Background Although the risk factors for coronavirus disease 2019 (COVID-19) mortality have been identified, there is limited information about the risk factors for disease progression after hospitalization among Japanese patients with COVID-19 exhibiting no or mild symptoms. Methods All 302 consecutive patients who were admitted to our institutions and diagnosed with COVID-19 between March and December 2020 were retrospectively assessed. Ultimately, 210 adult patients exhibiting no or mild symptoms on admission were included in the analysis. They were categorized into the stable (no oxygen needed) and worsened (oxygen needed) groups, and their characteristics and laboratory data were compared. Results Among 210 patients, 49 progressed to a severe disease stage, whereas 161 did not. The mean patient age was 52.14 years, and 126 (60.0%) patients were male. The mean body mass index (BMI) was 23.0 kg/m2, and 71 patients were overweight (BMI ≥ 25 kg/m2). Multivariate logistic analysis showed that old age, overweight, diabetes mellitus (DM), and high serum ferritin levels were independent risk factors for disease progression. Conclusions Clinicians should closely observe patients with COVID-19, especially those with risk factors such as old age, overweight, DM, and high serum ferritin levels, regardless of whether they have no or mild symptoms.
BackgroundThe role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been clarified. We previously demonstrated DNA damage in murine bronchioles in the early stages of bleomycin-induced pulmonary fibrosis that subsequently extended to alveolar cells at the advanced stages of the disease. Club cells are progenitor cells for bronchioles and are known to play protective roles against lung inflammation and damage. The aim of the present study was to elucidate the role of club cells in the development of pulmonary fibrosis.MethodsC57BL/6 J mice received naphthalene intraperitoneally on day −2 to deplete club cells and were given intratracheal bleomycin or a vehicle on day 0. Lung tissues were obtained on days 1, 7, and 14, and bronchoalveolar lavage was performed on day 14. Bronchiolar epithelial cells sampled by laser capture microdissection were analyzed by gene expression microarray analysis on day 14.ResultsClub cell depletion induced by naphthalene protected mice from bleomycin-induced lung injury and fibrosis. Bleomycin-triggered bronchiolar TGF-β1 expression was reduced. Gene expression microarray analysis revealed that genes associated with inflammatory response and chemokine activity were downregulated in the bleomycin-injured bronchiolar epithelium with club cell injury compared to that in bronchiolar epithelium without cell injury.ConclusionsClub cells are involved in the development of lung injury and fibrosis.
Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice. C57BL/6J mice received naphthalene (200 mg/kg) intraperitoneally on day 0. Gefitinib (250 or 300 mg/kg) was orally administered to mice from day -1 until day 13. Sivelestat (150 mg/kg) was administered intraperitoneally from day 1 until day 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14. Sivelestat treatment significantly reduced the protein level, neutrophil count, neutrophil elastase activity in BALF, and severity of histopathologic findings on day 14 for mice administered with 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved the survival of mice administered with 300 mg/kg of gefitinib. These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.
Bax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits the activation of Bax.The purpose of this study was to investigate whether the control of Bax activity by BIP-V5 reduces the degree of bleomycin-induced lung injury. C57BL/6J mice were administered bleomycin and BIP-V5 intratracheally on day 0. Bronchoalveolar lavage fluid and lung tissue were obtained on day 7. Human pulmonary alveolar epithelial cells (A549 cells) and mouse pulmonary alveolar epithelial cells (LA-4 cells) were stimulated with bleomycin to induce apoptosis.Administration of BIP-V5 improved the survival rate and degree of bleomycin-induced lung injury by suppressing Bax activation in mice. BIP-V5 treatment decreased bleomycin-induced apoptosis of alveolar epithelial cell lines (A549 cells and LA-4 cells) by suppressing Bax activation. These results indicate that administration of BIP-V5 may constitute a novel therapeutic strategy against lung injury.
Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice. C57BL/6J mice received naphthalene (200 mg/kg) intraperitoneally on day 0. Gefitinib (250 or 300 mg/ kg) was orally administered to mice from day À1 until day 13. Sivelestat (150 mg/kg) was administered intraperitoneally from day 1 until day 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14. Sivelestat treatment significantly reduced the protein level, neutrophil count, neutrophil elastase activity in BALF, and severity of histopathologic findings on day 14 for mice administered with 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved the survival of mice administered with 300 mg/kg of gefitinib. These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.
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