Life (Basel). 2022 Oct 5;12(10):1544. doi: 10.3390/life12101544.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell-cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential biomarkers of disease, allowing a non-invasive clinical diagnosis. In this review we summarize some studies, present in the literature, about the functions of extracellular vesicles and miRNAs contained in extracellular vesicles in chronic respiratory diseases and we discuss the potential clinical applications of EVs and EVs-miRNAs for their possible use such as future biomarkers.

PMID:36294979 | DOI:10.3390/life12101544

J Clin Med. 2022 Oct 17;11(20):6115. doi: 10.3390/jcm11206115.

ABSTRACT

BACKGROUND: The coupling of the right ventricle (RV) to the pulmonary circulation is an indicator of RV performance that can be non-invasively estimated by echocardiography. There are no data about its use in patients affected by fibrotic interstitial lung diseases (f-ILD).

METHODS: Fifty f-ILD patients, including 27 cases with idiopathic pulmonary fibrosis (IPF) (M = 37; mean age 67 ± 7 years), were studied with standard and speckle-tracking echocardiography and compared with 30 age-matched healthy volunteers. The mean patient follow-up was 70 ± 4 months.

RESULTS: Fibrotic ILD patients had a larger right ventricle (RV) and worse diastolic function because the RV global longitudinal strain (GLS) was significantly lower and the systolic pulmonary artery pressure (sPAP) estimates were higher in comparison with those of controls. Conversely, tricuspid annular systolic excursion (TAPSE) did not differ between controls and patients. Median values of TAPSE/sPAP and RV GLS/sPAP were significantly reduced in f-ILD patients (p < 0.0001). Patients with an RV GLS/sPAP below the median value had a shorter survival time (61 vs. 74 months, p = 0.01); this parameter was an independent predictor of a worse outcome.

CONCLUSION: Low estimates of RV GLS/sPAP are predictive of worse outcomes in f-ILD patients. RV coupling seems to be a promising surrogate biomarker of RV performance to discriminate the patient phenotype with significant management and prognosis implications.

PMID:36294435 | DOI:10.3390/jcm11206115

Cancers (Basel). 2022 Oct 18;14(20):5093. doi: 10.3390/cancers14205093.

ABSTRACT

Originally discovered as a hypothetical protein with unknown function, CEMIP (cell migration-inducing and hyaluronan-binding protein) has been implicated in the pathogenesis of numerous diseases, including deafness, arthritis, atherosclerosis, idiopathic pulmonary fibrosis, and cancer. Although a comprehensive definition of its molecular functions is still in progress, major functions ascribed to CEMIP include the depolymerization of the extracellular matrix component hyaluronic acid (HA) and the regulation of a number of signaling pathways. CEMIP is a promising biomarker for colorectal cancer. Its expression is associated with poor prognosis for patients suffering from colorectal and other types of cancer and functionally contributes to tumor progression and metastasis. Here, we review our current understanding of how CEMIP is able to foster the process of tumor growth and metastasis, focusing particularly on colorectal cancer. Studies in cancer cells suggest that CEMIP exerts its pro-tumorigenic and pro-metastatic activities through stimulating migration and invasion, suppressing cell death and promoting survival, degrading HA, regulating pro-metastatic signaling pathways, inducing the epithelial-mesenchymal transition (EMT) program, and contributing to the metabolic reprogramming and pre-metastatic conditioning of future metastatic microenvironments. There is also increasing evidence indicating that CEMIP may be expressed in cells within the tumor microenvironment that promote tumorigenesis and metastasis formation, although this remains in an early stage of investigation. CEMIP expression and activity can be therapeutically targeted at a number of levels, and preliminary findings in animal models show encouraging results in terms of reduced tumor growth and metastasis, as well as combating therapy resistance. Taken together, CEMIP represents an exciting new player in the progression of colorectal and other types of cancer that holds promise as a therapeutic target and biomarker.

