Chemical intolerance: involvement of brain function and networks after exposure to extrinsic stimuli perceived as hazardous.

BACKGROUND: Chemical intolerance (CI) is a chronic condition characterized by recurring and severe symptoms triggered by exposure to low levels of odorous or pungent substances. The etiology of CI has been a controversial subject for a long time. The aim of this review is to summarize findings on the neurological processing of sensory information during and after exposure to low levels of odorous or pungent substances in individuals with CI, focusing on the brain function and networks. METHODS: Scientific studies on CI published between 2000 and 2019 in academic peer-reviewed journals were systematically searched using medical and scientific literature databases. Only peer-reviewed articles reporting original research from experimental human studies directly associated with CI, and involving related neurological responses or brain imaging after exposure to odorous or pungent substances (i.e., in chemical provocation tests), were considered. RESULTS: Forty-seven studies were found to be eligible for a full-text review. Twenty-three studies met the selection criteria and were included in this review. Evidence indicated that differences between subjects with CI and healthy controls were observed by brain imaging during and after exposure to odorous or pungent substances. Differences in brain imaging were also observed between initial exposure and after exposure to these substances. Neurological processing of sensory information after exposure to extrinsic stimuli in the limbic system and related cortices were altered in subjects with CI. A previous documentable exposure event was likely to be involved in this alteration. CONCLUSIONS: This review documents consistent evidence for the altered neurological processing of sensory information in individuals with CI. Further neurophysiological research exploring the processing of extrinsic stimuli and cognition of sensation through the limbic system and related cortices in CI, and the appearance of symptoms in individuals with CI, are required.

Association of Odor Thresholds and Responses in Cerebral Blood Flow of the Prefrontal Area during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity.

Multiple chemical sensitivity (MCS) is a disorder characterized by nonspecific and recurrent symptoms from various organ systems associated with exposure to low levels of chemicals. Patients with MCS process odors differently than controls do. Previously, we suggested that this odor processing was associated with increased regional cerebral blood flow (rCBF) in the prefrontal area during olfactory stimulation using near-infrared spectroscopic (NIRS) imaging. The aim of this study was to investigate the association of odor thresholds and changes in rCBF during olfactory stimulation at odor threshold levels in patients with MCS. We investigated changes in the prefrontal area using NIRS imaging and a T&T olfactometer during olfactory stimulation with two different odorants (sweet and fecal) at three concentrations (zero, odor recognition threshold, and normal perceived odor level) in 10 patients with MCS and six controls. The T&T olfactometer threshold test and subjective assessment of irritating and hedonic odors were also performed. The results indicated that the scores for both unpleasant and pungent odors were significantly higher for those for sweet odors at the normal perceived level in patients with MCS than in controls. The brain responses at the recognition threshold (fecal odor) and normal perceived levels (sweet and fecal odors) were stronger in patients with MCS than in controls. However, significant differences in the odor detection and recognition thresholds and odor intensity score between the two groups were not observed. These brain responses may involve cognitive and memory processing systems during past exposure to chemicals. Further research regarding the cognitive features of sensory perception and memory due to past exposure to chemicals and their associations with MCS symptoms is needed.

Assessment of cerebral blood flow in patients with multiple chemical sensitivity using near-infrared spectroscopy--recovery after olfactory stimulation: a case-control study.

OBJECTIVES: Multiple chemical sensitivity (MCS) is a chronic acquired disorder characterized by non-specific symptoms in multiple organ systems associated with exposure to odorous chemicals. We previously observed significant activations in the prefrontal cortex (PFC) during olfactory stimulation using several different odorants in patients with MCS by near-infrared spectroscopy (NIRS) imaging. We also observed that the patients with MCS did not adequately distinguish non-odorant in the late stage of the repeated olfactory stimulation test. The sensory recovery of the olfactory system in the patients with MCS may process odors differently from healthy subjects after olfactory stimulation. METHODS: We examined the recovery process of regional cerebral blood flow (rCBF) after olfactory stimulation in patients with MCS. NIRS imaging was performed in 6 patients with MCS and in 6 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included a subjective assessment of the physical and psychological status and of the perception of irritating and hedonic odors. RESULTS: After olfactory stimulation, significant activations were observed in the PFC of patients with MCS on both the right and left sides compared with controls. The activations were specifically strong in the orbitofrontal cortex (OFC). Compared with controls, autonomic perception and feelings identification were poorer in patients with MCS. OFC is associated with stimuli response and the representation of preferences. CONCLUSIONS: These results suggest that a past strong exposure to hazardous chemicals activates the PFC during olfactory stimuli in patients with MCS, and a strong activation in the OFC remains after the stimuli.

Case study of airborne fungi according to air temperature and relative humidity in houses with semi-basements adjacent to a forested hillside.

We studied airborne concentrations of fungal spores and the thermal environment in houses with semi-basements surrounded by a natural forest. We examined the relationship between airborne fungi and the thermal environment, surrounding natural environment, structures of houses and use of a dehumidifier. The subject residential area was located in the northern part of Nara city, Nara prefecture, Japan. Six detached houses were included in this study. In residential areas, outdoor airborne concentrations were high during summer and autumn, correlated with humidity. The presence of Basidiomycetes was particularly notable, although the indoor concentration was lower than the outdoor level. In the semi-basement rooms, relative humidity was nearly always >80% when the residence was built; however, both the indoor humidity and fungal concentrations decreased greatly when a dehumidifier was used in this study. High levels of Aspergillus and Basidiomycetes were detected in semi-basements. Basidiomycetes are likely of outdoor origin, whereas Aspergillus might grow indoors. Moreover, the composition of fungal species differed according to room-structure and usage. Due to the health risks associated with high indoor concentrations of fungi, the utilization of the semi-basement or basement space requires adequate ventilation and dehumidification, beginning immediately after construction.

Changes in cerebral blood flow during olfactory stimulation in patients with multiple chemical sensitivity: a multi-channel near-infrared spectroscopic study.

Multiple chemical sensitivity (MCS) is characterized by somatic distress upon exposure to odors. Patients with MCS process odors differently from controls. This odor-processing may be associated with activation in the prefrontal area connecting to the anterior cingulate cortex, which has been suggested as an area of odorant-related activation in MCS patients. In this study, activation was defined as a significant increase in regional cerebral blood flow (rCBF) because of odorant stimulation. Using the well-designed card-type olfactory test kit, changes in rCBF in the prefrontal cortex (PFC) were investigated after olfactory stimulation with several different odorants. Near-infrared spectroscopic (NIRS) imaging was performed in 12 MCS patients and 11 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included subjective assessment of physical and psychological status and the perception of irritating and hedonic odors. Significant changes in rCBF were observed in the PFC of MCS patients on both the right and left sides, as distinct from the center of the PFC, compared with controls. MCS patients adequately distinguished the non-odorant in 10 odor repetitions during the early stage of the olfactory stimulation test, but not in the late stage. In comparison to controls, autonomic perception and negative affectivity were poorer in MCS patients. These results suggest that prefrontal information processing associated with odor-processing neuronal circuits and memory and cognition processes from past experience of chemical exposure play significant roles in the pathology of this disorder.