Inhaled oxitropium bromide is currently used as the first-line therapy of patients with chronic pulmonary disease in Japan.

With great interest, we read the article by CAZZOLA et al. [1] concerning the airway responses to salmeterol in combination with another bronchodilator in patients with chronic obstructive pulmonary disease (COPD). The authors concluded that "a pretreatment with a conventional dose of oxitropium bromide (OTB) did not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible COPD". Because inhaled OTB is widely used in treatment of patients with COPD in Japan [2±5], the results are clinically very important. We basically agree with the authors that further bronchodilating responses to salbutamol were not always investigated by pretreatment with OTB in patients with COPD. However, several possibilities still exist. The dose of OTB was not sufficient to prevent a further bronchodilation to salmeterol in the patients. Unfortunately the anthropometric data were not presented in the article, so it is difficult to evaluate whether a 200 mg of OTB was appropriate to elicit a maximal bronchodilation in the patients. It has been reported that OTB produces a dose-dependent increase of forced expiratory volume in one second (FEV1) in patients with COPD [6]. The other possibility is that the participants enrolled in the current study were asthmatic rather than stable COPD patients. Although anticholinergic drugs usually produce a greater bronchodilating response than b2-adrenergic drugs in stable COPD patients [7], the current study contradicted that b2-adrenergic agonists produced a better bronchodilation than anticholinergic inhalation. Because COPD is strictly differentiated from bronchial asthma in association with hyperresponsiveness to b2-adrenergic stimulants, patients having >20% reversibility on a b-adrenergic inhalational test were not determined as stable COPD patients. In the current study patients exhibited ~48% reversibility by a badrenergic inhalational drug. COPD also increases in frequency with age and is found more frequently in patients aged 70±80 yrs. Thus, age effect on the bronchodilator responses to the agents may be important. Bronchodilator responses to b2-adrenergic and/or anticholinergic inhalational drugs between younger and older patients with asthma or obstructive lung disease have been reported [3, 8, 9]. Impaired bronchodilator response to salbuterol was implicated in the elderly [9]. The age of patients in the current study, which was not mentioned in the article, may effect the airway responses to the bronchodilators. COPD is a slow but progressive disease. The main purposes of the treatment for COPD are considered to be prevention of exacerbation of the disease, and the production of a significant bronchodilating effect to maintain lung function, and subsequently achieving a standard level of quality of life (QoL). The b2-adrenergic agonists used to be the first-line bronchodilators for treatment of COPD. Although the current study demonstrated that an anticholinergic inhalation, OTB, did not produce a further bronchodilation with salbutamol in patients with COPD, the effects of other b2-adrenergic agonists on airway responses to OTB may be more important. Because the pathogenesis of COPD is closely related to the bronchomotor tone, which is based on the sympathetic and parasympathetic balance [7], inhaled OTB has already been used as the first line therapy of COPD in Japan. However, many elderly patients with COPD are often untreated despite some reversibility of airways obstruction in response to the drugs. As the inhaled anticholinergic drug may well be beneficial in these individuals in terms of reducing symptoms and improving the QoL [2±5, 10], older patients with chronic airflow limitation may be treated with the inhaled anticholinergic drug alone or its combination with b2adrenergic agents.