DYPJHS Volume 2, Issue 1 : Jan-Mar. 2014 D Y Patil Journal of Health Sciences

ISSN (Print) 2347-3665 ISSN (Online) 2347-8020

RESEARCH PAPER

COPD Phenotypes According to HRCT Findings Umang Shah*, Jayalakshmi T. K., Lavina Mirchandani, Aparna Iyer, Abhay Uppe and Girija Nair

Key words : HRCT, Pulmonary function test, Chronic Obstructive Pulmonary Disease, Emphysema, Bronchial wall thickening, Bronchiectasis.

Abstract Background High Resolution Computed Tomography Scan (HRCT) is now being used as an important diagnostic test in COPD patients. Various new patterns like emphysema (centriacinar, panacinar, and paraseptal) bronchial wall thickening, bronchiectasis, bullous disease, pulmonary hypertension and other vascular changes are being identified in these patients.

Introduction

Methods

The GOLD guidelines define COPD as a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases resulting in dyspnoea, exercise limitation and pulmonary arterial hypertension.[1] COPD shows pathological changes in lung parenchyma, central and peripheral airways and pulmonary vessels.[2]

50 patients (42 males and 8 females) of stable COPD attending a tertiary referral hospital were included. According to HRCT findings, 3 predominant patterns were identified as Emphysema, Bronchial wall thickening and Bronchiectasis. This was correlated with smoking status, Body Mass Index, 6 min walk test (6MWT), frequency of exacerbations, and spirometry parameters including bronchodilator reversibility.

However, relative contribution of small airway, large airway changes and emphysema towards lung function abnormality and clinical features vary in different individuals. Some patients have more severe emphysema without bronchial wall thickening.[3]

Objectives In this present study, we have evaluated various HRCT features to identify morphological patterns in COPD and correlated the same with clinical features.

Results

On the other hand some patients have no significant emphysema on HRCT but do show severe airflow limitation. Clinically, some patient shows partial reversibility to bronchodilators. There is also variability in 6MWT. So our hypothesis was that these different clinical features of COPD may be associated with different morphological features of HRCT.

COPD patients with Emphysema phenotype on HRCT were more severely affected i.e. they had severe COPD as per GOLD guidelines (55%) with lower (<250m) 6MWT values (55%) and poor bronchodilator reversibility (82.50%) on spirometry. 52% COPD patients with bronchial wall thickening phenotype predominantly had severe COPD as per GOLD guidelines with lower (<250m) 6MWT values (72.22%) and poor bronchodilator reversibility (63.88%) on spirometry.

To clarify this hypothesis, we classified COPD into three phenotypes according to presence of emphysema, bronchial wall thickening and bronchiectasis and correlated these 3 phenotypes with various parameters including sex, body mass index (BMI), severity of COPD according to spirometry, smoking status, bronchodilator reversibility, exacerbations, and 6 MWT values.

52% COPD patients with bronchiectasis phenotype predominantly had moderate COPD as per GOLD guidelines. They had better (>250m) 6MWT values (73.68%) with good bronchodilator reversibility (68.42%) on spirometry. However, these patients had higher frequency of infective exacerbation compared with other two groups (52.63%). Conclusion Morphological phenotypes as assessed by HRCT scan may help in identifying patients who will benefit from bronchodilator treatment and can also help to predict different clinical features such as 6 min walk test values, BMI, bronchodilator reversibility and severity of COPD.

Material and Methods 50 stable COPD patients attended pulmonary medicine outpatient department at our tertiary care hospital were included in the study. Patients were included after having written informed consent. They were evaluated with clinical

*Corresponding author: Umang Shah, E-mail: [email protected] Department of Pulmonary Medicine, Critical Care and Sleep Medicine, Padmashree Dr. D Y Patil Medical College, Hospital & Research Center, Padmashree Dr. D Y Patil University, Navi Mumbai - 400 706.

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history and physical examination, HRCT (Thorax), spirometry (pre and post bronchodilator), 6 min walk test and BMI (body mass index).

more than 50% of patients showing poor post bronchodilator reversibility in this group. More than 50% of patients with emphysema had poor (< 250m) 6 MWT values.

