Reversible Alterations in Immunoregulatory T Cells in Smoking

Miller, Lawrence G.; Goldstein, Gideon; Murphy, M. J.; Ginns, Leo C.

doi:10.1378/chest.82.5.526

Cited by 234 publications

(68 citation statements)

References 22 publications

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“…ϩ ratio are not confined to the bronchial mucosa (13,22), as they have also been reported in peripheral blood (23,25) and in pulmonary arteries (our present results), it might be speculated that tobacco smoking induces an alteration in the lymphocyte regulation that affects extensively the lung structures and contributes to the development of COPD. Alternatively, as suggested by O'Shaughnessy and colleagues (13), smokers with a genetically determined low CD4 ϩ…”

Section: /Cd8supporting

confidence: 85%

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Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Peinado

Barberà

Abate

et al. 1999

Am J Respir Crit Care Med

251

187

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Endothelial dysfunction and intimal thickening have been shown in pulmonary arteries (PA) of patients with mild chronic obstructive pulmonary disease (COPD). To investigate whether an inflammatory process related to tobacco smoking might be involved in the development of pulmonary vascular abnormalities in COPD, we characterized the inflammatory cell infiltrate and the endothelium-dependent relaxation in PA of 39 patients who underwent lung resection, divided into three groups: "nonsmokers" (n ϭ 7); "smokers," with normal lung function (n ϭ 12); and "COPD" (n ϭ 20). Endothelium-dependent relaxation was assessed in vitro by exposing PA rings to adenosine diphosphate (ADP). Inflammatory cell types were identified by immunohistochemistry. PA of COPD patients Structural and functional abnormalities of the pulmonary circulation are common features in the wide spectrum of chronic obstructive pulmonary disease (COPD). Dysfunction of the pulmonary endothelium, which is associated with an impaired release of endothelium-derived nitric oxide (NO), may play a critical role in the remodeling of pulmonary vessels in COPD. Endothelial dysfunction in pulmonary arteries was initially shown in end-stage COPD patients undergoing lung transplantation by Dinh-Xuan and coworkers (1). In a recent study we observed that endothelial dysfunction may also be present in pulmonary arteries of patients with mild COPD (2). However, whereas in end-stage COPD chronic severe hypoxemia may account for the impairment of the endothelial function (1), the mechanisms of such an impairment in patients with milder degrees of disease, who are not hypoxemic, are unknown.Several studies performed in lungs of patients with mild COPD have shown apparent abnormalities in the structure of the pulmonary muscular arteries, in most cases consisting of the thickening of the intimal layer (3-5). Interestingly, the intensity of the intimal thickening has been shown to correlate with the severity of the inflammatory infiltrate in small airways (5, 6), suggesting that an inflammatory process might also account for the structural abnormalities of the pulmonary artery wall. Indeed, inflammation has been shown to be involved in the pathogenesis of some forms of pulmonary hypertension (7) and also in the remodeling of systemic vessels (8). Accordingly, we hypothesized that the structural abnormalities and the endothelial dysfunction shown in pulmonary arteries of patients with mild COPD could be related to an inflammatory process.Cigarette smoking causes an inflammatory reaction in the airways of patients with COPD. Whereas in both asymptomatic smokers and patients with COPD the nature and characteristics of the inflammatory reaction in central and peripheral airways (9-14), as well as in alveolar septa (15), have been thoroughly evaluated, little is known about the degree, nature, and evolution of the inflammatory infiltrate in pulmonary arteries of COPD patients.The present study, results of which have been given in abstract form (16), was therefore addressed to inves...

