Research Review By Dr. Jeff Muir©

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Date Posted:

May 2021

Study Title:

Assessment of Studies Evaluating Spinal Manipulative Therapy and Infectious Disease and Immune System Outcomes: A Systematic Review

Authors:

Chow N, Hogg-Johnson S, Mior S, Cancelliere C, Injeyan S, Teodorczyk-Injeyan J, Cassidy JD, Taylor-Vaisey A & Côté P

Author's Affiliations:

Centre for Disability Prevention and Rehabilitation, Faculty of Health Sciences, Ontario Tech University, Oshawa, Canada; Canadian Memorial Chiropractic College, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Canada.

Publication Information:

JAMA Network Open 2021; 4(4): e215493. (Open access full text here)

Background Information:

With the onset of the COVID-19 pandemic, claims that spinal manipulative therapy (SMT) can improve immune function have increased (1-3). Such claims have long been part of the chiropractic profession, with proponents declaring support for their position in the scientific literature (4). The validity of claims of a link between SMT and a meaningful immune response, however, has been strongly questioned by others (5).

The guidance from regulatory bodies and licensing boards on SMT as a treatment option for infectious disease in both the USA and Canada during the COVID-19 pandemic has been limited and heterogenous (6). As part of an effort to examine the evidence in support of claims linking SMT and immune response, the College of Chiropractors of British Columbia requested that these authors conduct an independent rapid review of the available scientific literature.

This resultant paper is a systematic review of the literature, examining whether SMT is associated with efficacy and effectiveness for: 1) preventing the development of infectious disease; and 2) improving disease-specific health outcomes among patients with infectious disease. The authors also synthesized data from laboratory experiments to investigate the association between SMT and immunological, endocrine, and other physiological biomarkers.

Pertinent Results:

Eligible Studies:
From an initial pool of 2593 records, 598 duplicates were removed before screening 1995 titles and abstracts. 16 articles summarizing results from 13 studies (with a total of 795 patients) were ultimately deemed eligible for inclusion.

Risk of Bias Within Included Studies:
Of the 16 eligible studies, 1 was rated as being high-quality evidence, while 7 were rated as acceptable quality. The 8 remaining articles were deemed to be of low quality. As a result, only the 8 articles deemed of acceptable or better quality were included in the evidence synthesis. These studies summarized the results from 6 separate RCTs, including a total of 529 participants.

Study Characteristics:
Of the 8 included articles (including 6 RCTs), 6 evaluated SMT provided by chiropractors and 2 evaluated SMT provided by physiotherapists. 3 RCTs examined the association between SMT and immunological biomarkers; 3 examined SMT and levels of endocrine and other physiological biomarkers. 4 of the RCTs included healthy adults while 2 RCTs featured adult patients with low back pain.

Evidence Synthesis

No studies examined the association between SMT and either the prevention of infectious disease or improvement in disease-specific outcomes among patients with infectious disease.

The evidence indicated that SMT was associated with immediate changes in levels of immunological biomarkers (polymorphonuclear neutrophils, monocytes, tumour necrosis factor-alpha, interleukin-1-beta and 2, immunoglobulin G and M) in asymptomatic patients compared to either sham manipulation, venipuncture control or a lecture series. The duration of observed changes or the clinical significance, however, were not evaluated in any studies (these studies only measured immediate changes in these biomarkers). Further, SMT was not associated with changes in lymphocyte levels in studies evaluating patients with low back pain or asymptomatic subjects compared to the same comparators/controls mentioned above.

1 study reported that SMT was associated with changes in the level of salivary cortisol immediately following SMT in asymptomatic participants. In the remaining 7 studies, in vitro analysis indicated that SMT was not associated with levels of physiological markers (ex. substance P, testosterone, testosterone to cortisol ratio, oxyhaemoglobin, heart rate variability, norepinephrine or epinephrine).

Clinical Application & Conclusions:

Ultimately, no clinical evidence either in favour of or against a role for SMT in preventing or improving infectious disease was found in high-quality studies. Limited, exploratory (phase 0), in vitro evidence was found suggesting that SMT may be associated with immediate changes in immunological and endocrine biomarkers among healthy patients or those with low back pain (these are the studies that have been conducted at CMCC). The clinical relevance of these studies remains unknown at this time, pending further research.

The findings from this rapid review were based on phase 0 (exploratory) studies that included healthy participants or subjects with low back pain. They did not include patients with an infectious disease. None of the included studies were phase 2 (biologic activity), which would have (at least) established proof of concept that an intervention had any biologic activity.

The authors concluded that there is insufficient evidence to support an opinion on the effectiveness of SMT in treating infectious diseases and suggest that additional research is warranted before any claims can definitively be made.

