(Associate Editor: Shu Hashimoto).
Detection of chronic obstructive pulmonary disease in community-based annual lung cancer screening: Chiba Chronic Obstructive Pulmonary Disease Lung Cancer Screening Study Group
Article first published online: 23 DEC 2013
© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology
Volume 19, Issue 1, pages 98–104, January 2014
How to Cite
Sekine, Y., Fujisawa, T., Suzuki, K., Tsutatani, S., Kubota, K., Ikegami, H., Isobe, Y., Nakamura, M., Takiguchi, Y. and Tatsumi, K. (2014), Detection of chronic obstructive pulmonary disease in community-based annual lung cancer screening: Chiba Chronic Obstructive Pulmonary Disease Lung Cancer Screening Study Group. Respirology, 19: 98–104. doi: 10.1111/resp.12179
- Issue published online: 23 DEC 2013
- Article first published online: 23 DEC 2013
- Accepted manuscript online: 27 AUG 2013 07:10AM EST
- Manuscript Accepted: 3 JUL 2013
- Manuscript Revised: 7 MAY 2013
- Manuscript Revised: 6 MAY 2013
- Manuscript Revised: 1 MAR 2013
- Manuscript Revised: 3 JAN 2013
- Manuscript Received: 26 OCT 2012
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- chronic obstructive pulmonary disease;
- computed tomography;
- lung cancer;
- pulmonary function testing;
Background and objective
Detection of chronic obstructive pulmonary disease (COPD) is crucial in the management of COPD. The aim of this study was to establish the utility of a community-based lung cancer screening for detecting COPD.
In Japan, community-based lung cancer screening for residents who are 40 years or older using chest radiography is well established. A screening system in Chiba City, Japan, was used to detect COPD. The criteria to consider COPD at screening included age of 60 years or older, a smoking history and chronic respiratory symptoms. Participants fulfilling these criteria were referred for diagnostic evaluation consisting of pulmonary function testing (PFT) and chest computed tomography (CT).
Of 89 100 Chiba City residents who underwent lung cancer screening, 72 653 residents were 60 years or older. Among them, 878 (1.0%) were identified with suspected COPD and referred for further evaluation. Of those identified, a total of 567 residents (64.6%, 567/878) underwent further evaluations, and 161 (28.4%) were reported to have COPD, with 38.5% of them requiring COPD treatment. To verify the diagnoses from the secondary evaluation centres, PFT and CT data were collected from 228 study participants, and 24.9% were diagnosed with COPD. CT findings classified according to the Goddard classification revealed that 20.1% of these participants had moderate to severe emphysema.
COPD screening added to a community-based lung cancer screening programme may be effective in the detection of patients with COPD.
chronic obstructive pulmonary disease
forced expiratory volume in 1 s
forced vital capacity
pulmonary function testing
Chronic obstructive pulmonary disease (COPD) is a rapidly growing worldwide health problem. In 2008, the World Health Organization listed COPD as the fourth most common cause of death, with 3.28 million deaths annually (5.8% of all deaths). COPD is a very costly disease, with estimated direct medical costs of $14.7 billion in the United States in 1993. COPD is not only a pulmonary disease, but also a systemic inflammatory disease leading to various comorbidities, such as cardiovascular disease and lung cancer, and has been reported to be a risk factor of lung cancer independent from cigarette smoking.[4, 5] Mannino and Braman suggested that better public health and early medical interventions targeting the risk factors for COPD may decrease the growing public health impact of COPD. Therefore, encouraging smoking cessation and early detection of COPD are crucial for disease prevention and lung cancer screening.
COPD is substantially underdiagnosed[8, 9] and frequently misdiagnosed. Soriano et al. reported that 72–93% of COPD patients were not diagnosed with their condition. However, although pulmonary function testing (PFT) has been well recognized as an appropriate tool for detecting COPD, effective methods for early detection of COPD have not been identified. The aim of this clinical study was to evaluate the usefulness of a community-based lung cancer screening programme for detecting COPD.
