EPA Research on Ultrafine Particulate Matter

White Hat Bias

Hyping environmental and so-called toxic risk has gone on so long that many Americans have no sense of the truth when it comes to the causal consequences of personal, occupational, and environmental exposures.  Recently, I listened to a lecture given by Judge Calibresi of the Second Circuit.  In the course of talking about regulatory prohibitions and tort-law incentives, he told of his visit to the late Professor Bickel, who had then just been diagnosed with brain cancer.  In his lecture, Judge Calibresi stated that he knew that Bickel’s brain cancer was caused by his smoking, and went on to muse whether banning smoking would have saved his friend’s life.  Judge Calibresi’s ruminations upon the nature of regulation and tort law were profound; his cursory hipshot about what caused his friend’s terminal illness, juvenile.

Some years ago, a science journalist published an account of how dire predictions of asbestos deaths had not come to pass.  Tom Reynolds, “Asbestos-Linked Cancer Rates Up Less Than Predicted,” 84 J. Nat’l Cancer Instit. 560 (1992)

Reynolds quoted one scientist as saying that:

“the government’s exaggeration of the asbestos danger reflects a 1970s’ Zeitgeist that developed partly in response to revelations of industry misdeeds.  ‘It was sort of the “in” thing to exaggerate … [because] that would be good for the environmental movement’….  ‘At the time it looked like you were wearing a white hat if you made these wild estimates. But I wasn’t sure whoever did that was doing all that much good.”

Id. at 562.  Reynolds’ quote captures the nature of “white-hat” bias, a form of political correctness applied to issues that really depend upon scientific method and data for their resolution.  Perhaps the temptation to overstate the evidence against a toxic substance is unavoidable, but it diminishes the authority and credibility of regulators entrusted with promulgating and enforcing protective measures.

White-Hat Bias & Black-Hat Ethics

I recently came across a disturbing article in the Environmental Health Perspectives, a peer-reviewed journal, supported by the National Institute of Environmental Health Sciences, National Institutes of Health, United States Department of Health and Human Services.  The article detailed a case report of an individual woman experimentally exposed to ultrafine particulate matter (PM 2.5) in a test chamber.  Andrew J. Ghio, Maryann Bassett, Tracey Montilla, Eugene H. Chung, Candice B. Smith, Wayne E. Cascio, and Martha Sue Carraway, “Case Report: Supraventricular Arrhythmia after Exposure to Concentrated Ambient Air Pollution Particles,” 120 Envt’l Health Perspect. 2275 (2012) [Ghio article].  There were no controls.

The point of the case report was that a person exposed to PM 2.5, experimentally, experienced a “cardiac event,” (atrial fibrillation or AFib) which resolved after cessation of exposure.  The experiment was conducted in a federal agency facility, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Chapel Hill, North Carolina.

The authors stated that the experiment had the approval of the University of North Carolina School of Medicine Committee on the Protection of the Rights of Human Subjects. Given that the EPA has made extraordinary claims about the harmfulness of PM 2.5, including heart disease, lung disease, and cancers, and that there was no imaginable benefit to the subject from participating in the experiment, this experiment seemed dubious indeed.  The narrative of the case report, however, reveals even more disturbing information about the potential improprieties of the human experiment.

The PM Chamber

The human guinea pig was 58 years old.  Her age is significant. Although the authors claim that AFib is uncommon among those under 60, it does increase with age.  The human subject in the published experiment was close to the age at which AFib is no longer uncommon, and she was unwell to begin with.

The case report notes that the human subject had previously participated in the same exposure “protocol” without “complications.”  The report does not explain why this human subject was returning to the EPA center for being placed in a “chamber,” and being exposed sequentially to “filtered air and concentrated ambient particles (CAPs).” The implied suggestion is that she was a likely candidate to experience a “cardiac event” eventually from repeated exposures in the PM 2.5 chamber.

The “Subject”

The human subject was not well.  Although she was asymptomatic on the day of the experimental exposure to CAPs, she had a history of osteoarthritis and hypertension.  The latter condition was being treated with an angiotensin-converting enzyme inhibitor and a diuretic (10 mg. lisinopril and 12.5 mg. hydrochlorothiazide).  The subject had had surgeries for hernia repair, cholecystectomy, and knee arthroplasty. She was a little over 5 feet 6 inches tall, and obese, weighing over 230 pounds, with a 45 inch waist.

In addition to her chronic hypertension, morbid obesity, and musculoskeletal disease, the subject also had a family and personal history of heart disease.  Her father had died from a myocardial infarction, at the age of 57.  Immediately before the experimental exposure, a Holter monitor showed evidence of increased supraventricular ectopy, with 157 ± 34 premature atrial contractions/hour.

The investigators do not tell us how the experimental exposure relates to typical urban exposures, or to EPA regulatory standards, guidelines, or recommendations.  About 23 minutes after exposure to CAPs started (filter weight, 112 μg/m3; particle number, 563,912/cc), the human subject developed a “nonsustained atrial fibrillation that quickly organized into atrial flutter.”  The woman remained asymptomatic, and her EKG showed that she spontaneously reverted to a normal sinus rhythm.

The investigators acknowledge that there are many risk factors for AFib, and that the subject had several of them: hypertension, obesity, and possibly family history.  The woman had a history of premature atrial contractions, which may have increased her risk for AFib.

