Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Air Travel and DVT Risk: Is Hypobaric Hypoxia the Culprit?

That air travel is associated with increased risk of deep venous thrombosis (DVT) is well established. Recent data have suggested that very long flights (> 5 hours) are disproportionately associated with risk. We previously reviewed data that compared subjects sitting and watching movies for similar time periods as matched subjects taking a plane flight, and noted that there is something about air travel that activates coagulation factors differently than simply sitting in a chair.

Pressurization in airplane cabins produces a mean arterial oxygen saturation of about 93% in healthy persons (mean), but lower levels in older individuals and persons with cardiopulmonary disorders. Such relative hypoxemia has been shown in vitro to induce procoagulant activity as well as inhibit fibrinolysis; in vivo studies amongst healthy volunteers corroborate this.

Toff et al studied healthy volunteers (n = 73) in a single-blind fashion by comparing hemostatic markers after an 8-hour period of seated exposure in a hypobaric chamber. Persons with known thrombophilic disorders were excluded. Analyses included measurement of platelet aggregability, coagulation activation, fibrinolysis, platelet activation, and endothelial activation.

There was no demonstrable difference in measured markers of mean prothrombotic activity in these healthy volunteers. At least in healthy individuals, hypobaric hypoxemia does not appear to affect DVT risk in a meaningful fashion.

Toff WD, et al. JAMA. 2006;295:2251-2261. Erratum in: JAMA. 2006;296:46.

GERD: Size Matters

Obesity is a recognized risk factor for gastroesophageal reflux disease (GERD). In addition to the clinical observation that obese individuals suffer GERD more often, trial data have corroborated that BMI and GERD have a linear association. However, studies of the relationship between BMI and GERD have generally been restricted to overweight or obese individuals, rather than including all subjects. Hence, whether weight gain in non-overweight individuals increases their risk for GERD has not been previously reported.

Subjects for this report (n = 10,545) included participants in the Nurses Health Study. In response to a questionnaire about frequency and severity of GERD symptoms, there was a direct relationship between increasing weight and frequent GERD symptoms. When compared to women with a BMI of 20-22.4, there was a direct relationship between BMI and GERD: the relative odds ratio for frequent symptoms was 33% less for persons with a BMI < 20, 38% more for BMI 22.5-24.9, and there was a greater than 100% increase for persons with BMI 25.0-27.4 (all of these BMI measurements are below the threshold for overweight/obese). Weight change (an increase in weight, that is) was also associated with increased risk for GERD, even when persons simply increased their weight from one normal weight category to another.

Increased body weight, even in non-obese individuals, is associated with GERD. Weight reduction has been shown to improve these symptoms.

Jacobson et al. N Engl J Med. 2006;354:2340-2348

Does aTNFa for RA Increase Infections and Malignancies?

Anti-TNF antibody (aTNFa) therapy offers significant benefit to sufferers of rheumatoid arthritis (RA). TNF is involved in critical functions related both to infectious disease and tumor suppression. For instance, CD8 lymphoctye tumor killing is mediated by TNF. Hence, the risk that either infectious or malignant diseases might be more prevalent in persons who have been treated with aTNFa is plausible. Individual trials using aTNFa have not demonstrated a 'signal' of greater risk for infections or cancer, but because both are somewhat uncommon, they might be easily missed.

Bongartz et al pooled data from aTNFa trials which lasted at least 12 weeks, providing data on 3,493 patients. Serious infections were defined as those which required antimicrobial treatment and/or hospitalization. Ultimately, this pooled data set indicated that the odds ratio for malignancy was increased greater than 3-fold, and risk for serious infection was doubled. For malignancies, there was a dose-dependent effect: higher aTNFa doses produced increased risk. In their closing commentary, the authors suggest that because of the difficulty in identifying rare events during clinical trials submitted for FDA drug registration, planning meta-analysis ahead of time to include future ongoing trials might recognize signals of serious disease earlier.

Bongartz T, et al. JAMA. 2006;295:2275-2285. Erratum in: JAMA. 2006;295:2482.