tiotropium-bromide and Emphysema

The effects of tiotropium, an inhaled long-acting anti-cholinergic agent, on lung function were investigated in obstructed severe asthmatics with and without emphysematous changes despite maximal recommended treatments with high-dose of inhaled glucocorticoids and inhaled long-acting β(2)-agonists. We conducted a double-blind, placebo-controlled study of an inhaled single-dose of tiotropium in 18 asthmatics with emphysema and 18 without emphysema in a crossover manner. The primary efficacy outcome was the relative change in forced expiratory volume in 1 s (FEV(1)) from baseline to 60 min, and the secondary outcome was a relative change in FEV(1) from baseline to 12 h. Subsequently, the patients were treated with tiotropium inhaled once daily for 12 weeks in an open label manner, and lung function and symptoms were evaluated. At baseline, patients with or without emphysema had a mean FEV(1) of 55.9% before tiotropium and 56.8% before placebo, or 77.4% before tiotropium and 77.6% before placebo of the predicted value and were taking a mean dose of inhaled glucocorticoids of 1444 or 1422 μg/day. Among patients with emphysema, the increase from baseline FEV(1) was 12.6 percentage points higher at 60 min after tiotropium than after placebo. Among patients without emphysema, the increase from baseline FEV(1) was 5.4 percentage points higher at 60 min after tiotropium than after placebo. Tiotropium resulted in improved lung function and symptoms in asthmatics with and without emphysema. These findings suggest that tiotropium will provide a new strategy for the treatment of bronchial asthma and of overlapping asthma and COPD.

Topics: Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Emphysema; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Scopolamine Derivatives; Tiotropium Bromide; Vital Capacity

Airway remodelling and emphysema are major structural abnormalities in chronic obstructive pulmonary disease (COPD). In addition, pulmonary vascular remodelling may occur and contribute to pulmonary hypertension, a comorbidity of COPD. Increased cholinergic activity in COPD contributes to airflow limitation and, possibly, to inflammation and airway remodelling. This study aimed to investigate the role of acetylcholine in pulmonary inflammation and remodelling using an animal model of COPD. To this aim, guinea pigs were instilled intranasally with lipopolysaccharide (LPS) twice weekly for 12 weeks and were treated, by inhalation, with the long-acting muscarinic receptor antagonist tiotropium. Repeated LPS exposure induced airway and parenchymal neutrophilia, and increased goblet cell numbers, lung hydroxyproline content, airway wall collagen and airspace size. Furthermore, LPS increased the number of muscularised microvessels in the adventitia of cartilaginous airways. Tiotropium abrogated the LPS-induced increase in neutrophils, goblet cells, collagen deposition and muscularised microvessels, but had no effect on emphysema. In conclusion, tiotropium inhibits remodelling of the airways as well as pulmonary inflammation in a guinea pig model of COPD, suggesting that endogenous acetylcholine plays a major role in the pathogenesis of this disease.

Topics: Acetylcholine; Airway Remodeling; Animals; Animals, Outbred Strains; Cholinergic Antagonists; Disease Models, Animal; Emphysema; Goblet Cells; Guinea Pigs; Lipopolysaccharides; Lung; Male; Mucin 5AC; Muscarinic Antagonists; Neutrophils; Pneumonia; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Scopolamine Derivatives; Tiotropium Bromide

Very little information is known about patients with chronic obstructive pulmonary disease who travel to high altitude for work or pleasure. Even less is known about the outcomes at high altitude for patients with severe bullous lung disease. We present the case of a 54-yr-old man with vanishing lung syndrome, an idiopathic form of severe bullous emphysema, who has made repeated trips to altitudes as high as 3400 m, where he has engaged in physical activity, such as downhill skiing. We consider the issues of adequacy of oxygenation and the risks of barotrauma in patients with obstructive lung disease traveling to high altitude, and we also consider factors, such as improved air-flow limitation, maintenance of adequate ventilation-perfusion matching, and underlying physical fitness, which may affect our patient's ability to tolerate physical activity in this environment. The case demonstrates that the presence of severe lung disease does not necessarily preclude travel to and moderate activity at high altitude. Such travel may, in fact, be safe as long as the patient has undergone appropriate pretravel evaluation, and we provide recommendations regarding such evaluation in patients with chronic obstructive pulmonary disease.

Topics: Adrenergic beta-Agonists; Albuterol; Altitude; Androstadienes; Blister; Bronchodilator Agents; Cholinergic Antagonists; Emphysema; Exercise Test; Fluticasone; Humans; Male; Middle Aged; Respiratory Function Tests; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Tomography, X-Ray Computed; Treatment Outcome; Washington