Community-based lung cancer screening using chest radiography is well established in Japan.[12, 13] Japanese residents who are 40 years or older can undergo annual chest radiography. This screening programme has been supported by the national government under the Health and Medical Services Law for the Aged since 1987. Participants who are suspected to have lung cancer by chest X-ray or sputum cytology are offered further examinations to explore the diagnosis during a secondary evaluation.
For the purpose of this study, this initial lung cancer screening system was utilized to also detect COPD. While lung cancer screening utilizes only chest radiography, COPD screening utilized questionnaires on smoking status and daily symptoms. The following criteria were used to identify residents at risk for COPD at the primary screening: aged 60 years or older; a smoking history; and chronic respiratory symptoms, including cough, cough producing sputum, frequent respiratory infections and dyspnoea on effort. The reason for setting this age criterion was based on the report by Fukuchi et al. that the prevalence of COPD steeply increased at age 60 years and older (5.8% at 50–59 years, 15.7% at 60–69 years and 24.7% at 70 years and older). During the primary screening, residents were asked about their lifestyle, smoking status and past medical history. If they fulfilled all three criteria, the residents were offered a secondary evaluation to undergo additional examinations for COPD. The additional examinations consisted of PFT and computed tomography (CT) to detect COPD and radiological emphysema.
The diagnosis was recorded by the examining physicians at the secondary centres. The primary end-points of this study were the detection rate of COPD and identifying the distribution of COPD severity. The study protocol was approved by the committee of the Chiba COPD Lung Cancer Screening Study Group, and each participating hospital and clinic.
The screening system of Chiba City, Japan, the 13th largest city with approximately 960 000 inhabitants, was used for the study. The number of residents eligible for screening in Chiba City was 258 478 in the 2010 fiscal year. From April 2010 to March 2011, 89 100 residents (34.5%) underwent chest radiography at 257 clinics and hospitals. Of these, 72 653 residents were 60 years of age or older.
Chiba City has 39 secondary evaluation centres certified to diagnose pulmonary diseases. The diagnostic categories included the following: no abnormality, lung cancer (including suggestive findings), metastatic lung tumour, mediastinal tumour, tuberculosis, COPD/emphysema and others. The diagnosis of COPD was based on PFT, and the diagnosis of emphysema was based on CT findings. During the secondary evaluation, the evaluating physicians at the secondary centres determined the severity of COPD and made the following recommendations: no treatment and no follow-up, annual follow-up without treatment, and treatment.
To verify the reliability of the diagnoses reported from the secondary evaluation centres, the clinical data (PFT and/or CT) of 228 residents who had provided written informed consent were collected from the secondary centres and evaluated by the authors, and the authors' assessments were compared with the diagnoses of the evaluating physicians. A total of 173 participants underwent PFT and 185 underwent CT. The PFT diagnosis of COPD was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging. The functional criterion for COPD was the following: forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than 70%. The severity of radiological emphysema was visually assessed by two independent pulmonologists according to the modified Goddard scoring system.[16, 17] Six images of three lung slices (the right and left lungs were evaluated separately) were analyzed for each participant. Each image was classified and scored as follows: normal (score 0), ≤ 5% affected (score 0.5), ≤ 25% affected (score 1), ≤ 50% affected (score 2), ≤ 75% affected (score 3) and >75% affected (score 4), and the mean score of six images was considered to be representative of the severity of emphysema. The participants were then classified into three groups based on the severity of emphysema: (i) no/mild emphysema (emphysema score < 1, per cent low attenuation area in the assessed lung < 12.5% on average); (ii) moderate emphysema (emphysema score 1 to < 2.5, per cent low attenuation area in the assessed lung < 50% on average); and (iii) severe emphysema (emphysema score ≥ 2.5, per cent low attenuation area in the assessed lung ≥ 50% on average).
Data were analyzed using SPSS 20 (IBM, New York, NY, USA). Chi-square test was used to assess the correlation between the clinical diagnosis of COPD reported by the secondary examination centres and the results of PFT. The relationship between two quantitative variables was examined using Spearman tests. Possible predictor variables, including gender, age, smoking status and smoking index, were assessed as risk factors for developing airway obstruction (FEV1/FVC < 0.7) and emphysema (emphysema score ≥ 1) using multiple regression analysis. In all statistical analyses, a significance level of 5% was adopted, and the significance of predictor variables was tested by the likelihood ratio test.
