Prevalence, Symptom Burden, and Underdiagnosis of Chronic Obstructive Pulmonary Disease in a Lung Cancer Screening Cohort

Mamta Ruparel, Samantha L Quaife, Jennifer L Dickson, Carolyn Horst, Sophie Tisi, Helen Hall, Magali N Taylor, Asia Ahmed, Penny J Shaw, Stephen Burke, May-Jan Soo, Arjun Nair, Anand Devaraj, Karen Sennett, John R Hurst, Stephen W Duffy, Neal Navani, Angshu Bhowmik, David R Baldwin, Sam M Janes, Mamta Ruparel, Samantha L Quaife, Jennifer L Dickson, Carolyn Horst, Sophie Tisi, Helen Hall, Magali N Taylor, Asia Ahmed, Penny J Shaw, Stephen Burke, May-Jan Soo, Arjun Nair, Anand Devaraj, Karen Sennett, John R Hurst, Stephen W Duffy, Neal Navani, Angshu Bhowmik, David R Baldwin, Sam M Janes

Abstract

Rationale: Individuals eligible for lung cancer screening (LCS) by low-dose computed tomography (LDCT) are also at risk of chronic obstructive pulmonary disease (COPD) due to age and smoking exposure. Whether the LCS episode is useful for early detection of COPD is not well established.Objectives: To explore associations between symptoms, comorbidities, spirometry, and emphysema in participants enrolled in the Lung Screen Uptake Trial.Methods: This cross-sectional study was a prespecified analysis nested within Lung Screen Uptake Trial, which was a randomized study testing the impact of differing invitation materials on attendance of 60- to 75-year-old smokers and ex-smokers to a "lung health check" between November 2015 and July 2017. Participants with a smoking history ≥30 pack-years and who quit ≤15 years ago, or meeting a lung cancer risk of ≥1.51% via the Prostate Lung Colorectal Ovarian model or ≥2.5% via the Liverpool Lung Project model, were offered LDCT. COPD was defined and classified according to the GOLD (Global Initiative for Obstructive Lung Disease) criteria using prebronchodilator spirometry. Analyses included the use of descriptive statistics, chi-square tests to examine group differences, and univariable and multivariable logistic regression to explore associations between symptom prevalence, airflow limitation, and visually graded emphysema.Results: A total of 560 of 986 individuals included in the analysis (57%) had prebronchodilator spirometry consistent with COPD; 67% did not have a prior history of COPD and were termed "undiagnosed." Emphysema prevalence in those with known and "undiagnosed" COPD was 73% and 68%, respectively. A total of 32% of those with "undiagnosed COPD" had no emphysema on LDCT. Inhaler use and symptoms were more common in the "known" than the "undiagnosed" COPD group (63% vs. 33% with persistent cough [P < 0.001]; 73% vs. 33% with dyspnea [P < 0.001]). Comorbidities were common in all groups. Adjusted odds ratio (aOR) of respiratory symptoms were more significant for airflow obstruction (aOR GOLD 1 and 2, 1.57; confidence interval [CI], 1.14-2.17; aOR GOLD 3 and 4, 4.6; CI, 2.17-9.77) than emphysema (aOR mild, 1.12; CI, 0.81-1.55; aOR moderate, 1.33; CI, 0.85-2.09; aOR severe, 4.00; CI, 1.57-10.2).Conclusions: There is high burden of "undiagnosed COPD" and emphysema in LCS participants. Adding spirometry findings to the LDCT enhances identification of individuals with COPD.Clinical trial registered with www.clinicaltrials.gov (NCT02558101).

Keywords: case finding; chronic obstructive pulmonary disease; emphysema; low-dose computed tomography; lung cancer screening.

Figures

Figure 1.
Figure 1.
Prevalence of respiratory symptoms (inclusive of those with a history of persistent cough or dyspnea during the 12 months preceding the lung health check [LHC]) in participants with a FEV1:FVC <70% on the pre–low-dose computed tomography (LDCT), prebronchodilator spirometry, and with or without emphysema detected at LDCT. *Termed “chronic obstructive pulmonary disease” (COPD) solely on the basis of LHC spirometry. FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity.
Figure 2.
Figure 2.
Prevalence and grade of (A) airflow obstruction and (B) emphysema by chronic obstructive pulmonary disease (COPD) group. COPD groups: “no COPD” (FEV1:FVC ≥70%); “undiagnosed COPD” (FEV1:FVC <70% and no reported history of COPD); and “known COPD” (FEV1:FVC <70% and a reported history of COPD). FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; GOLD = Global Initiative for Obstructive Lung Diseases.
Figure 3.
Figure 3.
Prevalence of (A) reported respiratory symptoms within 12 months preceding the lung health check, (B) reported inhaler use, and (C) reported comorbidities, by chronic obstructive pulmonary disease (COPD) group. *P ≤ 0.05 and **P ≤ 0.001. COPD groups: “no COPD” (FEV1:FVC ≥70%); “undiagnosed COPD” (FEV1:FVC <70% and no reported history of COPD); and “known COPD” (FEV1:FVC <70% and a reported history of COPD). FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; ICS = inhaled corticosteroid; LABA = long-acting β-agonist; LAMA = long-acting antimuscarinic agent; LRTI = lower respiratory tract infection; SABA = short-acting β-agonist.
Figure 4.
Figure 4.
Prevalence of reported respiratory symptoms within 12 months preceding the lung health check in those with and without emphysema by chronic obstructive pulmonary disease (COPD) group. COPD groups: “no COPD” (FEV1:FVC ≥70%); “undiagnosed COPD” (FEV1:FVC <70% and no reported history of COPD); and “known COPD” (FEV1:FVC <70% and a reported history of COPD). *P ≤ 0.05. FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; LRTI = lower respiratory tract infection.

