Int J Clin Exp Pathol. 2022 Jan 15;15(1):20-28. eCollection 2022.

ABSTRACT

Traumatic brain injury (TBI) continues to be a significant public healthcare concern. Neuroinflammation that occurs in the secondary phase of TBI leads to cognitive and physical dysfunction. A number of therapeutic modalities have been evaluated in an attempt to find a suitable treatment. The only drug approved for the treatment of idiopathic pulmonary fibrosis, pirfenidone, has been evaluated for its antifibrotic, anti-inflammatory, and anti-oxidant properties for various disorders, but this is the first study to examine its effects in an experimental TBI model. Twenty-four Wistar rats were randomly divided into three groups: control, trauma, and pirfenidone. The two latter groups underwent experimental diffuse cortical injury mimicking TBI. Neurological assessment was performed using the Garcia test, histological analysis was performed to examine neuroprotective and anti-inflammatory effects, and biochemical analyses of neuron-specific enolase (NSE), S-100B, caspase-3, and thiobarbituric acid reactive substances were performed. The pirfenidone group had a better Garcia test score (P=0.001), an increased anti-inflammatory effect (P<0.001), and an enhanced neuroprotective effect (P=0.007) along with decreased NSE, S100B, and TBARS levels compared to the trauma group. However, pirfenidone did not show a beneficial effect on caspase-3 levels. Pirfenidone may help decrease mortality and morbidity rates after TBI through its anti-inflammatory and antioxidant effects.

PMID:35145580 | PMC:PMC8822207

Thorax. 2022 Feb 10:thoraxjnl-2021-217976. doi: 10.1136/thoraxjnl-2021-217976. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments.

METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework.

RESULTS: We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty).

CONCLUSION AND RELEVANCE: Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

PMID:35145039 | DOI:10.1136/thoraxjnl-2021-217976

Eur Respir J. 2022 Feb 10:2102806. doi: 10.1183/13993003.02806-2021. Online ahead of print.

NO ABSTRACT

PMID:35144990 | DOI:10.1183/13993003.02806-2021

Laryngoscope. 2022 Feb 10. doi: 10.1002/lary.30040. Online ahead of print.

ABSTRACT

OBJECTIVE: Characterize and quantify epithelium in multiple etiologies of laryngotracheal stenosis (LTS) to better understand its role in pathogenesis.

STUDY DESIGN: Controlled in vitro cohort study.

METHODS: Endoscopic brush biopsy samples of both normal (non-scar) and scar were obtained in four patients with idiopathic subglottic stenosis (iSGS) and four patients with iatrogenic LTS (iLTS). mRNA expression of basal, ciliary, and secretory cell markers were evaluated using quantitative PCR. Cricotracheal resection tissue samples (n = 5 per group) were also collected, analyzed using quantitative immunohistochemistry, and compared with rapid autopsy tracheal samples.

RESULTS: Both iSGS and iLTS-scar epithelium had reduced epithelial thickness compared with non-scar control epithelium (P = .0009 and P = .0011, respectively). Basal cell gene and protein expression for cytokeratin 14 was increased in iSGS-scar epithelium compared with iLTS or controls. Immunohistochemical expression of ciliary tubulin alpha 1, but not gene expression, was reduced in both iSGS and iLTS-scar epithelium compared with controls (P = .0184 and P = .0125, respectively). Both iSGS and iLTS-scar had reductions in Mucin 5AC gene expression (P = .0007 and P = .0035, respectively), an epithelial goblet cell marker, with reductions in secretory cells histologically (P < .0001).

CONCLUSIONS: Compared with non-scar epithelium, the epithelium within iSGS and iLTS is morphologically abnormal. Although both iSGS and iLTS have reduced epithelial thickness, ciliary cells, and secretory cells, only iSGS had significant increases in pathological basal cell expression. These data suggest that the epithelium in iSGS and iLTS play a common role in the pathogenesis of fibrosis in these two etiologies of laryngotracheal stenosis.

SETTING: Tertiary referral center (2017-2020).

LEVEL OF EVIDENCE: NA Laryngoscope, 2022.

PMID:35141889 | DOI:10.1002/lary.30040

Cell Death Discov. 2022 Feb 8;8(1):52. doi: 10.1038/s41420-022-00851-7.

