Fungal exposure had been repeatedly associated with a wide range of harmful health effects. The first association between mould exposure and asthma exacerbations was reported almost 300 years ago and since then, they are numerous data on the link between mould sensitization and asthma severity. Most of the data on fungi and asthma concern A. alternata, C. herbarum and A. fumigatus. However, some mould species are known for their more pronounced indoor tropism and since people tend to increase their time spent indoors, the impact of exposure to these “indoor” species cannot be neglected. In the first part of this work, we developed and validated a dot-blot assay for the detection of mould sensitizations against a panel of species. We worked with the classical A. alternata, C. herbarum and A. fumigatus but in addition, we included indoor-related species such as P. chrysogenum, P. brevicompactum, C. sphaerospermum, C. cladosporioides, A. versicolor and more ubiquitous A. niger, and A. flavus. The development of such an assay allowed us to detect sensitizations against species that are not routinely investigated or not available for testing with classical methods such as skin prick tests or CAP tests. In addition, to cope with cross-reactions, a well-described phenomenon with regard to response against moulds, we developed and validated the concept of “major sensitization”, defined as the antigenic response with the highest difference as compared to the variation of response of the negative control. As there are few data on mould sensitization in healthy individuals, the dot-blot assay was used in a large cohort of healthy subjects. The most frequent sensitizations were observed against A. alternata, A. flavus and A. niger and the commonest “major sensitizers” were A. niger and A. alternata. Of note, in this cohort, no “major sensitization” against A. fumigatus was detected while “major sensitization” against a group of species more specifically linked to the indoor environment (Penicillium spp, A. versicolor, C. cladosporioides) reached more than 25.1% of all sensitizations.These findings were quite surprising and since our laboratory had previous expertise with mouse-model of A. alternata-induced asthma, we investigated the inflammatory and allergenic properties of several fungal species to determine if they display different inner inflammatory potential. Six species were included in the panel A. alternata, A. fumigatus, C. cladosporioides, C. sphaerospermum, A. versicolor and P. chrysogenum. Results showed real differences between moulds and while the classification is not clear-cut, A. fumigatus or P. chrysogenum triggered a typical pro-Th2 response, A. alternata and C. sphaerospermum rather induced a neutrophilic inflammation and A. versicolor and C. cladosporioides induced a mixed Th2/Th17 response. In parallel, the sensitization rates and profile were also investigated in a group of mould-sensitized asthmatics and they both differed notably with the healthy cohort. Indeed, in asthmatic patients, the two most frequent major sensitizations were against A. fumigatus (32%) and A. alternata (28%). The last part of the work consisted in a case-control study to evaluate and compare asthma severity markers and indoor mould exposure between the group of mould-sensitized asthmatics (cases) and a group of asthmatics without mould sensitization (controls). Some interesting findings emerged from this study. First, the overall mould contamination (airborne, in settled dust or through visible mould marks) was very high and more than 90% of the visited dwellings were contaminated by at least one mould species/genus (Penicillium spp, A. versicolor, A. fumigatus and C. sphaerospermum) in at least one type of sample (air, dust and visible mould imprints). Of note, overall “indoor mould exposure” was not associated with markers of asthma severity. Second, exposure and sensitization but also sensitization alone to A. fumigatus in asthmatics were associated with asthma severity markers compared to the absence of mould sensitization which confirmed its noxious potential. This contrasted with the absence of significant severity markers associated with other sensitizations. Lastly, we observed a positive link between overall indoor exposure to Penicillium spp and a reduced lung function in asthmatics even in the absence of sensitization. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished
| Identifer | oai:union.ndltd.org:ulb.ac.be/oai:dipot.ulb.ac.be:2013/250383 |
| Date | 28 April 2017 |
| Creators | Vincent, Muriel |
| Contributors | Olivier, Michel, Denis, Olivier, Casimir, Georges, Pilette, C, Schleich, Florence N, Gulbis, Béatrice, Flamand, Véronique, De Vuyst, Paul |
| Publisher | Universite Libre de Bruxelles, Université libre de Bruxelles, Faculté de Médecine – Sciences biomédicales, Bruxelles |
| Source Sets | Université libre de Bruxelles |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:ulb-repo/semantics/doctoralThesis, info:ulb-repo/semantics/openurl/vlink-dissertation |
| Format | No full-text files |
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