Tiotropium does not affect lower urinary tract functions in COPD patients with benign prostatic hyperplasia
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.
Section snippets
Scoring using the IPSS and the QOL index
The IPSS is based on seven questions regarding micturition: (1) incomplete emptying, (2) frequency, (3) intermittency, (4) urgency, (5) weak urinary stream, (6) hesitancy, and (7) nocturia. Each question can be answered on a scale of 0–5 (ranging from “not at all” to “almost always”). The total score is the sum of the items 1–7 and may range from 0 to 35 (no symptoms to severe symptoms). The QOL index defined by the International Consultation on BPH included the response to the question “If you
Patient characteristics
Twenty-five adult males, with a mean age of 72.9 years, were enrolled in this study. The baseline characteristics of patients are shown in Table 1. According to the severity criteria of GOLD, the number of patients in stage I (mild), stage II (moderate), stage III (severe) and stage IV (very severe) was 3, 14, 6, and 2, respectively. Six patients had been treated with α1-blocker for BPH. PV measured by ultrasonography was 34.3±9.2 mL.
Efficacy of tiotropium for COPD
The changes in parameters related to COPD are shown in Table 1
Discussion
We carried out a prospective analysis of COPD patients with BPH to evaluate the effect of inhaled tiotropium on lower urinary tract functions. Tiotropium did not aggravate LUTS as assessed by the IPSS and the QOL index, or alter urinary flow or PVR as evaluated by uroflowmetry and ultrasonography, respectively. These data suggest that tiotropium does not exacerbate urinary retention in COPD patients with LUTD.
Systemic application of anticholinergics in effective dosages is often associated with
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2011, Side Effects of Drugs AnnualCitation Excerpt :Adequately powered randomized control trials with cardiovascular safety as their primary end-point are needed. In 25 patients with COPD and co-existing benign prostatic hyperplasia, tiotropium had no adverse effects on lower urinary tract function [96c]. In a randomized controlled trial in preschool children with asthma-like symptoms fluticasone had a beneficial effect on symptoms and montelukast on blood eosinophils compared with placebo [97c].
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