PMID:36291875 | DOI:10.3390/cancers14205093

Biomolecules. 2022 Oct 21;12(10):1531. doi: 10.3390/biom12101531.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease. Heme oxygenase-1 (HMOX1/HO-1) is an enzyme that catalyzes the degradation of heme. The role of HO-1 in the pathogenesis of IPF has been studied; however, the molecular regulation of HO-1 and its role in IPF are still unclear. In this study, we found that HO-1 protein levels significantly increased in lung myofibroblasts in IPF patients and in lungs in a murine model of bleomycin-induced lung fibrosis. In addition, we observed that administration of a E2F transcription factor inhibitor elevated HO-1 mRNA and protein levels in lung fibroblasts. Downregulation of E2F2 by siRNA transfection increased HO-1 mRNA and protein levels, while overexpression of E2F2 reduced HO-1 levels. However, overexpression of E2F2 did not alter hemin-induced HO-1 protein levels. Furthermore, modulation of HO-1 levels regulated TGF-β1-induced myofibroblast differentiation without altering the phosphorylation of Smad2/3 in lung fibroblast cells. Moreover, the phosphorylation of protein kinase B (Akt) was significantly upregulated in HO-1-depleted lung fibroblast cells. In summary, this study demonstrated that E2F2 regulates the baseline expression of HO-1, but has no effect on modulating HO-1 expression by hemin. Finally, elevated HO-1 expression contributes to the TGF-β1-induced lung myofibroblast differentiation through the activation of the serine/threonine kinase AKT pathway. Overall, our findings suggest that targeting E2F2/HO-1 might be a new therapeutic strategy to treat fibrotic diseases such as IPF.

PMID:36291740 | DOI:10.3390/biom12101531

Cells. 2022 Oct 21;11(20):3319. doi: 10.3390/cells11203319.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of older adults characterized by fibrotic replacement of functional gas exchange units in the lung. The strongest risk factor for IPF is a genetic variantin the promoter region of the gel-forming mucin, MUC5B. To better understand how the MUC5B variant influences development of fibrosis, we used the NicheNet R package and leveraged publicly available single-cell RNA sequencing data to identify and evaluate how epithelia participating in gas exchange are influenced by ligands expressed in control, MUC5B variant, and fibrotic environments. We observed that loss of type-I alveolar epithelia (AECI) characterizes the single-cell RNA transcriptome in fibrotic lung and validated the pattern of AECI loss using single nuclear RNA sequencing. Examining AECI transcriptomes, we found enrichment of transcriptional signatures for IL6 and AREG, which we have previously shown to mediate aberrant epithelial fluidization in IPF and murine bleomycin models. Moreover, we found that the protease ADAM17, which is upstream of IL6 trans-signaling, was enriched in control MUC5B variant donors. We used immunofluorescence to validate a role for enhanced expression of ADAM17 among MUC5B variants, suggesting involvement in IPF pathogenesis and maintenance.

PMID:36291184 | DOI:10.3390/cells11203319

Biomedicines. 2022 Oct 13;10(10):2556. doi: 10.3390/biomedicines10102556.

ABSTRACT

BACKGROUND: In idiopathic pulmonary fibrosis (IPF), 6-minute walking distance (6MWD) is an independent factor for mortality. Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disease with physical features such as emaciation, but the relationship between IPPFE and 6MWD is unclear. In this study, we investigated the factors that cause a decrease in the percent of the predicted value of a 6-minute walk distance (%6MWD), including the disease entities, IPF and IPPFE.

METHODS: This study included 100 patients (IPF: 75 patients, IPPFE: 25 patients, age: 73.5 ± 7.2 years, sex: 73 males) who visited the rehabilitation department. Patients with a %6MWD ≥ 80% were assigned to the normal group (n = 54), and patients with a %6MWD < 80% were assigned to the decreased group (n = 46). The items showing a significant difference between groups were used as independent variables, after the consideration of multicollinearity, for a logistic analysis where %6MWD < 80% was used as the dependent variable.

RESULTS: The 6MWD results show that there was no significant difference between IPF and IPPFE in the absolute value of 6MWD and in the number of people with 6MWD ≥ 250 m, but when 6MWD was compared with %6MWD, the IPPFE group showed a significantly lower value than the IPF group (p = 0.013). Logistic regression analysis showed that only BMI (p = 0.032), GAP index (p = 0.043), and mMRC (p = 0.026) were factors that caused a decrease in %6MWD in 100 patients.

