Longitudinal Impact of Sputum Inflammatory Phenotypes on Small Airway Dysfunction and Disease Outcomes in Asthma

Abdo, Mustafa; Pedersen, Frauke; Kirsten, Anne-Marie; Veith, Vera; Biller, Heike; Kopp, Matthias; Hansen, Gesine; Rabe, Klaus F.; Bahmer, Thomas; Watz, Henrik

doi:10.1016/j.jaip.2022.02.020

Cited by 36 publications

(31 citation statements)

References 42 publications

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“…As limitations, our cross-sectional descriptive study may incur possible selection bias; all our patients were required to have undergone specific testing for inclusion, and were patients with predominantly moderate-severe persistent asthma attending a specialist clinic in a tertiary care hospital. Another limitation is the small sample size compared to other studies (for instance, those by Schleich et al 3 and Abdo et al 53 ), and, within our sample, the fact that the patients with a mixed inflammatory phenotype were so few that we were unable to characterize them; note, however, that the mixed phenotype prevalence rate in our study reflects that of other studies. 3 A strength of our study is that inflammatory phenotypes were identified on the basis of SI, and comparisons were possible with biomarkers used in typical asthma consultations, such as peripheral eosinophilia and FeNO.…”

Section: Discussionmentioning

confidence: 62%

Characteristics of Induced-Sputum Inflammatory Phenotypes in Adults with Asthma: Predictors of Bronchial Eosinophilia

Crespo‐Lessmann

Curto

Medina

et al. 2023

JAA

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Purpose The objectives of this study were, for patients attending a specialist asthma clinic at a tertiary care hospital, to determine, from sputum induction (SI), proportions of bronchial inflammatory phenotypes, demographic, clinical and functional characteristics of each phenotype, and the most accessible non-invasive inflammatory marker that best discriminates between phenotypes. Patients and Methods Included were 96 patients with asthma, attending a specialist asthma clinic at a tertiary care hospital, who underwent testing as follows: SI, spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophilia, total immunoglobulin E (IgE), and a skin prick test. Results SI phenotypes were 46.9% eosinophilic, 33.3% paucigranulocytic, 15.6% neutrophilic, and 4.2% mixed. No significantly different clinical or functional characteristics were observed between the phenotypes. A positive correlation was observed between SI eosinophilia and both emergency visits in the last 12 months (p = 0.041; r = 0.214) and FeNO values (p = 0.000; r = 0.368). Blood eosinophilia correlated with SI eosinophilia (p = 0.001; r = 0.362) and was the best predictor of bronchial eosinophilia, followed by FeNO, and total blood IgE (area under the receiver operating characteristic curve (AUC-ROC) 72%, 65%, and 53%, respectively), although precision was only fair. Conclusion In consultations for severe asthma, the most frequent phenotype was eosinophilic. Peripheral blood eosinophilia is a reliable marker for discriminating between different bronchial inflammatory phenotypes, is useful in enabling doctors to select a suitable biologic treatment and so prevent asthma exacerbation, and is a better predictor of bronchial eosinophilia than FeNO and IgE values.

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Section: Discussionmentioning

confidence: 62%

Characteristics of Induced-Sputum Inflammatory Phenotypes in Adults with Asthma: Predictors of Bronchial Eosinophilia

Crespo‐Lessmann

Curto

Medina

et al. 2023

JAA

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“…Mixed granulocytic inflammation has been reported to be associated with clinical manifestations in asthma, including increased frequency with age, longer asthma duration, decreased pulmonary function, and condition stability [ 174 , 175 , 176 ]. The sputum mixed granulocytic subclass has been shown to largely lose interannual pulmonary function compared to the eosinophil predominant, the neutrophil predominant, and the paucigranulocytic subclass in asthma [ 149 , 158 , 177 ].…”

Section: Inflammaging Contributes To Immunopathophysiology In Asthma ...mentioning

confidence: 99%

“…In accordance with several studies showing that eosinophil counts or their large fluctuations are more strongly associated with altered pulmonary function than the neutrophil count in the airway, EDN has been associated with a decline in pulmonary function and NE in elderly patients with asthma [ 61 ], suggesting that activated eosinophils contribute to pulmonary function disturbance in these individuals. Patients with mixed granulocytic asthma and the eosinophil dominant subclasses likely experience frequent acute asthma exacerbations [ 175 , 177 ], and older asthma patients with increases in sputum neutrophil counts have more frequent acute exacerbations [ 93 ]. Thus, complicated inflammation with eosinophils and neutrophils might promote the clinical pathophysiology of asthma.…”

