Tuesday, April 04, 2006

You need more than FEV1 to judge bronchodilator response

Bronchodilator drug trials and often clinical followup have focused on the changes in the forced expiratory volume in one sec (FEV1) to judge therapeutic response. However, it is recognized that exercise intolerance and dyspnea may improve with no significant change in expiratory flow rates.
Improvement in exercise tolerance actually seems to correlate better with indicators of improvement in overinflation,a simple measure of which is the inspiratory capacity (IC).

The IC is the sum of the tidal volume and the inspiratory reserve capacity which is the volume of air inhaled on top of a tidal volume. In COPD the IC is reduced as a result of the hyperinflation ( increased residual volume and functional residual capacity) so that the tidal volume is performed at the upper part of the lung's pressure volume curve which is a region of low compliance and an increased load on the inspiratory muscles.The overinflation present at rest is worsened with increasing airtrapping during exercise with increased respiratory rate and decreased time to exhale and is currently thought to be a major variable that relates to exercise intolerance and the sensation of dyspnea.

In the March 2006 issue of Chest ( subscription required for full text), authors from Holland demonstrated that a long acting bronchodilator (LABA),formoterol plus once a day tioptropium ( a long acting anticholinergic) brought about significant improvement in expiratory flow rates and -probably more importantly from a symptom improvement point of view-a significant increase in the inspiratory capacity.

Scores of bronchodilator trials focused only ( or at least mainly) on FEV1 measurement. ( I was involved in several as a pulmonary fellow) and as we learn more about the pathophysiology and the clinical correlates of lung function measurements we are better able to develop therapeutic measures to improve the disabling exercise intolerance of COPD patients.

It may have taken the surgical lung volume reduction experience to remind lung doctors that we have been doing pharmcologic lung volume reduction therapy all along when we have been using bronchodilators.

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