Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart
  • Log out

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions

Predominant emphysema phenotype in chronic obstructive pulmonary disease patients

P. Boschetto, M. Miniati, D. Miotto, F. Braccioni, E. De Rosa, I. Bononi, A. Papi, M. Saetta, L.M. Fabbri, C.E. Mapp
European Respiratory Journal 2003 21: 450-454; DOI: 10.1183/09031936.03.00048703
P. Boschetto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Miniati
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D. Miotto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F. Braccioni
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E. De Rosa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
I. Bononi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Papi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Saetta
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L.M. Fabbri
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C.E. Mapp
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Patients with fixed airflow limitation are grouped under the heading of chronic obstructive pulmonary disease (COPD). The authors investigated whether COPD patients have distinct functional, radiological and sputum cells characteristics depending on the presence or absence of emphysema.

Twenty-four COPD outpatients, 12 with and 12 without emphysema on high-resolution computed tomography scan of the chest, were examined. Patients underwent chest radiography, pulmonary function tests and sputum induction and analysis.

Subjects with documented emphysema had lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio, and lower carbon monoxide diffusion constant (KCO), compared with subjects without emphysema. Chest radiograph score of emphysema was higher, chest radiograph score of chronic bronchitis was lower, and the number of sputum lymphocytes was increased in patients with emphysema, who also showed a negative correlation between KCO and pack-yrs.

Chronic obstructive pulmonary disease patients with emphysema, documented by high-resolution computed tomography scan, have a different disease phenotype compared with patients without emphysema. Identification of chronic obstructive pulmonary disease-related phenotypes may improve understanding of the natural history and treatment of the disease.

  • chronic obstructive pulmonary disease
  • computed tomography
  • emphysema

This study was supported by the Italian Ministry of University and Research Consorzio Ferrararicherche.

Chronic obstructive pulmonary disease (COPD) is characterised by the progressive development of airflow limitation that is not fully reversible 1. Chronic airflow limitation is caused by a mixture of small airways inflammatory disease, obstructive bronchiolitis and parenchymal destruction, and emphysema, the relative contributions of which vary from person to person 2.

Chronic inflammation causes remodelling and narrowing of the small airways and, theoretically, it responds to pharmacological treatment. Destruction of the lung parenchyma leads to the loss of alveolar attachments to the small airways and decreases lung elastic recoil. These changes, which are considered to be unresponsive to pharmacological treatment, diminish the ability of the airways to remain open during expiration.

COPD has a variable natural history and not all individuals follow the same course and have the same response to therapy. Patients with emphysema have the lowest survival rate and the highest rate of decline in pulmonary function among COPD patients 3. Thus, it is clinically relevant to detect, in the diagnostic work-up of patients with COPD, individuals with emphysema, possibly by using noninvasive methods. Although it has become increasingly clear that lung computed tomography (CT), especially when performed with thin-section, high-resolution techniques, is the most accurate imaging method for detecting the extent and severity of emphysema 4, lung function and chest radiography are invariably obtained in the clinical assessment of COPD. Recently, the application of sputum induction and refined methods of sputum examination have provided the opportunity to examine cell and molecular markers of airway inflammation in COPD 5, contributing to the characterisation of lung inflammation in the disease 6, 7.

The aim of this study was to investigate, by using classical diagnostic tests, such as lung function tests, radiological examination and sputum analysis, whether COPD patients with documented emphysema at high-resolution computed tomography (HRCT) of the chest have a different disease phenotype compared with COPD patients without emphysema.

Subjects and methods

Subjects

COPD patients (n=24) with fixed airflow limitation, i.e. forced expiratory volume in one second (FEV1) <70% of predicted values and FEV1/forced vital capacity (FVC) ratio <70%, were examined both before and after 200 µg of inhaled salbutamol (table 1⇓). Chronic bronchitis was defined as cough and sputum production occurring on most days of the month for at least 3 months per year, during the 2 yrs before the study 2. All subjects were recruited from the outpatient clinic of the Section of Respiratory Diseases of the University of Ferrara, Ferrara, Italy. The Ethics Committee of the University Hospital of Ferrara approved the study and all patients gave their written informed consent. COPD was diagnosed according to the criteria recommended by the European Respiratory Society 8. All patients were in stable conditions at the time of the study and free from acute exacerbations of symptoms and upper respiratory tract infections in the 2 months preceding the study.

