Combined pulmonary fibrosis and emphysema; prevalence and follow up among health-care personnel

Transcription

1 Combined pulmonary fibrosis and emphysema; prevalence and follow up among health-care personnel Poster No.: C-0698 Congress: ECR 2013 Type: Scientific Exhibit Authors: K. Chae, G. Jin, S. Chon, Y. Lee; Jeonju/KR Keywords: Lung, Respiratory system, Thorax, CT, Computer ApplicationsDetection, diagnosis, Chronic obstructive airways disease DOI: /ecr2013/C-0698 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 22

2 Purpose Combined pulmonary fibrosis and emphysema (CPFE) would be not just a distinct phenotype of idiopathic pulmonary fibrosis (IPF) and results from the characteristic imaging features (centrilobular and/or paraseptal emphysema in the upper lobe predominantly, and diffuse interstitial opacities suggestive of pulmonary fibrosis of the lower lobes). (1-4) The significance of changes in lung function appears to differ in patients with isolated IPF compared with patients with CPFE syndrome on the follow-up. Therefore, regular follow-up CT in CPFE patients in addition to pulmonary function to estimate progression of CPFE is needed. (5-6) A previously proposed models to estimate CPFE were in patient with lung cancer-related or diffuse lung disease but there is no data of prevalence of asymptomatic smoking related CPFE. Also, until now, there are no reports regarding the progression of CPFE at follow-up CT. The purpose of our study was to determine the prevalence of CPFE by initial CT and the rate of progression of CPFE by follow-up CT in asymptomatic smokers. Methods and Materials Study population We reviewed CT images of males aged greater than 40 (n=3102), who underwent low dose CT (LDCT) for screening of lung cancer in our health-care center hospital between January 2004 and December All subjects did not have pulmonary symptoms of them (43.2%) were smoker. One radiologist (CKJ: 2 years experience) and one graduate school student (KYS) who were trained to recognize CPFE evaluated LDCT (n=3102), paying attention to the presence or absence of CPFE. final inclusion populations were 2600 subjects (normal=2162, emphysema=375, and CPFE=63). Among these health care persons, 63 subjects (63/1339, 4.7%)among smokers were identified as CPFE. Pulmonary function tests and LDCT technique Pulmonary function tests (PFTs) were performed and the following values were evaluated: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and Page 2 of 22

3 the FEV1/ FVC ratio. All pulmonary function tests were performed on the same day as LDCT. 16 or 128 multi-detector CT (Somatom Sensation 16 or Somatom Definition AS, Siemens Medical solution) was performed at end inspiration in one breath hold with prone position. Examination parameters of LDCT were 50 mas, 120 kvp, 2 mm collimation, the Field of view was 300 mm, matrix size was 512x512mm. Imaging analysis The presence of emphysema was visually assessed and we divided both lungs into each lobe, right upper, middle, lower and left upper and lower. A score 0 to 4 was assigned to describe the amount of lung affected by emphysema in each portion as follows: score 0 (no emphysema); score 1 (mild, 1-25%); score 2 (moderate, 26-50%); score 3 (marked, 51-75%); score 4 (severe, >75%). The following patterns were identified (a) centrilobular; (b) paraseptal, (c) panlobular, (d) mixed emphysema, in which an equal amount of centrilobular and paraseptal emphysema was present. We divided fibrosis findings by two patterns, honeycombing and reticular-ground grass opacity (GGO). And the scores were assigned for both honeycombing and reticular-ggo of each hemithorax, from 0 to 4. Statistics Kappa value was calculated for agreement between first and second readers for the baseline read. One-way analysis of variance (ANOVA), including post hoc tests, was used to compare the characteristics of each group. Concordance between both observers in assigning each score of emphysema and fibrosis was assessed with intraclass correlation coefficients (ICCs). We conducted Spearman correlation analyses to evaluate the correlation among the emphysema, honeycombing, reticular-ggo, and overall fibrosis scorings. To assess the correlation between various demographic data (age, BMI, smoking pack-years, and spirometric measures) and CT fibrosis scorings, one-way analysis of variance (ANOVA) was used. Total follow-up intervals were divided into 3 groups, and each group's correlation of continuous smoking and progression of CPFE were used by Chi-square with fisher exact test. Statistical analysis was performed with software (SPSS for Windows; SPSS, Chicago, Ill), and a statistically significant difference was defined as P <.05. Images for this section: Page 3 of 22

