Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (14)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Domagala-Kulawik, J.
Right arrow Articles by Chazan, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Domagala-Kulawik, J.
Right arrow Articles by Chazan, R.
(Chest. 2003;123:1054-1059.)
© 2003 American College of Chest Physicians

The Cellular Composition and Macrophage Phenotype in Induced Sputum in Smokers and Ex-Smokers With COPD*

Joanna Domagala-Kulawik, MD, PhD; Marta Maskey-Warzechowska, MD; Izabela Kraszewska, MS and Ryszarda Chazan, MD, PhD, FCCP

* From the Department of Pneumonology and Allergology, Warsaw Medical University, Warsaw, Poland.

Correspondence to: Joanna Domagala-Kulawik, MD, PhD, Department of Pneumonology and Allergology, ul Banacha 1a, 02 097 Warsaw, Poland; e-mail: jokula{at}amwaw.edu.pl


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: The relationship between smoking and COPD has been well-documented. We investigated the impact of cigarette smoking on airway inflammation in COPD patients.

Design: Changes in cell profiles in induced sputum (IS) samples from smokers with COPD and patients who ceased smoking were compared.

Setting: Department of pneumonology in a university hospital.

Patients: IS samples were collected from 17 smokers and 17 ex-smokers with COPD.

Interventions: We examined IS samples for differential cell counts and macrophage phenotypes determined by immunocytochemistry with monoclonal antibodies anti-CD11b, anti-CD14, anti-CD54, and anti-CD71.

Measurements and results: The median IS volume was greater and the total cell count was higher in smokers than in ex-smokers. The difference, however, was not significant. We did not find any significant differences in the proportions of cells and in the phenotypes of macrophages between the two groups, with the proportion of eosinophils being slightly higher in the group of smokers. We found, however, a significant positive correlation between the decrease in pulmonary function parameters and the number of pack-years smoked, an inverse correlation of pulmonary function test results with the number of lymphocytes in IS, and a correlation between some changes in the expression of macrophage surface markers and smoking history. There was no correlation between the time from smoking cessation and any cellular component found in IS samples.

Conclusions: The analysis of IS samples in patients with COPD revealed no significant differences in cell count and macrophage phenotypes between active smokers and ex-smokers.

Key Words: COPD • ex-smokers • induced sputum • macrophages • smokers


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
COPD is a serious, progressive disorder that is characterized by poorly reversible airway obstruction and persistent inflammation in the lung. One of the major risk factors for developing COPD is cigarette smoking.1 The benefits of smoking cessation seen in the improvement in pulmonary function test results have been well-documented.1 2 By contrast, little is known about the effects of smoking cessation on the changes in the inflammatory response in the lung. The aim of this study was to investigate the effect of smoking cessation on cellular inflammation in the lungs of patients with COPD.

In the majority of studies on the cellular bases of COPD, findings from bronchial biopsy specimens, BAL fluid (BALF) samples, and induced sputum (IS) samples were analyzed. The IS sample examination is a well-tolerated, effective method for the analysis of bronchial cellular response.3 4 5 Several studies performed in patients with COPD revealed the role of neutrophils, macrophages, and CD8-positive lymphocytes in the pathogenesis of this disorder.6 7 8 9 Long-term smoke exposure causes similar changes in the IS cell profile with features of neutrophil and macrophage activation.10 11 It is difficult to establish the macrophage phenotype, since these cells represent a heterogeneous population with different stages of activation. The most stable surface markers seem to be the following: (1) the transferrin receptor CD71; (2) the adhesion associated molecules CD11a, CD11b, and CD11c; (3) the intercellular adhesion molecule-1 (CD54); and (4) the receptor to lipopolysaccharide-CD14.12 As shown in the investigation of the BALF from smokers, cigarette smoke alters the expression of the above markers.13 14

