Mediators of Inflammation / 2015 / Article / Tab 2

Review Article

Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma

Table 2

Biological mediators and biomarkers suggested to be involved in adult/late-onset asthma.

MediatorLevel of asthma severity includedInclusion of patients with adult/late-onset asthmaMain finding concerning the role of mediators in adult/late-onset asthma.References Adult/late-onset phenotype with possible significance

PeriostinSevere 80% with late-onset asthmaHigher levels in patients with fixed airflow limitation and eosinophilic inflammation.Bobolea et al. 2015 [26] Eosinophilic inflammation-predominant

Eotaxin-2AllGroups of early- and late-onset asthma comparedPatients with severe asthma showed higher epithelial expression of eotaxin-2. Levels of eotaxin-2 positively correlated with age of asthma onset, sputum eosinophils, and number of exacerbations and negatively correlated with FEV1 % predicted. Among patients with late-onset (but not early-onset) asthma, eotaxin-levels were higher in those with severe asthma. Sputum eosinophilia was more common among patients with late-onset asthma. Coleman et al. 2012 [114]Eosinophilic inflammation-predominant

L-arginine/ADMASevere Groups of early- and late-onset asthma comparedLower L-arginine/ADMA ratio and negative correlation to BMI in late- versus early-onset asthma; may partly explain the inverse relationship between FeNO and BMI. Reduced L-arginine/ADMA ratio associated with reduced IgE and lung volumes, increased respiratory symptoms, and worse quality of life in late- but not early-onset asthma. Holguin et al. 2013 [75] Obesity-related asthma

LeptinAllObese women with adult-onset asthmaLeptin in visceral fat associated with AHR but not airway inflammation. Adipokine receptor was expressed in airway epithelium suggesting direct effects of adipokines on the airways. Sideleva et al. 2012 [53]  
Leivo-Korpela et al. 2011 [58]
Obesity-related asthma
AllNonobese women with newly-onset adult asthmaLeptin correlated positively with asthma symptom score and negatively with lung function even though no difference was found on adipokine levels between patients with asthma and healthy subjects. High baseline resistin predicted steeper decrease in serum ECP, EPX, and MPO during glucocorticoid treatment.

YKL-40All Late- and early-onset groups comparedLevels of YKL-40 were higher in asthma with poor control and exacerbations and atopy. When phenotypes were compared, highest levels of YKL-40 in obesity-related asthma and early-onset atopic asthma. Lower levels in nonatopic late-onset asthma.Specjalski et al. 2015 [52]Obesity-related (and early-onset atopic)

IFN- and IL-8AllPatients with moderate and severe asthma compared, approx. 85% with asthma onset 12 years in both groupsLevels of IFN- and IL-8 increased but IL-4 decreased in airway subepithelium of patients with severe poorly controlled asthma when compared to moderate disease. Patients with severe asthma had also increased number of eosinophils and neutrophils in sputum. Shannon et al. 2008 [152]Severe and obstructive asthma?

Chlamydia pneumonia (IgG, IgA, and IgE) AllGroups of child- and adult-onset asthma comparedPatients with nonatopic adult-onset asthma and seropositivity to Chlamydia pneumoniae (IgG, IgA) had 4-fold-steeper decline in FEV1/FVC and accelerated decline in FEV1. C. pneumoniae infection might promote persistent airflow limitation in these patients. Brinke et al. 2001 [7] Severe and obstructive
AllPatients with adult-onset asthmaSeropositivity to C. pneumoniae (IgG/IgM, IgA) infection was found to accelerate the loss of lung function in subjects with new nonatopic asthma. Pasternack et al. 2005 [168]
All52% with adult-onset asthmaC. pneumoniae IgE was detected in 21% of mild intermittent and 79% of severe persistent asthma. C. pneumoniae IgE was associated with asthma and asthma severity.Hahn et al. 2012 [164]

Staphylococcus aureus enterotoxin- (SA-) IgE AllHealthy controls, severe and nonsevere asthmatics comparedSA-IgE found more often in patients with severe asthma when compared to healthy subjects. Age of asthma onset highest in SA-IgE-positive group. SA-IgE associated with increased risk for asthma, severe asthma, hospitalizations, use of oral steroids, and lower FEV1. Bachert et al. 2012 [157] Asthma in aged persons?
AllCommunity-based population with adult-onset asthmaRisk factors for presence of SA-IgE were current smoking, older age, male sex, and inhalant allergen sensitization. SA-IgE was associated with current adult-onset asthma. Correlation between SA-IgE and total IgE.Song et al. 2014 [158]

TSLPAllPatients with newly diagnosed asthma (age range 16–98 years) Smoking attenuated the age-related decrease in total IgE, blood eosinophils, and FeNO and maintained eosinophilic inflammation. Sputum TSLP levels were associated with sputum eosinophil % and pack-years. Current and ex-smokers had higher TSLP versus never-smokers. TSLP may be involved in elevating sputum eosinophils in smokers. Nagasaki et al. 2013 [231]Smoking asthma

NR = not reported. ADMA = asymmetric dimethyl arginine, AHR = airway hyperresponsiveness, ECP = eosinophilic cationic protein, EPX = eosinophil peroxidase, MPO = myeloperoxidase, IFN = interferon, IL = interleukin, SA-IgE = Staphylococcus Aureus enterotoxin-specific immunoglobulin E, FEV1 = forced expiratory volume in 1 second, and TSLP = thymic stromal lymphopoietin.

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