Ann Transl Med. 2021 Feb;9(4):357. doi: 10.21037/atm-20-8141.

ABSTRACT

BACKGROUND: Adult pulmonary Langerhans cell histiocytosis (PLCH) is a rare form of Langerhans cell histiocytosis (LCH) that typically occurs in cigarette smokers. The clinical course of PLCH is unpredictable; the disease may resolve spontaneously, or lead to multi-organ failure and death. To better understand this idiopathic disease, we retrospectively overviewed a cohort of Asian patients with PLCHs.

METHODS: Herein, we have provided detailed clinicopathological features and molecular findings of PLCHs in a Southwestern Chinese population, including the expressions of apoptotic protein P16, programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). Importantly, the BRAF V600E mutation was observed in this cohort.

RESULTS: In accordance with the follow up data, the cohort was subdivided into two groups, an isolated pulmonary group and extrapulmonary recidivism group. Among the isolated group, the participants were predominantly young males (<40 years old), with a history of smoking, respiratory symptoms (cough and difficulty breathing), showed more cystic lesions in computed tomography (CT) scanning, had more cellular Langerhans granulomas under the microscope, overexpression of P16 (66.7%), high PD-1 (100%) and low PD-L1 (33.3%) expressions, and no BRAF V600E mutation was detected. In contrast, the extrapulmonary recidivism group showed significantly older age (>40 years old), recurrent spontaneous pneumothorax, more nodular changes in CT scanning, more interstitial fibrosis histologically, expression rates of 100% of P16, 66.7% of PD-1, and 33.3% of PD-L1; and importantly, BRAF V600E mutation was detected in 33.3% of this subdivision.

CONCLUSIONS: We found that adult PLCH might consist of two distinct groups: an isolated form and extrapulmonary recidivism PLCH. Overexpression of P16 could be a diagnostic biomarker for PLCH. An extremely low mutation rate of the BRAF gene in adult PLCH in our cohort indicated that there might be other pathogeneses for this disease among Asian patients.

PMID:33708984 | PMC:PMC7944282 | DOI:10.21037/atm-20-8141

Multidiscip Respir Med. 2021 Jan 25;16(1):731. doi: 10.4081/mrm.2021.731. eCollection 2021 Jan 15.

ABSTRACT

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is a new technique that enables larger tissue collection than can be obtained by conventional transbronchial lung biopsy. TBLC is becoming popular worldwide and is performed for diffuse lung disease and lung cancer. However, only a few reports of TBLC have been published in Japan. This study was performed to evaluate the efficacy and safety of TBLC at our hospital and compare these findings with past reports.

METHODS: From April 2018 to January 2020, 38 patients who underwent TBLC for diffuse lung disease at our hospital were evaluated with respect to age, sex, biopsy site, biopsy size, diagnostic disease, and complications.

RESULTS: The patients who underwent TBLC were 20 men and 18 women with an average age of 63.7 years. The average sample size was 5.7 mm, and the diagnostic rate was 65.7% (25/38). Grade ≥2 complications included bleeding (15.8%), pneumothorax (2.6%), and atrial fibrillation (2.6%).

CONCLUSIONS: TBLC was considered to be useful for the diagnosis of diffuse lung disease and could be safely performed.

PMID:33708383 | PMC:PMC7941050 | DOI:10.4081/mrm.2021.731

Ther Adv Chronic Dis. 2020 Nov 27;11:2040622320968412. doi: 10.1177/2040622320968412. eCollection 2020.

ABSTRACT

BACKGROUND AND AIMS: Idiopathic pulmonary fibrosis (IPF) is a common and severe form of pulmonary fibrosis. Nintedanib, a triple angiokinase inhibitor, is approved for treating IPF. Galectin 3 (Gal-3) activates a variety of profibrotic processes. Currently, the Gal-3 inhibitor TD139 is being tested in phase II clinical trials. Since this treatment is given 'on top' of nintedanib, it is important to estimate its effect on Gal-3 levels. Therefore, we evaluated the impact of nintedanib on Gal-3 expression using both in vitro and in vivo models, in addition to serum samples from patients with IPF.

