Bronchodilator reversibility testing in an adult general population; the importance of smoking and anthropometrical variables on the response to a β2-agonist

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Abstract

Normative cut-off values for the bronchodilator reversibility test are published neglecting factors that may influence the test result other than disease.

The objective of this cross-sectional study of a general population was to examine how a salbutamol reversibility test response is depending on anthropometrical variables and smoking.

An age and gender stratified random sample of all adults aged 47–48 and 71–73 years living in Bergen, Norway, was invited. The 3506 attendants (69%) filled in a questionnaire and performed spirometry before and after inhalation of 400 μg salbutamol.

The mean (SD) absolute FEV1 bronchodilator response, the change in % predicted, and the change in % initial among middle-aged were 71 (122) ml, 2.0 (3.3)%, and 2.4 (4.1)%, and in the elderly 64 (113) ml, 2.4 (4.3)% and 3.3 (5.9)%, respectively. In a multiple linear regression analysis including adjustment for the initial FEV1 in % predicted, smoking and pack-years were negatively correlated to all indices. Current smoking was considerably more important than past smoking. Female gender, old age, and BMI were positively correlated with the percentage change indices, but the correlation with BMI decreased with increasing heights. These trends were unchanged after excluding subjects with obstructive lung disease or coronary heart disease.

This study demonstrates that smoking habits predict all indices expressing the salbutamol bronchodilator response among middle-aged and elderly from a general population. Also, the change in % predicted and the change in % initial indices are dependent on anthropometrical variables. However, although smoking and anthropometrical variables, as well as level of lung function predict the response to inhaled β2-agonists, these factors explain only 7–16% of the total variation of the measurement indices, and seem therefore of minor importance to the interpretation of the test result.

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.

Section snippets

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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