J Ethnopharmacol. 2021 Aug 12:114522. doi: 10.1016/j.jep.2021.114522. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Firstly prescribed in the ancient Chinese book Jingui Yaolue, Gancao Ganjiang decoction (GGD) is a traditional Chinese herbal formula that has been widely used to treat "atrophic lung disease". GGD is a popular and widely used traditional Chinese medicine. The decoction is extracted from the dried rhizomes and roots of Glycyrrhiza uralensis Fisch. and Zingiber officinale Roscoe (2:1).

AIM OF STUDY: To investigate the therapeutic effect of idiopathic pulmonary fibrosis (IPF) of GGD, a bleomycin-induced IPF murine model was used in this study.

MATERIALS AND METHODS: Mice were induced by bleomycin instillation and GGD was orally administered. Changes on mice weight were recorded during the experiment. Lung weight was recorded on days 14 and 28, and pulmonary index was calculated accordingly. Pathological evaluation, including fibrosis analysis of lung tissue, was assessed by H&E and Masson staining. The expression of PD-1, p-STAT3 and IL-17A were detected by immunohistochemistry (IHC). The expression of p-STAT3 in lung tissues of mice were detected by Western blot. The level of IL-17A in lung tissue were detected by ELISA. The expression of PD-1 in CD4+ T cells in peripheral blood of mice was detected by flow cytometry. The levels of hydroxyproline and TGF-β1 in lung tissue were detected by ELISA. The expression of E-cadherin, vimentin and α-SMA in lung tissues of mice were detected by qRT-PCR and Western blot.

RESULTS: GGD can increase body weight and reduce pulmonary index in mice with pulmonary fibrosis. As such, GGD can significantly improve the inflammatory and alleviate IPF in the lung tissue of mice. GGD treatment was capable of reducing the content of PD-1 in lung tissue as well as the expression of PD-1 in CD4+ T cells in peripheral blood. Likewise, GGD was able to reduce the content of p-STAT3, IL-17A and TGF-β1. In addition, GGD stimulation could inhibit epithelial-mesenchymal transformation (EMT) by increasing the expression of E-cadherin and reducing vimentin and α-SMA, thus reducing extracellular matrix (ECM) deposition.

CONCLUSION: Our results indicate that GGD positively affects IPF by regulating PD-1/TGF-β1/IL-17A pathway.

PMID:34391863 | DOI:10.1016/j.jep.2021.114522

Respir Res. 2021 Aug 14;22(1):228. doi: 10.1186/s12931-021-01821-w.

ABSTRACT

BACKGROUND: Transbronchial cryobiopsy in the evaluation of patients with interstitial lung diseases (ILD) is expected to reduce the need for surgical lung biopsy (SLB).

OBJECTIVE: To evaluate the diagnostic value of cryobiopsy in combination with bronchoalveolar lavage (BAL), radiologic and clinical data in patients with ILD.

METHODS: Between 08/15 and 01/20 patients with ILD underwent cryobiopsy if they: did not have (i) an usual interstitial pneumonia (UIP)-pattern on CT, (ii) predominant ground-glass opacities suggesting alveolitis, (iii) findings suggestive of sarcoidosis on CT, or if they had (i) a CT showing UIP-pattern, but had findings suggesting alternative diagnosis than idiopathic pulmonary fibrosis (IPF), or (ii) had previous non-diagnostic conventional transbronchial forceps biopsy. Histological findings were integrated into the multidisciplinary team discussion (MDTD) and a diagnostic consensus was sought.

RESULTS: One hundred patients underwent cryobiopsy. In 88/100 patients, cryobiopsy was representative with diagnostic findings in 45/88 and non-specific histological findings in 43/88 patients. In 25/43 with non-specific findings, a consensus diagnosis was reached after MDTD integrating BAL, radiologic and clinical data; eight of the remaining 18 patients with non-specific findings were referred to SLB. In 12/100 patients cryobiopsy was not representative and three of these patients were also referred to SLB. In 7/11 patients (64%) SLB was diagnostic. Complications of cryobiopsy included pneumothorax (14%) and locally controlled bleeding (24%).

CONCLUSIONS: The diagnostic yield of cryobiopsy was 70%:45% of cryobiopsies were diagnostic based on histology alone and an additional 25% provided non-specific, but valuable findings allowing a consensus diagnosis after MDTD. Our data demonstrate that the diagnostic value of cryobiopsy is high if combined with BAL, radiologic and clinical data.

