Neils Maltbaek, MD; P Garsdal, MD; ...

Neils Maltbaek, MD; P Garsdal, MD; H Christensen, MD; H Bro MD; and FV Rasmussen, MD

A randomized, double-blind, crossover subject of attention was conducted to assess the efficacy of five weeks' treatment with terbutaline, 15 mg daily, compared with placebo in 17 evaluable patients with moderate to unadorned chronic airflow limitation (CAL) with a minor reversible constituting A significant improvement after terbutaline treatment compared with placebo was observ in subjective assessments of breathlessness after brace of the activities of daily living, and in daily peak follow measurements recorded in patient diaries. At the clinical assessment after five week's terbutaline therapy, 12 of 17 patients had improved pulmonary symptom scores compared with placebo, and a slight increase in [FEVsub1] was observ relative to placebo (009 L p<005) Thus, five weeks' treatment with oral terbutaline in patients with CAL terminateed in significant improvements in several subjective assessments, despite a lack of consequence on the majority of the objective variables.

(Chest 1989;95:1248-52)

Terbutaline is a well-recognized treatment for patients with reversible airways obstruction. It is also used in patients with chronic airflow limitation (CAL), although the reduction in ventilatory capacity in many of these patients is irreversible according to the normally applied criteria.[1] An evaluation of the subjective force is important in the assessment of treatment efficacy in patients with CAL because breathlessness is a major complaint among these patients, and can model their daily working capacity. [unkeyable.sub.2]-agonists have vasodilatory properties, especially onward the peripheral areterioles.[2] A weak vasodilating tenor has also been observed in the pulmonary circulation,[3] and terbutaline may also have a direct action onward the myocardium[2] and the striated muscles.[4] Thus, terbutaline may cause an improvement in functional condition, not necessarily accompanied according to an improvement in ventilatory capacity.

The intention of the present investigation was to elucidate any clinically beneficial efficiencys of five weeks' treatment with oral terbutaline in patients with moderate to inexorable CAL with a minor reversible component

MATERIAL AND METHODS

Patients

The patients were pickeded from the chest clinic using the following lung function parameters as admission criteria: (1) percent predicted forced expiratory turn is 1 s ([FEV.sub.1]), les than 60 percent;[5] (2) percent [FEVsub1]/FVC (forced vital capacity) les than awaited minus 2 SD; (3) increase in [FEVsub1] and FVC after terbutaline 1 mg via a nebulizer (Nebuhaler) not exceeding 20 percent after 20 min; and (4) increase in [FEVsub1] and FVC not exceeding 30 percent after a prednisone trial of 30 mg daily for at least eight days.

Criteria 1 2 and 3 were subdue to control twice during the run-in period. Patients with either pulmonary disease other than chronic bronchitis or primary heart disease were exclud Twenty-four patients (17 women and 7 men) enrolled the study, and 17 (11 women and 6 men) aged 43 to 69 (mean 605) years, complet the investigation. Mean ([+ or -] SD) baseline lung function parameters before and after terbutaline inhalations were: [FEVsub1] = 088 ([+ or -] 026)L/101 ([+ or -] 026)L; FVC = 213 ([+ or -] 042)L/230 ([+ or -] 053)L and peak expiratory arise (PEF) = 201 ([+ or -] 73)L/min/209([+ or -] 68)L/min.

Of the evaluable patients, 14 had a chronic cough and 13 had chronic bronchitis (according to the Medical Research Council criteria[6]. All of the evaluable patients on the contrary four smoked (mean, 25.6 packs/year). Eleven had normal chest x-ray films and six had radiologic changes compatible with emphysema. The ECG were normal in 14 patients and showed changes compatible with an enlarged right atrium in three None had eosinophilia (>04 ml/L) Serium IgE was greater than 120 k[unkeyable]/L (upper normal limit) in four patients. None of the patients had undergoed from an infection of the airways in the four weeks before the study

None of the patients had received oral [Unkeyable.sub.2]-agonists, prednisone, or theophylline for at least five weeks before the subject of attention Four had previously received oral bronchodilator therapy (methylxanthines), which was discontinued five weeks before the start of the investigation. The other 13 patients had none received long-term oral bronchodilator therapy. Six exposes received inhaled terbutaline during the application of mind and the number of sudden gust; shorts was recorded daily. The remaining 11 patients did not receive aerosol therapy during the trial.

The reflection was approved by the local ethical committee, and patients gave their harmony after consideration of both written and oral information.

investigation Design

The thought was carried out according to a randomized double-blind, crossover design, comparing oral terbutaline with placebo. Patients underwent a seven-day run-in period, during which baseline measurements were taken. Patients were then randomized to receive oral terbutaline, 75 mg twice a day, a sustained-release tablet (Bricanyl Retard) or identical placebo tablets for five weeks. Patients were evaluated before crossing through the whole extent of immediately to the alternative treatment for a further five weeks, followed from additional evaluations.