The Future of Chronic Inflammatory Response Syndrome (CIRS)1 month, 2 weeks ago
Posted on Apr 12, 2023, 11 a.m.
Written By: Andrew Heyman, MD, MHSA
It is difficult, if not dangerous, to predict the future. But trends and good data can point the way toward possibilities and probabilities. There is momentum building in our understanding of Chronic Inflammatory Response Syndrome (CIRS), and the science has grown exponentially in the past 18 months thanks to transcriptomics. This new knowledge is sweeping our efforts forward in a more defined direction while we hone our understanding of the disease. The future is coming into focus.
There are also larger moving parts within the general CIRS practitioner community and even external social and market forces that seem to be creating a set of likely outcomes that are both exciting and important.
If we return to the fundamentals of CIRS, beginning with the seemingly innocuous Sarcin Ricin loop present in all living creatures that create the nexus and permanent vulnerability to biotoxins, it is obvious that this disease will never be fully eliminated. In fact, from an evolutionary perspective, CIRS can be seen as an adaptation to cellular threats, albeit a debilitating one for a large minority of the population.
I think back to my Family Medicine training at the University of Michigan, a stellar formal education already built on 20 years of professional work in Integrative Medicine. I thought I had the intellectual and diagnostic capabilities at my disposal to understand most patients who walked into my academic clinic. I could bring to bear the full power of scientific medicine through the resources of a major research center, but also slip into the other ‘medical languages’ of Traditional Chinese Medicine, Manual Therapies, Botanical Medicine, and the newer ‘Functional, Anti-Aging and Integrative approaches’ that would allow me to understand complex illnesses through different lenses.
With that broad foundation, still, patients presenting with fatigue, pain, mood issues, functional bowel disorders, weight gain, and much more would too often slip through my carefully erected expertise with ease. Yet, aren’t these complaints the hallmark of any primary care office? Our bread and butter? How was it that neither the healing wisdom of the ages nor the most advanced science of the day could not fully and completely understand and resolve these common complaints?
If we are honest with ourselves as professionals, scientists and healers, it felt as if I had reached a kind of cognitive and scientific frontier. What lay beyond? Were there answers out there already known, or would new ones need to be generated for these common complaints that have plagued humans for millennia and appeared resistant to just about every form of therapy across time and culture.
2014. I meet Dr. Ritchie Shoemaker in the countryside of Virginia. Sometimes you can feel your life-changing in the moment, and other significant events need distance and reflection to appreciate their enormity. In this case, I knew immediately I was in the presence of a genius but also did not fully comprehend the upheaval his work would bring to bear on my own. He spoke the language of science but used a dialect I had never heard before. He was riffing off emerging ideas called proteomics and genomics, applying unfamiliar measurement tools, and as a result, was generating clinical outcomes that appeared impossible.
A master of his art, one that he created in the backwaters of Pocomoke, all on his own.
Reminds me of the story of Robert Johnson. A relative unknown in the 1930s, who emerged from the obscurity of the delta to define a generation of blues and rock and roll. He recorded only 29 songs, having developed a unique playing technique that seemed to be inspired by something supernatural (some argue he met the devil at the crossroads, because no human could have figured out his brilliant style by himself ). He created an approach to music that would forever influence many famous musicians after him.
Every once in a while, we come across these almost mythic figures who blend creative insight, technique, and skill into something completely novel and transformative. In my humble opinion, CIRS represents that breakthrough. Dr. Shoemaker embodies that formidable genius whose medium is human suffering and makes music with molecules and cells.
There is a permanence to CIRS because humans have always lived with it. There is a brilliance to the diagnosis, since it is ubiquitous, but like quicksilver has escaped recognition to all those that came before us except one. A Robert Johnson-like figure who sat on the banks of the Chesapeake Bay and saw what no one else could see. Look around your practice. CIRS is everywhere. Look inside yourself. It may be in you too. Did you miss it? We all did.
So where do we go from here? First, we must recognize this is a disease squarely in the domain of primary care. It is my firm belief all PCPs should have command of this topic. Additionally, the health of our indoor spaces must be included as a vital sign for every patient. There is just no way around these ideas. Furthermore, the science that underpins CIRS has matured to the point where, I believe, it is almost malpractice to offer ‘medication management’ to these many broken humans in lieu of proper treatment that is actually curative.
Of course, there is still more to learn and understand about the subject. But as I started walking the research path with Dr. Shoemaker, and participated in carefully constructing a scientific framework for CIRS, one thing became clear. Every piece of new data would reinforce, expand or refine our understanding of CIRS. New findings would never fundamentally undermine the science that came before it. Even with the incredible power of transcriptomics, gene expression revealed the inner workings of the disease, yet did not alter our basic conceptions or knowledge base.
