Epigenetic landscape links upper airway microbiota in infancy with allergic rhinitis at 6 years of age.

BACKGROUND: The upper airways present a barrier to inhaled allergens and microbes, which alter immune responses and subsequent risk for diseases, such as allergic rhinitis (AR). OBJECTIVE: We tested the hypothesis that early-life microbial exposures leave a lasting signature in DNA methylation that ultimately influences the development of AR in children. METHODS: We studied upper airway microbiota at 1 week, 1 month, and 3 months of life, and measured DNA methylation and gene expression profiles in upper airway mucosal cells and assessed AR at age 6 years in children in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort. RESULTS: We identified 956 AR-associated differentially methylated CpGs in upper airway mucosal cells at age 6 years, 792 of which formed 3 modules of correlated differentially methylated CpGs. The eigenvector of 1 module was correlated with the expression of genes enriched for lysosome and bacterial invasion of epithelial cell pathways. Early-life microbial diversity was lower at 1 week (richness P = .0079) in children with AR at age 6 years, and reduced diversity at 1 week was also correlated with the same module's eigenvector (ρ = -0.25; P = 3.3 × 10-5). We show that the effect of microbiota richness at 1 week on risk for AR at age 6 years was mediated in part by the epigenetic signature of this module. CONCLUSIONS: Our results suggest that upper airway microbial composition in infancy contributes to the development of AR during childhood, and this trajectory is mediated, at least in part, through altered DNA methylation patterns in upper airway mucosal cells.

Association Between Microbiota and Nasal Mucosal Diseases in terms of Immunity.

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.

Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa.

BACKGROUND: The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models. RESULTS: Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. CONCLUSION: Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.

Gut microbial characteristics of adult patients with allergy rhinitis.

BACKGROUND: Although recent studies have indicated that intestinal microbiota dweller are involved in the pathogenesis of allergy rhinitis (AR), the influence of gut microbiota on AR adult has not been fully elucidated yet. Hence, we carried out this study to uncover the distinctive bacterial taxa that differentiate allergy rhinitis patients from healthy individuals. Feces samples from thirty three AR patients and thirty one healthy individuals were analyzed by 16S rRNA gene sequencing. RESULTS: Results showed that the bacterial diversity in AR group was significantly higher than that of the non-AR group. Bacterial communities between AR and non-AR group were significantly differentiated as revealed by Principal coordinates analysis (PCoA) and the variation within non-AR were higher than that of the counterpart. Firmicutes, Fusobacteria, Actinobacteria, Cyanobacteria and Chloroflexi were the significantly differed phyla taxa and the top significantly distinguished bacterial genus included Prevotella_9, Phascolarctobacterium, Roseburia, Megamonas, Alistipes, Lachnoclostridium and Fusobacterium. The higher network complexity in AR group were dominated by taxa belonging to Firmicutes. The predicted function, alpha linolenic acid metabolism and bacterial invasion of epithelial cells pathway were higher in non-AR group while gonadotropin-releasing hormone (GnRH) signaling pathway, Fc γ-R mediated phagocytosis and endocytosis were higher in AR patients. Although the bacterial diversity between moderate and severe AR patients showed no significant difference, the significant correlation between featured genus and total nasal symptom score or rhinoconjunctivitis quality of life questionnaire, such as Butyricicoccus and Eisenbergiella, revealed the potential to intervene the AR status by means of gut microbiota. CONCLUSIONS: In conclusion, patients with allergy rhinitis had distinguished gut microbiota characteritics in comparison with healthy controls. The results suggest that gut microbiota might play crucial roles in influencing the course and different symptoms of AR. Trial registration ChiCTR, ChiCTR1900028613. Registered 29 December 2019, https://www.chictr.org.cn/showproj.aspx?proj=47650 .

Outside-in hypothesis revisited: The role of microbial, epithelial, and immune interactions.