Despite this rich clinical background, the authors claim, without apparently trying very hard, that there was no “obvious” explanation for the subject’s arrhythmia while in the chamber.  They argue, however, that the exposure to PM 2.5 was causal because the arrhythmia began in the chamber, and resolved when the subject was removed from exposure.  The argument is rather weak considering that the subject may have been stressed by the mere fact of placement in a chamber, or being wired up to monitors.  See, e.g., Luana Colloca, MD, PhD, and Damien Finniss, MSc Med., “Nocebo Effects, Patient-Clinician Communication, and Therapeutic Outcomes,” 307 J. Am. Med. Ass’n 567, 567 (2012). The authors of the PM 2.5 case report acknowledge that “coincident atrial fibrillation cannot be excluded,” but they fail to deal with the potentially transient nature of AFib.

Human experimentation requires a strong rationale in terms of helping the experimental participant.  What was the rationale for this human experiment?  Here is what the EPA investigators posit:

“Although epidemiologic data strongly support a relationship between exposure to air pollutants and cardiovascular disease, this methodology does not permit a description of the clinical presentation in an individual case. To our knowledge, this is the first case report of cardiovascular disease after exposure to elevated concentrations of any air pollutant.”

Ghio at 275. The authors seemed to be saying that we know that PM 2.5 causes cardiovascular disease, but we wanted to be able to describe a person in the throes of a cardiovascular event brought on by exposure. See also Andrew J. Ghio, Jon R. Sobus, Joachim D. Pleil, Michael C. Madden, “Controlled human exposures to diesel exhaust,” 142 Swiss Med. Weekly w13597 (2012).

The Whole Truth

The Ghio article mentions only the one woman who experienced the mild, transient AFib.  A reader might wonder whether she was the only test subject.  Why was she retested after a previously incident-free experience in the chamber? How many other people were subjected to this protocol?

What is remarkable is that the authors claim not only an “association,” but causality, in a totally uncontrolled experiment, and without ruling out chance, bias, or confounding.  The article is both deficient in scientific methodological rigor, and dubious on ethical principles.

EPA – Hoisted With Its Own Petard

What I did not realize when I read this experimental case report is that the article had been a cause célèbre of the anti-regulatory right.  The EPA had walked right onto an ethical landmine by first sponsoring this research, and then by relying upon it to support a regulatory report. Steven Milloy editorialized about the EPA research, followed by a FOIA investigation. In September 2012, a regulatory watchdog group filed a lawsuit to strike an EPA report, which was based in part upon the questionable research.

Milloy’s strategy was designed to impale the EPA on the horns of a dilemma:

“I accused EPA of either: (1) conducting unethical human experimentation or exaggerating the dangers of fine airborne particulate matter (PM2.5). It must be one or the other; it can’t be neither, according to EPA’s own documents.”

Steven Milloy, “Did Obama’s EPA relaunch Tuskegee experiments?” (April 24, 2012).  The EPA had branded diesel particulate, which was used in the experiments, as “carcinogenic” and “lethal,” even from short exposures.  Accordingly, if the EPA were sincere, it should have never conducted the experiment documented in Environmental Health Perspectives.  If the agency believed that PM 2.5 was innocuous, then it unethically exaggerated and overstated its dangers.

In course of his FOIA initiative, Milloy did obtain answers to some of the questions I had from reading the Ghio article.  There were apparently about 40 human subjects, who were subjected to PM 2.5 exposure in chambers fed by diesel exhaust or other sources.  The exposure levels were upwards of 20 times what the EPA labeled a “permissible” level.  Of course, the EPA is positionally committed to a “linear, no-threshold” model of carcinogenesis, which makes any exposure to a substance it “knows” to cause cancer ethically improper.

The information from the FOIA requests puts the Ghio article in an extremely bad light.  The human subject on whom the authors reported had run about 40 other people through their chamber without ill effect, but failed to mention these cases.  The consent forms and IRB documents show that the investigators were specifically interested in “vulnerable” patients, who had diabetes, asthma, etc.  The fair inference is that the investigators wanted to provoke an anecdote that would support their causal narrative, which they believed had already been established with epidemiologic evidence.  This seems like a scientific hat trick: bad science, bad ethics, and bad publication practice.

The lawsuit did not fare well.  Predictably, it foundered on the lack of final agency action, and the lack of standing.  On January 31, 2013, Judge Anthony J. Trenga dismissed the complaint, after having previously denied a temporary restraining order.  The American Tradition Institute Environmental Law Center v. U.S. EPA, Case 1:12-cv-01066-AJT-TCB (E.D. Va. 2013).  While legally correct, the opinion is blandly devoid of any sense of ethical concern.

From a brief search, there does not appear to be an appeal to the Fourth Circuit in the works.  Of course, there were no personal injuries alleged in the ATI lawsuit, and the human subject in the Ghio article has appeared not to have sued.  Despite the lack of legal recourse, the science “right” is up in arms over EPA duplicity.  In a recent publication, Milloy and a co-author, quote former EPA Administrator Lisa Jackson, at a congressional hearing:

“Particulate matter causes premature death. It’s directly causal to dying sooner than you should.”

When Representative, now Senator, Edward J. Markey asked, “How would you compare [the benefits of reducing airborne PM2.5] to the fight against cancer?” Jackson answered hyperbolically:

“If we could reduce particulate matter to healthy levels, it would have the same impact as finding a cure for cancer in our country.”

Steve Milloy & John Dale Dunn, “Environmental Protection Agency’s Air Pollution Research: Unethical and Illegal?” 17 J. Am. Phys. & Surg. 109 (2012) (quoting Jackson).  The FOIA and other background materials from this EPA posturing can be found on one of Milloy’s websites.

Sadly, I found the answers raised by the Ghio article only because of the anti-regulatory activism of Milloy and the American Tradition Institute.  The white-hat bias remains a potent force in regulatory agencies, and in scientific laboratories.

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