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Section: /Cd8supporting

confidence: 85%

“…ϩ ratio in smokers with and without airflow obstruction has been shown in the peripheral blood (23), and in bronchoalveolar lavage samples (24). Overall, these studies along with the present results point to the potential involvement of CD8 ϩ T lymphocytes in the pathogenesis of COPD.…”

Section: /Cd8mentioning

confidence: 97%

Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Peinado

Barberà

Abate

et al. 1999

Am J Respir Crit Care Med

251

187

View full text Add to dashboard Cite

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“…Available results are of interest and point towards a possible alteration in the lymphocyte regulation in smokers that might be initiated locally in the lung and eventually be detected in the blood, at least in heavy smokers [85][86][87][88][89]. The study of lymphocyte inflammation in the small airways and its relationship to the inflammation of the parenchyma might give some clues about the mechanisms of lung destruction in these subjects.…”

Section: Lymphocytesmentioning

confidence: 99%

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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“…Results from functional studies of circulating T-lymphocytes are conflicting, with reports of increased [14], unchanged [15] and decreased [16,17] responses to mitogenic stimulation in vitro. Alterations in immunoregulatory T-lymphocyte subsets with a decreased fraction of helper/inducer and an increased fraction of cytotoxic/suppressor cells have been reported, both locally in the lung [18], and in the peripheral circulation [19,20].Bronchial infections are common in smokers [2], but why only some smokers develop problems with repeated bronchial infections is largely unknown. Hypothetically, smokers prone to bronchial infections might differ immunologically from smokers without this disposition.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Immunological findings in blood and bronchoalveolar lavage fluid in chronic bronchitis patients with recurrent infectious exacerbations

Qvarfordt

Riise²,

Larsson³

et al. 1998

Eur Respir J

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Tobacco smoking induces profound immunological and inflammatory changes, both in the airways and systemically. Smoking impairs host defences and increases susceptibility to infection [1,2].The literature on the effects of smoking on the immune system is extensive and has been reviewed by several authors [2][3][4]. Evidence of a considerable influence on both humoral and cell-mediated immunity has been presented. Decreased serum immunoglobulin (Ig) levels, mainly IgG, have been reported in smokers [5,6]. Data concerning immediate skin reactivity to common allergens [7,8] as well as specific antibody responses to inhaled antigens [9] and vaccinations [10], indicate depressed immune responses in smokers. There are several reports of decreased activity of natural killer (NK-) cells, both from peripheral blood [11,12] and the lung [13]. Results from functional studies of circulating T-lymphocytes are conflicting, with reports of increased [14], unchanged [15] and decreased [16,17] responses to mitogenic stimulation in vitro. Alterations in immunoregulatory T-lymphocyte subsets with a decreased fraction of helper/inducer and an increased fraction of cytotoxic/suppressor cells have been reported, both locally in the lung [18], and in the peripheral circulation [19,20].Bronchial infections are common in smokers [2], but why only some smokers develop problems with repeated bronchial infections is largely unknown. Hypothetically, smokers prone to bronchial infections might differ immunologically from smokers without this disposition. To our knowledge, there are no studies addressing this issue in which smoking habits of study and control groups have been taken fully into account.Since the disposition for bronchial infections in smokers seems to be related to the presence of chronic bronchitis (CB) [21], a state of chronic mucus hypersecretion [22], and appear in the form of recurrent infectious exacerbations, patients with CB prone to infectious exacerbations were chosen for the study group. We decided to analyse most of the immunological parameters known or thought A significantly (p<0.05) lower level of IgG 3 was found in the CB group, and a significantly (p<0.01) higher proliferative response of PBMCs was found in the CB group after stimulation with diphtheria toxoid. Detectable levels of interleukin (IL)-6, tumour necrosis factor-α (TNF-α) and interferon-γ, but not of IL-2, IL-4 or transforming growth factor-β2, were found in supernatants from cultured cells in both study groups. Stimulated TNF-α production was significantly (p<0.05) higher in the CB group. NK-cell activity did not differ significantly between the study groups. There were no major differences between the groups in lymphocyte subpopulations in blood or BAL.In conclusion, no major alterations in the analysed indices of cell-mediated and humoral immunity were found in patients with chronic bronchitis prone to recurrent infectious exacerbations when compared with asymptomatic smoking controls. Eur Respir J 1998; 11: 46-54.

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Reversible Alterations in Immunoregulatory T Cells in Smoking

Cited by 234 publications

References 22 publications

Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Morphological and cellular basis for airflow limitation in smokers

Immunological findings in blood and bronchoalveolar lavage fluid in chronic bronchitis patients with recurrent infectious exacerbations

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