Publications by authors named "Kazuyoshi Kuwano"

192 Publications

Effect of anti-interleukin-17 biologics on Krebs von den Lungen-6 level in patients with psoriasis.

J Dermatol 2021 Apr 16. Epub 2021 Apr 16.

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Interleukin (IL)-17 plays critical roles in the pathogenesis of both psoriasis and interstitial pneumonia (IP). We hypothesized that anti-IL-17 biologics might suppress both clinically relevant and latent IP activity and decrease Krebs von den Lungen-6 (KL-6) level in psoriasis patients. We aimed to elucidate the effects of anti-IL-17 biologics on KL-6 levels. We retrospectively analyzed the clinical data of psoriasis patients treated with anti-IL-17 biologics. KL-6 levels were measured before treatment (baseline) and at 3 and 6 months after the initiation of the treatment, and ratios of KL-6 levels at each time point to the baseline levels were calculated. Chest computed tomography (CT) was performed on patients with coexisting IP. The clinical characteristics and radiographic findings were evaluated. A total of 294 psoriasis patients were treated with anti-IL-17 biologics. Baseline KL-6 levels were higher than 401 U/mL in 34 patients (high baseline KL-6 group). While anti-IL-17 biologics did not affect KL-6 levels and ratios of KL-6 to the baseline levels at any time point in the overall study population, they decreased both KL-6 levels and ratios at 6 months after the initiation of the treatment in the high baseline KL-6 group. A total of 10 patients with coexisting IP showed decreasing ratios of KL-6 to the baseline levels at 6 months without affecting coexisting IP in CT performed at 3-12 months. Anti-IL-17 biologics decreased KL-6 levels in the high baseline KL-6 group regardless of recognizable IP. A decrease in KL-6 levels was not associated with a radiographic improvement of IP, which should be examined in large numbers with long-term observations in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1346-8138.15895DOI Listing
April 2021

Localized pleural metastasis without other organ metastases after nephrectomy for renal cell carcinoma.

Respir Med Case Rep 2021 19;33:101388. Epub 2021 Mar 19.

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

We present a case of a 69-year-old man who had localized pleural metastasis without other organ metastases after nephrectomy for right renal cell carcinoma (RCC). He complained of respiratory symptoms for more than two years after the operation and was confirmed to have right pleural effusion and multiple pleural masses on computed tomography (CT). There were no abnormal findings in the other organs, but the pleural mass gradually increased in size on CT. We suspected malignant tumors such as malignant pleural mesothelioma and synovial sarcoma in addition to RCC metastasis. Finally, we performed surgical resection of the pleural mass under general anesthesia, and we diagnosed pathologically as metastasis from RCC. Distant metastases of RCC are common in the lungs, bones, brain, and liver. To our knowledge, localized pleural metastases from RCC is rare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmcr.2021.101388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025045PMC
March 2021

Intercellular Communication by Vascular Endothelial Cell-Derived Extracellular Vesicles and Their MicroRNAs in Respiratory Diseases.

Front Mol Biosci 2020 29;7:619697. Epub 2021 Jan 29.

Division of Respiratory Disease, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Respiratory diseases and their comorbidities, such as cardiovascular disease and muscle atrophy, have been increasing in the world. Extracellular vesicles (EVs), which include exosomes and microvesicles, are released from almost all cell types and play crucial roles in intercellular communication, both in the regulation of homeostasis and the pathogenesis of various diseases. Exosomes are of endosomal origin and range in size from 50 to 150 nm in diameter, while microvesicles are generated by the direct outward budding of the plasma membrane in size ranges of 100-2,000 nm in diameter. EVs can contain various proteins, metabolites, and nucleic acids, such as mRNA, non-coding RNA species, and DNA fragments. In addition, these nucleic acids in EVs can be functional in recipient cells through EV cargo. The endothelium is a distributed organ of considerable biological importance, and disrupted endothelial function is involved in the pathogenesis of respiratory diseases such as chronic obstructive pulmonary disease, pulmonary hypertension, and acute respiratory distress syndrome. Endothelial cell-derived EVs (EC-EVs) play crucial roles in both physiological and pathological conditions by traveling to distant sites through systemic circulation. This review summarizes the pathological roles of vascular microRNAs contained in EC-EVs in respiratory diseases, mainly focusing on chronic obstructive pulmonary disease, pulmonary hypertension, and acute respiratory distress syndrome. Furthermore, this review discusses the potential clinical usefulness of EC-EVs as therapeutic agents in respiratory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2020.619697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890564PMC
January 2021

HSP90 inhibition overcomes EGFR amplification-induced resistance to third-generation EGFR-TKIs.

Thorac Cancer 2021 03 20;12(5):631-642. Epub 2021 Jan 20.

Division of Cancer Immunology, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Chiba, Japan.

Background: Patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are sensitive to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) but inevitably develop resistance to the inhibitors mostly through acquisition of the secondary T790M mutation. Although third-generation EGFR-TKIs overcome this resistance by selectively inhibiting EGFR with EGFR-TKI-sensitizing and T790M mutations, acquired resistance to third-generation EGFR-TKIs invariably develops.