OBJECTIVE: Our understanding of the origin of allergic diseases has increased in recent years, highlighting the importance of microbial dysbiosis and epithelial barrier dysfunction in affected tissues. Exploring the microbial-epithelial-immune crosstalk underlying the mechanisms of allergic diseases will allow the development of novel prevention and treatment strategies for allergic diseases. DATA SOURCES: This review summarizes the recent advances in microbial, epithelial, and immune interactions in atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma. STUDY SELECTIONS: We performed a literature search, identifying relevant recent primary articles and review articles. RESULTS: Dynamic crosstalk between the environmental factors and microbial, epithelial, and immune cells in the development of atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma underlies the pathogenesis of these diseases. There is substantial evidence in the literature suggesting that environmental factors directly affect barrier function of the epithelium. In addition, T-helper 2 (TH2) cells, type 2 innate lymphoid cells, and their cytokine interleukin 13 (IL-13) damage skin and lung barriers. The effects of environmental factors may at least in part be mediated by epigenetic mechanisms. Histone deacetylase activation by type 2 immune response has a major effect on leaky barriers and blocking of histone deacetylase activity corrects the defective barrier in human air-liquid interface cultures and mouse models of allergic asthma with rhinitis. We also present and discuss a novel device to detect and monitor skin barrier dysfunction, which provides an opportunity to rapidly and robustly assess disease severity. CONCLUSION: A complex interplay between environmental factors, epithelium, and the immune system is involved in the development of systemic allergic diseases.

IL-17C expression and its correlation with pediatric adenoids: a preliminary study.

Objective: Interleukin-17 (IL-17) C is a cytokine expressed by epithelial cells in response to bacterial stimulation. In contrast to other members of the IL-17 family of cytokines, IL-17C is upregulated early during infection, maintains integrity of the epithelial layer barrier, and mediates the innate immune response. We investigated the expression profile of IL-17C in pediatric adenoids. Methods: Pediatric adenoid tissues and lavage fluids were collected from a total of 38 subjects. The Limulus amebocyte lysate test and real-time PCR using Staphylococcus aureus primers were performed to evaluate bacterial contents in adenoids. Expression of IL-17RE in adenoids was analyzed using real-time polymerase chain reaction and western blot. The expression of IL-17C was evaluated by western blot and immunohistochemistry and compared between allergic rhinitis (AR) and control subjects. The levels of Hsp27, Hsp70, and IL-17C in adenoid lavage fluids were evaluated by enzyme-linked immunosorbent assay, and the correlation between these molecules was statistically analyzed. Results: The pediatric adenoids were found to be exposed to bacteria and had a normal flora comprising both gram-negative and -positive bacteria. IL-17RE, an IL-17C specific receptor, was highly expressed in the epithelium of adenoids. IL-17C was expressed in all evaluated adenoid tissue samples, irrespective of the allergic status of the patient. IL-17C secretion was detected in half of the adenoid lavage fluid samples and was associated with Hsp70 level. Conclusion: Our findings indicate the possible role of pediatric adenoids in innate immunity modulation via an innate immunity-associated cytokine.

Prognostic role of blood eosinophil and basophil levels in allergic fungal rhinosinusitis (AFRS).

PURPOSE: Allergic fungal rhinosinusitis (AFRS) forms a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) that is mainly characterized by eosinophilic nasal polyps, allergic mucin detected in the sinuses at surgery, and specific features on computerized tomography. Which biological markers predict disease recurrence in AFRS is still not clear, and the role of blood inflammatory cells in predicting recurrent polyps after surgery has yet to be investigated. The aim of this study was to newly investigate the prognostic role (in terms of recurrence rate) of preoperative blood eosinophil and basophil levels in AFRS. MATERIALS AND METHODS: A consecutive series of 17 adult patients who underwent endoscopic sinus surgery for AFRS was retrospectively assessed. RESULTS: Sinonasal polyps recurred in 7 of 17 patients. Considering the whole cohort, a significant positive correlation emerged between blood eosinophil and basophil counts, but not between blood and tissue eosinophil counts. Statistical analysis found significantly higher blood eosinophil and basophil levels in AFRS patients who relapsed than in those who did not. CONCLUSIONS: Considering the current difficulty of identifying more effective, personalized approaches to postoperative disease management in AFRS, our preliminary data support the impression that blood eosinophil and basophil levels warrant testing in further prospective and larger (preferably multi-institutional) investigations as part of the preoperative work-up for patients with AFRS in order to administer dedicated postoperative medical treatments for patients at higher risk of relapse.

Omalizumab versus intranasal steroids in the post-operative management of patients with allergic fungal rhinosinusitis.

