Nitric oxide (NO) has been detected in the exhaled air of animals and humans [1], and the exhaled NO level is often very high in patients with inflammatory airway diseases, such as upper respiratory tract infection [2], bronchiectasis [3], and bronchial asthma [4,5]. Exhaled NO levels are considered to be a useful marker for monitoring the activity of inducible NO synthase (NOS) (iNOS: type 2 NOS) associated with airway inflammation in asthma patients, and they have been used as an index of response to antiasthma therapies, such as inhaled glucocorticoids [6,7], leukotriene receptor antagonists [8], and an inhaled long-acting  2 stimulator [9].It is also well known, however, that exhaled NO levels are affected by many other factors, such as contamination by nasal NO [10,11], breath-holding time [12], exercise [13], and respiratory pattern [14], and for that reason the American Thoracic Society published guidelines for measurement of exhaled NO [15] to standardize this procedure.The degree and inhomogeneity of airway constriction may also influence the overall exhaled NO levels at the mouth. If the peripheral airways constrict in areas where airway inflammation is severe and high levels of NO are produced by type 2 NOS, the regional high NO level may not be fully detected at the mouth, since NO is trapped in the lung distal to the constricted airway. We therefore suspected that bronchodilators acutely increase exhaled NO levels by opening constricted airways, since the peripheral lung contains high levels of NO. This acute effect of bronchodilators on exhaled NO levels has never been systematically investigated, though many studies have been completed in which exhaled NO levels have been Key words: bronchial asthma, exhaled nitric oxide, bronchoconstriction, methacholine, salbutamol.
Abstract:In previous studies the exhaled nitric oxide (NO) level of asthma patients was investigated only in association with bronchial inflammation, and whether the degree of bronchoconstriction itself influences the exhaled NO level has never been investigated. We therefore evaluated the effect of inhalation of a bronchoconstrictor (methacholine) or a bronchodilator (salbutamol) on the exhaled NO level of healthy volunteers and asthma patients. The exhaled NO level of the healthy volunteers decreased after methacholine inhalation. The exhaled NO level of patients with mild or moderate persistent asthma, who had no asthma attacks on the day of measurement, increased after salbutamol inhalation, and the exhaled NO level of asthma patients during asthma attacks increased after salbutamol inhalation followed by intravenous drip infusion of aminophylline. It is suspected that large amounts of NO are trapped in the lung distal to the constricted airway, contributing little to the exhaled NO level at the mouth. However, we expect that the trapped NO is exhaled at a larger fraction after the dilatation of the constricted small airway, thereby increasing the exhaled NO level at the mouth. In conclusion, the results of this study suggest th...