 to 2020 in both study populations and was not affected by the COVID pandemic. (4) Conclusions: Patients with IPF account for almost a third of all lung transplants. The number of LTx increased over time in patients with and without IPF, but a marked reduction was observed from 2019 to 2020. Although the proportion of LTx complications increased significantly over time in both groups, the IHM did not change. IPF was not associated with increased complications or IHM after LTx.

TO STUDY CLINICORADIOLOGICAL PROFILE OF IDIOPATHIC PULMONARY FIBROSIS (IPF) PATIENTS

Background - The term "interstitial lung disease" (ILD), or diffuse parenchymal lung disease (DPLD), represents a group of about 200 distinct disorders. Idiopathic pulmonary brosis (IPF) is one of the most severe forms of IIP. This study aims to observe clinicoradiological prole of idiopathic pulmonary brosis patients. A cross-sectional observational study (inpatients and out Methods- patients) visiting the Department of Respiratory Medicine, Gandhi Medical College, Bhopal for the period of 18 months from November 2019 to April 2021, diagnosed to have Idiopathic Pulmonary Fibrosis (IPF) by HRCT who meet the inclusion and exclusion criteria. The incidence of IPF is higher in males as Resultcompared to females. It appears mainly between the fth and seventh decades of life ,the mean age of IPF was 58.86 ± 11.93, and the maximum number of patients came under the age of 51–60 years .In this study, breathlessness and cough were the predominant symptoms in denitive UIP. The severity of breathlessness is higher in denitive UIP. In our study every patient with IPF, we found to have an abnormal chest xray. Hence, chest xray should be the rst investigation in any suspected case of IPF. The commonest chest radiographic abnormality in patients with IPF is peripheral reticular opacity, most marked at the bases. In this study, the most common HRCT Chest ndings in IPF patients were reticulations, subpleural and basal involvement, and brosis. In this study, the most common pattern of idiopathi Conclusion- c pulmonary brosis was denitive UIP and most common age group was 51–60 years old and IPF reveals a male predominance. Clubbing was found in 39.4% of patient's maximum with denitive UIP (28.8%). On auscultation, the most common ndings are ne crackles and the most common ndings on HRCT are reticulations So, the nal diagnosis of IPF is a multidisciplinary approach. Further study is needed with a larger sample size to understand the disease in detail.

Nationwide epidemiologic study for fibrosing interstitial lung disease (F-ILD) in South Korea: a population-based study

BackgroundFibrosing interstitial lung disease (F-ILD) is a major public health concern due to its poor prognosis. Recent clinical evidence shows that antifibrotic approaches such as pirfenidone and nintedanib provide better clinical outcome prediction in idiopathic pulmonary fibrosis (IPF) as well as selected progressive fibrosing ILD (PF-ILD) patients. Having epidemiologic insight into these diseases will be essential for the efficient utilization of these therapeutic resources. This study aimed to estimate the current prevalence, incidence, and mortality of F-ILD classified as idiopathic pulmonary fibrosis (IPF), PF-ILD other than IPF, and non-progressive F-ILD and their temporal trend in Korea.MethodsPopulation-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment (HIRA) database (2011–2018). Patients with IPF were identified using ICD-10 code, RID code, and differential diagnosis approach. By leveraging medical records available from claim data and referencing those used in clinical trials, rigorous diagnostic criteria for PF-ILD detection were implemented.ResultsFor the past eight years, the prevalence of IPF and PF-ILD has progressively increased, while non-progressive F-ILD has remained stable. IPF, PF-ILD, and non-progressive F-ILD prevalence per 100,000 in 2018 were 16.9, 10.4, and 11.7, respectively. The incidence of IPF in 2018 was more than twice that of 2012. The incidence of PF-ILD in 2018 was 1.5 times higher than that in 2012. In 2018, the mortalites were 10.3% and 12.2% for IPF and PF-ILD, respectively. The mortality rate of PF-ILD was greater than that of IPF in all years. Unclassifiable PF-ILD and rheumatoid arthritis-PF-ILD had the highest proportion and mortality among the PF-ILD subtypes.ConclusionThe prevalence and incidence of IPF and PF-ILD have been steadily increasing in recent years. The mortality rate of PF-ILD remained consistently high and exceeded those of IPF in all years.

