The absence of serum IgE antibodies indicates non‐type 2 disease in young asthmatics

Tsolakis, Nikolaos; Malinovschi, Andreï; Nordvall, Lennart; Janson, Christer; Borres, Magnus P.; Alving, Kjell

doi:10.1111/cea.13103

Cited by 9 publications

(9 citation statements)

References 43 publications

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“…Another important observation derived from the stratification into different sIgE groups was that a significant reduction in lung function over time was seen in the elevated and detectable sIgE groups but was absent in the group with undetectable sIgE. This finding is supported by our recent study, highlighting the presence of clinically significant type‐2 inflammation in patients with low but detectable sIgE levels (0.10–0.34 kU A /L) but not in patients with undetectable sIgE 9 . The cut‐off of 0.10 kU A /L for ruling out IgE sensitization used in this study contrasts with clinical routine where a higher cut‐off level of 0.35 kU A /L or a wheal diameter for skin prick test greater than 3 mm is commonly used for defining atopy.…”

Section: Discussionsupporting

confidence: 71%

Relationship between longitudinal changes in type‐2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics

Tsolakis

Jacinto

Janson

et al. 2021

Clinical & Translational All

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Background Asthma is a heterogeneous condition where biomarkers may be of considerable advantage in diagnosis and therapy monitoring. However, the changes in asthma biomarkers and immunoglobulin E (IgE) over the course of life has not been extensively investigated. Objective To study longitudinal changes in type‐2 inflammatory biomarkers, IgE, and clinical outcomes, and the association between these changes, in young asthmatics. Methods Asthmatics (age 10–35 years, n = 253) were examined at baseline and at a follow‐up visit, 43 [23–65] (median [range]) months later. Subjects were analyzed using the multi‐allergen tests Phadiatop and fx5 (ImmunoCAP) and grouped based on the baseline allergen‐specific IgE antibody (sIgE) concentration: <0.10, 0.10–0.34, and ≥0.35 kUA/L. The relationship between changes (Δ values) in type‐2 biomarkers (individualized fraction of exhaled nitric oxide [FeNO%], blood eosinophil [B‐Eos] count, total IgE [tIgE] and sIgE, lung function [% predicted forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC)], and Asthma Control Test [ACT]) score were determined. Results At follow up, FEV1 and FEV1/FVC had decreased (93.6% vs. 95.8%, and 93.4% vs. 94.7% of predicted, respectively [p < 0.001 both]), whereas ACT score had increased (21.6 vs. 20.6, p = 0.001). A significant decline in lung function was seen in subjects with sIgE ≥ 0.10 kUA/L, but not in those with undetectable sIgE (<0.10 kUA/L). Furthermore, tIgE and sIgE declined over time (p < 0.001 all) whereas FeNO% and B‐Eos count were not significantly changed. In univariate analysis, significant negative correlations between ∆B‐Eos count and ∆FeNO%, on one hand, and changes in lung function, on the other hand, were seen, and multivariate analysis showed an independent relationship between ΔFeNO%, and ΔFEV1 (p < 0.05) and ΔFEV1/FVC% (p < 0.01). Sex‐specific analysis showed that the independent association between ΔFeNO%, and ΔFEV1 remained only in females (p = 0.005), and there was a significant interaction with sex (p = 0.02). Conclusion In young asthmatics, IgE levels declined over 43 months, whereas FeNO and B‐Eos remained unchanged. In spite of improved asthma control, an accelerated lung function decline was seen in patients with detectable sIgE at baseline, and the decline correlated with changes in type‐2 biomarkers. Particularly, the increase in individualized FeNO associated independently with decline in FEV1 in females.

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Section: Discussionsupporting

confidence: 71%

Relationship between longitudinal changes in type‐2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics

Tsolakis

Jacinto

Janson

et al. 2021

Clinical & Translational All

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“…The incidence of nonallergic asthma remains significantly higher in women than men throughout their reproductive years (>20 years old), with both higher incidence and prevalence of nonallergic asthma observed in the later reproductive years (>35 years old) 116 . Nonallergic asthma in young adults is also significantly increased in women and is associated with decreased allergen sensitization and decreased T2 markers consistent with T2-low asthma 117 . Older age, decreased allergen sensitization, and absence of allergic rhinitis are also associated with more severe asthma 118 .…”

Section: Discussionmentioning

confidence: 99%

Asthma and/or hay fever as predictors of fertility/impaired fecundity in U.S. women: National Survey of Family Growth