PURPOSE: Allergic fungal rhinosinusitis (AFRS) is a common disorder with a high prevalence and a very high incidence of recurrence. Management includes surgery and medical treatment in the form of local and/or systemic steroids. However, some cases are resistant to the action of steroids and further treatment is warranted. Being an immune-mediated disorder, targeting IgE seems a logical step. Immunotherapy drugs acting on the IgE (e.g. omalizumab) can modify the clinical course of the disease. This study aimed at evaluating the effect of omalizumab on the clinical course of patients undergoing surgery for AFRS. MATERIALS AND METHODS: This is a two-arm prospective, randomized, single blind clinical trial among patients with AFRS. Twenty patients were included and randomly divided into two groups: Group A; 10 patients received a single subcutaneous injection of omalizumab (Xolair ' Novartis) (150 mg) 2 weeks postoperatively. Group B: 10 patients received local steroids nasal sprays (budesonide or mometasone furoate, 100 µg twice daily for 6 months, starting 2 weeks postoperatively. All patients underwent history, examination, CT scan and IgE level estimation and were submitted to endoscopic sinus surgery. They were evaluated at 4 weeks interval for 6 months. RESULTS: In both groups there were highly significant differences between pre/post-operative SNOT-20 scores, TNSS scores, total IgE level and Philpott-Javer staging scores. Comparison between the two study groups at 24 weeks showed a highly significant difference (p = 0.001) between post-operative SNOT 20 and TNSS scores in favour of group A. There was no statistically significant difference between the two study groups as regarding postoperative total IgE or Philpott-Javer scores. There were two recurrences in both arms, but no significant side effects. DISCUSSION: We compared a single post operative injection of omalizumab with twice daily intranasal steroid spray for 6 months. Both treatments were effective, but the omalizumab group showed a more significant clinical and endoscopic response. There were no significant side effects in both arms. This novel approach used a single low dose injection of omalizumab increased the compliance of the patients with minimal complications. Longer follow-up of the patients is ongoing to determine the optimal time for re-injection. The only downside was the higher cost of omalizumab compared to that of local steroids.

Association of Staphylococcus aureus colonization with food allergy occurs independently of eczema severity.

BACKGROUND: Staphylococcus aureus has been implicated in the pathophysiology of eczema, allergic rhinitis, asthma, and food allergy. S aureus is a marker of more severe eczema, which is a risk factor for food sensitization/allergy. Therefore it might be that the association between S aureus and food allergy in eczematous patients is related to eczema severity. OBJECTIVE: We sought to investigate the association of S aureus colonization with specific IgE (sIgE) production to common food allergens and allergies in early childhood independent of eczema severity. We additionally determined the association of S aureus colonization with eczema severity and persistence. METHODS: In Learning Early About Peanut Allergy (LEAP) study participants eczema severity was assessed, and skin/nasal swabs were cultured for S aureus. Sensitization was identified by measuring sIgE levels. Peanut allergy was primarily determined by means of oral food challenge, and persistent egg allergy was primarily determined by using skin prick tests. RESULTS: Skin S aureus colonization was significantly associated with eczema severity across the LEAP study, whereas at 12 and 60 months of age, it was related to subsequent eczema deterioration. Skin S aureus colonization at any time point was associated with increased levels of hen's egg white and peanut sIgE independent of eczema severity. Participants with S aureus were more likely to have persistent egg allergy and peanut allergy at 60 and 72 months of age independent of eczema severity. All but one of the 9 LEAP study consumers with peanut allergy (9/312) were colonized at least once with S aureus. CONCLUSION: S aureus, independent of eczema severity, is associated with food sensitization and allergy and can impair tolerance to foods. This could be an important consideration in future interventions aimed at inducing and maintaining tolerance to food allergens in eczematous infants.

Characterization of ocular and nasopharyngeal microbiome in allergic rhinoconjunctivitis.

