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Personalized Understanding and Management of Asthma and Allergy
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Personalized Understanding and Management of Asthma and Allergy

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Epidemiology".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 18958

Special Issue Editors

Dr. Ramesh J. Kurukulaaratchy

E-Mail Website
Guest Editor
Clinical Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
Interests: difficult-to-control asthma; allergy; lifecourse of asthma and allergy
Dr. Hans Michael Haitchi

E-Mail Website
Guest Editor
Clinical Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
Interests: difficult-to-treat asthma; asthma and ADAM33; effect of maternal asthma on origin of asthma in early life

Special Issue Information

Dear Colleagues,

The last 50 years have seen a significant rise in the global burden of asthma and allergic diseases, creating impact on both societal and individual patient levels. In parallel, there is now a growing understanding of the diverse nature of both asthma and allergic disease and the fact that these terms cover a spectrum of underlying phenotypes with differing mechanistic foundations. From this framework has arisen the drive to adopt personalised treatment approaches to successfully manage asthma and allergy in the 21st Century. This Special Issue of the Journal of Personalized Medicine aims to provide a clinically relevant understanding of advances in the personalised medicine approach to asthma and allergy using basic science, epidemiological, and clinical approaches. We would like to invite your contributions as a key expert in the field to this Special Issue and welcome your input with either original research articles or review articles. This is a great opportunity to publish your work as part of a core collection of articles on advances in asthma and allergy in the context of personalised medicine. So do please join us in this Special Issue.

Kind regards,

Dr. Ramesh J. Kurukulaaratchy
Dr. Hans Michael Haitchi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Asthma
  • Allergy
  • Biomarkers
  • Biologic therapies
  • Endotypes
  • Personalized medicine
  • Phenotypes
  • Prediction
  • Prevention

Published Papers (7 papers)

