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Keywords:

  • COPD;
  • lymph node enlargement;
  • MSCT;
  • retrospective analysis

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Introduction:  To evaluate the frequency of enlarged hilar or mediastinal lymph nodes in patients suffering from chronic obstructive pulmonary disease (COPD).

Methods:  In a retrospective study, 89 patients with proven COPD were analysed. Exclusion criteria were history of malignant disease or clinical evidence of pneumonia. Prevalence, size, and localisation of enlarged lymph nodes were assessed by multi-slice computed tomography (MSCT) and correlated with the clinical stages following the GOLD classification as well as the MSCT findings of bronchitis and emphysema.

Results:  44/89 (49%) of our patients showed enlarged lymph nodes. Lymph node enlargement was more often seen in the mediastinum (48%) than the hilar region (20%). The most common localisation of enlarged mediastinal lymph nodes was the regional station 7 following the ATS mapping (infracarinal). Patients with a stage I following the GOLD classification showed enlarged lymph nodes in 49% (18/37), stage II in 46% (12/26), stage III in 58% (7/12) and stage IV in 50% (7/14). These findings did not differ significantly (P > 0.05). Severe airway wall thickening (42/89) was significantly more often associated with an increase of nodal enlargement (64%) (P < 0.05).

Conclusion:  The present study demonstrates that enlarged hilar and mediastinal lymph nodes may occur in a rather high percentage of patients suffering from COPD, especially in those with the MSCT finding of severe bronchitis.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

In the last two decades there has been an increasing interest in assessing the characteristics of chronic obstructive pulmonary disease (COPD) by use of high-resolution computed tomography (HRCT). It has already been demonstrated that HRCT is a valuable tool for evaluating the severity of COPD and that some CT findings correlate well with pulmonary function tests.1 In this setting, several CT findings have been described to be more or less specific for the presence of COPD including thickening of airway walls, low tracheal index, large sterno-aortic distance, presence of vascular distortion and mosaic pattern.2–6 Despite numerous publications dealing with this topic, no attention has been paid to the alterations of lymph nodes in COPD so far. While enlargement of lymph nodes is commonly interpreted as a sign of malignancy, it has not yet been proven how often enlarged lymph nodes may result from the chronic inflammatory processes underlying COPD. Hence, the purpose of this study was to evaluate the frequency, size, and localisation of hilar and mediastinal lymph node enlargement and to correlate these findings with the multi-slice computed tomography (MSCT) findings of COPD as well as the clinical stages following the GOLD classification.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

In a retrospective study a consecutive cohort of 89 patients suffering from COPD and undergoing MSCT within a 12-month period was analysed. All patients were examined as part of routine care. Because of the retrospective character of the investigation, the Local Ethics Committee waived the need for informed consent.

Inclusion criteria

Patients were enrolled if they showed findings of COPD in pulmonary MSCT and at least a clinical stage I following the GOLD classification.7

To avoid misinterpretation of enlarged lymph nodes due to malignancy or acute infections, patients were excluded from this evaluation if they had malignant diseases in their history or documented pneumonia with the need of antibiotic therapy within a time frame of 3 months before the examination. Other lower respiratory infections, e.g., acute bronchitis, were no criteria for exclusion. In total 89 patients (55 men, 34 women; mean age, 69 years; range, 39–94 years) were enrolled. Most of our patients belonged to stages I and II following the GOLD classification (GOLD I: 37 patients, GOLD II: 26 patients, GOLD III: 12 patients, GOLD IV: 14 patients). The majority of the enrolled patients underwent MSCT because of suspected pulmonary embolism in cases of dyspnoea (62%, 55/89).

Computed tomography acquisition and review

Multi-slice computed tomography was carried out using a Toshiba Aquilion 64 (Toshiba Medical Systems, Tokyo, Japan) or a Siemens Somatom 64 (Siemens Medical Solutions, Forchheim, Germany) CT scanner. Images were obtained in full inspiration using a 64 × 0.75 mm slice collimation with a tube voltage of 135 kV. The tube current (mA) was adjusted relative to patient attenuation by means of the Sure Exposure modus (Toshiba Medical Systems) or the Care Dose modus (Siemens Medical Solutions). The reconstruction slice thickness was 3–5 mm. During MSCT 100–120 mL of 300 mg or 400 mgI/L contrast medium (Imeron, Altana, Koblenz, Germany) were generally administered IV at a rate of 2–3 mL/s with a power injector followed by a 30-mL normal saline ‘chaser’.

