Am J Respir Cell Mol Biol. 2021 Jun 9. doi: 10.1165/rcmb.2020-0499OC. Online ahead of print.

ABSTRACT

The Wnt/β-catenin pathway initiates a signaling cascade critical in cell differentiation and normal development of multiple organ systems. The reactivation of this pathway has been documented in experimental and human idiopathic pulmonary fibrosis (IPF), wherein Wnt/β-catenin activation has been implicated in epithelial cell repair. Furthermore the canonical ligand Wnt3a is known to induce myofibroblast differentiation, however the role of non-canonical Wnt ligands remains unclear. This study showed significantly higher levels of Wnt11 expression in cells from both IPF patients and bleomycin-treated mice, as well as in TGFβ treated mouse lung fibroblasts. Moreover Wnt11 induced myofibroblast differentiation as manifested by increased α-smooth muscle actin (α-SMA) expression, which was similar to that induced by canonical Wnt3a/β-catenin signaling. Further investigation revealed that Wnt11 induction of α-SMA, was associated with the activation of JNK/c-Jun signaling and inhibited by a JNK inhibitor. The potential importance of this signaling pathway was supported by in vivo evidence showing significantly increased levels of Wnt11 and activated JNK in lungs of mice with bleomycin induced pulmonary fibrosis. Interestingly, fibroblasts did not express canonical Wnt3a but treatment of these cells with exogenous Wnt3a induced endogenous Wnt11 and Wnt5a resulting in repression of the Wnt3a/β-catenin target gene Axin2. These findings suggested that the non-canonical Wnt induction of myofibroblast differentiation mediated by JNK/c-Jun pathway might play a significant role in pulmonary fibrosis, in addition to, or synergy with canonical Wnt3a/β-catenin signaling. Moreover Wnt3a activation of non-canonical Wnt signaling might trigger a switch from canonical to non-canonical Wnt signaling to induce myofibroblast differentiation.

PMID:34107237 | DOI:10.1165/rcmb.2020-0499OC

Turk Gogus Kalp Damar Cerrahisi Derg. 2021 Apr 26;29(2):191-200. doi: 10.5606/tgkdc.dergisi.2021.9490. eCollection 2021 Apr.

ABSTRACT

BACKGROUND: In this study, we aimed to discuss our anesthesia management strategies, experiences, and outcomes in patients undergoing lung transplantation.

METHODS: Between December 2016 and December 2018, a total of 53 patients (43 males, 10 females; mean age: 46.1±13 years; range, 14 to 64 years) undergoing lung transplantation in our center were included. The anesthesia technique, patients" characteristics, and perioperative clinical and follow-up data were recorded. The stage of lung disease was assessed using the New York Heart Association functional classification.

RESULTS: Two patients underwent single lung transplantation, while 51 patients underwent double lung transplantation. Idiopathic pulmonary fibrosis was the most common indication in 41.5% of the patients. All patients had end-stage lung disease (Class IV) and 79% were oxygen-dependent. The extracorporeal membrane oxygenation support was given to 32 patients.

CONCLUSION: The anesthetic management of lung transplantation is challenging, either due to the deterioration of the recipient"s physical performance and the complexity of the surgical techniques used. In general, a kind of mechanical support may be needed and extracorporeal membrane oxygenation is the first choice in the majority of patients. A close communication should be maintained between the surgeons, perfusion technicians, and anesthesiologists to ensure an optimal multidisciplinary approach and to achieve successful outcomes.

PMID:34104513 | PMC:PMC8167475 | DOI:10.5606/tgkdc.dergisi.2021.9490

Respir Res. 2021 Jun 8;22(1):175. doi: 10.1186/s12931-021-01760-6.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse interstitial lung disease, of which the etiology has been poorly understood. Several studies have focused on the relationship between IPF and diabetes mellitus (DM) in the past years but have failed to reach a consensus. This meta-analysis aimed to examine the association between diabetes to IPF.

