Incorporating Baseline Lung Function in Lung Cancer Screening

Recently published lung cancer screening programs from the United Kingdom have targeted deprived communities and included routine baseline spirometry.1Balata H. Harvey J. Barber P.V. et al.Spirometry performed as part of Manchester community-based programme detects a high prevalence airflow obstruction in individuals without prior diagnosis COPD.Thorax. 2020; 75: 655-660Crossref PubMed Scopus (6) Google Scholar,2Ruparel M, Quaife SL, Dickson JL, al. Prevalence, symptom burden under-diagnosis chronic obstructive pulmonary disease cohort. Ann Am Thorac Surg. 2020 Jul;17(7):869-878.Google Scholar Although not widely recommended,3Sibelle Y. Decramer M. Nicod L.P. al.Directing future health: European Respiratory Roadmap.Eur Respir 2011; 38: 502-506Crossref (10) advocates for spirometry asymptomatic smokers described this “Lung Health Check,” an opportunity to identify COPD at presymptomatic stage basis maintaining good health through preventive measures.3Sibelle Scholar,4Young R.P. Hopkins R.J. Primary secondary prevention disease: where next?.Am J Crit Care Med. 2014; 190: 839-840Crossref (8) Using approach, these studies found that between 37% 67% their eligible had limitation consistent with COPD.1Balata In keeping many high-risk smokers, they also reported 50% 70% yet been diagnosed clinically having COPD. The question arises, “Does identifying ‘undiagnosed COPD’ predict outcomes help target screening?” We previously several post hoc analyses National Lung Screening Trial (NLST), which participants underwent spirometric assessment before randomization annual CT or chest radiography (CXR).5Hopkins Duan F. Chiles C. al.Reduced expiratory flow rate among heavy increases risk: results Trial-American College Radiology Imaging Network Cohort.Ann 2017; 14: 392-402Crossref (28) Scholar, 6Young Greco E. al.Lung cancer-specific mortality reduction screening: according ACRIN-NLST study (N = 18475).Am 2016; 193: A6166Google 7Young Chronic (COPD) screening.Transl Cancer Res. 2018; 7: 347-360Crossref (24) 34% subgroup (COPD), 65% those COPD.5Hopkins This is line findings undergoing “lung checks.”1Balata was associated increased risk cancer,5Hopkins only half observed non-COPD group after (15% 28%, respectively).6Young reduced benefit remains unclear, we NLST subjects more comorbid disease, less surgery, aggressive cancer.7Young brief communication, report preliminary subgroup, comparing undiagnosed spirometry. American (ACRIN) cohort NLST, consented undergo both blood sampling biomarker analysis 10,054, NLST-ACRIN).5Hopkins Demographic data, including doctor-diagnosed pre-morbid diseases, were collected extensive questionnaire (defined Table 1 legend). Prebronchodilator measured by trained staff using Spiropro spirometer (eResearchTechnology, GmbH). severity defined Global Initiative on Obstructive Disease (GOLD) grades 1-4.8Global Diseasehttps://goldcopd.org/Date accessed: May 24, 2020Google Each participant assigned four mutually exclusive phenotype groups airways spirometry-defined limitation, (Fig 1). cases all during full trial period (encompassing follow-up intervals; mean, 6.4 years) confirmed histology (n 389).Table 1Results High-Risk Smokers Sub-phenotyped According Presence Airflow Limitation and/or Doctor-Diagnosed Airways Disease: Baseline Variables OutcomesDemographic OutcomesNo LimitationAirflow LimitationHealthy