BMC Pulm Med. 2021 May 5;21(1):149. doi: 10.1186/s12890-021-01514-6.

ABSTRACT

BACKGROUND: Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis.

METHODS: The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily.

RESULTS: BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA.

CONCLUSIONS: These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.

PMID:33952237 | DOI:10.1186/s12890-021-01514-6

BMC Pulm Med. 2021 May 5;21(1):147. doi: 10.1186/s12890-021-01520-8.

ABSTRACT

INTRODUCTION: There is limited data available on the use of CPET as a predictive tool for disease outcomes in the setting of IPF. We investigated the feasibility of undertaking CPET and the relationship between CPET and quality of life measurements in a well-defined population of mild and moderate IPF patients.

METHODS: A prospective, single-centre observational study.

RESULTS: Thirty-two IPF patients (mild n = 23, moderate n = 9) participated in the study, n = 13 mild patients attended for repeat CPET testing at 12 months. At baseline, total K-BILD scores and total IPF-PROM scores significantly correlated with 6MWT distance, but not with baseline FVC % predicted, TLco % predicted, baseline or minimum SpO2. VO2 peak/kg at AT positively correlated with total scores, breathlessness/activity and chest domains of the K-BILD questionnaire (p < 0.05). VO2 peak significantly correlated with total IPF PROM scores and wellbeing domains (p < 0.05), with a trend towards statistical significance for total IPF-PROM and VO2 peak/kg at anaerobic threshold (p = 0.06). There was a statistically significant reduction in FVC% predicted at 12 months follow up, although the mean absolute decline was < 10% (p < 0.05). During this period VO2 peak significantly reduced (21.6 ml/kg/min ± 2.9 vs 19.1 ± 2.8; p = 0.017), with corresponding reductions in total K-BILD and breathlessness/activity domains that exceeded the MCID for responsiveness. Lower baseline VO2 peak/kg at anaerobic threshold correlated with greater declines in total K-BILD scores (r = - 0.62, 0.024) at 12 months. Whilst baseline FVC% predicted or TLco % predicted did not predict change in health status, CONCLUSION: We have shown that it is feasible to undertake CPET in patients with mild to moderate IPF. CPET measures of VO2 peak correlated with both baseline and change in K-BILD measurements at 1 year, despite relatively stable standard lung function (declines of < 10% in FVC), suggesting its potential sensitivity to detect physiological changes underlying health status.

PMID:33952224 | DOI:10.1186/s12890-021-01520-8

J Int Med Res. 2021 May;49(5):3000605211010734. doi: 10.1177/03000605211010734.

ABSTRACT

Secondary organizing pneumonia (SOP) is a nonspecific inflammatory response towards acute lung injuries caused by various diseases. However, organizing pneumonia (OP) secondary to occupational acute nitrogen oxide poisoning has been reported rarely. We report a 49-year-old man who suffered from nitrogen oxide poisoning after inhaling mixed gas at work. After pathological examination, he was diagnosed with OP. In the absence of other underlying factors causing OP, he was diagnosed with SOP owing to acute nitrogen oxide poisoning. After systematic treatment, the patient recovered and was discharged in better health. In patients with lung injury caused by acute nitrogen oxide poisoning, physicians should be alert to the risk of patients subsequently developing SOP, and timely diagnosis and treatment are essential for complete recovery.

PMID:33947260 | DOI:10.1177/03000605211010734

Respiration. 2021 May 5:1-10. doi: 10.1159/000515607. Online ahead of print.

ABSTRACT

Interstitial lung disease (ILD) is a cause of substantial morbidity and mortality amongst autoimmune diseases, including myositis. Despite first-line therapy with immunosuppression, many inflammatory ILDs advance to a fibrotic stage. In such patients, progressive fibrosis may be amenable to treatment with antifibrotic medications, which were initially studied and approved for the treatment of idiopathic pulmonary fibrosis. We here review the available data that support the use of antifibrotics in connective tissue diseases and progressive fibrosing ILDs. There is now a growing body of evidence in both large randomized clinical trials and on the evolving pathophysiologic pathways to support the use of antifibrotics in select patients with autoimmune ILD and a fibrotic phenotype. Further study of antifibrotics in combination with immunosuppressive medications, and in the myositis-ILD population, is needed.

PMID:33951665 | DOI:10.1159/000515607

Cureus. 2021 Mar 31;13(3):e14218. doi: 10.7759/cureus.14218.