Methods: Next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) analysis were performed in an EGFR T790M-mutated NSCLC patient who had progressed after a third-generation EGFR-TKI, TAS-121. EGFR-mutated cell lines were subjected to a cell proliferation assay and western blotting analysis with EGFR-TKIs and a heat shock protein 90 (HSP90) inhibitor.

Results: NGS and FISH analysis revealed EGFR amplification in the resistant cancer cells. While EGFR L858R/T90M-mutated cell line was sensitive to osimertinib or TAS-121 in vitro, EGFR-overexpressing cell lines displayed resistance to these EGFR-TKIs. Western blot analysis showed that EGFR phosphorylation and overexpression of EGFR in cell lines was not suppressed by third-generation EGFR-TKIs. In contrast, an HSP90 inhibitor reduced total and phosphorylated EGFR and inhibited the proliferation of resistant cell lines.

Conclusions: EGFR amplification confers resistance to third-generation EGFR-TKIs which can be overcome by HSP90 inhibition. The results provide a preclinical rationale for the use of HSP90 inhibitors to overcome EGFR amplification-mediated resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919131PMC
March 2021

Endobronchial neurogenic tumor consisting of the features of a solitary circumscribed neuroma.

J Thorac Dis 2020 Dec;12(12):7498-7500

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd-20-2365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797859PMC
December 2020

Characteristics of anti-IL-17/23 biologics-induced interstitial pneumonia in patients with psoriasis.

PLoS One 2021 7;16(1):e0245284. Epub 2021 Jan 7.

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Objectives: Anti-IL-17/23 biologics are increasingly used to treat psoriasis. We aimed to elucidate characteristics of drug-induced interstitial pneumonia (DIIP) caused by anti-IL-17/23 biologics.

Methods: We retrospectively analyzed the clinical data of psoriasis patients treated with anti-IL-17/23 biologics. Chest CT was performed to evaluate DIIP. Serum KL-6 levels were measured before treatment (baseline) and during treatment.

Results: A total of 603 psoriasis patients were treated with anti-IL-17/23 biologics with mean follow-up of 21.1 months. Six patients developed DIIP at mean 14 months after initiation of the therapy. Older age, higher baseline KL-6 value and more frequent pre-existing IPs were associated with development of DIIP by univariate analysis. At the onset of DIIP, elevated serum KL-6 levels with concomitantly increased ground glass opacity (GGO) in Chest CT were demonstrated. DIIP was improved by only cessation of causative agents in five patients but steroid therapy was needed in one patient.

Conclusions: DIIP is a plausible complication of anti-IL-17/23 biologics. Age, baseline KL-6 level and underlying IP could be the risk factors for DIIP development. Serum KL-6 levels and chest CT are useful for not only predicting but also detecting DIIP caused by anti-IL-17/23 biologics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245284PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790374PMC
January 2021

Successful treatment with methyl-prednisolone pulses for the late phase of COVID-19 with respiratory failure: A single-center case series.

Respir Med Case Rep 2020 9;31:101318. Epub 2020 Dec 9.

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.

Although some prospective studies provided the evidence of corticosteroids for critically ill patients with COVID-19, the optimal dosage or timing of corticosteroids is still unknown. This is a case series of four patients on methyl-prednisolone pulses for the late phase of Coronavirus disease 2019 (COVID-19) with respiratory failure in our hospital. All patients needed invasive mechanical ventilation and had bimodal worseness of their respiratory status with consolidation and volume loss after intubation. All cases could successfully discontinue oxygen therapy without any severe adverse events after this pulse therapy in the late phase of COVID-19. This therapy is believed to be effective on some optimal patients. Hence, further studies to explore this efficacy and safety were needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmcr.2020.101318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723782PMC
December 2020

The Usefulness of a Transbronchial Lung Cryobiopsy for Diffuse Bronchiolitis.

Intern Med 2021 May 7;60(9):1457-1462. Epub 2020 Dec 7.

Department of Respiratory Medicine, Saitama Red Cross Hospital, Japan.

We herein report four cases of diffuse bronchiolitis proven by a transbronchial lung cryobiopsy (TBLC). Based on various aspects, including the pathological findings, we definitively diagnosed two patients with diffuse panbronchiolitis (DPB) and the other two with primary ciliary dyskinesia (PCD). One of the DPB patients had more severe peribronchiolar fibrosis than the other, and the disease course was refractory to macrolide therapy. One of the PCD patients was additionally diagnosed with combined constrictive bronchiolitis. This report highlights the importance of a TBLC in the differentiation of bronchiolitis, suggesting its utility for helping pulmonologists formulate a treatment strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.6028-20DOI Listing
May 2021

Impact of emphysema on sputum culture conversion in male patients with pulmonary tuberculosis: a retrospective analysis.

BMC Pulm Med 2020 Nov 7;20(1):287. Epub 2020 Nov 7.

Department of Internal Medicine, Division of Respiratory Diseases, The Jikei University School of Medicine, Tokyo, Japan.

Background: Although cigarette smoking may have a negative impact on the clinical outcome of pulmonary tuberculosis (PTB), few studies have investigated the impact of smoking-associated lung diseases. Emphysema is a major pathological finding of smoking-related lung damage. We aimed to clarify the effect of emphysema on sputum culture conversion rate for Mycobacterium tuberculosis (MTB).

