Variability of sputum inflammatory cells in asthmatic patients receiving corticosteroid therapy: A prospective study using multiple samples

Alsamri, Mohammed T.; Benedetti, Andrea; Préfontaine, David; Olivenstein, Ron; Lemière, Catherine; Nair, Parameswaran; Martin, James G.; Hamid, Qutayba

doi:10.1016/j.jaci.2010.02.005

Cited by 62 publications

(47 citation statements)

References 9 publications

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“…However, both eosinophil and neutrophil sputum numbers show wide variability in severe asthma with patients demonstrating none to very high levels of either cell, despite being on high doses of corticosteroids [48][49][50]. The neutrophilic and eosinophilic components of sputum can vary substantially on a monthly basis [51]. However, sputum eosinophilia appears more stable, especially in severe asthma, when examined over longer yearly periods in adults [52].…”

Section: Inflammation and Adaptive Immunitymentioning

confidence: 99%

“…Determining either the level of 1) eosinophilic inflammation or 2) Th2 inflammation (or their absence) has the potential benefit of evaluating level of compliance/adherence, risk for exacerbations, as well as predicting response to corticosteroid therapy, and perhaps to targeted therapies such as anti-IL-5 or anti-IL-13, as well [18,33,58,59,[153][154][155]. The role of sputum neutrophilic inflammation in guiding therapy is generally less studied, with considerable day-to-day variability in patients with severe asthma [51]. It has been associated with reduced response to corticosteroid therapy [153].…”

Section: Remarksmentioning

confidence: 99%

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International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

et al. 2013

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Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults.A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations.When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided.Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

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Section: Inflammation and Adaptive Immunitymentioning

confidence: 99%

Section: Remarksmentioning

confidence: 99%

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

et al. 2013

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“…Whether these phenotypes are stable or subject to change over time is still unclear. A prospective evaluation of inflammatory phenotypes in induced sputum in moderate and severe asthma showed that only one-third maintained a stable inflammatory phenotype (11). In addition, inflammatory phenotypes appear to differ with age.…”

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confidence: 99%

Untangling asthma phenotypes and endotypes

Agache

Akdiş

Jutel

et al. 2012

Allergy

292

235

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Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term 'endotype'. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice.

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“…In addition, FeNO have become easily available and may provide important information about how OA is controlled. Unfortunately, not only the corticosteroid treatment, but also smoking decreases the result [8]. Our data show that the measurements of LTs, 8-ISO and other markers of oxidative stress in EBC may reflect the pathophysiological process of OA and provide the insights into its severity.…”

Section: Discussionmentioning

confidence: 80%

“…Therefore, it is crucial to find objective markers [5][6][7] that are not susceptible to malingering. The fraction of exhaled NO (FeNO) is the most extensively studied biomarker, however it is related primarily to eosinophilic inflammation and decreases after corticosteroid treatment [8]. Induced sputum is another candidate biomarker; after the withdrawal from the contact with the sensitizing agents it shows lower inflammation in patients with eosinophillic, but not neutrophillic inflammation [9].…”

Section: Objectivesmentioning

confidence: 99%

Occupational asthma follow-up — which markers are elevated in exhaled breath condensate and plasma?

Pelclová

Fenclová

Vlčková

et al. 2014

International Journal of Occupational Medicine and Environmental Health

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Objectives: To search for optimal markers in the exhaled breath condensate (EBC), plasma and urine that would reflect the activity/severity of occupational asthma (OA) after the withdrawal from the exposure to the allergen. Material and Methods: Markers of oxidative stress: 8-iso-prostaglandin F 2α (8-isoprostane, 8-ISO), malondialdehyde (MDA), 4-hydroxy-trans-2-nonenale (HNE), cysteinyl leukotrienes (LT) and LTB 4 were determined using liquid chromatography and mass spectrometry in 43 subjects with immunological OA (49.3±11.8 years), removed from the exposure to the sensitizing agent 10.5±6.5 years ago; and in 20 healthy subjects (49.0±14.9 years). EBC was harvested both before and after the methacholine challenge test. In parallel, identical markers were collected in plasma and urine. The results were analyzed together with forced expiratory volume in one second (FEV 1 ), blood eosinophils, immunoglobulin E (IgE) and eosinophilic cationic protein (ECP) and statistically evaluated (Spearman rank correlation r S , two-or one-sample t tests and alternatively Kruskal Wallis or pair Wilcoxon tests). Results: Several parameters of lung functions were lower in the patients (FEV1% predicted, MEF25% and MEF50%, Rtot%, p < 0.001). Shorter time interval since the removal from the allergen exposure correlated with higher ECP (r S = 0.375) and lower FEV 1 %, MEF25% and MEF50% after methacholine challenge (r S = -0.404, -0.425 and -0.532, respectively). In the patients, IgE (p < 0.001) and ECP (p = 0.009) was increased compared to controls. In EBC, 8-ISO and cysteinyl LTs were elevated in the asthmatics initially and after the challenge. Initial 8-ISO in plasma correlated negatively with FEV 1 (r S = -0.409) and with methacholine PD 20 (r S = -0.474). 8-ISO in plasma after the challenge correlated with IgE (r S = 0.396). Conclusions:The improvement in OA is very slow and objective impairments persist years after removal from the exposure. Cysteinyl LTs and 8-ISO in EBC and 8-ISO in plasma might enrich the spectrum of useful objective tests for the follow-up of OA.

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Variability of sputum inflammatory cells in asthmatic patients receiving corticosteroid therapy: A prospective study using multiple samples

Cited by 62 publications

References 9 publications

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

Untangling asthma phenotypes and endotypes

Occupational asthma follow-up — which markers are elevated in exhaled breath condensate and plasma?

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