ABSTRACT

Although the exact pathogenesis of idiopathic pulmonary fibrosis (IPF) is still unknown, the transdifferentiation of fibroblasts into myofibroblasts and the production of extracellular matrix components such as collagen, triggered by alveolar epithelial cell injury, are important mechanisms of IPF development. In the lungs of IPF patients, apoptosis is less likely to be induced in fibroblasts than in alveolar epithelial cells, and this process is involved in the pathogenesis of IPF. We used a library containing approved drugs to screen for drugs that preferentially reduce cell viability in LL29 cells (lung fibroblasts from an IPF patient) compared with A549 cells (human alveolar epithelial cell line). After screening, we selected eperisone, a central muscle relaxant used in clinical practice. Eperisone showed little toxicity in A549 cells and preferentially reduced the percentage of viable LL29 cells, while pirfenidone and nintedanib did not have this effect. Eperisone also significantly inhibited transforming growth factor-β1-dependent transdifferentiation of LL29 cells into myofibroblasts. In an in vivo study using ICR mice, eperisone inhibited bleomycin (BLM)-induced pulmonary fibrosis, respiratory dysfunction, and fibroblast activation. In contrast, pirfenidone and nintedanib were less effective than eperisone in inhibiting BLM-induced pulmonary fibrosis under this experimental condition. Finally, we showed that eperisone did not induce adverse effects in the liver and gastrointestinal tract in the BLM-induced pulmonary fibrosis model. Considering these results, we propose that eperisone may be safer and more therapeutically beneficial for IPF patients than current therapies.

PMID:35136056 | DOI:10.1038/s41420-022-00851-7

Respir Res. 2022 Feb 8;23(1):24. doi: 10.1186/s12931-022-01938-6.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a cryptogenic chronic interstitial pneumonia with progressive fibrosis and a poor prognosis. A substantial number of epidemiological studies have been conducted in Europe and the United States (US). In contrast, in Japan, only one study reported the prevalence of IPF (10.0 per 100,000 population) using clinical data (2003-2007) from one prefecture; thus, the nationwide prevalence of IPF remains unknown. This study aimed to estimate the nationwide prevalence of IPF in Japan using a nationwide claims database.

METHODS: We extracted data from a Japanese claims database provided by Medical Data Vision (MDV database, April 2008-March 2019) containing data from approximately 28 million patients from 385 acute-care hospitals. Patients with IPF (those diagnosed with IPF at least once) from April 2017 to March 2018 were identified in the MDV database. The number of patients in the MDV database was extrapolated nationwide using the fourth NDB Open Data (April 2017-March 2018), and the prevalence was estimated using demographic data as denominators. The prevalence in the US, considering the same definition of IPF, was also calculated and compared with that in Japan.

RESULT: The number of patients with IPF in the MDV database was 4278. The estimated nationwide number of patients in Japan was estimated to be 34,040 (mean age: 73 years, percentage of men: 73%), and the prevalence was 27 per 100,000 population. In comparison with that in the US, the prevalence was similar in men and relatively lower in women until the age of 75-79 years, and it was notably lower in both sexes aged ≥ 80 years.

CONCLUSIONS: We report the nationwide IPF prevalence in Japan using data from claims databases for the first time. The prevalence estimated in this study was higher than that reported in a previous study. The difference might be due to differences in study settings and definitions of IPF. Further research should be performed to determine the prevalence more accurately and compare it with those in other countries.

PMID:35135550 | DOI:10.1186/s12931-022-01938-6

Chest. 2022 Feb;161(2):e71-e73. doi: 10.1016/j.chest.2021.07.2160.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scar tissue formation. An acute exacerbation of IPF (AE-IPF) is a clinically significant respiratory decompensation that accounts for a significant proportion of IPF-related morbidity and mortality. AE-IPF can be idiopathic or associated with pulmonary embolism, infection, aspiration, surgery, and drug toxicity. In this novel case report, we describe a potential association between AE-IPF and BNT162b2 mRNA COVID-19 vaccination that was successfully treated with a short course of glucocorticoids. While our aim is to raise awareness for this yet-to-be-described adverse event, immunization against vaccine-preventable disease remains widely recommended in vulnerable patients with chronic lung disease such as IPF.

PMID:35131075 | DOI:10.1016/j.chest.2021.07.2160

Respir Res. 2022 Feb 7;23(1):20. doi: 10.1186/s12931-022-01940-y.

ABSTRACT

BACKGROUND: Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF).