Methods: We retrospectively studied 79 male patients with PTB confirmed by acid-fast bacillus smear and culture at Jikei University Daisan Hospital between January 2015 and December 2018. We investigated the sputum culture conversion rates for MTB after starting standard anti-TB treatment in patients with or without emphysema. Emphysema was defined as Goddard score ≥ 1 based on low attenuation area < - 950 Hounsfield Unit (HU) using computed tomography (CT). We also evaluated the effect on PTB-related CT findings prior to anti-TB treatment.

Results: Mycobacterial median time to culture conversion (TCC) in 38 PTB patients with emphysema was 52.0 days [interquartile range (IQR) 29.0-66.0 days], which was significantly delayed compared with that in 41 patients without emphysema (28.0 days, IQR 14.0-42.0 days) (p < 0.001, log-rank test). Multivariate Cox proportional hazards analysis showed that the following were associated with delayed TCC: emphysema [hazard ratio (HR): 2.43; 95% confidence interval (CI): 1.18-4.97; p = 0.015), cavities (HR: 2.15; 95% CI: 1.83-3.89; p = 0.012) and baseline time to TB detection within 2 weeks (HR: 2.95; 95% CI: 1.64-5.31; p < 0.0001). Cavities and consolidation were more often identified by CT in PTB patients with than without emphysema (71.05% vs 43.90%; p = 0.015, and 84.21% vs 60.98%; p = 0.021, respectively).

Conclusions: This study suggests that emphysema poses an increased risk of delayed TCC in PTB. Emphysema detection by CT might be a useful method for prediction of the duration of PTB treatment required for sputum negative conversion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-020-01325-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648401PMC
November 2020

Treatment and relapse of interstitial lung disease in nivolumab-treated patients with non-small cell lung cancer.

Cancer Sci 2021 Apr 24;112(4):1506-1513. Epub 2021 Feb 24.

The Jikei University School of Medicine, Tokyo, Japan.

Nivolumab, a human monoclonal antibody against programmed death-1, is approved for the treatment of non-small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune-related adverse event. Currently, there are limited data available on the treatment of nivolumab-induced ILD and its outcome. This retrospective cohort study based on a post-marketing study described the treatment of nivolumab-induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab-induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab-induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019226PMC
April 2021

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer.

Cancer Sci 2021 Apr 24;112(4):1495-1505. Epub 2021 Feb 24.

The Jikei University School of Medicine, Tokyo, Japan.

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019215PMC
April 2021

Benefits and Risks of Inhaled Corticosteroid Treatment in Patients with Chronic Obstructive Pulmonary Disease Classified by Blood Eosinophil Counts.

Lung 2020 12 17;198(6):925-931. Epub 2020 Oct 17.

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Background: Chronic obstructive pulmonary disease (COPD) typically includes neutrophilic airway inflammation and eosinophilic inflammation in some cases. Inhaled corticosteroid (ICS) suppresses eosinophilic inflammation of the airway and reduces acute exacerbation (AE). The present study investigated the relationship between ICS and AE in patients with COPD classified by blood eosinophil counts.

Methods: Overall, 244 patients with COPD were retrospectively evaluated between 2014 and 2017 and classified into two groups based on blood eosinophil counts (≥ 300/μL and < 300/μL). These patients were then reclassified into subgroups of those with and without ICS. Differences in the characteristics and incidence of AE and pneumonia with AE in each subgroup were evaluated retrospectively.

Results: All patients with ICS used 320 μg budesonide twice daily. In the group with blood eosinophil counts ≥ 300/μL, patients with ICS had a significantly lower incidence of AE than those without ICS (P = 0.023). Meanwhile, no significant differences were observed in incidence of AE in the group with blood eosinophil counts < 300/μL. In the group with blood eosinophil counts < 300/μL, patients with ICS had a higher incidence of pneumonia with AE (P = 0.009). Conversely, no significant differences were observed in the group with blood eosinophil counts ≥ 300/μL.

Conclusions: ICS significantly reduced AE in COPD patients with blood eosinophil counts ≥ 300/μL. Meanwhile, ICS significantly increased pneumonia rate in patients with blood eosinophil count < 300/μL. Blood eosinophil count may be a useful indicator to identify the benefits and risks of ICS in COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00408-020-00397-4DOI Listing
December 2020

The potential utility of anterior upper lobe honeycomb-like lesion in interstitial lung disease associated with connective tissue disease.

Respir Med 2020 10 21;172:106125. Epub 2020 Aug 21.

Department of Respiratory Medicine, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama, 330-8553, Japan. Electronic address:

Background: Interstitial lung disease (ILD) is associated with high morbidity and mortality in patients with connective tissue disease (CTD). Because some patients with CTD overlap present with ILD first, with CTD diagnosed later, specific radiologic signs are needed to help differentiate each CTD or CTD-ILD from idiopathic ILD.

Objectives: To determine whether specific CT findings can help differentiate CTD as rheumatoid arthritis (RA), systemic sclerosis (SSc), or polymyositis/dermatomyositis (PM/DM).

Methods: We analyzed 143 consecutive ILD patients with RA, SSc, or PM/DM. We assessed diagnostic accuracy of CT findings of CTD-ILD, CT pattern, and signs including "anterior upper lobe honeycomb-like lesion" and "low attenuation area (LAA) within an interstitial abnormality" for each CTD-ILD. Prognostic predictors were determined using Cox regression models.