Assessment of lymph nodes

Scan reading was performed consensually by two experienced radiologists. Analysis was performed in at least two reconstruction planes (usually axial and coronal reconstruction). Lymph node enlargement was defined as showing a size of more than 7–11 mm on the short axis depending on the regional nodal station.8 The enlarged lymph nodes were assessed for their density (prevalence of calcification or central low density as a sign of fatty involution), shape (oval, round) and contour (sharp, ill-defined). The localisation of the enlarged lymph nodes was documented on a standardised protocol following the regional lymph node classification of the American Thoracic Society.9

Computed tomography findings of COPD

The thickening of bronchial walls as a sign of chronic bronchitis was classified consensually by the two readers as moderate or severe compared with the representative HRCT images of airway wall thickness as published by Awadh et al.10 Vascular attenuation (thinning of pulmonary vessels and reduction in their number) and distortion (increased branching angle or straightening) were considered as signs of emphysema. We defined centrilobular emphysema as round areas of low attenuation up to 1 cm in diameter within a homogenous background of normal lung parenchyma, panlobular emphysema as large and extensive areas of uniform low attenuation.

Clinical and functional analysis

We retrospectively evaluated the patients' medical reports with regard to the indication for MSCT, underlying illnesses and results of lung function tests. The severity of COPD was graded using the GOLD classification released in the Global Initiative for Chronic Obstructive Lung Disease report7 as shown in Table 1.

Table 1.  GOLD classification of COPD severity based on Spirometry
STAGEClinic symptomsSpirometry
  1. The forced vital capacity(FVC) is the maximum volume of air which can be exhaled during a forced maneuver. The forced exspiratory volume in one second(FEV1) is the volume expired in the first second of maximal expiration after a full inspiration(useful measure of how quickly the lungs can be emptied). FEV1/ FVC, forced exspiratory volume in 1 s – vital capacity ratio expressed as percentage of predicted value(useful index of airflow limitation).

0 (at risk)Chronic cough and sputum productionnormal
I (mild)usually, but not always, chronic cough and sputum productionFEV1/FVC < 70% FEV1 ≥ 80% pred.
II (moderate)shortness of breath typically developing on exertionFEV1/FVC < 70% 50% ≤ FEV1 < 80% pred.
III (severe)increased shortness of breath, and repeated exacerbations with impact on patients' quality of lifeFEV1/FVC < 70% 30% ≤ FEV1 < 50% pred.
IV (very severe)quality of life is very appreciably impairedFEV1/FVC < 70% FEV1 < 30% pred. or FEV1 < 30% plus chronic respiratory failure

Statistical analysis

Descriptive data were presented as means with ranges, if appropriate; categoric data were given as counts and percentages. The chi-square test was used to compare the frequency of enlarged lymph nodes in different conditions (GOLD stages, bronchial wall thickening, emphysema). Statistical significance was set at a P-value of less than 0.05. Post-hoc sample size analysis was performed using the G*Power3.1 Program (Faul, Erdfelder, Lang, Buchner, Düsseldorf, Germany11). Eighty-eight patients were needed to reach an acceptable confidence level of 95% and statistical power of 80% at least.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The most common MSCT finding indicating COPD was bronchial wall thickening (69%, 61/89). Severe bronchial wall thickening was observed in 42/89 patients (47%). Lung emphysema was diagnosed in 37/89 (41%) patients. Among the subtypes of emphysema, panlobular emphysema was the most common type in 24/37 patients (65%), followed by the centriacinar type in 13/37 patients (35%). Twenty-nine of 89 patients (33%) showed both findings, advanced emphysema as well as severe bronchial wall thickening.