METHODS: We accumulated studies investigating the association between DM and IPF from databases including Medline, Cochrane Library, Embase, Web of Science, and China National Knowledge Infrastructure. RevMan 5.3 and the Newcastle-Ottawa Scale (NOS) were utilized to analyze the data and assess the quality of the included studies. The value of odds ratio (OR) with 95% confidence interval (CI) was used as the measure to estimate the risk of DM in IPF. Heterogeneity was assessed by I2 statistics. We also performed subgroup analysis, meta-regression, and Egger's test for bias analysis.

RESULTS: Nine case-control studies with 5096 IPF patients and 19,095 control subjects were included in the present meta-analysis, which indicated a positive correlation between DM and IPF (OR 1.65, 95% CI 1.30-2.10; P < 0.0001). Meta-regression and subgroup analysis negated the influence of covariates like cigarette smoking, age and gender, but the heterogeneity existed and could not be fully explained.

CONCLUSION: IPF and DM may be associated, but the causal relationship remains indeterminate till now. Further rigorously designed studies are required to confirm the present findings and investigate the possible mechanisms behind the effect of DM on IPF.

PMID:34103046 | DOI:10.1186/s12931-021-01760-6

BMC Pulm Med. 2021 Jun 8;21(1):193. doi: 10.1186/s12890-021-01559-7.

NO ABSTRACT

PMID:34103038 | DOI:10.1186/s12890-021-01559-7

Chest. 2021 Jun 5:S0012-3692(21)01090-4. doi: 10.1016/j.chest.2021.05.058. Online ahead of print.

NO ABSTRACT

PMID:34102142 | DOI:10.1016/j.chest.2021.05.058

Histopathology. 2021 Jun 8. doi: 10.1111/his.14427. Online ahead of print.

ABSTRACT

BACKGROUND: The recent recognition of the cicatricial organizing pneumonia (ciOP) indicates that the ciOP may resemble or simulate fibrotic interstitial pneumonia; however, there has been great uncertainty regarding the affected populations, pathogenesis, clinical relevance, and characteristics. In this study, we compared the characteristics of fibrotic interstitial pneumonia with and without ciOP.

METHOD: We enrolled 121 patients from the consultation archive whose pathological findings were fibrotic interstitial pneumonia and for whom follow-up clinical data were available. We reviewed these cases histopathologically and classified them according to whether or not they showed ciOP. We compared the clinicopathological features between the two groups.

RESULT: CiOP histopathologically characterized by deposition of dense collagenous fibers within the alveolar space without destruction of the lung structure was found in 48 patients (39.7%). None of the cases with ciOP experienced acute exacerbation during 12 months follow-up. The group with ciOP had more severe diffusion impairment but this, along with restrictive ventilatory impairment, improved significantly compared to the group without ciOP.

CONCLUSION: CiOP is a histopathological finding commonly found in fibrotic interstitial pneumonia. It does not relate to acute exacerbation or decrease in pulmonary function.

PMID:34101227 | DOI:10.1111/his.14427

J Pathol. 2021 Jul;254(4):303-306. doi: 10.1002/path.5687.

ABSTRACT

The 2021 Annual Review Issue of The Journal of Pathology contains 14 invited reviews on current research areas of particular importance in pathology. The subjects included here reflect the broad range of interests covered by the journal, including both basic and applied research fields but always with the aim of improving our understanding of human disease. This year, our reviews encompass the huge impact of the COVID-19 pandemic, the development and application of biomarkers for immune checkpoint inhibitors, recent advances in multiplexing antigen/nucleic acid detection in situ, the use of genomics to aid drug discovery, organoid methodologies in research, the microbiome in cancer, the role of macrophage-stroma interactions in fibrosis, and TGF-β as a driver of fibrosis in multiple pathologies. Other reviews revisit the p53 field and its lack of clinical impact to date, dissect the genetics of mitochondrial diseases, summarise the cells of origin and genetics of sarcomagenesis, provide new data on the role of TRIM28 in tumour predisposition, review our current understanding of cancer stem cell niches, and the function and regulation of p63. The reviews are authored by experts in their field from academia and industry, and provide comprehensive updates of the chosen areas, in which there has been considerable recent progress. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID:34097314 | DOI:10.1002/path.5687

Front Med (Lausanne). 2021 May 20;8:593874. doi: 10.3389/fmed.2021.593874. eCollection 2021.

