How Does Mild Asthma Differ Phenotypically from Difficult-to-Treat Asthma?

Background: Despite most of the asthma population having mild disease, the mild asthma phenotype is poorly understood. Here, we aim to address this gap in knowledge by extensively characterising the mild asthma phenotype and comparing this with difficult-to-treat asthma.

Methods: We assessed two real-world adult cohorts from the South of England using an identical methodology: the Wessex AsThma CoHort of difficult asthma (WATCH) (n=498) and a mild asthma cohort from the comparator arm of the Epigenetics Of Severe Asthma (EOSA) study (n=67).

Cytotoxic CD4 tissue-resident memory T cells are associated with asthma severity.

Background: Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. CD4 T2 cells play a central role in orchestrating asthma pathogenesis, and biologic therapies targeting their cytokine pathways have had promising outcomes. However, not all patients respond well to such treatment, and their effects are not always durable nor reverse airway remodeling.

Fucoxanthin levels in maternal serum at birth and eczema risk in offspring in early childhood: A birth cohort study.

Background: Fucoxanthin, a marine xanthophyll carotenoid, has been shown to exert beneficial health effects. Cell-based and animal-based experimental studies have shown that fucoxanthin has the potential to mitigate eczema symptoms. Hence, we sought to assess whether fucoxanthinol 3-arachidate, a fucoxanthin metabolite, measured in maternal serum at birth is associated with eczema development during early childhood.

The efficacy of the Dyson air purifier on asthma control: A single-center, investigator-led, randomized, double-blind, placebo-controlled trial.

Background: Air pollution is associated with poor asthma outcomes. High-efficiency particulate air air purifiers may reduce air pollution and thus improve asthma outcomes. However, the efficacy of such devices for this purpose remains inconclusive.

The role of epigenetics in multi-generational transmission of asthma: An NIAID workshop report-based narrative review.

There is mounting evidence that environmental exposures can result in effects on health that can be transmitted across generations, without the need for a direct exposure to the original factor, for example, the effect of grandparental smoking on grandchildren. Hence, an individual's health should be investigated with the knowledge of cross-generational influences. Epigenetic factors are molecular factors or processes that regulate genome activity and may impact cross-generational effects.

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Background: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.

Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium.

Evolution of Eczema, Wheeze, and Rhinitis from Infancy to Early Adulthood: Four Birth Cohort Studies.

The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts.

Does allergen immunotherapy for allergic rhinitis prevent asthma?

Asthma and allergic rhinitis (AR) have overlapping clinical and pathologic features, sustained by an underlying T helper 2 bias, resulting in airway inflammation that extends from the nose to the lung. Children who are monosensitized often develop polysensitization over time, and they are at high risk of developing asthma. The effect of allergen immunotherapy (AIT) is allergen specific, resulting in symptom improvement and reduction in medication requirement.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

Background: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age.

Methods: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC, forced expiratory flow at 75% of FVC (FEF) and asthma at a median (range) age of 7 (4-15) years.

MicroRNAs-A Promising Tool for Asthma Diagnosis and Severity Assessment: A Systematic Review.

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.

DNA Methylation and Asthma Acquisition during Adolescence and Post-Adolescence, an Epigenome-Wide Longitudinal Study.

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).

Modeling Wheezing Spells Identifies Phenotypes with Different Outcomes and Genetic Associates.

Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies. We propose that a more comprehensive description of wheeze may better describe trajectories than binary information on the presence/absence of wheezing. We derived six multidimensional variables of wheezing spells from birth to adolescence (including duration, temporal sequencing, and the extent of persistence/recurrence).

Newborn DNA methylation and asthma acquisition across adolescence and early adulthood.

Background: Little is known about the association of newborn DNA methylation (DNAm) with asthma acquisition across adolescence and early adult life.

Objective: We aim to identify epigenetic biomarkers in newborns for asthma acquisition during adolescence or young adulthood.

Methods: The Isle of Wight Birth Cohort (IOWBC) (n = 1456) data at ages 10, 18 and 26 years were assessed.

Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study.

Background: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.

Methods: We studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, >10-15, >15-20, >20-25 years, and overall, 5-25 years).

Sex-specific developmental trajectories of eczema from infancy to age 26 years: A birth cohort study.

Background: Eczema is a common inflammatory skin disease with varying developmental trajectories/patterns that are influenced by different risk factors. The aim of this study was to investigate eczema development from infancy to early adulthood by identifying distinct developmental trajectories that describe disease patterns over time and evaluate the role of prenatal and early-life risk factors.

Methods: The Isle of Wight Birth Cohort (n = 1456) was prospectively assessed at birth, 1, 2, 4, 10, 18 and 26 years.

Childhood food allergy and food allergen sensitisation are associated with adult airways disease: A birth cohort study.

Background: Childhood food allergy (FA) and food allergen sensitization (FAS) are associated with allergic airway disease(s) [AAD] (asthma and rhinitis) in childhood. However, the associations between childhood FA/FAS and AAD in adulthood are not well described.

Methods: We investigated the longitudinal relationship between childhood FA/FAS to common food allergens and AAD at 18 and 26 years, in the Isle of Wight birth cohort.

DNA Methylation at Birth is Associated with Childhood Serum Immunoglobulin E Levels.

Immunoglobulin E (IgE) is known to play an important role in allergic diseases. Epigenetic traits acquired due to modification of deoxyribonucleic acid (DNA) methylation (DNAm) in early life may have phenotypic consequences through their role in transcriptional regulation with relevance to the developmental origins of diseases including allergy. However, epigenome-scale studies on the longitudinal association of cord blood DNAm with IgE over time are lacking.

Real-world Omalizumab and Mepolizumab treated difficult asthma phenotypes and their clinical outcomes.

Background: Omalizumab and Mepolizumab are biologic drugs with proven efficacy in clinical trials. However, a better understanding of their real-world effectiveness in severe asthma management is needed.

Objectives: To better understand the real-world effectiveness of Omalizumab and Mepolizumab, elucidate the clinical phenotypes of patients treated with these drugs, identify baseline characteristics associated with biologic response and assess the spectrum of responses to these medications.

Epigenome-scale comparison of DNA methylation between blood leukocytes and bronchial epithelial cells.

Agreement in DNA methylation (DNAm) at the genome scale between blood leukocytes (BL) and bronchial epithelial cells (BEC) is unknown. We examine as to what extent DNAm in BL is comparable with that in BEC and serves as a surrogate for BEC. Overall agreement (paired -tests with false discovery rate adjusted p > 0.