Section: Inflammaging Contributes To Immunopathophysiology In Asthma ...mentioning

confidence: 99%

Immunosenescence, Inflammaging, and Lung Senescence in Asthma in the Elderly

Soma

Nagata

2022

Biomolecules

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Prevalence of asthma in older adults is growing along with increasing global life expectancy. Due to poor clinical consequences such as high mortality, advancement in understanding the pathophysiology of asthma in older patients has been sought to provide prompt treatment for them. Age-related alterations of functions in the immune system and lung parenchyma occur throughout life. Alterations with advancing age are promoted by various stimuli, including pathobionts, fungi, viruses, pollutants, and damage-associated molecular patterns derived from impaired cells, abandoned cell debris, and senescent cells. Age-related changes in the innate and adaptive immune response, termed immunosenescence, includes impairment of phagocytosis and antigen presentation, enhancement of proinflammatory mediator generation, and production of senescence-associated secretory phenotype. Immnunosenescence could promote inflammaging (chronic low-grade inflammation) and contribute to late-onset adult asthma and asthma in the elderly, along with age-related pulmonary disease, such as chronic obstructive pulmonary disease and pulmonary fibrosis, due to lung parenchyma senescence. Aged patients with asthma exhibit local and systemic type 2 and non-type 2 inflammation, associated with clinical manifestations. Here, we discuss immunosenescence’s contribution to the immune response and the combination of type 2 inflammation and inflammaging in asthma in the elderly and present an overview of age-related features in the immune system and lung structure.

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“…Despite evidence of an association between SAD and neutrophilic airway inflammation [ 33 ], it was recently demonstrated that eosinophilic rather than neutrophilic airway inflammation is the main driver of SAD in asthma [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Monoclonal antibodies targeting small airways: a new perspective for biological therapies in severe asthma

Lombardi

Cottini²,

Berti

et al. 2022

asthma res and pract

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Small airway dysfunction (SAD) in asthma is characterized by the inflammation and narrowing of airways with less of 2 mm in diameter between generations 8 and 23 of the bronchial tree. It is now widely accepted that small airways are involved in the pathogenesis of asthma and are a major determinant of airflow obstruction in this disease. In recent years, specialized tests have been developed, such as Impulse Oscillometry (IOS) and Multiple Breath Nitrogen Washout (MBNW) tests, which have been deemed more accurate in detecting SAD than conventional spirometry. Clinical studies show that SAD is associated with more severe bronchial hyperresponsiveness, worse asthma control, and a higher risk of exacerbations. Recent data from a large cohort study showed that the prevalence of SAD in asthma patients increases with asthma severity. Overall, SAD seems to represent a treatable trait, which makes it appealing for asthma control optimization and exacerbation rate reduction, especially in moderate-to-severe asthma.Biologic agents are now available for the treatment of different severe asthma phenotypes and endotypes. However, the effect of these therapies on SAD remains poorly characterized. Literature showing that biologic agents can also favorably improve small airway function is accumulating. In particular, anti-IL5 agents (mepolizumab and benralizumab) seems to have a greater impact on SAD as compared to other biological agents, but direct comparisons in prospective randomized controlled trials are lacking.In this mini-review article, we address the latest evidence on the effect of biological therapies on SAD in patients with severe asthma.

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Longitudinal Impact of Sputum Inflammatory Phenotypes on Small Airway Dysfunction and Disease Outcomes in Asthma

Cited by 36 publications

References 42 publications

Characteristics of Induced-Sputum Inflammatory Phenotypes in Adults with Asthma: Predictors of Bronchial Eosinophilia

Characteristics of Induced-Sputum Inflammatory Phenotypes in Adults with Asthma: Predictors of Bronchial Eosinophilia

Immunosenescence, Inflammaging, and Lung Senescence in Asthma in the Elderly

Monoclonal antibodies targeting small airways: a new perspective for biological therapies in severe asthma

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