CONCLUSION: The results suggest that leanness, shortness of breath and severity of illness are the most important factors that determine exercise tolerance, regardless of disease entity in IPF and IPPFE.

PMID:36289817 | DOI:10.3390/biomedicines10102556

Biomedicines. 2022 Sep 22;10(10):2362. doi: 10.3390/biomedicines10102362.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) causes progressive lung fibrosis with subsequent fatality and has limited treatment options. NICEFIT is the first Taiwan-based prospective, observational, and non-interventional registry for IPF progression under routine clinical practice in Taiwan. Data on 101 patients (aged 74.6 ± 9.1 years and 83.2% men) with IPF were collected over 2 years (2018-2020) from medical centers in Taiwan at baseline, 1 month, and subsequent 3-month intervals. Treated patients (n = 88) received the antifibrotics nintedanib or pirfenidone, compared with the untreated group (n = 13). The 2-year assessment revealed overall preserved lung functionality in the treated patients, with insignificant changes from baseline for percent predicted forced vital capacity or FVC (±1.7%). The presence of respiratory comorbidities significantly increased the risk of both AE and death (with or without AE) over the full study duration. Furthermore, the decline of predicted FVC significantly increased with the risk of acute exacerbations (AE) in the second year. Overall, antifibrotic medication was beneficial in stalling IPF progression, reducing AEs, and delaying mortality in the treated cohort, despite their lower baseline lung functions. Further, no new safety concerns over antifibrotic treatments were observed for the Taiwanese population.

PMID:36289624 | DOI:10.3390/biomedicines10102362

BMC Pulm Med. 2022 Oct 26;22(1):387. doi: 10.1186/s12890-022-02197-3.

ABSTRACT

BACKGROUND: Acute exacerbation (AE) of systemic autoimmune disease-related interstitial lung diseases (SAID-ILD) is less common than AE of idiopathic pulmonary fibrosis (IPF) and the details of AE-SAID-ILD have not been elucidated, but the prognosis is similarly devastating. This study was undertaken to determine the incidences of AE-ILD in each SAID and to elucidate the proportion of progressive fibrosing (PF)-ILD in AE-SAID-ILD.

METHODS: We retrospectively analysed data for patients with SAID-ILD who were diagnosed and observed at our hospital between 1999 and 2020.

RESULTS: Two hundred and thirty-two patients with SAID-ILD were enrolled, with a mean observation period of 100.2 months. AE-SAID-ILD was found in 25 patients (10.78%), mainly in patients with RA (17 patients, 68%) and elderly male patients with a smoking history. The overall incidence of AE-SAID-ILD was 1.29%/person-year, and the incidence for each SAID was as follows: RA 2.193, microscopic polyarteritis (MPA) 3.203, systemic sclerosis (SSc) 2.277, primary Sjögren syndrome 0.426, and polymyositis/dermatomyositis 0.222. The incidence of AE of RA/MPA/SSc-ILD was significantly higher than that of other AE-SAID-ILD (p < 0.001). Five of 25 patients (20%) fulfilled the criteria for PF-ILD. The 90-day survival rate was 48.0%, and a higher neutrophil count at AE (HR 13.27, 95%CI 2.447-246, p = 0.001) and early commencement of long-duration direct haemoperfusion with a polymyxin B-immobilised fibre column (HR 0.105, 95%CI 0.005-0.858, p = 0.035) were significant prognostic factors.

CONCLUSIONS: The incidence of AE-SAID-ILD was significantly higher in patients with RA, MPA, or SSc than in patients with other SAID. Furthermore, even in patients with AE-SAID-ILD, the proportion of PF-ILD just before AE was not high (20%).

PMID:36289542 | DOI:10.1186/s12890-022-02197-3

Respir Res. 2022 Oct 26;23(1):291. doi: 10.1186/s12931-022-02195-3.

ABSTRACT

BACKGROUND: Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF.

METHODS: In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering.

RESULTS: The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22-0.76] and 0.65 [0.36-1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14-0.99] and 0.27 [0.094-0.83] in the multi-center and administrative cohorts, respectively).

CONCLUSION: Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

PMID:36289512 | DOI:10.1186/s12931-022-02195-3

Ter Arkh. 2022 Mar 15;94(3):409-412. doi: 10.26442/00403660.2022.03.201407.