View this table:
  • View inline
  • View popup
Table 1

Characteristics of the chronic obstructive pulmonary disease (COPD) patients divided according to the presence or absence of emphysema on high-resolution computed tomography examination#

Study design

Emphysema was characterised using HRCT technique and a visual score >10 indicated emphysema 9. Each patient underwent medical history, physical examination, pulmonary function tests, chest radiography, CT, skin-prick tests, induced sputum, and α1-antitrypsin measurement, since three of the patients were nonsmokers.

Pulmonary function studies

In each patient, lung volumes (Biomedin, Padova, Italy), the carbon monoxide diffusion constant (KCO), by the single-breath technique, end-exhaled nitric oxide (NO) (Nitric oxide A 280 analyser; Sievers, Boulder, CO, USA), arterial oxygen (Pa,O2) and carbon dioxide tension (Pa,CO2) (Instrumentations Laboratories, Milan, Italy) were measured as described previously 8, according to published guidelines 10–12.

Chest radiography

Chest radiographs (postero-anterior and lateral) were obtained with the patients in an upright position, holding their breath at full inspiration. A standard 2 m focus-to-film distance was used. Exposure time was kept as short as possible to reduce motion blurring and was usually within 0.05 s. A fine lead grid (grid ratio 6) was used to reduce scattered X‐rays, thereby enhancing film resolution. Chest radiographs were obtained within 48 h of pulmonary function studies and prior to the sputum inductions. Chronic bronchitis and emphysema scores, ranging 0–16, were calculated as described previously 9, 13. Emphysema and chronic bronchitis scores have proved highly reproducible among different observers 9, 13.

Computed tomography

HRCT scans were performed at suspended full inspiration on a TOMOS 7000 scanner (Philips, Einthoven, The Netherlands), as described previously 9. No contrast medium was infused. Technical parameters were 1 mm collimation, 120 kV peak, 160 mA, and 3‐s scanning time. A visual score of emphysema was derived according to the method of Sakai et al. 14 and a cumulative score of emphysema, ranging 0–72 was obtained, as described previously 9.

Induced sputum

Sputum was collected after bronchodilator inhalation and analysed as described previously 8. To make the procedure safer, sputum was induced and spirometric measurements were performed as reported previously 15. Increasing concentrations of hypertonic saline were nebulised with an ultrasonic nebuliser (Mistogen EN 145 electronic nebuliser; Mistogen Equipment Co., Oakland, CA, USA).

Atopic status

Skin-prick tests to 12 common aeroallergens were performed according to a standard protocol 8.

α1-antitrypsin

A peripheral blood sample was drawn and the serum was separated. Antibodies against human α1-antitrypsin were added to the serum and the intensity of the light diffused by suspended particles, resulting from the formation of the antigen/antibody complex, was measured with a nephelometric method (Beckman Instruments, Milan, Italy).

Statistical analysis

Group data are expressed as mean±sem or as median and interquartile range when appropriate. Differences between groups were analysed using the Mann-Whitney U‐test and Bonferroni's correction was applied when indicated. Categorical values were analysed using Fisher's exact test. Spearman's rank correlation test was used to examine the association between lung and radiological data and cigarette smoking and/or sputum cells. To define the predictive value of the variables analysed, receiver-operating characteristic (ROC) curve analysis was performed for a comparison of ranked variables. The area under the ROC curves was determined and a value of >0.80 was accepted as indicating good discrimination 16. ROC curve analysis also allowed selection of the best cut-off point of the variables studied by analysing their sensitivity versus one minus specificity. A p‐value of <0.05 was accepted as significant.

Results

Clinical findings

Table 1⇑ shows the characteristics of the subjects examined. There was no significant difference in age, smoking history and body mass index between COPD patients with emphysema and patients with no emphysema. In all subjects, α1-antitrypsin values were within the normal range (83–199 mg·dL−1). Dyspnoea, graded according to the Medical Research Council dyspnoea scale 17, was mild and similar in the two groups. Three of the 12 COPD patients with and eight of the 12 without emphysema had symptoms of chronic bronchitis.

