Management of Chronic Obstructive Pulmonary Disease with Tiotropium Bromide

A. James Mamary and Gerard J. CrinerDivision Pulmonary and Critical Care Medicine, Temple University School of Medicine, Philadelphia PA 19140, USA. AbstractIn COPD, pathologic upregulation and stimulation of muscarinic (M) receptors contribute to bronchospasm, mucus hypersecretion and possibly airway remodeling. Tiotropium bromide (brand name Spiriva; Boehringer Ingelheim/Pfizer) inhalational powder was approved by the US Food and Drug Administration in January 2004 for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Tiotropium is recommended by the Global initiative for Chronic Obstructive Lung Disease (GOLD) as a first-line therapeutic in treating chronic moderate and severe COPD and is the only long acting inhaled anti-muscarinic (anti-cholinergic) therapy available for the treatment of COPD in the USA. The primary functional effect of tiotropium is mediated through antagonism of M3 receptors and the decreased acetylcholine induced airway smooth muscle bronchoconstriction. Tiotropium is associated with increased lung function, health related quality of life, and exercise tolerance and reduced dyspnea and acute exacerbations of COPD (AECOPD). On November 19, 2009 the Pulmonary-Allergy Drugs Advisory Committee voted 11-1 for new product labeling about the benefits of tiotropium stating that the data provide "substantial and convincing evidence" that tiotropium decreases AECOPD. This indication "for reducing COPD exacerbations" was added to product labeling in December 2009. Tiotropium is safe and well tolerated with few side effects. The large multicenter UPLIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium) trial demonstrated the long-term safety of tiotropium over four years of continuous use showing no increase in stoke and all cause mortality. Serious adverse events including respiratory failure, congestive heart failure and myocardial infarction were significantly less in the tiotropium group. In a pre-specified subgroup analysis Tiotropium retarded FEV1 decline in milder COPD. Additional review of cholinergic pathobiology relevant to COPD and asthma provides context for future therapeutic and preventative roles for tiotropium.