Improvements in exercise capacity and dyspnoea by inhaled anticholinergic drug in elderly patients with chronic obstructive pulmonary disease

Age and Ageing, July, 1995 by Shinji Teramoto, Yoshinosuke Fukuchi

Introduction

With the growth in the aged population, increasing numbers of patients with chronic obstructive pulmonary disease (COPD) are elderly. COPD is a slowly progressive disease, and the main objectives of treatment are prevention of exacerbations, production of bronchodilation to maintain lung function, and achievement of an acceptable quality of life (QOL) [1]. At present, [[beta].sub.2]-adrenergic agonists are usually the first-line bronchodilators for treatment of COPD [2]. Inhaled anticholinergic drugs are also effective for COPD patients, since the pathogenesis of COPD is closely related to bronchomotor tone, which reflects sympathetic and parasympathetic balance [3, 4]. The main benefit of inhaled anticholinergics is as additional bronchodilator therapy, either in addition to [[beta].sub.2]-adrenergic agonists or in place of them in subjects who are more sensitive to anticholinergics than [[beta].sub.2]-agonists [5, 6]. Because, [beta]-adrenergic receptors decrease with age [7], the response to anticholinergic agents in elderly subjects may be greater than that in young adults. However, older patients with airway obstruction, that has some reversibility to the drugs, may not always be treated. This may result from lack of information regarding effectiveness of the drugs for symptomatic relief.

In the present study, we tested the effects of the anticholinergic drug, oxitropium bromide (OTB), on lung function, exercise capacity, and exertional dyspnoea in elderly COPD patients (more than 75 years old) using a double-blind placebo-controlled study, in comparison with middle-aged patients (less than 65 years of age).

Methods

Patients: We studied 24 men with mild to moderate chronic obstructive pulmonary disease (COPD). The demographic and anthropometric data of the patients are shown in Table I. Our sample was defined by history and supporting radiological and pulmonary function criteria. All patients were smokers or ex-smokers. No patients had a forced expiratory volume in one second ([FEV.sub.1]) of more than 60% of that predicted, and no patient had more than 15% reversibility on a 6-adrenergic inhalation test. In addition, no patient had a diffusing capacity of the lung for CO (Dco) of more than 60% predicted. Predicted values for vital capacity and Dco were recalculated using the equation of Baldwin et al. [8] and Burrows et al. [9]. Prior to the beginning of this study, all patients gave informed consent to participate in the study, and all treatment was withheld for 4 weeks. Subjects were divided into two groups based on age: an elderly group of 75 years and older and a middle-aged group, 50-65 years old.

Table I. Clinical and physiological data
                                  Elderly            Middle-aged
                                  group              group
                                  (n = 12)           (n = 12)
Age (years)                       78.7 (1.1)          66.1 (1.0)
range                             75-86               55-64
Height (cm)                      162.2 (1.1)         163.7 (1.0)
Weight (kg)                       51.7 (1.6)          53.6 (2.1)
FVC (1)                            2.37 (0.06)         2.54 (0.09)
%VC (%)                           81.9 (1.8)          74.0 (2.5)
[FEV.sub.1] (1)                    1.25 (0.06)         1.33 (0.08)
[FEV.sub.1%] (%)                  41.3 (1.6)          38.9 (2.0)
DLco(ml/min/mmHg)                  5.08 (0.61)         7.64 (0.69)
DLco% (%)                         44.1 (4.4)           45.2 (3.1)
Presented as mean (SE).
FVC: forced vital capacity, %VC: FVC percentage of
predicted VC, [FEV.sub.1]: forced expiratory volume in  1s,
[FEV.sub.1%]: [FEV.sub.1] as a percentage of predicted VC, DLco:
diffusion capacity of the lung for carbon monoxide, DLco%:
DLco percentage of the predicted value.

Study design: Spirometry and exercise testing were performed twice a day on the 24 patients before and after inhalation of OTB 300 [mu]g or placebo 300 [mu]g (Figure 1). On-the next day, the same protocol was repeated using alternate inhalation. Each study started between 09 h 00 and 10 h 00. Spirometric indices were obtained for each patient from the best three maximal flow-volume curves using a dry-sealed-type box spirometer (ST-460, Fukuda Sangyo, Japan) immediately before (`Pre') and 30 minutes after (`Post') inhalation of OTB 300 [mu]g. Measurements were made on forced vital capacity (FVC) and [FEV.sub.1]. The OTB was administered by three puffs from identical metered-dose inhalers (MDI), delivered successively and without delay. The progressive 10 watt incremental exercise testing was repeated to a symptom-limited maximum on a bicycle ergometer (220 Wood RD, Collins Corp.) before and 45 minutes after inhalation of OTB or placebo (Figure 1). After 1 minute of cycling, the work-load was increased by 10 watt each minute until the patient was unable to continue. Patients stopped the exercise test mainly because of dyspnoea. Measurements were made of minute ventilation (VE), oxygen uptake ([Vo.sub.2]) and respiratory frequency (Rf) by mass spectrometer (WSMR-1400, Westron Corp., Japan)-pneumotachometer-computer (PC-9801, NEC Corp., Japan) system (WLCS-5100) [10]. Prior to each test, the spirometer was calibrated with a 2-1 calibration syringe, and the mass spectrometer was calibrated against gas mixtures of known concentrations ([O.sub.2] 20.9%, Ar 9.5%, C02 5.00%, [C.sub.2][H.sub.2] 0.650%, [N.sub.2] balance) [10]. Arterial oxygen saturation ([Sao.sub.2]) was continuously monitored from before to after exercise using a pulse oximeter (502-P, Criticare System Inc. . Rest [Sao.sub.2] was determined by the stable [Sao.sub.2] in the resting ventilation immediately before exercise. Nadir [Sao.sub.2] was determined as the minimum value which was observed during the exercise test.