METHODS: Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC).

RESULTS: Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions.

CONCLUSIONS: We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.

PMID:35130915 | DOI:10.1186/s12931-022-01940-y

J Med Imaging (Bellingham). 2022 Jan;9(1):014004. doi: 10.1117/1.JMI.9.1.014004. Epub 2022 Feb 3.

ABSTRACT

Purpose: Existing anomaly detection methods focus on detecting interclass variations while medical image novelty identification is more challenging in the presence of intraclass variations. For example, a model trained with normal chest x-ray and common lung abnormalities is expected to discover and flag idiopathic pulmonary fibrosis, which is a rare lung disease and unseen during training. The nuances of intraclass variations and lack of relevant training data in medical image analysis pose great challenges for existing anomaly detection methods. Approach: We address the above challenges by proposing a hybrid model-transformation-based embedding learning for novelty detection (TEND), which combines the merits of classifier-based approach and AutoEncoder (AE)-based approach. Training TEND consists of two stages. In the first stage, we learn in-distribution embeddings with an AE via the unsupervised reconstruction. In the second stage, we learn a discriminative classifier to distinguish in-distribution data and the transformed counterparts. Additionally, we propose a margin-aware objective to pull in-distribution data in a hypersphere while pushing away the transformed data. Eventually, the weighted sum of class probability and the distance to margin constitutes the anomaly score. Results: Extensive experiments are performed on three public medical image datasets with the one-vs-rest setup (namely one class as in-distribution data and the left as intraclass out-of-distribution data) and the rest-vs-one setup. Additional experiments on generated intraclass out-of-distribution data with unused transformations are implemented on the datasets. The quantitative results show competitive performance as compared to the state-of-the-art approaches. Provided qualitative examples further demonstrate the effectiveness of TEND. Conclusion: Our anomaly detection model TEND can effectively identify the challenging intraclass out-of-distribution medical images in an unsupervised fashion. It can be applied to discover unseen medical image classes and serve as the abnormal data screening for downstream medical tasks. The corresponding code is available at https://github.com/XiaoyuanGuo/TEND_MedicalNoveltyDetection.

PMID:35127968 | PMC:PMC8810298 | DOI:10.1117/1.JMI.9.1.014004

Acta Pharm Sin B. 2022 Jan;12(1):18-32. doi: 10.1016/j.apsb.2021.07.023. Epub 2021 Jul 29.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.

PMID:35127370 | PMC:PMC8799876 | DOI:10.1016/j.apsb.2021.07.023

Front Pharmacol. 2022 Jan 19;12:797292. doi: 10.3389/fphar.2021.797292. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal fibrotic lung disease that occurs primarily in middle-aged and elderly adults. It is a major cause of morbidity and mortality. With an increase in life expectancy, the economic burden of IPF is expected to continuously rise in the near future. Although the exact pathophysiological mechanisms underlying IPF remain not known. Significant progress has been made in our understanding of the pathogenesis of this devastating disease in last decade. The current paradigm assumes that IPF results from sustained or repetitive lung epithelial injury and subsequent activation of fibroblasts and myofibroblast differentiation. Persistent myofibroblast phenotype contributes to excessive deposition of the extracellular matrix (ECM) and aberrant lung repair, leading to tissue scar formation, distortion of the alveolar structure, and irreversible loss of lung function. Treatments of patients with IPF by pirfenidone and nintedanib have shown significant reduction of lung function decline and slowing of disease progression in patients with IPF. However, these drugs do not cure the disease. In this review, we discuss recent advances on the pathogenesis of IPF and highlight the development of novel therapeutic strategies against the disease.

PMID:35126134 | PMC:PMC8807692 | DOI:10.3389/fphar.2021.797292

Front Pharmacol. 2022 Jan 21;12:794997. doi: 10.3389/fphar.2021.794997. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by an abnormal reepithelialisation, an excessive tissue remodelling and a progressive fibrosis within the alveolar wall that are not due to infection or cancer. Oxidative stress has been proposed as a key molecular process in pulmonary fibrosis development and different components of the redox system are altered in the cellular actors participating in lung fibrosis. To this respect, several activators of the antioxidant machinery and inhibitors of the oxidant species and pathways have been assayed in preclinical in vitro and in vivo models and in different clinical trials. This review discusses the role of oxidative stress in the development and progression of IPF and its underlying mechanisms as well as the evidence of oxidative stress in human IPF. Finally, we analyze the mechanism of action, the efficacy and the current status of different drugs developed to inhibit the oxidative stress as anti-fibrotic therapy in IPF.