ABSTRACT

INTRODUCTION: The widespread use of artificial intelligence (AI) programs during the COVID-19 pandemic to assess the exact volume of lung tissue damage has allowed them to train a large number of radiologists. The simplicity of the program for determining the volume of the affected lung tissue in acute interstitial pneumonia, which has density indicators in the range from -200 HU to -730 HU, which includes the density indicators of "ground glass" and reticulation (the main radiation patterns in COVID-19) allows you to accurately determine the degree of prevalence process. The characteristics of chronic interstitial pneumonia, which are progressive in nature, fit into the same density framework. Аim. To аssess AI's ability to assess the progression of fibrosing lung disease using lung volume counting programs used for COVID-19 and chronic obstructive pulmonary disease.

RESULTS: Retrospective analysis of computed tomography data during follow-up of 75 patients with progressive fibrosing lung disease made it possible to assess the prevalence and growth of interstitial lesions.

CONCLUSION: Using the experience of using AI programs to assess acute interstitial pneumonia in COVID-19 can be applied to chronic interstitial pneumonia.

PMID:36286906 | DOI:10.26442/00403660.2022.03.201407

Eur J Health Econ. 2022 Oct 27. doi: 10.1007/s10198-022-01538-7. Online ahead of print.

ABSTRACT

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease found mostly in elderly persons, characterized by a high symptom burden and frequent encounters with health services. This study aimed to quantify the economic burden of IPF in Australia with a focus on resource utilization and associated direct costs.

METHODS: Participants were recruited from the Australian IPF Registry (AIPFR) between August 2018 and December 2019. Data on resource utilization and costs were collected via cost diaries and linked administrative data. Clinical data were collected from the AIPFR. A "bottom up" costing methodology was utilized, and the costing was performed from a partial societal perspective focusing primarily on direct medical and non-medical costs. Costs were standardized to 2021 Australian dollars ($).

RESULTS: The average annual total direct costs per person with IPF was $31,655 (95% confidence interval (95% CI): $27,723-$35,757). Extrapolating costs based on prevalence estimates, the total annual costs in Australia are projected to be $299 million (95% CI: $262 million-$338 million). Costs were mainly driven by antifibrotic medication, hospital admissions and medications for comorbidities. Disease severity, comorbidities and antifibrotic medication all had varying impacts on resource utilization and costs.

CONCLUSION: This cost-of-illness study provides the first comprehensive assessment of IPF-related direct costs in Australia, identifies the key cost drivers and provides a framework for future health economic analyses. Additionally, it provided insight into the major cost drivers which include antifibrotic medication, hospital admissions and medications related to comorbidities. Our findings emphasize the importance of the appropriate management of comorbidities in the care of people with IPF as this was one of the main reasons for hospitalizations.

PMID:36289130 | DOI:10.1007/s10198-022-01538-7

Tomography. 2022 Oct 13;8(5):2574-2587. doi: 10.3390/tomography8050215.

ABSTRACT

3D Single-breath Chemical Shift Imaging (3D-SBCSI) is a hybrid MR-spectroscopic imaging modality that uses hyperpolarized xenon-129 gas (Xe-129) to differentiate lung diseases by probing functional characteristics. This study tests the efficacy of 3D-SBCSI in differentiating physiology among pulmonary diseases. A total of 45 subjects-16 healthy, 11 idiopathic pulmonary fibrosis (IPF), 13 cystic fibrosis (CF), and 5 chronic obstructive pulmonary disease (COPD)-were given 1/3 forced vital capacity (FVC) of hyperpolarized Xe-129, inhaled for a ~7 s MRI acquisition. Proton, Xe-129 ventilation, and 3D-SBCSI images were acquired with separate breath-holds using a radiofrequency chest coil tuned to Xe-129. The Xe-129 spectrum was analyzed in each lung voxel for ratios of spectroscopic peaks, chemical shifts, and T2* relaxation. CF and COPD subjects had significantly more ventilation defects than IPF and healthy subjects, which correlated with FEV1 predicted (R = -0.74). FEV1 predicted correlated well with RBC/Gas ratio (R = 0.67). COPD and IPF had significantly higher Tissue/RBC ratios than other subjects, longer RBC T2* relaxation times, and greater RBC chemical shifts. CF subjects had more ventilation defects than healthy subjects, elevated Tissue/RBC ratio, shorter Tissue T2* relaxation, and greater RBC chemical shift. 3D-SBCSI may be helpful in the detection and characterization of pulmonary disease, following treatment efficacy, and predicting disease outcomes.