ABSTRACT

In addition to providing a macromolecular scaffold, the extracellular matrix (ECM) is a critical regulator of cell function by virtue of specific physical, biochemical, and mechanical properties. Collagen is the main ECM component and hence plays an essential role in the pathogenesis and progression of chronic lung disease. It is well-established that many chronic lung diseases, e.g., chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) primarily manifest in the elderly, suggesting increased susceptibility of the aged lung or accumulated alterations in lung structure over time that favour disease. Here, we review the main steps of collagen biosynthesis, processing, and turnover and summarise what is currently known about alterations upon lung ageing, including changes in collagen composition, modification, and crosslinking. Recent proteomic data on mouse lung ageing indicates that, while the ER-resident machinery of collagen biosynthesis, modification and triple helix formation appears largely unchanged, there are specific changes in levels of type IV and type VI as well as the two fibril-associated collagens with interrupted triple helices (FACIT), namely type XIV and type XVI collagens. In addition, levels of the extracellular collagen crosslinking enzyme lysyl oxidase are decreased, indicating less enzymatically mediated collagen crosslinking upon ageing. The latter contrasts with the ageing-associated increase in collagen crosslinking by advanced glycation endproducts (AGEs), a result of spontaneous reactions of protein amino groups with reactive carbonyls, e.g., from monosaccharides or reactive dicarbonyls like methylglyoxal. Given the slow turnover of extracellular collagen such modifications accumulate even more in ageing tissues. In summary, the collective evidence points mainly toward age-induced alterations in collagen composition and drastic changes in the molecular nature of collagen crosslinks. Future work addressing the consequences of these changes may provide important clues for prevention of lung disease and for lung bioengineering and ultimately pave the way to novel targeted approaches in lung regenerative medicine.

PMID:34095157 | PMC:PMC8172798 | DOI:10.3389/fmed.2021.593874

Cureus. 2021 Apr 29;13(4):e14756. doi: 10.7759/cureus.14756.

ABSTRACT

Idiopathic retroperitoneal fibrosis (RPF) is a rare disease characterized by a fibro-inflammatory mass encasing the abdominal aorta. We report a case of a 43-year-old man with an unusual presentation of RPF who was initially misdiagnosed with lymphoma. Our patient presented with constipation and did not have common findings such as ureteral displacement or renal impairment. Our patient had a complicated disease course complicated by multiple treatment failures and pulmonary embolism. We discuss the patient's first 100 months of treatment, which included the use of prednisone, mycophenolate, tamoxifen, methotrexate, azathioprine, and, now, colchicine. Our case demonstrates that physicians should maintain an index of suspicion for RPF in patients with a homogenously attenuated mass encasing the anterior aorta. It also serves as one example in which RPF appeared to be responsive to colchicine.