References

    1. World Health Organization. Global Health Observatory (GHO) data—mortality and global health estimates. Geneva: WHO. 2018 [accessed 2018 Jun 25]. Available from:
    1. Carr LL, Jacobson S, Lynch DA, Foreman MG, Flenaugh EL, Hersh CP, et al. Features of COPD as predictors of lung cancer. Chest. 2018;153:1326–1335.
    1. de Torres JP, Bastarrika G, Wisnivesky JP, Alcaide AB, Campo A, Seijo LM, et al. Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. Chest. 2007;132:1932–1938.
    1. Powell HA, Iyen-Omofoman B, Baldwin DR, Hubbard RB, Tata LJ. Chronic obstructive pulmonary disease and risk of lung cancer: the importance of smoking and timing of diagnosis. J Thorac Oncol. 2013;8:6–11.
    1. Seijo LM, Zulueta JJ. Understanding the links between lung cancer, COPD, and emphysema: a key to more effective treatment and screening. Oncology (Williston Park) 2017;31:93–102.
    1. Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.
    1. de Koning HJ, van der Aalst CM, de Jong PA, Scholten ET, Nackaerts K, Heuvelmans MA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382:503–513.
    1. Pastorino U, Silva M, Sestini S, Sabia F, Boeri M, Cantarutti A, et al. Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy. Ann Oncol. 2019;30:1162–1169.
    1. Young RP, Hopkins RJ. Chronic obstructive pulmonary disease (COPD) and lung cancer screening. Transl Lung Cancer Res. 2018;7:347–360.
    1. Young RP, Duan F, Chiles C, Hopkins RJ, Gamble GD, Greco EM, et al. Airflow limitation and histology shift in the National Lung Screening Trial: the NLST-ACRIN cohort substudy. Am J Respir Crit Care Med. 2015;192:1060–1067.
    1. de-Torres JP, Casanova C, Marín JM, Zagaceta J, Alcaide AB, Seijo LM, et al. Exploring the impact of screening with low-dose CT on lung cancer mortality in mild to moderate COPD patients: a pilot study. Respir Med. 2013;107:702–707.
    1. Mets OM, Buckens CFM, Zanen P, Isgum I, van Ginneken B, Prokop M, et al. Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans. JAMA. 2011;306:1775–1781.
    1. Çolak Y, Afzal S, Nordestgaard BG, Vestbo J, Lange P. Prognosis of asymptomatic and symptomatic, undiagnosed COPD in the general population in Denmark: a prospective cohort study. Lancet Respir Med. 2017;5:426–434.
    1. Hill K, Goldstein RS, Guyatt GH, Blouin M, Tan WC, Davis LL, et al. Prevalence and underdiagnosis of chronic obstructive pulmonary disease among patients at risk in primary care. CMAJ. 2010;182:673–678.
    1. Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, et al. SPIROMICS Research Group. Clinical significance of symptoms in smokers with preserved pulmonary function. N Engl J Med. 2016;374:1811–1821.
    1. Bridevaux PO, Gerbase MW, Probst-Hensch NM, Schindler C, Gaspoz J-M, Rochat T. Long-term decline in lung function, utilisation of care and quality of life in modified GOLD stage 1 COPD. Thorax. 2008;63:768–774.
    1. Siu AL, Bibbins-Domingo K, Grossman DC, Davidson KW, Epling JW, Jr, García FAR, et al. US Preventive Services Task Force (USPSTF) Screening for chronic obstructive pulmonary disease: US Preventive Services Task Force recommendation statement. JAMA. 2016;315:1372–1377.
    1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of COPD. 2017 [accessed 2018 Jun 25]. Available from: .
    1. Lange P, Marott JL, Vestbo J, Olsen KR, Ingebrigtsen TS, Dahl M, et al. Prediction of the clinical course of chronic obstructive pulmonary disease, using the new GOLD classification: a study of the general population. Am J Respir Crit Care Med. 2012;186:975–981.
    1. Global Initiative for Chronic Obstructive Lung Disease. GOLD reports for personal use. 2019 [accessed 2018 Jun 20]. Available from:
    1. Barr RG, Celli BR, Mannino DM, Petty T, Rennard SI, Sciurba FC, et al. Comorbidities, patient knowledge, and disease management in a national sample of patients with COPD. Am J Med. 2009;122:348–355.
    1. Quaife SL, Ruparel M, Beeken RJ, McEwen A, Isitt J, Nolan G, et al. The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and ‘hard-to-reach’ patients. BMC Cancer. 2016;16:281.
    1. Kovalchik SA, Tammemagi M, Berg CD, Caporaso NE, Riley TL, Korch M, et al. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med. 2013;369:245–254.