METHODS: Gal-3 levels were evaluated in IPF and control tissue samples, primary human lung fibroblasts (HLFs) following nintedanib treatment (10-100 nM, quantitative polymerase chain reaction), and in a silica-induced fibrosis mouse model with/without nintedanib (0.021-0.21 mg/kg) by immunohistochemistry. In addition, Gal-3 levels were analyzed in serum samples from 41 patients with interstitial lung disease patients with/without nintedanib treatment by ELISA.

RESULTS: Nintedanib addition to HLFs resulted in significant elevations in Gal-3, phospho-signal transducer and activator of transcription 3 (pSTAT3), as well as IL-8 mRNA levels (p < 0.05). Gal-3 expression was higher in samples from IPF patients compared with non-IPF controls at the protein and mRNA levels (p < 0.05). In the in vivo mouse model, Gal-3 levels were increased following fibrosis induction and even further increased with the addition of nintedanib, mostly in macrophages (p < 0.05). Patients receiving nintedanib presented with higher Gal-3 serum levels compared with those who did not receive nintedanib (p < 0.05).

CONCLUSION: Nintedanib elevates Gal-3 levels in both experimental models, along with patient samples. These findings highlight the possibility of using combined inhibition therapy for patients with IPF.

PMID:33708368 | PMC:PMC7907712 | DOI:10.1177/2040622320968412

Sci Rep. 2021 Mar 11;11(1):5762. doi: 10.1038/s41598-021-85539-1.

ABSTRACT

Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102-0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992-0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059-8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

PMID:33707643 | DOI:10.1038/s41598-021-85539-1

Sci Rep. 2021 Mar 11;11(1):5782. doi: 10.1038/s41598-021-85234-1.

ABSTRACT

Some patients with idiopathic pulmonary fibrosis (IPF) undergo recurrent acute exacerbations (AEs). This study aimed to elucidate the risk factors for recurrent AEs of IPF (AE-IPF). Consecutive patients with IPF admitted for their first AE-IPF between January 2008 and December 2018 were retrospectively recruited. Of 63 patients admitted for an AE-IPF and discharged alive, 9 (14.3%) developed a recurrence of AE within 1 year. The mean time to recurrence was 233 ± 103 days. Total doses (mg/month and mg/kg/month) of corticosteroids administered over day 1 to 30 after the AE were significantly higher in patients without recurrences of AE-IPF (5185 ± 2414 mg/month, 93.5 ± 44.0 mg/kg/month) than the doses in patients with recurrences (3133 ± 1990 mg/month, 57.2 ± 37.7 mg/kg/month) (p = 0.02 and p = 0.03, respectively). However, no differences were observed between the total doses of corticosteroids administered over days 31 to 60, 61 to 90, 91 to 120, and 151 to 180 after the AE. Furthermore, differences between the administration rates of immunosuppressive and antifibrotic treatments administered to the 2 patient groups were not significant. An increased total dose of corticosteroid administered over day 1 to 30 after an AE-IPF was associated with a decreased risk of subsequent recurrence of AE-IPF within 1 year after the first AE.

PMID:33707613 | DOI:10.1038/s41598-021-85234-1

Med Sci Monit. 2021 Mar 12;27:e928547. doi: 10.12659/MSM.928547.

