Optimizing and evaluation of a methacholine provocation test : with application in occupational research

• Main Author: Sundblad, Britt-Marie
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Klinisk fysiologi 2002
• Subjects: Physiology; Airway responsiveness; methacholine provocation; nitric oxide; eucapnic hyperventilation; organic dust; Fysiologi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2809; http://nbn-resolving.de/urn:isbn:91-554-5457-7

We have developed a methacholine provocation method, which detects bronchial responsiveness in more than 80% of healthy subjects. The method enables us to detect differences in bronchial responsiveness within the normal range. With this method FEV1 and Gaw had similar sensitivity in detecting small differences in bronchial responsiveness. Differences, between protocols when using doubling or fourfold concentration steps emphasize the importance to strictly adhere to a predefined protocol. Deep inhalation associated with the FEV1 manoeuvre decreases bronchial tone induced by methacholine for up to 6 minutes, which emphasizes the importance of exact timing between successive FEV1 measurements in bronchial provocation tests. There is a substantial overlap in bronchial responsiveness between healthy and asthmatic subjects and a deep inhalation at the end of the methacholine test challenge could not discriminate between asthmatic and non-asthmatic subjects. Inhalation of dust in a swine confinement building causes an intense airway inflammatory reaction with an extensive migration of inflammatory cells, predominantly neutrophils, into the upper and lower airways. Bronchial responsiveness to methacholine increased by about 3 doubling concentration steps and was normalized one week after exposure. However, exposure to dust in a swine confinement building did not yield increased bronchial responsiveness to eucapnic hyperventilation with dry air which is often observed in asthmatic subjects. Exhaled NO was approximately doubled five hours after exposure and in the present study we found no relationship between exhaled NO levels and bronchial responsiveness in healthy subjects. Protection with half-mask inhibited the dust induced increase of exhaled NO whereas the increase in bronchial responsiveness was influenced only to a minor extent. These findings, do not support the hypothesis that the increased bronchial responsiveness following organic dust exposure is directly caused by the inflammation. Instead, a possible direct effect on the smooth muscle and swelling of the airway mucosa and increased secretions due to the general inflammatory reaction probably leads to airway narrowing enhancing the post-exposure bronchial response to methacholine.