BACKGROUND: Allergic rhinoconjunctivitis (ARC) is a prevalent allergic condition in the pediatric population. Microbial dysbiosis has increasingly been recognized to influence on host immunity and allergic diseases. However, the microbial profile of ARC has not been characterized. This cross-sectional study aims to evaluate the changes in nasal and ocular surface microbiome of children with ARC. METHODS: Ocular and nasopharyngeal swabs were collected from controls and pediatric ARC cases for 16S rRNA amplicon sequencing. The bacterial community profile was analyzed. The correlation of the microbial diversity with the ARC-related clinical scores was studied. RESULTS: A total of 23 patients with ARC and 17 healthy controls were recruited;30 were ocular samples (15 controls vs 15 ARC), while 40 were nasal samples (17controls vs 23 ARC) The alpha diversity of nasopharyngeal microbiome was significantly higher in ARC patients than healthy controls (P < 0.01), but not for ocular microbiome. The clinical scores in all subjects were negatively correlated with the Shannon diversity for ocular (P = 0.014) and positively correlated with nasopharyngeal (P = 0.010) microbiome. While the ocular microbiome remained significantly distinct from nasopharyngeal microbiome in terms of both alpha and beta diversity in both healthy subjects and ARC patients, significant differences of relative abundance of certain phyla (Bacteroidetes, Cyanobacteria, and Deinococcus-Thermus) and genera (Dolosigranulum and Moraxella) between nasal and ocular surfaces were only detected in healthy controls, but not in the ARC subjects, suggesting the microbial composition at both body sites becoming more similar at disease state. CONCLUSION: This study reported (a) a higher alpha diversity in ocular than nasopharyngeal microbiome in both ARC patients and controls, and (b) nasopharyngeal microbiome became more diverse in ARC patients than in controls. Our results suggested an interaction of the microbiome between ocular and nasal compartments in patients with ARC.

The Role of Staphylococcus aureus in Patients with Chronic Sinusitis and Nasal Polyposis.

PURPOSE OF REVIEW: Staphylococcus aureus (S. aureus) is correlated with the development of persistent severe inflammatory disease of the upper airway including chronic rhinosinusitis with nasal polyps (CRSwNP). The presence of S. aureus is associated with atopic disease including allergic rhinitis and atopic dermatitis and is associated with poor outcomes. RECENT FINDINGS: Several different strains of S. aureus generate different toxins and gene products that can account for organism pathogenicity. S. aureus bacteria and its antigens shape the bacterial and fungal microbiome and the mucosal niche which generates host responses that can account for inflammation. The multiple disease phenotypes and molecular endotypes seen in CRSwNP can be characterized by T-helper cell environment within the inflammatory milieu, the presence of epithelial barrier dysfunction, aberrant eicosanoid metabolism, poor wound healing, and dysfunctional host-bacteria interactions which lead to recalcitrant disease and worse surgical outcomes. Understanding the pathomechanisms that S. aureus utilizes to promote nasal polyp formation, prolonged tissue inflammation, and bacterial dysbiosis are essential in our efforts to identify new therapeutic approaches to resolve this chronic inflammatory process.

Survey of 1012 moldy dwellings by culture fungal analysis: Threshold proposal for asthmatic patient management.

Different countries have tried to define guidelines to quantify what levels of fungi are considered as inappropriate for housing. This retrospective study analyzes indoor fungi by cultures of airborne samples from 1012 dwellings. Altogether, 908 patients suffering from rhinitis, conjunctivitis, and asthma were compared to 104 controls free of allergies. Portuguese decree law no 118/2013 (PDL118), ANSES (a French environmental and health agency) recommendations, and health regulations of Besançon University Hospital were applied to determine the rates of non-conforming dwellings, which were respectively 55.2%, 5.2%, and 19%. Environmental microbiological results and medical data were compared. The whole number of colonies per cubic meter of air was correlated with asthma (P < 0.001) and rhinitis (P = 0.002). Sixty-seven genera and species were detected in bedrooms. Asthma was correlated to Aspergillus versicolor (P = 0.004) and Cladosporium spp. (P = 0.02). Thresholds of 300 cfu/m3 for A. versicolor or 495 cfu/m3 for Cladosporium spp. are able to discriminate 90% of the asthmatic dwellings. We propose a new protocol to obtain an optimal cost for indoor fungi surveys, excluding surface analyses, and a new guideline to interpret the results based on >1000 cfu/m3 of whole colonies and/or above threshold levels for A. versicolor or Cladosporium spp.

Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis.

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (n = 20) and healthy controls (n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgElow), low microbial biodiversity with a high relative abundance of Firmicutes phylum (Staphylococcus aureus) and a low relative abundance of Actinobacteria phylum (Propionibacterium acnes) was observed in individuals with high total serum IgE levels (group IgEhigh). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgEhigh as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.

Role of preoperative versus postoperative itraconazole in allergic fungal rhinosinusitis.

