Bronchodilator reversibility testing in an adult general population; the importance of smoking and anthropometrical variables on the response to a β2-agonist
Introduction
Inhaled β2-adrenoceptor agonists are the bronchodilators most often applied to patients with obstructive lung disease [1], [2]. Nevertheless, the determinants of response have not received much attention. Traditionally, the bronchodilator reversibility test result (i.e. the difference in forced expiratory volume in one second (FEV1) before and after β2-agonist inhalation) has been used as a criterion to separate chronic obstructive pulmonary disease (COPD) from asthma, in guiding treatment, in establishing best attainable lung function, and in predicting the patient's prognosis [2]. However, the overlap in the bronchodilator responsiveness between COPD and asthma is so great that the two diagnoses cannot be distinguished on this basis [3]. Still, the bronchodilator response has been used as an exclusion or inclusion criterion in a large number of recent clinical trials on patients with COPD [4], [5], [6], [7] and asthma [8], [9].
The American [10] and European [11] recommendations on the interpretation of the reversibility test result differ. However, both guidelines state a single cut-off level for all subjects, such as an FEV1 increase of 200 ml and 12% from initial measurement [10] or 12% from predicted value [11], as the criterion for a positive bronchodilator response, without giving much scientific background for the recommendations. According to the ATS 1991 statement [10], studies of general populations are the appropriate reference when asking whether a subject has an increased bronchodilator response. Only one random sample [12] and one cluster sample [13] of general populations have examined the bronchodilator response. None of them addressed the question of whether the response varies with anthropometrical variables and smoking history.
The aim of our study was to describe the distribution of the salbutamol bronchodilator response in a middle-aged and an elderly population. The hypothesis was that age, gender, height, BMI, and smoking history could be predictors of the response, similarly to other spirometric variables.
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Population
The target population included all women and men born 1925–1927 and 1950–1951 living in the municipality of Bergen at the 31st of December 1992, who participated in the Hordaland Homocysteine Study [14] (n=7949, attendance rate: 67%). A follow-up study, the Hordaland Health Study (HUSK), was conducted during 1998–1999 as a collaborative study between the National Health Screening Service, the University of Bergen and local health services. An age and gender stratified random sample of 5099
Study sample characteristics
The attendance rate was 69% and did not differ by gender (70% women and 68% men, p=0.10), but it was higher in the middle-aged compared with the elderly (76% vs. 64%, p<0.0001). Overall, 3305 subjects (94% of attendants) performed a satisfactory reversibility test and were included in the analyses. The distribution of anthropometrical variables, smoking habits, and levels of lung function on initial spirometry are listed in Table 1. In women and men the mean (SD) of body heights were 163.3
Discussion
In the present general population study smoking and pack-years, as well as the initial FEV1 in % predicted were negatively correlated to the salbutamol bronchodilator response in multiple linear regression analyses. Old age and female gender indicated higher % change indices, and also body mass had a positive effect on the bronchodilator response at heights below 165 cm. These associations did not change after exclusion of subjects with obstructive lung disease or coronary heart disease.
Prior
Acknowledgements
The authors wish to thank Borghild Hovland, the operator at the pulmonary function test laboratory, for her competence and exertion during the study period, and all attendants for their kind co-operation. Sources of support: The Norwegian Research Council and GlaxoSmithKline, Norway.
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2008, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :The ATS [8,9] and ERS [10] first proposed FVC as a reversibility criterion in guidelines from the 1990s. It is thus surprising that, despite these recommendations and three decades of evidence, only the GOLD criterion of FEV1 is used to interpret airways response to short-acting BDs in the current literature [11–20] and most daily practices. One explanation for the contradiction between the evidence and the GOLD recommendation is that the studies assessing response to short-acting BDs had methodological limitations or recruited selected COPD patients.