PMID:34391420 | DOI:10.1186/s12931-021-01821-w

Sci Rep. 2021 Aug 13;11(1):16481. doi: 10.1038/s41598-021-95728-7.

ABSTRACT

The purpose of this study was to evaluate the implications of the 2018 updated guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) in clinical practice compared to 2011 guideline. This study involved 535 patients including 339 IPF and 196 non-IPF, and we retrospectively evaluated CT classifications of usual interstitial pneumonia (UIP) by two guidelines. Interobserver agreement of 2018 criteria showed moderate reliability (κ = 0.53) comparable to 2011 (κ = 0.56) but interobserver agreement for probable UIP was fair (κ = 0.40). CT pattern of indeterminate for UIP was associated with better prognosis compared with the other groups (adjusted hazard ratio [HR] = 0.36, p < 0.001). Compared to possible UIP, probable UIP demonstrated a lower positive predictive value (PPV, 62.9% vs 65.8%). In analysis of patients with CT patterns of non-definite UIP, diagnosing IPF when CT pattern showed probable UIP with lymphocyte count ≤ 15% in BAL fluid, and either male sex or age ≥ 60 years showed a high specificity of 90.6% and a PPV of 80.8% in the validation cohort. The 2018 criteria provide better prognostic stratification than the 2011 in patients with possible UIP. BAL fluid analysis can improve the diagnostic certainty for IPF diagnosis in patients with probable UIP CT pattern.

PMID:34389774 | DOI:10.1038/s41598-021-95728-7

Int J Surg Case Rep. 2021 Aug 4;85:106282. doi: 10.1016/j.ijscr.2021.106282. Online ahead of print.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Abdominal cocoon (AC) or Encapsulating Peritoneal Sclerosis (EPS) is a rare cause of bowel obstruction and due to non-specific presentation, it can be misdiagnosed and often mistreated.

CASE PRESENTATION: We present the case of 42 years male with a history suggestive of complete small bowel obstruction (SBO) without a history of pulmonary tuberculosis (TB) or peritoneal dialysis. CT imaging as well as the intraoperative finding of a cocoon membrane encasing the small bowel led to the diagnosis of abdominal cocoon.

CLINICAL DISCUSSION: Abdominal cocoon can be idiopathic or secondary to peritoneal dialysis, tuberculosis, or other rare causes. Patients usually present with features of SBO with varying severity. Diagnosis is aided by imaging investigations mainly CT scan and management is primarily surgical and usually involves adhesiolysis, total removal of the membrane with or without bowel loop resection.

CONCLUSION: Diagnosis of abdominal cocoon warrants awareness of the disease and a high index of suspicion of the treating clinician in patients with intestinal obstruction and an abdominal lump without a history of previous abdominal surgery. CT can guide diagnosis and early operative management seems to bear the best outcomes.

PMID:34388909 | DOI:10.1016/j.ijscr.2021.106282

Nat Aging. 2021 Feb;1(2):205-217. doi: 10.1038/s43587-021-00027-5. Epub 2021 Feb 11.

ABSTRACT

Aging is a risk factor for progressive fibrotic disorders involving diverse organ systems, including the lung. Idiopathic pulmonary fibrosis, an age-associated degenerative lung disorder, is characterized by persistence of apoptosis-resistant myofibroblasts. In this report, we demonstrate that sirtuin-3 (SIRT3), a mitochondrial deacetylase, is downregulated in lungs of IPF human subjects and in mice subjected to lung injury. Over-expression of the SIRT3 cDNA via airway delivery restored capacity for fibrosis resolution in aged mice, in association with activation of the forkhead box transcription factor, FoxO3a, in fibroblasts, upregulation of pro-apoptotic members of the Bcl-2 family, and recovery of apoptosis susceptibility. While transforming growth factor-β1 reduced levels of SIRT3 and FoxO3a in lung fibroblasts, cell non-autonomous effects involving macrophage secreted products were necessary for SIRT3-mediated activation of FoxO3a. Together, these findings reveal a novel role of SIRT3 in pro-resolution macrophage functions that restore susceptibility to apoptosis in fibroblasts via a FoxO3a-dependent mechanism.