To investigate the differences in the airway inflammatory process in active smokers and patients who had ceased smoking, we compared the cellular composition of IS from smokers and ex-smokers with COPD. For macrophage characteristics, we used the antibodies anti-CD11b, anti-CD14, anti-CD54, and anti-CD71. The correlation between the proportion of cells in IS and the expression of macrophage markers and smoking consumption, the length of time from smoking cessation, and pulmonary function test results were analyzed.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Subjects
In this prospective study, 38 patients with COPD were included. The diagnosis of COPD was established according to the standards of the Global Initiative for Chronic Obstructive Lung Disease.1 We managed to obtain IS samples from 34 patients. The clinical characteristics of the population under study are presented in Table 1 . Patients who had ceased smoking at least 1 year prior to entering the study were included in the group of ex-smokers. None of the subjects showed signs of infection during the investigation. Some of the subjects received therapy with oral steroids, with the number of treated patients and the mean dose of the steroids being comparable in the two groups of subjects. All participants gave their informed consent.


View this table:
[in this window]
[in a new window]

  		Table 1. Clinical Characteristics of the Study Population*

 
Study Design
Sputum Induction:
All the patients were hospitalized at the Department of Pneumonology and Allergology, Warsaw Medical University. Pulmonary function tests were performed (abc PNEUMO; abcMED; Warsaw, Poland) and arterial blood gas levels were assessed prior to sputum induction. The results are shown in Table 2 . The predicted values of the pulmonary function tests were taken from Knudson et al.15 The patients received 200 µg salbutamol before the induction. After undergoing spirometry after bronchodilator administration, they were asked to rinse their mouths thoroughly with water and to inhale sterile hypertonic saline solution (NaCl) at increasing concentrations (ie, solutions of 3%, 4%, and 5%) at room temperature via a pneumatic nebulizer with the output set at 0.35 mL/min. The duration of each inhalation was 5 min, and the induction was stopped after expectoration of an adequate amount of sputum (ie, 2 mL). After each inhalation, spirometry was performed in order to detect a possible FEV1 decrease. The whole procedure was stopped if a 20% FEV1 decline was observed (the postbronchodilator FEV1 was considered to be the baseline value). The sputum samples obtained were transferred to the laboratory for further analysis directly after expectoration.


View this table:
[in this window]
[in a new window]

  		Table 2. Functional Characteristics of Study Population at Baseline*

 
Sputum Processing:
IS was analyzed immediately on receipt. The volume of the sputum was measured, and the plugs were selected and weighed. A freshly prepared 0.1% solution of dithiothreitol (Sigma-Aldrich Co; St. Louis, MO) was added in a volume that was equal to the double weight of the sputum, and the mixture was vortexed for 15 min. Then a double volume of a phosphate-buffered saline solution was added, and the mixture was briefly vortexed. After filtration through two layers of a sterile gauze to remove debris and mucous, the sputum was centrifuged for 10 min at 800g. The cell pellet was resuspended in a phosphate-buffered saline solution. Cell viability was determined by a trypan blue exclusion test. The cells were counted using a Bürker chamber. A differential cell count was performed using slides stained with the May-Grünwald-Giemsa method. Three hundred cells were counted. Smears with < 50% of squamous cells and > 200 nonsquamous cells were qualified as adequate. An additional two slides stained with hematoxylin-eosin were prepared for analysis of the morphology of epithelial cells.

Immunocytochemistry:
For macrophage phenotyping, an immunocytochemistry method was used with the commercially available antibodies anti-CD14, anti-CD11b, anti-CD54, and anti-CD71 (Dako; Copenhagen, Denmark). The alkaline phosphatase anti-alkaline phosphatase reaction was performed on the air-dried slides according to the instructions of the manufacturer (LSAB2 kit; Dako). Two hundred macrophages on each reaction area were evaluated using a light microscope, and the percentages of positive cells were recorded.

Statistical Analysis
For data comparison, the nonparametric Mann-Whitney U test was used, with a p value of < 0.05 being regarded as significant. The relationship between the proportion of cells and smoking history, expressed as the number of pack-years, and the results of pulmonary function tests were tested by the Spearman correlation test.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
There were no significant differences in the severity of COPD, the median FEV1, median FVC, and median arterial blood gas levels in the two investigated groups (Table 2) . In both groups, the pulmonary function parameters (ie, FEV1, FVC, and maximal expiratory flow at 50% of vital capacity), expressed as percent predicted values, correlated adversely with cigarette consumption, expressed as the number of pack-years. There was also a positive correlation between cigarette consumption and arterial PCO2 values.