Turkeltaub¹,

Lockey

Holmes

et al. 2019

Sci Rep

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This study addresses whether asthma and/or hay fever predict fertility and impaired fecundity. The lifetime number of pregnancies (fertility) and spontaneous pregnancy losses (impaired fecundity) in 10,847 women representative of the U.S. population 15 to 44 years of age with histories of diagnosed asthma and/or hay fever are analyzed in the 1995 National Survey of Family Growth using multivariable Poisson regression with multiple covariates and adjustments for complex sampling. Smokers have significantly increased fertility compared to nonsmokers. Smokers with asthma only have significantly increased fertility compared to other smokers. Higher fertility is associated with impaired fecundity (ectopic pregnancy, miscarriage, stillbirth). Women with asthma (with and without hay fever) have significantly higher pregnancy losses than women without asthma. With increasing number of pregnancies, smokers have increased pregnancy losses compared to nonsmokers. Smokers, especially those with asthma only, have increased fertility and require special attention as to their family planning needs, reproductive health, and smoking cessation. Women with asthma, regardless of number of pregnancies, and smokers with higher numbers of pregnancies have high risk pregnancies that require optimal asthma/medical management prenatally and throughout pregnancy. Whether a proinflammatory asthma endotype underlies both the increased fertility and impaired fecundity associated with age and smoking is discussed.

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“…The present results further strengthen the earlier observations, since we managed to objectively confirm the presence of airway disease including airway hyper-responsiveness and reduced FEV 1 /FVC ratio. We have recently reported data showing weak type 2 inflammatory signals in young asthmatics with IgE antibody concentrations below 0.35 kU A /L, suggesting a cut-off of 0.10 kU A /L for ruling out the presence of such inflammation [4]. In the present study, 58% of the subjects that reported hypersensitivity to cow’s milk had undetectable IgE antibody concentrations (< 0.10 kU A /L).…”

Section: Discussionsupporting

confidence: 43%

“…It is well‐known that elevated fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B‐Eos) count are clinically useful type 2 biomarkers in asthma, and their simultaneous elevation has shown independent and additive predictive value for asthma morbidity [2, 3 ]. We have recently reported the persistence of clinically relevant type 2 inflammatory signals in young asthmatics with IgE antibody concentrations below 0.35 kU A /L, and we have suggested a cut‐off of 0.10 kU A /L for ruling out type 2 inflammation [4 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of a subgroup of non-type 2 asthma with cow’s milk hypersensitivity in young subjects

Tsolakis

Nordvall

Janson

et al. 2019

Clin Transl Allergy

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Background Asthma with atopy is often characterized by type 2 inflammation but less progress has been made in defining non-type 2 asthma. We have previously identified a subgroup of young non-atopic asthmatics with perceived food hypersensitivity and poor asthma control. Objective Our aim was to further characterize this subgroup of non-type 2 asthmatics, including the use of a broad panel of inflammation-related proteins. Methods Sex- and age-matched subjects (10–35 years old) were divided into three groups with regard to history of asthma and atopy: non-atopic asthmatics with perceived cow’s milk hypersensitivity but with IgE antibodies < 0.35 kU A /L (NAA; n = 24), non-atopic controls with IgE < 0.35 kU A /L (NAC; n = 24), and atopic asthmatics with IgE ≥ 0.35 kU A /L (AA; n = 29). Serum or plasma were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP), a multiplex immunoassay comprising 92 inflammation-related proteins (Proseek Inflammation), and an ELISA for human neutrophil lipocalin (S-HNL). Fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, C-reactive protein (CRP), airway responsiveness to methacholine (PD 20 ), and asthma-related quality of life (mAQLQ) were also measured. Results NAA had lower FeNO ( p < 0.001) and B-Eos count ( p < 0.001), but scored worse on mAQLQ ( p = 0.045) compared with AA. NAA displayed higher levels of matrix metalloproteinase-1 (MMP-1) compared with both NAC ( p = 0.011) and AA ( p = 0.001), and lower PD 20 compared with NAC ( p < 0.001). In NAA, S-HNL correlated negatively with PD 20 (rho = − 0.048, p < 0.05) and CRP correlated negatively with mAQLQ (rho = − 0.439, p < 0.05). Conclusion In a subgroup of non-atopic young asthmatics with perceived cow’s milk hypersensitivity we observed poor asthma-related quality of life, airway hyperresponsiveness, and clinically relevant non-type 2 inflammation. MMP-1 was elevated in this group, which deserves further studies. Electronic supplementary material The online version of this article (10.1186/s13601-019-0250-2) contains supplementary material, which is available to authorized users.

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The absence of serum IgE antibodies indicates non‐type 2 disease in young asthmatics

Abstract: Clinically relevant elevation of type 2 biomarkers was seen in young asthmatics with IgE antibodies <0.35 kU /L, but not those with IgE < 0.10 kU /L. It seems possible to define non-type 2 asthma through sensitive IgE-antibody measurement.

Cited by 9 publications

References 43 publications

Relationship between longitudinal changes in type‐2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics

Relationship between longitudinal changes in type‐2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics

Asthma and/or hay fever as predictors of fertility/impaired fecundity in U.S. women: National Survey of Family Growth

Characterization of a subgroup of non-type 2 asthma with cow’s milk hypersensitivity in young subjects

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