Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa

Laulajainen‐Hongisto, Anu; Lyly, Annina; Hanif, Tanzeela; Dhaygude, Kishor; Kankainen, Matti; Renkonen, Risto; Donner, Kati; Mattila, Pirkko; Jartti, Tuomas; Bousquet, Jean; Kauppi, Paula; Toppila‐Salmi, Sanna

doi:10.1186/s13601-020-00347-6

Cited by 31 publications

(16 citation statements)

References 151 publications

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“…Previous estimations have noted that genetic predisposition accounted for 25-80% of asthma risk and up to 90% of AR risk. 56 The chromosome 17q21 region is the most well described and consistently replicated region with asthma susceptibility. 57 ORMDL sphingolipid biosynthesis regulator codes for transmembrane proteins anchored in the endoplasmic reticulum.…”

Section: Asthma Genomicsmentioning

confidence: 99%

Managing Exacerbations in Thunderstorm Asthma: Current Insights

Chatelier

Chan

Tan

et al. 2021

JIR

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Epidemic thunderstorm asthma (ETSA) occurs following a thunderstorm due to the interaction of environmental and immunologic factors. Whilst first reported in the 1980s, the world's largest event in Melbourne, Australia, on November 21, 2016 has led to a wealth of clinical literature seeking to identify its mechanisms, susceptibility risk factors, and management approaches. Thunderstorm asthma (TA) typically presents during an aeroallergen season in individuals sensitized to perennial rye grass pollen (RGP) in Australia, or fungus in the United Kingdom, in combination with meteorological factors such as thunderstorms and lightning activity. It is now well recognized that large pollen grains, which usually lodge in the upper airway causing seasonal allergic rhinitis (SAR), are ruptured during these events, leading to sub-pollen particles respirable to the lower respiratory tract causing acute asthma. The identified risk factors of aeroallergen sensitization, specifically to RGP in Australians with a history of SAR, and individuals born in Australia of South-East Asian descent as a risk factor for TA has been key in selecting appropriate patients for preventative management. Moreover, severity-determining risk factors for ETSA-related asthma admission or mortality, including pre-existing asthma or prior hospitalization, poor inhaled corticosteroid adherence, and outdoor location at the time of the storm are important in identifying those who may require more aggressive treatment approaches. Basic treatments include optimizing asthma control and adherence to inhaled corticosteroid therapy, treatment of SAR, and education regarding TA to increase recognition of at-risk days. Precision treatment approaches may be more beneficial in select individuals, including the use of allergen immunotherapy and even biologic treatment to mitigate asthma severity. Finally, we discuss the importance of environmental health literacy in the context of concerns surrounding the increased frequency of ETSA due to climate change and its implications for the frequency and severity of future events.

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Section: Asthma Genomicsmentioning

confidence: 99%

Managing Exacerbations in Thunderstorm Asthma: Current Insights

Chatelier

Chan

Tan

et al. 2021

JIR

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“…7,8 AR involves an intricate cooperation between genetic predisposition and environmental factors, with implicated genes being intensely studied. 9 Genomic searches have verified the roles of chromosomes 2, 3, 4, and 9 9 . Some AR-related single nucleotide polymorphisms (SNPs) have also been discovered [10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

GARP Polymorphisms Associated with Susceptibility to House Dust Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population

Chen¹,

Zhu²,

Chen³

et al. 2022

JAA

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Background: Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese. Methods: In this hospital-based case-control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold. Results: rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019-1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427-0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥16 years (adjusted OR = 1.745, 95% CI = 1.103-2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021-2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676-0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699. Conclusion: SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.

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“…However, albeit humans are continuously in contact with allergens, not everyone develops allergic reaction which highlights the importance of both extrinsic as well as intrinsic factors for the inception of the disease. Numerous genetic studies correlated the risk of developing allergies with multiple genes many of which were immunity related [ 4 , 5 ]. Moreover, according to the hygiene hypothesis , the elevated prevalence of allergic diseases is due to increased sterile hygiene practices in the modern world leading to dysregulation of immune system and microbiome dysbiosis because of diminished exposure to immune-stimulating microbial agents in the early childhood [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Immune mechanisms induced by sublingual immunotherapy in allergic respiratory diseases

Gazi

Bahceciler

2022

Clinical and Experimental Immunology

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Allergic respiratory diseases (ARDs) are still a major burden on global public health. Sublingual immunotherapy (SLIT) is a mode of allergen immunotherapy (AIT) which involves administration of the allergen under the tongue, and benefits from tolerogenic properties of the oral mucosa. Studies revealed reduced levels of eosinophilia and eosinophil-dominated inflammation in airways of both animals and humans after SLIT. SLIT was also suggested to lower basophil responsiveness and innate lymphoid cell-2 function in blood samples collected from ARD patients. Moreover, apart from shifting pathogenic type 2 (TH2) to a type 1 (TH1) and protective regulatory (Treg) polarization of helper T-cell immune response, antibody isotype switch from IgE to IgG1, IgG2, IgG4 and IgA was also reported in ARD patients receiving SLIT. Today, the literature on SLIT-mediated activities is still scarce and more studies are required to further enlighten the mechanisms utilized by SLIT for the induction of tolerance. The aim of this review is to summarize the current knowledge about the immune-regulatory mechanisms induced by SLIT against ARDs.

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Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa

Cited by 31 publications

References 151 publications

Managing Exacerbations in Thunderstorm Asthma: Current Insights

Managing Exacerbations in Thunderstorm Asthma: Current Insights

GARP Polymorphisms Associated with Susceptibility to House Dust Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population

Immune mechanisms induced by sublingual immunotherapy in allergic respiratory diseases

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