Molecular mechanisms of alveolar epithelial cell senescence and idiopathic pulmonary fibrosis: a narrative review.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia of unknown etiology. An increasing number of studies have reported that the incidence of IPF increases with age. Simultaneously, the number of senescent cells increased in IPF. Epithelial cell senescence, an important component of epithelial cell dysfunction, plays a key role in IPF pathogenesis. This article summarizes the molecular mechanisms associated with alveolar epithelial cell senescence and recent advances in the applications of drugs targeting pulmonary epithelial cell senescence to explore novel therapeutic approaches for the treatment of pulmonary fibrosis. All literature published in English on PubMed, Web of Science, and Google Scholar were electronically searched online using the following keyword combinations: aging, alveolar epithelial cell, cell senescence, idiopathic pulmonary fibrosis, WNT/β-catenin, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB). We focused on signaling pathways associated with alveolar epithelial cell senescence in IPF, including WNT/β-catenin, PI3K/Akt, NF-κB, and mTOR signaling pathways. Some of these signaling pathways are involved in alveolar epithelial cell senescence by affecting cell cycle arrest and secretion of senescence-associated secretory phenotype-associated markers. We also found that changes in lipid metabolism in alveolar epithelial cells can be induced by mitochondrial dysfunction, both of which contribute to cellular senescence and development of IPF. Decreasing senescent alveolar epithelial cells may be a promising strategy for the treatment of IPF. Therefore, further investigations into new treatments of IPF by applying inhibitors of relevant signaling pathways, as well as senolytic drugs, are warranted.

Effect of M6A regulators on diagnosis, subtype classification, prognosis and novel therapeutic target development of idiopathic pulmonary fibrosis.

Molecular biology studies show that RNA N6-methyladenosine (m6A) modifications may take part in the incidence and development of idiopathic pulmonary fibrosis (IPF). Nonetheless, the roles of m6A regulators in IPF are not fully demonstrated. In this study, 12 significant m6A regulators were filtered out between healthy controls and IPF patients using GSE33566 dataset. Random forest algorithm was used to identify 11 candidate m6A regulators to predict the incidence of IPF. The 11 candidate m6A regulators included leucine-rich PPR motif-containing protein (LRPPRC), methyltransferase-like protein 3, FTO alpha-ketoglutarate dependent dioxygenase (FTO), methyltransferase-like 14/16, zinc finger CCCH domain-containing protein 13, protein virilizer homolog, Cbl proto-oncogene like 1, fragile X messenger ribonucleoprotein 1 and YTH domain containing 1/2. A nomogram model was constructed based on 11 candidate m6A regulators and considered beneficial to IPF patients using decision curve analysis. Consensus clustering method was used to distinctly divide IPF patients into two m6A patterns (clusterA and clusterB) based on 12 significant m6A regulators. M6A scores of all IPF patients were obtained using principal component analysis to quantify the m6A patterns. Patients in clusterB had higher m6A scores than those in clusterA. Furthermore, patients in clusterB were correlated with Th17 and Treg cell infiltration, innate immunity and Th1 immunity, while those in clusterA were correlated with adaptive immunity and Th2 immunity. Patients in clusterB also had higher expressions of mesenchymal markers and regulatory factors of fibrosis but lower expressions of epithelial markers. Lastly and interestingly, two m6A regulators, LRPPRC (p = 0.011) and FTO (p = 0.042), were identified as novel prognostic genes in IPF patients for the first time using an external GSE93606 dataset. Both of them had a positive correlation with a better prognosis and may serve as therapy targets. Thus, we conducted virtual screening to discover potential drugs targeting LRPPRC and FTO in the treatment of IPF. In conclusion, m6A regulators are crucial to the onset, development and prognosis of IPF. Our study on m6A patterns may provide clues for clinical diagnosis, prognosis and targeted therapeutic drugs development for IPF.