PMID:36287814 | DOI:10.3390/tomography8050215

Adv Respir Med. 2022 Oct 4;90(5):425-450. doi: 10.3390/arm90050052.

ABSTRACT

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

PMID:36285980 | DOI:10.3390/arm90050052

Am J Physiol Lung Cell Mol Physiol. 2022 Oct 25. doi: 10.1152/ajplung.00428.2021. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis is a progressive lung disease with limited survival. The specific roles of Janus Kinases - tyrosine kinases that transduce cytokine-mediated signals - in lung fibrosis are not well defined. In this study, the interactions between JAK1/STAT3 signaling and TGF-β induced fibroblast responses were investigated using both pharmacological and siRNA approaches in human normal and IPF-derived lung fibroblasts. We found that JAK1 directly interacts with the TGF-β receptor I (TβRI), and silencing JAK1 promotes myofibroblast trans-differentiation. However, the suppression of JAK1 signaling in vitro and in vivo using an inhibitor (Upadacitinib) did not alter lung fibroblast activation or fibrosis development. STAT3 was constitutively active in cultured primary lung fibroblasts: this STAT3 activation was JAK1 dependent and repressed myofibroblast trans-differentiation. Loss of phosphorylated STAT3 following transcriptional JAK1 silencing promoted myofibroblast trans-differentiation. In contrast, transcriptional silencing of unphosphorylated STAT3 suppressed TGF-β signaling, decreased SMAD3 activation, and reduced myofibroblast trans-differentiation and ECM production. Taken together, these observations support a role for JAK1/STAT3 as a direct regulator of TGF-β signaling in lung fibroblasts. Modulation of JAK1/STAT3 signaling in lung fibroblasts represents a non-canonical approach to regulate TGF-β induced fibrosis and suggests the potential for a novel approach to treat pulmonary fibrosis.

PMID:36283961 | DOI:10.1152/ajplung.00428.2021

Respir Med Res. 2022 Oct 18;82:100965. doi: 10.1016/j.resmer.2022.100965. Online ahead of print.

ABSTRACT

BACKGROUND: Sarcopenia, defined using abdominal computed tomography (CT), has been used as a prognostic marker for patients with idiopathic pulmonary fibrosis (IPF). However, no consensus on the impact of sarcopenia as defined using chest CT exists. Therefore, this study aimed to investigate the impact of sarcopenia, defined using CT at the carina-level, on the long-term prognosis of patients with IPF.

METHODS: This single-center retrospective cohort study included 117 patients with IPF. Sarcopenia was defined as skeletal muscle mass measured at the carina-level on chest CT images. All-cause mortality was analyzed using the Kaplan-Meier method, and the log-rank test was used to evaluate the differences between sarcopenia and non-sarcopenia groups. A Cox proportional hazards regression model was used to analyze the impact of sarcopenia on all-cause mortality in model 1 with adjustment for body mass index and gender-age-physiology stage as a confounding factor and in model 2 with sex, age, and% forced vital capacity (FVC).

RESULTS: The median follow-up period was 956 days, and 57 deaths were recorded. The sarcopenia group had a significantly lower survival rate than the non-sarcopenia group. The multivariate Cox proportional hazards analysis revealed that sarcopenia was a significant predictor of all-cause mortality in models 1 and 2. In patients with no diffusing capacity for carbon monoxide (DLCO) measurement, sarcopenia was a significant prognostic predictor of all-cause mortality independent of%FVC.

CONCLUSION: Sarcopenia, defined at the carina level, is a risk factor for all-cause mortality in patients with IPF. Assessment of sarcopenia by CT imaging is useful and less burdensome in patients with IPF.

PMID:36283327 | DOI:10.1016/j.resmer.2022.100965

Radiology. 2022 Oct 25:220292. doi: 10.1148/radiol.220292. Online ahead of print.

