Effects of steroid therapy on inflammatory cell subtypes in asthma

Boulet, Louis‐Philippe

doi:10.1136/thx.2009.131391

Cited by 10 publications

(3 citation statements)

References 37 publications

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“…Inhaled corticosteroids (ICS) are commonly prescribed for asthma and are considered to be more effective for Type 2-driven (eosinophilic) asthma. Inhaled corticosteroid use could also contribute to increased sputum neutrophils, another inflammatory phenotype [ 31 ]. Thus, ICS use may confound interpretation of VOCs in asthma.…”

Section: Discussionmentioning

confidence: 99%

Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes

et al. 2021

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Asthma is heterogeneous but accessible biomarkers to distinguish relevant phenotypes remain lacking, particularly in non-Type 2 (T2)-high asthma. Moreover, common clinical characteristics in both T2-high and T2-low asthma (e.g., atopy, obesity, inhaled steroid use) may confound interpretation of putative biomarkers and of underlying biology. This study aimed to identify volatile organic compounds (VOCs) in exhaled breath that distinguish not only asthmatic and non-asthmatic subjects, but also atopic non-asthmatic controls and also by variables that reflect clinical differences among asthmatic adults. A total of 73 participants (30 asthma, eight atopic non-asthma, and 35 non-asthma/non-atopic subjects) were recruited for this pilot study. A total of 79 breath samples were analyzed in real-time using an automated portable gas chromatography (GC) device developed in-house. GC-mass spectrometry was also used to identify the VOCs in breath. Machine learning, linear discriminant analysis, and principal component analysis were used to identify the biomarkers. Our results show that the portable GC was able to complete breath analysis in 30 min. A set of nine biomarkers distinguished asthma and non-asthma/non-atopic subjects, while sets of two and of four biomarkers, respectively, further distinguished asthmatic from atopic controls, and between atopic and non-atopic controls. Additional unique biomarkers were identified that discriminate subjects by blood eosinophil levels, obese status, inhaled corticosteroid treatment, and also acute upper respiratory illnesses within asthmatic groups. Our work demonstrates that breath VOC profiling can be a clinically accessible tool for asthma diagnosis and phenotyping. A portable GC system is a viable option for rapid assessment in asthma.

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Section: Discussionmentioning

confidence: 99%

Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes

et al. 2021

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“…Sputum is not routinely analyzed in children with acute respiratory symptoms, which could elucidate the finding and to avoid bias. Another hypothesis suggested would be that there would be an increase in neutrophils in the bronchial mucosa in response to treatment with corticosteroids inhaled by chemotaxis and inhibition of apoptosis of these cells in sputum 18,19 . In view of this, an initial eosinophilic pattern could hypothetically become mixed with treatment with inhaled corticosteroids.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Induced Sputum Cytology in Asthmatic Children

Chong-Silva¹,

Nascimento²,

Cunha³

et al. 2021

Preprint

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Objective: To evaluate the viability of sputum cytology in asthmatic children, recognizing inflammatory patterns and correlating them with clinical, epidemiological and functional variables of the disease. Methods: This was a cross-sectional and observational study of children with asthma who underwent sputum induction through increasing concentrations of nebulized hypertonic saline solution from 3% to 7%. The samples were processed according to the technique developed by Pizzichini et al. and the cytological pattern classified as pauci-granulocytic, neutrophilic, eosinophilic and mixed. Samples with cell viability> 50% were considered adequate. Asthma control was assessed using the asthma control test (ACT). Results: Seventy-nine children performed sputum induction. Thirty-three samples were excluded because they were not viable for analysis, resulting in 46 samples. The children’s average age was 9.4 (± 3) years. There was a predominance of eosinophilic (25/46, 54.3%), followed by mixed (13/46, 28.3%), pauci-granulocytic (7/46, 15.2%) and neutrophilic (1/46, 2.2%) pattern. Sixty-three percent of the children had severe asthma and 84.7% were treated with inhaled corticosteroids. The ACT showed that 25 (56.8%) patients had the disease under control. Forty-five children (97.8%) underwent pulmonary function tests (spirometry) and in 13 cases (28.9%) an obstructive ventilatory defect was found. Conclusions: The eosinophilic profile was predominant in the assessed asthmatic children. Non-eosinophilic phenotypes were found, but less frequently. There was no difference between the clinical variables and the sputum profile in this study group. Sputum induction in children with asthma is feasible and safe and can contribute to a specific and personalized approach to the disease.

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“…The disease is characterized by intermittent airflow obstruction, which develops on a background of chronic inflammation of the airways, driven by CD4 + T-lymphocytes, and episodes of acute inflammation, typically dominated by eosinophils ( 2 ). Airway eosinophilia is well-described in asthma ( 3 , 4 ), and currently available anti-inflammatory treatments for asthma almost exclusively target eosinophilic airway inflammation and IgE secretion. However, increased attention is focusing on the clinical heterogeneity of asthma and the argument that failure to recognize and diagnose the underlying mechanisms of different asthma subtypes is a major limitation to progress in asthma control ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Respiratory Chlamydia Infection Induce Release of Hepoxilin A3 and Histamine Production by Airway Neutrophils

Patel

Webley

2018

Front. Immunol.

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Background: Hepoxilins are biologically active metabolites of arachidonic acid that are formed through the 12-lipoxygenase pathway. Hepoxilin A3 is now known to be an important regulator of mucosal inflammation in response to infection by bacterial pathogens and was recently identified as a potent neutrophil chemoattractant in the intestinal mucosa. Our goal in this study was to determine if airway infection with Chlamydia in a murine model of allergic airway disease (AAD) induces hepoxilin secretion along with airway neutrophilia.Methods: We utilized an AAD adult Balb/c mouse model to evaluate airway pathology and immune response by assaying bronchoalveolar lavage (BAL) fluid cytokine, cellularity, histidine decarboxylase (HDC) as well as histamine released in response to in-vivo chlamydial antigen stimulation of purified airway neutrophils. Hepoxilin A3 production was determined by Western blot identification of 12-lipoxygenase precursor (12-LO).Results: Chlamydial infection induced increased production of IL-2, IL-12, TNF-α, and IFN-γ in BAL fluid compared to uninfected animals. Chlamydia-infected mice responded with robust airway neutrophil infiltration and upon induction of AAD increased their production of IL-4, IL-5, and IL-13 by >3 fold compared to unsensitized groups. In addition, 12-LO mRNA was upregulated in infected, but not in uninfected AAD mice, suggesting the production of hepoxilin A3. mRNA expression of HDC was induced only in neutrophils from the airways of Chlamydia-infected mice, but was not seen in AAD only or uninfected controls. When purified neutrophils from infected animals were challenged with chlamydial antigen in vitro there was significant histamine release.Conclusions: Our data confirms the production and release of hepoxilin A3 in the murine airways concomitant with airway neutrophilia in response to chlamydial infection. We further confirmed that Chlamydia provokes the production and release of histamine by these neutrophils. These findings suggest that neutrophils, provoked by Chlamydia infection can synthesize and release histamine, thereby contributing directly to airway inflammation.

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Effects of steroid therapy on inflammatory cell subtypes in asthma

Cited by 10 publications

References 37 publications

Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes

Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes

Evaluation of Induced Sputum Cytology in Asthmatic Children

Respiratory Chlamydia Infection Induce Release of Hepoxilin A3 and Histamine Production by Airway Neutrophils

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