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The Somatic Connection  |   July 2010
The Somatic Connection
Article Information
The Somatic Connection   |   July 2010
The Somatic Connection
The Journal of the American Osteopathic Association, July 2010, Vol. 110, 371-373. doi:
The Journal of the American Osteopathic Association, July 2010, Vol. 110, 371-373. doi:
In this month's installment of “The Somatic Connection,” Michael A. Seffinger, DO, reviews the research findings of the Multicenter Osteopathic Study of Pneumonia in the Elderly (MOPSE) study. The nature of the osteopathic manipulative treatment (OMT) used in MOPSE has long been thought to impact physiologic function and systemic disorders. There is a growing body of evidence that OMT and manual therapy do indeed affect the self-regulatory and healing mechanisms of the immune system. Hollis H. King, DO, PhD, has assembled three such studies—one pure bench basic science research study, one basic science study in an animal model, and one clinical study—all related to the impact of OMT and manual therapy on immune system function. 
Efficacy of OMT for Elderly Hospitalized Patients With Pneumonia
Noll DR, Degenhardt BF, Morley TF, Blais FX, Hortos KA, Hensel K, et al. Efficacy of osteopathic manipulation as an adjunctive treatment for hospitalized patients with pneumonia: a randomized controlled trial. Osteopath Med Prim Care. 2010;4: 2. http://www.om-pc.com/content/4/1/2. Accessed July 14 , 2010.  
Pneumonia is a common cause of hospitalization, is costly to manage, and leads to significant morbidity and mortality, especially in elderly patients. Osteopathic physicians have long advocated for the use of osteopathic manipulative treatment (OMT) to benefit these patients (J Am Osteopath Assoc. 1947;46[7]:385-392). More recently, JAOA—The Journal of the American Osteopathic Association has published pilot clinical trials on the efficacy of OMT for elderly patients hospitalized with pneumonia (1999;99[3]:143-146; 2000;100[12]:776-782). As a follow-up to these studies, Donald R. Noll, DO, and colleagues performed a multi-site, double-blinded, randomized, controlled clinical trial comparing conventional care with or without OMT or light touch (LT) on patients aged 50 years or older hospitalized with pneumonia. 
The OMT protocol used was developed by literature review and in consultation with OMT experts and can be found in the JAOA archives (2008;108[9]:508-516). Researchers recruited 406 participants at seven community hospitals in five states. Participants were randomly assigned to one of three groups: conventional care only (CCO); conventional care plus OMT (OMT); or conventional care plus LT. 
All study administrators, including the principal investigators and the physicians managing the patients, were blinded to group allocation except the physicians giving the study treatment. Both OMT and LT were provided by OMT specialists, osteopathic residents in training, or both using a standard 15-minute protocol twice daily. The protocol was administered until the patient was discharged, antibiotics were stopped, respiratory failure occurred, death, or the patient withdrew from the study. Researchers compared the effect of the three types of interventions using the following three primary outcomes: hospital length of stay (LOS), time to clinical stability, and a symptomatic and functional recovery score. 
Intention-to-treat analysis performed on 387 participants revealed no significant differences; however, per-protocol analysis (data from participants who received the protocol as prescribed without variation) performed on 318 participants showed a statistically significant reduction (P=.01) in the median LOS at the 95% confidence interval for the OMT group (3.5 [3.2-4.0] days) vs the CCO group (4.5 [3.9-4.9] days). The medial LOS was not statistically significant compared to the LT group (3.9 [3.5-4.8] days). 
Differences in secondary outcomes of duration of intravenous antibiotics and treatment endpoint were statistically significant between groups (CCO vs OMT, P=.05; CCO vs LT, P=.006). In addition, the OMT group had lower intravenous antibiotic duration and respiratory failure or death compared with the CCO group but not with the LT group. There were no adverse events attributed to OMT or LT in this study according to the Data and Safety Monitoring Board. 
Subgroup analysis found that both OMT and LT benefitted elderly patients aged 60 years or older. The researchers concluded that when OMT was administered in accordance with the protocol, reductions were seen in LOS, duration of intravenous antibiotics, and incidence of respiratory failure and death in the OMT group compared to the CCO group. Further research on the effect of OMT in this patient population is warranted. —M.A.S. 
In Vitro Modeling Suggests Impact of OMT on Immune System Function
Meltzer KR, Cao TV, Schad JF, King H, Stoll ST, Standley PR. In vitro modeling of repetitive motion injury and myofascial release. J Bodyw Mov Ther. 2010;14(2):162-171.  
Paul R. Standley, PhD, and colleagues have investigated the effect of osteopathic manipulative treatment (OMT) on immune cellular function. Two articles related to this topic were published in JAOA—The Journal of the American Osteopathic Association (2006; 106[3]:157-166 and 2007;107[12]:527-536), the most recent of which won the 2008 George W. Northup, DO, Medical Writing Award for its pioneering research examining the effect of simulated OMT on in vitro human fibroblast preparations. The latest article from Dr Standley and researchers further elaborates on these topics. 