ABSTRACT

Background Total lung capacity (TLC) has been estimated with use of chest radiographs based on time-consuming methods, such as planimetric techniques and manual measurements. Purpose To develop a deep learning-based, multidimensional model capable of estimating TLC from chest radiographs and demographic variables and validate its technical performance and clinical utility with use of multicenter retrospective data sets. Materials and Methods A deep learning model was pretrained with use of 50 000 consecutive chest CT scans performed between January 2015 and June 2017. The model was fine-tuned on 3523 pairs of posteroanterior chest radiographs and plethysmographic TLC measurements from consecutive patients who underwent pulmonary function testing on the same day. The model was tested with multicenter retrospective data sets from two tertiary care centers and one community hospital, including (a) an external test set 1 (n = 207) and external test set 2 (n = 216) for technical performance and (b) patients with idiopathic pulmonary fibrosis (n = 217) for clinical utility. Technical performance was evaluated with use of various agreement measures, and clinical utility was assessed in terms of the prognostic value for overall survival with use of multivariable Cox regression. Results The mean absolute difference and within-subject SD between observed and estimated TLC were 0.69 L and 0.73 L, respectively, in the external test set 1 (161 men; median age, 70 years [IQR: 61-76 years]) and 0.52 L and 0.53 L in the external test set 2 (113 men; median age, 63 years [IQR: 51-70 years]). In patients with idiopathic pulmonary fibrosis (145 men; median age, 67 years [IQR: 61-73 years]), greater estimated TLC percentage was associated with lower mortality risk (adjusted hazard ratio, 0.97 per percent; 95% CI: 0.95, 0.98; P < .001). Conclusion A fully automatic, deep learning-based model estimated total lung capacity from chest radiographs, and the model predicted survival in idiopathic pulmonary fibrosis. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Sorkness in this issue.

PMID:36283113 | DOI:10.1148/radiol.220292

J Korean Med Sci. 2022 Oct 24;37(41):e294. doi: 10.3346/jkms.2022.37.e294.

ABSTRACT

BACKGROUND: The demand for lung transplants continues to increase in Korea, and donor shortages and waitlist mortality are critical issues. This study aimed to evaluate the factors that affect waitlist outcomes from the time of registration for lung transplantation in Korea.

METHODS: Data were obtained from the Korean Network for Organ Sharing for lung-only registrations between September 7, 2009, and December 31, 2020. Post-registration outcomes were evaluated according to the lung disease category, blood group, and age.

RESULTS: Among the 1,671 registered patients, 49.1% had idiopathic pulmonary fibrosis (group C), 37.0% had acute respiratory distress syndrome and other interstitial lung diseases (group D), 7.2% had chronic obstructive pulmonary disease (group A), and 6.6% had primary pulmonary hypertension (group B). Approximately half of the patients (46.1%) were transplanted within 1 year of registration, while 31.8% died without receiving a lung transplant within 1 year of registration. Data from 1,611 patients were used to analyze 1-year post-registration outcomes, which were classified as transplanted (46.1%, n = 743), still awaiting (21.1%, n = 340), removed (0.9%, n = 15), and death on waitlist (31.8%, n = 513). No significant difference was found in the transplantation rate according to the year of registration. However, significant differences occurred between the waitlist mortality rates (P = 0.008) and the still awaiting rates (P = 0.009). The chance of transplantation after listing varies depending on the disease category, blood type, age, and urgency status. Waitlist mortality within 1 year was significantly associated with non-group A disease (hazard ratio [HR], 2.76, P < 0.001), age ≥ 65 years (HR, 1.48, P < 0.001), and status 0 at registration (HR, 2.10, P < 0.001).

CONCLUSION: Waitlist mortality is still higher in Korea than in other countries. Future revisions to the lung allocation system should take into consideration the high waitlist mortality and donor shortages.

PMID:36281485 | DOI:10.3346/jkms.2022.37.e294

Int J Tuberc Lung Dis. 2022 Nov 1;26(11):1001-1005. doi: 10.5588/ijtld.22.0212.

