Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD). Dutch Study Group.

The objective of the present study was to investigate the dose-dependent bronchodilator efficacy and duration of action of the newly developed antimuscarinic agent tiotropium bromide in patients with chronic obstructive pulmonary disease (COPD). In a randomized, double-blind, placebo-controlled, crossover design, patients inhaled single doses of 10-80 micrograms tiotropium bromide and placebo, formulated in lactose powder capsules. The washout period between test doses was 72 h. Thirty five patients were enrolled in the trial (32 males and 3 females; mean age 64 yrs). Baseline forced expiratory volume in one second (FEV1) (mean 1.34 L) was less than 65% of predicted and was < 70% of forced vital capacity (FVC). All subjects had a smoking history of more than 10 pack-years. The mean reversibility of FEV1 after inhalation of 40 micrograms ipratropium bromide was 28%. Pulmonary function testing was performed before and at regular time intervals for up to 32 h after test drug administration. Compared to placebo, tiotropium bromide produced significant improvements in FEV1, FVC, peak expiratory flow rate (PEFR) and forced mid-expiratory flow (FEF25-75%). The bronchodilator response was almost immediate; peak improvement in FEV1 was reached 1-4 h after test drug inhalation, and the duration of action extended to 32 h after the 20, 40 and 80 micrograms doses. A clear dose-response relationship was seen for peak FEV1 and for the average FEV1 over differing time periods during the 32 h observation period, 80 micrograms of test drug being superior to the 10 micrograms dose. Peak improvement in FEV1 ranged 19-26% of test-day baseline for tiotropium bromide doses compared to 16% for placebo. The large improvement for placebo is probably due to carry-over effect which was significant. After excluding carry-over effect, the peak response to placebo decreased to 11%, whilst for tiotropium bromide doses it ranged 20-25%; standard error for mean difference was about 4%. There was no evidence of systemic anticholinergic effects. In this population of patients with COPD, tiotropium bromide was found to be a safe and long-acting bronchodilator, demonstrating a clear dose-response relationship following single dose administration.

Lipoma of the external thoracic wall.

We report the case history of an external thoracic wall lipoma, which was noticed incidentally on a chest roentgenogram because of its calcification. A probable diagnosis was made by computer tomography. Because of the increase in size of the tumour it was removed surgically, but no evidence of malignant degeneration was found.

Agenesis of the right upper lobe.

Bronchoscopy and bronchography revealed a very rare abnormality in the embryonal anatomy of the right bronchial tree in a 54-year-old woman with cough. There was a proximal migration of the apical branch of the right upper bronchus toward the trachea and a distal migration of the two other branches toward the middle lobe bronchus. The proximal migration was accompanied by a narrowing of the trachea. This case is considered an extremely rare embryonal variation in the development of the right bronchial tree.

A patient with methotrexate lung and granulomatous changes in the liver--or just sarcoidosis?

A 57 year old ex-miner, who had been treated for his psoriasis with methotrexate 5 mg 3 times a week, taken orally (in total +/- 12 g) developed in the spring 1985 the symptoms of an allergic pneumonia. In biopsies of lung and liver non-caseating granulomata were found, compatible with the diagnosis sarcoidosis. The question whether one clinical entity is concerned or two superponed diseases, remains unanswered.

Chordoma of the thorax.

Chordomata are malignant tumours which arise from foetal notochordal rests. They occur alongside the vertebral column, mostly at the cranial or caudal extremities, but they are seldom found in the thorax. A description is given of a thoracic chordoma in a 70-year-old male patient who presented with difficulty in swallowing and breathing. Emphasis is placed on the role of computer-assisted tomography in reaching the diagnosis.

Bronchiolo-alveolar carcinoma after inhalation of vegetable oil through a tracheal cannula.

Ten cases of carcinoma of the lung, mostly alveolar cell carcinomata, arising in patients after continuous use of (mostly mineral) oils as nose drops or laxatives, have till now been reported in the literature. We describe another such case, a man who used sesame oil to lubricate his tracheal cannula.

A supernumerary bronchus of the right upper lobe.

A patient with a bronchogenic carcinoma in the right lower lobe was found during bronchography to have an accessory right superior cardiac bronchus. Inspection of the right lung at operation and a control bronchogram, made 6 months after right lower lobectomy, confirmed that the congenital anomaly was a supernumerary bronchus and not a cardiac bronchus which had migrated proximally.

Treatment of chronic and recurrent respiratory infections with intramuscular ceftazidime.

Two groups of patients were treated with ceftazidime intramuscularly for 10 days. There were 34 patients with acute purulent exacerbations of chronic bronchitis of whom 20 received 1-g and the other 142-g injections. A further 38 patients with chronic recurrent respiratory infections (mostly severe bronchiectasis associated with Pseudomonas aeruginosa) were treated with 2-g injections twice or thrice daily. Blood and sputum concentrations of ceftazidime were measured microbiologically on the first day of treatment. The peak serum concentrations (34.4 and 37.8 mg/l after the 2 different doses) were reached between 1/2 and 1 h after the injections and the mean areas under the concentration-time curves were 131 mg/l X h and 149 mg/l X h, respectively. The sputum concentrations after the 2 doses reached 3.0 mg/l after 1 g, and 3.5 mg/l after the 2 g doses. Sputum cultures before and after treatment showed that 32 of the 34 patients with chronic bronchitis had negative cultures at the end of the treatment although 6 had further infections by the 17th study day. Among the 38 patients with relapsing infections with Gram-negative organisms, one died early in the treatment course and one later on, but 28 of the 37 patients had negative sputum cultures on day 11 and 17 of the 36 remaining were clear of infection on day 17. The recurrences were all associated with Ps. aeruginosa or Ps. maltophilia. Some 69% of the 69 Ps. aeruginosa strains were inhibited by 2 mg/l of ceftazidime and 91% by 4 mg/l. All 3 Ps. maltophilia strains were resistant (MICs greater than 32 mg/l).

Neurofibroma of the trachea: a case report.

A tracheal tumour was discovered by radiology in a 36-year-old man with haemoptysis, bronchitis, and dyspnoea. The tumour was situated 5 cm below the vocal cords. A frozen section of a bronchoscopic biopsy specimen confirmed it to be a neurofibroma. Resection was performed endoscopically.