Pulmonary function findings

There was no significant difference in total lung capacity (TLC; % pred), exhaled NO, arterial blood gases and response to inhaled salbutamol between the COPD patients with and without emphysema (table 1⇑). Emphysema patients had a significantly lower FEV1 (% pred), FEV1/FVC ratio (%) and KCO (% pred) than patients with no emphysema. For similar values of TLC in the two groups, inspiratory capacity (IC; % pred) was significantly lower, whereas functional residual capacity (FRC; % pred) was significantly higher in COPD patients with emphysema, indicating greater pulmonary hyperinflation. Residual volume (RV; % pred) was higher (p=0.09) in the emphysema group. In this group, a negative correlation was found between KCO and cigarettes smoked (r=−0.83; p<0.01).

Chest radiography

As expected from the selection criteria, COPD patients with emphysema had a significantly higher chest radiograph score of emphysema (7.5 (4.5–10) versus 2 (0.5–3), p<0.001; fig. 1⇓) and a lower chest radiograph score of chronic bronchitis (3 (2–5.5) versus 6 (5.5–5.7); p<0.005; fig. 1⇓) than patients with no emphysema.

Fig. 1.—
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig. 1.—

Chest radiograph scores of emphysema (•) and chronic bronchitis (○) in chronic obstructive pulmonary disease patients, divided according to the presence or absence of emphysema. The horizontal solid bars indicate the median values for each group. ***: p<0.001; #: p<0.005.

Sputum findings

Patients with emphysema had more sputum lymphocytes than patients with no emphysema. No other significant differences were observed (table 2⇓). When all COPD patients were considered together, sputum lymphocytes correlated negatively with IC % pred (r=−0.46, p<0.05) and positively, albeit not to a significant extent, with the HRCT score of emphysema (r=0.40, p=0.06). In emphysematous patients, a positive correlation was found between the HRCT score of emphysema and sputum neutrophils (r=0.60, p<0.05; fig. 2⇓).

Fig. 2.—
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig. 2.—

Relationship between high-resolution computed tomography (HRCT) score of emphysema and percentage of sputum neutrophils (Spearman's rank correlation: p<0.05, r=0.60) in chronic obstructive pulmonary disease patients with emphysema.

View this table:
  • View inline
  • View popup
Table 2

Sputum cells in chronic obstructive pulmonary disease (COPD) patients divided according to the presence or absence of emphysema on high-resolution computed tomography examination

Receiver-operating characteristic curve analysis

FEV1, chest radiograph score of emphysema and sputum lymphocytes were shown to be the best predictive factors of emphysema. For FEV1 % pred, the area under the ROC curves was 0.89, for emphysema score it was 0.90, and for the percentage of lymphocytes in sputum it was 0.81. For FEV1 % pred, the best cut-off point was 49% pred, which had a sensitivity of 0.83 and a specificity of 0.83. For the chest radiograph score of emphysema, the best cut-off point was 4.0, which had a sensitivity of 0.75 and a specificity of 0.80. For sputum lymphocytes, the best cut-off point was 1%, which had a sensitivity of 0.67 and a specificity of 0.83.

Discussion

In this study, the authors have shown that patients with fixed airflow limitation (COPD) have a different disease phenotype, depending on the presence or absence of emphysema on chest HRCT. Patients were selected on the basis of functional criteria, i.e. FEV1 <70% pred and FEV1/FVC ratio <70% both before and after inhaled bronchodilator. These inclusion criteria were used as they define most of the COPD patients involved. COPD subjects with emphysema had lower FEV1, lower FEV1/FVC ratio, lower KCO, higher chest radiograph scores of emphysema, lower chest radiograph scores of chronic bronchitis, and an increased number of lymphocytes in induced sputum.

