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Christopher E Brightling - One of the best experts on this subject based on the ideXlab platform.

  • CASE STUDY Development of irreversible airflow obstruction in a patient with Eosinophilic Bronchitis without asthma
    2015
    Co-Authors: Christopher E Brightling, A J Wardlaw, Ian D Pavord, G. Woltmann, I. Pavord. #ers D. Journals, Eur Respir J
    Abstract:

    ABSTRACT: Eosinophilic Bronchitis is a recently described condition presenting with chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The patient, a 48-yr-old male who had never smoked, presented with an isolated chronic cough. He had normal spirometric values, peak flow variability and airway responsiveness, but an induced sputum eosinophil count of 33 % (normal <1%). Although his cough improved with inhaled corticosteroids the sputum eosinophilia persisted. Over 2 yrs he developed airflow obstruction, which did not improve following nebulized bronchodilators and a 2-week course of prednisolone 30 mg once daily sufficient to return the sputum eosinophilia to normal (0.5%). It is suggested that the progressive irreversible airflow obstruction was due to persistent structural change to the airway secondary to Eosinophilic airway inflammation, and it is further speculated that Eosinophilic Bronchitis may be a prelude to chronic obstructive pulmonary disease in some patients

  • mannitol and amp do not induce bronchoconstriction in Eosinophilic Bronchitis further evidence for dissociation between airway inflammation and bronchial hyperresponsiveness
    Respirology, 2010
    Co-Authors: Amisha Singapuri, Christopher E Brightling, Sue Mckenna, Peter Bradding
    Abstract:

    Background and objective:  Eosinophilic Bronchitis (EB) shares many pathological features with asthma. However, patients with EB do not develop the characteristic physiological abnormalities of asthma: variable airflow obstruction and bronchial hyperresponsiveness (BHR) to a direct bronchial challenge with methacholine. Indirect bronchial challenges with AMP and mannitol are dependent on the presence of airway inflammation, and positive in 10% of asthmatic subjects who have a negative response to methacholine. We have therefore investigated whether subjects with EB are responsive to indirect airway challenge with AMP and mannitol. Methods:  Subjects with asthma, EB and healthy controls attended on up to four occasions. After screening, subjects performed bronchial provocation tests to methacholine and then either AMP or mannitol. Each challenge was followed immediately by sputum induction for the measurement of airway inflammation and mast cell-derived histamine. Results:  No subjects with EB responded to either AMP (n = 5) or mannitol (n = 7) while 4/8 and 7/10 subjects with asthma responded to the respective challenges (P = 0.057 for AMP, P = 0.004 for mannitol). There was no difference in induced sputum concentrations of histamine or eosinophil cell counts following methacholine challenge compared with AMP or mannitol. Conclusions:  The airways of patients with EB are not responsive to either direct or indirect bronchial challenge. This supports the view that it is the presence of functionally abnormal airway smooth muscle that is the key determinant of BHR in asthma, and that while this may be aggravated by the presence of mucosal airway inflammation, it is not caused by it.

  • cough due to asthma cough variant asthma and non asthmatic Eosinophilic Bronchitis
    Otolaryngologic Clinics of North America, 2010
    Co-Authors: Dhan Desai, Christopher E Brightling
    Abstract:

    Among the most common causes of chronic cough are asthma (25%) and nonasthmatic Eosinophilic Bronchitis (10%). In asthma, cough may present as an isolated symptom, in which case it is known as cough variant asthma. Variable airflow obstruction and airway hyper-responsiveness are cardinal features of asthma, which are absent in nonasthmatic Eosinophilic Bronchitis. The presence of Eosinophilic airway inflammation is a common feature of asthma and is a diagnostic criterion for nonasthmatic Eosinophilic Bronchitis. At a cellular level, mast cell infiltration into the airway smooth muscle bundle, narrowing of the airway wall, and increased interleukin-13 expression are features of asthma and not nonasthmatic Eosinophilic Bronchitis. In most cases, the trigger that causes the cough is uncertain, but occasionally occupational exposure to a sensitizer is identified, and avoidance is recommended. In both conditions, there is improvement following treatment with inhaled corticosteroids, which is associated with the presence of an airway eosinophilia and increased exhaled nitric oxide. Generally, response to therapy in both conditions is very good, and the limited long-term data available suggest that both usually have a benign course, although in some cases fixed airflow obstruction may occur.