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Research

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23 pages, 1235 KiB  
Article
Pharmacogenomics of Leukotriene Modifiers: A Systematic Review and Meta-Analysis
by Yuxuan Zhao, Xinyi Zhang, Congxiao Han, Yuchun Cai, Sicong Li, Xiaowen Hu, Caiying Wu, Xiaodong Guan, Christine Lu and Xiaoyan Nie
J. Pers. Med. 2022, 12(7), 1068; https://doi.org/10.3390/jpm12071068 - 29 Jun 2022
Cited by 2 | Viewed by 2166
Abstract
Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May [...] Read more.
Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response. Full article
(This article belongs to the Special Issue Personalized Understanding and Management of Asthma and Allergy)
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18 pages, 3076 KiB  
Article
DNA Methylation and Asthma Acquisition during Adolescence and Post-Adolescence, an Epigenome-Wide Longitudinal Study
by Aniruddha Rathod, Hongmei Zhang, Syed Hasan Arshad, Susan Ewart, Caroline L. Relton, Wilfried Karmaus and John W. Holloway
J. Pers. Med. 2022, 12(2), 202; https://doi.org/10.3390/jpm12020202 - 02 Feb 2022
Cited by 4 | Viewed by 2204
Abstract
The role of epigenetics in the pathogenesis of asthma acquisition in adolescence and post-adolescence has been unknown. We carried out a longitudinal epigenome-wide association study, using data from the Isle of Wight Birth Cohort (IOWBC). To improve statistical power, we first screened CpGs [...] Read more.
The role of epigenetics in the pathogenesis of asthma acquisition in adolescence and post-adolescence has been unknown. We carried out a longitudinal epigenome-wide association study, using data from the Isle of Wight Birth Cohort (IOWBC). To improve statistical power, we first screened CpGs based on associations of DNA methylation (DNAm) at an age of 10 years (pre-adolescence) with asthma acquisition at 10–18 years (during adolescence). A logistic regression with repeated measures was applied to CpGs that passed screening to examine the associations of pre-adolescence DNAm with asthma acquisition from 10–18 years and 18–26 years, with an interaction term to evaluate transition period specificity. Findings were further tested in an independent birth cohort, ALSPAC. In total, 205 CpGs (with 150 being females) showed associations with asthma acquisition (main or interaction effects) at FDR = 0.05 in IOWBC, of which 112 (90 being females) showed consistent associations in the ALSPAC. Genes that the identified CpGs were mapped to, e.g., AKAP1 and ENO1, have been shown to be associated with the risk of asthma. Our findings indicated that DNAm at specific CpGs was associated with asthma acquisition. CpGs showing such associations were likely to be different between males and females and, at certain CpGs, were unique to a specific transition period. Full article
(This article belongs to the Special Issue Personalized Understanding and Management of Asthma and Allergy)
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13 pages, 1538 KiB  
Article
Integration of Genomic Risk Scores to Improve the Prediction of Childhood Asthma Diagnosis
by Dilini M. Kothalawala, Latha Kadalayil, John A. Curtin, Clare S. Murray, Angela Simpson, Adnan Custovic, William J. Tapper, S. Hasan Arshad, Faisal I. Rezwan, John W. Holloway and on behalf of STELAR/UNICORN investigators
J. Pers. Med. 2022, 12(1), 75; https://doi.org/10.3390/jpm12010075 - 08 Jan 2022
Cited by 9 | Viewed by 2871
Abstract
Genome-wide and epigenome-wide association studies have identified genetic variants and differentially methylated nucleotides associated with childhood asthma. Incorporation of such genomic data may improve performance of childhood asthma prediction models which use phenotypic and environmental data. Using genome-wide genotype and methylation data at [...] Read more.
Genome-wide and epigenome-wide association studies have identified genetic variants and differentially methylated nucleotides associated with childhood asthma. Incorporation of such genomic data may improve performance of childhood asthma prediction models which use phenotypic and environmental data. Using genome-wide genotype and methylation data at birth from the Isle of Wight Birth Cohort (n = 1456), a polygenic risk score (PRS), and newborn (nMRS) and childhood (cMRS) methylation risk scores, were developed to predict childhood asthma diagnosis. Each risk score was integrated with two previously published childhood asthma prediction models (CAPE and CAPP) and were validated in the Manchester Asthma and Allergy Study. Individually, the genomic risk scores demonstrated modest-to-moderate discriminative performance (area under the receiver operating characteristic curve, AUC: PRS = 0.64, nMRS = 0.55, cMRS = 0.54), and their integration only marginally improved the performance of the CAPE (AUC: 0.75 vs. 0.71) and CAPP models (AUC: 0.84 vs. 0.82). The limited predictive performance of each genomic risk score individually and their inability to substantially improve upon the performance of the CAPE and CAPP models suggests that genetic and epigenetic predictors of the broad phenotype of asthma are unlikely to have clinical utility. Hence, further studies predicting specific asthma endotypes are warranted. Full article
(This article belongs to the Special Issue Personalized Understanding and Management of Asthma and Allergy)
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12 pages, 772 KiB  
Article
Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients
by Maruša Kopač Šokić, Matija Rijavec, Peter Korošec, Urška Bidovec-Stojkovič, Izidor Kern, Romana Vantur and Sabina Škrgat
J. Pers. Med. 2022, 12(1), 70; https://doi.org/10.3390/jpm12010070 - 07 Jan 2022
Cited by 3 | Viewed by 1901
Abstract
Many questions concerning responders (R) and nonresponders (NR) in severe eosinophilic asthma (SEA) after blocking the IL-5 (interleukin 5) pathway are still not clear, especially regarding the early parameters of response to biologics in personalized treatment strategies. We evaluated 17 SEA patients treated [...] Read more.
Many questions concerning responders (R) and nonresponders (NR) in severe eosinophilic asthma (SEA) after blocking the IL-5 (interleukin 5) pathway are still not clear, especially regarding the early parameters of response to biologics in personalized treatment strategies. We evaluated 17 SEA patients treated with anti-IL-5 biologics (16 patients mepolizumab, one patient benralizumab) before the introduction of biologics, and at a week 16 follow-up. Clinical, cellular and immunological parameters in peripheral blood were measured in R and NR. Sputum induction with the measurement of cellular and immunological parameters was performed at 16 weeks only. There were 12 R and 5 NR to biologics. After 16 weeks, there was a significant improvement in percentages of FEV1 (p = 0.001), and asthma control test (ACT) (p = 0.001) in the R group, but not in NR. After 16 weeks, the eosinophils in induced sputum were 27.0% in NR and 4.5% in R (p = 0.05), with no difference in IL-5 concentrations (p = 0.743). Peripheral eosinophilia decreased significantly in NR (p = 0.032) and R (p = 0.002). In patients with SEA on anti-IL-5 therapy, there was a marked difference in airway eosinophilic inflammation between R and NR already at 16 weeks, after anti-IL-5 introduction. Full article
(This article belongs to the Special Issue Personalized Understanding and Management of Asthma and Allergy)
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11 pages, 889 KiB  
Article
Vitamin D Levels in Asymptomatic Children and Adolescents with Atopy during the COVID-19 Era
by Gavriela Feketea, Vasiliki Vlacha, Georgios Tsiros, Panagiota Voila, Raluca Maria Pop, Ioana Corina Bocsan, Luminita Aurelia Stanciu and Mihnea Zdrenghea
J. Pers. Med. 2021, 11(8), 712; https://doi.org/10.3390/jpm11080712 - 25 Jul 2021
Cited by 6 | Viewed by 2748
Abstract
This study assessed vitamin D status in asymptomatic children and adolescents in Greece, with and without atopy, and possible changes during the coronavirus disease 2019 (COVID-19) pandemic. Serum levels of 25-hydroxy-vitamin D (25(OH)D) and total immunoglobulin E (IgE), and eosinophil count were measured [...] Read more.
This study assessed vitamin D status in asymptomatic children and adolescents in Greece, with and without atopy, and possible changes during the coronavirus disease 2019 (COVID-19) pandemic. Serum levels of 25-hydroxy-vitamin D (25(OH)D) and total immunoglobulin E (IgE), and eosinophil count were measured in 340 asymptomatic children and adolescents (155 males, 185 females), mean age 8.6 ± 4.6 years, recruited over a period of 24 months (February 2019–January 2021). Atopy, defined by high level of IgE for age, was associated with vitamin D deficient status (p = 0.041). Subjects with and without atopy showed similar rates of insufficient and normal levels of 25(OH)D. The median level of 25(OH)D was significantly higher in subjects recruited during the pandemic, when home confinement rules were observed, than before the pandemic, and significantly more children had normal levels of 25(OH)D (p < 0.001), but no differences were noticed for IgE levels or eosinophil count. These results support a link between vitamin D and allergic and infectious inflammations, and specifically the association of vitamin D deficiency with asymptomatic atopy, defined as increased IgE level for age. Full article
(This article belongs to the Special Issue Personalized Understanding and Management of Asthma and Allergy)
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Review

