Airway responsiveness in chronic obstructive pulmonary disease

Abstract

Airway resistance measured at FRC (functional residual capacity) and related to a specific thoracic gas volume (Vtg × Raw) by plethysmographic technic is the most sensitive measurement, among other currently used measurements, of the effectiveness of bronchodilator drugs. The product Vtg × Raw (thoracic gas volume × airway resistance) is shown to correlate best with the MEFR (maximal expiratory flow rate) in a group of normal subjects. In patients with chronic obstructive lung disease there is a significant negative correlation between Vtg × Raw and the MEFR, FEV 1 (one second forced expiratory volume) and MMF (maximal mid-flow). A group of selected patients with chronic obstructive lung disease, exclusive of bronchial asthma, demonstrated significant responsiveness of the airway to bronchodilator drugs, indicating that airway obstruction is not “fixed” in these subjects. Isoproterenol delivered directly to the bronchial tree by IPPB (intermittent positive pressure breathing) produced statistically significant reduction in the product Vtg × Raw. Comparable reduction was noted in the normal group. Epinephrine given subcutaneously in a 0.3 ml. dose produced greater favorable changes in Vtg × Raw than did 0.5 gm. theophyllin injected intravenously. Neither drug produced statistically significant reductions in Vtg × Raw when compared to IPPB with saline solution. Theophyllin administered intravenously and isoproterenol by IPPB resulted in statistically significant improvement in spirometric indices of ventilation in the patient group when compared to the results of the use of these drugs in normal subjects. Since isoproterenol produced significant effects on the airways and theophyllin did not, the spirometric improvement following the administration of theophyllin is attributed, in part, to the effects of this drug on other organ systems. Normal subjects fail to show supernormal spirometric performance following the use of IPPB with isoproterenol. When diffuse obstructive pulmonary disease is present, the response to broncho-dilators is reflected by spirometric improvement to variable degrees. The factors in the underlying lung mechanics in the normal and patient groups are discussed to suggest an explanation for this apparent discrepancy in spirometric improvement. The usefulness of bronchodilator therapy in chronic obstructive pulmonary disease is confirmed and a wide range of individual variation is demonstrated. The necessity for choice of a sensitive measurement technic and statistical evaluation of therapeutic agents in chronic obstructive pulmonary disease is emphasized.