PMID:35126133 | PMC:PMC8815729 | DOI:10.3389/fphar.2021.794997

Cell Signal. 2022 Feb 2:110274. doi: 10.1016/j.cellsig.2022.110274. Online ahead of print.

ABSTRACT

We sought to pinpoint the potential role of C-MYC in pulmonary fibroblast proliferation in idiopathic pulmonary fibrosis (IPF) and its mechanism. A mouse model of IPF was established by injection of bleomycin. C-MYC and miR-9-5p expression was determined by RT-qPCR and Western blot analysis. The interaction among C-MYC, miR-9-5p, and TBPL1 was detected by ChIP assay and dual luciferase reporter gene assay. After alteration of C-MYC, miR-9-5p, and TBPL1, their roles in pulmonary fibrosis and collagen fiber deposition in mice as well as proliferation and differentiation of pulmonary fibroblasts were assessed. Upregulated C-MYC expression was seen in the lung tissues of IPF mice and its silencing retarded IPF in mice. C-MYC could activate miR-9-5p that negatively regulated TBPL1 expression. Up-regulated C-MYC promoted proliferation and differentiation of pulmonary fibroblasts by inhibiting TBPL1 via activation of miR-9-5p, thus triggering IPF. Moreover, in the lung tissues-derived cells of IPF mice, C-MYC inhibitor, 10,058-F4, was observed to inhibit miR-9-5p expression, thereby repressing pulmonary fibrosis by up-regulating TBPL1. Our data provided evidence pinpointed the aggravative role of C-MYC in IPF by activating miR-9-5p to regulate TBPL1 expression.

PMID:35122989 | DOI:10.1016/j.cellsig.2022.110274

Eur J Pharmacol. 2022 Feb 2:174792. doi: 10.1016/j.ejphar.2022.174792. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and eventually fatal lung disease with a complex etiology. Approved drugs, nintedanib and pirfenidone, modify disease progression, but IPF remains incurable and there is an urgent need for new therapies. We identified chitotriosidase (CHIT1) as new driver of fibrosis in IPF and a novel therapeutic target. We demonstrate that CHIT1 activity and expression are significantly increased in serum (3-fold) and induced sputum (4-fold) from IPF patients. In the lungs CHIT1 is expressed in a distinct subpopulation of profibrotic, disease-specific macrophages, which are only present in patients with ILDs and CHIT1 is one of the defining markers of this fibrosis-associated gene cluster. To define CHIT1 role in fibrosis, we used the therapeutic protocol of the bleomycin-induced pulmonary fibrosis mouse model. We demonstrate that in the context of chitinase induction and the macrophage-specific expression of CHIT1, this model recapitulates lung fibrosis in ILDs. Genetic inactivation of Chit1 attenuated bleomycin-induced fibrosis (decreasing the Ashcroft scoring by 28%) and decreased expression of profibrotic factors in lung tissues. Pharmacological inhibition of chitinases by OATD-01 reduced fibrosis and soluble collagen concentration. OATD-01 exhibited anti-fibrotic activity comparable to pirfenidone resulting in the reduction of the Ashcroft score by 32% and 31%, respectively. These studies provide a preclinical proof-of-concept for the antifibrotic effects of OATD-01 and establish CHIT1 as a potential new therapeutic target for IPF.

PMID:35122869 | DOI:10.1016/j.ejphar.2022.174792

Int Immunopharmacol. 2022 Feb 1;105:108576. doi: 10.1016/j.intimp.2022.108576. Online ahead of print.

ABSTRACT

INTRODUCTION: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder that causes severe physiological disturbance. Evidence showed that OSAHS is an important associated comorbidity that can affect the survival of patients with pulmonary fibrosis. Until now, the potential mechanisms by which OSAHS accelerates the progression of lung fibrosis remain unclear. By constructing a pathological model of chronic intermittent hypoxia (CIH), the present study aimed to explore the pathological progress and potential mechanism of lung injury caused by OSAHS. Meanwhile, SMND-309 was given for treatment to evaluate its potential therapeutic role in CIH-induced lung injury.