PMID:34386777 | PMC:PMC8357317 | DOI:10.1038/s43587-021-00027-5

Front Immunol. 2021 Jul 27;12:720876. doi: 10.3389/fimmu.2021.720876. eCollection 2021.

ABSTRACT

BACKGROUND: C-reactive protein (CRP) has been used as a biomarker of chronic low-grade inflammation in observational studies. We aimed to determine whether genetically determined CRP was associated with hundreds of human phenotypes to guide anti-inflammatory interventions.

METHODS: We used individual data from the UK Biobank to perform a phenome-wide two-stage least squares (2SLS) Mendelian randomization (MR) analysis for CRP with 879 diseases. Summary-level data from the FinnGen consortium were utilized to perform phenome-wide two-sample MR analysis on 821 phenotypes. Systematic two-sample MR methods included MR-IVW, MR-WME, MR-Mod, and MR-PRESSO as sensitivity analyses combined with multivariable MR to identify robust associations. Genetic correlation analysis was applied to identify shared genetic risks.

RESULTS: We found genetically determined CRP was robustly associated with 15 diseases in the UK Biobank and 11 diseases in the FinnGen population (P < 0.05 for all MR analyses). CRP was positively associated with tongue cancer, bronchitis, hydronephrosis, and acute pancreatitis and negatively associated with colorectal cancer, colon cancer, cerebral ischemia, electrolyte imbalance, Parkinson's disease, epilepsy, anemia of chronic disease, encephalitis, psychophysical visual disturbances, and aseptic necrosis of bone in the UK Biobank. There were positive associations with impetigo, vascular dementia, bipolar disorders, hypercholesterolemia, vertigo, and neurological diseases, and negative correlations with degenerative macular diseases, metatarsalgia, interstitial lung disease, and idiopathic pulmonary fibrosis, and others. in the FinnGen population. The electrolyte imbalance and anemia of chronic disease in UK Biobank and hypercholesterolemia and neurological diseases in FinnGen pass the FDR corrections. Neurological diseases and bipolar disorders also presented positive genetic correlations with CRP. We found no overlapping causal associations between the populations. Previous causal evidence also failed to support these associations (except for bipolar disorders).

CONCLUSIONS: Genetically determined CRP was robustly associated with several diseases in the UK Biobank and the FinnGen population, but could not be replicated, suggesting heterogeneous and non-repeatable effects of CRP across populations. This implies that interventions at CRP are unlikely to result in decreased risk for most human diseases in the general population but may benefit specific high-risk populations. The limited causal evidence and potential double-sided effects remind us to be cautious about CRP interventions.

PMID:34386016 | PMC:PMC8353321 | DOI:10.3389/fimmu.2021.720876

Eur Respir J. 2021 Aug 12:2101714. doi: 10.1183/13993003.01714-2021. Online ahead of print.

NO ABSTRACT

PMID:34385277 | DOI:10.1183/13993003.01714-2021

Eur Respir J. 2021 Aug 12:2101372. doi: 10.1183/13993003.01372-2021. Online ahead of print.

NO ABSTRACT

PMID:34385270 | DOI:10.1183/13993003.01372-2021

Eur Respir J. 2021 Aug 12:2101739. doi: 10.1183/13993003.01739-2021. Online ahead of print.

NO ABSTRACT

PMID:34385267 | DOI:10.1183/13993003.01739-2021

BMJ Open. 2021 Aug 12;11(8):e050578. doi: 10.1136/bmjopen-2021-050578.

ABSTRACT

OBJECTIVE: To learn about the attitudes and behaviours of patients with idiopathic pulmonary fibrosis (IPF) in relation to the difficulties experienced during the COVID-19 pandemic.

DESIGN: A cross-sectional, multicentre phone call survey.

SETTING: Four university hospitals in Turkey.

PARTICIPANTS: The study included patients with IPF receiving antifibrotics for at least 3 months and with doctor appointment and/or scheduled routine blood analysis between March and May 2020 (the first 3 months after the official announcement of the COVID-19 pandemic in Turkey).

INTERVENTIONS: Phone calls (a 5 min interview) were performed in June 2020. A questionnaire and the Hospital Anxiety-Depression Scale were applied.

MAIN OUTCOME MEASURES: Patients' preferences for disease monitoring, patients' attitudes and behaviours towards IPF, drug continuation, COVID-19 diagnosis and anxiety/depression status.