4 Fig. 2: Axial LDCT images in 67-year-old man show CPFE with smoking cessation. (a), (b) Baseline LDCT shows emphysema (centrilobular and paraseptal type) of both upper lobes, and subpleural reticular opacity with honeycombing of bilateral lower lobes. (c), (d) Follow-up CT after 3.47 years, CT findings of CPFE have no change. Page 4 of 22

5 Fig. 4: Axial LDCT images in 63-year-old man show progression of CPFE with continued smoking. (a, b) Baseline LDCT shows predominantly centrilobular emphysema of both upper lobes, and subpleural ground grass opacity with mild reticular opacity of bilateral lower lobes. (c), (d) Follow-up LDCT after 7.70 years shows progression of bilateral subpleural honeycombing. Page 5 of 22

6 Results Prevalence Among all examined subjects, the prevalence of CPFE among smokers was 4.7% (63/1339) (95% CI; ), and their median pack-years of cigarette smoking was 20.0 ± 23.1 (95% CI ). Agreement between two readers for the baseline LDCT review was very good (#=0.803). Demographic factors Normal (I) (n = 126) Emphysema CPFE (III) (II) (n = 63) (n = 126) P Value 62.5 ± ± ± Height (cm)* ± ± ± Weight (kg)* 64.3 ± ± ± BMI (kg/m )* 23.3 ± ± ± Age (years) Post-hoc Smoking status never 73 (58) 39 (31) 0 (0) former 2 (2) 0 (0) 16 (25) current 51 (40) 87 (69) 47 (75) smoking PY 0 ± ± ± 18.2 <.001 VC%* 93.4 ± ± ± FVC%* 93.6 ± ± ± FEV1%* 92.7 ± ± ± FEV1/FVC* 77.9 ± ± ± I, II, III I III, II Table1. Demographic findings between normal, emphysema, CPFE groups * Data are means ± standard deviation + Data are median ± standard deviation Page 6 of 22

7 Table 1 shows characteristics of the three groups (normal, emphysema-only, and CPFE). All CPFE cases were current (n=47, 75%) or ex-smokers (n=16, 25%), their median pack-years of cigarette smoking were 40.0 ± 18.2 (95% CI: 38.97, 47.95), and it was significantly higher than normal (0 ± 18.0, p <.001) and emphysema (14.3 ± 22.8, p <.001) groups. CPFE was much influenced by smoking (odd ratio 1.08, 95% CI: 1.06, 1.11) compared with emphysema (odd ratio 1.02, 95% CI: 1.01, 1.03). Mean FEV1 of CPFE subjects (FEV1 = 91.6 ± 22.1) had higher than emphysema-only subjects (FEV1=82.1 ± 24.3), and it was statistically significant (P =.02). But there were no significant differences (P =.99) when CPFE subjects (FEV1 = 91.6 ± 22.1) were compared with normal subjects (FEV1 = 92.7 ± 22.0). Other characteristics such as age, height, weight, BMI were not significantly different among three groups, and spirometric values of FVC, VC, FEV1/FVC ratio were also not significantly different. Image findings ICC 95% CI Emphysema type , 0.81 RUL emphysema , 0.97 RML emphysema , 0.86 RLL emphysema , 0.94 LUL emphysema , 0.94 LLL emphysema , 0.90 Total emphysema , 0.94 Rt lung honeycomb , 0.89 Lt lung honeycomb , 0.93 Total honeycomb , 0.91 Rt lung reticular-ggo , 0.94 Lt lung reticular-ggo , 0.95 Total reticular-ggo , 0.94 Total fibrosis , 0.97 Table 2. Interobserver variability between two readers scoring CPFE and emphysema degree In CPFE subjects, intraclass correlations for emphysema score [ ] and fibrosis score [ ] were found to have good or very good agreement between the two readers. Most common type of emphysema was paraseptal emphysema (54.0%, 34/63). Page 7 of 22