PMID:34094726 | PMC:PMC8169009 | DOI:10.7759/cureus.14756

Theranostics. 2021 May 13;11(14):7110-7125. doi: 10.7150/thno.61085. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fatal interstitial lung disease characterized by abnormal transition and proliferation of fibroblasts. The uncontrolled transition of fibroblasts, commonly known as myofibroblasts, are the principal source of the enormous extracellular matrix (ECM) depositing in lung parenchyma, leading to gradual failure of gas exchange and mortality of the patients. However, up to now, rare effective therapeutic strategies have been developed to blockade fibroblast-to-myofibroblast transition (FMT) in IPF. Method: We illustrated that the lungs originated from IPF patients and mice with pulmonary fibrosis are characterized by the overexpression of sushi-repeat-containing protein, X-linked 2 (SRPX2). Further functionality studies identified the pivotal role of SRPX2 in FMT. Mechanistically, SRPX2 was involved in a TGFβR1/SMAD3/SRPX2/AP1/SMAD7 positive feedback loop. Specifically, SRPX2 was upregulated by TGF-β1 in a TGFβR1/SMAD3-dependent manner, after which SRPX2 in turn repressed the expression of AP1, subsequently minimized SMAD7 expression, through which it reduced the formation of inhibitory complex with TGFβR1 and enhanced SMAD signaling pathway to promote FMT and exacerbate pulmonary fibrosis. Notably, intratracheal administration of siRNA-loaded liposomes could effectively suppress the expression of Srpx2 in the lung and remarkably protect mice against BLM-induced pulmonary fibrosis, concomitant with a significant reduction of FMT. Results: Accordingly, these data indicate that Srpx2 plays an essential role in the pathogenesis of pulmonary fibrosis and suggests the strategy aiming at silencing Srpx2 could be a promising therapeutic approach against pulmonary fibrosis in clinical settings.

PMID:34093874 | PMC:PMC8171094 | DOI:10.7150/thno.61085

Front Immunol. 2021 May 19;12:631235. doi: 10.3389/fimmu.2021.631235. eCollection 2021.

ABSTRACT

Interactions between the lung epithelium and the immune system involve a tight regulation to prevent inappropriate reactions and have been connected to several pulmonary diseases. Although the distal lung epithelium and local immunity have been implicated in the pathogenesis and disease course of idiopathic pulmonary fibrosis (IPF), consequences of their abnormal interplay remain less well known. Recent data suggests a two-way process, as illustrated by the influence of epithelial-derived periplakin on the immune landscape or the effect of macrophage-derived IL-17B on epithelial cells. Additionally, damage associated molecular patterns (DAMPs), released by damaged or dying (epithelial) cells, are augmented in IPF. Next to "sterile inflammation", pathogen-associated molecular patterns (PAMPs) are increased in IPF and have been linked with lung fibrosis, while outer membrane vesicles from bacteria are able to influence epithelial-macrophage crosstalk. Finally, the advent of high-throughput technologies such as microbiome-sequencing has allowed for the identification of a disease-specific microbial environment. In this review, we propose to discuss how the interplays between the altered distal airway and alveolar epithelium, the lung microbiome and immune cells may shape a pro-fibrotic environment. More specifically, it will highlight DAMPs-PAMPs pathways and the specificities of the IPF lung microbiome while discussing recent elements suggesting abnormal mucosal immunity in pulmonary fibrosis.

PMID:34093523 | PMC:PMC8170303 | DOI:10.3389/fimmu.2021.631235

Intern Med. 2021 Jun 5. doi: 10.2169/internalmedicine.7016-21. Online ahead of print.

ABSTRACT

Acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) is associated with invasive procedures and respiratory infections. However, there have been no reports of AE-IIP triggered by catheter ablation. We herein report a case of AE-IIP after catheter ablation for atrial fibrillation in an 82-year-old man who was diagnosed with IIP. Cardiac ablation has become an increasingly common procedure for managing patients with arrhythmias. Considering that catheter ablation causes AE-IIP, a detailed clinical interview, physical examination, and chest radiography are necessary before catheter ablation. We should additionally consider AE-IIP as a differential diagnosis of respiratory failure after catheter ablation.

PMID:34092730 | DOI:10.2169/internalmedicine.7016-21

Respir Med Res. 2020 Oct 2;80:100792. doi: 10.1016/j.resmer.2020.100792. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function.

METHODS: Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy.

RESULTS: Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72-0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68-1.12). There was no statistically significant association between statin use and decline in FVC % predicted.

CONCLUSION: There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment.

PROSPERO REGISTRATION NUMBER: CRD42019122745.

