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Biomedical subjects

Nicholas J Gross

Publications and source records attributed to Nicholas J Gross.

5 recordsLinked to original sources

Anticholinergic agents in asthma and COPD.

Anticholinergic agents have important uses as bronchodilators for the treatment of obstructive airway diseases, both asthma and, more particularly, chronic obstructive pulmonary disease (COPD). Those in approved clinical use are synthetic quaternary ammonium congeners of atropine, and include ipratropium bromide, oxitropium bromide, and tiotropium bromide, each of which is very poorly absorbed when given by inhalation. Ipratropium and oxitropium have relatively short durations of action (4-8 h). They have been widely used for many years, either alone or in combination with short-acting beta-adrenergic agents such as albuterol and fenoterol, for both maintenance treatment of stable disease and for acute exacerbations of airway obstruction. Tiotropium, which was introduced in the early 2000s, has a duration of action of at least 1-2 days making it suitable for once-daily maintenance treatment of COPD. All of the above agents have a wide therapeutic margin and are safe and well tolerated by patients.

Asthma↗

Chronic obstructive pulmonary disease outcome measurements: what's important? What's useful?

The severity of chronic obstructive pulmonary disease (COPD) and patients' response to therapy are difficult to assess. The traditional measure, spirometry, correlates poorly with important clinical features of the disease, such as survival and quality of life (QOL). Moreover, COPD has recently been recognized as a systemic disease, and its systemic manifestations, such as weight loss and muscle weakness, are only poorly related to lung function. Therefore, although lung function remains an important outcome, other outcomes must be included in any overall assessment of disease severity or response to interventions. Examples include refinements of spirometry, such as measurement of FEV6 and inspiratory capacity; functional outcomes, such as dyspnea indexes and exercise tests; and global-clinical outcomes, such as QOL questionnaires and assessment of frequency and severity of acute exacerbations. For scoring disease severity, making a prognosis, or determining the outcome of novel interventions, composite measures need to be developed that take into account as many aspects of COPD as practicable.

Dyspnea↗

Tiotropium bromide.

Tiotropium bromide is a novel, inhaled, once-daily anticholinergic bronchodilator that has recently been approved in the United States for use in patients with COPD. Its unique feature is the persistence of bronchodilation for > 24 h due to prolonged M(3) muscarinic receptor blockade. Tiotropium provides significant improvement in spirometry and lung volumes. Clinically relevant outcomes such as the relief of dyspnea, improvement in the quality of life (health status), and reductions in the frequency and severity of acute exacerbations have been consistently obtained with tiotropium in clinical trials. In head-to-head trials, tiotropium administered once daily resulted in bronchodilation (peak, trough, and area under the curve) that was statistically superior to ipratropium administered four times daily and salmeterol administered twice daily. Clinical outcomes (dyspnea, quality of life, exacerbation frequency) were numerically but not always statistically better with tiotropium than salmeterol. Long-term studies of the combination of tiotropium with adrenergic agents, methylxanthines, or inhaled corticosteroids have not been reported in full. Several 1-year studies demonstrate that the only significant side effect of tiotropium was dryness of the mouth, which occurred in approximately 10 to 16% of patients; it is well tolerated by patients and safe.

Acute Disease↗