  • Cough Due to Asthma and Nonasthmatic Eosinophilic Bronchitis
    Lung, 2010
    Co-Authors: Christopher E Brightling
    Abstract:

    Asthma and nonasthmatic Eosinophilic Bronchitis are among the most common causes of chronic cough, accounting for about 25 and 10% of cases, respectively. Chronic cough due to asthma may present in isolation in which case it is known as cough-variant asthma. Nonasthmatic Eosinophilic Bronchitis is characterized by the presence of Eosinophilic airway inflammation in the absence of variable airflow obstruction or airway hyperresponsiveness. Both conditions share many immunopathological features with the exceptions to date of mast cell infiltration into the airway smooth muscle, increased IL-13 expression, and narrowing and thickening of the airway wall, which are features reserved to asthma. In most cases the trigger that causes the cough is uncertain. However, removal of potential triggers is important to consider, in particular with respect to occupational exposure to known sensitisers. In both conditions there is subjective and objective improvement following treatment with inhaled corticosteroids, which is associated with the presence of an airway eosinophilia. Whether Eosinophilic inflammation is the cause of cough or an epiphenomenon is uncertain, but the failure of anti-IL-5 to modify cough in asthma has questioned a causal association. In asthma, β-agonist theophylline, leukotriene receptor antagonist, and oral corticosteroid therapy improve cough. In nonEosinophilic Bronchitis, some patients require oral corticosteroids but the benefit of other additional therapies is unknown. In general, response to therapy in both conditions is very good and the limited long-term data available suggest that both usually have a benign course, although in some cases persistent airflow obstruction may occur.

  • il 13 expression by blood t cells and not eosinophils is increased in asthma compared to non asthmatic Eosinophilic Bronchitis
    BMC Pulmonary Medicine, 2009
    Co-Authors: Salman Siddiqui, A J Wardlaw, S Mckenna, Glenn Cruse, W Monteiro, Vijay Mistry, Christopher E Brightling
    Abstract:

    Background In asthma interleukin (IL)-13 is increased in the airway compared with non-asthmatic Eosinophilic Bronchitis. Whether this differential expression is specific to the airway or is more generalised is uncertain.

Nanshan Zhong - One of the best experts on this subject based on the ideXlab platform.

  • establishment of a mouse model with all four clinical features of Eosinophilic Bronchitis
    Scientific Reports, 2020
    Co-Authors: Liyan Chen, Kefang Lai, Jiaxing Xie, Min Peng, Nanshan Zhong
    Abstract:

    Eosinophilic Bronchitis (EB) is a clinical disease characterized by chronic cough, airway eosinophil infiltration, and responsive to steroid therapy but with the absence of airway hyperreactivity (AHR). This study established an EB mouse model with all the above features. First, 42 mice were divided into 7 groups to investigate the optimal time interval between cough and AHR detections. Afterward, 28 mice were divided into the asthma, EB, normal saline (NS), and dexamethasone (DXM) groups. Mice were challenged using nasal drops of 200 µg ovalbumin (OVA), 10 µg OVA, NS, or intraperitoneal injections of 5 mg/kg of DXM one hour prior to 10 µg OVA challenge. Airway reactivity was measured 6 h after cough was observed. The frequency of coughs in the asthma and EB groups increased significantly compared to mice in the NS group. After DXM administration, frequency of coughs was significantly decreased compared to mice in the asthma and EB groups. Lung resistance in the asthma group was significantly higher compared to mice in the NS, EB, and DXM groups. Obvious airway Eosinophilic inflammation in BALF and lung tissues were observed in the asthma and EB groups, while DXM administration could attenuate airway inflammatory infiltration. In summary, we developed a mouse EB model with all four clinical features of EB by the administration of 10 µg OVA nasal drops.

  • Eotaxin and IL-4 levels are increased in induced sputum and correlate with sputum eosinophils in patients with nonasthmatic Eosinophilic Bronchitis.
    Medicine, 2017
    Co-Authors: Rui Zhang, Ruchong Chen, Zhenyu Liang, Wenju Lu, Nanshan Zhong
    Abstract:

    Nonasthmatic Eosinophilic Bronchitis (NAEB) is characterized by chronic cough and airway Eosinophilic inflammation. Airway and systemic inflammation cytokine profile have not been comprehensively described in patients with NAEB. The aim of the study was to identify the cytokine profile in sputum and serum of NAEB patients. Furthermore, the relationship between cytokines and clinical features would be evaluated. Induced sputum and serum were collected from untreated NAEB patients and healthy subjects. The cytokine profile in sputum and serum was analyzed by a bead-based multiplex cytokine assay including 21 cytokines. The levels of EGF, eotaxin, GM-CSF, GRO, IFN-γ, IL-1β, IL-4, IL-6, IL-17A, IP-10, MIP-1α, and TNF-α in sputum were significantly higher in NAEB patients than that in healthy subjects (all P 

  • eotaxin and il 4 levels are increased in induced sputum and correlate with sputum eosinophils in patients with nonasthmatic Eosinophilic Bronchitis
    Medicine, 2017
    Co-Authors: Rui Zhang, Wei Luo, Ruchong Chen, Zhenyu Liang, Yaxia Tan, Nanshan Zhong
    Abstract:

    Nonasthmatic Eosinophilic Bronchitis (NAEB) is characterized by chronic cough and airway Eosinophilic inflammation. Airway and systemic inflammation cytokine profile have not been comprehensively described in patients with NAEB. The aim of the study was to identify the cytokine profile in sputum and serum of NAEB patients. Furthermore, the relationship between cytokines and clinical features would be evaluated. Induced sputum and serum were collected from untreated NAEB patients and healthy subjects. The cytokine profile in sputum and serum was analyzed by a bead-based multiplex cytokine assay including 21 cytokines. The levels of EGF, eotaxin, GM-CSF, GRO, IFN-γ, IL-1β, IL-4, IL-6, IL-17A, IP-10, MIP-1α, and TNF-α in sputum were significantly higher in NAEB patients than that in healthy subjects (all P < 0.05). Values of area under the receiver operating characteristic curve (AUROC) of these cytokines were all above 0.750. The concentrations of eotaxin and IL-4 were positively correlated with sputum eosinophil percentage (r = 0.726, P = 0.002; r = 0.511, P = 0.043; respectively). No significant correlations between other cytokines (EGF, GM-CSF, GRO, IFN-γ, IL-1β, IL-6, IL-17A, IP-10, MIP-1α, and TNF-α) in sputum and sputum eosinophil percentage were found. The level of IL-4 in serum was slightly higher in NAEB patients than in healthy subjects. However, there was no correlation between serum IL-4 levels and sputum eosinophil percentage. We identified the cytokine profile in sputum and serum from NAEB patients. Sputum eotaxin and IL-4 could have the potential to become the biomarkers for NAEB and might be useful to assist in the diagnosis of NAEB.

  • Re-Challenge with Ovalbumin Failed to Induce Bronchial Asthma in Mice with Eosinophilic Bronchitis
    2016
    Co-Authors: Liyan Chen, Nanshan Zhong, Kefang Lai
    Abstract:

    Objective: To investigate whether Eosinophilic Bronchitis without airway hyperresponsiveness will develop bronchial asthma in allergic mice. Methods: Mice were sensitized with OVA on days 0, 7, and 14, challenged on days 21 to 23 (1st OVA challenge), and re-challenged on days 46 to 48 (2nd OVA challenge), intranasally with 10 (the EB group) and 200 (the AS group) μg OVA. Lung resistance (RL) was assessed 24 h after each challenge and on day 45 followed by analysis of leukocyte distribution in the bronchoalveolar lavage (BAL) fluid and histological examination. Results: Twenty-four hours after the 1st OVA challenge, aerosolized methacholine caused a dose-dependent increase in RL in all groups. At doses ≥1.56 mg/mL, RL in the AS group was significantly higher than that of the NS-1 group (P<0.01 or 0.05) and at doses ≥12.5 mg/mL, RL was markedly higher in the AS group than that of the EB group (P<0.01). The percentage of eosinophils in both the EB group and the AS group was markedly higher than that of the control group. Twenty-four hours after the 2nd OVA challenge, at doses ≤12.5 mg/mL, there was no significant difference in RL among all groups (P>0.05). At doses ≥12.5 mg/mL, RL in the AS group was significantly higher than that of the control group and EB group (P<0.01 or 0.05). The percentage of eosinophils in the AS group was noticeably higher than that of the EB group(P<0.05). Furthermore, there was apparent infiltration by inflammator

  • will nonasthmatic Eosinophilic Bronchitis develop into chronic airway obstruction a prospective observational study
    Chest, 2015
    Co-Authors: Kefang Lai, Lina Han, Baojuan Liu, Wei Luo, Qiaoli Chen, Ruchong Chen, Ling Lin, Faxia Wang, Nanshan Zhong
    Abstract:

    OBJECTIVE The long-term prognosis of nonasthmatic Eosinophilic Bronchitis (NAEB) is still unclear. The aim of this study was to observe the frequency of relapse among patients with NAEB and the likelihood of NAEB developing into chronic airflow obstruction over time. METHODS Patients with NAEB were followed for at least 1 year between 2003 and 2013. During this period, we evaluated clinical symptoms, sputum eosinophil count, spirometry, and bronchial hyperresponsiveness. A linear mixed model was adopted to determine the relationship between time and lung function. RESULTS A total of 234 patients with NAEB were identified, of whom 141 were followed for > 1 year (median, 4.1 years). Up to 59.6% of patients had a relapse after treatment. Both allergic rhinitis (OR, 4.37; 95% CI, 1.049-18.203; P =.043) and sputum eosinophilia after 4 weeks of treatment with inhaled corticosteroids (OR, 9.493; 95% CI, 2.381-37.850; P =.001) were risk factors for relapse. Among the 141 patients, mild asthma developed in eight (5.7%). During the follow-up period, no progressive decline in FVC, FEV1, and FEV1/FVC were observed (P > .05). Although the proportion of small airway dysfunction (maximum midexpiratory flow [MMEF] CONCLUSIONS More than 50% of patients with NAEB have repeated episodes associated with persistent sputum eosinophilia after treatment and allergic rhinitis. In the current cohort, chronic airway obstruction does not develop despite small airway dysfunction increases over time.