RESULTS: The study included 115 patients with IPF (82 male; mean age, 68.43±7.44 years). Of the patients, 73.9% had doctor appointment and 52.2% had scheduled routine blood testing; 54.5% of patients with doctor appointment self-cancelled their appointments and 53.3% of patients with scheduled routine blood testing did not undergo testing. Of the patients, 32.2% were on nintedanib and 67.8% were on pirfenidone; self-initiated drug discontinuation rate was 22.6%. The percentage of patients communicating with their physicians was 35.7%. The route of communication was by phone (34.8%). The frequency of depression and anxiety was 27.0% and 38.3%, respectively. The rates of drug discontinuation (35.1% vs 16.7%, p<0.05) and depression (37.8% vs 21.8%, p=0.07) were higher in nintedanib users than in pirfenidone users. Only two (1.7%) patients had COVID-19 diagnosis.

CONCLUSIONS: During the COVID-19 pandemic, a significant proportion (>50%) of patients self-cancelled their appointments and nearly a quarter of patients discontinued their medications. Providing a documentation of the problems experienced by patients with IPF about management of the necessary requirements during the COVID-19 pandemic, this study may be a model for patients with chronic diseases.

PMID:34385255 | DOI:10.1136/bmjopen-2021-050578

Front Neurol. 2021 Jul 26;12:687088. doi: 10.3389/fneur.2021.687088. eCollection 2021.

ABSTRACT

Moyamoya disease is an idiopathic chronically progressive cerebrovascular disease, which causes both ischemic and hemorrhagic stroke. Genetic studies identified RNF213/Mysterin and GUCY1A3 as disease-causing genes. They were also known to be associated with non-moyamoya intracranial large artery disease, coronary artery disease and pulmonary artery hypertension. This review focused on these two molecules and their strong linker, calcineurin/NFAT signaling and caveolin to understand the pathophysiology of moyamoya disease and related vascular diseases. They are important regulators of lipid metabolism especially lipotoxicity, NF-κB mediated inflammation, and nitric oxide-mediated vascular protection. Although intimal thickening with fibrosis and damaged vascular smooth muscle cells are the distinguishing features of moyamoya disease, origin of the fibrous tissue and the mechanism of smooth muscle cell damages remains not fully elucidated. Endothelial cells and smooth muscle cells have long been a focus of interest, but other vascular components such as immune cells and extracellular matrix also need to be investigated in future studies. Molecular research on moyamoya disease would give us a clue to understand the mechanism preserving vascular stability.

PMID:34381413 | PMC:PMC8350054 | DOI:10.3389/fneur.2021.687088

Ann Rheum Dis. 2021 Aug 11:annrheumdis-2021-220493. doi: 10.1136/annrheumdis-2021-220493. Online ahead of print.

ABSTRACT

OBJECTIVES: Interstitial lung disease is a significant comorbidity and the leading cause of mortality in patients with systemic sclerosis. Transcriptomic data of systemic sclerosis-associated interstitial lung disease (SSc-ILD) were analysed to evaluate the salient molecular and cellular signatures in comparison with those in related pulmonary diseases and to identify the key driver genes and target molecules in the disease module.

METHODS: A transcriptomic dataset of lung tissues from patients with SSc-ILD (n=52), idiopathic pulmonary fibrosis (IPF) (n=549), non-specific interstitial pneumonia (n=49) and pulmonary arterial hypertension (n=81) and from normal healthy controls (n=331) was subjected to filtration of differentially expressed genes, functional enrichment analysis, network-based key driver analysis and kernel-based diffusion scoring. The association of enriched pathways with clinical parameters was evaluated in patients with SSc-ILD.

RESULTS: SSc-ILD shared key pathogenic pathways with other fibrosing pulmonary diseases but was distinguishable in some pathological processes. SSc-ILD showed general similarity with IPF in molecular and cellular signatures but stronger signals for myofibroblasts, which in SSc-ILD were in a senescent and apoptosis-resistant state. The p53 signalling pathway was the most enriched signature in lung tissues and lung fibroblasts of SSc-ILD, and was significantly correlated with carbon monoxide diffusing capacity of lung, cellular senescence and apoptosis. EEF2, EFF2K, PHKG2, VCAM1, PRKACB, ITGA4, CDK1, CDK2, FN1 and HDAC1 were key regulators with high diffusion scores in the disease module.