ABSTRACT

Prostate cancer is the most commonly diagnosed malignancy and the second most common cause of death in men after lung cancer. Isolated pulmonary metastasis from prostate cancer, without bone or lymph node involvement, is rare and accounts for less than 1% of cases. The diagnosis of solitary lung metastasis is even more challenging in patients with concomitant pulmonary disease and often mandates tissue biopsy from the lung nodule. We herein present a case of an elderly man with idiopathic pulmonary fibrosis who presented with a solitary lung nodule three years after a laparoscopic radical prostatectomy for localized prostate cancer. Initially thought as a primary lung lesion secondary to his pulmonary fibrosis, further workup and ultimately a lung segmentectomy proved a metastatic prostatic adenocarcinoma. The serum prostatic specific antigen dropped to nadir following resection, and he remained stable six months later.

PMID:33948408 | PMC:PMC8086736 | DOI:10.7759/cureus.14218

Respir Res. 2021 May 4;22(1):135. doi: 10.1186/s12931-021-01714-y.

ABSTRACT

BACKGROUND: Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. In France, pirfenidone and nintedanib are only reimbursed for documented IPF, with similar reimbursement criteria with respect to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in multidisciplinary discussion.

RESEARCH QUESTION: The data of the comprehensive French National Health System were used to evaluate outcomes in patients newly treated with pirfenidone or nintedanib in 2015-2016.

STUDY DESIGN AND METHODS: Patients aged < 50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. All-cause mortality, acute respiratory-related hospitalisations and treatment discontinuations up to 31 December 2017 were compared using a Cox proportional hazards model adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period.

RESULTS: During the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical contacts prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.8; 95% confidence interval [CI] 1.3-2.6), a greater risk of acute respiratory-related hospitalisations (HR 1.3; 95% CI 1.0-1.7) and a lower risk of treatment discontinuation at 12 months (HR 0.7; 95% CI 0.6-0.9).

INTERPRETATION: This observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.

PMID:33947414 | DOI:10.1186/s12931-021-01714-y

Biomedicines. 2021 Apr 30;9(5):498. doi: 10.3390/biomedicines9050498.

ABSTRACT

The interleukin (IL)-6 family of cytokines and exaggerated signal transducer and activator of transcription (STAT)3 signaling is implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis, but the mechanisms regulating STAT3 expression and function are unknown. Suppressor of cytokine signaling (SOCS)1 and SOCS3 block STAT3, and low SOCS1 levels have been reported in IPF fibroblasts and shown to facilitate collagen production. Fibroblasts and lung tissue from IPF patients and controls were used to examine the mechanisms underlying SOCS1 down-regulation in IPF. A significant reduction in basal SOCS1 mRNA in IPF fibroblasts was confirmed. However, there was no difference in the kinetics of activation, and methylation of SOCS1 in control and IPF lung fibroblasts was low and unaffected by 5'-aza-2'-deoxycytidine' treatment. SOCS1 is a target of microRNA-155 and although microRNA-155 levels were increased in IPF tissue, they were reduced in IPF fibroblasts. Therefore, SOCS1 is not regulated by SOCS1 gene methylation or microRNA155 in these cells. In conclusion, we confirmed that IPF fibroblasts had lower levels of SOCS1 mRNA compared with control fibroblasts, but we were unable to determine the mechanism. Furthermore, although SOCS1 may be important in the fibrotic process, we were unable to find a significant role for SOCS1 in regulating fibroblast function.

PMID:33946612 | DOI:10.3390/biomedicines9050498

JCI Insight. 2021 May 4:141061. doi: 10.1172/jci.insight.141061. Online ahead of print.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is characterized by aberrant repair that diminishes lung function via mechanisms that remain poorly understood. C-C chemokine receptor (CCR10) and its ligand, CCL28, were both elevated in IPF compared with normal donors. CCR10 was highly expressed by various cells from IPF lungs, most notably stage-specific embryonic antigen (SSEA)-4+ mesenchymal progenitor cells (MPCs). In vitro, CCL28 promoted the proliferation of CCR10+ MPCs while CRISPR-Cas9-mediated targeting of CCR10 resulted in the death of MPCs. Following the intravenous injection of various cells from IPF lungs into immunodeficient (NSG) mice, human CCR10+ cells initiated and maintained fibrosis in NSG mice. Eph receptor A3 (EphA3) was among the highest expressed receptor tyrosine kinases detected on IPF CCR10+ cells. Ifabotuzumab-targeted killing of EphA3+ cells significantly reduced the numbers of CCR10+ cells and ameliorated pulmonary fibrosis in humanized NSG mice. Thus, human CCR10+ cells promote pulmonary fibrosis and EphA3 mAb-directed elimination of these cells inhibits lung fibrosis.