These findings of a higher degree of airflow obstruction in patients with emphysema are in agreement with the results of previous studies that focused on the relationship between severity and extent of emphysema and lung function data 18–22. By contrast, these findings may appear to conflict with those of Fletcher et al. 23, who found no differences in clinical and lung function features between emphysema and chronic bronchitis patients. However, they examined a different population: patients were younger, 20% exhibited reversible airflow limitation after inhaled bronchodilator, and the majority had a history of wheezing.

In the present study, a reduction in KCO was found in COPD patients with emphysema. The reduction of CO diffusing capacity is a physiological abnormality known to be associated with pulmonary emphysema, and it has been shown to correlate with the extent of emphysema 24. In emphysematous patients, a negative correlation between KCO and pack-yrs was also observed, which supports and extends the findings of other studies 25, 26 that have shown a negative correlation between lung function and pack-yrs even in asymptomatic subjects 26. The emphysematous subjects in this study exhibited baseline values of IC and FRC smaller and greater, respectively, than those of patients with no emphysema. As baseline TLC was not different between the two groups, these data reflect a greater pulmonary hyperinflation in emphysematous patients. In these patients, RV and TLC were higher, but not significantly so, thus indicating that subjects with emphysema do not have a pure emphysema phenotype and, therefore, lack the fairly uniform pattern of abnormal pulmonary function tests characteristic of emphysema. The lack of significant differences in these variables, however, does not exclude meaningful differences.

In the present COPD patients, the distinction between emphysema and no emphysema on the HRCT was based on a cut-off of 10 of the applied visual score, which ranged from 0–72. According to previous findings 9, the authors were confident that an HRCT score of emphysema that did not exceed 14% of the maximal score obtainable, was compatible with no or with only trivial emphysema.

With regard to imaging tests, it has been demonstrated that conventional chest radiography is useful in the clinical evaluation of emphysema 9. The fact that, in this study, a higher chest radiograph score of emphysema and a lower score of chronic bronchitis were present in patients with emphysema, confirms that this examination is useful to discriminate the two phenotypes, i.e. emphysema and no emphysema. When all the patients were considered together, chest radiograph scores of chronic bronchitis showed a negative correlation with the HRCT emphysema score (data not shown), suggesting that the features of bronchial and/or bronchiolar inflammation are predominant in patients with no emphysema. In this study, symptoms of chronic bronchitis were present in the majority of patients without emphysema, but only in three subjects with emphysema, confirming that hypersecretion of mucus is present more in patients with no or trivial emphysema 22. Three subjects without emphysema on HRCT scan and without symptoms of chronic bronchitis were also observed. These subjects had a high radiograph score of chronic bronchitis, 6.5, 5.5 and 8.5 (scores ranging 1.5–8.5), suggesting that chest radiography detects bronchial and/or bronchiolar inflammation better than the symptoms. Another possible explanation for this lack of relationship between symptoms and chest radiograph is a different time course for the two events, with early radiological changes later followed by symptoms.

This study, using induced sputum, demonstrated a slight but significant increase in the number of sputum lymphocytes in patients with emphysema. No differences were observed in other sputum inflammatory cells, supporting the evidence that these patients did not have a pure component of lung parenchymal destruction, i.e. a pure emphysema phenotype, and also an airway inflammatory component. Lymphocytes, particularly CD8+ cytolytic T‐cells, have been recognised recently as the predominant cells in the alveolar wall of smokers with emphysema 27. The results, obtained by a noninvasive method, such as sputum induction, confirm this finding. Moreover, a negative correlation was found between sputum lymphocytes and IC, which typically decreases in emphysema due to pulmonary hyperinflation. Taken together, all the above data suggest that lymphocytes are the inflammatory cells best associated with emphysema and they may be obtained by sputum induction. Therefore, it could be useful to introduce this noninvasive method into the regular work-up of COPD patients, given that it is also simple and safe 28. Finally, regarding sputum differential cell counts, it should also be noted that there was a correlation between the HRCT score of emphysema and the number of neutrophils. This finding seems to support the hypothesis that neutrophils are implicated in the severe stage of COPD, as other studies have also suggested 29, 30.

Although in COPD patients the two components of airflow limitation, small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), often coexist, it could be clinically relevant to distinguish subjects with predominant emphysema phenotype.

