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

Hille Suojalehto,Antti Lauerma,Kirsi Karvala,Harri Alenius,Liisa Airaksinen,Irmeli Lindström,Sanna Toppila-Salmi,Paula Kauppi,Joseph Ndika,Piia Karisola

doi:10.3390/ijms221910679

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.

Highlights

Asthma is a heterogeneous disease driven by interactions between airway epithelium, the immune system, and environmental exposure
There is a lack of knowledge on the mechanisms of adult-onset asthma and Idiopathic environmental intolerance (IEI) [1,15,16]
We used a combination of clinical assessment and global transcriptomic analysis of blood and airway epithelium to investigate whether specific pathobiological mechanisms of adult-onset asthma associated with dampness and molds could be identified

Summary

Introduction

Asthma is a heterogeneous disease driven by interactions between airway epithelium, the immune system, and environmental exposure. It can be sub-classified into several pheno- and endotypes based on clinical, functional, and inflammatory features [1]. Adult-onset asthma initiated during exposure to building dampness and molds does not demographically differ from the adult-onset asthma phenotype; it is more common in females and predominantly non-allergic [5,6]. These patients use asthma medication excessively, suggesting poor prognosis. The underlying mechanisms are poorly known; it seems immunoglobin E (IgE)-mediated sensitization to molds is not an essential factor for asthma onset in these environments [5]

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