Integrated analysis reveals the protective mechanism and therapeutic potential of hyperbaric oxygen against pulmonary fibrosis.
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ABSTRACT:
SUBMITTER: Yuan Y
PROVIDER: S-EPMC7614583 | biostudies-literature | 2023 May
REPOSITORIES: biostudies-literature
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Integrated analysis reveals the protective mechanism and therapeutic potential of hyperbaric oxygen against pulmonary fibrosis.
Yuan Yuan Y Qiao Guoqiang G Zhou Jiajiao J Zhou Yilu Y Li Yali Y Li Xia X Jiang Zhenglin Z Wang Yihua Y Wang Yihua Y
Genes & diseases 20230501 3
Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive disease leading to death with few effective treatments. Our previous study suggested that repetitive hyperbaric oxygen (HBO) treatment alleviates bleomycin-induced pulmonary fibrosis in mice. Here, we investigated the protective mechanism of HBO treatment against pulmonary fibrosis using an integrated approach. Analyzing publicly available expression data from the mouse model of bleomycin-induced pulmonary f ...[more]
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Project description:IntroductionAlthough hyperbaric oxygen therapy (HBOT) has beneficial effects, some patients experience fatigue and pulmonary complaints after several sessions. The current limits of hyperbaric oxygen exposure to prevent pulmonary oxygen toxicity (POT) are based on pulmonary function tests (PFT), but the limitations of PFT are recognized worldwide. However, no newer modalities to detect POT have been established. Exhaled breath analysis in divers have shown volatile organic compounds (VOCs) of inflammation and methyl alkanes. This study hypothesized that similar VOCs might be detected after HBOT.MethodsTen healthy volunteers of the Royal Netherlands Navy underwent six HBOT sessions (95 min at 253 kPa, including three 5-min "air breaks"), i.e., on five consecutive days followed by another session after 2 days of rest. At 30 min before the dive, and at 30 min, 2 and 4 h post-dive, exhaled breath was collected and followed by PFT. Exhaled breath samples were analyzed using gas chromatography-mass spectrometry (GC-MS). After univariate tests and correlation of retention times, ion fragments could be identified using a reference database. Using these fragments VOCs could be reconstructed, which were clustered using principal component analysis. These clusters were tested longitudinally with ANOVA.ResultsAfter GC-MS analysis, eleven relevant VOCs were identified which could be clustered into two principal components (PC). PC1 consisted of VOCs associated with inflammation and showed no significant change over time. The intensities of PC2, consisting of methyl alkanes, showed a significant decrease (p = 0.001) after the first HBOT session to 50.8%, remained decreased during the subsequent days (mean 82%), and decreased even further after 2 days of rest to 58% (compared to baseline). PFT remained virtually unchanged.DiscussionAlthough similar VOCs were found when compared to diving, the decrease of methyl alkanes (PC2) is in contrast to the increase seen in divers. It is unknown why emission of methyl alkanes (which could originate from the phosphatidylcholine membrane in the alveoli) are reduced after HBOT. This suggests that HBOT might not be as damaging to the pulmonary tract as previously assumed. Future research on POT should focus on the identified VOCs (inflammation and methyl alkanes).
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Project description:Introduction: The hyperbaric oxygen treatment table 6 (TT6) is widely used to manage dysbaric illnesses in divers and iatrogenic gas emboli in patients after surgery and other interventional procedures. These treatment tables can have adverse effects, such as pulmonary oxygen toxicity (POT). It is caused by reactive oxygen species' damaging effect in lung tissue and is often experienced after multiple days of therapy. The subclinical pulmonary effects have not been determined. The primary aim of this study was to measure volatile organic compounds (VOCs) in breath, indicative of subclinical POT after a TT6. Since the exposure would be limited, the secondary aim of this study was to determine whether these VOCs decreased to baseline levels within a few hours. Methods: Fourteen healthy, non-smoking volunteers from the Royal Netherlands Navy underwent a TT6 at the Amsterdam University Medical Center-location AMC. Breath samples for GC-MS analysis were collected before the TT6 and 30 min, 2 and 4 h after finishing. The concentrations of ions before and after exposure were compared by Wilcoxon signed-rank tests. The VOCs were identified by comparing the chromatograms with the NIST library. Compound intensities over time were tested using Friedman tests, with Wilcoxon signed-rank tests and Bonferroni corrections used for post hoc analyses. Results: Univariate analyses identified 11 compounds. Five compounds, isoprene, decane, nonane, nonanal and dodecane, showed significant changes after the Friedman test. Isoprene demonstrated a significant increase at 30 min after exposure and a subsequent decrease at 2 h. Other compounds remained constant, but declined significantly 4 h after exposure. Discussion and Conclusion: The identified VOCs consisted mainly of (methyl) alkanes, which may be generated by peroxidation of cell membranes. Other compounds may be linked to inflammatory processes, oxidative stress responses or cellular metabolism. The hypothesis, that exhaled VOCs would increase after hyperbaric exposure as an indicator of subclinical POT, was not fulfilled, except for isoprene. Hence, no evident signs of POT or subclinical pulmonary damage were detected after a TT6. Further studies on individuals recently exposed to pulmonary irritants, such as divers and individuals exposed to other hyperbaric treatment regimens, are needed.