    1. Tammemägi MC. Application of risk prediction models to lung cancer screening: a review. J Thorac Imaging. 2015;30:88–100.
    1. U.S. Preventive Services Task Force. Final recommendation statement. AHRQ Pub. no. 13-05196-EF-3. September 24 2014 [accessed 2014 Nov 28]. Available from: .
    1. Tammemägi MC, Katki HA, Hocking WG, Church TR, Caporaso N, Kvale PA, et al. Selection criteria for lung-cancer screening. N Engl J Med. 2013;368:728–736.
    1. Cassidy A, Myles JP, van Tongeren M, Page RD, Liloglou T, Duffy SW, et al. The LLP risk model: an individual risk prediction model for lung cancer. Br J Cancer. 2008;98:270–276.
    1. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005;26:319–338.
    1. Bellamy D, Booker R, Connellan S, Halpin D, Jennings J, Wiltshire L. Spirometry in practice: a practical guide of using spirometry in primary care, 2nd ed. London: British Thoracic Society (BTS) COPD Consortium; 2005. p. 3.
    1. Gietema HA, Müller NL, Fauerbach PV, Sharma S, Edwards LD, Camp PG, et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Quantifying the extent of emphysema: factors associated with radiologists’ estimations and quantitative indices of emphysema severity using the ECLIPSE cohort. Acad Radiol. 2011;18:661–671.
    1. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–174.
    1. Steiger David, Filopei Jason, Siddiqi Mohammad, Yip Rowena, Yankelevitz David, Henschke Claudia. Evidence of emphysema in a cohort of participants without symptoms undergoing low dose chest CT screening for lung cancer [abstract] Am J Respir Crit Care Med. 2017;195:A5177.
    1. Jairam PM, van der Graaf Y, Lammers J-WJ, Mali WPTM, de Jong PA PROVIDI Study group. Incidental findings on chest CT imaging are associated with increased COPD exacerbations and mortality. Thorax. 2015;70:725–731.
    1. Zhou Y, Zhong NS, Li X, Chen S, Zheng J, Zhao D, et al. Tiotropium in early-stage chronic obstructive pulmonary disease. N Engl J Med. 2017;377:923–935.
    1. Warnier MJ, van Riet EES, Rutten FH, De Bruin ML, Sachs APE. Smoking cessation strategies in patients with COPD. Eur Respir J. 2013;41:727–734.
    1. Vrbica Ž, Labor M, Gudelj I, Labor S, Jurić I, Plavec D MARKO study group. Early detection of COPD patients in GOLD 0 population: an observational non-interventional cohort study—MARKO study. BMC Pulm Med. 2017;17:36.
    1. Vestbo J, Lange P. Can GOLD stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2002;166:329–332.
    1. Oelsner EC, Hoffman EA, Folsom AR, Carr JJ, Enright PL, Kawut SM, et al. Association between emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: a cohort study. Ann Intern Med. 2014;161:863–873.
    1. Hollands GJ, Hankins M, Marteau TM. Visual feedback of individuals’ medical imaging results for changing health behaviour. Cochrane Database Syst Rev. 2010;(1):CD007434.
    1. ISRCTN. ISRCTN63825779: Yorkshire Enhanced Stop Smoking (YESS). September 25 2018 [updated 2020 Jan 15; accessed 2019 Jul 11]. Available from .
    1. Rivera MP, Tanner NT, Silvestri GA, Detterbeck FC, Tammemägi MC, Young RP, et al. American Thoracic Society Assembly on Thoracic Oncology. Incorporating coexisting chronic illness into decisions about patient selection for lung cancer screening: an official American Thoracic Society research statement Am J Respir Crit Care Med 2018198e3–e13.
    1. Crosbie PA, Balata H, Evison M, Atack M, Bayliss-Brideaux V, Colligan D, et al. Implementing lung cancer screening: baseline results from a community-based ‘Lung Health Check’ pilot in deprived areas of Manchester. Thorax. 2018;74:405–409.
    1. Arvanitis R, Jones L, Gaynor E, Gardner K, Hubbert C, Timoney M, et al. Proactive approaches to individuals at high risk of lung cancer: Accelerate, Coordinate, Evaluate (ACE) Programme. February 2018 [accessed 2018 May 23]. Available from: .
    1. ten Haaf K, Tammemägi MC, Bondy SJ, van der Aalst CM, Gu S, McGregor SE, et al. Performance and cost-effectiveness of computed tomography lung cancer screening scenarios in a population-based setting: a microsimulation modeling analysis in Ontario, Canada. PLoS Med. 2017;14:e1002225.
    1. . The SUMMIT study: a cancer screening study (SUMMIT). May 2, 2019 [updated 2019 May 2; accessed 2020 Jan 24]. Available from: .

Source: PubMed

3
Subscribe