Transcriptomic Profiling of Adult-Onset Asthma Related to Damp and Moldy Buildings and Idiopathic Environmental Intolerance

A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.

Idiopathic Environmental Intolerance: A treatment model

Idiopathic environmental intolerance (IEI) refers to a health condition characterized by the presence of multiple symptoms in different organ systems in response to a variety of environmental cues, such as chemical exposures, electromagnetic radiation, infrasound from windmill farms, (parts of) buildings, foods etc. Typically, the symptoms arise in response to triggers and at dosages that do not cause symptoms in the majority of people, and no clear link with any physiological dysfunction can be found. The condition varies in a dimensional way from very mild, for which no medical help is sought, to very disabling compromising normal life. The condition is controversial, but several indications strongly suggest that the symptoms result from nocebo mechanisms. Currently, different psychological treatments are explored, but they are generally not based on a clear understanding of the aetiopathological mechanisms and the treatment effects are not well documented. In the present paper, we describe a treatment protocol based on a comprehensive explanatory model of IEI. The goal is to contribute to standardized, mechanism-based treatments as a basis for more systematic treatment studies.

Unproved and controversial methods and theories in allergy/immunology

Unproved methods and controversial theories in the diagnosis and management of allergy/immunology are those that lack scientific credibility. Some definitions are provided for perspective, as in chronic medical conditions, frequently nonscientifically based treatments are developed that can have a profound psychological effect on the patients in the absence of objective physical benefit. Standard practice uses methods of diagnosis and treatment used by reputable physicians in a particular subspecialty or primary care practice, with the understanding that diagnosis and treatment options are consistent with established mechanisms of conditions or diseases. Conventional medicine (Western or allopathic medicine) is that which is practiced by the majority of physicians, osteopaths, psychologists, registered nurses, and physical therapists. Complementary medicine involves diverse practices or products that are used with the practice of conventional medicine, such as using acupuncture in addition to opioids for pain relief. Alternative medicine implies use of complementary practices in place of conventional medicine. Unproved and controversial methods and theories do not have supporting data, validation, or sufficient scientific scrutiny, and they should not be used in the practice of allergy/immunology. Some examples of unproven theories about allergic/immunologic conditions include allergic toxemia, idiopathic environmental intolerance, and toxic disease from indoor molds. Unconventional diagnostic methods for allergic conditions include cytotoxic tests, provocation-neutralization, electrodermal diagnosis, applied kinesiology assessments, chemical analysis of body fluids, and serum immunoglobulin G (IgG) or IgG4 testing. Unproven treatments and intervention methods for allergic/immunologic conditions include acupuncture, homeopathy, halotherapy, and autogenous urine injections.