What is the place of the Dutch hypothesis in COPD

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A relationship between increased airway reactivity, atopy and the development of COPD was first proposed by Orie et al. in 1961 [69]. In other words, smokers with hyperreactive airways could be the susceptible ones who will develop COPD. This hypothesis is still open to debate, as it is not clear whether hyperresponsiveness is the cause or the effect of the decrease in FEV1 in smokers. Airways reactivity and atopy are complex disorders related to a number of genetic and environmental factors leading to allergic inflammation (asthma). This inflammation, however, has recently been shown to be different from that caused by cigarette smoke [70]. In addition, other investigators have suggested that the hyperresponsiveness seen in smokers is the result of abnormal geometry of the airways caused by prolonged smoking, leading to 'reactivity'. In addition, the majority of the studies investigating FEV1 decline have tested airways reactivity at the end of the study (after the initiation of smoking)

[71,72] and only a few have tested it at the beginning [73,74]. Recently, two studies that reported an association of hyperresponsiveness in subgroups of smokers lacked statistical analysis of the smoking status [75,76]. When the smoking status was accounted for [77,78], the association between reactivity and smoking was not significant. In conclusion, the Dutch hypothesis has failed to clarify the issue of the susceptible smoker, which is still open to debate.

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