PMID:33945505 | DOI:10.1172/jci.insight.141061

J Clin Lab Anal. 2021 May 4:e23782. doi: 10.1002/jcla.23782. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD-ILD) has not been determined.

METHODS: A two-stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD-ILD cases, and 225 controls).

RESULTS: We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212-4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376-4.128, p = 0.002 in stage two). However, we did not observe this association in CTD-ILD (OR = 1.401, 95% CI = 0.790-2.485, p = 0.248).

CONCLUSION: Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD-ILD.

PMID:33942374 | DOI:10.1002/jcla.23782

Cell Biochem Biophys. 2021 May 3. doi: 10.1007/s12013-021-00987-w. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, which was caused by a complex interplay of inflammatory responses and chronic damage. miR-21 is increased in patients with IPF, but its function in the embryonic lung-derived diploid fibroblasts cells subjected to LPS is elusive. miRNA expression profile was obtained from GEO database and target genes of miRNAs were forecasted by TargetScan. To mimic the LPS-induced injury, different concentrations of LPS were applied to treat WI-38 cells. Functional in vitro experiments were conducted to examine the role of miR-21 and TIMP3. Luciferase report assay was performed to verify the relationship between miR-21 and TIMP3. qRT-PCR, western blotting, and ELISA were conducted to detect the levels of the related miRNAs, proteins, and inflammatory factors. miR-21 presented higher levels in interstitial pneumonia patients and LPS-induced WI-38 cells. Overexpression of miR-21 was negatively correlated with the proliferative capability of LPS-treated WI-38 cells. miR-21 directly targets TIMP3. TIMP3 restored the suppressive impact of miR-21 mimic on the proliferation, while TIMP3 alleviated the promoting impact of miR-21 mimic on the apoptosis of WI-38 cells treated by LPS. miR-21 inhibited Bcl-2 but increased Bax, cleaved caspase-3, and cleaved caspase-9. Besides, miR-21 elevated the levels of IL-6 and IL-β but reduced the IL-10, which were weakened by TIMP3. Totally, miR-21 aggravated the LPS-induced lung injury and modulated inflammatory responses by targeting TIMP3.

PMID:33942238 | DOI:10.1007/s12013-021-00987-w

BMC Pulm Med. 2021 May 3;21(1):145. doi: 10.1186/s12890-021-01516-4.

ABSTRACT

BACKGROUND: Pirfenidone is an anti-fibrotic agent shown to slow the progression of idiopathic pulmonary fibrosis (IPF). However, its effectiveness in association with serological autoimmune features in IPF remains unclear.

METHODS: We retrospectively reviewed the medical records of patients with IPF treated at a tertiary care hospital in South Korea. The autoantibody status was defined as positive if we detected autoantibodies meeting the serological domain criteria for interstitial pneumonia with autoimmune features or anti-neutrophil cytoplasmic antibodies.

RESULTS: We included 142 patients with IPF treated with pirfenidone for over six months (93 were autoantibody-positive and 49 were autoantibody-negative). The mean age was 69.5 ± 7.3 years, and 77.5% of the patients were male. The adjusted mean changes over one year were - 34.4 and - 112.2 mL (p = 0.168) in forced vital capacity (FVC), and - 0.53 and - 0.72 mL/mmHg/min (p = 0.356) in the lungs diffusion capacity for carbon monoxide (DLCO) in the autoantibody-negative and autoantibody-positive groups, respectively.

CONCLUSIONS: Reductions in FVC and DLCO were similar in autoantibody-positive and autoantibody-negative patients with IPF treated with pirfenidone. Pirfenidone is effective in attenuating the progression of IPF, irrespective of the autoantibody status.

PMID:33941141 | DOI:10.1186/s12890-021-01516-4

Eur J Pharmacol. 2021 Apr 30:174135. doi: 10.1016/j.ejphar.2021.174135. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease resulting in respiratory failure with no efficient treatment options. We investigated the protective effect of RS4651 on pulmonary fibrosis in mice and the mechanism.

