Immunological corollary of the pulmonary mycobiome in bronchiectasis:The Cameb study

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis. Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes. The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations. The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio

Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research

FUNCTIONAL CHARACTERIZATION OF GENES ASSOCIATED WITH ATOPIC DERMATITIS

Ph.DDOCTOR OF PHILOSOPH

Exonic mutations associated with atopic dermatitis disrupt lympho-epithelial Kazal-type related inhibitor action and enhance its degradation

10.1111/all.14018ALLERGY752403-41

Functional Polymorphisms of the Arachidonic Acid Pathway Associate with Risks and Clinical Outcomes of Allergic Diseases

10.1159/000530393International Archives of Allergy and Immunology184

IgE-binding residues analysis of the house dust mite allergen Der p 23

10.1038/s41598-020-79820-ySCIENTIFIC REPORTS11

Different phenotypes and factors associated with atopic dermatitis in the young adult Singaporean Chinese population: A cross-sectional study

Background: Atopic dermatitis (AD) is a chronic allergic disease typically accompanied by atopy and thus, a tendency to develop allergic diseases such as allergic rhinitis, asthma or food allergies. Currently, individuals with AD are classified into those presenting with AD alone and those presenting with AD along with other allergic diseases (AD+). It is important to identify the various endophenotypes of AD using anthropometric, environmental, socio-economic, and disease history data in order to improve disease management. To characterize the phenotypic differences among Singaporean Chinese individuals with AD alone and AD+, and identify the socioeconomic, lifestyle, and environmental factors associated with these different presentations. Methods: Based on data collected via a standardized/validated questionnaire, 4604 participants (mean age: 22.1 years) were classified into three groups: 1) AD alone group; 2) AD with other allergic diseases group (AD+); and 3) Control group. Results: Participants were less sensitized to common inhalant allergens in the AD alone group versus the Control group (67% vs. 72%, respectively; p  23) was associated with the disease and the difference was more pronounced in the AD alone group compared to the AD+ group (Odds Ratio: 1.38; 95% Confidence Interval: 1.4–1.67; p < 0.001). No major differences in habits were observed between the AD alone and AD+ groups. Conclusions: The two presentations of AD may have different underlying pathogenesis and associated risk factors. Keywords: Atopic dermatitis, Allergy, Singaporean Chinese population, Phenotypes, Risk factor

Functional CTLA-4 variants associate to both allergic asthma and rhinitis potentially by modulating naïve regulatory T cells.

10.1111/all.15386Allerg

The ERBB2 Exonic Variant Pro1170Ala Modulates Mitogen-Activated Protein Kinase Signaling Cascades and Associates with Allergic Asthma

10.1159/000530960International Archives of Allergy and Immunolog

Golgin A7 family member B (GOLGA7B) is a plausible novel gene associating high glycaemic index diet with acne vulgaris

10.1111/exd.14575EXPERIMENTAL DERMATOLOG