Inclusion Criteria

In also Bronchial wall thickening phenotype group, only 2 (5%) patients had mild COPD, 15 (41%) patients had moderate COPD and 19 (52%) patients had severe COPD with more than 50% of patients showing poor post bronchodilator reversibility in this group. More than 50% of patients with bronchial wall thickening had poor (<250m) 6MWT values.

All Patients with age more than 18 years diagnosed with COPD on medical management with history of cough and expectoration of at least 3 months duration in 2 consecutive years, history of breathlessness of long standing duration with or without cough with smoking or Chula exposure and other features consistent with COPD.

In Bronchiectasis phenotype group, only 2 (10%) patients had mild COPD, 10 (52%) patients had moderate COPD and 07 (36.84%) patients had severe COPD suggesting that lung function was better preserved in this group. These patients had better BMI (31.57%) compared to other two groups, and had fewer (36. 84%) patients of severe COPD. Patients also had better bronchodilator reversibility (68.42%) but had more frequency of exacerbations. Patients also had better (>250m) 6MWT values compared with other 2 groups.

Exclusion Criteria History of Chronic lung disease other than COPD, Pulmonary TB, Interstitial lung disease, Bronchial asthma. Any primary cardiac disease and patients with Acute Exacerbation of COPD in last 3 months, Myocardial Infarction in previously 3 months and who are unable to perform Spirometry (Pulmonary Function Test) or patients not willing for investigations.

Patients with emphysema and bronchial wall thickening had more severe COPD (moderate to severe COPD) when compared with patients with bronchiectasis. Infective exacerbations were most frequent in bronchiectasis subgroup. Patients with bronchial wall thickening showed least distance covered in 6MWT compared with other two subgroups.

Results 50 patients with stable COPD were classified into 3 phenotypes according to HRCT findings. All 42 males patients included in this study were smokers and the 8 females were exposed to chulla smoke at some point. In Emphysema phenotype group, only 2 (5%) patients had mild COPD, 16 (40%) patients had moderate COPD and 22 (55%) patients had severe COPD suggesting that patients in this subtype had more severe COPD compared to other groups with

Significant bronchodilator reversibility was seen more in subgroup with bronchiectasis 13/19 (68.42%) than in groups with emphysema and bronchial wall thickening.

Table 1 : Clinical Comparison in patients with demonstrable presence of CT scan evidence of Emphysema, Bronchial wall thickening or Bronchiectasis Emphysema (N = 40) (%)

Bronchial wall thickening (N = 36) (%)

Bronchiectasis (N = 19) (%)

Male (N = 42)

34/40 (85)

32/36 (88.88)

13/19 (68.42)

Female (N = 8)

06/40 (15)

04/36 (11.11)

06/19 (31.57)

BMI > 20

07/40 (17.5)

06/36 (16.66)

06/19 (31.57)

BMI < 20

33/40 (82.5)

30/36 (83.33)

13/19 (68.42)

Mild COPD (N = 2)

02/40 (5)

02/36 (5)

02/19 (10)

Moderate COPD (N = 18)

16/40 (40)

15/36 (41)

10/19 (52)

Severe COPD (N = 30)

22/40 (55)

19/36 (52)

07/19 (36.84)

Smoking (N = 42)

34/40 (85)

32/36 (88.88)

13/19 (68.42)

15/40 (37.5)

15/36 (41.66)

10/19 (52.63)

6 MWT > 250

18/40 (45)

13/36 (36.11)

14/19 (73.68)

6 MWT < 250

22/40 (55)

26/36 (72.22)

05/19 (26.31)

Exacerbations (N = 20)

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Table 2 : Spirometry comparison in patients with demonstrable presence of CT scan evidence of Emphysema, Bronchial wall thickening or Bronchiectasis Emphysema (N = 40)

Bronchial wall thickening (N = 36)

Bronchiectasis (N = 19)