Initially, 34 patients were included in the study. Sputum samples with a volume of at least 2 mL were obtained from 29 patients (sputum expectoration after inhalation of 3% NaCl solution, 49% of patients; sputum expectoration after inhalation of 4% NaCl solution, 38% of patients; and sputum expectoration after inhalation of after 5% NaCl solution, 13% of patients). No clinical signs of bronchoconstriction were observed during sputum induction. A decreased value of FEV1 exceeding 20% of the baseline was observed only in one case, and it was not accompanied by dyspnea or wheezing on auscultation.

The median volume of the sputum in the smokers group (3.5 mL) was larger than that in the ex-smokers group (2.5 mL), but the difference was not significant. Eighty-five percent of all sputum samples containing < 50% squamous cells were adequate for the analysis, and, finally, the sputum obtained from 24 patients (14 smokers and 10 ex-smokers) was subjected to further analysis. The mean cell viability was > 90%. The total cell count was elevated in the group of smokers (mean, 9.7 x 106 cells/mL; median, 4.8 x 106 cells/mL; range, 0.8 to 52.0 x 106 cells/mL). In the ex-smokers group, the mean total cell count was 4.2 x 106 cells/mL, the median was 3.0 x 106 cells/mL, and the range was 0.3 to 13.0 x 106 cells/mL. This difference was not significant. We did not find any significant differences in the proportion of macrophages, lymphocytes, neutrophils, or eosinophils in the IS between smokers and ex-smokers (Table 3 ). The proportion of eosinophils was slightly higher in the smokers group (median, 8%; range, 0.6 to 36.0%) than in the ex-smokers group (median, 4%; range, 0 to 28.0%), but it was not significant. There were no differences between the two groups when the differential cell count also was expressed in terms of absolute cell counts. We found a significant positive correlation between the total count of lymphocytes and the proportion of lymphocytes with FEV1 percent predicted (r = 0.4; p < 0.05) and FVC percent predicted (r = 0.4; p < 0.05). We found an inverse correlation of the total lymphocyte count in IS samples with arterial blood PCO2 (r = -0.44; p < 0.05). We did not find any neoplastic or atypical epithelial cells in the IS smears.


View this table:
[in this window]
[in a new window]

  		Table 3. Total and Differential Cell Counts in IS Samples of Study Groups*

 
The results of the analysis of macrophage surface antigens revealed no differences between the two groups (Fig 1 ). The intensity of reaction with antibody anti-CD71 and anti-CD11b in the cytoplasm of macrophages was stronger, but the intensity of the reaction with antibody anti-CD14 was weak.



View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Macrophage phenotype in the IS samples of the study groups. The data are shown as the median (p25-p75) percentage of macrophages. sm = smokers; ex = ex-smokers.

 
The proportion of macrophages with the expression of CD14 correlated negatively with FVC percent predicted (r = -0.7; p < 0.05). There was a reverse correlation between the proportion of macrophages with positive reaction to CD71 and the number of pack-years smoked (r = -0.7; p < 0.05), and with PCO2 (r = -0.6; p < 0.05). The proportion of CD11b-positive macrophages correlated with the number of pack-years smoked (r = 0.7; p < 0.05) and with PCO2 (r = 0.6; p < 0.05).

We did not find any correlation between the proportion of cells or macrophage markers and the length of time from smoking cessation. There was no correlation of the mean dose of steroids with any of the investigated parameters.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study showed that there are no significant differences in the cellular profile of IS samples between patients with COPD who are active smokers and those who have ceased smoking. To the best of our knowledge, ours is the first comparison between these groups of patients. In the majority of studies on IS samples from patients with COPD, what was compared was the sputum samples received from healthy subjects or a group of smokers with those from nonsmokers. There have been few studies of the effect of smoking cessation on cellular changes in the airways. Skold et al16 presented the results of BALF analyses in healthy persons, Turato et al17 showed the results of examinations of bronchial biopsy specimens in patients with chronic bronchitis, and Wright et al18 found similar structural changes in the lungs of smokers and ex-smokers with emphysema. In these investigations, no differences in the changes in the cellular profiles of smokers vs ex-smokers were found.