ABSTRACT

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a disease related to aging, which has become increasingly prevalent as the population has aged. However, there remains no effective treatment for the disease. Alveolar epithelial type II cell (AEC II) senescence plays an important role in the occurrence and development of IPF. Therefore, enhancing our understanding of aging AEC IIs might facilitate the development of a new therapeutic strategy for the prevention and treatment of IPF. The aim of this study was to investigate the effect of citrus alkaline extracts (CAE) on senescence in A549 cells and elucidate the mechanism by which CAE function. MATERIAL AND METHODS Adriamycin RD (ARD) induces the senescence of A549 cells. Relevant indicators were identified following administration of 3 concentrations of CAE (50 μg/mL, 100 μg/mL, and 200 μg/mL) to A549 cells. RESULTS CAE inhibited senescence in ARD-induced A549 cells. It inhibited p16, p21, p53, and a senescence-associated secretory phenotype, and reduced expression of the senescence-related positive cells of ß-galactosidase. Further study revealed that activation of the ß-catenin signaling pathway is closely associated with p53. CAE inhibited senescence in A549 cells via the ß-catenin/p53 pathway. Further, inhibition of b-catenin was associated with reduced expression levels of p53 and p21, and the anti-aging effects of CAE were enhanced. When expression of p53 was inhibited, expression levels of ß-catenin also tended to decrease. CONCLUSIONS In summary, our study showed that CAE can inhibit aging in A549 cells to alleviate pulmonary fibrosis, and thus limit the secretion of the extracellular matrix and collagen in lung fibroblasts.

PMID:33707405 | DOI:10.12659/MSM.928547

Part Fibre Toxicol. 2021 Mar 11;18(1):11. doi: 10.1186/s12989-021-00404-3.

ABSTRACT

BACKGROUND: Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.

RESULTS: In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.

CONCLUSIONS: These data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.

PMID:33706759 | DOI:10.1186/s12989-021-00404-3

JCI Insight. 2021 Mar 11:143626. doi: 10.1172/jci.insight.143626. Online ahead of print.

ABSTRACT

Compromised regenerative capacity of lung epithelial cells can lead to cellular senescence, which may precipitate fibrosis. While increased markers of senescence have been reported in idiopathic pulmonary fibrosis (IPF), the origin and identity of these senescent cells remain unclear, and tools to characterize context-specific cellular senescence in human lung are lacking. We observed that the senescent marker p16 is predominantly localized to bronchiolized epithelial structures in scarred regions of IPF and systemic sclerosis associated interstitial lung disease ILD (SSc-ILD) lung tissue, overlapping with the basal epithelial markers Keratin 5 and Keratin 17. Using in vitro models, we derived transcriptional signatures of senescence programming specific to different types of lung epithelial cells, and interrogated these signatures in a single-cell RNA-seq data set derived from control, IPF, and SSc-ILD lung tissue. We identified a population of basal epithelial cells defined by, and enriched for, markers of cellular senescence, and identified candidate markers specific to senescent basal epithelial cells in ILD that can enable future functional studies. Notably, gene expression of these cells significantly overlaps with terminally differentiating cells in stratified epithelia, where it is driven by p53 activation as part of the senescence program.

PMID:33705361 | DOI:10.1172/jci.insight.143626

ERJ Open Res. 2020 Nov 10;6(4):00190-2019. doi: 10.1183/23120541.00190-2019. eCollection 2020 Oct.

ABSTRACT

The inter-relationship between chronic respiratory disease and reflux disease in the airway reflux paradigm is extremely complex and remains poorly characterised. Reflux disease is reported to cause or contribute to the severity of a number of respiratory tract diseases including laryngeal disorders, sinusitis, chronic cough, asthma, COPD, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis and bronchiolitis obliterans post lung transplant. It is now appreciated that reflux disease is not simply caused by liquid acid reflux but rather by a variety of chemical refluxates originating from the stomach and duodenum due to a number of different mechanisms. Reflux disease can be challenging to diagnose, particularly proving its role in the causation of direct respiratory epithelial damage. Significant advances in oesophageal assessment and gastric biomarkers have emerged in recent years as our understanding increases. There are a number of treatments available for reflux disease, both medical and surgical, but there is a paucity of large randomised trials to evaluate their efficacy in the setting of chronic respiratory disease. Everyday clinical practice, however, informs us that treatment failure in reflux disease is common. This clinical review summarises associations between reflux disease in the setting of chronic respiratory diseases and examines available evidence regarding potential therapeutic strategies.

PMID:33693049 | PMC:PMC7927787 | DOI:10.1183/23120541.00190-2019

Rev Med Suisse. 2021 Mar 10;17(729):492-496.