In conclusion, the authors showed that forced expiratory volume in one second, chest radiograph score of emphysema and sputum lymphocytes are the three indices that better distinguish emphysema from nonemphysema patients. Such distinction could be useful in clinical practice, may improve understanding of the natural history of the disease, and may help to focus treatment strategies for different chronic obstructive pulmonary disease phenotypes, as, for example, the more the lung destructive component is widespread, the less anti-inflammatory drugs are expected to be of benefit.

Acknowledgments

The authors would like to thank G. Caramori, C. Piola, A. Potena and L. Ballarin for their expert collaboration, A. Rambaldi and E. Forini for helping in the statistical analysis and O. Di Maria for technical assistance.

  • Received June 6, 2002.
  • Accepted November 20, 2002.
  • © ERS Journals Ltd

References

  1. ↵
    American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:S77–S121.
  2. ↵
    Pauwels RA, Buist AS Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001;163:1256–1276.
    OpenUrlCrossRefPubMed
  3. ↵
    Burrows B, Bloom JW, Traver GA, Cline MG. The course and prognosis of different forms of chronic airways obstruction in a sample from the general population. N Engl J Med 1987;317:1309–1314.
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    Thurlbeck WM, Muller NL. Emphysema: definition, imaging, and quantification. AJR Am J Roentgenol 1994;163:1017–1025.
    OpenUrlPubMedWeb of Science
  5. ↵
    Peleman RA, Rytila PH, Kips JC, Joos GF, Pauwels RA. The cellular composition of induced sputum in chronic obstructive pulmonary disease. Eur Respir J 1999;13:839–843.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med 2000;343:269–280.
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    Papi A, Romagnoli M, Baraldo S, et al. Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1773–1777.
    OpenUrlCrossRefPubMedWeb of Science
  8. ↵
    Siafakas NM, Vermeire P, Pride NB, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J 1995;8:1398–1420.
    OpenUrlFREE Full Text
  9. ↵
    Miniati M, Filippi E, Falaschi F, et al. Radiologic evaluation of emphysema in patients with chronic obstructive pulmonary disease. Chest radiography versus high resolution computed tomography. Am J Respir Crit Care Med 1995;151:1359–1367.
    OpenUrlPubMedWeb of Science
  10. ↵
    Quanjer PhH, Tammeling GJ, Cotes JE, Pederson OF, Peslin R, Yernault J‐C. Lung volumes and forced ventilatory flows. Eur Respir J 1993;6:Suppl. 16, 5–40.
    OpenUrlFREE Full Text
  11. Cotes JE, Chinn DJ, Quanjer PhH, Roca J, Yernault J‐C. Standardization of the measurement of transfer factor (diffusing capacity). Eur Respir J 1993;6:Suppl. 16, 41–52.
  12. ↵
    Kharitonov S, Alving K, Barnes PJ. Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. Eur Respir J 1997;10:1683–1693.
    OpenUrlCrossRefPubMedWeb of Science
  13. ↵
    Milne ENC, Pistolesi M.. Detecting and quantifying chronic bronchitis and emphysemaIn: Milne ENC, Pistolesi M, editors. Reading the Chest Radiograph. A Physiologic ApproachMosby, St. Louis, 1993; pp. 267–310.
  14. ↵
    Sakai F, Gamsu G, Im JG, Ray CS. Pulmonary function abnormalities in patients with CT-determined emphysema. J Comput Assist Tomogr 1987;11:963–968.
    OpenUrlPubMedWeb of Science
  15. ↵
    Rytila PH, Lindqvist AE, Laitinen LA. Safety of sputum induction in chronic obstructive pulmonary disease. Eur Respir J 2000;15:1116–1119.
    OpenUrlAbstract
  16. ↵
    Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143:29–36.
    OpenUrlPubMedWeb of Science
  17. ↵
    Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581–586.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Coxson HO, Rogers RM, Whittall KP, et al. A quantification of the lung surface area in emphysema using computed tomography. Am J Respir Crit Care Med 1999;159:851–856.