METHODS: Intratracheal injection of bleomycin (BLM) was used to induce pulmonary fibrosis in mice. RS4561 was administered intraperitoneally at different doses. Histopathological changes were observed. The level of alpha-smooth muscle actin (α-SMA) were also tested. In vitro, the proliferation and migratory effects of RS4651 treatment on MRC-5 cells pre-treated with transforming growth factor (TGF-β1) were examined. RNA-sequencing was used to detect differentially expressed target genes. Then, the expression of α-SMA, pSMAD2 and SMAD7 were analysed during RS4651 treatment of MRC-5 cells with or without silencing by SMAD7 siRNA.

RESULTS: Histopathological staining results showed decreased collagen deposition in RS4651 administered mice. Additionally, a lower level of α-SMA was also observed compared to the BLM group. The results of in vitro studies confirmed that RS4651 can inhibit the proliferation and migration, as well as α-SMA and pSMAD2 expression in MRC-5 cells treated with TGF-β1. RNA-sequencing data identified the target gene SMAD7. We found that RS4651 could upregulate SMAD7 expression and inhibit the proliferation and migration of MRC-5 cells via SMAD7, and RS4651 inhibition of α-SMA and pSMAD2 expression was blocked in SMAD7-siRNA MRC-5 cells. In vivo studies further confirmed that RS4651 could upregulate SMAD7 expression in BLM-induced lung fibrosis in mice.

CONCLUSIONS: Our data suggest that RS4651 alleviates BLM-induced pulmonary fibrosis in mice by inhibiting the TGF-β1/SMAD signalling pathway.

PMID:33940030 | DOI:10.1016/j.ejphar.2021.174135

J Med Chem. 2021 May 3. doi: 10.1021/acs.jmedchem.1c00138. Online ahead of print.

ABSTRACT

Mounting evidence from the literature suggests that blocking S1P2 receptor (S1PR2) signaling could be effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, only a few antagonists have been so far disclosed. A chemical enablement strategy led to the discovery of a pyridine series with good antagonist activity. A pyridazine series with improved lipophilic efficiency and with no CYP inhibition liability was identified by scaffold hopping. Further optimization led to the discovery of 40 (GLPG2938), a compound with exquisite potency on a phenotypic IL8 release assay, good pharmacokinetics, and good activity in a bleomycin-induced model of pulmonary fibrosis.

PMID:33939425 | DOI:10.1021/acs.jmedchem.1c00138

Front Pharmacol. 2021 Apr 15;12:601438. doi: 10.3389/fphar.2021.601438. eCollection 2021.

ABSTRACT

The demographics of the population with cystic fibrosis (CF) is continuously changing, with nowadays adults outnumbering children and a median predicted survival of over 40 years. This leads to the challenge of treating an aging CF population, while previous research has largely focused on pediatric and adolescent patients. Chronic inflammation is not only a hallmark of CF lung disease, but also of the aging process. However, very little is known about the effects of an accelerated aging pathology in CF lungs. Several chronic lung disease pathologies show signs of chronic inflammation with accelerated aging, also termed "inflammaging"; the most notable being chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In these disease entities, accelerated aging has been implicated in the pathogenesis via interference with tissue repair mechanisms, alterations of the immune system leading to impaired defense against pulmonary infections and induction of a chronic pro-inflammatory state. In addition, CF lungs have been shown to exhibit increased expression of senescence markers. Sustained airway inflammation also leads to the degradation and increased turnover of cystic fibrosis transmembrane regulator (CFTR). This further reduces CFTR function and may prevent the novel CFTR modulator therapies from developing their full efficacy. Therefore, novel therapies targeting aging processes in CF lungs could be promising. This review summarizes the current research on CF in an aging population focusing on accelerated aging in the context of chronic airway inflammation and therapy implications.

PMID:33935699 | PMC:PMC8082404 | DOI:10.3389/fphar.2021.601438

Am J Surg Pathol. 2021 May 3. doi: 10.1097/PAS.0000000000001725. Online ahead of print.