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24 pages, 1260 KiB  
Review
Multimorbidity in Difficult Asthma: The Need for Personalised and Non-Pharmacological Approaches to Address a Difficult Breathing Syndrome
by Judit Varkonyi-Sepp, Anna Freeman, Ben Ainsworth, Latha Perunthadambil Kadalayil, Hans Michael Haitchi and Ramesh J. Kurukulaaratchy
J. Pers. Med. 2022, 12(9), 1435; https://doi.org/10.3390/jpm12091435 - 31 Aug 2022
Cited by 6 | Viewed by 2981
Abstract
Three to ten percent of people living with asthma have difficult-to-treat asthma that remains poorly controlled despite maximum levels of guideline-based pharmacotherapy. This may result from a combination of multiple adverse health issues including aggravating comorbidities, inadequate treatment, suboptimal inhaler technique and/or poor [...] Read more.
Three to ten percent of people living with asthma have difficult-to-treat asthma that remains poorly controlled despite maximum levels of guideline-based pharmacotherapy. This may result from a combination of multiple adverse health issues including aggravating comorbidities, inadequate treatment, suboptimal inhaler technique and/or poor adherence that may individually or collectively contribute to poor asthma control. Many of these are potentially “treatable traits” that can be pulmonary, extrapulmonary, behavioural or environmental factors. Whilst evidence-based guidelines lead clinicians in pharmacological treatment of pulmonary and many extrapulmonary traits, multiple comorbidities increase the burden of polypharmacy for the patient with asthma. Many of the treatable traits can be addressed with non-pharmacological approaches. In the current healthcare model, these are delivered by separate and often disjointed specialist services. This leaves the patients feeling lost in a fragmented healthcare system where clinical outcomes remain suboptimal even with the best current practice applied in each discipline. Our review aims to address this challenge calling for a paradigm change to conceptualise difficult-to-treat asthma as a multimorbid condition of a “Difficult Breathing Syndrome” that consequently needs a holistic personalised care attitude by combining pharmacotherapy with the non-pharmacological approaches. Therefore, we propose a roadmap for an evidence-based multi-disciplinary stepped care model to deliver this. Full article
(This article belongs to the Special Issue Personalized Understanding and Management of Asthma and Allergy)
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Other

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13 pages, 7055 KiB  
Systematic Review
MicroRNAs—A Promising Tool for Asthma Diagnosis and Severity Assessment: A Systematic Review
by Mohammed Aref Kyyaly, Elena Vladimirovna Vorobeva, Dilini M. Kothalawala, Wei Chern Gavin Fong, Peijun He, Collin L. Sones, Mohammad Al-Zahrani, Tilman Sanchez-Elsner, Syed Hasan Arshad and Ramesh J. Kurukulaaratchy
J. Pers. Med. 2022, 12(4), 543; https://doi.org/10.3390/jpm12040543 - 29 Mar 2022
Cited by 11 | Viewed by 2916
Abstract
Micro RNAs (miRNAs) are short, non-coding RNAs (Ribonucleic acids) with regulatory functions that could prove useful as biomarkers for asthma diagnosis and asthma severity-risk stratification. The objective of this systematic review is to identify panels of miRNAs that can be used to support [...] Read more.
Micro RNAs (miRNAs) are short, non-coding RNAs (Ribonucleic acids) with regulatory functions that could prove useful as biomarkers for asthma diagnosis and asthma severity-risk stratification. The objective of this systematic review is to identify panels of miRNAs that can be used to support asthma diagnosis and severity-risk assessment. Three databases (Medline, Embase, and SCOPUS) were searched up to 15 September 2020 to identify studies reporting differential expression of specific miRNAs in the tissues of adults and children with asthma. Studies reporting miRNAs associations in animal models that were also studied in humans were included in this review. We identified 75 studies that met our search criteria. Of these, 66 studies reported more than 200 miRNAs that are differentially expressed in asthma patients when compared to non-asthmatic controls. In addition, 16 studies reported 17 miRNAs that are differentially expressed with differences in asthma severity. We were able to construct two panels of miRNAs that are expressed in blood and can serve as core panels to further investigate the practicality and efficiency of using miRNAs as non-invasive biomarkers for asthma diagnosis and severity-risk assessment, respectively. Full article
(This article belongs to the Special Issue Personalized Understanding and Management of Asthma and Allergy)
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