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Research Committee Report on Diagnosis and Treatment Of Research Committee Report on Diagnosis and Treatment of Chronic Inflammatory Response Syndrome Caused by Exposure to the Interior Environment of Water-Damaged Buildings JULY 27, 2010 Committee Members Treating Physicians: Ritchie C. Shoemaker MD* Laura Mark MD Scott McMahon MD Consulting Committee Members: Jack D. Thrasher PhD Carl Grimes HHS, CIEC * Corresponding author. Phone 410-957-1550 COPYRIGHT 2010 Pocomoke, Maryland 2 Table of Contents Overview ......................................................................................................3 Background .................................................................................................8 Agency opinion IOM, GAO, WHO, NIOSH............................................9 Biocontaminants in WDB; Dr. Thrasher ...............................................19 Biocontaminants causing human illness .................................................32 Animal health: mechanisms and physiology..........................................47 Human health effects................................................................................61 Mechanisms of illness acquisition............................................................74 The relevant scientific community ..........................................................93 Why No One Should Accept both the ACOEM and AAAAI Consensus Statements.............................................103 Epidemiology primer..............................................................................116 Cognitive deficits and inflammation .....................................................123 Inflammation from WDB.......................................................................135 What does human research tell us? ......................................................151 Diagnosis and treatment.........................................................................154 Treatment protocols ...............................................................................158 References on therapy from Dr. Shoemaker’s group .....................................................160 Biographies and Conflict of Interest.....................................................161 3 Overview: The Mold Research Committee presents our position statement on the current state of the science regarding human health effects acquired following exposure to the multiple microbes and microbial contaminants and their metabolites found in the interior environment of water-damaged buildings (WDB). These contaminants include but are not limited to fungi, bacteria, actinomycetes, and mycobacteria and their toxins; as well as inflammagens from fragments of fungal structures; and beta glucans, mannans, hemolysins, proteinases, spirocyclic drimanes and microbial volatile organic compounds (VOCs). Exposure to these WDB environments can cause a readily identifiable illness syndrome characterized by specific metabolic disturbances stemming from lack of neuropeptide control of host inflammatory responses, genetic susceptibility and abnormal downstream inflammatory parameters that not only define the illness but also provide the academic basis for sequential therapeutic interventions. Our findings are focused on abnormal physiologic changes in health, documented by health care professionals who are actively involved with case management of those made ill from exposure in WDB. The current body of literature describing the multiple adverse health effects acquired following exposure to the interior environments of WDB is extensive. The physiology unveiled by such literature mirrors the physiologic findings in chronic inflammatory response syndromes. The literature we cite throughout this document supports the concept that exposure to the interior environment of WDB creates abnormal inflammatory responses that are both biomarkers for the presence of the illness and guides for therapy. We note that the readily recognized abnormalities in host immune responses are initiated both by (i) the adverse effects of toxins such as mycotoxins, endotoxins and toxins made by actinomycetes; and (ii) effects of inflammagens. As the many possible sources of compounds that are found in WDB can each lead to the diversity of host responses seen, it is impossible to distinguish a unique source of such abnormal immune responses in patients with illness acquired following exposure to the interior environment of WDB. Several consensus statements have been composed in the past decade. Yet none have included (a) assessments made by physicians involved with diagnosis and treatment of these adverse health effects; (b) academic papers written by physicians reporting both baseline and treatment data on the human illness; (c) reporting of results from published studies using treatment protocols or studies on prospective human or animal experimentation; (d) reporting based on objective parameters found in affected patients; and (e) clinical status after interventions. Despite these substantial shortcomings of pertinent information, these prior consensus statements are being used (i) in legal matters to report the state of human health effects from exposure in WDB and (ii) to serve as the basis for public health policy. 4 A more current reporting of accepted science that is based on literature review and includes, but is not limited to, experience of actual treating physicians is the foundation for our consensus opinion. As identified by the US Government Accountability Office (GAO, 2008) report and the World Health Organization report (WHO, 2009), there are many compounds, both toxigens and inflammagens, present in the indoor air of a WDB that have been identified within the complex mixture found in the air and in the dust of the interior environments of WDB. Further, there is clear data showing that each of these compounds can initiate an inflammatory host response such that no single compound can be identified as the sole cause of the inflammatory responses seen in affected patients. Since many sources of inflammatory stimulus exist, some of which are synergistic, and no single causative agent within the WDB can be deemed to be solely responsible for the symptoms exhibited, the sole causative agent becomes the interior environment of the WDB itself. It is our consensus opinion that this syndrome acquired after exposure to water damaged buildings with evidence of amplification of microbial growth shall be referred to as, “Chronic Inflammatory Response Syndrome acquired following exposure to the interior environment of Water-Damaged Buildings (CIRS-WDB).” We note in recent years a dramatic increase in published studies from the private sector, US governmental agencies and international health agencies with a focus on various and diverse human health effects acquired following exposure to the interior environment of WDB. These substantive papers support the understanding that: (1) CIRS-WDB is a multisystem, multisymptom illness acquired following exposure to the interior environment of WDB and it exists as a recognizable syndrome. When defined by i) exposure; ii) symptom evaluation; and iii) epidemiologic similarities between studies of similar hosts and similar exposures, CIRS-WDB is both identifiable and treatable. A proven and consistent pattern of symptoms is demonstrated among published research findings involving both animal and human studies. (2) CIRS-WDB is identified as immunologic in origin, with differential inflammatory responses seen according to (i) genetic susceptibility and (ii) unique aspects of host innate immune responses. Direct effects of microbial toxins, particularly mycotoxins, in pathogenesis are recognized to act synergistically with those toxins made by actinomycetes, gram negative bacteria, and possibly mycobacteria causing the effects shown in CIRS-WDB. Cellular immunity affecting T-cells and Th-17 plays a role in CIRS-WDB, as do immunologic changes activated by both toxins and inflammagens that are found in the interior environment of WDB. It is scientifically demonstrated that innate immune host responses are similar in their appearance following human exposure to many of the toxins and inflammagens that are simultaneously found to be present inside WDB. Documenting those immune abnormalities will not (and cannot) implicate any one, isolated, specific source. Given the current scientific information and readily available physiologic abnormalities that patients with CIRS-WDB experience, we must expand our assessment beyond the known effects of simple, individual toxins when establishing public health policy and private sector physician treatment protocols. 5 (3) CIRS-WDB consistently involves (but is not limited to) abnormalities in levels of regulatory neuropeptides MSH and VIP; pro-inflammatory cytokines IL-1B, IL-6, 8, 12, 13 and others; split products of complement activation, especially C4a; responses of hypoxia inducible factor, including but not limited to vascular endothelial growth factor (VEGF), erythropoietin and transforming growth factor beta-1 (TGF B-1); and cellular immunity. This type of cellular immunity includes effects on T-regulatory cells; Th-17 immunity impacting IL-17 and IL-23 functions; and auto-immunity, primarily anti- gliadin and anti-cardiolipin antibodies. Additional problems commonly seen are hormonal dysregulation involving corticosteroids (identified when ACTH and cortisol measured simultaneously), regulation of body osmolality (identified when ADH and osmolality measured simultaneously) and androgens; and coagulation factors,
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