PMID:34091200 | DOI:10.1016/j.resmer.2020.100792

Biochem Biophys Res Commun. 2021 Jun 2;565:43-49. doi: 10.1016/j.bbrc.2021.05.085. Online ahead of print.

ABSTRACT

Fibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased in the plasma and peripheral blood mononuclear cells (PBMCs) from idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) patients (P < 0.05). The percentages of peripheral blood fibrocytes in the IPF group (4.2550 ± 0.3483%) and CTD-ILD group (4.7100 ± 0.4811%) were higher than that in the control group (1.6340 ± 0.2549%) (both P < 0.05). In vitro, PBMCs transfected with siRNA-CFL-1 showed lower expression of CFL-1, and the percentage of fibrocytes was lower than that of the control (P < 0.05). PBMCs transfected with Lv-CFL-1 to increase the expression of CFL-1 showed a higher percentage of fibrocytes than the control (P < 0.05). In mice with bleomycin-induced pulmonary fibrosis, the relative expression of CFL-1 was increased, and the percentage of fibrocytes was higher than that in the saline group (P < 0.05). In bleomycin-induced mice, interference with Lv-CFL-1 decreased the expression of CFL-1, the percentage of fibrocytes was lower, and the lung tissue showed less fibrosis (P < 0.05). The overexpression of CFL-1 is associated with pulmonary fibrogenesis. CFL-1 could promote the differentiation of fibrocytes from monocyte peripheral blood mononuclear cells and promote pulmonary fibrosis.

PMID:34090209 | DOI:10.1016/j.bbrc.2021.05.085

BMC Pulm Med. 2021 Jun 4;21(1):188. doi: 10.1186/s12890-021-01550-2.

ABSTRACT

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a degenerative interstitial lung disease with both a poor prognosis and quality of life once the diagnosis is made. In the last decade many features of the disease have been investigated to better understand the pathological steps that lead to the onset of the disease and, moreover, different types of biomarkers have been tested to find valid diagnostic, prognostic and therapy response predictive ones. In the complexity of IPF, microRNA (miRNAs) biomarker investigation seems to be promising.

METHODS: We analysed the expression of five exosomal miRNAs supposed to have a role in the pathogenesis of the disease from serum of a group of IPF patients (n = 61) and we compared it with the expression of the same miRNAs in a group of healthy controls (n = 15).

RESULTS: In the current study what emerged is let-7d down-regulation and, unexpectedly, miR-16 significant down-regulation. Moreover, through a cross-sectional analysis, a clustering of the expression of miR-16, miR-21 and miR-26a was found.

CONCLUSIONS: These findings could help the individuation of previously unknown key players in the pathophysiology of IPF and, most interestingly, more specific targets for the development of effective medications.

PMID:34088304 | DOI:10.1186/s12890-021-01550-2

PLoS One. 2021 Jun 4;16(6):e0252594. doi: 10.1371/journal.pone.0252594. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis is a chronic, fibrosing interstitial pneumonia that presents with various clinical courses and progression ranging from rapid to slow. To identify novel biomarkers that can support the diagnosis and/or prognostic prediction of idiopathic pulmonary fibrosis, we performed gene expression analysis, and the mRNA of interleukin-18 binding protein was increasingly expressed in patients with idiopathic pulmonary fibrosis compared with healthy controls. Therefore, we hypothesized that the interleukin-18 binding protein can serve as a diagnostic and/or prognostic biomarker for idiopathic pulmonary fibrosis. We investigated the expression of interleukin-18 binding protein in lung tissue, bronchoalveolar lavage fluid, and serum. Additionally, the correlation between interleukin-18 binding protein expression levels and the extent of fibrosis was investigated using mouse models of lung fibrosis induced by subcutaneous bleomycin injections. Serum interleukin-18 binding protein levels were significantly higher in idiopathic pulmonary fibrosis patients (5.06 ng/mL, interquartile range [IQR]: 4.20-6.35) than in healthy volunteers (3.31 ng/mL, IQR: 2.84-3.99) (p < 0.001). Multivariate logistic regression models revealed that the correlation between serum interleukin-18 binding protein levels and idiopathic pulmonary fibrosis was statistically independent after adjustment for age, sex, and smoking status. Multivariate Cox proportional hazard models revealed that serum interleukin-18 binding protein levels were predictive of idiopathic pulmonary fibrosis disease prognosis independent of other covariate factors (hazard ratio: 1.655, 95% confidence interval: 1.224-2.237, p = 0.001). We also demonstrated a significant positive correlation between lung hydroxyproline expression levels and interleukin-18 binding protein levels in bronchoalveolar lavage fluid from bleomycin-treated mice (Spearman r = 0.509, p = 0.004). These results indicate the utility of interleukin-18 binding protein as a novel prognostic biomarker for idiopathic pulmonary fibrosis.