    OpenUrlCrossRefPubMedWeb of Science
  19. Park KJ, Bergin CJ, Clausen JL. Quantitation of emphysema with three-dimensional CT densitometry: comparison with two-dimensional analysis, visual emphysema scores, and pulmonary function test results. Radiology 1999;211:541–547.
    OpenUrlCrossRefPubMedWeb of Science
  20. Burrows B, Fletcher CM, Heard BE, Jones NL, Wootliff JS. The emphysematous and bronchial types of chronic airways obstruction. A clinicopathological study of patients in London and Chicago. Lancet 1966;1:830–835.
    OpenUrlPubMedWeb of Science
  21. Zompatori M, Fasano L, Battista G, Pacilli AM, Stopazzoni C, Cavina M. Role of emphysema in the etiology of functional impairment in patients with severe chronic obstructive pulmonary disease. Study with high resolution computerized tomography. Radiol Med (Turin) 1999;97:26–32.
    OpenUrl
  22. ↵
    Mitchell RS, Stanford RE, Johnson JM, Silvers GW, Dart G, George MS. The morphologic features of the bronchi, bronchioles, and alveoli in chronic airway obstruction: a clinicopathologic study. Am Rev Respir Dis 1976;114:137–145.
    OpenUrlPubMedWeb of Science
  23. ↵
    Fletcher CM, Jones NL, Burrows B, Niden AH. American emphysema and British bronchitis. A standardized comparative study. Am Rev Respir Dis 1964;90:1–13.
  24. ↵
    Baldi S, Miniati M, Bellina CR, et al. Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164:585–589.
    OpenUrlPubMedWeb of Science
  25. ↵
    Enright PL. Smoking, lung function, and atherosclerosis in the 5,000 elderly participants of the Cardiovascular Health Study. Am J Geriatr Cardiol 1994;3:35–38.
    OpenUrlPubMed
  26. ↵
    Burrows B, Knudson RJ, Cline MG, Lebowitz MD. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 1977;115:195–205.
    OpenUrlPubMedWeb of Science
  27. ↵
    Majo J, Ghezzo H, Cosio MG. Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema. Eur Respir J 2001;17:946–953.
    OpenUrlAbstract/FREE Full Text
  28. ↵
    Pizzichini E, Pizzichini MMM, Leigh R, Djukanovic R, Sterk PJ. Safety of sputum induction. Eur Respir J 2002;20:Suppl. 37, 9s–18s.
    OpenUrl
  29. ↵
    Retamales I, Elliott WM, Meshi B, et al. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med 2001;164:469–473.
    OpenUrlCrossRefPubMedWeb of Science
  30. ↵
    Di Stefano A, Capelli A, Lusuardi M, et al. Severity of airflow limitation is associated with severity of airway inflammation in smokers. Am J Respir Crit Care Med 1998;158:1277–1285.
    OpenUrlCrossRefPubMedWeb of Science
View Abstract
PreviousNext
Back to top
View this article with LENS
Vol 21 Issue 3 Table of Contents
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Predominant emphysema phenotype in chronic obstructive pulmonary disease patients
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Predominant emphysema phenotype in chronic obstructive pulmonary disease patients
P. Boschetto, M. Miniati, D. Miotto, F. Braccioni, E. De Rosa, I. Bononi, A. Papi, M. Saetta, L.M. Fabbri, C.E. Mapp
European Respiratory Journal Mar 2003, 21 (3) 450-454; DOI: 10.1183/09031936.03.00048703

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Predominant emphysema phenotype in chronic obstructive pulmonary disease patients
P. Boschetto, M. Miniati, D. Miotto, F. Braccioni, E. De Rosa, I. Bononi, A. Papi, M. Saetta, L.M. Fabbri, C.E. Mapp
European Respiratory Journal Mar 2003, 21 (3) 450-454; DOI: 10.1183/09031936.03.00048703
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Subjects and methods
    • Results
    • Discussion
    • Acknowledgments
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Exacerbations in α1-antitrypsin deficiency
  • Imbalance between vascular endothelial growth factor and endostatin in emphysema
  • Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema
Show more Original Articles: Emphysema

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society