Tiotropium does not affect lower urinary tract functions in COPD patients with benign prostatic hyperplasia

Abstract

Background

Tiotropium is widely used for the treatment of chronic obstructive pulmonary disease (COPD), but it is not usually prescribed for patients with micturition disorder, such as benign prostatic hyperplasia (BPH), because of the potential to increase the risk of acute urinary retention through its anticholinergic effects. However, no data are available to prove a true causal relationship between tiotropium and lower urinary tract dysfunction (LUTD) using quantitative symptomatic scoring or objective parameters evaluated by uroflowmetry.

Objective

To clarify the effect of tiotropium on lower urinary tract functions in COPD patients with BPH.

Methods

This prospective pilot study comprised 25 male COPD patients with BPH as defined by the International Prostate Symptom Score (IPSS), the quality of life (QOL) index, maximum flow rate (Q-max) in uroflowmetry, and prostate volume. Patients were given tiotropium once a day for 3 months. At baseline and after treatment, lower urinary tract functions were assessed symptomatically by the IPSS and the QOL index, and objectively by urinary parameters, including Q-max, average flow rate (Q-ave), postvoid residual urine volume (PVR), and bladder voiding efficiency (BVE).

Results

Acute urinary retention was not observed in any patients. Subjectively, no significant difference was found in the IPSS or the QOL index between baseline and after tiotropium treatment. Additionally, tiotropium treatment did not change Q-max, Q-ave, time to Q-max, or overall flow time compared to baseline (Q-max (mL/s), 9.66±3.63, 9.11±3.68 and 10.51±3.88, P=0.15; Q-ave (mL/s), 4.20±1.76, 4.14±1.55, and 4.71±1.81, P=0.31; time to Q-max (s), 12.1±8.0, 16.2±11.4, and 13.0±11.3, P=0.10; flow time (s), 39.4±19.6, 40.4±20.1, and 38.3±19.1; baseline, 1 month after treatment and 3 months after treatment, respectively). No significant increase was found in PVR or BVE (PVR (mL), 57.9±51.2, 55.4±47.2 and 66.1±52.7, P=0.36; BVE (%), 75.8±18.4, 73.3±19.1 and 73.9±17.3, P=0.67; baseline, 1 month after treatment, and 3 months after treatment, respectively).

Conclusion

In our preliminary study, tiotropium did not adversely affect lower urinary tract functions in COPD patients with BPH, suggesting the possibility that tiotropium can be safely given to those patients. This warrants future studies in a larger series of COPD patients to validate our observations.

Introduction

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in the world. It is thought to be the only major disease that is continuing to increase in prevalence and mortality [1]. By 2020, COPD is estimated to become the fifth most common cause of disability and the third most frequent cause of death, just behind coronary and cerebrovascular disease [2]. Despite such enormous burden, no drugs for COPD have been shown to modify the long-term decline in lung function.

Tiotropium is a novel inhaled anticholinergics that exerts its effect through prolonged blockade of muscarinic M3 receptor [3], [4]. Various randomized clinical trials have demonstrated consistent improvements in lung function as well as dyspnea, health-related quality of life (QOL), exacerbations, and exercise tolerance [5]. Tiotropium has become widely used for the treatment of COPD. The latest international guideline published by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends tiotropium alongside other long-acting bronchodilators as first-line maintenance therapy for the management of COPD [6].

Systemic anticholinergic agents cause decreased tone of the ureter and bladder and their amplitude contraction [7]. Most COPD patients are elderly males in whom lower urinary tract dysfunction (LUTD), such as benign prostatic hyperplasia (BPH), is common. Thus, anticholinergic agents are not usually prescribed for COPD patients with LUTD, because they may cause voiding problems and increase the risk of acute urinary retention. Therefore, tiotropium should be prescribed with caution in patients with BPH, or bladder-neck obstruction [8]. Several meta-analyses demonstrated an increased risk of urinary retention in COPD patients receiving tiotropium [9], [10]. In contrast, no significant increase in the incidence of urinary retention was reported in COPD patients treated with tiotropium, compared to those taking placebo, in several randomized placebo-controlled trials [5], [11], [12], [13]. With this regard, the latest GOLD guidelines state that, although occasional prostatic symptoms have been reported, there are no data to prove a true causal relationship [6]. Whether tiotropium adversely affects lower urinary tract functions must be urgently clarified, because many elderly COPD patients have LUTD.

In previous studies determining the risk of urinary retention by tiotropium, the retention was subjectively defined by the “presence” or the “absence” of symptoms. Objective measurements to assess lower urinary tract functions, such as urinary flow rate and postvoid residual urine volume (PVR), were absent. Recently, a more accurate symptomatic scoring system—the International Prostate Symptom Score (IPSS)—was developed to evaluate lower urinary tract symptoms (LUTS) associated with BPH [14]. The IPSS, which comprises seven questions about voiding symptoms, is designed to semiquantitatively assess severity of LUTS. The QOL index is recommended to evaluate QOL associated with micturition disorders by the International Consultation on BPH. In addition, uroflowmetry has been utilized in patients with BPH to provide an objective and precise grading of LUTD. Using the IPSS, the QOL index, uroflowmetry, and PVR would be advantageous for evaluating the effect of tiotropium on lower urinary tract functions more precisely.

The present study was conducted to ascertain if inhaled tiotropium deteriorates lower urinary tract functions in COPD patients, particularly in those with BPH, who were likely to be more susceptible to anticholinergic effects on lower urinary tract functions. We prospectively evaluated LUTS by the IPSS and the QOL index, carried out uroflowmetry, and measured PVR during tiotropium therapy.