In the most recent study, researchers based at the University of Arizona College of Medicine used in vitro preparations of normal human dermal fibroblasts (NHDF) to confirm and expand upon findings from their previous studies. The NHDF cells were cultured in Fibroblast Basal Medium (FBM) in a six-well-perplate, flexible, collagen-coated membrane system that used a vacuum attachment to strain and vibrate cells on the membrane surface. Using protocols developed in previous studies, computer-controlled strain and vibration profiles deformed the collagen membrane, impacting the implanted fibroblasts. 
The two studies cited above showed changes in cytokine levels (interleukins 1α, 3, 4, and 6), which suggested pro-inflammatory and anti-inflammatory responses to the repetitive motion strain (RMS). The RMS-modeled injury, such as overexertion of a person`s musculoskeletal system in an 8-hour period (eg, the “weekend warrior” doing yard work). In the 2007 JAOA article, the researchers modeled indirect OMT (intended to simulate strain-counterstrain) by releasing the strain and ceasing the repetitive vibration for 60 seconds. The cell arrays showed a decrease in levels of pro-inflammatory cytokines IL-3 and IL-6, which were suggestive of a possible mechanism of action for understanding the impact of OMT on humans with strain or sprain injuries. 
In the latest article, the researchers developed a strain profile to simulate myofascial release (MFR) by the vacuum attachment to the flexible collagen membrane with NHDF cells. This technical procedure involved an equiradial gradual slope reduction of vacuum strain and RMS. Multiple six-well plates were run for each condition, and a random selection was made as to which plates were subjected to photomicrograph and cell viability analyses. The following four strain regimens were tested: 
  1. Control—Cells were not subjected to any strain protocol.
  2. RMS (repetitive motion strain)—Cells were subjected to the RMS profile for 8 hours and then sampled immediately upon cessation of RMS.
  3. MFR (myofascial release)—Cells were subjected to the MFR profile for 60 seconds and then sampled immediately upon cessation of MFR.
  4. RMS + MFR—Cells were subjected to 8 hours RMS protocol followed 3 hours later by the 60 second MFR and then sampled immediately after cessation of MFR.
The results pertaining to cell morphology revealed that the RMS cells showed statistically significant decreases in cell area compared to the other three groups. The RMS cells also showed a statistically significant increase in apoptosis compared to the other three groups. Of the 20 cytokines measured, there was a statistically significant increase in GRO (a neutrophil chemotractant) secretion in the RMS + MFR group compared to control and MFR alone. This result suggests that GRO may play a role in fibroblast actin-extracellular matrix remodeling as observed in this study. Though other cytokines were not significantly different between groups, it was observed that there was a trend for IL-1α increase in the RMS group compared to the control group—a finding consistent with the 2007 JAOA report. 
The authors also observed that RMS-induced IL-1α expression was attenuated with the addition of MFR after RMS. The authors speculated that a 24-hour posttreatment investigation of cytokines, not possible in the present study, may show more changes consistent with the often reported human “delayed treatment response” to OMT and will be included in future studies. These findings suggest that immune system function is affected by OMT. —H.H.K. 
Lymphatic Pump Treatment Increases Leukocyte Count in Thoracic Duct Lymph
Hodge LM, King HH, Williams AG, Reder SJ, Belavadi T, Simecka JW, et al. Abdominal lymphatic pump treatment increases leukocyte count and flux in thoracic duct lymph. Lymphat Res Bio. 2007;5(2):127-133.  
Researchers at the University of North Texas Health Science Center in Fort Worth, including principle investigator Lisa Hodge, PhD, the Osteopathic Heritage Basic Science Chair at the Osteopathic Research Center, used an animal model to measure leukocyte count and flux in response to osteopathic manipulative treatment. The research was carried out in the same laboratory that produced the groundbreaking finding that an abdominal lymphatic pump procedure on conscious dogs significantly increased thoracic duct lymph flow (J Am Osteopath Assoc. 2005;105[10]:447-456). 
Eight mongrel dogs were anesthetized and intubated and underwent left thoracotomies. Thoracic ducts were catheterized and allowed to drain freely, with lymph collected over ice. Lymph flow was measured by either time collection (n=5) or ultrasonic flow transducer applied to the thoracic duct (n=3). Flow data and samples were collected at baseline and at 2- to 3-minute intervals during the 8-minute application of lymphatic pump treatment (LPT). 
Animals were placed in lateral recumbent positions. The LPT was performed with the operators hands placed bilaterally at the costo-diaphragmatic junction. Pressure was exerted medially to compress the lower ribs. Once significant resistance was encountered, then pressure was released. The rate of rib compressions was about 1 per second for 8 minutes. 
Differential cell counts were enumerated by standard laboratory methods. Flow cytometry utilizing two-color immunofluorescent staining was used to identify T and B cell populations. The proportion of each cell population was expressed as the percentage of the number of stained cells. To determine the total number of specific lymphocyte population, their percentage was multiplied by the total number of cells in a milliliter of lymph. 