PMID:34086758 | DOI:10.1371/journal.pone.0252594

ERJ Open Res. 2021 May 31;7(2):00691-2020. doi: 10.1183/23120541.00691-2020. eCollection 2021 Apr.

ABSTRACT

Pulmonary fibrosis is strongly associated with telomere shortening and increased DNA damage. Key cells in the pathogenesis involve alveolar type 2 (AT2) cells, club cells and myofibroblasts; however, to what extent these cells are affected by telomere shortening and DNA damage is not yet known. We sought to determine the degree of, and correlation between, telomere shortening and DNA damage in different cell types involved in the pathogenesis of progressive fibrosing interstitial lung disease. Telomere length and DNA damage were quantified, using combined fluorescence in situ hybridisation and immunofluorescence staining techniques, in AT2 cells, club cells and myofibroblasts of controls and patients with pulmonary fibrosis and a telomerase reverse transcriptase mutation (TERT-PF), idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). In IPF and TERT-PF lungs, AT2 cells contained shorter telomeres and expressed higher DNA damage signals than club cells and myofibroblasts. In fHP lungs, club cells contained highly elevated levels of DNA damage, while telomeres were not obviously short. In vitro, we found significantly shorter telomeres and higher DNA damage levels only in AT2 surrogate cell lines treated with telomerase inhibitor BIBR1532. Our study demonstrated that in IPF and TERT-PF lungs, telomere shortening and accumulation of DNA damage primarily affects AT2 cells, further supporting the importance of AT2 cells in these diseases, while in fHP the particularly high telomere-independent DNA damage signals in club cells underscores its bronchiolocentric pathogenesis. These findings suggest that cell type-specific telomere shortening and DNA damage may help to discriminate between different drivers of fibrogenesis.

PMID:34084786 | PMC:PMC8165375 | DOI:10.1183/23120541.00691-2020

BMJ Open. 2021 Jun 2;11(6):e048808. doi: 10.1136/bmjopen-2021-048808.

ABSTRACT

OBJECTIVES: To assess the acceptability of neuromuscular electrical stimulation (NMES) of the quadriceps muscles in people with idiopathic pulmonary fibrosis (IPF) and to identify whether a future definitive trial is feasible.

DESIGN: A randomised, parallel, two-group, participant and assessor-blinded, placebo-controlled feasibility trial with embedded qualitative interviews.

SETTING: Outpatient department, Royal Brompton and Harefield Hospitals.

PARTICIPANTS: Twenty-two people with IPF: median (25th, 75th centiles) age 76 (74, 82) years, forced vital capacity 62 (50, 75) % predicted, 6 min walk test distance 289 (149, 360) m.

INTERVENTIONS: Usual care (home-based exercise, weekly telephone support, breathlessness management leaflet) with either placebo or active NMES for 6 weeks, with follow-up at 6 and 12 weeks.

PRIMARY OUTCOME MEASURES: Feasibility of recruitment and retention, treatment uptake and adherence, outcome assessments, participant and outcome assessor blinding and adverse events related to interventions.