Results: Subjects were 78 patients with RA-ILD, 38 with SSc-ILD, 24 with PM/DM-ILD, and 3 with overlapping CTD-ILD. High frequency of anterior upper lobe honeycomb-like lesion suggests that CTD-ILD is due to RA-ILD (22%) rather than SSc-ILD (8%) or PM/DM-ILD (8%), whereas LAA within an interstitial abnormality suggests that CTD-ILD is due to SSc-ILD (26%) rather than RA-ILD (4%) or PM/DM-ILD (0%). Multivariate analysis showed that while not associated with survival, current or ex-smoker, honeycombing, and acute exacerbation were negative prognostic factors of mortality.

Conclusions: The tendency is high for RA-ILD, in which anterior upper lobe honeycomb-like lesion is a specific feature, to show UIP or NSIP/UIP pattern, combined emphysema, and honeycombing; SSc-ILD to show NSIP pattern and LAA within an interstitial abnormality; and PM/DM-ILD to show NSIP pattern and non-honeycombing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2020.106125DOI Listing
October 2020

Chaperone-mediated autophagy receptor modulates tumor growth and chemoresistance in non-small cell lung cancer.

Cancer Sci 2020 Nov 7;111(11):4154-4165. Epub 2020 Sep 7.

Department of Internal Medicine, Division of Respiratory Diseases, The Jikei University School of Medicine, Tokyo, Japan.

Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Lysosome-associated membrane protein type 2a (LAMP2A) is the key receptor protein of CMA; downregulation of LAMP2A leads to CMA blockade. Although CMA activation has been involved in cancer growth, CMA status and functions in non-small cell lung cancer (NSCLC) by focusing on the roles in regulating chemosensitivity remain to be clarified. In this study, we found that LAMP2A expression is elevated in NSCLC cell lines and patient's tumors, conferring poor survival and platinum resistance in NSCLC patients. LAMP2A knockdown in NSCLC cells suppressed cell proliferation and colony formation and increased the sensitivity to chemotherapeutic drugs in vitro. Furthermore, we found that intrinsic apoptosis signaling is the mechanism of cell death involved with CMA blockade. Remarkably, LAMP2A knockdown repressed tumorigenicity and sensitized the tumors to cisplatin treatment in NSCLC-bearing mice. Our discoveries suggest that LAMP2A is involved in the regulation of cancer malignant phenotypes and represents a promising new target against chemoresistant NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648026PMC
November 2020

Clinical utility of thoracoscopy in elderly tuberculous pleurisy patients under local anesthesia.

J Infect Chemother 2021 Jan 23;27(1):40-44. Epub 2020 Aug 23.

Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Introduction: Diagnosing tuberculous pleurisy is important in Japan because it currently has a moderate tuberculosis prevalence. However, physicians often have difficulty making a diagnosis. It was reported that thoracoscopy under local anesthesia is useful for the diagnosis of tuberculous pleurisy, but there are no reports focusing on elderly patients.

Methods: In this study, the usefulness of thoracoscopy under local anesthesia was evaluated in elderly patients. Among 170 patients who underwent thoracoscopy under local anesthesia at our hospital during 11 years from January 2008 to December 2018, those aged 75 years or older (n = 75) were investigated retrospectively.

Results: A total of 55 patients underwent thoracoscopy under local anesthesia for detailed examination of pleural effusion of unknown cause. Of these, 18 were diagnosed as tuberculous pleurisy. The median age was 82 years (range: 75-92 years). The diagnosis of tuberculous pleurisy was made in 11 patients in whom Mycobacterium tuberculosis was detected and in four patients whose pathological findings indicated epithelioid granuloma accompanied by caseous necrosis. Clinical diagnosis was made in the remaining three patients based on thoracoscopic findings of the pleural cavity and a high level of adenosine deaminase in pleural fluid. No serious complications attributable to the examination were observed in any patient.

Conclusions: Thoracoscopy under local anesthesia was useful for the diagnosis of tuberculous pleurisy in elderly patients, with useful information being also obtained for the treatment of tuberculosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiac.2020.08.008DOI Listing
January 2021

Efficacy of benralizumab for patients with severe eosinophilic asthma: a retrospective, real-life study.

BMC Pulm Med 2020 Aug 3;20(1):207. Epub 2020 Aug 3.

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Background: Benralizumab, an anti-interleukin-5 (IL-5) receptor α monoclonal antibody, significantly reduces the number of annual exacerbations and oral corticosteroid (OCS) maintenance doses for patients with severe eosinophilic asthma (SEA). However, few studies on the efficacy of this biologic in real life are available. The aim was to elucidate the efficacy of benralizumab by evaluating changes in clinical parameters after benralizumab treatment in patients with SEA.

Methods: From July 2018 to December 2019, 24 Japanese patients with SEA received benralizumab at Jikei University Hospital. We retrospectively evaluated the patients' characteristics, parameters, numbers of exacerbations and maintenance OCS doses.