ABSTRACT

Interstitial lung diseases (ILDs) include a large variety of fibrotic lung conditions caused by genetic and environmental factors. Occupational exposures might also play a significant role, but the real health burden is currently unknown. Here, we aim to evaluate the role of work-related exposures in ILDs, focussing on idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP). We performed a focused review of the literature on work-related HP and IPF over the past 5 years. Using a meta-analytic approach, we quantified the occupational burden of IPF and HP, and estimated that occupational exposures to metal, silica and environmental tobacco smoke increased IPF risk with a pooled odds ratio of 1.7 (95% CI 1.42-2.03). The proportion of HP cases related to workplace exposure was 17% (95% CI 7-28). Our review supports the hypothesis that occupational exposures are a significant risk factor in the aetiopathogenesis of IPF and HP. We recommend that further research be performed to identify the underlying occupational factors and the maximum permitted exposure to reduce the associated IPF and HP burden.

PMID:36281049 | DOI:10.5588/ijtld.22.0212

Dtsch Med Wochenschr. 2022 Oct;147(21):1383-1390. doi: 10.1055/a-1825-4967. Epub 2022 Oct 24.

ABSTRACT

The interstitial lung diseases ILDs are a heterogeneous group of diseases that often lead to progressive fibrosis of the lungs with corresponding functional impairment. With nintedanib, a tyrosinkinase inhibitor and angiokinase inhibitor, as well as pirfenidone, which unfolds its effect among other things by inhibiting the transforming growth factor β, there are currently 2 approved antifibrotic drugs. In the rapidly progressing idiopathic pulmonary fibrosis IPF, the antifibrotic drugs nintedanib and pirfenidone have been established and approved in therapy for several years. The initiation of antifibrotic therapy should be carried out early after diagnosis by multidisciplinary discussion (MDD). In systemic scleroderma with lung involvement nintedanib should be used in the case of relevant fibrosis in addition to immunosuppressive therapy. Recently, nintedanib has also become a new option for the treatment of progressive fibrosing ILDs (PF-ILDs). This describes the course of various disease entities such as connective tissue disease associated ILDs (CTD-ILDs), fibrosing hypersensitivity pneumonitis or fibrosing courses of non-IPF idiopathic interstitial pneumonitis (non-IPF IIPs) that have a corresponding fibrose-related worsening of respiratory symptoms, a deterioration of lung-functioning parameters or a disease progression in CT. Although pirfenidone also shows positive signals for this group of patients in some selected studies, its use in PF-ILD is not yet recommended. In particular, gastrointestinal side effects can occur under therapy with antifibrotic drugs and require a long-term close interdisciplinary connection of patients.

PMID:36279864 | DOI:10.1055/a-1825-4967

Exp Biol Med (Maywood). 2022 Oct 22:15353702221128564. doi: 10.1177/15353702221128564. Online ahead of print.

ABSTRACT

In recent years, with the increase of air pollution, smoking, aging, and respiratory infection, the incidence rate and mortality of lung diseases are increasing annually, which has become a major hazard to human health. N6-methyladenosine (m6A) RNA methylation is the most abundant modifications in eukaryotes, and such modified RNA can be specifically recognized and combined by m6A recognition proteins and then mediate RNA splicing, maturation, enucleation, degradation, and translation. More and more studies have revealed that the m6A modification is involved in the pathogenesis and development of some diseases; however, the mechanisms of m6A in lung diseases are poorly understood. In this review, we summarize the latest progress in the biological function of m6A modifications in lung diseases and discuss the potential therapeutic and prognostic strategies. The dysregulation of global m6A levels and m6A regulators may affect the occurrence and development of asthma, chronic obstructive pulmonary disease, lung cancer, and other lung diseases through inflammation and immune function. In lung cancer, this modification has an important impact on malignant cell proliferation, migration, invasion, and drug resistance. In addition, abnormally changed m6A-modified proteins in lung cancer tissue samples and circulating tumor cells (CTCs) may be used as diagnostic and prognostic markers of lung cancer. Models composed of multiple m6A regulators can be used to evaluate the risk prediction or prognosis of asthma and pulmonary fibrosis. In general, the in-depth study of m6A modifications is a frontier direction in disease research. It provides novel insights for understanding of the molecular mechanisms underlying disease occurrence, development, and drug resistance, as well as for the development of effective novel therapeutics.

PMID:36278325 | DOI:10.1177/15353702221128564