At the inclusion visit, therapy with inhaled corticosteroids, when used, was discontinued, after which the subjects had to be stable for 2 months. At the second visit, 2 months later, spirometry was performed followed by SI. The results of these latter measurements were used as baseline, stable phase values. From the second visit, therapy with all long-acting β2-sympaticomimetic agents was withdrawn. After this, patients were asked to contact the research doctor at any time of the day or night to report any deterioration in symptoms for which they would normally contact either their primary care physician or their pulmonologist. An exacerbation was defined according to the criteria of Davies et al11 (ie, a history of increased breathlessness; and at least two of the following symptoms for ≥ 24 h: increased cough frequency or severity, increased sputum volume or purulence, and increased wheeze). During an exacerbation, the postbronchodilator FEV1 had to be < 70% predicted. Patients were not accepted for SI treatment if their FEV1 was < 0.8 L and the arterial oxygen pressure was < 8.0 kPa.