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Project description:Hyperbaric oxygen therapy (HBOT) is known to be associated with pulmonary oxygen toxicity. However, the effect of modern HBOT protocols on pulmonary function is not completely understood. The present study evaluates pulmonary function test changes in patients undergoing serial HBOT. We prospectively collected data on patients undergoing HBOT from 2016-2021 at a tertiary referral center (protocol registration NCT05088772). Patients underwent pulmonary function testing with a bedside spirometer/pneumotachometer prior to HBOT and after every 20 treatments. HBOT was performed using 100% oxygen at a pressure of 2.0-2.4 atmospheres absolute (203-243 kPa) for 90 minutes, five times per week. Patients' charts were retrospectively reviewed for demographics, comorbidities, medications, HBOT specifications, treatment complications, and spirometry performance. Primary outcomes were defined as change in percent predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75), after 20, 40, and 60 HBOT sessions. Data was analyzed with descriptive statistics and mixed-model linear regression. A total of 86 patients were enrolled with baseline testing, and the analysis included data for 81 patients after 20 treatments, 52 after 40 treatments, and 12 after 60 treatments. There were no significant differences in pulmonary function tests after 20, 40, or 60 HBOT sessions. Similarly, a subgroup analysis stratifying the cohort based on pre-existing respiratory disease, smoking history, and the applied treatment pressure did not identify any significant changes in pulmonary function tests during HBOT. There were no significant longitudinal changes in FEV1, FVC, or FEF25-75 after serial HBOT sessions in patients regardless of pre-existing respiratory disease. Our results suggest that the theoretical risk of pulmonary oxygen toxicity following HBOT is unsubstantiated with modern treatment protocols, and that pulmonary function is preserved even in patients with pre-existing asthma, chronic obstructive lung disease, and interstitial lung disease.
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Project description:BackgroundIncreased expression of nitric oxide synthase (NOS) and an increase in plasma nitrite plus nitrate (NOx) have been reported in patients with pulmonary fibrosis, suggesting that nitric oxide (NO) plays an important role in its development. However, the roles of the entire NO and NOS system in the pathogenesis of pulmonary fibrosis still remain to be fully elucidated. The aim of the present study is to clarify the roles of NO and the NOS system in pulmonary fibrosis by using the mice lacking all three NOS isoforms.MethodsWild-type, single NOS knockout and triple NOS knockout (n/i/eNOS-/-) mice were administered bleomycin (BLM) intraperitoneally at a dose of 8.0 mg/kg/day for 10 consecutive days. Two weeks after the end of the procedure, the fibrotic and inflammatory changes of the lung were evaluated. In addition, we evaluated the effects of long-term treatment with isosorbide dinitrate, a NO donor, on the n/i/eNOS-/- mice with BLM-induced pulmonary fibrosis.ResultsThe histopathological findings, collagen content and the total cell number in bronchoalveolar lavage fluid were the most severe/highest in the n/i/eNOS-/- mice. Long-term treatment with the supplemental NO donor in n/i/eNOS-/- mice significantly prevented the progression of the histopathological findings and the increase of the collagen content in the lungs.ConclusionsThese results provide the first direct evidence that a lack of all three NOS isoforms led to a deterioration of pulmonary fibrosis in a BLM-treated murine model. We speculate that the entire endogenous NO and NOS system plays an important protective role in the pathogenesis of pulmonary fibrosis.
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