ABSTRACT

Interstitial lung diseases (ILDs) in patients with shortened telomeres have not been well characterized. We describe demographic, radiologic, histopathologic, and molecular features, and p16 expression in patients with telomeres ≤10th percentile (shortened telomeres) and compare them to patients with telomere length >10th percentile. Lung explants, wedge biopsies, and autopsy specimens of patients with telomere testing were reviewed independently by 3 pathologists using defined parameters. High-resolution computed tomography scans were reviewed by 3 radiologists. p16-positive fibroblast foci were quantified. A multidisciplinary diagnosis was recorded. Patients with shortened telomeres (N=26) were morphologically diagnosed as usual interstitial pneumonia (UIP) (N=11, 42.3%), chronic hypersensitivity pneumonitis (N=6, 23.1%), pleuroparenchymal fibroelastosis, fibrotic nonspecific interstitial pneumonia, desquamative interstitial pneumonia (N=1, 3.8%, each), and fibrotic interstitial lung disease (fILD), not otherwise specified (N=6, 23.1%). Patients with telomeres >10th percentile (N=18) showed morphologic features of UIP (N=9, 50%), chronic hypersensitivity pneumonitis (N=3, 16.7%), fibrotic nonspecific interstitial pneumonia (N=2, 11.1%), or fILD, not otherwise specified (N=4, 22.2%). Patients with shortened telomeres had more p16-positive foci (P=0.04). The number of p16-positive foci correlated with outcome (P=0.0067). Thirty-nine percent of patients with shortened telomeres harbored telomere-related gene variants. Among 17 patients with shortened telomeres and high-resolution computed tomography features consistent with or probable UIP, 8 (47.1%) patients showed morphologic features compatible with UIP; multidisciplinary diagnosis most commonly was idiopathic pulmonary fibrosis (N=7, 41.2%) and familial pulmonary fibrosis (N=5, 29%) in these patients. In conclusion, patients with shortened telomeres have a spectrum of fILDs. They often demonstrate atypical and discordant features on pathology and radiology leading to diagnostic challenges.

PMID:33935155 | DOI:10.1097/PAS.0000000000001725

Eur J Intern Med. 2021 Apr 27:S0953-6205(21)00118-7. doi: 10.1016/j.ejim.2021.04.005. Online ahead of print.

ABSTRACT

BACKGROUND: Broncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive, and specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing healthy individuals from patients with lung diseases.

OBJECTIVES: In our study, BCT was applied for the first time to the analysis of interstitial lung diseases (ILDs), investigating its potential for differential diagnosis. Combinations of BAL cells that improve diagnostic accuracy for ILDs were studied and are proposed.

METHODS: A retrospective analysis of BAL samples was performed. We considered more than 1000 BAL samples from patients investigated for ILD, performed at Siena University Hospital. The samples enrolled for the study included 468 patients: 413 with and 55 without ILD. BAL was performed for diagnostic purposes in line with international guidelines. BCT were calculated according to available literature.

RESULTS: Among ILDs, patients with fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis showed significantly lower BCTs than unclassified ILD. Asbestosis patients showed significantly lower BCTs than nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), connective tissue disease related ILD (CTD-ILD), sarcoidosis and unclassified ILD patients. COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT.

CONCLUSION: The analysis of BAL features is currently included in the diagnostic algorithm of ILDs. BAL cell patterns and BCT index can provide useful information for distinguishing ILDs, reducing the need for invasive procedures. Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.

PMID:33931268 | DOI:10.1016/j.ejim.2021.04.005

Pharmacol Res. 2021 Apr 27:105635. doi: 10.1016/j.phrs.2021.105635. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by an inexorable decline in lung function. The development of IPF involves multiple positive feedback loops; and a strong support role of the Hippo/YAP signalling pathway, which is essential for regulating cell proliferation and organ size, in IPF pathogenesis has been unveiled recently in cell and animal models. YAP/TAZ contributes to both pulmonary fibrosis and alveolar regeneration via the conventional Hippo/YAP signalling pathway, G protein-coupled receptor signalling, and mechanotransduction. Selectively inhibiting YAP/TAZ in lung fibroblasts may inhibit fibroblast proliferation and extracellular matrix deposition, while activating YAP/TAZ in alveolar epithelial cells may promote alveolar regeneration. In this review, we explore, for the first time, the bidirectional and cell-specific regulation of the Hippo/YAP pathway in IPF pathogenesis and discuss recent research progress and future prospects of IPF treatment based on Hippo/YAP signalling, thus providing a basis for the development of new therapeutic strategies to alleviate or even reverse IPF.

PMID:33930530 | DOI:10.1016/j.phrs.2021.105635

Eur Rev Med Pharmacol Sci. 2021 Apr;25(8):3254-3263. doi: 10.26355/eurrev_202104_25734.