EDITOR’S COMMENT: This remains a controversial topic, with many practicing clinicians strongly believing that there is a clinically relevant link between SMT and immune system function. Currently, as these authors mention, we do not have sufficient, high-quality scientific evidence to support (nor refute) this potential relationship. Most of the relevant, higher-quality phase 0 studies included here were performed at CMCC in Toronto, by researchers included in the author group of this paper. In their studies, they typically drew blood as a baseline measure, delivered SMT to a particular spinal region, they re-drew blood samples. The changes they have demonstrated, while present in many cases, have not been measured over time and as even the researchers themselves appropriately admit in their papers – the clinical relevance of these findings remain to be further studied. There are numerous possible mechanisms of action for spinal manipulation improving human health including biomechanical changes, modulation of pain signalling and others. The potential impact of SMT on immune function via serological markers is only one area of investigation, which like the others just noted, remain in progress from a research perspective.

Study Methods:

Study Eligibility:
The study was conducted using methodology recommended by the World Health Organization (7-10) and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (11). MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Index to Chiropractic Literature (ICL), the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 15, 2020. Relevant search terms included: musculoskeletal manipulations, immunity, and communicable disease, plus free-text words relevant to the study objective and design. RCTs and cohort studies, published in English, including SMT provided by any practitioner, measuring clinical outcomes or changes in levels of relevant biomarkers were included.

Data Extraction:
Study characteristics, patient demographics, intervention characteristics and outcome data were extracted. The Scottish Intercollegiate Guidelines Network (SIGN) criteria (12) were used to critically appraise the internal validity of each included study. RCTs were categorized by study phase; evidence was synthesized based on the Synthesis Without Meta-analysis guidelines (13). The authors only analyzed studies with high and acceptable quality, since those with low and unacceptable quality were more likely to produce biased estimates of relevant effect sizes.

Study Strengths / Weaknesses:

Strengths:
  • Strict adherence to PRISMA and WHO guidelines.
  • Formulation of a clear research question and a priori study protocols.
  • A robust literature search including 2 librarians.
  • Content experts were consulted and included in this author group.
  • A review process conducted by senior scientists, epidemiologists and a biostatistician.
Weaknesses:
  • Only English-language studies were included.
  • Screening, critical appraisal and data extraction were conducted by a single investigator rather than two reviewers. The authors did employ a structured quality assurance methodology to minimize errors in the screening process, however.

Additional References:

  1. Kawchuk G, Hartvigsen J, Harsted S, Nim CG, Nyiro L. Misinformation about spinal manipulation and boosting immunity: an analysis of Twitter activity during the COVID-19 crisis. Chiropr Man Therap 2020; 28(1): 34.
  2. Kawchuk G, Hartvigsen J, Innes S, Simpson JK, Gushaty B. The use of internet analytics by a Canadian provincial chiropractic regulator to monitor, evaluate and remediate misleading claims regarding specific health conditions, pregnancy, and COVID-19. Chiropr Man Therap 2020; 28(1): 24.
  3. Axen I, Bergstrom C, Bronson M, et al. Misinformation, chiropractic, and the COVID-19 pandemic. Chiropr Man Therap 2020; 28(1): 65.
  4. International Chiropractors Association. Immune function and chiropractic: what does the evidence provide? Revised March 28, 2020. Accessed November 19, 2020. https://www.chiropractic.org/immune-function-andchiropractic-what-does-the-evidence-provide-revised/
  5. Côté P, Bussieres A, Cassidy JD et al. A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity. Chiropr Man Therap 2020; 28(1): 21.
  6. Neff SM, Roecker CB, Okamoto CS, et al. Guidance concerning chiropractic practice in response to COVID-19 in the U.S.: a summary of state regulators’ web-based information. Chiropr Man Therap 2020; 28(1): 44.
  7. Tricco AC, Antony J, ZarinW, et al. A scoping review of rapid review methods. BMC Med 2015; 13: 224.
  8. Tricco AC, Langlois EV, Straus SE, eds. Rapid reviews to strengthen health policy and systems: a practice guide. World Health Organization; 2017. Accessed April 6, 2020. https://apps.who.int/iris/bitstream/handle/10665/258698/9789241512763-eng.pdf?sequence=1
  9. Varker T, Forbes D, Dell L et al. Rapid evidence assessment: increasing the transparency of an emerging methodology. J Eval Clin Pract 2015; 21(6): 1199-1204.
  10. Featherstone RM, Dryden DM, Foisy M et al. Advancing knowledge of rapid reviews: an analysis of results, conclusions and recommendations from published review articles examining rapid reviews. Syst Rev 2015; 4: 50.
  11. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6(7): e1000097.
  12. Scottish Intercollegiate Guidelines Network. Checklists. 2013. Accessed August 23, 2020. https://www.sign.ac.uk/what-we-do/methodology/checklists/
  13. Campbell M, McKenzie JE, Sowden A, et al. Synthesis Without Meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 2020; 368: l6890.