TY - JOUR
T1 - Efficacy of Targeted Mast Cell Inhibition Therapy in Chronic Prostatitis/Chronic Pelvic Pain Syndrome
AU - Pattabiraman, Goutham
AU - Engel, Geoffrey
AU - Osborn, Catherine V.
AU - Murphy, Stephen Fintan
AU - Schaeffer, Anthony J
AU - Thumbikat, Praveen
N1 - Funding Information:
Funding Support: This work was supported by the National Institute of Diabetes and Digestive and Kidney (NIDDK) grant R01DK083609 to Praveen Thumbikat. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript.
Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/10
Y1 - 2023/10
N2 - Objective: To identify a subgroup of patients with mast cell dysfunction in chronic prostatitis/chronic pelvic pain syndrome and evaluate efficacy of mast cell-directed therapy. Materials and Methods: Men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited and evaluated in an open-label, interventional uncontrolled trial after therapy with cromolyn sodium and cetirizine hydrochloride. The primary endpoint was a change in mast cell tryptase concentrations after treatment while secondary endpoints were changes in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and AUA-SI. Isolated cells from postprostatic massage urine were evaluated for immune changes using mRNA expression analysis. Results: 31 patients with a diagnoses of Category III CP/CPPS were consented, 25 patients qualified and 20 completed the study after meeting a prespecified threshold for active tryptase in expressed prostatic secretions. After treatment with cromolyn sodium and cetirizine dihydrochloride for 3-week, active tryptase concentrations were significantly reduced from 49.03 ± 14.05 ug/mL to 25.49 ± 5.48 ug/mL (P < .05). The NIH-CPSI total score was reduced with a mean difference of 5.2 ± 1 along with reduction in the pain, urinary and quality of life subscores (P < .001). A reduction in the AUA-SI was observed following treatment (P < .05). NanoString mRNA analysis of isolated cells revealed downregulation of immune-related pathways including Th1 and Th17 T cell differentiation and TLR signaling. Marked reduction in CD45+ cells and specifically macrophages and neutrophil abundance was observed. Conclusion: Identification of CP/CPPS patients with mast cell dysfunction may be achieved using tryptase as a discriminating biomarker. Mast cell-directed therapy in this targeted subgroup may be effective in reducing symptoms and modulating the immune inflammatory environment.
AB - Objective: To identify a subgroup of patients with mast cell dysfunction in chronic prostatitis/chronic pelvic pain syndrome and evaluate efficacy of mast cell-directed therapy. Materials and Methods: Men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited and evaluated in an open-label, interventional uncontrolled trial after therapy with cromolyn sodium and cetirizine hydrochloride. The primary endpoint was a change in mast cell tryptase concentrations after treatment while secondary endpoints were changes in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and AUA-SI. Isolated cells from postprostatic massage urine were evaluated for immune changes using mRNA expression analysis. Results: 31 patients with a diagnoses of Category III CP/CPPS were consented, 25 patients qualified and 20 completed the study after meeting a prespecified threshold for active tryptase in expressed prostatic secretions. After treatment with cromolyn sodium and cetirizine dihydrochloride for 3-week, active tryptase concentrations were significantly reduced from 49.03 ± 14.05 ug/mL to 25.49 ± 5.48 ug/mL (P < .05). The NIH-CPSI total score was reduced with a mean difference of 5.2 ± 1 along with reduction in the pain, urinary and quality of life subscores (P < .001). A reduction in the AUA-SI was observed following treatment (P < .05). NanoString mRNA analysis of isolated cells revealed downregulation of immune-related pathways including Th1 and Th17 T cell differentiation and TLR signaling. Marked reduction in CD45+ cells and specifically macrophages and neutrophil abundance was observed. Conclusion: Identification of CP/CPPS patients with mast cell dysfunction may be achieved using tryptase as a discriminating biomarker. Mast cell-directed therapy in this targeted subgroup may be effective in reducing symptoms and modulating the immune inflammatory environment.
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U2 - 10.1016/j.urology.2023.05.047
DO - 10.1016/j.urology.2023.05.047
M3 - Article
C2 - 37442295
AN - SCOPUS:85168004089
SN - 0090-4295
VL - 180
SP - 200
EP - 208
JO - Urology
JF - Urology
ER -