Results showed statistical significance (P<.05) in every cell count comparison between baseline lymph levels and lymph collected during LPT. Total (standard error) leukocyte count at baseline was 4.8 (1.7) and during LPT was 11.8 (3.6). Neutrophils increased from 0.31 (0.08) to 1.19 (0.26); macrophages, 0.27 (0.04) to 1.16 (0.28); lymphocytes, 3.94 (2.02) to 9.41 (3.99); T cells, 3.55 (1.65) to 9.22 (3.87); and B cells, 0.80 (0.36) to 2.4 (0.073). Remarkably, the differences in differential count percentages between cells were not significant, staying virtually the same from baseline to LPT. Leukocyte flux, which was computed from the product of lymph flow and cell count, increased from 8.2 (4.10) to 60.0 (25.0), with corresponding increases for neutrophils, macrophages, and lymphocytes. 
The authors reported that these finding were consistent with human study findings of increased leukocyte numbers in peripheral blood after LPT. The authors concluded that the reported increased mobilization of leukocytes provided a potential mechanistic basis for increased immune responses and recovery from infectious disease shown in studies that have used LPT, including MOPSE. —H.H.K. 
Massage Reduces Immune System Deterioration in Women With Breast Cancer
Billhult A, Lindholm C, Gunnarsson R, Stener-Victorin E. The effect of massage on immune function and stress in women with breast cancer—a randomized controlled trial. Auton Neurosci.. (2009). ;150(1-2):111-115.  
Researchers at The Sahlgrenska Academy in Göteborg, Sweden, conducted a randomized controlled trial on women receiving radiation therapy after breast cancer surgery. Thirty women aged 50 or older were randomly assigned to receive one 45- to 50-minute light pressure massage (intervention group) or a 45- to 50-minute unstructured conversation (control group). The same nurse, trained in massage, conducted the conversation sessions for both groups and administered the massage. 
Exclusion criteria were chemotherapy and hormonal treatment or any other medication with potential immunomodulatory effects. Patients were also excluded if they were still ovulating. Outcome measures included blood samples analyzed for Natural Killer Cell Cytotoxicity (NKCC), NK cell number and frequency, and frequency of activated NK cells; saliva collections for cortisol level; and recordings of blood pressure and heart rate. 
The results showed a statistically significant difference for NKCC. At baseline, the NKCC level was same for both groups. However, while the NKCC level markedly decreased in the control group, it did not deteriorate in the massage group. There was no difference between groups for NK cell number or frequency. After the intervention, the massage group had significantly lower heart rates and systolic blood pressures, but the cortisol levels and diastolic blood pressures were not significantly different between groups. 
The authors conceded that it was unknown how long this effect would last, but that maintaining levels of NKCC was an important factor in the innate immune system in the defense against tumor cells. The authors speculated that the decrease in NKCC levels in the control group was due to the fact that the patients were undergoing radiation therapy, which could have acted as a psychological stressor, thereby suppressing NKCC levels. In the massage group, it appeared that the massage counteracted the NKCC deterioration for those patients. 
The authors also noted that the mechanisms behind the effect of massage are unknown but speculated that massage leads to a release of neuropeptides or histamine, which may exert immunomodulatory effects on leukocytes. The significant reduction in heart rate and systolic blood pressure suggests that the massage group patients had decreased anxiety, which could be an indication that activity in the autonomic nervous system regulating the circulatory organs was indeed modulated. 
While it is unclear whether or not OMT would have the same effect as the massage protocol carried out in this study, the point of the present review is that a manual therapy modality had measurable impact on immune system function. Such effects may encourage the application of OMT in the treatment of patients with systemic disorders, especially now that credible research is suggestive of benefit. —H.H.K. 
 “The Somatic Connection” highlights and summarizes important contributions to the growing body of literature on the musculoskeletal system's role in health and disease. This section of JAOA—The Journal of the American Osteopathic Association strives to chronicle the significant increase in published research on manipulative methods and treatments in the United States and the renewed interest in manual medicine internationally, especially in Europe.
 
 To submit scientific reports for possible inclusion in “The Somatic Connection,” readers are encouraged to contact JAOA Editorial Advisory Board Member Michael A. Seffinger, DO (mseffinger@westernu.edu), or Editorial Board Member Hollis H. King, DO, PhD (hking@atsu.edu).
 
 Drs Seffinger and King were not involved in the decision to publish these contributions.
 
 Editor`s Note: Dr Seffinger discloses that several years ago, he received payment as the chair of the data and safety monitoring board for the study described above. He does not receive any financial benefit from this contribution to “The Somatic Connection,” its subject matter, or the research study itself.
 
 Editor`s Note: Dr King was a coauthor of the reviewed study.
 
 Editor`s Note: Dr King was a coauthor of the reviewed study.