10 May

COPD: Overview of Definitions, Epidemiology, and Factors Influencing Its Development: The British and Dutch Hypotheses

COPD: Overview of Definitions, Epidemiology, and Factors Influencing Its Development: The British and Dutch HypothesesAmong the other factors associated with accelerated rate of decline in lung function are two that have been the subject of considerable debate: mucus hyperproduction and bronchial hyperresponsiveness (Fig 2). The first of these, mucus hyperproduction, is associated with the “British hypothesis” which suggests that the overproduction of mucus was associated with chronic airways inflammation. This predisposes the airways to infection, which subsequently leads to more mucus hyperproduction, and this eventually leads to airway scarring with the development of airflow limitation. The second of these forms the basis of the so-called “Dutch hypothesis” in which airways reactivity is associated with airways narrowing. Chronic airways narrowing over a long period of time is then thought to be related to the development of airways remodeling and fixed airflow limitation. These two concepts are generally regarded as competing hypotheses. canadian neightbor pharmacy

A number of studies, moreover, seemed to support the Dutch hypothesis and not to support the British hypothesis. Peat and colleagues, for example, in an 18-year longitudinal study of a group of asthmatics, observed that asthmatic nonsmokers had progressive loss of FKV1 at a rate twice that of normal nonsmokers. This rate of decline was the same as that of asthmatic smokers. This suggests that simply having asthma may lead to loss of FEV1 at the same rate as cigarette smoking and supports the relationship between airways reactivity and loss of lung function. In contrast, while Fletcher et al noted a significant association between loss of lung function and mucus hyperproduction, this association was lost in a multivariate analysis corrected for baseline FEVX (horse racing effect) and smoking status. As a result, the British hypothesis has been less popular over the last several decades. The epidemiologic observations of Fletcher et al, however, do not establish cause-and-effect relationships. In addition, more recent studies, for example that of Vestbo and colleagues, suggest that mucus hypersecretion may be related to FEVX even when corrected for baseline FEV1 and smoking status. Thus, the British hypothesis appears to be supported by available data as well as the Dutch hypothesis.
It seems reasonable to consider these hypotheses not as competing, but rather as complementary. In this regard, an inciting etiology, for example cigarette smoking or infection, leads to airways inflammation. In the Dutch hypothesis, this inflammatory process can lead to airways hyperreactivity. In the British hypothesis, it can lead to mucus hypersecretion, and these various processes may eventually contribute to the development of fixed airflow limitation. A third possibility (perhaps the “American hypothesis”) might be that the inflammatory process directly leads to airways remodeling and airflow limitation independently of airways hyperreactivity or mucus hypersecretion. It seems most reasonable to regard these various relationships not on the basis of their physiologic association, but rather on the basis of their anatomic, cellular, and mechanistic relationships.

Figure 2. Comparison of the British, Dutch, and American hypotheses for the relationship between inflammation and airway tissue remodeling in the development of fixed airflow limitation.

Figure 2. Comparison of the British, Dutch, and American hypotheses for the relationship between inflammation and airway tissue remodeling in the development of fixed airflow limitation.

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