8 Stage Emphysema Honeycomb ReticularGGO Fibrosis (<.001)* (.115) (.001)* (.955) (<.001)* (Mean ± SD) Emphysema 1.30 ± 0.64 Honeycomb 1.17 ± 0.53 ReticularGGO 0.65 ± (.009)* Fibrosis 1.38 ± Table 3. Spearman correlation coefficient test results in 63 CT image finding Mean score of total emphysema was 1.27 ± 0.51: mild, 76% (48/63, 95% CI; ); moderate, 21% (13/63, 95% CI; ); severe, 3% (2/63, 95% CI; ). Mean honeycombing score was 1.19 ± 0.59, and mild honeycombing [79% (50/63), 95% CI; ] was most common. Mean reticular-ggo score was 0.65 ± 0.67, and 48% (30/63, 95% CI; ) had mild reticular-ggo. Severity of emphysema had moderate positive correlation with that of honeycombing (r=0.439, p<.001) and total fibrosis (r=0.302, p=.016). Mild (n = 44) Above moderate P Value (n = 19) Age (years) ± ± Height (cm)* ± ± Weight (kg)* 62.7 ± ± BMI (kg/m2)* 22.9 ± ± smoking PY 45.0 ± ± VC%* 93.9 ± ± FVC%* 95.6 ± ± FEV1%* 91.2 ± ± FEV1/FVC* 76.7 ± ± 2.2 Table 4. Demographic findings between fibrosis grade.037 * Data are means ± standard deviation + Data are median ± standard deviation Page 8 of 22

9 Fibrosis scoring on LDCT and demographic factors (age, height, weight, BMI, smoking pack-years, spirometric measures) for CPFE subjects revealed no significant correlation except FEV1/FVC. (Table 4). Follow-up Follow-up periods of 42 participants with CPFE ranged from 1.0 to 8.3 years. Their median follow-up period was 50.4 months. (95% CI; ). Excellent agreement was found for assessment of progression on follow-up LDCT between two readers (#=0.81). Among followed up participants, 20 participants (47.6%) ceased smoking, and 19 participants (95%) of them have not progressed of CPFE on last follow-up CT. (Fig. 1,2) However, 22 participants (52.4%) continued smoking, and 16 participants (72.7%) of them have progressed of CPFE on last follow-up CT. (Fig. 3,4) One participant (5%) has been progressed regardless of smoking cessation. There was significant correlation between continued smoking and CPFE progression (p<.001, odds ratio=50.7, 95% CI; 5.5, 466.0) (Table 5). 3 participants (3/42, 7.14%, 95%CI; 2.46, 19.01) had newly developed lung cancer on follow-up CT. (Fig 5,6). Two of them were continuous smokers, but other one participant was ex-smoker. f/u Patients Continuous smoking Quit smoking P-value Progression Unchanged Progression Unchanged Interval (years) < (25%) 6 (75%) 0 (0%) 8 (100%) (100%) 0 (0%) 0 (0%) 7 (100%).000 > (100%) 0 (0%) 1 (20%) 4 (80%).010 Total (72.7%) 6 (27.3%) 1 (5%) 19 (95%) <.001 OR = 50.7 Table 5. Correlation of progression with continuous smoking during follow up Page 9 of 22

10 Fig. 1: Axial LDCT images in 72-year-old man show CPFE with smoking cessation. (a,b) Baseline LDCT shows emphysema (centrilobular and paraseptal type) of both upper lobes, and subpleural reticular opacity with honeycombing of bilateral lower lobes. (c, d) Follow-up CT after 1.94 years, CT findings of CPFE have no change. References: radiology, Chonbuk national university hospital - Jeonju/KR Page 10 of 22

11 Fig. 2: Axial LDCT images in 67-year-old man show CPFE with smoking cessation. (a), (b) Baseline LDCT shows emphysema (centrilobular and paraseptal type) of both upper lobes, and subpleural reticular opacity with honeycombing of bilateral lower lobes. (c), (d) Follow-up CT after 3.47 years, CT findings of CPFE have no change. References: radiology, Chonbuk national university hospital - Jeonju/KR Page 11 of 22

12 Fig. 3: Axial LDCT images in 73-year-old man show progression of CPFE with continued smoking. (a) and (b) Baseline LDCT shows predominantly centrilobular emphysema of both upper lobes, and subpleural ground grass opacity with mild reticular opacity of bilateral lower lobes. (c), (d) Follow-up LDCT after 3.44 years shows progression of bilateral subpleural honeycombing with ground grass opacity. References: radiology, Chonbuk national university hospital - Jeonju/KR Page 12 of 22

13 Fig. 4: Axial LDCT images in 63-year-old man show progression of CPFE with continued smoking. (a, b) Baseline LDCT shows predominantly centrilobular emphysema of both upper lobes, and subpleural ground grass opacity with mild reticular opacity of bilateral lower lobes. (c), (d) Follow-up LDCT after 7.70 years shows progression of bilateral subpleural honeycombing. References: radiology, Chonbuk national university hospital - Jeonju/KR Page 13 of 22

