St. Sauver et al. Respond to "Lower Urinary Tract Symptoms and Inflammation"

Abstract

We appreciate the opportunity to respond to the erudite commentary by Drs. Freedland and Aronson (1) regarding our manuscript examining associations between C-reactive protein levels and development of lower urinary tract symptoms (LUTS) and other urologic outcomes (2). The authors correctly note that the associations we found of elevated C-reactive protein levels with irritative LUTS and peak fl ow rates were restricted to only the most rapid worsening of these outcomes. Because C-reactive protein is a very nonspecific marker of systemic inflammation, it may be that inflammation in the urogenital tract needs to be substantial before systemic inflammatory markers are affected; consequently, this possibility may be why we saw associations of only elevated C-reactive protein levels with the most rapid increases in irritative LUTS and the most rapid declines in peak flow rates. Therefore, we completely agree with the authors that better markers of inflammation that are more proximal to the urologic system could substantially enhance our understanding of the role of inflammation in the development of LUTS and prostatic enlargement. Additionally, as noted by the authors (1), inflammation found in prostate biopsies has been only weakly associated with either irritative or obstructive symptoms (3). It is clear that LUTS may develop even in the absence of increases in prostate volume, and it is possible that inflammation in other components ofthe urogenital system could play an important role in the development of LUTS. Unfortunately, prostate biopsies are invasive, and the question of how to measure inflammation in the bladder, the bladder neck, or even the urethra remains perplexing. The discovery of inflammatory markers that are tightly linked to inflammation in the urogenital tract but that could be tested from serum or urine would be extremely useful in furthering our understanding of how prostatic versus nonprostatic inflammation might contribute to the development of LUTS. Drs. Freedland and Aronson (1) also note that prospective trials of antiinflammatory medications to treat established LUTS or prostatic enlargement have been disappointing. However, the benefit of antiinflammatory agents might be realized in primary rather than secondary prevention of these conditions. It is possible that inflammation may play a role in the development of LUTS or prostatic enlargement, but, once these conditions are established, antiinflammatory agents might have little effect in alleviating these conditions. Intervening earlier in the pathogenic process might help prevent their development. Indeed, the authors note the recent study in which statins were associated with a reduction in prostate-specific antigen levels in healthy men, suggesting an effect on the prostate (4). Additionally, in our own cohort, we previously found that long-term nonsteroidal antiinflammatory drug use was associated with a decreased likelihood of developing LUTS and an enlarged prostate (5). Future studies could help determine whether inhibiting inflammatory processes before LUTS or prostatic enlargement is established might be useful in preventing these conditions.