The Effect of Repeated Ozone Exposures on  Inflammatory Markers in Bronchoalveolar Lavage Fluid and Mucosal Biopsies

Jörres, Rudolf A.; Holz, Olaf; Zachgo, Wolfgang; Timm, Petra; Koschyk, Silke; Müller, Bernd; Grimminger, Friedrich; Seeger, Werner; Kelly, Frank J.; Dunster, Christine; Frischer, Thomas; Lubec, Gert; Waschewski, Marc; Niendorf, Axel; Magnussen, H

doi:10.1164/ajrccm.161.6.9908102

Cited by 120 publications

(79 citation statements)

References 25 publications

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“…Inhalation of ozone is well known to cause acute pulmonary neutrophilia [11,12,16,19]. The inflammatory response to ozone is transient and shows reproducible differences between subjects [19].…”

Section: Discussionmentioning

confidence: 99%

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SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects

Holz¹,

Khalilieh²,

et al. 2009

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SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates neutrophil trafficking in animal models, characteristics that may be beneficial in the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive pulmonary disease. The purpose of this proof-of-principle study was to determine whether SCH527123 inhibits ozone-induced neutrophil recruitment in healthy humans.In a randomised, double-blind, placebo-controlled, three-way crossover study, oral SCH527123 (50 mg once daily, 4 days), prednisolone (50 mg once), or placebo was alternated with 2-week washouts. 18 healthy ozone responders (.20% increase in sputum neutrophils) underwent ozone challenge tests (250 ppb, 3 h intermittent exercise) 1 h after the last treatment dose. Sputum was induced at 3 h post-challenge.After SCH527123 treatment, the ozone challenge resulted in significantly lower sputum neutrophil counts (0.13610 6 ?mL -1 ) compared with prednisolone (0.84610; p,0.001) or placebo (2.98610 6 ?mL -1 ; p,0.001). Comparable results were obtained for total cell count, percentage of sputum neutrophils, and for interleukin-8 and myeloperoxidase in sputum supernatant. Post-challenge, SCH527123 inhibited neutrophilia in peripheral blood but significantly less than in sputum. All treatments were safe and well tolerated. SCH527123 causes significant attenuation of ozone-induced airway neutrophilia in healthy subjects. Further evaluation in a large trial of patients with pulmonary disorders is warranted.

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Section: Discussionmentioning

confidence: 99%

“…A washout interval of at least 2 weeks separated each treatment period and ozone challenge test [16,17].…”

Section: Day -28--21mentioning

confidence: 99%

SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects

Holz¹,

Khalilieh²,

et al. 2009

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“…Acute exposure to ozone leads to an increase in the numbers of neutrophils and mononuclear cells, increases in the concentrations of total protein and interleukins (IL)-6 and IL-8, and a reduced concentration of glutathione in bronchoalveolar lavage fluid without changes in bronchial biopsy results. Furthermore, bronchial biopsy showed prominent neutrophilic inflammation of the airway [38].…”

Section: The Cellular Inflammatory Infiltrate In the Airwaysmentioning

confidence: 99%

Disease of the airways in chronic obstructive pulmonary disease

Piqueras

Cosio²

2001

Eur Respir J

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The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). The functional consequence of these abnormalities is airflow limitation.Airway abnormalities and emphysema interact in a complex fashion in the development of airflow limitation in COPD. In an attempt to improve understanding of the role of the airways in COPD, the morphological counterparts of airflow limitation, the cellular inflammatory infiltrate in the airways and the relationship between emphysema type and airway abnormalities are reviewed.Significant correlation between airway remodelling and functional measurements are found in earlier stages of COPD. In advanced COPD, airflow limitation is reflected by airway narrowing, airway deformity and extent of emphysema. The cellular inflammatory infiltrate is mainly composed of neutrophils in early stages of COPD. However, the presence of CD8z T-cells seems to differentiate smokers with COPD from smokers that would not develop the disease. The inflammatory changes and remodelling found in the airways and their contribution to airflow obstruction might be modulated by the type of emphysema smokers develop, with centrilobular emphysema showing more severe inflammatory changes and narrower airways than panlobular emphysema.In conclusion, the degree of airway involvement in chronic obstructive pulmonary disease can vary greatly for the same degree of airflow obstruction, depending on the type of emphysema smokers develop. If the underlying lung abnormalities in chronic obstructive pulmonary disease vary, as the evidence suggests, the study of cigaretteinduced lung disease as a single entity will further delay understanding of chronic obstructive pulmonary disease. The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). The functional consequence of these abnormalities is airflow limitation.Bronchiolitis contributes to airflow limitation by narrowing and obliterating the airway lumen and by actively constricting the airway. Emphysema, by reducing the elastic recoil of the lung through parenchymal destruction and increase in alveolar size, as well as reducing the elastic load applied to the airways through destruction of alveolar attachments, also contributes to the airflow limitation characteristic of smokers. Although there is increasing evidence that the large airways are inflamed in patients with COPD, this is not believed to contribute directly to the airflow limitation in these patients.It has become apparent that airway abnormalities and emphysema interact in a complex fashion, rather than simply additively in the development of airflow limitation and COPD. The type of emphysema that smokers develop seems to determine, to a great extent, the quantity and possibly type of inflammation and airway remodelling found, suggesting that different pathogenetic mechani...

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“…The impact of this air pollutant has been studied in different areas [2][3][4][5]. Concerning human health, O 3 can cause injuries to airway epithelial cells (and lung diseases such as asthma), hyperplasia, headaches, and nausea, particularly in sensitive people, such as children and elderly [6][7][8][9][10]. Regarding vegetation, O 3 can damage plant leaves (decreases in both leaf photosynthesis and leaf area), reducing crop yields associated with a high negative economic impact [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Surface Ozone Behavior at Different Regimes

Afonso

Pires

2017

Applied Sciences

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Previous studies showed that the influence of meteorological variables and concentrations of other air pollutants on O 3 concentrations changes at different O 3 concentration levels. In this study, threshold models with artificial neural networks (ANNs) were applied to characterize the O 3 behavior at an urban site (Porto, Portugal), describing the effect of environmental and meteorological variables on O 3 concentrations. ANN characteristics, and the threshold variable and value, were defined by genetic algorithms (GAs). The considered predictors were hourly average concentrations of NO, NO 2 , and O 3 , and meteorological variables (temperature, relative humidity, and wind speed) measured from January 2012 to December 2013. Seven simulations were performed and the achieved models considered wind speed (at 4.9 m·s −1 ), temperature (at 17.5 • C) and NO 2 (at 26.6 µg·m −3 ) as the variables that determine the change of O 3 behavior. All the achieved models presented a similar fitting performance: R 2 = 0.71-0.72, RMSE = 14.5-14.7 µg·m −3 , and the index of agreement of the second order of 0.91. The combined effect of these variables on O 3 concentration was also analyzed. This statistical model was shown to be a powerful tool for interpreting O 3 behavior, which is useful for defining policy strategies for human health protection concerning this air pollutant.

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The Effect of Repeated Ozone Exposures on Inflammatory Markers in Bronchoalveolar Lavage Fluid and Mucosal Biopsies

Cited by 120 publications

References 25 publications

SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects

SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects

Disease of the airways in chronic obstructive pulmonary disease

Characterization of Surface Ozone Behavior at Different Regimes

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