CONCLUSIONS: Integrative transcriptomic analysis of lung tissues revealed key signatures of fibrosis in SSc-ILD. A network-based Bayesian approach provides deep insights into key regulatory genes and molecular targets applicable to treating SSc-ILD.

PMID:34380701 | DOI:10.1136/annrheumdis-2021-220493

Br J Pharmacol. 2021 Aug 11. doi: 10.1111/bph.15655. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Development of pulmonary fibrosis is associated with altered DNA methylation modifications of fibrogenic gene expressions; however, their causal relationships and the underlying mechanisms remain unclear. This study investigates the critical role of DNA methylation aberration-associated suppression of PPARγ (peroxisome proliferator-activated receptor-gamma) in pulmonary fibrosis.

EXPERIMENTAL APPROACH: Expressions of PPARγ and bioactive DNA methyltranferases, and PPARγ promoter methylation status were examined from fibrotic lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin (Blm)-treated mice. DNA demethylating agent 5-Aza-2'-deoxycytidine (5aza) and glycyrrhizic acid (GA) derived from medicinal plant were assessed for their PPARγ derepression and anti-pulmonary fibrosis activities. PPARγ knockout mice were created to determine the critical role of PPARγ in the protections.

KEY RESULTS: Lung PPARγ expressions were markedly suppressed in IPF patients and Blm mice, accompanied by increased methyltransferase (DNMT) 1/DNMT3a and PPARγ promoter hypermethylation. Administrations of 5aza and GA similarly demethylated PPARγ promoter, recovered the PPARγ loss and alleviated the fibrotic lung pathologies, including structural alterations and adverse expressions of fibrotic mediators and inflammatory cytokines. In cultured lung fibroblast and alveolar epithelial cells, GA alleviated the fibrotic PPARγ suppression in a gain of DNMT-sensitive manner, and in PPARγ knockout mice, the anti-fibrotic effects of 5aza and GA were significantly reduced, suggesting that PPARγ is a critical mediator of epigenetic pulmonary fibrogenesis.

CONCLUSION AND IMPLICATIONS: Aberrant DNMT1/3a elevations and the resultant PPARγ suppression contribute significantly to the development of pulmonary fibrosis, and strategies targeting DNMT/PPARγ axis by synthetic or natural small compounds might benefit patients with pulmonary fibrotic disorders.

PMID:34378791 | DOI:10.1111/bph.15655

J Extracell Vesicles. 2021 Aug;10(10):e12124. doi: 10.1002/jev2.12124. Epub 2021 Aug 2.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis, resulting in poor patient prognosis. An aberrant recapitulation of developmental lung gene expression, including genes for transforming growth factor (TGF)-β and WNT, has been widely implicated in the pathogenic IPF wound healing process that results from repetitive alveolar epithelial injury. Extracellular vesicles (EVs) have been shown to carry bioactive molecules and to be involved in various physiological and pathological processes. Here, we demonstrate that, by attenuating WNT signalling, human bronchial epithelial cell-derived EVs (HBEC EVs) inhibit TGF-β mediated induction of both myofibroblast differentiation and lung epithelial cellular senescence. This effect of HBEC EVs is more pronounced than that observed with mesenchymal stem cell-derived EVs. Mechanistically, the HBEC EV microRNA (miRNA) cargo is primarily responsible for attenuating both myofibroblast differentiation and cellular senescence. This attenuation occurs via inhibition of canonical and non-canonical WNT signalling pathways. Among enriched miRNA species present in HBEC EVs, miR-16, miR-26a, miR-26b, miR-141, miR-148a, and miR-200a are mechanistically involved in reducing WNT5A and WNT10B expression in LFs, and in reducing WNT3A, WNT5A, and WNT10B expression in HBECs. Mouse models utilizing intratracheal administration of EVs demonstrate efficient attenuation of bleomycin-induced lung fibrosis development accompanied by reduced expression of both β-catenin and markers of cellular senescence. These findings indicate that EVs derived from normal resident lung HBECs may possess anti-fibrotic properties. They further suggest that, via miRNA-mediated inhibition of TGF-β-WNT crosstalk, HBEC EVs administration can be a promising anti-fibrotic modality of treatment for IPF.