METHODS: Mice were randomly divided into (C57BL/6 wild-type) WT+(room air) RA, WT + CIH, SMND-309 + RA, and SMND-309 + CIH groups. The WT + CIH and SMND-309 + CIH groups were exposed to CIH condition for 12 weeks, while the other groups were processed in normal oxygen at the same time. The SMND-309 + RA and SMND-309 + CIH groups were intraperitoneally injected with SMND-309 at the last week of the modeling period. After 12 weeks of treatment, three mice from each group were perfused through the heart. Lung tissues were isolated, fixed, sectioned, and stained with H&E, Masson, and immunofluorescence stain. The rest of the lung tissues were harvested for Western blot and ELISA assays.

RESULTS: CIH treatment increased the expression of pro-inflammatory factors (TNF-α and IL-6), resulting in lung tissue structure disorder, inflammatory cell infiltration, increased pulmonary capillary permeability, and pulmonary edema. The activation of the NF-κB signaling pathway played a crucial role in the process of inflammation. Noticeably, we observed M2 macrophage accumulation in the lung after CIH exposure, which promoted epithelial-mesenchymal transition (EMT) and pulmonary tissue fibrosis. ELISA assays showed the increased expression of TGF-β, IL-10, and IL-4 in the CIH group. SMND-309 inhibited pulmonary inflammation, reduced the accumulation of M2 macrophage, alleviated collagen deposition andlung damage.

CONCLUSION: CIH could induce chronic lung inflammation, promote the activation of M2 macrophages, trigger the occurrence of EMT, and accelerate the deposition of lung collagen, eventually leading to lung tissue damage. This study presents a possible explanation by which interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF) with OSAHS, are usually associated with fast progress and poor prognosis. SMND-309 showed a good protective effect on CIH-induced lung damage.

PMID:35121224 | DOI:10.1016/j.intimp.2022.108576

Histol Histopathol. 2022 Feb 4:18428. doi: 10.14670/HH-18-428. Online ahead of print.

ABSTRACT

Sphingosine 1-phosphate (S1P) is a bioactive metabolite of sphingomyelin. S1P activates a series of signaling cascades by acting on its receptors S1PR1-3 on endothelial cells (ECs), which plays an important role in endothelial barrier maintenance, anti-inflammation, antioxidant and angiogenesis, and thus is considered as a potential therapeutic biomarker for ischemic stroke, sepsis, idiopathic pulmonary fibrosis, cancers, type 2 diabetes and cardiovascular diseases. We presently review the levels of S1P in those vascular and vascular-related diseases. Plasma S1P levels were reduced in various inflammation-related diseases such as atherosclerosis and sepsis, but were increased in other diseases including type 2 diabetes, neurodegeneration, cerebrovascular damages such as acute ischemic stroke, Alzheimer's disease, vascular dementia, angina, heart failure, idiopathic pulmonary fibrosis, community-acquired pneumonia, and hepatocellular carcinoma. Then, we highlighted the molecular mechanism by which S1P regulated EC biology including vascular development and angiogenesis, inflammation, permeability, and production of reactive oxygen species (ROS), nitric oxide (NO) and hydrogen sulfide (H2S), which might provide new ways for exploring the pathogenesis and implementing individualized therapy strategies for those diseases.

PMID:35118637 | DOI:10.14670/HH-18-428

Sarcoidosis Vasc Diffuse Lung Dis. 2022;38(4):e2021042. doi: 10.36141/svdld.v38i4.11465. Epub 2022 Jan 13.

ABSTRACT

BACKGROUND: Secondary spontaneous pneumothorax (SSP) in interstitial lung disease (ILD) may influence prognosis of any ILD, and SSP onset predicts poor outcome in idiopathic pulmonary fibrosis (IPF). Recently, progressive fibrosing ILD (PF-ILD) has rapidly acquired importance.

OBJECTIVE: We hypothesized that PF-ILD would strongly influence the prognosis of patients with any ILD complicated with SSP.

METHODS: We retrospectively surveyed and collected data from patients hospitalized for SSP from January 2016 to June 2020. PF-ILD was defined as the following occurring within 24 months before SSP develops: relative decline in %forced vital capacity (FVC) ≥10% or two of the following: relative decline in %FVC between 5% and 10%, worsening respiratory symptoms, or increased extent of fibrosis on high-resolution computed tomography.