ABSTRACT

The connectivitides are autoimmune diseases that affect many organs. All of them can cause interstitial lung disease, the most frequent forms being the NSIP (nonspecific interstitial pneumonia) and the UIP (usual interstitial pneumonia). The best screening method is the high-resolution chest CT. The treatment of ILD includes glucocorticoids, immunosuppressive and antifibrotic agents, as well as non-pharmacological therapies. We present the screening and treatment algorithm for the ILD in systemic sclerosis, which is very well established. We also discuss the management of the ILD in rheumatoid arthritis, a very prevalent disease, and though of large public interest.

PMID:33689246

Am J Respir Crit Care Med. 2021 Mar 9. doi: 10.1164/rccm.202008-3093OC. Online ahead of print.

ABSTRACT

Rationale: Disease activity in idiopathic pulmonary fibrosis (IPF) remains highly variable, poorly understood, and difficult to predict. Objective: To identify a predictor using short-term longitudinal changes in gene-expression that forecasts future forced vital capacity (FVC) decline and to characterize involved pathways and cell types. Methods: Seventy-four patients from Correlating Outcomes with biochemical Markers to Estimate Time-progression in IPF (COMET) cohort were dichotomized as progressors (≥10% FVC decline) or stable. Blood gene-expression changes within individuals were calculated between baseline and 4 months, and regressed with future FVC status, allowing determination of expression variations, sample size, and statistical power. Pathway analyses were conducted to predict downstream effects and identify new targets. An FVC-predictor for progression was constructed in COMET and validated using independent cohorts. Peripheral blood mononuclear single-cell RNA-seq (PBMC scRNA-seq) data from healthy controls were used as references to characterize cell type compositions from bulk PBMC RNA-seq data that were associated with FVC decline. Results: The longitudinal model reduced gene-expression variations within stable and progressor groups, resulting in increased statistical power when compared to a cross-sectional model. The FVC-predictor for progression anticipated patients with future FVC decline with 78% sensitivity and 86% specificity across independent IPF cohorts. Pattern recognition receptor pathways and mTOR pathways were down- and up-regulated, respectively. Cellular deconvolution using scRNA-seq data identified natural killer (NK) cells as significantly correlated with progression. Conclusions: Serial transcriptomic change predicts future FVC decline. Analysis of cell types involved in the progressor signature supports the novel involvement of NK cells in IPF progression.

PMID:33689671 | DOI:10.1164/rccm.202008-3093OC

Am J Respir Cell Mol Biol. 2021 Mar 9. doi: 10.1165/rcmb.2020-0387OC. Online ahead of print.

ABSTRACT

B-cell activation is increasingly linked to numerous fibrotic lung diseases and it is well-known that aggregates of lymphocytes form in the lung of many of these patients (1, 2). Activation of B-cells by pattern recognition receptors (PRR) drives the release of inflammatory cytokines, chemokines and metalloproteases important in the pathophysiology of pulmonary fibrosis (3-6). However, the specific mechanisms of B-cell activation in patients with idiopathic pulmonary fibrosis (IPF) are poorly understood. Herein, we have demonstrated that B-cell activation by microbial antigens contribute to the inflammatory and pro-fibrotic milieu seen in IPF patients. B-cell stimulation by CpG and β-glucan via PRR resulted in activation of mTOR-dependent and independent pathways. Moreover, we showed that the B-cell secreted inflammatory milieu is specific to the inducing antigen and causes differential fibroblast migration and activation. B-cell responses to infectious agents and subsequent B-cell-mediated fibroblast activation are modifiable by antifibrotics but each seems to exert a specific and different effect. These results suggest that upon PRR activation by microbial antigens, B-cells can contribute to the inflammatory and fibrotic changes seen in IPF patients and antifibrotics are able to at least partially reverse these responses.

PMID:33689587 | DOI:10.1165/rcmb.2020-0387OC

Pulm Ther. 2021 Mar 10. doi: 10.1007/s41030-021-00148-7. Online ahead of print.