Results: Among the 24 patients, eleven patients had received mepolizumab treatment and were directly switched to benralizumab. The peripheral blood eosinophil and basophil counts significantly decreased after benralizumab treatment regardless of previous mepolizumab treatment. Pulmonary function, Asthma Control Test scores, the numbers of annual exacerbations and maintenance OCS doses in patients without previous mepolizumab treatment tended to improve without significant differences. Fourteen patients (58%) were responders according to the Global Evaluation of Treatment Effectiveness (GETE) score. The proportion of GETE responders among patients with aspirin-exacerbated respiratory disease (AERD) tended to be lower than that among patients without AERD (p = 0.085). After benralizumab treatment, the change in the forced expiratory volume in 1 s from baseline was 200 ml or greater in eight patients (33%), including three patients who were switched from mepolizumab.

Conclusion: Benralizumab treatment improved and controlled asthma symptoms based on the GETE score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-020-01248-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398222PMC
August 2020

Extracellular Vesicles from Fibroblasts Induce Epithelial-Cell Senescence in Pulmonary Fibrosis.

Am J Respir Cell Mol Biol 2020 11;63(5):623-636

Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.

Aberrant epithelial-mesenchymal interactions have critical roles in regulating fibrosis development. The involvement of extracellular vesicles (EVs), including exosomes, remains to be elucidated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Here, we found that lung fibroblasts (LFs) from patients with IPF induce cellular senescence via EV-mediated transfer of pathogenic cargo to lung epithelial cells. Mechanistically, IPF LF-derived EVs increased mitochondrial reactive oxygen species and associated mitochondrial damage in lung epithelial cells, leading to activation of the DNA damage response and subsequent epithelial-cell senescence. We showed that IPF LF-derived EVs contain elevated levels of microRNA-23b-3p (miR-23b-3p) and miR-494-3p, which suppress , resulting in the epithelial EV-induced phenotypic changes. Furthermore, the levels of miR-23b-3p and miR-494-3p found in IPF LF-derived EVs correlated positively with IPF disease severity. These findings reveal that the accelerated epithelial-cell mitochondrial damage and senescence observed during IPF pathogenesis are caused by a novel paracrine effect of IPF fibroblasts via microRNA-containing EVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1165/rcmb.2020-0002OCDOI Listing
November 2020

Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial.

Eur Respir J 2021 Jan 5;57(1). Epub 2021 Jan 5.

Dept of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan.

Background: A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown.

Methods: This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide () and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability.

Results: 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300 mL and -123 mL, respectively (difference -178 mL, 95% CI -324--31 mL; p=0.018). Serial change in , 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups.

Conclusions: Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00348-2020DOI Listing
January 2021

Chaperone-Mediated Autophagy Suppresses Apoptosis via Regulation of the Unfolded Protein Response during Chronic Obstructive Pulmonary Disease Pathogenesis.

J Immunol 2020 09 22;205(5):1256-1267. Epub 2020 Jul 22.

Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 104-8461, Japan.

Cigarette smoke (CS) induces accumulation of misfolded proteins with concomitantly enhanced unfolded protein response (UPR). Increased apoptosis linked to UPR has been demonstrated in chronic obstructive pulmonary disease (COPD) pathogenesis. Chaperone-mediated autophagy (CMA) is a type of selective autophagy for lysosomal degradation of proteins with the KFERQ peptide motif. CMA has been implicated in not only maintaining nutritional homeostasis but also adapting the cell to stressed conditions. Although recent papers have shown functional cross-talk between UPR and CMA, mechanistic implications for CMA in COPD pathogenesis, especially in association with CS-evoked UPR, remain obscure. In this study, we sought to examine the role of CMA in regulating CS-induced apoptosis linked to UPR during COPD pathogenesis using human bronchial epithelial cells (HBEC) and lung tissues. CS extract (CSE) induced LAMP2A expression and CMA activation through a Nrf2-dependent manner in HBEC. LAMP2A knockdown and the subsequent CMA inhibition enhanced UPR, including CHOP expression, and was accompanied by increased apoptosis during CSE exposure, which was reversed by LAMP2A overexpression. Immunohistochemistry showed that Nrf2 and LAMP2A levels were reduced in small airway epithelial cells in COPD compared with non-COPD lungs. Both Nrf2 and LAMP2A levels were significantly reduced in HBEC isolated from COPD, whereas LAMP2A levels in HBEC were positively correlated with pulmonary function tests. These findings suggest the existence of functional cross-talk between CMA and UPR during CSE exposure and also that impaired CMA may be causally associated with COPD pathogenesis through enhanced UPR-mediated apoptosis in epithelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2000132DOI Listing
September 2020

Intractable diffuse pulmonary diseases: Manual for diagnosis and treatment.

Respir Investig 2021 Jan 2;59(1):8-33. Epub 2020 Jul 2.

National Hospital Organization Tokyo Medical Center, Tokyo, Japan. Electronic address:

This manual has been compiled by a joint production committee with the Diffuse Lung Disease Assembly of the Japanese Respiratory Society (JRS) to provide a practical manual for the epidemiology, diagnosis, and treatment of intractable diffuse pulmonary diseases. The contents are based upon the results of research into these diseases by the Diffuse Pulmonary Diseases Study Group (principal researcher: Sakae Homma) supported by the FY2014-FY2016 Health and Labor Sciences Research Grant on Intractable Diseases. This manual focuses on: 1) pulmonary alveolar microlithiasis, 2) bronchiolitis obliterans, and 3) Hermansky-Pudlak Syndrome with interstitial pneumonia. As these are rare/intractable diffuse lung diseases (2 and 3 were first recognized as specified intractable diseases in 2015), there have not been sufficient epidemiological studies made, and there has been little progress in formulating diagnostic criteria and severity scales; however, the results of Japan's first surveys and research into such details are presented herein. In addition, the manual provides treatment guidance and actual cases for each disease, aiming to assist in the establishment of future modalities. The manual was produced with the goal of enabling clinicians specialized in respiratory apparatus to handle these diseases in clinical settings and of further advancing future research and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.resinv.2020.04.004DOI Listing
January 2021

Dasatinib-induced Nonspecific Interstitial Pneumonia That Developed 7 Years after the Initiation of Dasatinib.