Kefang Lai - One of the best experts on this subject based on the ideXlab platform.

  • establishment of a mouse model with all four clinical features of Eosinophilic Bronchitis
    Scientific Reports, 2020
    Co-Authors: Liyan Chen, Kefang Lai, Jiaxing Xie, Min Peng, Nanshan Zhong
    Abstract:

    Eosinophilic Bronchitis (EB) is a clinical disease characterized by chronic cough, airway eosinophil infiltration, and responsive to steroid therapy but with the absence of airway hyperreactivity (AHR). This study established an EB mouse model with all the above features. First, 42 mice were divided into 7 groups to investigate the optimal time interval between cough and AHR detections. Afterward, 28 mice were divided into the asthma, EB, normal saline (NS), and dexamethasone (DXM) groups. Mice were challenged using nasal drops of 200 µg ovalbumin (OVA), 10 µg OVA, NS, or intraperitoneal injections of 5 mg/kg of DXM one hour prior to 10 µg OVA challenge. Airway reactivity was measured 6 h after cough was observed. The frequency of coughs in the asthma and EB groups increased significantly compared to mice in the NS group. After DXM administration, frequency of coughs was significantly decreased compared to mice in the asthma and EB groups. Lung resistance in the asthma group was significantly higher compared to mice in the NS, EB, and DXM groups. Obvious airway Eosinophilic inflammation in BALF and lung tissues were observed in the asthma and EB groups, while DXM administration could attenuate airway inflammatory infiltration. In summary, we developed a mouse EB model with all four clinical features of EB by the administration of 10 µg OVA nasal drops.

  • elevated circulating cd4 cd25 cd127 low regulatory t cells in patients with non asthmatic Eosinophilic Bronchitis
    Lung, 2020
    Co-Authors: Jieru Huang, Wei Luo, Kefang Lai, Chen Zhan, Jiaxing Liu, Yansi Xian, Bixia Liu, Wanqin Liang, Ruchong Chen
    Abstract:

    PURPOSE Non-asthmatic Eosinophilic Bronchitis (NAEB) is a common cause of chronic cough. It is characterized by sputum eosinophilia like asthma but lacks airway hyperresponsiveness. Regulatory T cells (Tregs) are recognized as immune suppressors and are involved in the pathogenesis of asthma. However, the relationship between Tregs and NAEB remains unknown. This study aimed to preliminarily explore the role of Tregs in NAEB by comparing circulating Tregs levels to asthma and healthy controls. METHODS Fractional exhaled nitric oxide (FeNO), spirometry with bronchial provocation test, sputum induction and blood routine test were performed in all subjects. Peripheral blood mononuclear cells were used to detect the Tregs (CD4+CD25+CD127-/low) by flow cytometry. Relationship between the levels of circulating Tregs and clinical indexes was also observed. RESULTS A total of 15 patients with NAEB, 20 patients with asthma and 11 healthy controls were included. The absolute numbers of circulating Tregs in the NAEB group (49.8 ± 18.9 × 103 cells/ml) and asthma group (53.3 ± 18.7 × 103 cells/ml) were higher than that in healthy control group (32.7 ± 11.6 × 103 cells/ml) (both P < 0.01). In total, the level of circulating Tregs showed positive correlation with FeNO (r = 0.30, P < 0.05). CONCLUSION Tregs may play a key role not only in asthmatic patients, but also in patients with NAEB, as reflected by the elevated Tregs in peripheral blood.

  • response to bronchodilator and clinical pathophysiological features in patients with nonasthmatic Eosinophilic Bronchitis
    Clinical Respiratory Journal, 2020
    Co-Authors: Kefang Lai, Lina Han, Baojuan Liu, Wei Luo, Xu Zhang, Yongxin Xue, Qiaoli Chen
    Abstract:

    INTRODUCTION Whether nonasthmatic Eosinophilic Bronchitis (NAEB) shows response to bronchodilator (RB) remains unclear. OBJECTIVES To investigate the RB and its relationship with clinical and pathophysiological features in NAEB. METHODS Fifty-one patients with NAEB were assigned in a 2:1 ratio to receive oral bambuterol hydrochloride (n = 34, 10 mg, once daily, for 3 days) or matched placebo (n = 17) randomly, of whom 48 patients (32 with bronchodilator and 16 with placebo) completed the study. Sputum induction, spirometry and cough reflex sensitivity were measured. RB was considered when cough Visual analogue scale (VAS) score decreased 30% or more after treatment. Cough reflex sensitivity was defined as the lowest concentration of capsaicin inducing five coughings or more (C5), and presented as Log C5. RESULTS The responsive rate of patients with bronchodilator was significantly higher than that with placebo (34.4% vs 6.3%, P < 0.05). The VAS score decreased significantly in patients with bronchodilator (median: 6.0-3.0, P < 0.01). There was a significantly higher median Log C5 (2.7 vs 1.3, P < 0.05), and a higher trend of decline in FEV1 % predicted and MMEF% predicted after bronchial provocation in patients with RB as compared with patients without RB. No significant differences in baseline percentages of sputum eosinophil were found between patients with RB and that without RB. CONCLUSIONS One third of patients with NAEB respond well to bronchodilator treatment, which are related with lower cough reflex sensitivity and increased airway responsiveness. The relationship between NAEB and asthma needs to be investigated further.

