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Clinical update on the use of biomarkers of airway inflammation in the management of asthma.

Wadsworth S, Sin D, Dorscheid D - J Asthma Allergy (2011)

Bottom Line: Pulmonary function tests are most often used objectively to confirm the diagnosis.Biomarkers have the potential to indicate an individual's disease phenotype and thereby guide clinicians in their decisions regarding treatment.We discuss biomarkers obtained from multiple physiological sources, including sputum, exhaled gases, exhaled breath condensate, serum, and urine.

View Article: PubMed Central - PubMed

Affiliation: UBC James Hogg Research Centre, Providence Heart and Lung Institute, St Paul's Hospital, Vancouver, Canada.

ABSTRACT
Biological markers are already used in the diagnosis and treatment of cardiovascular disease and cancer. Biomarkers have great potential use in the clinic as a noninvasive means to make more accurate diagnoses, monitor disease progression, and create personalized treatment regimes. Asthma is a heterogeneous disease with several different phenotypes, generally triggered by multiple gene-environment interactions. Pulmonary function tests are most often used objectively to confirm the diagnosis. However, airflow obstruction can be variable and thus missed using spirometry. Furthermore, lung function measurements may not reflect the precise underlying pathological processes responsible for different phenotypes. Inhaled corticosteroids and β(2)-agonists have been the mainstay of asthma therapy for over 30 years, but the heterogeneity of the disease means not all asthmatics respond to the same treatment. High costs and undesired side effects of drugs also drive the need for better targeted treatment of asthma. Biomarkers have the potential to indicate an individual's disease phenotype and thereby guide clinicians in their decisions regarding treatment. This review focuses on biomarkers of airway inflammation which may help us to identify, monitor, and guide treatment of asthmatics. We discuss biomarkers obtained from multiple physiological sources, including sputum, exhaled gases, exhaled breath condensate, serum, and urine. We discuss the inherent limitations and benefits of using biomarkers in a heterogeneous disease such as asthma. We also discuss how we may modify our study designs to improve the identification and potential use of potential biomarkers in asthma.

No MeSH data available.


Related in: MedlinePlus

The airways in asthma undergo significant structural remodeling. Medium-sized airways from a normal individual and a severe asthmatic patient were sectioned and stained using Movat’s pentachrome stain. The epithelium in asthma shows mucous hyperplasia and hypersecretion (blue), and significant basement membrane (Bm) thickening. Smooth muscle (Sm) volume is also increased in asthma. Scale bar 100 μm.Abbreviations: Bv, blood vessel; Ep, epithelium; Bm, basement membrane; Sm, smooth muscle.
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f2-jaa-4-077: The airways in asthma undergo significant structural remodeling. Medium-sized airways from a normal individual and a severe asthmatic patient were sectioned and stained using Movat’s pentachrome stain. The epithelium in asthma shows mucous hyperplasia and hypersecretion (blue), and significant basement membrane (Bm) thickening. Smooth muscle (Sm) volume is also increased in asthma. Scale bar 100 μm.Abbreviations: Bv, blood vessel; Ep, epithelium; Bm, basement membrane; Sm, smooth muscle.

Mentions: Although asthma is considered an inflammatory disease, there are many structural changes in the airways. Figure 2 shows cross-sections through the large airways of two patients, one normal and one a severe asthmatic. The Movat’s pentachrome stain clearly highlights the various architectural remodeling events occurring in the asthmatic airway. Obstruction of the airways by excessive mucus production is a common finding in severe asthmatics, and blue staining in the epithelium and lumen demonstrates mucous cell hyperplasia, with excessive mucus deposition into the airway. Under the asthmatic epithelium, a thicker basement membrane is present which contains several different extracellular matrix factors (including tenascin-C) compared with normals.6 Deeper into the airway, red-stained muscle mass is increased in the asthmatic, owing to a combination of smooth muscle hypertrophy and hyperplasia.7 The airways of severe asthmatics also demonstrate a fibrotic response, with increased connective tissue deposition and fibroblast and myofibroblast proliferation. Opinion is divided as to whether inflammation precedes airway remodeling, or whether the two occur in parallel.8–10 Evidence tends to favor the latter because, firstly, remodeling occurs very early on in the disease, in some cases in the absence of inflammation,11 secondly, there is only a weak link between airway inflammation and symptoms,12 and, thirdly, epidemiological data demonstrate that steroids do not work in all asthmatics.13 In reality, it is likely that effective therapies will need to target both airway inflammation and remodeling.


