Density Dependence of Expiratory Flow and Bronchodilator Response in Asthma

Atropine is a potent bronchodilator and has been used in children as well as adults with asthma and chronic bronchitis. Some of these studies have shown it to be useful especially in the presence of chronic bronchitis. Other workers have found it to be inferior to adrenergic agents. Most of these studies refer only to the acute bronchodilator effects of atropine, and its role in the long term treatment of asthma remains unclear. The uncertainty about its role in the treatment of asthma has led to its use being abandoned and it is not available in the United States for use as a bronchodilator. The possibility remains that in some subjects with asthma, atropine might be a more effective bronchodilator than isoproterenol. While most studies agree that disodium cromoglycate and Sch 1000 is partially effective in the prevention of asthma.

Asthmatic subjects vary greatly in their response to the different drugs used for the treatment of asthma. At the present time, there are no tests available to identify the subjects who would respond better to one drug than another. This leads to a trial and error approach to drug selection and might be responsible for the conflicting results obtained in the different studies cited above.


Because airflow in the small airways is independent of the density of the inspired gas in contrast to the large airways where airflow is density dependent, the change in the maximum expiratory flow volume curve (MEFV) in response to breathing a 20 percent oxygen-80 percent Helium gas-mixture (Helox) has recently been used to determine the major site of obstruction in patients with asthma. Ingram et al suggested that the relative effect of atropine was greater on large airways than on small, while that of isoproterenol was more variable. Therefore, we reasoned that the change in MEFV curve breathing Helox (MEFV Helox) from that breathing air (MEFV air) could be used in selecting individuals who would respond better to atropine from those who would to isoproterenol.

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The purpose of our study was: 1) to assess the usefulness of the measurement of density dependence of the maximal expiratory flow (D/MEF) in determining the response of asthmatic subjects to isoproterenol or atropine, and 2) to determine the relative effectiveness of atropine in comparison to isoproterenol as a therapeutic agent in adults with long standing asthma.