Antifungals used as adjuvant to surgery in AFRS (Allergic Fungal Rhinosinusitis) have shown varying success in delaying recurrences. Itraconazole has been used both as preoperative and postoperative adjuvant. This study investigates the role of itraconazole in AFRS and compares its role between preoperative and postoperative administration of the drug. Patients were randomly divided into groups as: Group 1 (n = 25), received 4 weeks itraconazole in the preoperative period and operated subsequently, Group 2 (n = 25), received 4 weeks itraconazole in the postoperative period, Group 3 (n = 50), matched patients of AFRS, who didn't receive itraconazole. All the groups received oral steroids in tapering doses staring from 1 mg/kg for 6 weeks in the postoperative period. Symptomatic (SNOT 20), radiologic (Lund Mackay, LM) scores and endoscopic (Kupferberg's NE Grades) were noted. Primary postoperative follow-up was for 24 weeks with routine CT scans and nasal endoscopies, followed by which all the patients were followed with nasal endoscopies only with CT scans when required. Both preoperative and postoperative itraconazole showed significant improvement in the SNOT, LM, and Kupferberg's grades in the follow-up period. Preoperative itraconazole therapy showed significantly better results compared to postoperative itraconazole therapy though the recurrence rates were similar in both groups. Itraconazole is a better preoperative adjunct in AFRS than postoperative.

[FEATURES OF MICROBIOCENOSIS OF NOSE MUCOUS MEMBRANE DURING ATOPIC AND POLYPOUS RHINOSINUSITIS].

AIM: Study of microbiocenosis of nose mucous membrane during allergic rhinosinusitis. MATERIALS AND METHODS: Patients with polypous (PRS) and atopic (ARS) rhinosinusitis were examined, as well-as a control group.. Standard general clinical methods taking differential diagnostics ofatopic diseases and rhinitis into consideration were used for the PRS and ARS diagnosis. RESULTS: Microbial content during different forms of rhinosinusitis has varying directionality that is deter- mined by different pathogenetic mechanisms. ARS microflora has a significantly extended range and was characterized by an increase of concentration. of opportunistic microorganisms not characteristic for normoflora. Microbial composition for PRS was significantly depleted by a lack of certain permanent members of microflora, whereas the quantity of opportunistic bacteria was significantly above normal.. CONCLUSION: Disturbance of microbiocenosis in patients with allergic rhinosinusitis was detected, more pronounced in the PRS group. Staphylococcus strains isolated from patients with ARS and PRS possess pathogenic properties in equal ratios, wherein the per- centage of strains in ARS group that have persistence properties is higher than in other studied groups. This could give evidence regarding their role in development of inflammatory process on the nose mucous membrane.

The impact of indoor air quality and contaminants on respiratory health of older people living in long-term care residences in Porto.

BACKGROUND: persons who are 65 years or older often spend an important part of their lives indoors thus adverse indoor climate might influence their health status. OBJECTIVE: to evaluate the influence of indoor air quality and contaminants on older people's respiratory health. DESIGN: cross-sectional study. SETTING: 21 long-term care residences (LTC) in the city of Porto, Portugal. SUBJECTS: older people living in LTC with ≥65 years old. METHODS: the Portuguese version of BOLD questionnaire was administered by an interviewer to older residents able to participate (n = 143). Indoor air contaminants (IAC) were measured twice, during winter and summer in 135 areas. Mixed effects logistic regression models were used to study the association between the health questionnaire results and the monitored IAC, adjusted for age, smoking habits, gender and number of years living in the LTC. RESULTS: cough (23%) and sputum (12%) were the major respiratory symptoms, and allergic rhinitis (22%) the main self-reported illness. Overall particulate matter up to 2.5 micrometres in size median concentration was above the reference levels both in winter and summer seasons. Peak values of particulate matter up to 10 micrometres in size (PM10), total volatile organic compounds, carbon dioxide, bacteria and fungi exceeded the reference levels. Older people exposed to PM10 above the reference levels demonstrated higher odds of allergic rhinitis (OR = 2.9, 95% CI: 1.1-7.2). CONCLUSION: high levels of PM10 were associated with 3-fold odds of allergic rhinitis. No association was found between indoor air chemical and biological contaminants and respiratory symptoms.

[Health risks associated with the environmental presence of toxigenic moulds].

INTRODUCTION: This study reviews the occurrence and most common health effect of exposure to moulds in different environment. The short characteristic of chosen toxigenic fungi and the major mycotoxin classes was also presented. Exposure to allergens may cause human disease, including allergic rhinitis, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis asthma and sick building syndrome. Moulds also reveal carcinogenic, cytotoxic, and neurotoxic properties.

Exposure to visible mould or dampness at home and sleep problems in children: Results from the LISAplus study.