Transcriptomics appears to be the true breakthrough in diagnosing CIRS. Gene expression has revealed the hallmarks of the disease – molecular hypometabolism, altered immune efficiency, defective apoptosis, aerobic glycolysis – and linked these molecular abnormalities to risk for vascular dementia, diabetes, thrombotic events, and pulmonary hypertension, to name a few.
We will continue to identify patterns of aberrant gene expression, and conduct the difficult work to make meaning of these findings. Who knew your home could make you fat, depressed, and demented? Who knew that water damage leads to amplified microbial growth of bacteria more commonly than fungal elements? Who knew that this is as much a proliferative disorder as inflammatory? Now we know.
Additionally, applying new metabolomics techniques to measure mitochondrial production of downstream small molecule patterns may also help identify subsets of CIRS patients and unlock issues
around those resistant to standard therapy, chemically sensitive individuals, and elucidate the impact of the exposome on cellular health. Better diagnostics in general, and the ‘Omics revolution in particular, will allow us to diagnose CIRS patients more quickly and may generate more targeted therapeutic countermeasures.
Where we lag behind is a broad array of treatments that reliably cure the illness. Currently, we are blessed with Vasoactive Intestinal Peptide. A miraculous but single arrow in our therapeutic quiver, that restores the individual back to health, heals the brain and corrects gene response.
We know certain molecular and genomic features of CIRS respond to earlier interventions before VIP is administered. We follow the steps of therapy, conclude with VIP and hope for cure. But can we develop treatment strategies that rapidly and precisely induce cure while bypassing the intermediary steps of treatment? Is there an alternative to VIP?
I believe this is the next important stage in CIRS – reliable, powerful, and precise treatments – validated through restored transcriptomics. Maybe new treatments will be discovered in the family of emerging regenerative techniques, such as peptides, exosomes, stem cells, phage therapy, CRISPR, nutrients, or even high-extract natural compounds. Or maybe, as was the case with cholestyramine, an old drug will be identified that demonstrates unique characteristics well suited for CIRS.
As we dive deeper into the pathophysiology of the condition, a key finding is the profound orchestration the mitochondria have on cell behavior, and the shift towards a pathologic but permanent altered state of gene expression. While downstream consequences of this molecular activity are measurable changes in levels of signaling molecules, nutrients, amino acids, lipids, inflammatory markers, the microbiome and more, these are merely the leaves on the tree.
Without casting aspersions, ‘Functional Medicine’ has been overly focused on assessing and treating these abnormal small molecule findings, while ignoring the key insight transcriptomics offers – to cure these patients, we have to find therapies that shift genomic expression of the mitochondria back to a healthy state of oxidative phosphorylation and normal cellular energetics. Merely treating the leaves on the tree will not achieve this end. We have to fix the roots of this disease instead.
Overall, the clinical imperative should be to heal patients more quickly, build resiliency and resistance to future exposures, and ensure complete resolution in all tissues and organs. Unfortunately, there is currently little (read: no) extramural funding for CIRS. How do we get to these conclusions? Will there be a Robert Johnson who emerges from the mist, or can we leverage another trend?
I am an educator by nature. I enjoy watching students grow in their careers. It is especially satisfying in clinical medicine since every practitioner I train will go on to help thousands of patients during their lifetime. Over a 30-year career in academia and education, I would selfishly like to think I have reached well over a million patients through my students. While I have broad education responsibilities now, my main concentration is in CIRS.
Dr. Shoemaker and I are committed to offering a graduate-level learning experience on the subject. We are able to leverage the assets of online learning capabilities to reach dozens of willing practitioners, and this year alone, we will have formally trained over 100 practitioners in the Science of CIRS. Wow. What an honor and privilege.
This community of excellent providers will grow and they will treat hundreds of thousands of CIRS patients over the coming years. The ‘music’ of Dr. Shoemaker will continue to change lives.
With that said, this expanding network of trained professionals offers a larger opportunity to conduct patient-centered outcomes research. There is power in numbers. If we cannot obtain funding for formal investigations, we can draw upon the collective contributions of many providers to aggregate properly sized data sets to assess outcomes.
Technology, especially cloud-based, has been a game changer in this regard. New ‘point of care’ platforms, wearables, apps and iOT devices can act as the glue between practitioner and patient while funneling data across large populations to centralized research hubs.
Family Medicine, in the 1990s, was the first medical specialty to assemble practice-based research networks (PBRN) to achieve just this goal. Although at the time, EMRs were still new, if not uncommon, and accessing data at the clinic level required superhuman efforts to mine paper charts. Now, the efficiencies of technology have reduced these barriers to entry on large-scale research.