The efficacy and safety of pirfenidone in the treatment of HPS-related pulmonary fibrosis and Idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

The incidence of idiopathic pulmonary fibrosis is increasing year by year in the world, which has a greater impact on the quality of life of patients. In the past, symptomatic treatment was used in clinical practice, but the overall effect is still not good. Multiple clinical studies have demonstrated the efficacy of pirfenidone in the treatment of idiopathic pulmonary fibrosis; however, adverse reactions have been reported. We, therefore, systematically evaluated the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis. Relevant studies were retrieved from the Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature (CBM), Wanfang and Weipu databases between January 1999 and May 2020, including the keywords "pirfenidone" and "idiopathic pulmonary fibrosis", were included in our systematic review. Review Manager 5.4 software was used for data synthesis, and analyses of publication bias and sensitivity. Our systematic review included 13 studies involving a total of 13247 patients with idiopathic pulmonary fibrosis. Pirfenidone was associated with reduced declines in vital capacity (VC) and forced vital capacity (FVC) from baseline in patients with hermansky-pudlak syndrome (HPS)-related pulmonary fibrosis and to moderate idiopathic pulmonary fibrosis (IPF). Pirfenidone treatment was associated with lower reductions in FVC, lower reductions in 6-minute walking test distance, lower decreases in minimum oxygen saturation during the 6-minute walking test, lower all-cause death, lower relative risk of IPF-related death and increased progression-free survival compared to placebo. Progression-free survival was significantly longer in the pirfenidone group. The incidence of gastrointestinal, skin, nervous system, and liver function-related adverse events was significantly higher in the pirfenidone group compared to the control group. Pirfenidone has efficacy in delaying the progression of idiopathic pulmonary fibrosis. Pirfenidone is well-tolerated by the majority of patients; however, mild adverse reactions related to the gastrointestinal tract, skin, nervous system, and liver function are common. Overall, Pirfenidone may be an effective and well-tolerated treatment option for idiopathic pulmonary fibrosis.

Air pollutants, genetic susceptibility and risk of incident idiopathic pulmonary fibrosis.

Air pollutants are considered as non-negligible risk factors of idiopathic pulmonary fibrosis (IPF). However, the relationship between long-term air pollution and the incidence of IPF is unknown. Our objective was to explore the associations of air pollutants with IPF risk and further assess the modification effect of genetic susceptibility. We used land-use regression model estimated concentrations of nitrogen dioxide (NO2), nitrogen oxides (NO x ) and particulate matter (fine particulate matter with diameter <2.5 μm (PM2.5) and particulate matter with diameter <10 μm (PM10)). The polygenic risk score (PRS) was constructed using 13 independent single nucleotide polymorphisms. Cox proportional hazard models were used to evaluate the associations of air pollutants with IPF risk and further investigate the modification effect of genetic susceptibility. Additionally, absolute risk was calculated. Among 433 738 participants from the UK Biobank, the incidence of IPF was 27.45 per 100 000 person-years during a median follow-up of 11.78 years. The adjusted hazard ratios of IPF for each interquartile range increase in NO2, NO x and PM2.5 were 1.11 (95% CI 1.03-1.19), 1.07 (95% CI 1.01-1.13) and 1.09 (95% CI 1.02-1.17), respectively. PM2.5 had the highest population attribution risk, followed by NO x and NO2. There were additive interactions between NO2, NO x and PM2.5 and genetic susceptibility. Participants with a high PRS and high air pollution had the highest risk of incident IPF compared with those with a low PRS and low air pollution (adjusted hazard ratio: NO2 3.94 (95% CI 2.77-5.60), NO x 3.08 (95% CI 2.21-4.27), PM2.5 3.65 (95% CI 2.60-5.13) and PM10 3.23 (95% CI 2.32-4.50)). Long-term exposures to air pollutants may elevate the risk of incident IPF. There are additive effects of air pollutants and genetic susceptibility on IPF risk.

