Effect Measure

A new class of air pollutant?

I used to joke that the only plan the Bush administration had for dealing with air pollution was to put all the free radicals in jail. If you don’t know what a free radical is, it is a highly reactive form of a chemical, usually involving an unpaired electron. Radicals often are short lived intermediates in other reactions and can have half lives in the microseconds or less. In any event we’re talking seconds. It is free radicals that are formed by ionizing radiation. They quickly react with whatever chemicals are in their vicinity and if that chemical happens to be your genetic material, you can get the kind of programming error that leads to cancer.

Now a combustion chemist is reporting a new kind of free radical which he calls a “persistent free radical,” almost a chemical oxymoron:

Most atmospheric free radicals exist for less than a second. What’s different and distressing about the substances Dellinger found, he said, is that they persist.

The process begins when combustion in an industrial smokestack, automotive tailpipe or even a household chimney releases fine particles of unburned material, such as soot.

As the gases begin to cool, altered versions of chemicals in the exhaust – the persistent free radicals – form and attach themselves to the soot particles.

A substance’s persistent free radicals may be more toxic than the substance itself, [H. Barry Dellinger, Dellinger, Patrick F. Taylor Chair of Environmental Chemistry at Louisiana State University] said.

Bill Suk, acting deputy director of the National Institute of Environmental Health Sciences, said the research was “significant” because “it takes the monitoring and the exposure of products of incomplete combustion to yet another level of potential impact on people’s health.”

Whether it actually affects people’s health, however, remains unknown, he said. (Philadelphia Inquirer)

In recent years air pollution epidemiologists have shown that levels of fine particles are strongly related to daily morbidity and mortality. But measurement of particulates in the air is related only to their size (technically not their physical size but the size of standard particles that have the same aerodynamic behavior). They can be made of anything: heavy metals, sand, vegetable fiber, whatever. But clearly the chemical composition makes a biological difference. If some of these particles are actually free radicals, they are even more significant.

This was a news report of a paper given at the American Chemical Society’s annual meeting, so I’m not sure what allows these particles to persist in this highly reactive form. There is so much science news these days that separating the wheat from the chaff is becoming increasingly difficult. This work seems to have gotten the attention of the number two person, Bill Suk, at NIH’s main institute for research into the basic science of environmental health.

We breathe about 20 cubic meters of air a day, i.e., the volume of air in a cube 20 2.7 meters on a side. That’s a lot of air. Trying to figure out exactly what are the harmful agents in the complicated physical and chemical mixtures in the modern urban air shed is a daunting task.

If this is indeed a new, general class of pollutant it is a significant finding. Once there is a way to measure it accurately, some good epidemiology is called for. We know how to do these epidemiological studies using sized particulate measurements. They are expensive and time consuming but have revealed extremely valuable information. If we can sharpen the exposure assessments by better characterizing the active components in fine particulates we may be able to make a qualitative advance in our understanding of the health effects of air pollution.

We’ll have to see.


  1. #1 Michael Albert
    August 29, 2008

    “We breathe about 20 cubic meters of air a day, i.e., the volume of air in a cube 20 meters on a side. ”

    Bzzzt. That’d be the volume of air in a cube about 2.7m on a side. Unless of course we actually breathe 8000 cubic metres of air a day, but somehow I doubt that!

  2. #2 song
    August 29, 2008

    A cube with a 20 m side contains 20^3 = 8000 cubic metres of air.

    Sorry for picking on details. Interesting post!

  3. #3 revere
    August 29, 2008

    Michael, song: My face is red. Yes, a serious mental lapse on the part of a tired grandpa who had his 15 month old for the day (daycare is closed last week of August!). Thanks you. It has been corrected.

  4. #4 Ren
    August 29, 2008

    Nice catch on the math. Now, about these persistent radicals (which is an awesome name for a punk rock band, by the way)… I’m racking my brain over it, and I can’t see under what circumstances the free electron would stay that way without pairing up with something else (or with other radicals). This is very, very interesting.

    Curiouser and curiouser.

  5. #5 daedalus2u
    August 29, 2008

    Nitric oxide, NO has an unpaired electron and so can be considered a “free radical”. It is a stable molecule and is stable indefinitely at ambient temperatures. It is quite reactive, but only with some things.