During the community-based lung cancer screening, 19 screened residents were found to have primary lung cancer, of these 12 had metastatic lung cancer. The lung cancer detection rate was 0.02% (19/89 100). Furthermore, 142 screened residents (0.16%) had findings suggestive of lung cancer and were recommended for continuous follow-up.
Figure 1 shows the flow chart for this study. Of the 72 653 eligible residents who were aged 60 years or older and underwent the initial screening, including chest radiography, 878 (1.0%) were suspected to have COPD because of their self-reported screening questionnaires and were referred for further examination. Of those referred, 567 (64.6%; 482 males and 85 females) underwent secondary diagnostic evaluations, including PFT and/or chest CT. Of these, 369 (65.1%, 369/567) underwent PFT and 480 (84.7%, 480/567) underwent CT.
Table 1 shows the final diagnoses and treatment recommendations from the secondary evaluation centres for the 567 screened residents suspected to have COPD. COPD/emphysema was diagnosed in 161 (28.4%), and of these 62 (38.5%) required medical treatment. The COPD/emphysema detection rate was 0.18% (161/89 100). Seven residents were thought to have lung cancer necessary for further follow-up, and four were diagnosed with lung cancer (detection rate 0.7%, 4/567).
|Required annual follow-up||Treatment unnecessary||Required treatment||Others||Total|
|Metastatic lung tumour||1||0||0||0||1|
|Suspected lung cancer||7||0||4||0||11|
|COPD/emphysema||51 (31.7%)||28 (17.4%)||62 (38.5%)||20 (12.4%)||161|
|Total||119 (21.0%)||336 (59.3%)||77 (13.6%)||35 (6.2%)||567|
Table 2 shows the final diagnoses reported for the 369 screened residents who underwent PFT. Similar to the results shown in Tables 1 and 102 (27.6%) were diagnosed with COPD/emphysema, and 47 of these (46.1%) required medical treatment. One resident was diagnosed with lung cancer.
|Required follow-up||Treatment unnecessary||Required treatment||Others||Total|
|Metastatic lung tumour||1||0||0||0||1|
|Known lung cancer||0||0||0||0||0|
|Lung cancer suspected||5||0||1||1||7|
|Chronic obstructive pulmonary disease/emphysema||33 (32.3%)||14 (13.7%)||47 (46.1%)||8 (7.8%)||102|
|Total||71 (19.2%)||228 (61.8%)||54 (14.6%)||16 (4.3%)||369|
Of the 228 participants providing informed consent who were found to have COPD at the secondary evaluation, 84 (36.8%) were current smokers and 144 (63.2%) were ex-smokers. The smoking index was 35.0 ± 24.9 pack years. Table 3 shows the GOLD classifications of 173 participants who underwent PFT. COPD was diagnosed in 43 (24.9%), and there were 28 (65.1%, 28/43) with stage II or higher.
|GOLD stage||n||FVC (L)||%FVC||FEV1 (L)||%FEV1||FEV1/FVC|
|Non-COPD||130 (75.1%)||3.07 ± 0.68||97.0 ± 17.8||2.44 ± 0.54||102.4 ± 20.6||80.0 ± 7.1|
|Stage I||15 (8.7%)||3.41 ± 0.69||107.8 ± 18.2||2.28 ± 0.47||98.9 ± 13.4||66.9 ± 7.0|
|Stage II||21 (12.1%)||2.66 ± 0.43||82.7 ± 10.0||1.62 ± 0.28||67.4 ± 9.7||62.7 ± 6.8|
|Stage III/IV||7 (4.1%)||2.19 ± 0.76||68.7 ± 20.7||0.92 ± 0.18||39.3 ± 8.0||45.0 ± 12.5|
|Total||173||3.02 ± 0.70||95.0 ± 18.9||2.27 ± 0.63||95.3 ± 24.7||75.4 ± 11.5|
We verified the reliability of COPD diagnosis (FEV1/FVC < 0.7) reported from the secondary evaluation centres in 173 participants who underwent PFT (Table 4). The sensitivity, specificity, positive predictive value and negative predictive value were 0.81, 0.92, 0.78 and 0.94, respectively (P < 0.0001).