CIRS providers must make a commitment to participate in the PBRN model to accelerate research findings. While the early, and ongoing work of Drs. Shoemaker and Ryan have been singular and heroic, it is time for the current generation of CIRS providers to give back to them, to their patients, and to medicine overall by engaging in the research effort as well.
An organized network of trained and certified providers, unified by their education and connected within a technological ecosystem, will allow for an acceleration of discoveries in CIRS. While we can wait for another ‘Robert Johnson,’ instead, we have the tools at our disposal to test new diagnostics and therapeutics in an organized fashion.
This is not an easy choice for some, since it requires a participatory spirit, adoption of unified technology platforms, and a commitment to expand the practitioner identity to include researcher as well. The time is now, though. I hope we can usher in a shared spirit of collaborative research in the coming years to accelerate our understanding of CIRS.
Everyone deserves health. It is a social good that should not be reserved for only those who can afford it. A person cannot reach his or her potential, compete in the marketplace, or participate effectively in society if they are sickened by their living environment. It does not take much thought to see the financial, social and cultural implications of CIRS. This may be the largest, and most expensive, unrecognized public health crisis of the modern era.
It has particular implications for the underserved who lack access to medical care, proper nutrition and social opportunities. But in all my years of working in inner-city Philadelphia, Washington DC and Detroit, I never considered the contribution a sick building may play in the overall disease burden of this particular population.
We already struggled with managing their obesity, diabetes and heart disease, mental health disorders and substance abuse, violence and neglect. I have often been impressed by the number of CIRS patients that report anger, and even rage, generated by the illness. Add poverty, poor coping skills and a gun to this mix. A scary thought indeed. I think this is a particularly vulnerable population for CIRS, and one that has little recourse for proper diagnosis and treatment, let alone remediation.
Additionally, we do not have nearly enough properly trained practitioners, PCPs in particular, to manage the millions of CIRS patients currently living in the US. The amount of resources required to match health services to this particular population is underfunded and grossly under-recognized by medical institutions. Health advocacy that leads to meaningful policy changes will need to occur on the state and federal level to support formal education, inclusion in clinical guidelines, and recognition as a distinct disease category that has a particular impact on vulnerable populations.
Large-scale clinical outcomes data will likely lead the way as the basis for policy-related changes. I see this public health advocacy work occurring in the near future, but it is not imminent. In the meantime, patient groups can act as a vehicle for meaningful dialogue as a starting point, beyond the chat rooms inhabited by individuals only seeking medical advice for themselves.
Awareness-raising activities, recognition of healthy environments as a form of social justice, and lobbying for protections against landlords, building owners, construction companies and employers will need to be energized by effective advocates for change. This is an uphill battle at best, but pressure from the public on politicians, the medical community and social institutions have a track record of success in other movements for change.
At some point, public awareness will reach a critical mass. But we are only a few voices in the wilderness right now. Practitioners need to take their role as cultural leader as seriously as their role as researcher. I suggest beginning by giving local talks on CIRS. Raise awareness, advocate for change, and encourage community-based groups to take the issue seriously as a public health problem, while continuing to treat patients and help collect data to change medicine. A lot to do…..
But we have approached the point of no return. CIRS is real. CIRS is common. It has enormous socioeconomic and health services implications that deserve its own social movement for change. Otherwise, practitioners remain vulnerable to state medical boards. Patients remain underdiagnosed and untreated. Those responsible for assuring clean interior environments are not held to account. And the crisis continues on a grand scale.
We have a roadmap for the clinical aspects of CIRS. The scientific foundation is now relatively firm and offers a framework to expand our data sets overall, seek additional effective therapies, and apply new research methods to a very old disease. Medicine, and society, needs to catch up. Dr. Shoemaker gave us a gift through his insights and almost 30 years of work on the subject.
It is time for the next generation of providers, in partnership with the public, to raise awareness of CIRS, conduct high-quality outcomes research, establish reliable clinical guidelines, and assure people have access to clean interior environments. My hope is that the rush of satisfaction and relief practitioners feel when they cure a CIRS patient can be focused into these other activities to inspire meaningful change in medical, public health, policy and legal domains. No one is coming to save us. We have to build on the current momentum to create a better future for ourselves, our patients, and the general population.
Dr. Andrew Heyman invites you to join him at the upcoming 31st Annual Spring Congress, where he will be discussing the latest advancements in the field of CIRS and speaking at concurrent advanced modules. Click here to learn more about the upcoming event and sign up today!
As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before changing your wellness routine. This article is not intended to provide a medical diagnosis, recommendation, treatment, or endorsement.
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