Morphological and cellular basis for airflow limitation in smokers

Saetta, Marina; Finkelstein, Richard A.; Mg, Cosio

doi:10.1183/09031936.94.07081505

Cited by 100 publications

(63 citation statements)

References 72 publications

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“…Panacinar emphysema involves the uniform destruction of the alveolar walls and is usually found in smokers who develop emphysema early in life and in those with ␣ 1 -antitrypsin deficiency. Panacinar emphysema is associated with a loss of elastic recoil and higher lung compliance, whereas centrilobular emphysema is associated with a higher degree of airway inflammation and hyperresponsiveness (47)(48)(49)(50). In centrilobular emphysema, there is a higher total pathologic score of small airways than in lungs with panacinar emphysema (48).…”

Section: Relationship Of Changes In Remodeling To Lung Functionmentioning

confidence: 91%

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

Chung¹

2005

Proceedings of the American Thoracic Society

105

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Airway wall remodeling processes are present in the small airways of patients with chronic obstructive pulmonary disease, consisting of tissue repair and epithelial metaplasia that contribute to airway wall thickening and airflow obstruction. With increasing disease severity, there is also increased mucous metaplasia and submucosal gland hypertrophy, peribronchial fibrosis, and an increase in airway smooth muscle mass. Apart from its contractile properties, airway smooth muscle produces inflammatory cytokines, proteases, and growth factors, which may contribute to the remodeling process and induce phenotypic changes of the muscle. Airflow limitation responds minimally to ␤-agonists and corticosteroid therapy, unlike asthma, perhaps because of alterations in ␤-receptor or glucocorticoid receptor numbers, alterations in receptor signaling, or the constrictive limitation imposed by peribronchial fibrosis. Better response is observed with the combination of inhaled long-acting ␤-agonists and corticosteroids. This could result from effects at the level of airway smooth muscle. Airway wall remodeling may involve the release of growth factors from inflammatory or resident cells. The influence of smoking cessation or of current therapies on airway wall remodeling is unknown. Specific therapies for airway wall remodeling may be necessary, together with noninvasive methods of imaging small airway wall remodeling to assess responses.

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Section: Relationship Of Changes In Remodeling To Lung Functionmentioning

confidence: 91%

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

Chung¹

2005

Proceedings of the American Thoracic Society

105

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“…Eur Respir J 2000; 15: 505±511. In humans, a major site of inflammatory action of cigarette smoke has been attributed to the so-called small airways, stimulating a number of studies aimed at characterizing and detecting structural change in the lung periphery [1,2]. The phase III slope of the N 2 single breath washout (SBW) test became a popular index of small airways alteration since the work by COSIO et al [3] showed its correlation with morphological scores of small airways abnormalities in smokers with normal spirometry.…”

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confidence: 99%

N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats

et al. 2000

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This study investigated the effect of cigarette smoke exposure and the potential protection N-acetylcysteine (NAC) in rat lungs.Forty-eight rats were exposed to cigarette smoke (CS) for 10 weeks, without (CS group) or with (CS+NAC group) oral intake of NAC 200 mg . rat -1 . day -1 , or to fresh air (Control). All rat lungs were assessed in terms of lung function, ventilation distribution (nitrogen, helium and sulphur hexafluoride phase III slopes), and morphometry (airway wall thickening of small, medium and large bronchi).The small bronchi, defined as the airways with an internal perimeter <1,000 mm showed significantly thicker airway walls in the CS than in the Control group. By contrast, no airway wall thickening was observed in the CS+NAC group with respect to Control. Except for decreased lung volumes and compliance in CS and CS+NAC groups, which were entirely attributable to smaller body weight gain, lung function was indistinguishable from Control. Phase III slopes were significantly increased only in the CS group.In conclusion, smoke-induced alterations in the rat lungs were reflected in wall thickening of the small bronchi and increased ventilation maldistribution. These smoke-induced morphometric and ventilation distribution alterations were prevented by N-acetylcysteine. Eur Respir J 2000; 15: 505±511. In humans, a major site of inflammatory action of cigarette smoke has been attributed to the so-called small airways, stimulating a number of studies aimed at characterizing and detecting structural change in the lung periphery [1,2]. The phase III slope of the N 2 single breath washout (SBW) test became a popular index of small airways alteration since the work by COSIO et al. [3] showed its correlation with morphological scores of small airways abnormalities in smokers with normal spirometry. A later SBW study by VAN MUYLEM et al. [4], which included helium and sulphur hexafluoride tracer concentrations, also revealed distinct correlations between indices derived from He and SF 6 slopes and airway pathology scores. Due to the fact that the diffusion front is located more peripherally for SF 6 than for He, the respective phase III slopes are indicative of the site where ventilation inhomogeneities occur.Although animal studies are well-suited for the study of lung function in the diseased lung, the difficulty often resides in reproducing a lesion which is comparable to that encountered in the human lung [5]. Previous studies in rats have led to conflicting results as to whether the cigarette smoke induces emphysematous lesions [6,7] or not [8,9] and not all studies provide any information about the extent to which the nonalveolated airways are affected [10]. Despite these difficulties, rat lungs have been used to investigate the possible protective role of N-acetylcysteine (NAC) over cigarette smoke induced lesions. NAC is an antioxidant and can therefore be expected to change lung oxidant-antioxidant imbalance induced by cigarette smoke which is a source of oxidants. Previous histopathology...

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“…Inflammation of the airways and the lungs is thought to play a major role in the pathogenesis of COPD [2][3][4][5]. The progression of COPD is strongly associated with infiltration of the small airway walls by inflammatory cells and the accumulation of inflammatory mucous exudates in the lumen [6].…”

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confidence: 99%

Time course of cigarette smoke-induced pulmonary inflammation in mice

D’hulst¹

2005

Eur Respir J

287

245

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Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease. In the present study a murine model of tobacco smoke-induced emphysema was used to investigate the time course of airway and pulmonary inflammatory response, with a special emphasis on pulmonary dendritic cell (DC) populations.Groups of mice were exposed to either cigarette smoke or to control air for up to 24 weeks. In response to cigarette smoke, inflammatory cells (i.e. neutrophils, macrophages and lymphocytes) progressively accumulated both in the airways and lung parenchyma of mice. Furthermore, a clear infiltration of DCs was observed in airways (10-fold increase) and lung parenchyma (1.5-fold increase) of cigarette-exposed mice at 24 weeks.Flow cytometric analysis of bronchoalveolar lavage (BAL) DCs of smoke-exposed mice showed upregulation of major histocompatability complex II molecules and costimulatory molecules CD40 and CD86, compared with BAL DCs of air-exposed mice. Morphometric analysis of lung histology demonstrated a significant increase in mean linear intercept and alveolar wall destruction after 24 weeks of smoke exposure.In conclusion, the time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.

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Morphological and cellular basis for airflow limitation in smokers

Cited by 100 publications

References 72 publications

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats

Time course of cigarette smoke-induced pulmonary inflammation in mice

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