    Radicals tend to react at near diffusion limited kinetics with each other. That is why flames react so quickly, they are composed almost entirely of free radicals which are thermally generated and propagated. Free radicals can also initiate free radical chain reactions where as radicals are consumed, more are generated leading to a self-sustaining chain reaction. Lipid peroxidation occurs via this mechanism.

    Your nasal passages put a few hundred ppb NO into the air that you breath. That NO would react with any free radicals by the time they reached your lungs. The adverse effects of these particulates containing free radicals are likely to be on the nasal passages where that NO is produced. Nitric oxide synthase generates NO, but it also can generate superoxide (which is a charged free radical). NO and superoxide react at near diffusion controlled kinetics (more than 10^9 L mol?1 s?1) and make peroxynitrite which has the effect of oxidizing a critical Zn-thiol couple in NOS making it “uncoupled” so it produces only superoxide. Peroxynitrite is quite reactive, but it is not a “free radical”. NO does detoxify the effects of peroxynitrite, so when excess NO is present, the oxidizing effects of peroxynitrite are not observed.

    This could be one of the mechanisms by which inhaled particles decrease NO levels and cause/exacerbate heart disease and lung problems.

    To stop propagating chain reactions, something that reacts with a free radical and quenches the chain reaction is necessary. Those are what anti-oxidants are. A small concentration of antioxidant can prevent the propagation of free radical chains before they do much damage.

    Nitric oxide happens to be an absolutely fabulous antioxidant, some 3000 times better than vitamin E.

  6. #6 natural cynic
    August 29, 2008

    This explains why it may not be a good idea to exercise in a polluted environment. Ventilation during moderate aerobic exercise will increase by about five-fold and those in serious training might increase ten-fold. This would increase exposure to these free radicals by the same amount so transiently overloading the lung’s antioxidant capacity.

  7. #7 David Marjanovi?
    August 29, 2008

    The more the position of the unpaired electron is smeared out over more space, the more stable the radical is. Ultimately this comes from Heisenberg’s uncertainty relation.

  8. #8 daedalus2u
    August 29, 2008

    NC, exactly. Because of the properties of nitric oxide synthase becoming uncoupled, a transient overload of nasal antioxidant capacity can become long term, even permanant.

  9. #9 Militant Agnostic
    August 30, 2008

    I see another marketing opportunity for the supplement peddlers.

    Deadalus – do you think breating through your mouth while exercising would increase the possible harm done by these radicals significantly?

  10. #10 Jonathon Singleton
    August 31, 2008

    My former editor-employer, Gavin McGuren, currently working with Oz’s GAYinWA dot com @ http://www.gayinwa.com.au/ , actually named my late 90s newspaper column FREE RADICAL as yours truly pretty much hyperactivated like an “unpaired electron” — still do:*)

    I just read “An Open Letter to God”, from Michael Moore (Sunday, August 31, 2008) and he does remind me of me back in the late 90s — an ironic political irreverancy in the time before a storm is so like a FREE RADICAL. It may have been a crime to believe in a transgenic pandemic back in the late 90s but at least I was fed in the Aussie loonybin… If Gustav fracks New Orleans, will the Bush administration continue past dysfunctional and delusional behavioral patterns!?!

    PS: I can’t be bothered voting in the West Oz state election cos the tosser bureaucrats in gov admin will continue to behave like sociopathic homophobe-retards in spite of JIM McGINTY MLA ATTORNEY GENERAL, MINISTER FOR HEALTH; ELECTORAL AFFAIRS FOR WESTERN AUSTRALIA’s words (see below)…

    Saturday, May 31, 2008
    Re: Our ref: 22-015231 email (Tuesday, May 27, 2008 11:51 PM)
    Howdy Jim,
    Ta for acknowledging my e-mail dated 22 May 2008 — an excerpt from your response has been posted by me — freelance transgenic pathogen research analyst — at a workplace blog (see my reader posting linked in H5N1 blog below). I’ve attached an email containing a jpg which outlines a series of questions in my initial 12th Nov, 2001 FOI application. Only a few of these questions have actually been responded to and some documents received by me have been blanked out and censored — eg. the names of taxpayer funded homophobic queer-bashing police officers, no doubt now [languishing like toxic cockroaches in five] hundred thousand dollar suburban homes whilst I struggle on medical benefits.
    A question re: your response: are WA government employees going to continue acting like complete toss-pots vis a vis my emailed requests for info, or what (see FOI’s Tim Kennedy attached email)!?!
    H5N1 Blog — A digression into US politics (May 18, 2008)

