This review focuses on new findings in the clinical and inflammatory aspects that can help to better identify the different phenotypes of work-related asthma and the development of specific ...biomarkers useful in diagnosis and follow-up.
Studies on phenotyping of occupational asthma, a subtype of work-related asthma, have mainly compared the clinical, physiological, and inflammatory patterns associated with the type of agent causing occupational asthma, namely, high-molecular-weight and low-molecular-weight agents. Most of this research has found that patients with occupational asthma due to high-molecular-weight agents have an associated presence of rhinitis, conjunctivitis, atopy, and a pattern of early asthmatic reactions during specific inhalation challenge. The inflammatory profile (blood eosinophils, sputum cell count, or exhaled nitric oxide) may be similar when occupational asthma is caused by either type of agent. In some studies, severity of asthma and exacerbations have been associated with exposure to low-molecular-weight agents. The most reliable biomarkers in diagnosis and follow-up are eosinophilia in induced sputum and exhaled nitric oxide.
There are several phenotypes, characterized by its pathogenesis and inflammatory profile. Avoidance of the causative agents does not warrant complete recovery of occupational asthma. Treatment with biologic agents may be considered in severe occupational asthma.
To describe the recent insights of how molecular diagnosis can be useful to improve indication and selection of suitable allergens for specific immunotherapy and to increase its safety.
As specific ...allergen immunotherapy is allergen-specific, the identification of the disease-eliciting allergen is a prerequisite for accurate prescription of anti-allergic treatment. In areas of complex sensitization to aeroallergens or in hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may change indication and selection of allergens for immunotherapy in a large proportion of patients when compared with the use of skin prick testing and/or specific IgE determination with commercial extracts. These changes in the prescription of immunotherapy after using molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Some patterns of sensitization to grass or olive pollen allergens may identify patients with higher risk of adverse reaction during immunotherapy.
Molecular diagnosis, together with other tools and patients' clinical history, can help clinicians better select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions.
Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co‐morbidities, complexity in care pathways and ...differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home‐based) and its cost‐effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.
Eosinophil‐derived exosomes can act as functional units and are able to autoregulate eosinophil function.
Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. ...We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n = 58) and healthy volunteers (n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil‐derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM‐1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma.
Molecular diagnosis and immunotherapy Sastre, Joaquín; Sastre-Ibañez, Marina
Current opinion in allergy and clinical immunology,
2016-December, Letnik:
16, Številka:
6
Journal Article
To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy.
As specific ...allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy.
Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.
There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different ...types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment (
< 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the biosynthesis/degradation of glucans (
< 0.05). However, it did not correlate with an improvement in lung function. MiRNA-338-3p could be used as a biomarker of early response to reslizumab and mepolizumab in severe eosinophilic asthmatic patients. In fact, this miRNA could be involved in airway remodeling, targeting genes related to MAPK and TGF-β signaling pathways.
Occupational exposure to foods is responsible for up to 25% of cases of occupational asthma and rhinitis. Animal and vegetable high‐molecular‐weight proteins present in aerosolized foods during food ...processing, additives, preservatives, antioxidants, and food contaminants are the main inhalant allergen sources. Most agents typically cause IgE‐mediated allergic reactions, causing a distinct form of food allergy (Class 3 food allergy). The allergenicity of a food protein, allergen exposure levels, and atopy are important risk factors. Diagnosis relies on a thorough medical and occupational history, functional assessment, assessment of sensitization, including component‐resolved diagnostics where appropriate, and in selected cases specific inhalation tests. Exposure assessment, including allergen determination, is a cornerstone for establishing preventive measures. Management includes allergen exposure avoidance or reduction (second best option), pharmacological treatment, assessment of impairment, and worker's compensation. Further studies are needed to identify and characterize major food allergens and define occupational exposure limits, evaluate the relative contribution of respiratory versus cutaneous sensitization to food antigens, evaluate the role of raw versus cooked food in influencing risk, and define the absolute or relative contraindication of patients with ingestion‐related food allergy, pollinosis, or oral allergy syndrome continuing to work with exposure to aerosolized food allergens.
Background
Asthma is a syndrome characterized by airway inflammation and obstruction. Due to its heterogeneity, the difficulties in asthma diagnosis and treatment make the discovery of new biomarkers ...a focus of research. So, we determined the differential miRNA expression of eosinophils between healthy and asthmatic patients and to establish a differentially expressed miRNA profile detectable in sera for use as biomarker.
Methods
MicroRNAs from peripheral eosinophils from healthy and asthmatic subjects were isolated and analyzed by next‐generation sequencing and confirmed by quantitative PCR in 29 asthmatics and 10 healthy individuals. The levels of serum miRNAs were performed by quantitative PCR in 138 asthmatics and 39 healthy subjects. Regression analysis and Random Forest models were performed.
Results
We found a set of miRNAs whose expression differs between eosinophils from asthmatics and healthy subjects. These miRNAs can classify asthmatics into two clusters that differed in the number of eosinophils and periostin concentration in serum. Some of these miRNAs were also confirmed in sera, as miR‐185‐5p which discriminates asthmatics from healthy subjects. Together with other two miRNAs, miR‐185‐5p allowed us to create a logistic regression model to discriminate better both conditions and a Random Forest model that can even sort the asthmatics into intermittent, mild persistent, moderate persistent, and severe persistent asthma.
Conclusion
Our data show that miRNAs profile in eosinophils can be used as asthma diagnosis biomarker in serum and that this profile is able to rank asthma severity.
Eosinophils from asthmatics present a different profile in microRNAs (miRNAs) compared to eosinophils from healthy subjects. As eosinophils obtention from patients is not a standardized method, we analyzed these miRNAs in serum showing that miRNAs profile expression in this biofluid can be used for asthma diagnosis and for severity classification.
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