In this study, the clinical characteristics of the groups of smokers and ex-smokers did not differ significantly. We found a significant inverse correlation between the results of pulmonary function tests, and we found a positive correlation between the arterial blood PCO2 values and smoking consumption, which were expressed as the number of pack-years in both groups that were analyzed. The group of ex-smokers was composed of patients who had ceased smoking > 1 year earlier, and the maximum time from smoking cessation was 20 years. We did not find any correlation between the results of pulmonary function tests and the length of time from smoking cessation.

The effectiveness of sputum induction was comparable in both groups. The mean volume of sputum and the total cell count were higher in active smokers when compared with those of ex-smokers and was close to normal values in healthy subjects. Skold et al16 found that the normalization of the total cell count and the cell concentration in the BALF samples to be in proportion to the length of time from smoking cessation.

No significant differences were found when the comparison of total and differential cell counts was made between the groups. The differential cell count in IS samples from our patients with COPD was similar to those reported by other authors.19 20 21 22 23 However, in other investigations the percentage of neutrophils in smokers with COPD was higher than in our patients,21 22 23 but the number of neutrophils was similar.22 We noted an elevated proportion of eosinophils and higher total number of eosinophils in both smokers and ex-smokers with COPD, and a slightly higher proportion of these cells in smokers when compared with ex-smokers (difference not significant). In the study of Hargreave and Leigh,20 the participation of eosinophils in bronchial constriction in smokers was observed. Lebowitz et al24 concluded that eosinophilia is an important aspect of bronchial constriction in smokers. Cosio and Guerassimov25 divided case of COPD in smokers into the following two types: one with eosinophilia; and the other without eosinophilia. There were no differences in IS or BAL samples in the proportion of eosinophils between healthy smokers and nonsmokers in the study of Lensmar et al.11 It may be that eosinophilia found in IS samples may reflect the presence of inflammation in smokers with COPD who have airway responsiveness to corticosteroids, which is an asthmatic pattern of COPD.8 A slightly lower proportion of eosinophils observed in IS samples from ex-smokers may indicate a normalization of the inflammatory process in the airways after smoking cessation.

Pulmonary macrophages are a heterogeneous population of cells. Most studies have been concerned with alveolar macrophages (AMs) obtained by BAL of the peripheral airways. The cells in IS samples originate from the proximal airways, and it has been shown that macrophages in IS samples represent a more mature phenotype.3 However, it is possible to find an expression of the same markers on IS macrophages as that of the same markers on the AMs present in the BALF.11 For the analysis of pulmonary macrophages, we used antibodies recognizing some of the most stable surface markers, such as CD11b, CD14, CD54, and CD71.12 The proportion of CD54-positive macrophages and the proportion of CD71-positive macrophages in IS samples from active smokers with COPD in our study were lower than those in the group of healthy smokers reported by Lensmar et al,11 but the proportion of macrophages with expression of CD11b was higher in our study than in theirs.11 Long-term exposure to cigarette smoke has been shown to alter the expression of these markers. The proportion of CD11b-positive, CD14-positive, CD54-positive, and CD71-positive macrophages was lower in the BALF and IS samples of smokers when compared with those of nonsmokers.11 26 27 In the study of Schaberg et al,13 the increased expression in CD11/CD18 on AMs from smokers was found. In our analysis, the proportion of macrophages expressing CD11b, CD14, CD54, and CD71 did not differ significantly between smokers and ex-smokers with COPD.

CD11b seems to be an important agent in eosinophil activation.28 We found a slightly elevated proportion of eosinophils in current smokers, but there was no correlation with the proportion of CD11b-positive macrophages. A positive correlation between CD11b macrophages and smoking history, expressed as the number of pack-years smoked, and blood PCO2 that was observed in our study may reflect the role of this molecule in the pathogenesis of COPD in smokers. This was also a hypothesis put forward by Saetta et al.8 We found a correlation between the proportion of macrophages expressing CD14 and FVC, and between the proportion of macrophages expressing CD71 and arterial PCO2. The role of these cells in the structural changes that occur in COPD has not been elucidated. In the study of Turato et al17 on the influence of smoking cessation on cellular changes found in bronchial biopsy specimens from COPD patients, no changes in macrophage count were found.