  • duration of treatment with inhaled corticosteroids in nonasthmatic Eosinophilic Bronchitis a randomized open label trial
    Therapeutic Advances in Respiratory Disease, 2019
    Co-Authors: Wenzhi Zhan, Jiaman Tang, Xiaomei Chen, Lina Han, Baojuan Liu, Wei Luo, Qiaoli Chen, Kefang Lai
    Abstract:

    Background:Nonasthmatic Eosinophilic Bronchitis (NAEB) responds well to inhaled corticosteroids (ICS), while recurrence is common after discontinuing treatment. There are no data available to show ...

  • increased sputum il 17a level in non asthmatic Eosinophilic Bronchitis
    Lung, 2018
    Co-Authors: Chen Zhan, Wei Luo, Ruchong Chen, Jiaxing Liu, Shengfang Zhang, Kefang Lai
    Abstract:

    BACKGROUND Non-asthmatic Eosinophilic Bronchitis (NAEB) is one common cause of chronic cough which is characterized as airway Eosinophilic inflammation like asthma but lack of airway hyper-responsiveness. Previous studies showed that Th2-pathway plays a role in NAEB, but the role of non-Th2 pathway in mechanism of NAEB remains unknown. Recently, IL-17A, a Th17-pathway cytokine, has been demonstrated to be involved in asthma development. However, the relationship between Th17-pathway and NAEB is unknown. METHODS We aim to assess the airway level of IL-17A in the subjects with NAEB. Relationships between the IL-17A level and airway function in NAEB or asthma are also observed. We measured IL-17A concentrations in the sputum supernatant from 12 subjects with EB, 16 subjects with asthma [9 Eosinophilic asthmatic (EA) and 7 non-Eosinophilic asthmatic (NEA) according to the sputum eosinophil ≥ 3%], and 9 healthy control subjects. RESULTS Increasing IL-17A level was found in NAEB group (29.65 ± 8.13 pg/ml), EA group (32.45 ± 3.22 pg/ml), and NEA group (29.62 ± 6.91 pg/ml) compared with the healthy control group (17.05 ± 10.30 pg/ml) (P < 0.05, P < 0.01, P < 0.05, respectively). The sputum IL-17A level was correlated with FENO (r = 0.44, P < 0.01), FEV1/FVC% (r = - 0.38, P < 0.05), MMEF%pred (r = - 0.34, P < 0.05), and sputum neutrophil% (r = 0.33, P < 0.05) in total. CONCLUSION Th17-pathway may play a role not only in asthmatics, but also in subjects with NAEB, as reflected by increasing IL-17A concentrations in sputum supernatant.

Ian D Pavord - One of the best experts on this subject based on the ideXlab platform.

  • CASE STUDY Development of irreversible airflow obstruction in a patient with Eosinophilic Bronchitis without asthma
    2015
    Co-Authors: Christopher E Brightling, A J Wardlaw, Ian D Pavord, G. Woltmann, I. Pavord. #ers D. Journals, Eur Respir J
    Abstract:

    ABSTRACT: Eosinophilic Bronchitis is a recently described condition presenting with chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The patient, a 48-yr-old male who had never smoked, presented with an isolated chronic cough. He had normal spirometric values, peak flow variability and airway responsiveness, but an induced sputum eosinophil count of 33 % (normal <1%). Although his cough improved with inhaled corticosteroids the sputum eosinophilia persisted. Over 2 yrs he developed airflow obstruction, which did not improve following nebulized bronchodilators and a 2-week course of prednisolone 30 mg once daily sufficient to return the sputum eosinophilia to normal (0.5%). It is suggested that the progressive irreversible airflow obstruction was due to persistent structural change to the airway secondary to Eosinophilic airway inflammation, and it is further speculated that Eosinophilic Bronchitis may be a prelude to chronic obstructive pulmonary disease in some patients

  • vascular remodeling is a feature of asthma and nonasthmatic Eosinophilic Bronchitis
    The Journal of Allergy and Clinical Immunology, 2007
    Co-Authors: Salman Siddiqui, Peter Bradding, A J Wardlaw, Ian D Pavord, Lucy Woodman, Amanda Sutcliffe, Aarti Shikotra, Camille Doe, Sue Mckenna, Christopher E Brightling
    Abstract:

    Rationale Increased vascularity and expression of vascular endothelial growth factor (VEGF) are recognized features of the asthmatic airway. The association of vascular remodeling with airway hyperresponsiveness (AHR) is unclear. Objective To assess vascular remodeling and sputum VEGF concentration in subjects with asthma, subjects with nonasthmatic Eosinophilic Bronchitis (EB), and healthy controls. Methods In cohort 1, 19 patients with asthma (Global Initiative for Asthma [GINA] 1-2, n=9; GINA 3-5, n=10), 10 patients with EB, and 11 healthy matched controls were recruited. Expression of the endothelial marker EN4 was assessed in bronchial biopsy samples. Vessels were counted using the validated mean Chalkley count by a blind observer. For cohort 2, a second independent cohort of 31 patients with asthma (GINA 1-2, n=11; GINA 3-5, n=20), 14 patients with EB, and 15 matched controls was recruited. Induced sputum supernatant VEGF was measured by ELISA. Results The mean chalkley count was significantly greater in GINA 3-5 asthma (5.2 [0.4]) and EB (4.8 [0.3]) compared with controls (3.5 [0.5]) and demonstrated a significant inverse correlation with the postbronchodilator FEV 1 % predicted in patients with asthma ( R 2 = 0.28; P = .02). Sputum VEGF concentration was also increased in GINA 3-5 asthma (2365 [1361-4110] pg/g) and EB (4699 [2818-7834] pg/g) compared with controls (1094 [676-1774] pg/g) and was inversely related to postbronchodilator FEV 1 % predicted in asthma ( R 2 = 0.2; P  = .01). Conclusion Vascular remodeling is a feature of asthma, and EB and is inversely associated with the postbronchodilator FEV 1 in asthma, suggesting that vascular remodeling is associated with airflow obstruction but not AHR. Clinical implications Vascular remodeling is dissociated from AHR in asthma and associated with airflow limitation.

  • chemokine concentrations and mast cell chemotactic activity in bal fluid in patients with Eosinophilic Bronchitis and asthma and in normal control subjects
    Chest, 2006
    Co-Authors: Lucy Woodman, Peter Bradding, Ian D Pavord, M A Berry, Amanda Sutcliffe, Davinder Kaur, Christopher E Brightling
    Abstract:

    Background Asthma and Eosinophilic Bronchitis share many immunopathologic features including increased numbers of eosinophils and mast cells in the superficial airway. The mast cell chemotactic activity of airway secretions has not been assessed in patients with Eosinophilic Bronchitis. Objectives To investigate the concentration of chemokines in bronchial wash samples and BAL fluid, and the mast cell chemotactic activity in BAL fluid from subjects with asthma and Eosinophilic Bronchitis, and from healthy control subjects. Methods We measured the concentrations of CCL11, CXCL8, and CXCL10 in bronchial wash samples and BAL fluid from 14 subjects with Eosinophilic Bronchitis, 14 subjects with asthma, and 15 healthy control subjects. Mast cell chemotaxis to BAL fluid from these subjects was examined using the human mast cell line HMC-1. Results The bronchial wash sample and BAL fluid concentrations of CXCL10 and CXCL8 was increased in subjects with Eosinophilic Bronchitis compared to those in subjects with asthma and healthy control subjects (p r = 0.42; p = 0.031) and CXCL10 ( r = 0.52; p = 0.007). Conclusion In subjects with Eosinophilic Bronchitis, CXCL8 and CXCL10 concentrations were elevated in airway secretions. These chemokines may play a key role in mast cell recruitment to the superficial airway in this condition.

  • observational study of the natural history of Eosinophilic Bronchitis
    Clinical & Experimental Allergy, 2005
    Co-Authors: M A Berry, Christopher E Brightling, A J Wardlaw, Beverley Hargadon, S Mckenna, Dominick E Shaw, R H Green, Ian D Pavord
    Abstract:

    Summary Background Eosinophilic Bronchitis is an important cause of chronic cough. Treatment with inhaled corticosteroids is associated with a short-term improvement in cough and reduced sputum eosinophil count but the long-term outcome is uncertain. Objective To determine the long-term outcome in patients diagnosed with and treated for Eosinophilic Bronchitis. Methods We have performed a longitudinal study of symptoms, Eosinophilic airway inflammation, spirometry and airway hyper-responsiveness in all patients diagnosed with Eosinophilic Bronchitis over 7 years. Results We identified 52 patients with Eosinophilic Bronchitis and longitudinal data of greater than 1 year (mean 3.1 years) was available in 32 patients, all of whom were treated with inhaled steroids. Three (9%) patients developed symptoms consistent with asthma and a methacholine PC20<8 mg/mL on one or more occasion. Five (16%) patients developed fixed airflow obstruction defined by a persistent post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity <70%. One (3%) patient had complete resolution of symptoms and Eosinophilic airway inflammation off treatment. The remaining patients had ongoing Eosinophilic airway inflammation and/or continuing symptoms. Multiple linear regression identified smoking, female gender and area under the curve of sputum eosinophil count over time as the most important predictors of decline in FEV1. Conclusions The most common outcome in Eosinophilic Bronchitis is continuing disease and complete resolution is rare. Asthma and fixed airflow obstruction developed in relatively few patients. The most important factors associated with a more rapid decline in FEV1 were female gender, smoking and prolonged Eosinophilic airway inflammation.