FEV1

41.08

40.30

44.40

FVC

86.40

89.47

87.37

FEV1 / FVC

47.54

45.04

50.81

Reversibility > 12%

07/40 (17.50 %)

13/36 (36.11 %)

13/19 (68.42 %)

Reversibility < 12%

33/40 (82.50 %)

23/36 (63.88 %)

06/19 (31.57 %)

Figure 1. Relative proportion of Mild, Moderate and Severe COPD

60% 50%

Emphysema (N = 40) (%)

40%

Bronchial wall thickening (N = 36) (%)

30%

Bronchiectasis (N = 19) (%)

20% 10% 0% Mild COPD (N = 2)

Moderate COPD (N = 18)

Severe COPD (N = 30)

Table 3 : Analysis of HRCT findings HRCT Findings

Figure 2. HRCT axial scan showing directly visible small airways as air filled ring like structures. No. of cases (n=50)

Directly visible small airways

36 (72%)

Centriacinar emphysema

16 (32%)

Panacinar emphysema

11 (22%)

Paraseptal emphysema

13 (26%)

Any type of emphysema / Bullae

11 (22%)

Bronchiectasis

19 (38%)

Among the three types of emphysema, centriacinar emphysema was observed most frequently (16 patients, 40%) (Figure 3), followed by distal acinar (13 patients, 32.5%) (Figure 2) and panacinar emphysema (11 patients, 27.5%) (Figure 4). Twentyfive (62.5%) patients had at least one type of emphysema (Figure 5).

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Figure 3. HRCT scan in patients with centriacinar emphysema showing multiple, round lucent regions of various sizes surrounded by normal parenchyma.

Discussion COPD is a disease state characterised by airflow limitation that is not fully reversible to bronchodilators. However degree of reversibility varies among individuals. It has been shown that in patients with COPD, airway eosinophilia is related to reversibility of airflow limitation in response to beta 2 agonists.[1] Complete reversibility of airflow limitation is typical of asthma but significant reversibility has been noted in subgroup of patients with COPD particularly with bronchiectasis. Significant reversibility of airflow limitation after use of bronchodilators and to corticosteroids is present in up to 30% of patients with COPD.[4] The morphologic classification of COPD can be achieved in accordance with the presence or absence of apparent emphysema, bronchiectasis and bronchial wall thickening. However, as mentioned earlier, the relationship between the morphologic phenotypes and airflow limitation is complicated because airflow limitation in COPD results from a combination of small airway remodeling and a loss of lung elastic recoil. [5]

Figure 4. (A-B): Panacinar emphysema: HRCT scans showing diffuse low attenuation lung parenchyma - typical of panacinar emphysema.

The relative contributions of these pathologic abnormalities may vary among patients with the same degree of airflow limitation. Identifying the causes of airflow limitation in patients with COPD is crucial for determining the appropriate therapeutic strategy. In the present study, 50 stable COPD patients were classified showing predominant emphysema (group 1), bronchial wall thickening (group 2) and bronchiectasis (group 3) in accordance with finding on HRCT scan. In group 1 and 2 patients, it was observed less number of patients who had significant poor reversibility in airflow obstruction in response to inhaled beta 2 agonists. Patients with this phenotype also showed worse 6 min walk test values, decreased BMI and less frequency of exacerbations compared with other phenotype group.

Figure 5. HRCT scan showing small subpleural areas of hyperlucency - characteristic of paraseptal emphysema.

In group 3 patients, it was observed increased number of patients who had increased frequency of exacerbations but had better BMI, better reversibility to bronchodilators and better 6 min walk test values. The present study indicated that there are a higher number of patients showing partial reversibility of airflow limitation in response to bronchodilators in group 3 (i.e. subset of patients with bronchiectasis). It was observed that poor reversibility in response to bronchodilators was associated with severe

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emphysema and presence of bronchial wall thickening on HRCT scans.

Quantitative CT Assessment of Chronic Obstructive Pulmonary Disease ; Radiographics. January 2010; 30, 55-66.

