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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:

Bronchodilator effect Increase in FEV1
None < 9% of predicted value and < 200 mL
Moderate between 9% and 12% of predicted value and/or > 200 mL
Unambiguous > 12% of predicted value

Relationship between FEV1 and airways resistanceThe 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) .

Ref. 1 - ECCS and ERS
In the revised 1993 version of the 1983 report ( Quanjer PhH (ed.) Standardized lung function testing. Bull Eur Physiopathol Respir 1983; 19 suppl. 5: 45-51) of the European Community for Coal and Steel (ECCS) predicted values of lung indices were unchanged. They are almost universally applied in Europe. The 1993 report was officially adopted by the European Respiratory Society (ERS).
The following chapter deals with spirometry, predicted values and bronchodilator responsiveness: 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.
 
Ref. 2 - Do not use PEF to assess airway obstruction
Thiadens HA, de Bock GH, van Houwelingen JC, Dekker FW, de Waal MWM, Springer MP, Postma DS. Can peak expiratory flow measurements reliably identify the presence of airway obstruction and bronchodilator response as assessed by FEV1 in primary care patients presenting with a persistent cough? Thorax 1999; 54: 1055-1060.
 
Ref. 3 - Literature on bronchodilatation
1 Sourk RL, Nugent: Bronchodilator testing: confidence intervals derived from placebo inhalations. Am Rev Respir Dis 1983; 128: 153-157.
2 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.
3 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.
4 Meslier N, Racineux JL. Tests of reversibility of airflow obstruction. Eur Respir Rev 1991; 1: 34-40.
5 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.
6 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.
7 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.
8 Casan P, Roca J, Sanchis J: Spirometric response to a bronchodialtor. Reference values for healthy children and adolescents. Bull Europ Physiopath Resp 1983; 19: 567-569.
9 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.
10 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.

Ref. 4 - Bronchodilator and symptomatic improvement
1 Eliasson O, Degraff AC. The use of criteria for reversibility and obstruction to define patient groups for bronchodilator trials. Am Rev Respir Dis 1985; 132: 858-864.
2 Guyatt GH, Townsend M, Nogradi S, Pugsley SO, Keller JL, Newhouse MT. Acute response to bronchodilator: an imperfect guide for bronchodilator therapy in chronic airflow limitation. Arch Intern Med 1988; 148: 1949-1952.
3 Redelmeier DA, Goldstein RS, Min ST, Hyland RT. Spirometry and dyspnea in patients with COPD. When small differences mean little. Chest 1996; 109: 1163-1168.
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