Bronchodilator response

A response to bronchodilator drugs is regarded as unambiguous if the change in FEV1 >12% of the predicted value. An isolated increase in (F)VC of >340 mL may be due either to better subject cooperation or a limited bronchodilator effect. In adults an increase in PEF larger than 60 L/s has been attributed to a bronchodilator response (ref. 1). A recent study suggests that, whilst PEF may be used to assess airways obstruction and exclude a response to bronchodilator drugs, it should not be used for assessing bronchodilator responsiveness in patients with chronic cough (ref. 2).

Often the change of FEV1, FVC or another index is expressed as a percentage of the initial value. This is wrong for various reasons, the most important being:

1. The change is not proportional to initial level. In patients with a ‘poor’ initial value the change in FEV1 due to a bronchodilator drug even has the tendency to be somewhat larger than in the case of a favorable initial value. Indeed the response to a bronchodilator drug may diminish if treatment with e.g. corticosteroids has been effective (view experimental data in the animation).
2. When measurements of FEV1 in adult patients with respiratory disease are repeated at short time intervals, spontaneous variability is up to 200 mL (ref. 3). In a patient whose initial FEV1 is 700 mL this comes to 29% change due to spontaneous variability. Yet, if the initial value were 2 liter, the 200 mL spontaneous variability would come to only 10%.

In healthy subjects the change in FEV1 or VC due to a bronchodilator drug is maximally 9-11% (ref. 3) . Bronchodilator responsiveness is therefore categorized as follows:

The FEV1 is the best-studied index of lung function; hence the relationship of FEV1 and bronchodilator responsiveness with clinical condition or prognosis is well documented. One should keep in mind that a small increase in FEV1 due to a bronchodilator drug may be accompanied by a considerable fall in airway resistance during normal tidal breathing, and therefore in viscous work of breathing, which may be clinically relevant. Also, there may be symptomatic improvement without a significant increase in the FEV1 (ref. 4).

It is not yet generally appreciated that FEV1 bronchodilator responsiveness differs significantly from that in FVC. The reason is as follows (see references 5). First, during a forced expiration intrahoracic gas is compressed, often by well over 10%. At that lower lung volume the elastic recoil pressure is reduced compared to that at the uncompressed lung volume. Due to the diminished tethering forces which extend the airways, airway diameter diminishes. The dual effect is that forced expiratory flow falls, and that the change in thoracic gas volume is larger than the volume measured at the mouth. The more severe the initial airways obstruction, the more pronounced this effect. Towards the end of the FVC manoeuvre large intrathoracic pressures cannot be sustained, so that the FVC is less affected by this compression effect; it is then determined by airway closure. In 2,371 healthy non-smokers and 29,157 clinical patients (age 4-95 years), in whom the severity of respiratory impairment was classified according to the ATS/ERS grading system, the median FEV1 response in subjects with mild obstruction was twice as large as in those without airways obstruction, was marginally larger in moderate airways obstruction, but then declined to the same level as that in subjects without airways obstruction. Conversely, the FVC response increased virtually linearly with the level of respiratory impairment. The net result was that the improvement in the FEV1/FVC ratio fell almost linearly to the level in patients with respiratory impairment. These findings signify that bronchodilation leads to opening up airways, thus diminishing airway closure, as testified by the important FVC response; the improvement the the FVC rsponse is proportional to the level of initial respiratory impairment. Conversely, in patients with airways obstruction there is little difference in the FEV1 response except in those with the severest respiratory impairment, where it falls to the same level as in subjects with airways obstruction. Because of the large age range and the age dependence of FEV1 or FVC expressed as percent of predicted, data were transformed to z-scores (see Quanjer et al., Chest 2017).