Small Airways Disease: Reproducibility of Measurements and Correlation with Lung Function

Berend, Norbert; Wright, Joanne L.; Thurlbeck, William M.; Marlin, G. E.; Woolcock, Ann J.

doi:10.1378/chest.79.3.263

Cited by 60 publications

(22 citation statements)

References 9 publications

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“…The majority of studies on peripheral airway inflammation in COPD subjects have been based on classic histologic examination (10)(11)(12)(13)(14)(15)(16), not allowing for a clear distinction between different inflammatory cells, which instead can be achieved with immunohistochemical methods. Several studies have used these methods to investigate the inflammatory cell types infiltrating the mucosa of central airways in COPD subjects, and have demonstrated that the inflammatory process consists predominantly of mononuclear cells (17)(18)(19)(20), and in particular of CD8 ϩ T-lymphocytes (21).…”

Section: Discussionmentioning

confidence: 99%

CD8⁺ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

Saetta

Stefano

Turato

et al. 1998

Am J Respir Crit Care Med

704

500

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To investigate whether the inflammatory process in peripheral airways is different in smokers who develop symptoms of chronic bronchitis and chronic airflow limitation and in asymptomatic smokers who do not develop chronic airflow limitation, we examined surgical specimens obtained from 16 smokers undergoing lung resection for localized pulmonary lesions. Nine had symptoms of chronic bronchitis and chronic airflow limitation and seven were asymptomatic with normal lung function. In peripheral airways, immunohistochemical methods were performed to identify neutrophils, macrophages, CD4+ and CD8+ T-lymphocytes infiltrating the airway wall, and morphometric methods were used to measure the internal perimeter, the airway wall area, and the smooth muscle area. The number of CD8+ T-lymphocytes and the smooth muscle area were increased in smokers with symptoms of chronic bronchitis and chronic airflow limitation as compared with asymptomatic smokers with normal lung function, while the number of neutrophils, macrophages, and CD4+ T-lymphocytes were similar in the two groups of subjects examined. We concluded that smokers who develop symptoms of chronic bronchitis and chronic airflow limitation have an increased number of CD8+ T-lymphocytes and an increased smooth muscle area in the peripheral airways as compared with asymptomatic smokers with normal lung function, supporting the important role of CD8+ T-lymphocytes and airway remodeling in the pathogenesis of chronic obstructive pulmonary disease.

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Section: Discussionmentioning

confidence: 99%

CD8⁺ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

Saetta

Stefano

Turato

et al. 1998

Am J Respir Crit Care Med

704

500

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“…BEREND and co-workers [5] showed that the tests of small airway function correlated best with the total pathology score of the small airways and, in particular, with the inflammatory score. They also found that the closing volume and the mid-expiratory flow correlated significantly with a measure of airway luminal size [6].…”

Section: Small Airway Abnormalities In "Normal" Smokersmentioning

confidence: 97%

Morphological and cellular basis for airflow limitation in smokers

Saetta¹,

Finkelstein²,

Mg³

1994

Eur Respir J

100

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M Mo or rp ph ho ol lo og gi ic ca al l a an nd d c ce el ll lu ul la ar r b ba as si is s f fo or r a ai ir rf fl lo ow w l li im mi it ta at ti io on n i in n s sm mo ok ke er rs s ABSTRACT: Airflow limitation has two well-defined components, increased resistance, which is found predominantly in the small airways, and loss of elastic recoil. Small airways contribute to the increased resistance to flow by the narrowing of the airway lumen. Morphometric studies have shown that smokers have increased epithelial abnormalities, cellular inflammatory infiltrates in the airway wall, increased muscle and fibrosis, when compared with nonsmokers. Along with these anatomical changes, an increased percentage of airways <400 µm in diameter is found. In addition to the measured changes, other nonmeasurable, dynamic events occur in the airways of smokers, which further decrease lumen diameter. There is ample evidence to show that the airways of smokers react to nonspecific stimuli by constricting, which results in increased resistance and decreased forced expiratory volume in one second (FEV 1 ). The pathological changes found in smokers, that could be responsible for active muscle constriction and airway narrowing include: 1) airway epithelial damage, resulting in increased permeability and impairment of other epithelial function; 2) chronic airway inflammation; 3) structural changes in the airway wall; and 4) loss of alveolar attachments.However, not all smokers develop the abovementioned airway abnormalities. We describe how smokers could develop either centrilobular emphysema (CLE), or panlobular emphysema (PLE). We have found that smokers with CLE have more abnormal and narrower small airways, and flow limitation is correlated with the small airway abnormalities and not with loss of recoil. In contrast, smokers with PLE have much less severe airway abnormalities, diffuse emphysema that can be detected microscopically at a stage when FEV 1 might be only mildly abnormal, and early changes in elastic recoil as evidenced by the changes in the pressure-volume curve of the lung. Furthermore, in PLE, airflow limitation is correlated with loss of recoil but not with abnormalities in the small airways.We believe that the mechanisms involved in the pathogenesis of the two types of emphysema in smokers are different; an airborne mechanism for CLE, possibly related to airway hyperresponsiveness, and a bloodborne mechanism for PLE, which may be related to dysfunction of α 1 -antiproteases. We conclude that the separation of smokers based on their emphysema type is essential if we are to understand the pathogenesis of chronic obstructive pulmonary disease (COPD) in these subjects.

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“…BEREND et al [5] showed that the results of tests of small airway function correlated best with the total pathological score of the small airways and, in particular, with the inflammatory score. They also found that the closing volume and mid-expiratory flow correlated significantly with a measure of airway luminal size [6].…”

Section: Morphology and Function Correlationmentioning

confidence: 99%

Disease of the airways in chronic obstructive pulmonary disease

Piqueras

Cosio²

2001

European Respiratory Journal

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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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Small Airways Disease: Reproducibility of Measurements and Correlation with Lung Function

Cited by 60 publications

References 9 publications

CD8⁺ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

CD8⁺ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

Morphological and cellular basis for airflow limitation in smokers

Disease of the airways in chronic obstructive pulmonary disease

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Small Airways Disease: Reproducibility of Measurements and Correlation with Lung Function

Cited by 60 publications

References 9 publications

CD8+ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

CD8+ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

Morphological and cellular basis for airflow limitation in smokers

Disease of the airways in chronic obstructive pulmonary disease

Contact Info

Product

Resources

About

CD8⁺ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

CD8⁺ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease