ascorbic-acid and Lung-Diseases--Interstitial

The year 1995 marked the onset of interstitial pneumonia spread in Nagoya, Japan. For the last 9 years, we have been accumulating clinical experience with the disease control using the combination of prophylactic use of anti-biotics and regular practice of megadose vitamin C infusion with either dehydroepiandrosterone-annex or dehydroepiandrosterone-cortisol annex. The purpose of this study is to assess the usefulness of our new treatment system for the control of interstitial pneumonia alias chronic fatigue syndrome. The results obtained are given as follows: i) The long-term maintenance of the above treatment system was effective not only for decreasing the risk for recurrence of active form pneumonia, but also for prevention of malignancy emergence in aged patients with interstitial pneumonia. ii) Evidence is presented to indicate that interstitial pneumonia was associated with increased risk for depression of which the emergence is a candidate subject causally related to the long-term use of glucocorticoid. iii) A patient with both interstitial pneumonia and depression was found to be less responsive to our treatment system. It is suggested that the use of more dehydroepiandrosterone at the sacrifice of cortisol in the infusion annex may be a choice for the control of both interstitial pneumonia and depression. iv) The description of chronic fatigue syndrome as regards the endocrinological, epidemiological and psychiatric characteristics are in good agreement with our experience on patients having interstitial pneumonia, evidence in support of our proposal that there is no convincing reasoning to separate chronic fatigue syndrome from interstitial pneumonia. v) The long-term practice of our treatment system for the control of interstitial pneumonia (an autoimmune disease) was found to suppress the inflammatory process but not the fibrotic process in the long run. vi) A few innovations were made in our treatment system to reduce the risk of bleeding or thrombosis--vascular complications of pneumonia. vii) The merit of our treatment system is to create a new hormonal environment to improve the state of immunodeficiency by use of a non-steroid substance--vitamin C which encounters little resistance from the feedback mechanism of steroid metabolism in the in vivo system.

Topics: Adult; Aged; Ascorbic Acid; Dehydroepiandrosterone; Depression; Fatigue Syndrome, Chronic; Female; Follow-Up Studies; Humans; Hydrocortisone; Infusions, Intravenous; Lung Diseases, Interstitial; Male; Time Factors

The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents.. A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings.. In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis.. The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression.

Topics: Animals; Ascorbic Acid; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Mice; Pneumonia; Pulmonary Fibrosis; Tumor Microenvironment

Increasing evidence indicates that disequilibrium of the alveolar oxidant-antioxidant balance may play a role in the pathogenesis of chronic fibrosing lung diseases. Excessive production of oxidants and a differential regulation of antioxidant enzymes have been described under these conditions. We characterized for the first time numerous nonenzymatic low-molecular-weight antioxidants in bronchoalveolar lavage fluids from patients with different forms of lung fibrosis initiated either by injury to the alveolar epithelium (idiopathic pulmonary fibrosis, IPF) or by inflammation (chronic sarcoidosis/hypersensitivity pneumonitis). Footprints of oxidative stress accompanied by an increase in the majority of antioxidants assessed were observed in all patient groups: elevated levels of uric acid, ascorbic acid, retinol, and alpha-tocopherol were noted, whereas glutathione levels were unchanged. The expression of Nrf2, an important redox-sensitive transcriptional regulator of antioxidants, was increased in IPF lungs. Our findings were corroborated in the bleomycin model of lung fibrosis where--aside from uric acid--nonenzymatic antioxidants were elevated during the fibrotic phase. In conclusion, alveolar levels of nonenzymatic antioxidants are elevated in fibrosing lung diseases, but are incapable of restoring oxidative balance. This increase may be part of an adaptive response to oxidative stress. However, a leakage from the blood may also contribute to our findings.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Bronchoalveolar Lavage Fluid; Glutathione; Humans; Idiopathic Pulmonary Fibrosis; Immunohistochemistry; Inflammation; Lung Diseases, Interstitial; Oxidative Stress; Pulmonary Fibrosis; Rabbits; Uric Acid; Vitamin A