Aspirin Use and Lung Cancer Risk: A Possible Relationship? Evidence from an Updated Meta-Analysis

<div><p>Background and Purpose</p><p>Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships.</p><p>Methods</p><p>We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR) and its 95% confidence interval (CI) were used for cohort studies, while odds ratio (OR) were employed for case-control studies. The random effects and fixed effects models were used for analyses.</p><p>Results</p><p>18 studies were identified including 19835 lung cancer cases, which were eligible for inclusion in the present meta-analysis. Pooled data from case-control studies showed a significant inverse association between regular aspirin use and lung cancer risk. But for cohort studies, insignificant association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI: 0.95 – 1.16; I²: 10.3%, p value: 0.351). In case-control studies, standard aspirin use (>325mg) was related to lower lung cancer incidence, compared with low-dose aspirin use (75–100mg). A similar trend was observed in cohort studies. Besides, when analysis was restricted to long time regular aspirin use (>5 years), insignificant results were reported in both cohort and case-control studies. Finally, regular aspirin use might result in higher reduction of non-small cell lung cancer incidence among men.</p><p>Conclusions</p><p>Our findings do not support the protective effect of regular aspirin use on lung cancer risk. Long time aspirin use, sex, dose and type of lung cancer might alter the effect of aspirin use on lung cancer risk. More well-designed studies are needed to further clarify these associations.</p></div

Begg’s funnel plot of studies on aspirin use and risk of lung cancer for evaluation of publication bias.

<p>Begg’s funnel plot of studies on aspirin use and risk of lung cancer for evaluation of publication bias.</p

Forest plot and meta-analysis of long time regular aspirin use and lung cancer risk among cohort studies, stratified by study design.

<p>ES refers to relative risk among cohort studies and odds ratio among case-control studies. Long time regular aspirin use was defined as “regular aspirin use for more than 5 years, regardless of the dose”. The solid diamonds and horizontal lines correspond to the study-specific estimated risks and 95% CIs. Besides, the hollow diamonds represent the pooled relative risk and 95% CIs. Abbreviation: CI: confidence interval.</p

Forest plot and meta-analysis of regular aspirin use and incidence of lung cancer, stratified by dose of usage.

<p>Standard aspirin use refers to “regular aspirin use with dose ≥325mg”, while low-dose aspirin use is considered for “regular aspirin use with dose between 75 to 100mg”. The solid diamonds and horizontal lines correspond to the study-specific estimated risks and 95% CIs. Besides, the hollow diamonds represent the pooled relative risk and 95% CIs. Abbreviation: RR: relative risk, CI: confidence interval.</p

Characteristics of studies included in the meta-analysis of aspirin use and risk of lung cancer.

<p>^∗: Represents ‘Post-trial of Randomized Controlled Trial’.</p><p>^£: McCormack VA et.al investigated 8 studies from ILCCO that had data on aspirin or NSAID use prior to diagnosis, including 7 case-control studies and 1 cohort study.</p><p>^Ф: In this cohort, ‘total average use over the 10 years’ was estimated by multiplying usual days per week by the number of years, using the midpoints of the categories, divided by 10.</p><p>^Я: Reference defined as “no self-reported use or prescriptions more than 1 year before index date”.</p><p>Adjustment: 1. Age, 2. Education, 3. Fruit consumption, 4. Vegetable consumption, 5. Housing type, 6. History of cancer in 1^st degree relative, 7. Sex, 8. Race, 9. Body mass index, 10. Smoking status, 11. Pack-years, 12. History of chronic obstructive pulmonary disease, 13. History of ulcer, migraine or chronic headache, osteoarthritis or chronic joint pain, rheumatoid arthritis, coronary artery disease, 14. Use of other NSAIDs, 15. Year of birth, 16. Study, 17. Study region, 18. Interview year, 19. Alcohol use, 20. Physical activity level, 21. Use of hormone replacement therapy, 22. History of mammography or colorectal endoscopy, 23. History of PSA testing, 24. Diabetes, 25. Hypertension, 26. Calendar year.</p><p>Abbreviation: VITAL: VITamins And Lifestyle cohort, RCT: Randomized controlled study, C: case-control study, H: Hospital-based, P: Population-based, d: day, Wk: week, y: year, vs: versus, F: female, M: male, RR: relative risk, OR: odds ratio, ILCCO: International Lung Cancer Consortium, SCLC: Small cell lung cancer, CPS II NC: Cancer Prevention Study II Nutrition Cohort, IWHS: Iowa Women’s Health Study, HPFS: The Health Professionals Follow-Up Study, NHEFS: NHANES I Epidemiologic Follow-up Studies, NHANES: National Health and Nutrition Examination Survey.</p><p>Characteristics of studies included in the meta-analysis of aspirin use and risk of lung cancer.</p

The detailed steps of literature search in the present meta-analysis.

