© 2006 American Thoracic Society
Beyond the Dutch HypothesisTo the Editor:In their recent Pro/Con editorial debate, Kraft and Barnes agree that the Dutch hypothesis considers asthma and chronic obstructive pulmonary disease (COPD) as a single entity whose pathogenesis involves environmental and host factors (1–4). Barnes acknowledges that some patients exhibit features of both asthma and COPD, but states it is likely that they occur concurrently rather than as the continuum posited by the Dutch hypothesis. Concurrence of unrelated diseases should be random, but this is not the case for asthma and COPD. Of 2,926 subjects in a population-based cohort, 7.3% had asthma, 4.3% had asthma and COPD, and 11.1% had COPD (5). Concurrence predicts a prevalence of 0.8% (7.3% x 11.1%), but the actual prevalence was more than five times higher, and in fact 37% of all patients with asthma had concomitant COPD. Further evidence undermining the concept of concurrence derives from a 20-yr prospective study finding that asthma was the strongest risk factor for subsequent COPD (hazard ratio [HR] =12.5; attributable risk [AR] =18.5%); tobacco smoking had an HR of 2.9 for current smoking and an AR of 6.7% for ever-smoking (6). Primary care clinicians who practice long enough report patients with acute bronchitis that morphs into chronic asthma that then develops into severe COPD (7). Kraft correctly notes that atopy and airway hyperresponsiveness are the two cardinal host characteristics emphasized by the Dutch hypothesis. However, epidemiologic evidence now strongly suggests that atopy plays a minor role in asthma (8). Barnes asserts that the Dutch hypothesis predicts that the susceptibility genes should be the same and that environmental factors determine the difference in clinical presentation. I suggest the opposite possibility, that a common environmental factor is responsible for a large proportion of asthma and COPD, and that disease phenotype (including not having disease) is determined by host genetic factors. Consider an analogy with a set of known chlamydial disease entities: acute cervicitis, endometritis, salpingitis, and tubal infertility. Taken separately, each of these four entities has a unique clinical presentation and histopathology, yet the same infectious organism causes them all. Not all women with acute cervicitis will develop tubal pathology and infertility; other women with asymptomatic infections will develop infertility. Why? Probably because of different genetic response(s) to infection (9). As Adlai Stevenson once said when put in a difficult political position, "I agree with everything you said that was correct, and disagree with everything you said that was incorrect." I suggest that we do the same with the Dutch hypothesis, and move to the next level of understanding.
Dean Medical Center and University of Wisconsin Medical School, Madison, Wisconsin FOOTNOTES Conflict of Interest Statement: D.L.H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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