Left-sided heart failure burden and mortality in idiopathic pulmonary fibrosis: a population-based study

BackgroundCardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data.MethodsClinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression.ResultsFrom 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2–34.6) in 2010 to 20.9% (20.0–21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9–4.8) in 2017 to 3.4 (3.0–3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03–1.14) for all-cause mortality; 1.32 (1.09–1.59) for cardiovascular mortality).ConclusionLeft-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors. Comorbid left-sided HF is also a poor prognostic marker. More substantial reduction in left-sided HF prevalence than incidence suggests persistently high IPF mortality. Given rising IPF incidence in the UK, this calls for better management of comorbidities such as left-sided HF to help optimise IPF survival.

Occurrence of Idiopathic Pulmonary Fibrosis in Italy: Latest Evidence from Real-World Data.

The aim of the study was to evaluate the trend in the incidence of idiopathic pulmonary fibrosis (IPF) in a real-world setting of the Marche region, a region of Central Italy, between 2014 and 2019. This observational prospective study was based on administrative databases of hospital discharges and drug prescriptions. All adult residents in the Marche Region with a first prescription of antifibrotic drugs, or a first hospitalization with a diagnosis of IPF during the study period, were identified as incident cases of IPF. A multiple Poisson regression analysis was used to estimate the IPF incidence trend, adjusted for age, sex, and health conditions. The mean incidence rate was 9.8 cases per 100,000 person-years. A significant increasing trend of 6% per year was observed. The incidence rates were significantly higher in males than females, older subjects, and those with poorer health conditions. To our knowledge, this is the first study evaluating incidences of IPF over a 6-year period in Italy, combining hospital discharge and drug prescription databases. The study highlights that the combined use of two secondary sources is a reliable strategy to accurately identify new cases of IPF when the appropriate disease registry is lacking.

Idiopathic pulmonary fibrosis in the practice of a family doctor

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology, mainly characterized by a progressive deterioration in lung function due to active fibrosis. It is a variant of chronic progressive fibrosing interstitial pneumonia. The disease most often occurs between the ages of 50 and 70. According to the disease register in the Russian Federation, the prevalence of the disease in the Russian Federation is 4-7 people per hundred thousand of the population [1].Worldwide, the IPF incidence, prevalence and mortality increases over time [2, 3]. In a systematic review of the study by Hutchinson et al. [2] based on data on IPF morbidity and mortality in 21 countries between 1968 and 2012, it was determined that both morbidity and mortality have increased worldwide since 2000.

Sex Differences in the Incidence and Outcomes of Patients Hospitalized by Idiopathic Pulmonary Fibrosis (IPF) in Spain from 2016 to 2019.

(1) Background: To assess sex differences in the incidence, characteristics, procedures and outcomes of patients admitted with idiopathic pulmonary fibrosis (IPF); and to analyze variables associated with in-hospital mortality (IHM). (2) Methods: We analyzed data collected by the Spanish National Hospital Discharge Database, 2016–2019. (3) Results: We identified 13,278 hospital discharges (66.4% men) of IPF (primary diagnosis 32.33%; secondary diagnosis: 67.67%). Regardless of the diagnosis position, IPF incidence was higher among men than women, increasing with age. Men had 2.74 times higher IPF incidence than women. Comorbidity was higher for men in either primary or secondary diagnosis. After matching, men had higher prevalence of pulmonary embolism and pneumonia, and women of congestive heart failure, dementia, rheumatoid disease and pulmonary hypertension. Invasive ventilation, bronchoscopy and lung transplantation were received more often by men than women. IHM was higher among men with IPF as primary diagnosis than among women and increased with age in both sexes and among those who suffered cancer, pneumonia or required mechanical ventilation. (4) Conclusions: Incidence of IPF was higher among men than women, as well as comorbidity and use of bronchoscopy, ventilation and lung transplantation. IHM was worse among men than women with IPF as primary diagnosis, increasing with age, cancer, pneumonia or mechanical ventilation use.

Incidence and predictors of idiopathic pulmonary fibrosis complicating Type 2 diabetes: the Fremantle Diabetes Study Phase I.

