Differential effects of ozone on airway and tissue mechanics in obese mice

Rivera-Sanchez, Yadira; Johnston, Richard A.; Schwartzman, Igor N.; Valone, Joanne M.; Silverman, Eric S.; Fredberg, Jeffrey J.; Shore, Stephanie A.

doi:10.1152/japplphysiol.00960.2003

Cited by 59 publications

(81 citation statements)

References 49 publications

(76 reference statements)

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“…Ozone has been shown to exacerbate asthma and increase airway hyperreactivity (5,6), and to contribute to increased morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) (7,8). Similar alterations in lung function and increases in sensitivity to ozone have been described in animal models of asthma and allergic inflammation (9)(10)(11).…”

mentioning

confidence: 84%

Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

Groves

Gow

Massa

et al. 2012

Am J Respir Cell Mol Biol

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Surfactant protein-D (Sftpd) is a pulmonary collectin important in down-regulating macrophage inflammatory responses. In these experiments, we analyzed the effects of chronic macrophage inflammation attributable to loss of Sftpd on the persistence of ozoneinduced injury, macrophage activation, and altered functioning in the lung. Wild-type (Sftpd 1/1 ) and Sftpd 2/2 mice (aged 8 wk) were exposed to air or ozone (0.8 parts per million, 3 h). Bronchoalveolar lavage (BAL) fluid and tissue were collected 72 hours later. In Sftpd 2/2 mice, but not Sftpd 1/1 mice, increased BAL protein and nitrogen oxides were observed after ozone inhalation, indicating prolonged lung injury and oxidative stress. Increased numbers of macrophages were also present in BAL fluid and in histologic sections from Sftpd 2/2 mice. These cells were enlarged and foamy, suggesting that they were activated. This conclusion was supported by findings of increased BAL chemotactic activity, and increased expression of inducible nitric oxide synthase in lung macrophages. In both Sftpd 1/1 and Sftpd 2/2 mice, inhalation of ozone was associated with functional alterations in the lung. Although these alterations were limited to central airway mechanics in Sftpd 1/1 mice, both central airway and parenchymal mechanics were modified by ozone exposure in Sftpd 2/2 mice. The most notable changes were evident in resistance and elastance spectra and baseline lung function, and in lung responsiveness to changes in positive endexpiratory pressure. These data demonstrate that a loss of Sftpd is associated with prolonged lung injury, oxidative stress, and macrophage accumulation and activation in response to ozone, and with more extensive functional changes consistent with the loss of parenchymal integrity. Keywords: ozone; surfactant protein-D; macrophages; iNOS; lung functionOzone is a ubiquitous urban air pollutant generated as a component of photochemical smog. Inhaled ozone causes ozonation and the peroxidation of proteins and lipids in the epithelial lining fluid layer of the lung, resulting in the production of oxidized proteins, aldehydes, and free radicals, which can damage surrounding tissue (1, 2). This is accompanied by an accumulation of activated macrophages in the lung and the production of additional cytotoxic and proinflammatory mediators, including reactive oxygen and reactive nitrogen species (ROS and RNS, respectively) that contribute to tissue injury (3). Airway and tissue mechanics are also altered after ozone exposure. Thus, in humans, ozone inhalation leads to a deterioration of pulmonary function, as measured by decreases in respiratory frequency, forced expiratory volume in 1 second, and forced vital capacity, and increases in airway resistance (1,4,5). Ozone has been shown to exacerbate asthma and increase airway hyperreactivity (5, 6), and to contribute to increased morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) (7,8). Similar alterations in lung function and increases in sensitivity to ozone have b...

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mentioning

confidence: 84%

Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

Groves

Gow

Massa

et al. 2012

Am J Respir Cell Mol Biol

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“…Increased responses to ozone are also reported in different models of obese mice (19,74,75). Williams and colleagues showed that augmented airway inflammation and reactivity in obese mice in response to ozone depended on TNFa (22).…”

Section: Irritant-and Pollutioninduced Asthma In Obesitymentioning

confidence: 95%

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

Dixon

Poynter

2016

Am J Respir Cell Mol Biol

128

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The majority of patients with severe or difficult-to-control asthma in the United States are obese. Epidemiological studies have clearly established that obese patients tend to have worse asthma control and increased hospitalizations and do not respond to standard controller therapy as well as lean patients with asthma. Less clear are the mechanistic underpinnings for the striking clinical differences between lean and obese patients with asthma. Because obesity is principally a disorder of metabolism and energy regulation, processes fundamental to the function of every cell and system within the body, it is not surprising that it affects the respiratory system; it is perhaps surprising that it has taken so long to appreciate how dysfunctional metabolism and energy regulation lead to severe airway disease. Although early investigations focused on identifying a common factor in obesity that could promote airway disease, an appreciation has emerged that the asthma of obesity is a manifestation of multiple anomalies related to obesity affecting all the different pathways that cause asthma, and likely also to de novo airway dysfunction. Consequently, all the phenotypes of asthma currently recognized in lean patients (which are profoundly modified by obesity), as well as those unique to one's obesity endotype, likely contribute to obese asthma in a particular individual. This perspective reviews what we have learned from clinical studies and animal models about the phenotypes of asthma in obesity, which show how specific aspects of obesity and altered metabolism might lead to de novo airway disease and profoundly modify existing airway disease.

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“…Largely through the work of Shore et al, molecular and physiologic characteristics of the murine model of obese asthma are currently being elucidated. 23,[26][27][28][29][30][31][32][33][34] However, assessing lung inflammation and lung responses among obese children remains challenging and limited by current technologies. Studies in children involving bronchodilator responsiveness, bronchoconstricting agonists (e.g., methacholine challenge), and airway inflammatory markers have yet to show the same consistent pattern of hyperresponsiveness that have been demonstrated in mice.…”

Section: If Obesity Leads To Asthma What Is the Mechanism?mentioning

confidence: 99%

Obesity, Nutrition, and Asthma in Children

Lang

2012

Pediatric Allergy, Immunology, and Pulmonology

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Differential effects of ozone on airway and tissue mechanics in obese mice

Cited by 59 publications

References 49 publications

Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

Obesity, Nutrition, and Asthma in Children

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