|Reports from the second examination centres||COPD||35||10|
CT data were collected from 185 participants with 205 findings (Table 5). Although 117 had no abnormal findings, 38 (20.1%) were diagnosed with moderate to severe emphysema. The numbers of no/mild, moderate and severe emphysema were 147, 31 and 7 participants, respectively, according to the modified Goddard classification. Figure 2 shows the relationship between FEV1/FVC and emphysema score in 139 participants who underwent both PFT and CT. The emphysema score was significantly correlated with FEV1/FVC (P < 0.0001). Multiple logistic regression analysis identified age as a risk factor for FEV1/FVC < 0.7, and the smoking index as a risk factor for moderate to severe emphysema (Table 6).
|No abnormality||117 (63.2%)|
|Pulmonary fibrosis||11 (5.9)|
|Old tuberculosis with calcification||19 (10.3)|
|Inflammatory nodule||3 (1.6)|
|Pleural thickness/plaque||6 (3.2)|
|Lung cancer||1 (0.5)|
|Diffuse granular shadow||1 (0.5)|
|Giant bullae||3 (1.6)|
|Emphysema (moderate to severe)||38 (20.1)|
|Risk factors||n (%)||n (%)||95% CI for OR||P-value|
|FEV1/FVC < 0.7||FEV1/FVC ≥ 0.7|
|Male||39 (25.7)||113 (74.3)|
|Female||2 (9.5)||19 (90.5)|
|60–69||11 (15.5)||60 (84.5)|
|70–79||23 (29.1)||56 (60.9)|
|80–||7 (30.4)||16 (69.6)|
|Ex-smoker||21 (19.3)||88 (80.7)|
|Current smoker||20 (31.3)||44 (68.7)|
|Smoking index (pack years)||0.999–1.000||0.120|
|−20||8 (13.1)||53 (86.9)|
|21–40||15 (27.3)||40 (72.7)|
|41–60||12 (30.0)||28 (70.0)|
|61–||6 (35.3)||11 (64.7)|
|Risk factors||Moderate/severe emphysema||No/mild emphysema||95% CI for OR||P-value|
|Male||36 (21.8)||129 (78.2)|
|Female||2 (10.0)||18 (90.0)|
|60–69||16 (22.5)||55 (77.5)|
|70–79||17 (19.1)||72 (80.9)|
|80–||5 (20.0)||20 (80.0)|
|Ex-smoker||20 (17.5)||94 (82.5)|
|Current smoker||18 (25.4)||53 (74.6)|
|−20||5 (7.8)||59 (92.2)|
|21–40||14 (26.4)||39 (73.6)|
|41–60||10 (21.7)||36 (88.3)|
|61–||9 (40.9)||13 (59.1)|
This is the first report of the utilization of a community-based lung cancer screening programme to screen for COPD. From our results, approximately 1.0% of eligible residents undergoing screening were suspected to have COPD, approximately 30% of them were diagnosed with COPD/emphysema and 40% of them required medical treatment. Previously we reviewed the association between COPD and lung cancer, and proposed that early detection of COPD is important for lung cancer surveillance.
Using data from lung cancer screening in Chiba City performed in 2006 and 2007, we determined that approximately 2–4% of screened residents fulfilled the criteria suggestive of COPD (data not shown). COPD screening in Chiba City began in 2008. Initially, few patients were referred to the secondary evaluation centres because of inadequate and hard-to-understand questionnaires and lack of information among physicians about the COPD screening system. Because of the improved and ongoing medical education of physicians, the number of patients identified as suspected to have COPD has since been increasing.
