Does bronchial hyperresponsiveness precede or follow airway obstruction in asthma or COPD?

Neth J Med. 1994 Oct;45(4):145-53.


Objective: The following hypothesis was tested: The degree of bronchial hyperresponsiveness (BHR) is a risk factor for the progression of airway obstruction in asthma, while in chronic obstructive pulmonary disease (COPD) it reflects the existing airway obstruction.

Methods: The relationships between the (annual change in) PC20 histamine and the (annual change in) FEV1 were investigated in a 2-year prospective controlled study. The FEV1 and the PC20 histamine were assessed at 6-month intervals. 183 patients (74 asthma, 109 COPD) participated. The investigated relationships were assessed by means of multiple analysis of variance (ANOVA). Patients used bronchodilator therapy alone. No steroids were permitted during the study.

Results: The results demonstrated that the PC20 at the start of the study was related to the subsequent annual decline of FEV1 in asthma (r = 0.32, p < 0.05) but not in COPD (r = -0.10, p = 0.89). Asthmatic patients with a PC20 value < or = 2 mg/ml had an average decline of 118 ml/yr, those with a PC20 value > 2 mg/ml of 27 ml/yr. The change in PC20 histamine during the 2-year study period was related to the annual change in FEV1 in COPD (r = 0.45, p < 0.05), but not in asthma (r = 0.06, p = 0.90). The disturbing influence of possible confounders was investigated and if necessary controlled for.

Conclusions: It was concluded that BHR, assessed with PC20 histamine, is probably involved in the progression of airway obstruction in asthma. In COPD, however, the degree of BHR probably only reflects the degree of existing airway obstruction. This conclusion may contribute to the ongoing debate whether it is useful to combine the diagnosis of asthma, COPD and emphysema under the umbrella-term CARA (or CNSLD = chronic non-specific lung disease). The so-called "Dutch hypothesis" which laid the foundation for this term, suggested that bronchial hyperresponsiveness plays a central role in the pathogenesis of CNSLD. The present study supports evidence that at least BHR does not seem to play the same role in the pathogenesis of asthma and COPD.

MeSH terms

  • Adult
  • Analysis of Variance
  • Asthma / diagnosis
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity*
  • Disease Progression
  • Female
  • Forced Expiratory Volume
  • Histamine
  • Humans
  • Lung Diseases, Obstructive / diagnosis
  • Lung Diseases, Obstructive / physiopathology*
  • Male
  • Prospective Studies
  • Risk Factors


  • Histamine