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

Abstract

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.

Transcriptional Regulation and Its Misregulation in Human Diseases

“…), together with gene signatures of nasal biopsies and peripheral blood mononuclear cells. Overall, the results of this study revealed a greater degree of similarity between idiopathic environmental intolerance and dampness related asthma than between the same patients and those with asthma not associated to dampness and mold [16]. Transcriptome analysis revealed well defined pathological mechanisms for asthma without exposure to dampness, but not dampness-and-mold-related asthma patients.…”

“…Transcriptome analysis revealed well defined pathological mechanisms for asthma without exposure to dampness, but not dampness-and-mold-related asthma patients. Besides, a distinct molecular pathological profile in nasal and blood immune cells of idiopathic environmental intolerance subjects was found, including several differentially expressed genes (DEGs) that were also detected in dampness-and-mold-related asthma samples, thereby suggesting idiopathic environmental intolerance-type mechanisms [16].…”

“…In this Special Issue, a total of 18 excellent and interesting papers [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], consisting of 13 original research studies [3][4][5][6][10][11][12][14][15][16][18][19][20], as well as five reviews, are published [7][8][9]13,17]. They cover many subjects of transcriptional regulation, including studies on cis-regulatory elements, transcription factors (TF), chromatin regulators, and ncRNAs.…”

“…Furthermore, in the study of Suojalehto et al [16], transcriptome profiling was assessed to investigate whether a distinct clinical subtype of adult-onset asthma could be related to damp and moldy buildings, which are symptoms of idiopathic environmental intolerance, thus identifying potential molecular similarities with this disease. To this purpose, fifty female adult-onset asthma patients were categorized based on their exposure to building dampness and molds and other clinical parameters (inflammation, cytokine profile, etc.…”

Medizinisch klinische Diagnostik bei Schimmelpilzexposition in Innenräumen – Update 2023 (AWMF-Register-Nr. 161/001)

“…In einigen Studien wird ein möglicher Zusammenhang zwischen Feuchte-/Schimmelbefall im Innenraum und MCS diskutiert [118,167,459,520,[548][549][550][551][552][553][554][555][556]. Vereinzelt wird auch von einem Dampness and Mold Hypersensitivity Syndrom [552,557] oder Toxic Mold Syndrome [459,558] gesprochen; letztes nicht ohne Widerspruch [456].…”