ABSTRACT

Air pollution has been associated with respiratory diseases such as chronic obstructive pulmonary disease (COPD) and lung malignancies. The aim of this narrative review is to analyze the current data on the possible association between air pollution and interstitial lung disease (ILD). There are multiple studies showing the association of ILD with air pollution but the mechanism remains unclear. Although some of the environmental factors have been associated with idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), and pneumoconiosis, data about other ILDs are scarce and not well known. Air pollution as an etiology for ILD may act in multiple ways, leading to disease pathogenesis or exacerbation of underlying ILD. Clinical implications of this association are manifold; limiting the exposure to poor-quality air could possibly reduce the fall in lung functions and the risk of acute exacerbations of the underlying ILD.

PMID:33689161 | DOI:10.1007/s41030-021-00148-7

J Exp Med. 2021 May 3;218(5):e20202033. doi: 10.1084/jem.20202033.

ABSTRACT

Aging is a strong risk factor and an independent prognostic factor for progressive human idiopathic pulmonary fibrosis (IPF). Aged mice develop nonresolving pulmonary fibrosis following lung injury. In this study, we found that mouse double minute 4 homolog (MDM4) is highly expressed in the fibrotic lesions of human IPF and experimental pulmonary fibrosis in aged mice. We identified MDM4 as a matrix stiffness-regulated endogenous inhibitor of p53. Reducing matrix stiffness down-regulates MDM4 expression, resulting in p53 activation in primary lung myofibroblasts isolated from IPF patients. Gain of p53 function activates a gene program that sensitizes lung myofibroblasts to apoptosis and promotes the clearance of apoptotic myofibroblasts by macrophages. Destiffening of the fibrotic lung matrix by targeting nonenzymatic cross-linking or genetic ablation of Mdm4 in lung (myo)fibroblasts activates the Mdm4-p53 pathway and promotes lung fibrosis resolution in aged mice. These findings suggest that mechanosensitive MDM4 is a molecular target with promising therapeutic potential against persistent lung fibrosis associated with aging.

PMID:33688918 | DOI:10.1084/jem.20202033

J Clin Sleep Med. 2021 Mar 8. doi: 10.5664/jcsm.9212. Online ahead of print.

NO ABSTRACT

PMID:33682677 | DOI:10.5664/jcsm.9212

J Clin Sleep Med. 2021 Mar 8. doi: 10.5664/jcsm.9204. Online ahead of print.

NO ABSTRACT

PMID:33682674 | DOI:10.5664/jcsm.9204

Rev Med Liege. 2021 Mar;76(3):166-172.

ABSTRACT

Pulmonary fibrosis is a pathological entity still too little understood today, burdened with significant morbidity and mortality. Idiopathic pulmonary fibrosis is a complex diagnostic disease requiring a multidisciplinary approach and in some cases the performance of a lung biopsy. In addition, the early identification of the pathology remains the key in order to preserve lung function as much as possible. In this context and in view of the diagnostic difficulty, it seems essential to identify new biomarkers to help with the differential diagnosis, the evaluation of the prognosis and the response to treatment. In addition, the evolution of the pathology remaining inexorable despite anti-fibrotic treatments, it appears critical to be able to identify new potential therapeutic routes.

PMID:33682385

ERJ Open Res. 2021 Mar 1;7(1):00196-2020. doi: 10.1183/23120541.00196-2020. eCollection 2021 Jan.

ABSTRACT

BACKGROUND: There are no established therapeutic options available for idiopathic pleuroparenchymal fibroelastosis (IPPFE) apart from supportive care and lung transplantation. Furthermore, it is known that IPPFE with a usual interstitial pneumonia (UIP) pattern and lower lobe predominance is a disease entity distinct from idiopathic pulmonary fibrosis (IPF). To our knowledge, few studies are available that report on the efficacy of antifibrotic agents for IPPFE with UIP.

AIM: The aim of this study was to compare the efficacy of antifibrotic agents between IPPFE with UIP and typical IPF in real-world clinical practice.