14 Fig. 5: Axial LDCT images in 66-year-old man who stopped smoking show lung cancer development without progression of CPFE. (a, b) Baseline LDCT shows predominantly paraseptal emphysema of both upper lobes, and subpleural reticular opacity with honeycombing. (c, d) Follow-up CT after 4.48 years shows newly detected solitary pulmonary nodule (arrow) in LLL beside honeycombing area. It was confirmed to NSCLC (SqCC) in PTNB. References: radiology, Chonbuk national university hospital - Jeonju/KR Page 14 of 22

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16 Fig. 6: Axial LDCT images in 67-year-old man show lung cancer development and progression of CPFE with continuous smoking. (a-c) Baseline LDCT shows predominantly paraseptal emphysema of both upper lobes, and subpleural reticular opacity with honeycombing, traction bronchiectasis of bilateral lower lobes. (d-f) Followup CT after 1.91 years shows newly detected solitary pulmonary nodule (arrow) in LLL beside honeycombing area, and progression of honeycombing. References: radiology, Chonbuk national university hospital - Jeonju/KR Images for this section: Fig. 1: Axial LDCT images in 72-year-old man show CPFE with smoking cessation. (a,b) Baseline LDCT shows emphysema (centrilobular and paraseptal type) of both upper lobes, and subpleural reticular opacity with honeycombing of bilateral lower lobes. (c, d) Follow-up CT after 1.94 years, CT findings of CPFE have no change. Page 16 of 22

17 Fig. 3: Axial LDCT images in 73-year-old man show progression of CPFE with continued smoking. (a) and (b) Baseline LDCT shows predominantly centrilobular emphysema of both upper lobes, and subpleural ground grass opacity with mild reticular opacity of bilateral lower lobes. (c), (d) Follow-up LDCT after 3.44 years shows progression of bilateral subpleural honeycombing with ground grass opacity. Page 17 of 22

18 Fig. 5: Axial LDCT images in 66-year-old man who stopped smoking show lung cancer development without progression of CPFE. (a, b) Baseline LDCT shows predominantly paraseptal emphysema of both upper lobes, and subpleural reticular opacity with honeycombing. (c, d) Follow-up CT after 4.48 years shows newly detected solitary pulmonary nodule (arrow) in LLL beside honeycombing area. It was confirmed to NSCLC (SqCC) in PTNB. Page 18 of 22

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20 Fig. 6: Axial LDCT images in 67-year-old man show lung cancer development and progression of CPFE with continuous smoking. (a-c) Baseline LDCT shows predominantly paraseptal emphysema of both upper lobes, and subpleural reticular opacity with honeycombing, traction bronchiectasis of bilateral lower lobes. (d-f) Followup CT after 1.91 years shows newly detected solitary pulmonary nodule (arrow) in LLL beside honeycombing area, and progression of honeycombing. Page 20 of 22

21 Conclusion In conclusion, the prevalence of CPFE in asymptomatic smokers enrolled in a health screen center was not low. The progression of CPFE was associated with smoking status, 72.7% of continued smoker have progressed CPFE on the last follow-up CT. Therefore, when we encounter CPFE patient who is smoker, a serial CT follow up with smoking cessation should be recommended. References (1) Cottin V, Cordier JF. The syndrome of combined pulmonary fibrosis and emphysema. Chest. 2009;136(1):1-2 (2) Zhao Y, Cui A, Wang F, et al. Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema. Chinese medical journal. 2012;125(17): (3) Cottin V, Nunes H, Brillet PY, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2005;26(4): (4) Jankowich MD, Rounds SI. Combined pulmonary fibrosis and emphysema syndrome: a review. Chest. 2012;141(1): (5) Akagi T, Matsumoto T, Harada T, et al. Coexistent emphysema delays the decrease of vital capacity in idiopathic pulmonary fibrosis. Respiratory medicine. 2009;103(8): (6) Sverzellati N, Guerci L, Randi G, et al. Interstitial lung diseases in a lung cancer screening trial. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2011;38(2): Personal Information Kumju Cae MD, Department of Radiology, The Chonbuk National University Hospital, University of Chonbuk, Korea; para2727@gmail.com Gongyong Jin MD, Department of Radiology, The Chonbuk National University Hospital, University of Chonbuk, Korea; gyjin@jbnu.ac.kr Page 21 of 22

22 Subin Chon MD, Department of Radiology, The Chonbuk National University Hospital, University of Chonbuk, Korea;' Youngsun Lee MD, Department of Radiology, The Chonbuk National University Hospital, University of Chonbuk, Korea; Page 22 of 22