PMID:34377373 | PMC:PMC8329991 | DOI:10.1002/jev2.12124

Sci Rep. 2021 Aug 10;11(1):16250. doi: 10.1038/s41598-021-95869-9.

ABSTRACT

TOLLIP polymorphism has been implicated in the development and prognosis of idiopathic pulmonary fibrosis (IPF), mainly in whites. However, ethnic differences in the characteristics of other interstitial pneumonia (non-IPF) subtypes are unclear. We evaluated the association between the rs3750920 genotype and the clinical characteristics of Japanese patients with fibrosing interstitial lung diseases (ILD). We genotyped 102 patients with fibrosing ILD (75 IPF and 27 non-IPF patients) and analyzed the interaction between the rs3750920 genotype distribution and their clinical characteristics. The overall frequencies of the C/C, C/T, and T/T genotypes were 69%, 25%, and 6%, respectively. The proportion of minor T allele carriers was larger in IPF patients than in non-IPF patients (37% vs. 15%, P = 0.031). In addition, survival at 3 years was significantly better for carriers than for non-carriers of the T allele. There was no significant association between genotype distribution and change in pulmonary function after introduction of antifibrotic agents. The frequency of the minor T allele of rs3750920 was low in Japanese patients with fibrosing ILD, particularly in non-IPF patients. Carriers of the minor T allele had better survival than non-carriers. Presence of the T allele might thus be an indicator of better outcomes for fibrosing ILD.

PMID:34376770 | DOI:10.1038/s41598-021-95869-9

BMJ Open Respir Res. 2021 Aug;8(1):e000969. doi: 10.1136/bmjresp-2021-000969.

ABSTRACT

INTRODUCTION: Outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with pre-existing idiopathic pulmonary fibrosis (IPF) remain understudied, and it is unknown if IPF is an independent predictor of worse disease course. Herein, we report the clinical outcomes in a large cohort of 251 patients with COVID-19 in the setting of known IPF. Outcomes were compared with a propensity matched cohort of patients with COVID-19 without IPF.

METHODS: Analysis of a federated multicentre research network TriNetX was performed including patients more than 16 years of age diagnosed with SARS-CoV-2 infection. Outcomes in patients diagnosed as positive for SARS-CoV-2 infection with concurrent IPF were compared with a propensity matched cohort of patients without IPF.

RESULTS: A total of 311 060 patients with SARS-CoV-2 infection on the research network were identified, 251 patients (0.08%) carried a diagnosis of IPF. Mean age of patients with IPF was 68.30±12.20 years, with male predominance (n=143, 56.97%). Comorbidities including chronic lower respiratory diseases, diabetes mellitus, ischaemic heart disease and chronic kidney disease were more common in patients with IPF when compared with the non-IPF cohort. After propensity matching, higher rates of composite primary outcome (death or mechanical ventilation) at 30 and 60 days, as well as need for hospitalisation, critical care, and acute kidney injury were observed in the IPF cohort.

CONCLUSION: Poor outcomes of COVID-19 disease were observed in patients with IPF after robust matching of confounders. Our data confirm that patients with IPF constitute a high-risk cohort for poor outcomes related to COVID-19 disease.

PMID:34376400 | DOI:10.1136/bmjresp-2021-000969

Am J Respir Crit Care Med. 2021 Aug 10. doi: 10.1164/rccm.202104-0847OC. Online ahead of print.

ABSTRACT

RATIONALE: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. HRCT resolution is limited while surgical lung biopsy (SLB) carries risks of morbidity/mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis.

OBJECTIVES: We performed a prospective diagnostic accuracy study of EB-OCT in ILD patients with a low-confidence diagnosis undergoing SLB. Primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern.

METHODS: EB-OCT was performed immediately prior to SLB. The resulting EB-OCT images and histopathology were interpreted independently by blinded, independent pathologists. Clinical diagnosis was obtained from the treating pulmonologists after SLB, blinded to EB-OCT.

MEASUREMENTS AND MAIN RESULTS: We enrolled 31 patients, and four were excluded due to inconclusive histopathology or lack of EB-OCT data. Twenty-seven patients were included in the analysis (16 men, average age: 65.0 years): twelve were diagnosed with UIP and fifteen with non-UIP ILD. Average forced vital capacity and DLCO were 75.3% (SD:18.5) and 53.5% (SD:16.4), respectively. Sensitivity and specificity of EB-OCT was 100% (95% CI: 75.8-100.0%) and 100% (79.6-100%), respectively, for both histopathologic UIP and clinical diagnosis of IPF. There was high agreement between EB-OCT and histopathology for diagnosis of ILD fibrosis pattern (weighted κ: 0.87, (0.72-1.0)).