Intern Med 2020 Sep 15;59(18):2297-2300. Epub 2020 Jun 15.

Division of Respiratory Medicine, Department of Internal Medicine, Jikei University School of Medicine, Japan.

We report the case of a 56-year-old man with chronic myeloid leukemia (CML) who developed dasatinib-induced interstitial lung disease (ILD) 7 years after starting dasatinib, a BCR-ABL1 inhibitor. The patient presented with dyspnea. Chest imaging showed diffuse ground-glass opacities. A surgical lung biopsy showed cellular non-specific interstitial pneumonia (NSIP). Corticosteroid treatment ameliorated his condition. Bosutinib, another BCR-ABL1 inhibitor, was successfully re-instituted. The present case and relevant literature suggest that dasatinib-induced ILD can present as NSIP after an extended period, responds to corticosteroids, and is amenable to re-challenge at a lower-dose or with alternative BCR-ABL1 inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.4714-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578610PMC
September 2020

Acute exacerbation of idiopathic interstitial pneumonias related to chemotherapy for lung cancer: nationwide surveillance in Japan.

ERJ Open Res 2020 Apr 26;6(2). Epub 2020 May 26.

Nerima-Hikarigaoka Hospital, Tokyo, Japan.

Background: Chemotherapy-induced acute exacerbation (AEx) of idiopathic interstitial pneumonias (IIPs) seriously compromises the success of treatment of Japanese lung cancer patients. Here, we conducted a nationwide surveillance to clarify the risk of AEx and compare it with the survival benefit of chemotherapy for this population.

Methods: Advanced nonsmall cell lung cancer (NSCLC) or small cell lung cancer (SCLC) patients with IIPs were retrospectively analysed. For the surveillance of first-line chemotherapy in 2009, we gathered clinical data from 396 patients who received chemotherapy at 19 institutions between January 1990 and July 2009. In a consecutive retrospective study in 2012, we analysed data from 278 patients from 17 institutions who received second-line chemotherapy between April 2002 and March 2012.

Results: Of the 396 patients analysed, 13.1% developed chemotherapy-related AEx. Combination chemotherapies of carboplatin plus paclitaxel (CP) or carboplatin plus etoposide (CE) were frequently used as first-line treatments. The lowest incidence of AEx was 3.7% in CE, followed by 8.6% in CP. In the retrospective study, 16.2% of the 278 patients developed a second-line chemotherapy-related AEx. The overall response rate by second-line chemotherapy was 7.4% in NSCLC and 25.7% in SCLC. The median overall survival from second-line and first-line chemotherapy was 8.0 and 14.3 months in NSCLC, and 8.7 and 16.0 months in SCLC, respectively.

Conclusion: Combination chemotherapies consisting of CP or CE are candidates for standard first-line treatments for patients with advanced lung cancer accompanied by IIP. Second-line chemotherapy should be considered for patients remaining fit enough to receive it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00184-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248335PMC
April 2020

Algicidal hydroxylated C18 unsaturated fatty acids from the red alga Tricleocarpa jejuensis: Identification, synthesis and biological activity.

Fitoterapia 2020 Sep 28;145:104639. Epub 2020 May 28.

Graduate School of Fisheries and Environmental Sciences, Nagasaki University, 1-14 Bunkyo-Machi, Nagasaki 852-8521, Japan. Electronic address:

Bioassay-guided separation of a methanol extract of Tricleocarpa jejuensis by monitoring algicidal activity against the red tide phytoplankton Chattonella antiqua led to the isolation of an active fraction consisting of a mixture of four isomeric compounds. The active compounds were identified as (E)-9-hydroxyoctadec-10-enoic acid (1), (E)-10-hydroxyoctadec-8-enoic acid (2), (E)-11-hydroxyoctadec-12-enoic acid (3) and (E)-12-hydroxyoctadec-10-enoic acid (4) by NMR, IR and mass spectral data. The structures were confirmed by comparison of the NMR and MS data with those of authentic samples of 1-4 obtained by unambiguous syntheses. Synthesized hydroxy acids 1-4 and related compounds were assessed for algicidal activity against C. antiqua and it was found that all of 1-4 had high activity (>80% mortality at 24 h) at a concentration of 20 μg/mL. A structure-activity relationship study using 11 related compounds revealed that the presence of the hydroxyl group is important for the activity and the double bond may be replaced with a triple bond.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2020.104639DOI Listing
September 2020

Correlation between the expression of folate receptor alpha (FRα) and clinicopathological features in patients with lung adenocarcinoma.

Lung Cancer 2020 07 11;145:152-157. Epub 2020 May 11.

Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Objectives: Folate receptor alpha (FRα) is expressed on the cell surface, mediates its intracellular transport via receptor-mediated endocytosis, and is involved in cell division. Whether FRα could be a potential therapeutic target in FRα-expressing cancers remains unknown. Here, we retrospectively investigated the correlations between tumor FRα expression in lung adenocarcinoma (LADC) and clinicopathological features.

Materials And Methods: FRα expression was evaluated using a tissue microarray (TMA) constructed from surgical specimens of LADC and compared with clinicopathological features including the EGFR mutation status and the expressions of PD-L1, PD-L2, PD-1, CD4, CD8, CD204, and αSMA. If the proportion of positively stained tumor cells was greater than or equal to 5%, the tumor was considered to show FRα expression; if the H-score was more than or equal to 60, the tumor was considered to show high FRα expression.

Results: Overall, 466 TMA cores created from 233 LADC patients were evaluated: FRα-positive expression (FRα-pos)/negative (FRα-neg), 222/11; FRα high expression (FRα-HE)/low (FRα-LE), 190/43. AnEGFR mutation was present in 53.2 % of the patients. The median H-score of FRα expression, FRα-pos rate, and FRα-HE rate for EGFR mutation/wild type were 159/104 (p = 0.0002), 97.6/92.7 % (p = 0.0773), and 88.7/73.4 % (p = 0.0026), respectively. The H-scores for FRα had mild correlations with the proportion of tumor cells with positive staining for PD-L1 (r=-0.2557, p < 0.0001), the number of CD8-positive cells per square millimeter (r=-0.1767, p = 0.0069), and the area with positive staining for αSMA (r = 0.2049, p = 0.0017). No correlations were seen between FRα expression and other cancer-immunity markers.

Conclusion: Tumor FRα expression was significantly higher in LADCs withEGFR mutation than in those with wild-type EGFR. This study suggested that FRα expression was related to cancer and microenvironment-immunity markers such as PD-L1 expression, CD8 cells, and αSMA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2020.05.002DOI Listing
July 2020

Successful treatment of steroid-refractory immune checkpoint inhibitor-related pneumonitis with triple combination therapy: a case report.

Cancer Immunol Immunother 2020 Oct 15;69(10):2033-2039. Epub 2020 May 15.

Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, 3-19-18 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.

Immune checkpoint inhibitor (ICI)-related pneumonitis is a relatively rare but clinically serious and potentially life-threatening adverse event. The majority of cases can be managed by drug discontinuation, with the administration of corticosteroids added in severe cases. However, worsening of pneumonitis can develop in a subset of patients despite treatment with high doses of corticosteroids. We herein report a case of steroid-refractory ICI-related pneumonitis in a recurrent non-small cell lung cancer (NSCLC) patient treated with pembrolizumab that was successfully improved by triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide). After 3 weeks of initial pembrolizumab administration, the patient was diagnosed with ICI-related pneumonitis. Chest computed tomography (CT) showed patchy distributed bilateral consolidation and ground-glass opacities (GGOs) with traction bronchiectasis and bronchiolectasis resembling the diffuse alveolar damage (DAD) radiographic pattern. Although methylprednisolone pulse therapy was initiated, worsening of respiratory failure resulted in the patient being transferred to the intensive care unit. Because of an insufficient therapeutic response to high-dose corticosteroids, tacrolimus and cyclophosphamide pulse therapy were additively performed as triple combination therapy according to the treatment strategy for pulmonary complications of clinically amyopathic dermatomyositis (CADM). In response to this triple combination therapy, the patient's respiratory condition gradually improved, and chest CT showed the marked amelioration of pulmonary opacities. This is the first report suggesting the efficacy of triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide) for steroid-refractory ICI-related pneumonitis complicated with respiratory failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-020-02600-0DOI Listing
October 2020

Characteristics of pleural effusion in IgG4-related pleuritis.

Respir Med Case Rep 2020 6;29:101019. Epub 2020 Feb 6.

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Here we describe the case of a 78-year-old man with respiratory failure and right pleural effusion. Computed tomography showed right pleural effusion with pleural calcification, tumor-like shadows induced by passive atelectasis, and enlarged mediastinal lymph nodes. Positron emission tomography showed right pleural thickening, rounded atelectasis, and enlarged mediastinal lymph nodes, without fluid accumulation in other organs. The pleural effusion showed lymphocyte-dominated exudates with elevated adenosine deaminase (ADA) levels. Tuberculous pleuritis was suspected, but thoracoscopic pleural biopsy revealed lymphoplasmacytic infiltration and fibrosis, with 10 immunoglobulin G4 (IgG4)-positive plasma cells/high-power field, and IgG4/IgG ratio of 40%. IgG4 concentrations in serum and right pleural effusion were 929 and 1120 mg/dL, respectively. The patient was diagnosed with IgG4-related pleuritis without other systemic manifestations, and reduction in right pleural effusion was confirmed by corticosteroid therapy. IgG4-related disease is typically a systemic disease causing lymphoplasmacytic inflammation in multiple organs. We describe a rare form of IgG4-related pleuritis showing pleural effusion with no other systemic manifestation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmcr.2020.101019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016278PMC
February 2020

Predictive factors of mortality in rheumatoid arthritis-associated interstitial lung disease analysed by modified HRCT classification of idiopathic pulmonary fibrosis according to the 2018 ATS/ERS/JRS/ALAT criteria.

