NEW RISK FACTORS FOR ADULT-ONSET INCIDENT ASTHMA. A NESTED CASE-CONTROL STUDY OF HOST ANTIOXIDANT DEFENSE
Larkin EK, Gao YT, Gebretsadik T, et al
Am J Respir Crit Care Med. 2015;191:45-53
Study Summary
Asthma typically begins early in life but occasionally it begins in adulthood, sometimes in middle life or even later.
The risk factor(s) for adult-onset asthma have been puzzling. It is rarely due to atopy.[1] The possibility that antioxidants or their deficiency may play a role has been tested but so far remains unsubstantiated.[2]
An appropriately designed and powered study now shines some new light on the antioxidant theory of adult-onset asthma.
The question posed by Larkin and colleagues was whether a deficit in plasma biomarkers of antioxidant host defense precedes onset of adult asthma.
A nested case-control study was carried out on 65,372 women in Shanghai, China, with a mean age of 52 years.
The study subjects had no history of previous asthma. Baseline urinary F2-isoprostanes, plasma concentrations of antioxidant micronutrients (tocopherols, xanthines, carotenes, and lycopene), and antioxidant enzyme activity (platelet-activating factor acetylhydrolase [PAF-AH] and superoxide dismutase) were measured at enrollment.
The women were followed for a mean of 7.5 years. During this time, 150 developed asthma, which was confirmed both by symptoms and either methacholine challenge or beta-agonist reversibility. The investigators matched these asthma subjects at a ratio of 1:2 with 299 of the control subjects from the same cohort who had not developed asthma.
The levels of the various antioxidants as measured at trial onset in the two groups were then compared. Investigators found that, compared with the control group, the adult-onset asthma subjects had significantly lower levels of alpha-tocopherol and PAF-AH. Other antioxidant biomarker levels were not different between the two groups. The authors suggest that deficiencies of the two aforementioned antioxidant biomarkers are risk factors for the subsequent development of adult-onset asthma.
VIEWPOINT
The study was limited to a very specific population and may not be generalizable to other populations.
All of the biomarker measurements were made at a single timepoint. Thus, one cannot be certain that they remained the same throughout the study period, nor is it stated at what time asthma began during the observation period.
Asthma, when it occurred, was validated by pulmonary function testing as well as symptomatology. But the absence of asthma in the control group was not verified by any pulmonary function tests.
The relationship between antioxidant plasma levels and reduction of asthma risk was unclear. However, in the case of PAF-AH, it can be suggested that the lower level of that modality allowed PAF levels to increase, and PAF is known to be a proinflammatory molecule.
The study also has strengths. It is prospective, large, and of long duration, providing the power necessary for statistical validation. The population, all females—essentially all nonsmokers with normal basal metabolic indexes, living and working in the same industrial environment—minimizes several potential confounding factors.
In addition, the levels of antioxidant biomarkers were determined before the onset of the trial and therefore preceded the onset of asthma.
It is notable that although levels of PAH-AH and alpha-tocopherol were relatively lower in the asthma group, they were still within what is considered the “normal” range. This suggests that replacement of antioxidants could be easily obtained by dietary means—for example, eating more fruits and vegetables—rather than with high-dose supplemental replacement of micronutrients.
References
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de Nijs SB, Venekamp LN, Bel EH. Adult-onset asthma, is it really different? Eur Respir Rev. 2013;22:44-52.
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Devereux G. The increase in the prevalence of asthma and allergy: food for thought. Nat Rev Immunol. 2006;6:869-874. Abstract
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