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Pulmonary Function Following Hyperbaric Oxygen Therapy: A Longitudinal Observational Study

Connor T. A. Brenna, Shawn Khan, George Djaiani, Darren Au, Simone Schiavo, Mustafa Wahaj, Ray Janisse, Rita Katznelson

Abstract
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.

Introduction
Hyperbaric oxygen therapy (HBOT) has been recognized as a valuable intervention for a variety of acute and chronic conditions (S1 Table) [1, 2]. Treatment protocols include repeated sessions of exposure to 100% oxygen (O2) at 1.3–2.8 atmospheres absolute (ATA) or 132–284 kPa for a predetermined amount of time per session, with a variable number of sessions per week and up to 60 total sessions depending on the indication. Although individual treatments may incorporate air breaks to avoid potential pulmonary and neurological O2 toxicity, the cumulative effect of multiple longitudinal sessions of HBOT on pulmonary function is not completely understood.

Materials and Methods
Patient demographic data and past medical history characteristics were summarized using descriptive statistics, and continuous data were expressed as means ± standard deviations. Linear mixed effect regression models were used to estimate the adjusted sample mean scores of PFT outcomes FEV1%, FVC%, and FEF25-75% at each timepoint for the cohort. Timepoint was included as the fixed effect and individual subject as the random effect for each outcome for the overall cohort. PFT outcomes were also modeled for subgroups by timepoint interaction for pre-existing respiratory disease, smoking status, and treatment pressure (in ATA). Similarly, individual subjects were included as random effects. The maximum likelihood estimation was used to prepare the mixed models and analyzed under the intention-to-treat principle. Post-hoc pairwise comparisons between timepoints were conducted for each grouping of pre-existing respiratory disease, smoking status, and treatment pressure, for each PFT variable. Pairwise comparisons were adjusted using Tukey’s HSD.

Results
The results of PFTs performed at baseline (n = 86) and after 20 (n = 81), 40 (n = 52), and 60 (n = 12) treatments are illustrated in Fig 2. There was no significant change in FEV1%, FVC%, or FEF25-75% across the four timepoints. A subgroup analysis comparing patients with and without pre-existing respiratory disease is presented in Fig 3. Among those with pulmonary comorbidities, 14 patients completed PFTs at baseline, 14 after 20 treatments, and 11 after 40 treatments. No patients in this group underwent 60 treatments. Among those without pulmonary comorbidities, 72 completed PFTs at baseline, 67 after 20 treatments, 41 after 40 treatments, and 12 after 60 treatments.

Discussion
 This study is among the largest describing PFT changes in patients undergoing repetitive HBOT, and we report on a representative sample which is broadly generalizable to other conventional HBOT treatment facilities. Subgroup analysis identified that patients with pre-existing lung disease and those who currently or formerly smoked tended to have a greater degree of mild-to-moderate PFT abnormality at baseline; despite this, there were no significant changes in PFT trends during HBOT among these subgroups. Patients treated at 2.0 ATA (203 kPa) similarly exhibited a greater degree of mild abnormality at baseline (in all three parameters, although most markedly in FEV1%, reflecting baseline differences in large airway performance). The reason for this is unclear; we speculate that providers may have elected to use more conservative treatment protocols among patients with high-risk features or whose pulmonary function already exhibited some degree of impairment prior to treatment.

Conclusion
The present study provides further evidence for the safety profile of HBOT, both with respect to potentially insidious consequences of treatment on pulmonary function and to acute iatrogenic injury. Our analysis of a large cohort of patients undergoing serial HBOT with periodic PFTs offers clarity to conflicting reports in the extant literature, demonstrating no significant changes in critical markers of dynamic lung function over the course of treatment. Our data also illustrate this finding in patients with prior respiratory disease or smoking histories. Future directions for this work include dose-finding studies for the safe maximum treatment pressure and duration to maximize therapeutic possibilities without impairing pulmonary function, investigations of possible delayed effects of HBOT on pulmonary function in the long term, and experiments to further characterize parenchymal changes in the hyperoxic response which may take place at the sub-clinical level.
Citation: Brenna CTA, Khan S, Djaiani G, Au D, Schiavo S, Wahaj M, et al. (2023) Pulmonary function following hyperbaric oxygen therapy: A longitudinal observational study. PLoS ONE 18(5): e0285830. https://doi.org/10.1371/journal.pone.0285830

Editor: Eman Sobh, Al-Azhar University, EGYPT

Received: November 8, 2022; Accepted: May 2, 2023; Published: May 31, 2023

Copyright: © 2023 Brenna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The source data from our study cannot be shared publicly, in full, because of an ethical restriction levied by our institutional research ethics board. This is because the data contains sensitive information from patient’s medical charts (e.g., birth dates and personal health information). Taken together, this information may allow for the identification of individual study participants. We offer that an anonymized minimal data set can be prepared in aggregate and made available upon reasonable request via email to the study’s first author (connor.brenna@mail.utoronto.ca) or the Hyperbaric Medicine Unit, Toronto General Hospital, Toronto, Ontario, Canada (hyperbaricmedicineunit@uhn.ca).

Funding: CTAB gratefully acknowledges the William S. Fenwick Research Fellowship received from the University of Toronto Temerty Faculty of Medicine in support of this study.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RK is a shareholder in the Rouge Valley Hyperbaric Medical Center, Toronto, ON. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Abbreviations: HBOT, hyperbaric oxygen therapy; O2, oxygen; POT, pulmonary oxygen toxicity; ATA, atmosphere absolute; PFT, pulmonary function test; FEV1, percentage of predicted forced expiration volume in one second; FVC, percentage of predicted forced vital capacity; FEF25-75%, percentage of predicted mid-expiratory flow; DC, diffusion capacity; PEF, peak expiratory flow; RV,

residual volume; TLC, total lung capacity; VC, vital capacity; UPTD, unit of pulmonary toxic dose

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285830#sec009
 

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