Lymph node enlargement

Forty-four of 89 patients (49%) showed either enlarged hilar or mediastinal lymph nodes (Fig. 1). Patients suffering from COPD stage I following the GOLD classification showed lymph node enlargement in 49% (18/37). Patients suffering from stage II showed lymph node enlargement in 46% (12/26), and suffering from stage IV in 50% (7/14). See Table 2. Patients suffering from stage III showed the highest percentage of lymph node enlargement (58%, 7/12). These differences were not statistically significant (chi-square test, P > 0.05).

image

Figure 1. Enlargement of mediastinal lymph nodes in a 74-year-old smoker (30 pack years) suffering from chronic obstructive pulmonary disease GOLD II. The frontal reconstruction shows enlarged lymph nodes (arrows) in the region 4L (short axis 11 mm, long axis 17 mm) and 7 (7/14 and 11/16). Some more not enlarged lymph nodes are visible (on the left paratracheal space and above the left main bronchius).

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Table 2.  Correlation of COPD stages, different CT findings and lymph node enlargement
GOLD stageIIIIIIIV
Patients (n)37261214
nodal enlargement (n)18 (49%)12 (46%)7 (58%)7 (50%)
CT findingmoderate bronchial wall thickeningsevere bronchial wall thickeningEmphysemaEmphysema and severe bronchial wall thickening
Patients (n)19423729
nodal enlargement (n)6 (32%)27 (64%)17 (46%)17 (59%)

In cases with moderate bronchial wall thickening (n = 19), enlarged lymph nodes were identified in 32% (6/19); 64% (27/42) of patients with severe thickening of the bronchial wall (n = 42) showed enlargement of lymph nodes. This difference was statistically significant (chi-square test, P < 0.025).

Forty-six per cent (17/37) of patients with emphysema and only moderate thickening of the bronchial wall (n = 37) revealed lymph node enlargement. The combination of emphysema and severe bronchial wall thickening resulted in nodal enlargement in 59% of patients (17/29). A statistically significant difference between those groups was not found (chi-square test, P > 0.05).

Size and localisation

In total, 948 lymph nodes were evaluated and 128/948 (14%) were found to be enlarged (Table 3). Hilar lymph node enlargement was found in 18 patients (20%); mediastinal lymph node enlargement was diagnosed in 43 patients (48%). Twenty-three (18%) enlarged hilar and 105 (82%) enlarged mediastinal lymph nodes were documented. The mean size of enlarged hilar lymph nodes was 10.4 mm (short axis) and 14.8 mm (long axis); the mean size of mediastinal lymph nodes was 11.1 mm (short axis) and 16.5 mm (long axis). The maximal size of hilar lymph nodes was 14 mm (short axis) and 22 mm (long axis). The maximal size of mediastinal lymph nodes was 22 mm (short axis) and 33 mm (long axis). The largest lymph nodes were identified in the right lower paratracheal area (regional nodal station following the ATS mapping 4R) and caudal to the carina of the trachea (regional station 7) .

Table 3.  Distribution and size of enlarged lymph nodes (following the ATS Mapping9 and recommendations of Glazer et al. regarding the threshold size for thoracic lymph node enlargement8)
ATS regionThreshold size (short axis in mm)LK < thresholdEnlarged LKShort axis average (median) (mm)Long axis average (median) (mm)Max. size short axis (mm)Max. size long axis (mm)
(n)Pat.(n)Pat.
X105027000000
2 R71427518149.6(8)15.3(14)1621
2 L78153229.5(–)17.0(–)1117
4 R109769191711.9(11)16.7(15)1430
4 L106439141210.2(10)14.7(14)1520
59835013119.6(9)13.7(13)1124
685033119(–)11(–)911
7118361332912.8(13)19.6(18)2233
8 R1028224410.8(11)13.2(13)1215
8 L722161110(–)12(–)1012
10 R1025168710.4(10)13.9(12)1320
10 L73925339.3(9)12.0(11)1014
11 R1031197710.7(10)16.3(15)1422
11 L1025195510.6(12)15.6(13)1322

The majority of both normal and enlarged lymph nodes was documented in the right upper (14%, 18/128) and lower paratracheal region (15%, 19/128) or caudal to the carina of the trachea (26%, 33/128). See Fig. 3. Enlarged lymph nodes were less frequently observed anterior to the ascending aorta (0.8%, 1/128) or the left upper paratracheal space (1.6%, 2/128). Enlargement of supraclavicular or axillar lymph nodes was not documented.

image

Figure 3. Graphic representation of the distribution of the enlarged lymph nodes in the ATS regions 2R, 2L, 4R, 4L, 5, 7, 10R, 10L, 11R and 11L; the locations of regions 6, 8R and 8L are not illustrated because they lie in front of or behind other regions in drawing.