    Refer to reader response posting by:Jonathon Singleton (May 27, 2008)

  11. #11 daedalus2u
    August 31, 2008

    MA, yes I think breathing through your mouth does have adverse effects which usually are slight.

    Nitric oxide is normally one of the things that reduces inflammation and keeps things in check. Low NO does increase the sensitivity of mast cells to degranulation, and I think that is part of the problem when hypersensitivity occurs.

    What is interesting about mouth breathing is that in COPD, resolution of breathlessness takes longer using mouth breathing than when breathing through a mask (where presumably there is some nasal breathing). Breathing air or O2 made no difference (p= 0.15 mouth, p=0.32 mask) but breathing O2 or air through a mask was much better than breathing either through the mouth with a nose clip (p=0.04). This data is given in the last couple of paragraphs before the discussion.


    See the comment which specifically discusses this finding.


    They discuss potential changes in the mechanics of breathing, but I have another explanation. My conclusion is that some of the dyspnoea of COPD is not solely due to O2 or CO2 levels but also involves NO levels. It is known that S-nitrosothiols do regulate breathing, but the details are much less well understood than how O2 or CO2 regulate it. Nose breathing would increase NO levels delivered to the lung slightly. Presumably it is enough to be physiologically relevant (or evolution would not have configured it to happen).

    I speculate that it is the acute reduction in NO levels that occur during acute stress that trigger hyperventilation. If you need to “run from a bear”, you need to maximize gas exchange ASAP so you don’t get into O2 debt or CO2 excess during your escape. I think it is the reduction in NO levels that trigger that. Until the NO levels get back up, the person is going to feel breathless. Breathing O2 even through the nose may cause difficulty if nitric oxide synthase becomes uncoupled.

  12. #12 revere
    August 31, 2008

    daedalus: Very interesting. My minor comment is that without seeing the actual ambient air versus O2 data I can’t tell whether there was a difference or not. p-values aren’t measures of effect (as in “effect measure”) but of estimate stability. Thus a p-value of .15 merely means that the existing difference would have a one in seven chance of occurring IF there was in fact no difference and all measurements were unbiased (without systematic error). It doesn’t mean there was no difference, only that whatever the values for each, random variation as an explanation could not be taken off the table. Minor, nit picking point unless there was in fact a large difference that was not significant because of few sample points. I couldn’t see the original paper as it was behind a subscription fire wall (BMJ used to be Open Access until Fiona Godlee took it over; ironically she came from BMC, an open access publisher).

  13. #13 daedalus2u
    August 31, 2008

    Revere, I think it is free if you register. I can see the whole paper and I haven’t paid them anything, but I have registered so their black helicopters are able to track me down. I sent you the pdfs, so you can remain secure in your undisclosed location.

    You are correct; a p value in isolation doesn’t mean much. It was an n of 18, which isn’t great, but if the breathlessness problem in COPD were due to lack of O2, pure O2 should resolve that a lot faster than air at 21% O2. I would have liked to see O2 saturations too, but they didn’t include that data. I suspect there isn’t a good inverse correlation between O2 saturations and breathlessness. If there was, I presume they would use the instrumental measure instead.

    I am starting to think that the problem of COPD may be low NO in the lung, the same way that I think most of the other degenerative diseases are due to low NO in that organ system. Exactly how that might work in the lung is not clear to me. Any kind of chronic inflammation is going to cause lower NO due to destruction by superoxide. That will produce mast cell hyper reactivity which will exacerbate inflammation. Once the lung degrades enough to cause systemic hypoxia, even if only episodically, that could cause low NO stuff to get worse too.

    If the problem in COPD is not enough NO, giving O2 may accelerate the decline. Once the lung degrades enough there may not be another alternative to giving O2.

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