PATIENTS AND METHODS: A retrospective analysis was performed on the medical records of all patients at two interstitial lung disease centres. Sixty-four patients were diagnosed as having IPPFE with UIP and 195 patients were diagnosed with typical IPF. We compared the efficacy of antifibrotic agents between these two groups.

RESULTS: Survival time was significantly shorter in the patients with IPPFE with UIP. Some 125 patients were administered antifibrotic agents for over 6 months (34 with IPPFE with UIP and 91 with typical IPF). Reduced forced vital capacity (FVC) 6 months after treatment with antifibrotic agents was significantly greater in the IPPFE with UIP group than in those in the typical IPF group. Moreover, the change in % predicted FVC was significantly greater during the follow-up in patients with IPPFE with UIP compared with those with typical IPF.

CONCLUSIONS: The efficacy of antifibrotic agents was limited in patients with IPPFE with UIP. Thus, IPPFE with UIP remains a fatal and progressive disease.

PMID:33681342 | PMC:PMC7917230 | DOI:10.1183/23120541.00196-2020

Front Med (Lausanne). 2021 Feb 17;8:640020. doi: 10.3389/fmed.2021.640020. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressively and ultimately fatal lung disease. Previously it has been shown that intratracheal administration of alveolar epithelial type II cells (AE2C) in the animal model of bleomycin-induced pulmonary fibrosis is able to reverse fibrosis and restore surfactant protein levels. However, to date, it has not been evaluated whether these changes involve any improvement in alveolar dynamics. Consequently, the aim of the present work was to study lung physiology after AE2C transplantation at different time points during the development of injury and fibrosis. Lung fibrosis was induced by intratracheal instillation of bleomycin (4U/kg) in rat lungs. The animals were transplanted with AE2C (2.5 × 106 cells/animal) 3 or 7 days after bleomycin instillation. Assessments were done at day 7 and 14 after the induction of fibrosis to plot time dependent changes in lung physiology and mechanics. To assess the pressures and rates at which closed alveoli reopens invasive pulmonary tests using a small-animal mechanical ventilator (Flexivent®, Scireq, Canada) including de-recruitability tests and forced oscillation technique as well as quasi-static pressure volume loops were performed. Afterwards lungs were fixed by vascular perfusion and subjected to design-based stereological evaluation at light and electron microscopy level. AE2C delivered during the lung injury phase (3 days) of the disease are only able to slightly recover the volume of AE2C and volume fraction of LB in AE2C. However, it did not show either positive effects regarding ventilated alveolar surface nor any increase of lung compliance. On the other hand, when AE2C are delivered at the beginning of the fibrotic phase (7 days after bleomycin instillation), an increased ventilated alveolar surface to control levels and reduced septal wall thickness can be observed. Moreover, transplanted animals showed better lung performance, with increased inspiratory capacity and compliance. In addition, a detailed analysis of surfactant active forms [mainly tubular myelin, lamellar body (LB)-like structures and multilamellar vesicles (MLV)], showed an effective recovery during the pro-fibrotic phase due to the healthy AE2C transplantation. In conclusion, AE2C transplantation during fibrogenic phases of the disease improves lung performance, structure and surfactant ultrastructure in bleomycin-induced lung fibrosis.

PMID:33681265 | PMC:PMC7925848 | DOI:10.3389/fmed.2021.640020

Radiol Case Rep. 2021 Feb 24;16(5):1019-1022. doi: 10.1016/j.radcr.2021.02.019. eCollection 2021 May.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease. Although high-resolution computed tomography (HRCT) is important for the diagnosis of IPF, the changes in the HRCT findings in IPF are not fully understood. The patient was a 66-year-old man. His HRCT findings had atypically developed from a probable usual interstitial pneumonia pattern to a nonspecific interstitial pneumonia (NSIP) like pattern over 6 years. On the basis of the histologic examination and multidisciplinary discussion, IPF was diagnosed, and nintedanib, administered. This case can be useful for the differential diagnosis of IPF and NSIP.

PMID:33680269 | PMC:PMC7917460 | DOI:10.1016/j.radcr.2021.02.019