SECONDARY OUTCOME MEASURES: Outcome measures with potential to be primary or secondary outcomes in a definitive clinical trial. In addition, purposively sampled participants were interviewed to capture their experiences and acceptability of the trial.

RESULTS: Out of 364 people screened, 23 were recruited: 11 were allocated to each group and one was withdrawn prior to randomisation. Compared with the control group, a greater proportion of the intervention group completed the intervention, remained in the trial blinded to group allocation and experienced intervention-related adverse events. Assessor blinding was maintained. The secondary outcome measures were feasible with most missing data associated with the accelerometer. Small participant numbers precluded identification of an outcome measure suitable for a definitive trial. Qualitative findings demonstrated that trial process and active NMES were acceptable but there were concerns about the credibility of placebo NMES.

CONCLUSIONS: Primarily owing to recruitment difficulties, a definitive trial using the current protocol to evaluate NMES in people with IPF is not feasible.

TRIAL REGISTRATION NUMBER: NCT03499275.

PMID:34083348 | DOI:10.1136/bmjopen-2021-048808

Inflamm Regen. 2021 Jun 3;41(1):16. doi: 10.1186/s41232-021-00166-7.

ABSTRACT

Vascular endothelial growth factor (VEGF) is not only an important factor for angiogenesis but also lung development and homeostasis. VEGF-A binds three tyrosine kinase (TK) receptors VEGFR1-3. Idiopathic pulmonary fibrosis (IPF) is one of the poor prognoses of lung diseases. The relationship of VEGF and IPF remains to be clarified. Treatment with nintedanib used for the treatment of IPF reduced fibroblast proliferation, inhibited TK receptors, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and VEGFR. Because the effect of that treatment is still not satisfactory, the emergence of new therapeutic agents is needed. This review describes the enhancement of pulmonary fibrosis by VEGFR1-TK signal and suggests that the blocking of the VEGFR1-TK signal may be useful for the treatment of pulmonary fibrosis.

PMID:34082837 | DOI:10.1186/s41232-021-00166-7

BMC Pulm Med. 2021 Jun 2;21(1):185. doi: 10.1186/s12890-021-01555-x.

ABSTRACT

BACKGROUND: It is not well-known if diagnosing and treating sleep breathing disorders among individuals with idiopathic pulmonary fibrosis (IPF) improves health outcomes. We evaluated the association between receipt of laboratory-based polysomnography (which is the first step in the diagnosis and treatment of sleep breathing disorders in Ontario, Canada) and respiratory-related hospitalization and all-cause mortality among individuals with IPF.

METHODS: We used a retrospective, population-based, cohort study design, analyzing health administrative data from Ontario, Canada, from 2007 to 2019. Individuals with IPF were identified using an algorithm based on health administrative codes previously developed by IPF experts. Propensity score matching was used to account for potential differences in 41 relevant covariates between individuals that underwent polysomnography (exposed) and individuals that did not undergo polysomnography (controls), in order minimize potential confounding. Respiratory-related hospitalization and all-cause mortality were evaluated up to 12 months after the index date.

RESULTS: Out of 5044 individuals with IPF identified, 201 (4.0%) received polysomnography, and 189 (94.0%) were matched to an equal number of controls. Compared to controls, exposed individuals had significantly reduced rates of respiratory-related hospitalization (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.24-0.75), p = 0.003) and all-cause mortality (HR 0.49, 95% CI 0.30-0.80), p = 0.004). Significantly reduced rate of respiratory-related hospitalization (but not all-cause mortality) was also observed among those with > = 1 respiratory-related hospitalization (HR 0.38, 95% CI 0.15-0.99) and systemic corticosteroid receipt (HR 0.37, 95% CI 0.19-0.94) in the year prior to the index date, which reflect sicker subgroups of persons.

CONCLUSIONS: Undergoing polysomnography was associated with significantly improved clinically-important health outcomes among individuals with IPF, highlighting the potential importance of incorporating this testing in IPF disease management.

PMID:34078346 | DOI:10.1186/s12890-021-01555-x