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Other findings

Calcifications within enlarged lymph nodes were seen in 8/89 (9%) patients. A central low density as a sign of fatty involution (Fig. 2) was seen in 5/128 (4%) enlarged lymph nodes, but these patients showed further enlarged lymph nodes too. All enlarged lymph nodes had a well-defined contour; any conglomeration of enlarged lymph nodes was not found. The majority of the enlarged lymph nodes showed an oval shape (111/128, 87%). The 17 enlarged lymph nodes with a round shape did not show any preference regarding their localisation.

image

Figure 2. Enlarged lymph node (arrow) in the region 4R (same patient as Fig. 1). The frontal reconstruction clearly depicts lymph node enlargement (13 mm short axis, 23 mm long axis) and central low density as a sign of fatty involution.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

In the clinical literature, many studies have already demonstrated the coherent appearance of malignancy and enlarged lymph nodes in CT.12,13 Nevertheless, thoracic lymph node enlargement can also be found in multiple benign conditions such as granulomatous disease,14 pneumoconiosis15 or even heart failure.16 To the best of our knowledge, this study seems to be the first dealing with the findings of enlarged lymph nodes in patients with COPD. Our study suggests that chronic bronchitis is often associated with an enlargement of mediastinal lymph nodes.

The definition of lymph node enlargement in clinical practice is not standardised. Rounded off cut-offs (10 mm short axis for all localisations and 15 mm for station 7) are most often used. Because often normal nodes are smaller, particularly in the upper paratracheal region, we have used lymph node criteria as published by Glazer et al.8 The authors intended to obtain a better specificity if size thresholds were established for specific mediastinal lymph node regions and introduced different short axis criteria for different ATS stations.

Enlarged lymph nodes in COPD are very often located in the surrounding of the carina and the aorto-pulmonary window. It seems that enlargement of hilar lymph nodes less frequently occurs.

Our study demonstrates that enlarged lymph nodes are more often identified in patients with signs of severe bronchitis. This seems to be logical because the inflammatory processes as seen in chronic bronchitis might result in both remodelling and narrowing of airways and reactive nodal enlargement. Nevertheless, our study could not demonstrate a significant correlation between the degree of COPD according to GOLD stages and the extent of nodal enlargement. Perhaps this observation contributes to the well-known problems with staging of COPD by the GOLD classification which is only based on the severity of airflow obstruction.17,18 Because the airflow limitation is caused by both airway disease and parenchymal destruction (emphysema), the similar GOLD stage may describe very different degrees of bronchial inflammatory activity (the presumed cause of reactive nodal enlargement).

It has been demonstrated that it is not possible to differentiate between malignant and benign lymph node enlargement reliably by size19–22 and that the likelihood of metastases increases with the lymph node size.23 Nevertheless, some of our patients showed lymph nodes larger than 20 mm in the short axis with a maximum of 22 mm in the short axis and 33 mm in the long axis; these sizes would have increased the threshold suggested as the upper limit for normal lymph nodes.

Neither calcification nor central low attenuation of enlarged lymph nodes was seen in a high percentage of our patients; therefore, the absence of such findings is not a reliable sign of potential malignancy. Lymph node shape cannot be used to differentiate benign from malignant nodes, although the most nodes seen in our study were oval.

There were some limitations to our study. First, owing to the relative small number of patients, we do not know whether the rather untypical distribution of enlarged lymph nodes might be a diagnostic clue to differentiate this benign cause from systemic lymphoma or other malignant genesis.

Second, the findings of enlarged benign lymph nodes were not proven by a gold standard such as histological examination. Because of the study design (no evidence for malignancy) there was no indication for performing invasive investigations. Nevertheless, a correlation with PET might have been helpful in our series. Follow-up studies using gadolinium enhanced MRI or PET-CT might be useful in validating the results of our study.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The results of our study demonstrate that enlarged hilar and mediastinal lymph nodes are a common finding in patients suffering from COPD. The lymph nodes are predominantly located in the lower paratracheal space, the aorto-pulmonary window and below the carina. Radiologists should be aware of the presence of such enlarged lymph nodes, especially in cancer patients, because those entities may result from chronic airway inflammation in COPD.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References
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