  • sputum and bronchial submucosal il 13 expression in asthma and Eosinophilic Bronchitis
    The Journal of Allergy and Clinical Immunology, 2004
    Co-Authors: M A Berry, Peter Bradding, A J Wardlaw, Ian D Pavord, Deborah Parker, N Neale, Lucy Woodman, Angela Morgan, Phillip Monk, Christopher E Brightling
    Abstract:

    Background Nonasthmatic Eosinophilic Bronchitis is a condition characterized by the presence of Eosinophilic airway inflammation in the absence of airflow obstruction or airway hyperresponsiveness. In asthma, the T H 2-type cytokine IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. Whether the expression of IL-13 is different between these 2 conditions is unknown. Objective We sought to investigate whether IL-13 expression is increased in asthma compared with Eosinophilic Bronchitis. Methods Sputum samples from subjects with mild asthma (n=30) and Eosinophilic Bronchitis (n=15) and normal controls (n=16) were dialyzed, and IL-13 concentration was measured by ELISA. In a subgroup of these patients, IL-13 protein expression in bronchial biopsies was assessed by immunohistochemistry. Results The concentration of sputum IL-13 was higher in patients with mild asthma than in normal controls ( P =.03) and in patients with Eosinophilic Bronchitis ( P =.03). The median (interquartile range) number of IL-13 + cells/mm 2 submucosa was significantly higher in asthma 4 (8) than Eosinophilic Bronchitis 1.7 (1.9) and normal controls 0.5 (1.1; P =.004). Eighty-three percent of the cells expressing IL-13 in the submucosa were eosinophils, and 8% were mast cells. The median (interquartile range) proportion of eosinophils that expressed IL-13 was higher in the subjects with asthma, 16 (10)%, than those with Eosinophilic Bronchitis, 7 (3)% ( P =.02). Conclusion The increased expression of IL-13 in asthma compared with Eosinophilic Bronchitis supports the concept that IL-13 may play a critical role in the pathophysiology of asthma.

Frederick E Hargreave - One of the best experts on this subject based on the ideXlab platform.

  • Eosinophilic Bronchitis in asthma a model for establishing dose response and relative potency of inhaled corticosteroids
    The Journal of Allergy and Clinical Immunology, 2006
    Co-Authors: Margaret M Kelly, Richard Leigh, L Jayaram, Charles H Goldsmith, Krishnan Parameswaran, Frederick E Hargreave
    Abstract:

    Background Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency. Objective We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers. Methods Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of ≥2.5% entered a 6-week sequential, placebo-controlled, patient-blinded, cumulative dose-response study. After 7 days of placebo, they received incremental doses of fluticasone propionate (FP), 50, 100, 200, and 400 μg/d, each for 7 days. Measurements were made of sputum and blood eosinophils, exhaled nitric oxide, spirometry, airway responsiveness to methacholine (methacholine PC 20 ), and symptom scores before and after each dose. Results Sputum eosinophils and exhaled nitric oxide were extremely sensitive to the effects of FP, and exhibited significant dose-dependent reductions of 99.4% and 99.8 parts per billion, respectively, where each variable was expressed per 100 μg/d FP. This compared with a 0.5 doubling dose increase of airway responsiveness to methacholine and a 0.3 decrease in symptom scores. Airway responsiveness to methacholine was the only variable that increased throughout the study. Conclusion These results suggest that the model of Eosinophilic Bronchitis could be used to compare the effect of cumulative doses of an inhaled corticosteroid delivered by different types of delivery systems or preparations using a relatively small number of patients. Clinical implications Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.

  • Induced Sputum, Eosinophilic Bronchitis, and Chronic Obstructive Pulmonary Disease
    American Journal of Respiratory and Critical Care Medicine, 1999
    Co-Authors: Frederick E Hargreave, Richard Leigh
    Abstract:

    AM J RESPIR CRIT CARE MED 1999;160:S53−S57.The application of sputum induction and refined methods of sputum examination has provided the opportunity to examine cell and molecular markers of airway inflammation in asthma, COPD, and other airway diseases. The measurements are relatively noninvasive and can be applied safely, with care, even in more severe exacerbations of asthma and severe COPD. Induced sputum examination can be applied at random and repeatedly and gives results that are reproducible, valid, and responsive to changes in treatment. An Eosinophilic Bronchitis, defined as sputum eosinophilia, is typical of asthma but can also occur in patients with a chronic cough without asthma, and in some patients with COPD in whom the classic inflammatory response is neutrophilic without eosinophilia. When eosinophilia occurs in COPD, it has been considered to be the result of cigarette smoking but it may be due to other causes. The clinical importance of Eosinophilic Bronchitis is that it responds to tre...

