Pathophysiological Mechanisms of Asthma

The recent commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes cough. The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection...

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Veröffentlicht in:Frontiers in pediatrics Jg. 7; S. 68
1. Verfasser: Bush, Andrew
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media S.A 19.03.2019
Schlagworte:
airway inflammation
biomarker
bronchial biopsy
bronchial brushings
induced sputum
Pediatrics
transcriptomics
airway inflammation
bronchial brushings
asthma phenotype
endotype
bronchial biopsy
induced sputum
transcriptomics
biomarker
ISSN:2296-2360, 2296-2360
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Abstract The recent commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes cough. The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection and altered cough reflex, setting the airway disease in the context of extra-pulmonary co-morbidities and social and environmental factors. The emphasis is always on delineating treatable traits, including variable airflow obstruction caused by airway smooth muscle constriction (treated with short- and long-acting β-2 agonists), eosinophilic airway inflammation (treated with inhaled corticosteroids) and chronic bacterial infection (treated with antibiotics with benefit if it is driving the disease). It is also important not to over-treat the untreatable, such as fixed airflow obstruction. These can all be determined using simple, non-invasive tests such as spirometry before and after acute administration of a bronchodilator (reversible airflow obstruction); peripheral blood eosinophil count, induced sputum, exhaled nitric oxide (airway eosinophilia); and sputum or cough swab culture (bacterial infection). Additionally, the pathophysiology of risk domains must be considered: these are risk of an asthma attack, risk of poor airway growth, and in pre-school children, risk of progression to eosinophilic school age asthma. Phenotyping the airway will allow more precise diagnosis and targeted treatment, but it is important to move to endotypes, especially in the era of increasing numbers of biologicals. Advances in -omics technology allow delineation of pathways, which will be particularly important in TH2 low eosinophilic asthma, and also pauci-inflammatory disease. It is very important to appreciate the difficulties of cluster analysis; a patient may have eosinophilic airway disease because of a steroid resistant endotype, because of non-adherence to basic treatment, and a surge in environmental allergen burden. Sophisticated -omics approaches will be reviewed in this manuscript, but currently they are not being used in clinical practice. However, even while they are being evaluated, management of the asthmas can and should be improved by considering the pathophysiologies of the different airway diseases lumped under that umbrella term, using simple, non-invasive tests which are readily available, and treating accordingly.
AbstractList The recent Lancet commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes cough. The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection and altered cough reflex, setting the airway disease in the context of extra-pulmonary co-morbidities and social and environmental factors. The emphasis is always on delineating treatable traits, including variable airflow obstruction caused by airway smooth muscle constriction (treated with short- and long-acting β-2 agonists), eosinophilic airway inflammation (treated with inhaled corticosteroids) and chronic bacterial infection (treated with antibiotics with benefit if it is driving the disease). It is also important not to over-treat the untreatable, such as fixed airflow obstruction. These can all be determined using simple, non-invasive tests such as spirometry before and after acute administration of a bronchodilator (reversible airflow obstruction); peripheral blood eosinophil count, induced sputum, exhaled nitric oxide (airway eosinophilia); and sputum or cough swab culture (bacterial infection). Additionally, the pathophysiology of risk domains must be considered: these are risk of an asthma attack, risk of poor airway growth, and in pre-school children, risk of progression to eosinophilic school age asthma. Phenotyping the airway will allow more precise diagnosis and targeted treatment, but it is important to move to endotypes, especially in the era of increasing numbers of biologicals. Advances in -omics technology allow delineation of pathways, which will be particularly important in TH2 low eosinophilic asthma, and also pauci-inflammatory disease. It is very important to appreciate the difficulties of cluster analysis; a patient may have eosinophilic airway disease because of a steroid resistant endotype, because of non-adherence to basic treatment, and a surge in environmental allergen burden. Sophisticated -omics approaches will be reviewed in this manuscript, but currently they are not being used in clinical practice. However, even while they are being evaluated, management of the asthmas can and should be improved by considering the pathophysiologies of the different airway diseases lumped under that umbrella term, using simple, non-invasive tests which are readily available, and treating accordingly.The recent Lancet commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes cough. The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection and altered cough reflex, setting the airway disease in the context of extra-pulmonary co-morbidities and social and environmental factors. The emphasis is always on delineating treatable traits, including variable airflow obstruction caused by airway smooth muscle constriction (treated with short- and long-acting β-2 agonists), eosinophilic airway inflammation (treated with inhaled corticosteroids) and chronic bacterial infection (treated with antibiotics with benefit if it is driving the disease). It is also important not to over-treat the untreatable, such as fixed airflow obstruction. These can all be determined using simple, non-invasive tests such as spirometry before and after acute administration of a bronchodilator (reversible airflow obstruction); peripheral blood eosinophil count, induced sputum, exhaled nitric oxide (airway eosinophilia); and sputum or cough swab culture (bacterial infection). Additionally, the pathophysiology of risk domains must be considered: these are risk of an asthma attack, risk of poor airway growth, and in pre-school children, risk of progression to eosinophilic school age asthma. Phenotyping the airway will allow more precise diagnosis and targeted treatment, but it is important to move to endotypes, especially in the era of increasing numbers of biologicals. Advances in -omics technology allow delineation of pathways, which will be particularly important in TH2 low eosinophilic asthma, and also pauci-inflammatory disease. It is very important to appreciate the difficulties of cluster analysis; a patient may have eosinophilic airway disease because of a steroid resistant endotype, because of non-adherence to basic treatment, and a surge in environmental allergen burden. Sophisticated -omics approaches will be reviewed in this manuscript, but currently they are not being used in clinical practice. However, even while they are being evaluated, management of the asthmas can and should be improved by considering the pathophysiologies of the different airway diseases lumped under that umbrella term, using simple, non-invasive tests which are readily available, and treating accordingly.