J Thorac Dis 2019 Dec;11(12):5247-5257

Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan.

Background: Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Although usual interstitial pneumonia (UIP) pattern was reported as a poor prognostic factor, in clinical practice, we often cannot classify high-resolution computed tomography (HRCT) patterns specifically as UIP or nonspecific interstitial pneumonia (NSIP). This study of RA-ILD aimed to elucidate prognosis by using our modified HRCT pattern classification according to the latest guideline on idiopathic pulmonary fibrosis (IPF).

Methods: We analysed the medical records of 96 consecutive patients diagnosed as having RA-ILD. The modified HRCT classifications were defined as definite UIP, probable UIP, indeterminate for UIP (i.e., early UIP or NSIP/UIP), NSIP, organizing pneumonia (OP), NSIP+OP, and unclassifiable. Predictors of prognosis were determined using Cox regression models.

Results: Our RA-ILD cohort included definite UIP (21%), probable UIP (20%), indeterminate for UIP (30%) including NSIP/UIP (27%), alternative diagnosis (29%) including NSIP (14%), and other patterns. Interrater agreement for HRCT pattern was good (κ=0.75). Multivariate analysis showed that older age, history of acute exacerbation, and radiological honeycombing were negative prognostic factors of mortality.

Conclusions: NSIP/UIP pattern of indeterminate for UIP was the major pattern in RA-ILD. Although classifications of HRCT patterns were not related to survival, the presence of radiological honeycombing could be a useful predictor of poor prognosis, and acute exacerbation of ILD can seriously impact patient survival regardless of the presence of a UIP or indeterminate for UIP pattern. Our modified HRCT classification based on the latest IPF guideline might be useful to assess appropriate strategies of diagnosis in future RA-ILD studies, and radiological honeycombing could better predict poor prognosis rather than HRCT pattern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2019.11.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987998PMC
December 2019

Regulated Necrosis in Pulmonary Disease. A Focus on Necroptosis and Ferroptosis.

Am J Respir Cell Mol Biol 2020 05;62(5):554-562

Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan; and.

To date, increasing evidence suggests the possible involvement of various types of cell death in lung diseases. The recognized regulated cell death includes necrotic cell death that is immunogenic, releasing damage-associated molecular patterns and driving tissue inflammation. Necroptosis is a well-understood form of regulated necrosis that is executed by RIPK3 (receptor-interacting protein kinase 3) and the pseudokinase MLKL (mixed lineage kinase domain-like protein). Ferroptosis is a newly described caspase-independent form of regulated necrosis that is characterized by the increase of detrimental lipid reactive oxygen species produced via iron-dependent lipid peroxidation. The role of these two cell death pathways differs depending on the disease, cell type, and microenvironment. Moreover, some experimental cell death models have demonstrated shared ferroptotic and necroptotic cell death and the synergistic effect of simultaneous inhibition. This review examines the role of regulated necrotic cell death, particularly necroptosis and ferroptosis, in lung disease pathogenesis in the context of recent insights into the roles of the key effector molecules of these two cell death pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1165/rcmb.2019-0337TRDOI Listing
May 2020

Impact of radiological honeycombing in rheumatoid arthritis-associated interstitial lung disease.

BMC Pulm Med 2020 Jan 30;20(1):25. Epub 2020 Jan 30.

Department of Respiratory Medicine, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama, 330-8553, Japan.

Background: Interstitial lung disease (ILD) is the most common and important pulmonary manifestation of rheumatoid arthritis (RA). A radiological honeycomb pattern has been described in diverse forms of ILD that can impact survival. However, the clinical course and sequential radiological changes in the formation of the honeycomb pattern in patients with RA-ILD is not fully understood.

Methods: We evaluated the sequential changes in computed tomography findings in 40 patients with chronic forms of RA-ILD without the honeycomb pattern at initial diagnosis. We classified the patients into the Non-honeycomb group and Honeycomb group, and then analyzed the characteristics and prognosis of the two groups. The term "honeycomb formation" indicated a positive finding of honeycombing on any available follow-up CT.

Results: Our RA-ILD cohort included patients with probable usual interstitial pneumonia (UIP) (35%), nonspecific interstitial pneumonia (NSIP) (20%), and mixed NSIP/UIP (45%). Among all RA-ILD patients, 16 (40%) showed honeycomb formation on follow-up CT (median time between initial and last follow-up CT was 4.7 years). Patient characteristics and prognosis were not significantly different between the Non-honeycomb and Honeycomb groups. However, Kaplan-Meier survival curve for the time from the date of honeycomb formation to death showed a poor median survival time of 3.2 years.

Conclusions: A certain number of patients with RA-ILD developed a honeycomb pattern during long-term follow-up, regardless of whether they had UIP or NSIP. Prognosis in the patients with characteristics of both progressive ILD and honeycomb formation could be poor. Although radiological findings over the disease course and clinical disease behavior in RA-ILD are heterogenous, clinicians should be alert to the possibility of progressive disease and poor prognosis in patients with RA-ILD who form a honeycomb pattern during follow-up observation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-020-1061-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993451PMC
January 2020