Early diagnosis of COPD has been attempted for high-risk patients,[18, 19] and spirometry was proven to play an important role in COPD screening and early diagnosis. Our study results were similar to those of other investigators. Buffels et al. reported that spirometry confirmed airflow obstruction in 18% of individuals with respiratory symptoms and in 4% of those without symptoms. van Schayck et al. investigated the effectiveness of cross-sectional case findings for patients with a history of cigarette smoking who were at risk for developing COPD using a standardized questionnaire and spirometry. They reported that 18% of participants had airway obstruction, and that when smokers were preselected based on respiratory symptoms, such as chronic cough, the percentage of patients with airway obstruction increased to 48% among those older than 60 years of age. Ulrik et al. reported that 34.8% of general practice patients who were older than 35 years of age, with no previous diagnosis of COPD, and at least one of the following symptoms, cough, dyspnoea, wheezing, sputum or recurrent respiratory infection, had airway obstruction (FEV1/FVC ratio < 0.7).
Recently, the COPD criteria of both a simple fixed FEV1/ FVC ratio (GOLD definition) and the use of a threshold for the per cent of predicted FEV1 values to define lung function impairment (recommended by the National Institute for Health and Clinical Excellence) have been shown to overestimate COPD with increasing age, particularly among men, compared with statistical approaches, such as the lower limit of normal. However, Güder et al. reported that GOLD criteria resulted in more overdiagnosed COPD, while lower limit of normal definitions resulted in more underdiagnosed COPD in elderly patients as compared with an expert panel diagnosis. They suggested that incorporating FEV1 and RV/TLC into the GOLD-COPD or lower limit of normal-based definition would make both definitions closer to the expert panel diagnosis of COPD. However, GOLD criteria are clear and easy to understand for identifying COPD during screening. During this mass screening, the age distribution was very wide, from 40 to over 80 years of age. Therefore, we thought that an FEV1/FVC of <70% still had value to classify COPD and applied this criterion for this screening.
Our study and screening system have several advantages. Screening for COPD can be performed on a large population with minimal additional expense because it can be added to an already established screening system for lung cancer. Pulmonary specialists can diagnose COPD at the secondary evaluation. Once COPD is diagnosed, the patient can be established on appropriate treatment and followed up. The reasons for the low COPD detection rate may be the lack of knowledge and understanding about the seriousness of COPD in the general population and the late appearance of symptoms.
This study had several limitations. First, COPD screening was additionally performed during lung cancer screening. Primary physicians and the participants did not always follow the recommendation for further evaluation, resulting in only 567 of 878 (64.6%) attending the secondary evaluations. Second, this was not a comparative study. However, population screening with or without a targeted approach based on risk factors or symptoms has been reported to yield acceptable diagnostic rates of around 20%.[8, 23] In our study, approximately 30% of screened individuals were diagnosed with COPD/emphysema. The reliability of COPD diagnosis reported from secondary centres was uncertain. However, we verified the accuracy of these reports from the collected data. Last, at present, this system may only be established in a country that has a lung cancer screening system. However, once this screening system has been validated, it can be widened to general practice.
Future work includes validating this screening system and establishing the treatment and follow-up modalities for patients diagnosed with COPD.
In conclusion, community-based lung cancer screening may be utilized to diagnose COPD/emphysema. The rate of detection can be increased by educating general practitioners on the importance of COPD screening. The cost-effectiveness, risks of this screening system and the appropriateness of the current COPD criteria need further evaluation.
We greatly appreciate the efforts of the participating residents and physicians involved in the screening and secondary evaluation. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Y. Sekine.
- 1World Health Organization. The top 10 causes of death, Programmes and projects in World Health Organization (WHO). 2012. [Accessed 9 July 2012.] Available from URL: http://www.who.int/mediacentre/factsheets/fs310/en/index.html
- 4Chronic obstructive pulmonary disease and altered risk of lung cancer in a population-based case-control study. PLoS ONE 2009; 4: e7380. [Accessed 3 June 2012.] Available from URL: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007380 updated: July 23 2011., , et al.
- 15Global initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of COPD. 2011. [Accessed 3 June 2012.] Available from URL: http://www.goldcopd.org/Guidelineitem.asp?l1=2&l2=1&intId=989