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Time domain and flow indices of bronchial hyperresponsiveness: association with asthma symptoms, atopy and smoking

¹ Dept of Medicine, University of Birmingham, UK. ² Dept of Environmental and Occupational Medicine, University of Aarhus and ³ Dept of Occupational Medicine, Aalborg Regional Hospital, Denmark

CORRESPONDENCE: M.R. Miller, Dept of Medicine, Selly Oak Hospital, Birmingham, B29 6JD, UK. Fax: 44 1216278292. E-mail: martin.miller@uhb.nhs.uk

Keywords: bronchial hyperresponsiveness, lung function

Received: January 29, 2001
Accepted January 23, 2002

This study was supported by, the Danish Medical Research Council and the Danish Agricultural Research Council.

Conventional measures of bronchial hyperresponsiveness (BHR) are only weakly associated with respiratory symptoms in epidemiological studies. Partial and maximal forced expiratory manoeuvres were recorded during histamine challenge testing in 1,959 young male farmers. Analysis was performed to test whether novel measures of BHR, using alternative flow and time domain indices, are more closely associated with asthma symptoms, smoking status and atopy than forced expiratory volume in one second (FEV₁) and conventional measures of BHR.

The first moments to 75% and 90% of the forced vital capacity (FVC) were calculated from full (F) and partial (P) forced expiratory manoeuvres (i.e. ₁75%F, ₁75%P), together with the instantaneous flows when 40% and 30% of the FVC remained to be expired (MEF₄₀ and MEF₃₀). BHR was measured by the provocative dose causing a 20% change (PD₂₀) in the FEV₁ and ₁75%, and also by the method of log dose slopes (LDS).

Asthma was diagnosed from symptoms associated with asthma in 158 (8.1%) of the subjects. PD₂₀ FEV₁ could only be recorded in 190 subjects (9.7%), of whom only 48 had asthma, whereas LDSFEV₁ was recorded in 1,725 (88%) subjects. From the prechallenge data, ₁75%, expressed as standardised residuals, showed the largest difference between smokers with and without asthma symptoms, and no indices showed significant differences between nonsmokers with and without asthma symptoms. From BHR data in both smokers and nonsmokers, LDSFEV₁ showed one of the largest differences between those with and without asthma symptoms. With smoking status and atopy accounted for, the greatest partial correlation with asthma diagnosis was found for LDSMEF₄₀P, and then for LDSFEV₁, but LDSMEF₄₀P was measurable in only just over one-half of the subjects.

The authors conclude that time-domain indices are promising measures for longitudinal epidemiological studies concerning the relationship between bronchial hyperresonsiveness and environmental exposures. However, indices from the partial flow-volume loop suffer from censored data.

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