The recent commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes cough. The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection and altered cough reflex, setting the airway disease in the context of extra-pulmonary co-morbidities and social and environmental factors. The emphasis is always on delineating treatable traits, including variable airflow obstruction caused by airway smooth muscle constriction (treated with short- and long-acting β-2 agonists), eosinophilic airway inflammation (treated with inhaled corticosteroids) and chronic bacterial infection (treated with antibiotics with benefit if it is driving the disease). It is also important not to over-treat the untreatable, such as fixed airflow obstruction. These can all be determined using simple, non-invasive tests such as spirometry before and after acute administration of a bronchodilator (reversible airflow obstruction); peripheral blood eosinophil count, induced sputum, exhaled nitric oxide (airway eosinophilia); and sputum or cough swab culture (bacterial infection). Additionally, the pathophysiology of risk domains must be considered: these are risk of an asthma attack, risk of poor airway growth, and in pre-school children, risk of progression to eosinophilic school age asthma. Phenotyping the airway will allow more precise diagnosis and targeted treatment, but it is important to move to endotypes, especially in the era of increasing numbers of biologicals. Advances in -omics technology allow delineation of pathways, which will be particularly important in TH2 low eosinophilic asthma, and also pauci-inflammatory disease. It is very important to appreciate the difficulties of cluster analysis; a patient may have eosinophilic airway disease because of a steroid resistant endotype, because of non-adherence to basic treatment, and a surge in environmental allergen burden. Sophisticated -omics approaches will be reviewed in this manuscript, but currently they are not being used in clinical practice. However, even while they are being evaluated, management of the asthmas can and should be improved by considering the pathophysiologies of the different airway diseases lumped under that umbrella term, using simple, non-invasive tests which are readily available, and treating accordingly.
The recent Lancet commission has highlighted that “asthma” should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes cough. The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection and altered cough reflex, setting the airway disease in the context of extra-pulmonary co-morbidities and social and environmental factors. The emphasis is always on delineating treatable traits, including variable airflow obstruction caused by airway smooth muscle constriction (treated with short- and long-acting β-2 agonists), eosinophilic airway inflammation (treated with inhaled corticosteroids) and chronic bacterial infection (treated with antibiotics with benefit if it is driving the disease). It is also important not to over-treat the untreatable, such as fixed airflow obstruction. These can all be determined using simple, non-invasive tests such as spirometry before and after acute administration of a bronchodilator (reversible airflow obstruction); peripheral blood eosinophil count, induced sputum, exhaled nitric oxide (airway eosinophilia); and sputum or cough swab culture (bacterial infection). Additionally, the pathophysiology of risk domains must be considered: these are risk of an asthma attack, risk of poor airway growth, and in pre-school children, risk of progression to eosinophilic school age asthma. Phenotyping the airway will allow more precise diagnosis and targeted treatment, but it is important to move to endotypes, especially in the era of increasing numbers of biologicals. Advances in -omics technology allow delineation of pathways, which will be particularly important in TH2 low eosinophilic asthma, and also pauci-inflammatory disease. It is very important to appreciate the difficulties of cluster analysis; a patient may have eosinophilic airway disease because of a steroid resistant endotype, because of non-adherence to basic treatment, and a surge in environmental allergen burden. Sophisticated –omics approaches will be reviewed in this manuscript, but currently they are not being used in clinical practice. However, even while they are being evaluated, management of the asthmas can and should be improved by considering the pathophysiologies of the different airway diseases lumped under that umbrella term, using simple, non-invasive tests which are readily available, and treating accordingly.
Author Bush, Andrew
AuthorAffiliation Departments of Paediatrics and Paediatric Respiratory Medicine, Royal Brompton Harefield NHS Foundation Trust and Imperial College , London , United Kingdom
AuthorAffiliation_xml – name: Departments of Paediatrics and Paediatric Respiratory Medicine, Royal Brompton Harefield NHS Foundation Trust and Imperial College , London , United Kingdom
Author_xml – sequence: 1
  givenname: Andrew
  surname: Bush
  fullname: Bush, Andrew
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30941334$$D View this record in MEDLINE/PubMed
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Keywords airway inflammation
bronchial brushings
asthma phenotype
endotype
bronchial biopsy
induced sputum
transcriptomics
biomarker
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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This article was submitted to Pediatric Pulmonology, a section of the journal Frontiers in Pediatrics
Reviewed by: Richard Leigh, University of Calgary, Canada; Alvaro Augusto Cruz, Federal University of Bahia, Brazil
Edited by: Mario Barreto, Sapienza University of Rome, Italy
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PublicationTitle Frontiers in pediatrics
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Snippet The recent commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes...
The recent Lancet commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and...
The recent Lancet commission has highlighted that “asthma” should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and...
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StartPage 68
SubjectTerms airway inflammation
biomarker
bronchial biopsy
bronchial brushings
induced sputum
Pediatrics
transcriptomics
Title Pathophysiological Mechanisms of Asthma
URI https://www.ncbi.nlm.nih.gov/pubmed/30941334
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