Virginia Research Day 2021

TNF- α levels as an indicator of facial effleurage efficacy in patients with acute rhinosinusitis Abigail White, OMSIII; Chelsea Weidman, M.S; Jillian Bradley, Ph.D. The Edward Via College of Osteopathic Medicine – Carolinas Campus, Department of Microbiology and Immunology, Spartanburg, SC

CRM-11

Conclusions

Background

Results

Acute rhinosinusitis is a sinus mucosa inflammatory condition that 12% of Americans face every year. 1 Treatment is based solely on clinical diagnosis: a viral infection presents with symptoms for less than 7 days, while a bacterial infection lasts longer and causes more severe symptomology. Guidelines direct physicians to prescribe antibiotics only in severe cases when symptoms last beyond 10 days and a non-viral cause is suspected. This leaves many patients without adequate treatment options and many patients receive antibiotics unnecessarily. 2 A potential alternative treatment for patients suffering from acute rhinosinusitis is an osteopathic manipulative treatment called facial effleurage (FE). Tumor necrosis factor- α ( TNF α) is a cytokine produced during infections and has been determined to significantly increase at the site of sinusitis. 3 This cytokine has various functions including stimulating chemokine release to attract neutrophils and macrophages, increasing vascular permeability, and recruiting leukocytes. To test FE effectiveness, serum levels of the pro-inflammatory cytokine TNF α were collected.

The difference in serum TNF α between sick patients and healthy controls prior to treatment was not statistically significant, but sick patients tend to have higher levels. In all three groups treated with facial effleurage (FE) the movement of TNF α increased significantly in comparison to patients who received the sham treatment (RS+PT), and the patients who only received antibiotics (RS+Ab) (Figure 3). Additionally, facial effleurage increased TNF α levels in healthy patients 1 hour after treatment (HC+FE). On follow-up 7 days after FE, TNF α is increased significantly in both rhinosinusitis groups that received facial effleurage (RS+FE and RS+Ab+FE) compared to the healthy control with facial effleurage (HC+FE) (Figure 4). TNF α is significantly upregulated in the blood one hour after FE treatment, and this increase persisted for at least a week. Since pre-treatment values of serum TNF α did not statistically differ from healthy patients, the increase in TNF α after FE may be indicative of the technique causing substantial change to lymphatic circulation. One hour after FE, the HC appear to have more serum TNF α than the sick patients receiving FE. This may be due to sick patients utilizing more TNF α since its helping fight the infection. However, this appears to be short lived in HC, as serum TNF α remains significantly elevated in only RS groups one week after FE. This suggests that sick patients derive extended benefits from FE. A possible explanation for this significant increase in serum TNFα levels is that increasing amounts of this cytokine gain the ability to the escape the site of infection. Excess TNF α exodus potentially decreases the swelling and pain the patients experience, as well as ushers in the healing response rather than prolonging the state of inflammation. This is particularly valuable when the proinflammatory response is no longer warranted. This research demonstrates the potential for an improved standard of care for acute rhinosinusitis involving FE, as well as a decreased reliance on antibiotics. Further research could explore the connection between FE and other measurable serum cytokine changes.

Figure 1 . Serum concentration of TNF α is not statistically up-regulated in patients with acute rhinosinusitis . Blood was drawn from patients with and without acute rhinosinusitis prior to treatment. The serum concentration of TNF α was measured via ELISA. Student’s t-test was utilized and * indicates a p-value of 0.05

Figure 2 . Serum concentration of TNF α prior to, 1 hour after the beginning of treatment, and 7 days after treatment . Blood was drawn from a patient with acute rhinosinusitis prior to treatment (Pre-Tx). Patients were then randomized into one of eight treatment groups. Blood was drawn again 1 hour after the beginning of treatment (Post-Tx), and at the follow-up visit 7 days later (F/U). The serum concentration of TNF α was measured via ELISA. ANOVA test was utilized and * indicates a p-value of 0.05

Hypothesis TNF α levels should increase in the blood after facial effleurage because increasing amounts of this cytokine can leave the site of infection

Methods

Figure 3. Serum concentration of TNF α 1 hour after treatment . Blood was drawn from patients with and without acute rhinosinusitis prior to treatment (Pre-Tx). Patients were then randomized into one of eight treatment groups. Blood was drawn again 1 hour after the beginning of treatment (Post-Tx). The serum concentration of TNF α was measured via ELISA. ANOVA test was utilized and * indicates a p-value of 0.05

In a parallel-arm, randomized, placebo-controlled clinical trial, patients that presented to two outpatient, direct primary care clinics in a mid-sized manufacturing town are asked to participate. Informed consent and enrollment eligibility is confirmed. A total of 137 patients enrolled. Participants are then randomly assigned to one of eight treatment groups: ▪ Healthy control (HC)

Acknowledgements

Thank you to Palmetto Proactive Healthcare, Dr. Chris McCarthy, Dr. Jerome Aya-Ay, and Dr. Oshea Escamilla for patient recruitment. Thank you to Drs. Matthew Cannon D.O., Oshea Escamilla D.O., and Jordan Lakin D.O. for performing OMT. Thank you to: Alexis Stoner, MPH, Ph.D.; Randal Gregg, Ph.D.; Ning Cheng, Ph.D. Funded by The American Osteopathic Association (Grant Number - 2031815722). Pilot data provided by Research Eureka Accelerator Program at Edward Via College of Osteopathic Medicine.

▪ HC with physical touch (PT) ▪ HC with Facial Effleurage (FE) ▪ Rhinosinusitis (RS) with antibiotics (Ab)

References

Figure 4. Serum concentration of TNF α is still elevated 7 days after facial effleurage . Blood was drawn from patients with and without acute rhinosinusitis prior to treatment (Pre-Tx). Patients were then randomized into one of eight treatment groups. Blood was drawn again 7 days after treatment (Follow-up). The serum concentration of TNF α was measured via ELISA. ANOVA test was utilized and * indicates a p-value of 0.05

▪ RS with PT ▪ RS with FE

▪ RS with Ab and PT ▪ RS with Ab and FE

Physical touch is the sham/placebo treatment. Peripheral blood samples are collected before treatment. The treatment is then performed and 1 hour after samples are collected again. Peripheral blood is also collected at a follow-up appointment 7 days after treatment. Serum TNF α levels are then measured via ELISA.

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