ABSTRACT

OBJECTIVE: To test the correlation between the visual semi-quantitative score (VSQS) and different quantitative computed tomography (QCT) analyses and pulmonary physiology variables, and to determine the performance of these types of analyses on the Gender, Age, and Physiology (GAP) model for the prediction of mortality risk of idiopathic pulmonary fibrosis (IPF).

PATIENTS AND METHODS: High-resolution computed tomography (HRCT) images of IPF patients were reviewed and the VSQS was calculated. Evaluations were made of the QCT score of interstitial lung disease (ILD) using four different previously defined methods. Respiratory function tests (RFT) and the 6-minute walk test (6MWT) were applied to all the patients. The GAP model was used to evaluate the mortality risk. The performance of the VSQS score and QCT methods on the GAP model to predict the mortality risk of the disease was calculated with ROC analysis.

RESULTS: The study included 40 patients who met the criteria. A statistically significant correlation was determined between all the quantitative and semi-quantitative measurement results (p<0.001). A significant correlation was determined between the VSQS and QCT parameters and the RFT and 6MWT. In the ROC analysis, method 4 of the QCT parameters (a value of the voxels between -700 and -950 HU) and the VSQS showed the best performance in the differentiation of stage I, stage II, and stage III, according to the GAP model.

CONCLUSIONS: The selection of a quantitative method was useful in the evaluation of spread in patients with IPF. According to the GAP model, VSQS performed best in predicting mortality risk. Furthermore, method 4 of the QCT parameters, which shows well-aerated lungs, were deemed to have good potential for the estimation of mortality risk.

PMID:33928611 | DOI:10.26355/eurrev_202104_25734

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2021 Mar 28;46(3):309-315. doi: 10.11817/j.issn.1672-7347.2021.190402.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal pulmonary disease characterized by complex illness condition. There is no effective treatment at present except lung transplantation. The comprehensive evaluation is helpful for the management of patients with IPF in hierarchical stages. Therefore, it is very important to evaluate IPF by various independent factors. At present, the commonly used methods for clinical evaluation on IPF include assessment of health-related quality of life, assessment of physiological function, assessment of imaging, assessment of laboratory examination, and multi-dimensional assessment system. However, there are different advantages and disadvantages on diverse evaluation methods for the evaluation of IPF.

PMID:33927079 | DOI:10.11817/j.issn.1672-7347.2021.190402

Thorax. 2021 Apr 29:thoraxjnl-2020-216749. doi: 10.1136/thoraxjnl-2020-216749. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with interstitial lung disease (ILD) are at risk of developing nocturnal hypoxaemia due to ventilatory restriction and impaired gas exchange that worsen with supine posture and reduced ventilatory drive during sleep. This systematic review synthesised literature on the diagnostic evaluation, epidemiology, associations, management and prognosis of nocturnal hypoxaemia in ILD.

METHODS: Ovid MEDLINE, Embase and CENTRAL databases were searched for eligible studies. Meta-analyses with subgroup analyses were conducted, where possible.

RESULTS: Fifty-three studies were included (total participant number=2590). The most common definition for clinically significant nocturnal hypoxaemia was ≥10% of total sleep time with oxyhaemoglobin saturation <90%, with pooled prevalence of 37%. There were no significant differences in pooled prevalence according to ILD subtype and comorbid obstructive sleep apnoea status. Study heterogeneity precluded meta-analysis of associations and prognosis. Diffusing capacity for carbon monoxide (DLCO) and echocardiographic features for pulmonary hypertension were consistently associated with nocturnal hypoxaemia. There were inconsistent associations between nocturnal hypoxaemia with ILD subtype and severity. Multivariable analyses in most studies demonstrated significant associations of nocturnal hypoxaemia with survival. Two small short-term intervention studies demonstrated that supplemental oxygen of 1-3 L/min corrected nocturnal hypoxaemia, with improved heart rate control during in-laboratory observation and increased serum antioxidant levels after 1 month of therapy.

CONCLUSION: Nocturnal hypoxaemia is common, associated with DLCO impairment and markers suggestive of pulmonary hypertension, and a potential prognostic factor in patients in ILD. There is a need to establish a consensus definition of nocturnal hypoxaemia and evaluate long-term effects of nocturnal supplemental oxygen in ILD.

PMID:33927018 | DOI:10.1136/thoraxjnl-2020-216749