We have not found any differences in the cellular profiles and macrophage phenotypes of patients with COPD, when comparing smokers with ex-smokers. It may be that smoking causes persistent inflammatory changes in the airways in patients who are predisposed to COPD.


   Footnotes
 
Abbreviations: AM = alveolar macrophage; BALF = BAL fluid; IS = induced sputum

Received for publication January 7, 2002. Accepted for publication October 9, 2002.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. National Institutes of Health. Global initiative for chronic obstructive lung disease. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, April 2001; Publication No. 2701
  2. Murray, RP, Anthonisen, NR, Connett, JE, et al Effects of multiple attempts to quit smoking and relapses to smoking on pulmonary function: Lung Health Study Research Group. J Clin Epidemiol 1998;51,1317-1326[CrossRef][ISI][Medline]
  3. Holz, O, Kips, J, Magnussen, H Update on sputum methodology. Eur Respir J 2000;16,355-359[Abstract]
  4. Bhowmik, A, Seemungal, TA, Sapsford, RJ, et al Comparison of spontaneous and induced sputum for investigation of airway inflammation in chronic obstructive pulmonary disease. Thorax 1998;53,953-956[Abstract/Free Full Text]
  5. Pizzichini, E, Pizzichini, MM, Efthimiadis, A, et al Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med 1996;154,308-317[Abstract]
  6. Lams, BE, Sousa, AR, Rees, PJ, et al Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;158,1518-1523[Abstract/Free Full Text]
  7. Rutgers, SR, Timens, W, Kaufmann, HF, et al Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD. Eur Respir J 2000;15,109-115[Abstract]
  8. Saetta, M, Turato, G, Maestrelli, P, et al Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163,1304-1309[Free Full Text]
  9. Stanescu, D, Sanna, A, Veriter, C, et al Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. Thorax 1996;51,267-271[Abstract]
  10. Jayaram, L, Parameswaran, K, Sears, MR, et al Induced sputum cell counts: their usefulness in clinical practice. Eur Respir J 2000;16,150-158[Abstract]
  11. Lensmar, C, Elmberger, G, Sandgren, P, et al Leukocyte counts and macrophage phenotypes in induced sputum and bronchoalveolar lavage fluid from normal subjects. Eur Respir J 1998;12,595-600[Abstract]
  12. Lohmann-Matthes, ML, Steinmuller, C, Franke-Ullmann, G Pulmonary macrophages. Eur Respir J 1994;7,1678-1689[Abstract]
  13. Schaberg, T, Klein, U, Rau, M, et al Subpopulations of alveolar macrophages in smokers and nonsmokers: relation to the expression of CD11/CD18 molecules and superoxide anion production. Am J Respir Crit Care Med 1995;151,1551-1558[Abstract]
  14. Striz, I, Costabel, U Effect of smoking on the alveolar macrophage phenotype. Am Rev Respir Dis 1993;148,1427-1428[Medline]
  15. Knudson, RJ, Slatin, RC, Lebowitz, MD, et al The maximal expiratory flow-volume curve: normal standards, variability, and effects of age. Am Rev Respir Dis 1976;113,587-600[ISI][Medline]
  16. Skold, CM, Hed, J, Eklund, A Smoking cessation rapidly reduces cell recovery in bronchoalveolar lavage fluid, while alveolar macrophage fluorescence remains high. Chest 1992;101,989-995[Abstract/Free Full Text]
  17. Turato, G, Di Stefano, A, Maestrelli, P, et al Effect of smoking cessation on airway inflammation in chronic bronchitis. Am J Respir Crit Care Med 1995;152,1262-1267[Abstract]
  18. Wright, JL, Hobson, JE, Wiggs, B, et al Airway inflammation and peribronchiolar attachments in the lungs of nonsmokers, current and ex-smokers. Lung 1988;166,277-286[ISI][Medline]
  19. Richter, K, Holz, O, Jorres, RA, et al Sequentially induced sputum in patients with asthma or chronic obstructive pulmonary disease. Eur Respir J 1999;14,697-701[Abstract]
  20. Hargreave, FE, Leigh, R Induced sputum, eosinophilic bronchitis, and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160,S53-S57[Abstract/Free Full Text]
  21. Peleman, RA, Rytila, PH, Kips, JC, et al The cellular composition of induced sputum in chronic obstructive pulmonary disease. Eur Respir J 1999;13,839-843[Abstract]
  22. Keatings, VM, Barnes, PJ Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med 1997;155,449-453[Abstract]
  23. Culpitt, SV, Maziak, W, Loukidis, S, et al Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160,1635-1639[Abstract/Free Full Text]
  24. Lebowitz, MD, Postma, DS, Burrows, B Adverse effects of eosinophilia and smoking on the natural history of newly diagnosed chronic bronchitis. Chest 1995;108,55-61[Abstract/Free Full Text]
  25. Cosio, MG, Guerassimov, A. Chronic obstructive pulmonary disease: inflammation of small airways and lung parenchyma. Am J Respir Crit Care Med 1999;160,S21-S25[Abstract/Free Full Text]
  26. Lensmar, C, Elmberger, G, Skold, M, et al Smoking alters the phenotype of macrophages in induced sputum. Respir Med 1998;92,415-420[CrossRef][ISI][Medline]
  27. Skold, CM, Lundahl, J, Hallden, G, et al Chronic smoke exposure alters the phenotype pattern and the metabolic response in human alveolar macrophages. Clin Exp Immunol 1996;106,108-113[CrossRef][ISI][Medline]
  28. in ’t Veen, JC, Grootendorst, DC, Bel, EH, et al CD11b and L-selectin expression on eosinophils and neutrophils in blood and induced sputum of patients with asthma compared with normal subjects. Clin Exp Allergy 1998;28,606-615[CrossRef][ISI][Medline]



