Autism Street

There’s another “hyperbaric therapy as a treatment for autism” study underway. It appears to be headed up by Dr. Rossignol, and has three clinical locations supervised by Doctors Liz Mumper (Virginia), Cindy Schneider (Arizona) and Jeff Bradstreet (Florida) - none of which appear (according to a search at ABMS) to have board certification in Developmental-Behavioral Pediatrics, Child Neurology, Neurodevelopmental Disabilities or Undersea & Hyperbaric Medicine.

In his recent interview, Dr. Rossignol apparently acknowledged some criticism/skepticism (see comments of linked post) of the use of less than 1.3 ATA hyperbaric therapy as a potential autism treatment. The entire interview is available online for anyone interested (simply Google the title), but I intend to comment only on a couple of points.

For the moment, set aside anything you may know about the role of hemoglobin in oxygen transport and how the minute increases (probably around 3-4%) in total blood oxygen content afforded by this kind of hyperbaric therapy, or simple O2 therapy, are likely to be insignificant. 

From: D.A. Rossignol, T. Small/Medical Veritas 3 (2006) 1–4
Interview with Dr. Dan A. Rossignol: Hyperbaric Oxygen Therapy Improves Symptoms in Autistic Children

Dr. Rossignol states:

Some people have criticized using mild hyperbarics at 1.3 ATA because they state that when compared to this pressure, you can get just as high an oxygen concentration in the blood with oxygen by face mask without a chamber. And this may be true in some cases.

Please correct me if I have made any errors in the calculations below. The quantity of oxygen that will dissolve into blood plasma is a direct function of PO2 that includes both the percentage of oxygen in the inspired air and the atmospheric pressure, with well-known constants for dissolution. PO2 of Air at 1.0 ATA is approximately 159 mmHg, PO2 of enriched air (24% O2) at 1.29 ATA is approximately 235 mmHg, and PO2 with supplemental oxygen via face mask at 5-8 lpm and 1.0 ATA is approximately 266-418 mmHg (depending on respiratory attributes). From that point on, anything that impacts the oxygen cascade affects it regardless of the original PO2 source.

Note: Even higher FIO2 is achievable with simple partial rebreather mask - FIO2 50-70% @ 6-10 lpm

*Source: National Institutes of Health - Critical Care Medicine Department, Critical Care Therapy and Respiratory Care Section Category: Clinical, Section: Medicinal Gas Therapy, Title: Oxygen Therapy Procedure, Policy: 01, Revised: 02/02  

So, it would seem likely to be true in MOST (if not all) cases, that you will get a higher oxygen concentration into the blood by using simple supplemental O2 via mask without a hyperbaric chamber, compared to mild hyperbarics as being tested.

Dr. Rossignol also states:

However, we must remember we are dealing with 2 separate components with HBOT—the oxygen and the pressure. So it appears that many of the effects of HBOT are from the increased oxygen, but we cannot dismiss the pressure effect. I think we need more studies on this as well.

To my knowledge there are no such studies indexed on Pubmed specific to the effects of atmospheric pressure and autism at all. This looks more like it could be a hypothesis on his part. It would be ethical to test this hypothesis (which could be done in an appropriate hyperbaric facility that can isolate application of atmospheric pressure with gas mixture control to maintain normal oxygenation characteristics).

Only after benefit is proven for the application of pressure alone or for pressure and oxygen enrichment combined, would the sale of hyperbaric slightly enriched air therapy to individuals or insurance companies as a treatment for autism be appropriate. Otherwise, if the benefits of mild hyperbarics (~1.29 ATA) are confined to enriching the blood with oxygen, then it would seem much more appropriate to deliver this oxygen with home oxygen equipment for about $200 per month (typical rental price for high-flow oxygen concentrators), rather than suggesting the much higher priced mild hyperbaric therapy.

Addendum 28 Jul 2006: Dr. Rossignol refers to a pressure study in his interview:

A study from 2002 I recently came across shows that the decrease in inflammation obtained with HBOT is due to the increased pressure provided by HBOT, not necessarily by the increased oxygen. In the study I am referring to, hyperbaric pressure (without oxygen) caused a decrease in inflammation, whereas 100% oxygen without the pressure did not decrease inflammation at all.

The study Dr. Rossignol is referring to (confirmed by him via e-mail):

Undersea Hyperb Med. 2002 Fall;29(3):216-25.

Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans.

This study examines the effects of hyperoxia, increased atmospheric pressure, and hyperbaric oxygen on cytokine synthesis. Five healthy volunteers were exposed to 90 min of room air, 100% oxygen, 10.5% oxygen at 2 atm abs, or 100% oxygen at 2 atm abs (HBO2). All subjects were blinded and randomly exposed to each of the 4 conditions. Immediately before entering the chamber, immediately after exposure, and 3 and 24 h later, blood was drawn and stimulated ex vivo with phorbol myristate acetate (PMA) and phytohemagglutinin A (PHA). Since lymphocytes are the primary source of PMA/PHA-induced interferon-gamma (IFN-gamma), these results were expressed as IFN-gamma production per 10(6) lymphocytes. Following the HBO2 exposure, PMA/PHA-stimulated lymphocytes released 51% less IFN-gamma than cells obtained before the exposure. This suppression persisted for 24 h following HBO2 (P < 0.05). Surprisingly, increased atmospheric pressure alone also inhibited IFN-gamma secretion (P < 0.05). Room air and hyperoxia alone had no significant effect upon IFN-gamma release. HBO2's anti-inflammatory effect may, in part, be due to inhibition of IFN-gamma release.

A. This small in vivo study is at 2.0 ATA, not 1.29 (this is a significant difference).

B. Possible anti-inflammatory effect by the same proposed mechanism (IFN-gamma release inhibition) at 1.29 ATA would still appear to be pure hypothesis.

C. Although in vitro, there was apparently a follow-up study about this proposed mechanism.

Clin Exp Immunol. 2003 Oct;134(1):57-62.

Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages

Increased atmospheric pressure alone does not affect stimulus-induced cytokine synthesis

Previous investigations have shown that increased atmospheric pressure can affect such cellular functions as interferon- g secretion [16] and apoptosis [17,18]. To assess the effects of increased atmospheric pressure on cytokine production, monocytemacrophages were cultured in 8.75% O2, 2.1% CO2 at 2.4 ATA (increased atmospheric pressure). We used 8.75% O2 and 2.1% CO2 so that cells at 2.4 ATA would be exposed to the equivalent of 21% O2, 5% CO2 at sea level. When compared to cells cultured in normoxia at sea level, up to 12 h of increased atmospheric pressure did not affect IL-1 b or TNF- a synthesis (data not shown).

Note: [16] References the 2002 study in Undersea Hyperb Med.