Type 2 immunity in asthma

Juan Carlos Ivancevich Thursday, 28 June 2018 00:08
 
Marco Caminati, Duy Le Pham, Diego Bagnasco and Giorgio Walter Canonica
 
World Allergy Organization Journal 2018 11:13

https://doi.org/10.1186/s40413-018-0192-5

Abstract

Type 2-immunity represents the typical adaptive response to allergen exposure in atopic individuals. It mainly involves Th2 cells and immunoglobulin E, as the main orchestrators of type 2-inflammation. Recently, it has been highlighted that allergens may be responsible for a Th2 response beside specific IgE activation and that a number of other environmental stimuli, such as viruses and pollutants, can trigger the same pattern of inflammation beyond atopy. Emerging data sustain a substantial role of the so-called epithelial dysfunction in asthma pathogenesis, both from anatomic and functional point of view. Furthermore an increasing amount of evidence demonstrates the relevance of innate immunity in polarizing a Th2 impaired response in asthmatic patients. Under this perspective, the complex cross-talking between airway epithelium, innate and adaptive immunity is emerging as a major determinant of type 2-inflammation beyond allergens.

This review will include an update on the relevance of dysregulation of innate and adaptive type 2-immunity in asthma pathogenesis, particularly severe asthma, and on the role of the allergens that are associated with severe asthma. Type 2-immunity also will be reviewed in the light of the current and upcoming targeted treatments for severe asthma.

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Mount Sinai Team Diagnoses Asthma With Nasal Brush Test

Juan Carlos Ivancevich Monday, 18 June 2018 23:12

RNA sequencing and machine learning applied to develop new asthma biomarker

“Mild to moderate asthma can be difficult to diagnose because symptoms change over time and can be complicated by other respiratory conditions,” said Supinda Bunyavanich, MD, physician and researcher at the Icahn School of Medicine. “Our nasal brush test takes seconds to collect. For time-strapped clinicians, particularly primary care providers at the front lines of asthma diagnosis, this could greatly improve patient outcomes through early and accurate diagnosis.”

Currently, pulmonary function testing (PFT) is the most reliable diagnostic tool for asthma. However, the equipment and expertise needed to perform these tests are not always available in primary care settings where asthma is frequently diagnosed and treated. It is also difficult to differentiate between asthma and other respiratory diseases using PFT alone, while the nasal brush and subsequent analysis for this asthma biomarker provides a binary result of asthma or not asthma.

Data scientists leading the study applied machine learning algorithms to the genetic (RNA) data acquired from nasal brushes of patients with and without asthma. This robust data collection, and machine learning analysis, identified a 90-gene biomarker indicative of asthma status. “One of the most exciting components of this study is demonstrating the power of machine learning when applied to biomedical data,” said Gaurav Pandey, PhD, who led data science efforts to develop the biomarker. “Collaborations between computational scientists and biomedical researchers and clinicians are advancing medicine at an inspiring pace. We have the power of many insights we didn’t have in the past, and that opens a window to an entirely new world of diagnostic tools and treatments”

Similar genetic biomarker tests are currently being used in other disease areas, including MammaPrint and Oncotype DX®, both used for certain types of breast cancer prognosis. In fact, the Oncotype DX tool was used in the largest clinical trial of personalized breast cancer prognosis ever conducted, demonstrating that mammography testing is unnecessary to diagnose breast cancer in a large fraction of breast cancer patients. The positive clinical impact that biomarker tests such as this have shown indicates great potential for further diagnostic tools based on biomarkers.

Dr. Bunyavanich says the next step to bringing this test into clinical practice is a study in a larger population of patients. “With prospective validation in large cohorts, our asthma biomarker could lead to the development of a minimally invasive test to aid asthma diagnosis at clinical frontlines where time and resources often preclude pulmonary function testing.”

Asthma affects 10 percent of children and adults in the United States. When undiagnosed, it can lead to restricted activity, emergency room visits, and hospitalizations. “We’re hopeful that further studies can help bring this test into primary care settings, transforming the ease and accuracy of diagnosing asthma and our ability as doctors to appropriately treat our patients,” said Dr. Bunyavanich.

About the Icahn School of Medicine at Mount Sinai

The Icahn School of Medicine at Mount Sinai is an international leader in medical and scientific training, biomedical research, and patient care. It is the medical school for the Mount Sinai Health System, which includes seven hospital campuses, and has more than 5,000 faculty and nearly 2,000 students, residents and fellows. The School is made up of 36 multidisciplinary research, educational, and clinical institutes and 33 academic departments. It ranks 13th among U.S. medical schools for NIH funding and 2nd in research dollars per principal investigator among U.S. medical schools by the Association of American Medical Colleges (AAMC). The School was named 4th among "World's Most Innovative Companies in Data Science" by Fast Company magazine in 2016. For more information, visit http://icahn.mssm.edu

 

Outdoor air pollution and respiratory health: a bibliometric analysis of publications in peer-reviewed journals (1900 – 2017)

Juan Carlos Ivancevich Saturday, 02 June 2018 18:20
Waleed M. SweilehSamah W. Al-JabiSa’ed H. Zyoud and Ansam F. Sawalha 

Abstract

Background

Outdoor air pollution is a major threat to global public health that needs responsible participation of researchers at all levels. Assessing research output is an important step in highlighting national and international contribution and collaboration in a certain field. Therefore, the aim of this study was to analyze globally-published literature in outdoor air pollution – related respiratory health.