During 106 865 person-years of follow up, 17 (1.3%) Fremantle Diabetes Study Phase I participants with Type 2 diabetes and 57 (1.1%) matched individuals without diabetes developed idiopathic pulmonary fibrosis (IPF), an incidence rate ratio (95% confidence interval) of 1.40 (0.76-2.44) (P = 0.22). In the diabetes cohort, age at diabetes diagnosis and total serum cholesterol (inversely) predicted incident IPF in competing risk multivariable models. The incidence of IPF was low in community-based cohorts, regardless of Type 2 diabetes status.

The relationship between the severity of pulmonary fibrosis and the lung cancer stage.

Background: The incidence of idiopathic pulmonary fibrosis (IPF) and mortality related to the disease have steadily increased in recent years. The risk of cancer is approximately eight times higher in IPF patients than in the general population. The purpose of this study is to determine whether the severity of IPF is related to the time interval between IPF diagnosis and lung cancer diagnosis and to the stage of lung cancer at diagnosis.Methods: In this retrospective cohort study, we reviewed the medical records of patients with lung cancer after IPF diagnosis from two tertiary hospitals in South Korea between 2003 and 2018. We identified 61 patients diagnosed with lung cancer at least 3 months after being diagnosed with IPF.Results: The included patients had a mean age of 71.0 years, and all but one were men (98.4%). The interval between IPF diagnosis and lung cancer diagnosis was not related to the gender-age-physiology (GAP) stage (p=0.662). However, in cox proportional hazard models, a higher GAP stage was significantly correlated with an advanced lung cancer stage (odds ratio 11.1, p=0.003).Conclusions: The lung cancer stage at diagnosis was higher in patients with a higher GAP stage than in those with a lower GAP stage. Physicians should consider implementing more frequent surveillance with computed tomography scans for patients with advanced IPF.

MUTYH Deficiency Is Associated with Attenuated Pulmonary Fibrosis in a Bleomycin-Induced Model

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible lung disease of unknown etiology with limited survival. IPF incidence and prevalence increase significantly with aging, which is associated with an age-related accumulation of oxidative DNA damage. The Mutyh gene is involved in the base excision repair (BER) system, which is critical for repairing the misincorporated adenine that is opposite to the oxidized guanine base, 8-oxoguanine, and maintaining the fidelity of DNA replication. We used Mutyh knockout mice and a bleomycin-induced pulmonary fibrosis model to test the effect of MUTYH deficiency on lesion progression. Unexpectedly, a much less severe lesion of pulmonary fibrosis was observed in Mutyh−/− than in Mutyh+/+mice, which was supported by assay on protein levels of TGF-β1 and both fibrotic markers, α-SMA and Vimentin, in pulmonary tissues of the model animals. Mechanically, MUTYH deficiency prevented the genomic DNA of pulmonary tissue cells from the buildup of single-strand breaks (SSBs) of DNA and maintained the integrity of mtDNA. Furthermore, increased mitochondrial dynamic regulation and mitophagy were detected in pulmonary tissues of the bleomycin-induced Mutyh−/− model mice, which could reduce the pulmonary epithelial cell apoptosis. Our results suggested that MUTYH deficiency could even induce protective responses of pulmonary tissue under severe oxidative stress.

Research Progress in the Pathogenesis of Idiopathic Pulmonary Fibrosis with Lung Cancer

特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）是一种原因不明，以弥漫性肺泡炎和肺泡结构紊乱最终导致肺间质纤维化为特征的疾病。针对IPF尚无有效的治疗手段，主要以延缓疾病进展、改善患者生活质量为主。而目前IPF合并肺癌（IPF with lung cancer, IPF-LC）的发病率越来越高，致使患者死亡率明显增加、生活质量显著下降。IPF-LC多见于男性、高龄和吸烟者，是一种临床表现缺乏特异性、无明确治疗方案、中位生存期短、预后较差的致死性疾病。目前IPF-LC发病机制及治疗方案尚不明确。本文就目前IPF-LC的危险因素、发病机制、临床特征和治疗的相关研究进展作简要综述。