1. Nasal Irrigation for Chronic Rhinosinusitis and Fatigue in Patients with Gulf War Illness: Preliminary data from a 3-arm randomized controlled trial. 1 Chidi Obasi, MD MS PhD Department of Family Medicine University of Wisconsin, Madison-USA Saturday, August 8th, 2015 The 2015 Integrative Medicine for the Underserved conference Tufts University School of Medicine, Boston MA

3. 1 st Objective Recognize the quality of life and burden of Gulf War Illness (GWI) among the afflicted.  Affects 1 in 7 returned Gulf War veterans  No known cure  Chronic sinus symptoms and fatigue are common http://www.publichealth.va.gov/exposures/gulfwar/military-service.asp

4. Exclusionary Conditions:  Chronic conditions that can produce diverse symptoms or  interferes with self-reporting abilities Inclusionary criteria:  Fatigue  Pain  Neurological/Cognitive  Skin  Gastrointestinal  Respiratory

5. The Science:  improve sinus symptoms and fatigue by thinning, cleaning and clearing mucus  improve the protective function of the nasal cavity 2 nd Objective Integrative medicine use of nasal irrigation as a treatment for GWI.

6. Study Organization  3 Groups of nasal irrigation  Saline: Best Studied  Xylitol nasal irrigation: Up and Coming  Waitlist: Essential for comparison (without this, we’ve got nothing…)  Primary outcomes include  the validated Sinonasal Outcome Test (SNOT-20, 0-100 points)  the Multidimensional Fatigue Index (MFI).  Secondary outcomes include  pro-inflammatory cellular and  cytokine profiles,  cost-benefit analysis and  participant satisfaction.  Assessment is at baseline, 8 and 26 weeks.  Analysis  ITT analysis of within- and between-group differences by Mann- Whitney ‘U’ and Cohen’s ‘d’ effect size tests.

7. We assessed effects of NI-S and NI-X on participants with GWI, sinus symptoms and fatigue @ 8weeks. Study Aim

8. S-NI (N=8)X-NI (N=8)Control (N=7) Demographics Male (%)62.5%87.5%71.4% Income (≥$50,000)50.0%62.5%85.7% Education(≥college graduate)12.5%37.5%57.1% Age, mean (SD)50.1(7.7)52.4 (6.4)51.9 (7.4) Outcome Measures, mean (SD)  SNOT-20, mean total score (SD) Baseline visit 8 week visit Difference between visits 54.3 (7.8) 37.1(19.1) 17.1 (16.4) 42.0 (14.5) 34.3 (19.33) 7.8 (11.6) 48.3 (9.6) 44.3 (8.5) 4.0 (4.2)  MFI, mean total score (SD) Baseline visit 8 week visit Difference between visits 57.5(6.0) 56.1 (7.3) 1.4 (10.3) 60.0(7.5) 71.5(33.7) -11 (34.3) 59.9 (5.1) 60.7 (6.4) -0.9 (7.2)

9. Rhinologic symptoms Ear/Facial Symptoms Sleep Function Psychological SNOT-20  Saline showed significantly improved scores compared to Control group  Xylitol showed minimally improved scores compared to Control group

10. Pooled effect size d+ = 0.45 P < 0.0001  SNOT-20: Saline vs. Control Rhinologic symptoms d+ = 0.33 P = 0.065 Ear/Facial Symptoms d+ = 0.48 P = 0.037 Sleep Function d+ = 0.93 P < 0.001 Psychological d+ = 0.26 P = 0.10

11.  SNOT-20: Xylitol vs. Control Pooled effect size d+ = 0.17 P =0.07 Rhinologic symptoms d+ = 0.49 P = 0.40 Ear/Facial Symptoms d+ = 0.11 P = 0.48 Sleep Function d+ = 0.57 P= 0.016 Psychological d+ = 0.26 P = 0.12

12. General Fatigue Physical Fatigue Mental Fatigue Reduced Activity Reduced Motivation MFI  Saline and Xylitol showed minimally improved scores compared to Control group

13. Conclusions Preliminary data suggest that NI-S and NI-X may improve chronic sinus symptoms among participants with Guld War Illness. Progress to date suggests robust study conduct, protocol adherence to nasal irrigation use, and satisfaction with care. Eight-week data on secondary outcomes, and all 26-week data on current participants, are pending.

14. Acknowledgments Co-authors: University of Wisconsin-Madison School of Medicine & Public Health  David Rabago, MD, Department of Family Medicine  Tony Kille, MD, Department of Pediatric Otolaryngology  Rachel Molander, MD, Department of Psychiatry  Supriya Hayer MD, Department of Family Medicine  Ian Hauffe, Department of Family Medicine  Ina Kansariwala, Department of Family Medicine  Daniel Fehrenbach, Department of Family Medicine  Lily Comp, Department of Family Medicine Funding: Department of Defense (DOD) Gulf War Illness Research Program (GWIRP) of the Office of the Congressionally Directed Medical Research Programs (CDMRP) We would also like to thank the following: UW Health Sciences Institutional Review Board US Department of Defense Gulf War Illness Research Project (GWIRP) UW School of Medicine & Public Health Departments of Family Medicine and Surgery US Veterans Administration System

16.  MFI: Saline vs. Control Pooled effect size d+ = 0.091 P =0.21 General Fatigue d+ = -0.07; P=0.39 Mental Fatigue d+ = 0.39; P=0.07 Reduced Motivation d+ = 0.13; P=0.30 Reduced Activity d+ = -0.12; P=0.32 Physical Fatigue d+ = 0.13; P=0.31

17.  MFI: Xylitol vs. Control Pooled effect size d+ = 0.077 P =0.25 General Fatigue d+ = 0.16; P=0.28 Mental Fatigue d+ = -0.13; P=0.32 Reduced Motivation d+ = 0.02; P=0.44 Reduced Activity d+ = -0.11; P=0.34 Physical Fatigue d+ = 0.44; P=0.047