Method

Outdoor air pollution documents related to respiratory health were retrieved from Scopus database. The study period was up to 2017. Mapping of author keywords was carried out using VOSviewer 1.6.6.

Results

Search query yielded 3635 documents with an h-index of 137. There was a dramatic increase in the number of publications in the last decade of the study period. The most frequently encountered author keywords were: air pollution (835 occurrences), asthma (502 occurrences), particulate matter (198 occurrences), and children (203 occurrences). The United States of America ranked first (1082; 29.8%) followed by the United Kingdom (279; 7.7%) and Italy (198; 5.4%). Annual research productivity stratified by income and population size indicated that China ranked first (22.2) followed by the USA (18.8). Analysis of regional distribution of publications indicated that the Mediterranean, African, and South-East Asia regions had the least contribution. Harvard University (92; 2.5%) was the most active institution/organization followed the US Environmental Protection Agency (89; 2.4%). International collaboration was restricted to three regions: Northern America, Europe, and Asia. The top ten preferred journals were in the field of environmental health and respiratory health. Environmental Health Perspective was the most preferred journal for publishing documents in outdoor pollution in relation to respiratory health.

Conclusion

Research on the impact of outdoor air pollution on respiratory health had accelerated lately and is receiving a lot of interest. Global research networks that include countries with high level of pollution and limited resources are highly needed to create public opinion in favor of minimizing outdoor air pollution and investing in green technologies.

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Asthma research collection

Juan Carlos Ivancevich Monday, 11 June 2018 14:35

Elsevier and the editors of the official journals of the American Academy of Allergy, Asthma & Immunology (AAAAI) would like to make these recent Asthma research articles available free through July 10th, 2018.

The Journal of Allergy and Clinical Immunology

Featuring a 13.081 Impact Factor

Inflammatory Phenotypes in Patients with Severe Asthma are Associated with Distinct Airway Microbiology
Toll-like Receptor 3 Blockade in Rhinovirus-induced Experimental Asthma Exacerbations: A Randomized Controlled Study
Overweight/obesity Status in Preschool Children Associates with Worse Asthma But Robust Improvement on Inhaled Corticosteroids
Managing Asthma in Pregnancy (MAP) Trial: FeNO Levels and Childhood Asthma

 

The Journal of Allergy and Clinical Immunology: In Practice

Featuring a 5.317 Impact Factor

Taming Asthma in School-Aged Children: A Comprehensive Review
The Tempest: Difficult To Control Asthma in Adolescence
Asthma over the age of 65: All's Well That Ends Well
Effects of exercise and diet in non-obese asthma patients - a randomized controlled trial

Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma

Juan Carlos Ivancevich Thursday, 24 May 2018 13:21

Abstract

Background

The fractional exhaled nitric oxide (FeNO) and blood eosinophils are biomarkers of eosinophilic airway inflammation used in the diagnosis and management of asthma, although induced sputum is the gold standard test for phenotypic asthma. Nevertheless, the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils is controversial.

Objective

To investigate the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils with uncontrolled asthmatic patients. It also examined the relationships between these biomarkers in bronchial reversibility and bronchial hyper-responsiveness (BHR).

Methods

This study evaluated 75 uncontrolled asthmatic patients (symptom control and future risk of adverse outcomes). All patients underwent the following on the same day: FeNO, spirometry, BHR or bronchodilator reversibility, sputum induction and blood collection. Eosinophilic airway inflammation was defined as sputum eosinophils ≥ 2.5% or FeNO levels ≥ 32 parts per billion (ppb).

Results

A significant positive relationship was between percentage of sputum eosinophils and FeNO (r = 0.4556; p < 0.0001) and percentage of blood eosinophils (r = 0.3647; p = 0.0013), and a significant negative correlation was between percentage of sputum neutrophils and FeNO (r = − 0.3653; p = 0.0013). No relationship between FeNO and percentage of blood eosinophils (p = 0.5801). ROC curve analysis identified FeNO was predictive of sputum eosinophilia [area under the curve (AUC) 0.707, p = 0.004] at a cutoff point of 35.5 ppb (sensitivity = 67.3%, specificity = 73.9%). Percentage of blood eosinophils was also highly predictive with an AUC of 0.73 (p = 0.002) at a cut-off point of 1.5%, sensitivity and specificity were 61.5 and 78.3%, respectively. Although the sputum neutrophil percentage was correlated with FeNO, ROC curve of these parameters did not show useful values (AUC = 0.297, p = 0.003; AUC = 0.295, p = 0.021).

Conclusions and clinical relevance

Blood eosinophils and FeNO can accurately predict eosinophilic airway inflammation in uncontrolled asthmatic patients. FeNO is poor surrogates for sputum neutrophils and blood eosinophils. The FeNO level and blood eosinophils, which determine an optimal cutoff for sputum eosinophilia, need more studies.

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Editor: Juan C. Ivancevich, MD

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