CONCLUSIONS: EB-OCT is a safe, accurate method for microscopic ILD diagnosis, as a complement to HRCT and alternative to SLB.

PMID:34375171 | DOI:10.1164/rccm.202104-0847OC

Phytother Res. 2021 Aug 10. doi: 10.1002/ptr.7239. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by epithelial cell damage, fibroblast activation, and collagen deposition. IPF has high mortality and limited therapies, which urgently needs to develop safe and effective therapeutic drugs. Bergenin, a compound derived from a variety of medicinal plants, has demonstrated multiple pharmacological activities including anti-inflammatory and anti-tumor, also acts as a traditional Chinese medicine to treat chronic bronchitis, but its effect on the pulmonary fibrosis is unknown. In this study, we demonstrated that bergenin could attenuate bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro studies indicated that bergenin inhibited the transforming growth factor-β1 (TGF-β1)-induced fibroblast activation and the extracellular matrix accumulation by inhibiting the TGF-β1/Smad signaling pathway. Further studies showed that bergenin could induce the autophagy formation of myofibroblasts by suppressing the mammalian target of rapamycin signaling and that bergenin could promote the myofibroblast apoptosis. In vivo experiments revealed that bergenin substantially inhibited the myofibroblast activation and the collagen deposition and promoted the autophagy formation. Overall, our results showed that bergenin attenuated the BLM-induced pulmonary fibrosis in mice by suppressing the myofibroblast activation and promoting the autophagy and the apoptosis of myofibroblasts.

PMID:34375009 | DOI:10.1002/ptr.7239

Pneumologie. 2021 Aug;75(8):601-610. doi: 10.1055/a-1273-4105. Epub 2021 Aug 9.

ABSTRACT

Acute exacerbations (AE) are a life-threatening complication in patients with idiopathic pulmonary fibrosis (IPF). In-hospital mortality is high and the overall prognosis poor. The underlying causes of AE-IPF still remain unclear and there are no focused guidelines for its management. In most cases high-dose steroids combined with an antibiotic therapy are applied. Preventive and palliative measures are very important. Intensive research is necessary to improve management of AE-IPF.

PMID:34374062 | DOI:10.1055/a-1273-4105

Heart Vessels. 2021 Aug 9. doi: 10.1007/s00380-021-01917-9. Online ahead of print.

ABSTRACT

In this prospective study on patients with acute myocarditis (AM), we aimed to describe the new concept of AMAF (AM with autoimmune features) similar to the previously described interstitial pneumonia with autoimmune features (IPAF). IPAF has recently emerged as a new entity, and IPAF patients appear to have fewer episodes of exacerbation and better survival than patients with idiopathic pulmonary fibrosis. Consecutive patients with infarct-like CMR-confirmed AM were classified AMAF if their serologic status measured from blood sampled at presentation was positive (antinuclear antibodies (ANA) ≥ 1:320), but without meeting established classification criteria for connective tissue disease (CTD). The myocardial tissue abnormalities and their progression were assessed on cardiac magnetic resonance (CMR) within 7 days following symptom onset and at 1 year according to their seropositivity. Among the 64 AM patients included, seven presented AMAF (11%). At baseline CMR, patients with AMAF had half as much late gadolinium enhancement (LGE) as seronegative AM patients (4.41% (1.47-4.41) of myocardial volume versus 8.82% (5.88-14.71), p = 0.01, respectively). At 1-year of follow-up, persistent myocardial scarring was less frequent in AMAF patients (n = 2 (28.6%) than seronegative AM patients (n = 38 (66.7%) (p = 0.021). AMAF, diagnosed as seropositive AM without a specific autoimmune disease, is not rare and is associated with less extensive LGE in the acute phase. In addition, AMAF patients had more favorable outcomes on 12-month CMR. Prospective studies are needed to address the clinical significance of this new concept and its long-term cardiovascular impact.

PMID:34373946 | DOI:10.1007/s00380-021-01917-9