RESULTS: We analyzed 32 patients hospitalized for SSP in ILD. This study comprised 18 patients with PF-ILD and 14 patients with non-PF-ILD. PF-ILD patients had lower body mass index (BMI) and %FVC. No significant differences in survival regarding follow-up period from the time of ILD diagnosis and hospitalization for SSP were observed between the PF-ILD and non-PF-ILD patients. Older age and lower BMI were significant predictors of mortality by multivariate Cox regression analysis. ROC analysis showed BMI ≤17.8 kg/m2 to reliably predict poor prognosis.

CONCLUSIONS: Regardless of whether patients have PF-ILD, older age and lower BMI in patients with ILD places them at higher risk of developing SSP, and prognosis is poor if SSP develops. Therefore, clinical management of physique is important to improve the prognosis of ILD patients.

PMID:35115749 | PMC:PMC8787380 | DOI:10.36141/svdld.v38i4.11465

Eur Respir J. 2022 Feb 3:2200024. doi: 10.1183/13993003.00024-2022. Online ahead of print.

NO ABSTRACT

PMID:35115340 | DOI:10.1183/13993003.00024-2022

Eur Respir J. 2022 Feb 3:2101814. doi: 10.1183/13993003.01814-2021. Online ahead of print.

ABSTRACT

Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis (IPF), however it is not known if ILA are associated with decreased mean telomere length (MTL).Telomere length was measured with quantitative polymerase chain reaction in COPDGene and AGES-Reykjavik, and southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality.In all three cohorts ILA were associated with decreased MTL. In COPDGene and AGES-Reykjavik, after adjustment there was greater than two-fold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (odds ratio [OR]=2.2, 95% confidence interval [CI] 1.5-3.4, p=0.0001 and OR=2.6, 95% CI 1.4-4.9, p=0.003), respectively. In the FHS, those with ILA had shorter telomeres compared to those without ILA (-767 bp, 95% CI 76-1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR=1.3, 95% confidence interval [CI] 1.1-1.6, p=0.01) in COPDGene the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death, when comparing the shortest quartile of telomere length (hazard ratio [HR]=0.82, 95% CI 0.4-1.7, p=0.6 and HR=1.2, 95% CI 0.6-2.2, p=0.5) in COPDGene and AGES-Reykjavik respectively.ILA are associated with decreased mean telomere length when compared to those without ILA.

PMID:35115336 | DOI:10.1183/13993003.01814-2021

J Surg Res. 2022 Jan 31;274:9-15. doi: 10.1016/j.jss.2021.12.025. Online ahead of print.

ABSTRACT

INTRODUCTION: Currently, standard practice is to use the continuous suturing technique on the bronchial anastomosis during lung transplantation. This study used a large cohort to investigate and contrast continuous and interrupted suturing techniques, comparing survival outcomes and occurrence of postoperative bronchial complications to examine if utilization of interrupted suturing has merit.

METHODS: Survival outcomes of 740 single-center lung transplant recipients over 8 y (February 2012-March 2020) were compared by suturing techniques: either continuous or interrupted at the bronchial anastomosis. Clinical parameters and demographics were compared between two suturing groups, with P values < 0.05 considered significant. The groups were compared for postoperative morbidity, including need for bronchial interventions. Survival was compared using Kaplan-Meier curves and log-rank tests. Cox regression analysis was run with statistically significant variables to study association with survival.

RESULTS: Of the 740 patients, 462 received the continuous suturing technique and 278 received the interrupted suturing technique. Most demographic and clinical data were not statistically significant between the two groups, and those that were significant were not associated with worse survival outcomes, with the exception of the variable diagnosis. Bronchial complications were comparable between the continuous and interrupted groups (12.6% versus 10.4%, P = 0.382). Extracorporeal membrane oxygenation (ECMO) use did not differ significantly between the two groups (P = 0.12). The Kaplan-Meier curve showed comparable survival between groups (P = 0.98), and Cox regression analysis showed that only diagnosis, bronchial complications, and ECMO utilization were associated with different survival outcomes. Chronic obstructive pulmonary disorder was shown to be associated with more favorable survival outcomes as opposed to idiopathic pulmonary fibrosis and the category "other". The need for ECMO and the occurrence of a bronchial complication were also associated with worse survival outcomes.

CONCLUSIONS: Both techniques showed reasonable post-transplant outcomes, as our study demonstrated similar survival outcomes and bronchial complication rates.

PMID:35114484 | DOI:10.1016/j.jss.2021.12.025