  • Induced sputum, Eosinophilic Bronchitis, and chronic obstructive pulmonary disease.
    American journal of respiratory and critical care medicine, 1999
    Co-Authors: Frederick E Hargreave, Richard Leigh
    Abstract:

    The application of sputum induction and refined methods of sputum examination has provided the opportunity to examine cell and molecular markers of airway inflammation in asthma, COPD, and other airway diseases. The measurements are relatively noninvasive and can be applied safely, with care, even in more severe exacerbations of asthma and severe COPD. Induced sputum examination can be applied at random and repeatedly and gives results that are reproducible, valid, and responsive to changes in treatment. An Eosinophilic Bronchitis, defined as sputum eosinophilia, is typical of asthma but can also occur in patients with a chronic cough without asthma, and in some patients with COPD in whom the classic inflammatory response is neutrophilic without eosinophilia. When eosinophilia occurs in COPD, it has been considered to be the result of cigarette smoking but it may be due to other causes. The clinical importance of Eosinophilic Bronchitis is that it responds to treatment with corticosteroid. In contrast, there is increasing evidence that an absence of sputum eosinophilia is associated with steroid resistance. Hargreave FE, Leigh R. Induced sputum, Eosinophilic Bronchitis, and chronic obstructive pulmonary disease.

  • occupational Eosinophilic Bronchitis without asthma an unknown occupational airway disease
    The Journal of Allergy and Clinical Immunology, 1997
    Co-Authors: C Lemiere, A Efthimiadis, Frederick E Hargreave
    Abstract:

    The introduction of reliable methods to measure inflammatory Cells in sputum has made it possible to identify the occurrence of Eosinophilic Bronchitis without asthma? Patients are first seen with a chronic cough without variable airflow limitation or airway hyperresponsiveness, and the condition Js reversed by glucocorticoid treatment. 2 For the first time, we descrlbe a case of Eosinophilic Bronchitis related to exposure to acrylates in the workplace. CASE REPORT A 50-year-old woman was employed for 2 years at a company that produced weather strips for vehicles. The job required her to use glue containing cyanoacrylate and methacrylate, which are known to induce occupational asthma. Three months after starting this work she noticed shortness of breath, chest tighthess, wheezing, and persistent dry cough, as well as nasal symptoms such as a runny, stuffy nose and sneezing when at work. These symptoms improved substantially on weekends. She was a 15 pack-year smoker and quit 20 years ago. Her family history was negative for allergies and asthma. Results of physical examination and chest radiography were normal. Allergy skin prick test responses to 19 common extracts were negative. Her treatment had consisted of albuterol inhaler as needed and budesonide nasal spray (200 ixg/day) for 1.5 months and Tegretol (200 mg/day) for petit mal epilepsy.

  • chronic cough with Eosinophilic Bronchitis examination for variable airflow obstruction and response to corticosteroid
    Clinical & Experimental Allergy, 1995
    Co-Authors: Peter G Gibson, Frederick E Hargreave, A Girgisgabardo, M M Morris, Judah A Denburg, J Dolovich
    Abstract:

    Summary The purpose of this study was to examine airway responsiveness, sputum cells and the effects of inhaled corticosteroid in the chronic cough syndrome associated with Eosinophilic Bronchitis. We studied nine consecutive referrals with chronic cough, sputum with >10% eosinophils, normal spirometry, and normal methacholine airway responsiveness. Clinical assessment, sputum analysis, allergy skin tests and a methacholine inhalation test were performed at the first visit. Peak expiratory flow (PEF) was measured twice daily for 1 week followed by an adenosine monophosphate (AMP) inhalation test. Subjects were then treated with inhaled beclomethasone 0.4 mg twice daily for 7 days. Sputum analysis and measurement of methacholine responsiveness were then repeated. Excessive airway narrowing to methacholine was not present in any of the subjects. A methacholine plateau response was present in five subjects. Hyperresponsiveness to AMP was absent in six of the nine subjects, and PEF variability was not increased for eight subjects. Corticosteroid therapy led to a reduction in sputum eosinophil counts from 40.1 (so 21.4)% to 4.0 (4.5)% but there was no significant change in metachromatic cell counts (0.8 so 0.5% vs 0.6 sd 0.6%) or total cell counts. Methacholine responsiveness improved within the normal range in the three subjects in whom it could be determined. Chronic cough associated with Eosinophilic airway inflammation can occur in the absence of variable airflow obstruction (asthma) and can improve after treatment with inhaled corticosteroid. This treatment can reduce the level of methacholine responsiveness within the normal range and reduces sputum eosinophils but not mast cells. These results suggest that the occurrence of variable airflow obstruction depends on the baseline level of methacholine responsiveness, the degree of Eosinophilic infiltration and the degree to which methacholine responsiveness becomes heightened.