Clinical update on the use of biomarkers of airway inflammation in the management of asthma.

Wadsworth S, Sin D, Dorscheid D - J Asthma Allergy (2011)

The airways in asthma undergo significant structural remodeling. Medium-sized airways from a normal individual and a severe asthmatic patient were sectioned and stained using Movat’s pentachrome stain. The epithelium in asthma shows mucous hyperplasia and hypersecretion (blue), and significant basement membrane (Bm) thickening. Smooth muscle (Sm) volume is also increased in asthma. Scale bar 100 μm.Abbreviations: Bv, blood vessel; Ep, epithelium; Bm, basement membrane; Sm, smooth muscle.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140298&req=5

f2-jaa-4-077: The airways in asthma undergo significant structural remodeling. Medium-sized airways from a normal individual and a severe asthmatic patient were sectioned and stained using Movat’s pentachrome stain. The epithelium in asthma shows mucous hyperplasia and hypersecretion (blue), and significant basement membrane (Bm) thickening. Smooth muscle (Sm) volume is also increased in asthma. Scale bar 100 μm.Abbreviations: Bv, blood vessel; Ep, epithelium; Bm, basement membrane; Sm, smooth muscle.
Mentions: Although asthma is considered an inflammatory disease, there are many structural changes in the airways. Figure 2 shows cross-sections through the large airways of two patients, one normal and one a severe asthmatic. The Movat’s pentachrome stain clearly highlights the various architectural remodeling events occurring in the asthmatic airway. Obstruction of the airways by excessive mucus production is a common finding in severe asthmatics, and blue staining in the epithelium and lumen demonstrates mucous cell hyperplasia, with excessive mucus deposition into the airway. Under the asthmatic epithelium, a thicker basement membrane is present which contains several different extracellular matrix factors (including tenascin-C) compared with normals.6 Deeper into the airway, red-stained muscle mass is increased in the asthmatic, owing to a combination of smooth muscle hypertrophy and hyperplasia.7 The airways of severe asthmatics also demonstrate a fibrotic response, with increased connective tissue deposition and fibroblast and myofibroblast proliferation. Opinion is divided as to whether inflammation precedes airway remodeling, or whether the two occur in parallel.8–10 Evidence tends to favor the latter because, firstly, remodeling occurs very early on in the disease, in some cases in the absence of inflammation,11 secondly, there is only a weak link between airway inflammation and symptoms,12 and, thirdly, epidemiological data demonstrate that steroids do not work in all asthmatics.13 In reality, it is likely that effective therapies will need to target both airway inflammation and remodeling.

Bottom Line: Pulmonary function tests are most often used objectively to confirm the diagnosis.Biomarkers have the potential to indicate an individual's disease phenotype and thereby guide clinicians in their decisions regarding treatment.We discuss biomarkers obtained from multiple physiological sources, including sputum, exhaled gases, exhaled breath condensate, serum, and urine.

View Article: PubMed Central - PubMed

Affiliation: UBC James Hogg Research Centre, Providence Heart and Lung Institute, St Paul's Hospital, Vancouver, Canada.

ABSTRACT
Biological markers are already used in the diagnosis and treatment of cardiovascular disease and cancer. Biomarkers have great potential use in the clinic as a noninvasive means to make more accurate diagnoses, monitor disease progression, and create personalized treatment regimes. Asthma is a heterogeneous disease with several different phenotypes, generally triggered by multiple gene-environment interactions. Pulmonary function tests are most often used objectively to confirm the diagnosis. However, airflow obstruction can be variable and thus missed using spirometry. Furthermore, lung function measurements may not reflect the precise underlying pathological processes responsible for different phenotypes. Inhaled corticosteroids and β(2)-agonists have been the mainstay of asthma therapy for over 30 years, but the heterogeneity of the disease means not all asthmatics respond to the same treatment. High costs and undesired side effects of drugs also drive the need for better targeted treatment of asthma. Biomarkers have the potential to indicate an individual's disease phenotype and thereby guide clinicians in their decisions regarding treatment. This review focuses on biomarkers of airway inflammation which may help us to identify, monitor, and guide treatment of asthmatics. We discuss biomarkers obtained from multiple physiological sources, including sputum, exhaled gases, exhaled breath condensate, serum, and urine. We discuss the inherent limitations and benefits of using biomarkers in a heterogeneous disease such as asthma. We also discuss how we may modify our study designs to improve the identification and potential use of potential biomarkers in asthma.

No MeSH data available.


Related in: MedlinePlus