Medical Journal Review
WAO Reviews - Editors' Choice
Articles are selected for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases by Juan Carlos Ivancevich, MD, WAO Web Editor-in-Chief, and John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor.
1.) Climate Change and Air Pollution: Effects on Respiratory Allergy
D’Amato G, Pawankar R, Vitale C, Lanza M, Molino A et al. Climate Change and Air Pollution: Effects on Respiratory Allergy. Allergy, Asthma and Immunology Research 2016; 8(5): 391-395. (doi:10.4168/aair.2016.8.5.391)
Over the last century, there has been a major industrial growth worldwide. A consequence of this advance has been an increase in the concentration of greenhouse gasses, global warming, and air pollution. In this review by D’Amato and colleagues, the authors examine the effects of climate change on respiratory allergy. They note that what knowledge we have regarding these associations are derived from epidemiological and experimental studies regarding the relationship between allergic respiratory diseases and environmental factors, including air pollution.
It is clear from these studies that urbanization and its resultant high levels of vehicle emissions, as well as westernized lifestyle, are correlated with an increased frequency of respiratory allergy primarily in those who live in urban areas (in comparison with people living in rural areas). The authors conclude that much more work is needed, however, to better understand this relationship and develop tools and implement policies to reduce future impact.
2.) Atopic Dermatitis Susceptibility Variants In Filaggrin Hitchhike Hornerin Selective Sweep
Eaaswarkhanth M, Xu D, Flanagan C, Rzhetskaya M, Hayes MG et al. Atopic Dermatitis Susceptibility Variants In Filaggrin Hitchhike Hornerin Selective Sweep. Genome Biology and Evolution 2016; published online ahead of print, September 27. (doi:10.1093/gbe/evw242)
The filaggrin (FLG) gene has been widely studied for its skin-barrier function in humans with established variation in this gene, especially common loss-of-function (LoF) mutations, being a primary risk factor for atopic dermatitis. In this study by Eaaswarkhanth and colleagues, investigate the evolution of the FLG gene by analyzing 2,504 human genomes and genotyping the copy number variation of FLG repeats within FLG in 126 individuals from diverse ancestral backgrounds. From this, they present evidence suggesting that FLG genetic variation, including LoF variants, have little or no effect on fitness in modern humans. Their results further suggest that the target of the adaptive sweep is hornerin (HRNR) gene function, and the functional FLG variants that involve susceptibility to atopic dermatitis, seem to hitchhike the selective sweep on HRNR.
3.) Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation
Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S et al. National gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature Medicine 2016; 22: 1187-1191. (doi:10.1038/nm.4176)
Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma. In this study, Fujimura and colleagues hypothesized that compositionally distinct human neonatal gut microbiota (NGM) exist, and are differentially related to relative risk (RR) of childhood atopy and asthma. Using stool samples (n = 298; aged 1–11 months) from a US birth cohort and 16S rRNA sequencing, neonates (median age, 35 d) were stratified into three microbiota composition states (NGM1–3). Each demonstrated a substantially different RR for allergen sensitization at age 2 and doctor-diagnosed asthma at age 4 years. The highest risk group, labeled NGM3, showed a lower relative abundance of certain bacteria (for example, Bifidobacterium, Akkermansia, and Faecalibacterium), a higher relative abundance of particular fungi (Candida and Rhodotorula) and a distinct fecal metabolome enriched for pro-inflammatory metabolites. Ex vivo culture of human adult peripheral T cells with sterile fecal water from NGM3 subjects increased the proportion of CD4+ cells producing interleukin (IL)-4 and reduced the number of CD4+CD25+FOXP3+ cells.
These findings suggest that neonatal gut microbiome dysbiosis might promote CD4+ T cell dysfunction associated with childhood atopy.
4.) Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Diseases. A Systematic Review and Meta-analysis.
Lerodiakonou D, Garcia-Larsen V, Logan A, Groome A, Cunha S et al. Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Diseases. A Systematic Review and Meta-analysis. JAMA 2016; 316(11): 1181-1192. (doi:10.1001/jama.2016.12623)
Recent research indicates that the timing of introduction of allergenic foods to the infant diet appears to influence the risk of allergic disease. In this paper by Ierodiakonou and colleagues, the authors perform a meta-analysis to better understand the impact of timing of allergenic food introduction during infancy and its influence on the risk of allergic disease. To do so, they performed an extensive literature search of Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic disease or allergic sensitization were included.
The authors noted that of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. From this they found that there was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95%CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95%CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95%CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95%CI, 6-22 cases) per 1000 population. It should be noted, however, that the certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Also, the timing of egg or peanut introduction was not associated with risk of allergy to other foods. Lastly, there was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis.
5.) Untargeted metabolic profiling of saliva by liquid chromatography-mass spectrometry for the identification of potential diagnostic biomarkers of asthma.
Malkar A, Wilson E, Harrison T, Shaw D, Creaser C. Untargeted metabolic profiling of saliva by liquid chromatography-mass spectrometry for the identification of potential diagnostic biomarkers of asthma. Analytical Methods 2016; 27(8): 5407-5413. (doi:10.1039/C6AY00938G)
Recent research has highlighted the heterogeneous nature of asthma. It is important for clinicians to be able to better our asthmatic patients. One potential tool is the use of non-invasive metabolic profiling technologies. In this study by Malkar, the authors rely on a rapid analytical method for metabolite profiling of saliva using ultra-high performance liquid chromatography combined with high-resolution time-of-flight mass spectrometry (UHPLC-MS). This method is applied in this pilot study of saliva samples obtained by passive drool from well-phenotyped patients with asthma and healthy controls. Stepwise data reduction and multivariate statistical analysis were performed on this dataset obtained from the UHPLC-MS analysis in an attempt to identify potential metabolomic biomarkers of asthma in saliva. The authors found ten discriminant features that distinguished between moderate asthma and healthy control samples with an overall recognition ability of 80% during training of the model and 97% for model cross-validation. The reported method demonstrates the potential for a non-invasive approach to the clinical diagnosis of asthma using mass spectrometry-based metabolic profiling of saliva.