BACKGROUND: Exposure to mould or dampness at home has been associated with adverse respiratory effects in all age groups. This exposure has also been related to insomnia in adults. We aimed to investigate the association between exposure to visible mould or dampness at home and sleep problems in children. METHODS: The study population consisted of 1719 10-year-old children from the German population-based birth cohort LISAplus with available data on current mould or dampness at home and sleep problems. The presence of visible mould or dampness at home was assessed by questionnaire. Parent-reported sleep problems of their child were analysed by four binary variables: presence of any sleep problems, problems to fall asleep, problems sleeping through the night and a 24h sleep time of less than 9h. Logistic regression models adjusted for study centre, sex, age and level of parental education were applied to examine the association between visible mould or dampness at home and sleep problems. Sensitivity analyses included a further adjustment for bedroom sharing and subgroup analyses in children without current allergic diseases. RESULTS: Thirteen percent of parents reported visible mould or dampness at home. We observed increased risks for all four sleep problem variables for children exposed to visible mould or dampness at home. Results were significant for any sleep problems (odds ratio (OR)=1.77 (95%-confidence interval (CI): 1.21-2.60), problems sleeping through the night (OR=2.52(1.27-5.00) and a short sleep time (OR=1.68(1.09-2.61)). While a further adjustment for bedroom sharing and the exclusion of children with asthma or eczema led to similar results, only the association with a short sleep time was still present in children without allergic rhinoconjunctivitis. CONCLUSION: Our data suggests that visible mould or dampness at home might negatively influence sleep in children. The influence of allergic rhinoconjunctivitis on this association needs to be investigated in future studies.

Analysis of the nasal vestibule mycobiome in patients with allergic rhinitis.

Advances in culture-independent sequencing methods have been utilised in recent studies to understand the phylogenetic composition of the human microbiome of healthy and diseased skin. Allergic rhinitis (AR) is an inflammatory condition of the nasal cavity caused by environmental allergens. Although nasal microbial communities have been considered important contributors in human health, no studies to date have comprehensively compared fungal communities (mycobiome) of the nasal vestibule using the culture-independent pyrosequencing method. This study aimed to investigate how fungal communities of the nasal vestibule skin surface are influenced by AR. The phylogenetic composition of the nasal vestibule mycobiome of patients with AR was analysed by culture-independent pyrosequencing methods and compared with healthy individuals. A total of 69 fungal genera were identified from both AR samples and healthy controls, and the genus Malassezia predominated in the nasal vestibule. Species-level analysis classified eight different Malassezia species including M. pachydermatis and M. cuniculi, which were normally isolated from animals, and revealed M. restricta to be the most abundant species in the nasal vestibule. Although high interpersonal variation was observed, some of the AR samples displayed significantly higher diversities than healthy controls at both the genus and species level.

Omalizumab therapy for refractory allergic fungal rhinosinusitis patients with moderate or severe asthma.

PURPOSE: 1. To assess the efficacy of omalizumab therapy in improving sinonasal outcomes in refractory allergic fungal rhinosinusitis (AFRS) patients with moderate or severe asthma. 2. To determine if omalizumab therapy reduces the usage of corticosteroids or antifungal therapy in AFRS patients DESIGN: The clinical charts of patients with AFRS with moderate or severe asthma who received at least three subcutaneous injections of omalizumab therapy between 1st January 2012 and 1st May 2014 were retrospectively reviewed. These patients had undergone bilateral functional endoscopic sinus surgery (FESS) and failed adjunct medical treatments (oral or topical corticosteroids and/or antifungal therapy) prior to omalizumab therapy. RESULTS: Seven patients met the inclusion criteria and were included in this study. The mean age of the patients was 48.14. The average number of subcutaneous omalizumab injections was 7.57 (range 6-11) with a mean dosage of 287mg (range 225-375mg). The mean pre-omalizumab treatment Sino-Nasal Outcome Test-22 (SNOT-22) score was 52.14 while the mean post-omalizumab treatment SNOT-22 score was 35.86 (31% improvement). The mean pre-omalizumab therapy Phillpott-Javer endoscopic score (over the last one year before omalizumab therapy) was 36 while the mean post-omalizumab therapy endoscopic score (from the last clinic visit) was 14 (61% improvement). Omalizumab therapy reduced the dependence of AFRS patients on corticosteroid and antifungal treatments. CONCLUSION: Omalizumab therapy can be considered as a potential adjunct for the treatment for patients with refractory AFRS with moderate or severe asthma. However, larger prospective studies to confirm the findings of this study will be required.