<p>The detailed steps of literature search in the present meta-analysis.</p

Intravesical Resiniferatoxin for the Treatment of Storage Lower Urinary Tract Symptoms in Patients with Either Interstitial Cystitis or Detrusor Overactivity: A Meta-Analysis

<div><p>Background</p><p>While Resin­iferatoxin (RTX) has been widely used for patients with storage lower urinary tract symptoms (LUTS), its clinical efficiency hasn't yet been well evaluated. A meta-analysis was performed to evaluate the exact roles of intravesical RTX for the treatment of storage LUTS in patients with either interstitial cystitis (IC) or detrusor overactivity (DO).</p><p>Methods</p><p>A meta-analysis of RTX treatment was performed through a comprehensive search of the literature. In total, 2,332 records were initially recruited, 1,907 from Elsevier, 207 from Medline and 218 from the Web of Science. No records were retrieved from the Embase or Cochrane Library. Seven trials with 355 patients were included and one trial was excluded because of the lack of extractable data. The analyses were all performed using RevMan 5.1 and MIX 2.0.</p><p>Results</p><p>Bladder pain was significantly reduced after RTX therapy in patients with either IC or DO. The average decrease of the visual an alogue pain scale was 0.42 after RTX treatment (p = 0.02). The maximum cystometric capacity (MCC) was significantly increased in patients with DO (MCC increase, 53.36 ml, p = 0.006) but not in those with IC (MCC increase, −19.1 ml, p = 0.35). No significant improvement in urinary frequency, nocturia, incontinence or the first involuntary detrusor contraction (FDC) was noted after RTX therapy (p = 0.06, p = 0.52, p = 0.19 and p = 0.41, respectively).</p><p>Conclusions</p><p>RTX could significantly reduce bladder pain in patients with either IC or DO, and increase MCC in patients with DO; however, no significant improvement was observed in frequency, nocturia, incontinence or FDC. Given the limitations in the small patient size and risk of bias in the included trials, great caution should be taken when intravesical RTX is used before a large, multicenter, well-designed random control trial with a long-term follow-up is carried out to further assess the clinical efficacy of RTX in in patients with storage LUTS.</p></div

Nocturia changes in all the patients (A; mean difference −0.16, 95% CI −0.64 to 0.33, p = 0.52) and subgroup analyses of nocturia in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; mean difference for IC −0.25, 95% CI −1.00 to 0.49, p = 0.51; mean difference for DO −0.09, 95% CI −0.73 to 0.55, p = 0.78). Incontinence changes in all the patients (C; mean difference −2.26, 95% CI −5.68 to 1.15, p = 0.19).

<p>Nocturia changes in all the patients (A; mean difference −0.16, 95% CI −0.64 to 0.33, p = 0.52) and subgroup analyses of nocturia in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; mean difference for IC −0.25, 95% CI −1.00 to 0.49, p = 0.51; mean difference for DO −0.09, 95% CI −0.73 to 0.55, p = 0.78). Incontinence changes in all the patients (C; mean difference −2.26, 95% CI −5.68 to 1.15, p = 0.19).</p

Visual an­alogue scale (VAS) score changes for bladder pain in all the patients (A; average decrease of VAS score 0.42, 95% CI 0.07 to 0.76, p = 0.02) and subgroup analyses in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; average decrease of VAS score for IC 0.35, 95% CI 0 to 0.7, p = 0.05; average decrease of VAS score for DO 1.4, 95% CI 0.03 to 2.77, p = 0.05).

<p>Visual an­alogue scale (VAS) score changes for bladder pain in all the patients (A; average decrease of VAS score 0.42, 95% CI 0.07 to 0.76, p = 0.02) and subgroup analyses in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; average decrease of VAS score for IC 0.35, 95% CI 0 to 0.7, p = 0.05; average decrease of VAS score for DO 1.4, 95% CI 0.03 to 2.77, p = 0.05).</p

FDC (A; mean difference −16.56 ml, 95% CI −55.79 to 22.67 ml, p = 0.41) and MCC (B; mean difference 34ml, 95% CI -16.54 to 84.53ml, p = 0.19) changes in all the patients and subgroup analyses of MCC in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (C; MCC mean difference for IC −19.10 ml, 95% CI −59.37 to 21.17 ml, p = 0.35; MCC mean difference for DO 53.36 ml, 95%CI 15.42 to 91.29 ml, p = 0.006).

<p>FDC (A; mean difference −16.56 ml, 95% CI −55.79 to 22.67 ml, p = 0.41) and MCC (B; mean difference 34ml, 95% CI -16.54 to 84.53ml, p = 0.19) changes in all the patients and subgroup analyses of MCC in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (C; MCC mean difference for IC −19.10 ml, 95% CI −59.37 to 21.17 ml, p = 0.35; MCC mean difference for DO 53.36 ml, 95%CI 15.42 to 91.29 ml, p = 0.006).</p