Airflow limitation in COPD is mainly due to airway wall thickening in small airways. However it has been demonstrated that large or intermediate airway wall thickening reflects wall thickening in small airways. This may also be associated with increased airway inflammation. Bronchodilator reversibility may be caused because of small airway wall inflammation.[6]

3. Mona Bafadhel, Imran Umar, Sumit Gupta, J. Vimal Raj, Dhiraj D. Vara, James J. Entwisle, Ian D. Pavord, Christopher E., and Salman S; The Role of CT Scanning in Multidimensional Phenotyping of COPD ; CHEST 2011; 140(3):634–642 4. O'Donnell AE. Bronchiectasis in patients with COPD: a distinct COPD phenotype? Chest. 2011 Nov; 140(5): 1107-8

In group 1 and 2 patients with predominant emphysema and bronchial wall thickening, airway wall thickening is less and airflow limitation is thought to be mainly due to decreased elastic recoil. Therefore they show hardly any reversibility in response to treatment with bronchodilators.

5. Sudhakar N. J. Pipavath, Rodney A. Schmidt, Julie E. Takasugi, and J. David GodwinJ; Chronic Obstructive Pulmonary Disease Radiology-Pathology Correlation;Thoracic Imaging 2009; 24:171–180

Spirometry and FEV1 is currently used to diagnose severity of COPD. However this is less accurate for small airway dysfunction (i.e. airflow in airways with internal diameter <2mm). The application of CT imaging provided additionally clinically important information as a non-invasive biomarker of COPD. One limitation of this study is that we use qualitative classification of emphysema, bronchial wall thickening and bronchiectasis and not quantitative.[7]

6. Gupta PP, Yadav R, Verma M, Gupta KB, Agarwal D; High Resolution Computed Tomography and Chronic Obstructive Pulmonary Disease; Singapore Med J. 2009 Feb;50(2):193-200 7. Prem P. Gupta, Rohtash Yadav, Manish Verma, Dipti Agarwal, Manoj Kumar ; Correlation between HRCT features and patients characteristics in COPD; Ann Thorac Med. 2008 Jul-Sep; 3(3): 87–93.

In conclusion, our study results indicate that airway limitation derived from three spirometrically gated thin section CT scans obtained at defined anatomic levels can enable the differentiation of patients who have COPD with emphysema, bronchial wall thickening and bronchiectasis, which is a distinction that correlates with pulmonary functional impairment.

8. Miller M , Ramsdell J , Friedman PJ , Cho JY , Renvall M ,Broide DH . Computed tomographic scan-diagnosed chronic obstructive pulmonary disease-emphysema: eotaxin-1 is associated with bronchodilator response and extent of emphysema.J Allergy Clin Immunol. 2007 ; 120 ( 5 ): 1118 – 1125.

Future Directions

9. Lamers RJ, Thelissen GR, Kessels AG, Wouters EF,van Engelshoven JM. Chronic obstructive pulmonary disease: evaluation with spirometrically controlled CT lung densitometry. Radiology 1994; 193:109–113.

Only 3 main predominant features of HRCT were studied and correlated with main clinical features. However further studies need to be done incorporating various other features like bullous disease, ground glass opacity, vascular changes, and correlate with more clinical parameters including arterial blood gas analysis, DLco (Diffusing lung capacity), response to steroids, sputum evaluation, and response to steroids.

10. Nakano Y, Sakai H, Muro S,. Comparison of low attenuation areas on computed tomographic scans between inner and outer segments of the lung in patients with chronic obstructive pulmonary disease: incidence and contribution to lung function. Thorax 1999; 54:384–389.

References 1. Orlandi I, Moroni C, Camiciottoli G, Bartolucci M, Pistolesi M, Villari N, Mascalchi M.Chronic Obstructive Pulmonary Disease: Thin-Section CT Measurement of Airway Wall Thickness and Lung Attenuation ; Radiology. 2005 Feb;234(2):604-10. 2. Shin Matsuoka, Tsuneo Yamashiro, George R. Washko, Yasuyuki Kurihara, Yasuo Nakajima, Hiroto Hatabu: 30