This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
R. Chaudhuri, E. Livingston, A. D. McMahon, J. Lafferty, I. Fraser, M. Spears, C. P. McSharry, and N. C. Thomson
Effects of Smoking Cessation on Lung Function and Airway Inflammation in Smokers with Asthma
Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 127 - 133.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
R O'Donnell, D Breen, S Wilson, and R Djukanovic
Inflammatory cells in the airways in COPD
Thorax, May 1, 2006; 61(5): 448 - 454.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
E. F. M. Wouters
Local and Systemic Inflammation in Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, April 1, 2005; 2(1): 26 - 33.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
S. Hodge, G. Hodge, M. Holmes, and P. N. Reynolds
Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation
Eur. Respir. J., March 1, 2005; 25(3): 447 - 454.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
N.C. Thomson, R. Chaudhuri, and E. Livingston
Asthma and cigarette smoking
Eur. Respir. J., November 1, 2004; 24(5): 822 - 833.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
S. I. Rennard
Antiinflammatory Therapies Other Than Corticosteroids
Proceedings of the ATS, November 1, 2004; 1(3): 282 - 287.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Laan, S. Bozinovski, and G. P. Anderson
Cigarette Smoke Inhibits Lipopolysaccharide-Induced Production of Inflammatory Cytokines by Suppressing the Activation of Activator Protein-1 in Bronchial Epithelial Cells
J. Immunol., September 15, 2004; 173(6): 4164 - 4170.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
D. C. Grootendorst and K. F. Rabe
Mechanisms of Bronchial Hyperreactivity in Asthma and Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, April 1, 2004; 1(2): 77 - 87.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
D. D. Sin, F. A. McAlister, S. F. P. Man, and N. R. Anthonisen
Contemporary Management of Chronic Obstructive Pulmonary Disease: Scientific Review
JAMA, November 5, 2003; 290(17): 2301 - 2312.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (14)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Domagala-Kulawik, J.
Right arrow Articles by Chazan, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Domagala-Kulawik, J.
Right arrow Articles by Chazan, R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS