## Bronchodilator responsiveness: children, adolescents and adults

The following holds for children, adolescents and adults.

In 110 children with asthma Waalkens [see literature] administered salbutamol and then expressed the change in FEV1 as a % of the initial value; he then plotted this change as a function of FEV1 % of the predicted value. The graph seems to show that the poorer the initial values the greater the response to salbutamol. Most of us would expect this to be the case intuitively, so it enforces our prejudice, which is: the more extensive the airway obstruction, the more it can be improved in particular in patients with asthma, who after all have reversible airway obstruction by definition.

The change observed after administration of salbutamol is made up of two components:

- Spontaneous fluctuations in FEV1, as in any repeated measurements, which have nothing to do neither with the initial value nor with a bronchodilator effect. If one divides such chance changes by a progressively smaller denominator, this artificially inflates the ‘response’. A large percentage change then merely indicates a small initial value, which can be demonstrated in a more straightforward fashion.
- The ‘real’ change due to bronchodilatation.
This response tends to be somewhat larger in children and
adolescents with asthma the smaller the initial values.

Expressing the response (ΔFEV1) as a % of the predicted value circumvents artificially inflating the response by dividing it by a progressively smaller initial value.

Due to spontaneous fluctuations the FEV1 will be higher on one occasion, and lower on another occasion.
If the first measurement happens to be relatively small, then
chances are that the next observation will be larger, and vice
versa (‘regression to the mean’ ).

Let us assume that a subject’s average FEV1 is 1000 mL, but we find 900 mL and 1100 mL, respectively in
two measurements. If 900 mL represents the initial observation,
the relative change comes to 100·(1100-900)/900 = 22%;
if, however, 1100 mL is measured first, then the relative change
is 100·(900-1100)/1100 = -18%. By using the initial value,
with its chance errors, in the denominator, the magnitude of
observed changes is asymmetric. Expressing change as a percentage
of the average of observed values may circumvent this: in either
case the 'changes' now come to 10%. When applied to the response
to a bronchodilator drug the trend has virtually vanished (figure
on the right), but the ‘true’ response to the bronchodilator
drug is now incorrectly mixed with chance fluctuations.

Please note that in patients with severe airways obstruction (COPD, pulmonary emphysema) a clinically relevant response in the VC may occur even when there is no response in FEV1.

### Literature on bronchodilatation

- Sourk RL, Nugent: Bronchodilator testing: confidence intervals derived from placebo inhalations. Am Rev Respir Dis 1983; 128: 153-157.
- Casan P, Roca J, Sanchis J: Spirometric response to a bronchodilator. Reference values for healthy children and adolescents. Bull Europ Physiopath Resp 1983; 19: 567-569.
- Eliasson O, Degraff AC. The use of criteria for reversibility and obstruction to define patient groups for bronchodilator trials. Influence of clinical diagnosis, spirometric, and anthropometric variables. Am Rev Respir Dis 1985; 132: 858-864.
- Tweeddale PM, Alexander F, McHardy GJR. Short term variability in FEV1 and bronchodilator responsiveness in patients with obstructive ventilatory defects. Thorax 1987; 42: 487-490.
- Dales RE, Spitzer WO, Tousignat P, Schechter M, Suissa S: Clinical interpretation of airway response to a bronchodilator. Epidemiologic considerations. Am Rev Respir Dis 1988; 138: 317-320.
- Meslier N, Racineux JL. Tests of reversibility of airflow obstruction. Eur Respir Rev 1991; 1: 34-40.
- Brand PLP, Quanjer PhH, Postma DS, Kerstjens HAM, Koëter GH, Dekhuyzen PNR, Sluiter HJ, Dutch CNSLD Study Group. Interpretation of bronchodilator response in patients with obstructive airway disease. Thorax 1992; 47: 429-436.
- Quanjer PhH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Eur Respir J 1993; 6 suppl. 16: 5-40. Erratum Eur Respir J 1995; 8: 1629.
- Waalkens HJ, Merkus PJFM, van Essen-Zandvliet EEM, Brand PLP, Gerritsen J, Duiverman EJ, Kerrebijn KF, Knol K, Quanjer PhH. Dutch CNSLD Study Group. Assessment of bronchodilator response in children with asthma. Eur Respir J 1993; 6: 645-651.
- Pardos Martinez C, Fuertes Fernández-Espinar J, Nerín de la Puerta I, González Pérez-Yarza E: Cuándo se considera positivo el test de broncodilatación. Anales Españoles de Pediatria 2002; 57: 5-11.