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Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment.

ABSTRACT: A genetic predisposition has been identified in 30% of idiopathic pulmonary fibrosis (IPF) cases. Although it is highly probable that the genotype affects the disease susceptibility and course in almost all patients, the specific genotype goes undetected. The aim of the present study was to explore the effects of variants of the genes encoding interleukin-4 (IL-4), mucin 5B (MUC5B), toll interacting protein (TOLLIP), surfactant protein A (SFPTA), transforming growth factor-β (TGF-β) and transporters associated with antigen processing (TAP1 and TAP2) on the course of IPF. A total of 50 patients with IPF were enrolled, and variants of these genes were assessed. Lung function at the time of diagnosis and after 6, 12 and 18 months, and the number of acute exacerbations and deaths in each observation period were measured. ANOVA was used to test the association between gene polymorphisms and the decrease in lung function. There was no significant effect of the gene polymorphisms on the outcomes of patients up to 6 months during the observation period. After 12 months, an effect of an IL-4 single nucleotide polymorphism (SNP) (rs 2070874) on patient outcomes was observed [relative risk (RR) for T allele: 5.6; 95% confidence interval (CI), 0.79-39.0; P=0.053]. The RR of progression in patients with the IL-4 SNP (rs 2243250) and the CT and TT genotypes was 4.3 (95% CI, 1.1-17.5; P=0.046). A total of 18 months after the diagnosis of IPF, an effect of the TOLLIP polymorphism on patient outcome was detected (rs 111521887; risk allele GC; RR: 7.2; 95% CI, 0.97-53.6; P=0.052). Thus, IL-4 and TOLLIP gene polymorphisms may represent disease course-modifying factors, but not drivers of IPF.

SUBMITTER: Sterclova M

PROVIDER: S-EPMC8444193 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Effect of genotype on disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment

Project description:Genotyping of SNPs in IPF patients

2021-05-07 | PRJEB44734 | EVA

Effect of sildenafil added to antifibrotic treatment in idiopathic pulmonary fibrosis.

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| S-EPMC8426395 | biostudies-literature

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| S-EPMC8017848 | biostudies-literature

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| S-EPMC6731623 | biostudies-literature

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| S-EPMC6780456 | biostudies-literature

Antifibrotic treatment improves clinical outcomes in patients with idiopathic pulmonary fibrosis: a propensity score matching analysis.

Project description:In patients with idiopathic pulmonary fibrosis (IPF), the effects of antifibrotic agents on the prognosis remain unclear. This study aimed to investigate the impact of antifibrotic treatment on the risks of mortality, hospitalisation, and acute exacerbation in real-world patients with IPF. A total of 1213 IPF patients (biopsy-proven cases: 405) were included in this retrospective study. Propensity score matching was used to adjust for differences in baseline characteristics between patients who received antifibrotic treatment and who did not. A Cox proportional hazard model was used to compare the risks of all-cause mortality, hospitalisation, acute exacerbation, and mortality following acute exacerbation between the two groups. From the 1213 patients, 474 matched pairs were generated. The mean age of the patients in the matched cohort was 65.8 years and 82.8% were men. The median follow-up duration was 27 months. Antifibrotic treatment significantly reduced the risks of mortality [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.48-0.72; p < 0.001], all-cause hospitalisation (HR 0.71), respiratory-related hospitalisation (HR 0.67), acute exacerbation (HR 0.69), and mortality after acute exacerbation (HR 0.60). Our results suggest that antifibrotic treatment may reduce the risks of all-cause mortality, hospitalisation, acute exacerbation, and mortality after acute exacerbation in patients with IPF.

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Antifibrotic treatment response and prognostic predictors in patients with idiopathic pulmonary fibrosis and exposed to occupational dust.

Project description:BACKGROUND:Idiopathic Pulmonary Fibrosis (IPF) is an aggressive interstitial lung disease with an unpredictable course. Occupational dust exposure may contribute to IPF onset, but its impact on antifibrotic treatment and disease prognosis is still unknown. We evaluated clinical characteristics, respiratory function and prognostic predictors at diagnosis and at 12?month treatment of pirfenidone or nintedanib in IPF patients according to occupational dust exposure. METHODS:A total of 115 IPF patients were recruited. At diagnosis, we collected demographic, clinical characteristics, occupational history. Pulmonary function tests were performed and two prognostic indices [Gender, Age, Physiology (GAP) and Composite Physiologic Index (CPI)] calculated, both at diagnosis and after the 12?month treatment. The date of long-term oxygen therapy (LTOT) initiation was recorded during the entire follow-up (mean?=?37.85, range 12-60?months). RESULTS:At baseline, patients exposed to occupational dust [? 10?years (n?=?62)] showed a lower percentage of graduates (19.3% vs 54.7%; p?=?0.04) and a higher percentage of asbestos exposure (46.8% vs 18.9%; p 0.002) than patients not exposed [<?10?years (n?=?53)]. Both at diagnosis and after 12?months of antifibrotics, no significant differences for respiratory function and prognostic predictors were found. The multivariate analysis confirmed that occupational dust exposure did not affect neither FVC and DLCO after 12?month therapy nor the timing of LTOT initiation. CONCLUSION:Occupational dust exposure lasting 10?years or more does not seem to influence the therapeutic effects of antifibrotics and the prognostic predictors in patients with IPF.

| S-EPMC6727559 | biostudies-literature

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Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high-lethality fibrotic lung disease characterized by excessive fibroblast proliferation, extracellular matrix accumulation, and, ultimately, loss of lung function. Although dysregulation of some microRNAs (miRs) has been shown to play important roles in the pathophysiological processes of IPF, the role of miRs in fibrotic lung diseases is not well understood. In this study, we found downregulation of miR-26a in the lungs of mice with experimental pulmonary fibrosis and in IPF, which resulted in posttranscriptional derepression of connective tissue growth factor (CTGF), and induced collagen production. More importantly, inhibition of miR-26a in the lungs caused pulmonary fibrosis in vivo, whereas overexpression of miR-26a repressed transforming growth factor (TGF)-?1-induced fibrogenesis in MRC-5 cells and attenuated experimental pulmonary fibrosis in mice. Our study showed that miR-26a was downregulated by TGF-?1-mediated phosphorylation of Smad3. Moreover, miR-26a inhibited the nuclear translocation of p-Smad3 through directly targeting Smad4, which determines the nuclear translocation of p-Smad2/Smad3. Taken together, our experiments demonstrated the antifibrotic effects of miR-26a in fibrotic lung diseases and suggested a new strategy for the prevention and treatment of IPF using miR-26a. The current study also uncovered a novel positive feedback loop between miR-26a and p-Smad3, which is involved in pulmonary fibrosis.

| S-EPMC4048895 | biostudies-other

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