ControlSubjectsAirways DiseaseOnlyUndiagnosedCOPDDiagnosedCOPDaP < .01.N 9,880,b174 (1.7%) Subjects 10,054 did excluded analyses. No. (% total)5,453 (55)1,005 (10)2,209 (22)1,213 (12)Race, age, sex White, (%)5,053 (92.7)940 (93.5)2,062 (93.3)1,156 (95.3)aP .01. Age, mean (SD)61.1 (4.9)61.3 (5.0)62 (5.3)cP .0001.63.2 .0001. Male, (%)3,136 (57.5)382 (38)cP .0001.1,434 (65)cP .0001.653 (53.8)aP .01.Smoking history Current smoker, (%)2,496 (45.8)472 (47)1,287 (58.3)cP .0001.588 (48.5)cP Pack years, (SD)52.9 (21.3)57 (24.1)cP .0001.58.8 (24.8)cP .0001.62.0 (25.3)cP Cigarettes/day, (SD)27.5 (10.8)28.9 (11.3)cP .0001.28.1 (10.9)aP .01.29.4 Years quit, (SD)4.0 (5.2)3.7 (5.0)aP .01.2.8 (4.6)cP .0001.3.4 (4.8)cP Smoking duration, years (SD)39.2 (7.3)40.1 (7.5)cP .0001.42.1 (7.2)cP .0001.42.6 (7.1)cP .0001.Other variables FHx cancer, Yes, (%)1,285 (23.6)249 (25)511 (23)291 (%)dAirways “Has doctor ever told you any following conditions…” COPD, Emphysema, Bronchitis, Adult Asthma (where childhood asthma excluded).01,005 (100)01,213 (100) BMI, (SD)28.4 (5.0)29.2 (6.1)cP .0001.26.7 (4.7)cP .0001.26.8 (5.1)cP Education leveleExcludes other/unknown. (%) High school less, (%)1,478 (27.1)316 (31.4)cP .0001.665 (30.1)aP .01.418 (34.5)cP Post school/some college, (%)1,941 (35.6)395 (39.3)744 (33.7)427 (35.2) Graduate/postgraduate, (%)1,905 (35.0)258 (25.7)744 (33.7)335 (27.6)Lung function FEV1/FVC, (SD)77.4 (4.8)76.8 .0001.61.0 (8.4)cP .0001.56.5 (10.0)cP FEV1, % predicted (SD)90.3 (15.2)83.6 (15.9)cP .0001.70.7 (18.6)cP .0001.58.7 (18.9)cP FVC, (SD)89.1 (14.8)83.5 (15.6)cP .0001.87.8 (20.3)cP .0001.78.2 (19.6)cP .0001.GOLD grade GOLD 1-2, (%)……1,934 (87.7)812 (67.0) 3-4, (%)……272 (12.3)398 (32.8)aP .01.Doctor-diagnosed comorbiditiesdAirways excluded). Pneumonia, (%)1,200 (22.0)468 (46.6)cP .0001.550 (24.9)aP .01.507 (41.8)cP Heart (%)660 (12.1)168 (16.7)cP .0001.278 (12.6)196 (16.2)fP .001. Hypertension, (%)1,931 (35.4)407 (40.5)fP .001.788 (35.7)446 (36.8) Stroke, (%)141 (2.6)42 (4.2)fP .001.47 (2.1)61 (5)cP Diabetes, (%)539 (9.9)138 (13.7)cP .0001.167 (7.6)107 (8.8) Any history, (%)189 (3.5)55 (5.5)fP .001.93 .001.68 (5.6)fP .001.Lung cancer—patient years792.0206.7561.4431.5 Diagnosis (/1,000)151 (27.7)41 (40.8)aP .01.117 (53.0)cP .0001.80 (66.0)cP deaths/1,000 patient (95% CI)2.1 (1.6-2.5)3.7 (2.4-5.5)cP .0001.4.5 (3.4-5.7)cP .0001.3.1 (2.2-4.2)aP Death, cancer)68 (45)23 (56)60 (51)37 (46) Surgery, cancer)93 (62)20 (49)aP .01.55 (47)aP .01.38 (48)aP .01.Relative “Healthy Control Subjects” (Group 1), achieved statistical differences: Dunnett’s continuous variable/FDR categorical test. FDR false discovery rate; family history; Disease.a P .01.b 174 analyses.c .0001.d excluded).e Excludes other/unknown.f Open table new tab Relative Disease. Differences characteristics stratification compared against referent (healthy control subjects), test pairwise Fisher exact For each three comparisons, overall significance level variable maintained 5% discovery-protected value (Benamini-Hochberg). Rate differences, ORs, mid-P statistics comparisons calculated OpenEpi.9Open Source Epidemiologic Statistics Public Healthwww.openepi.comDate August 6, From participants, 9,880 (98%) satisfactory classified into phenotypic demographic variables, results, co-morbid diseases are summarized 1. Compared healthy subjects, likely be older, male, current greater smoking pack lower educated, worse function. younger, smoke cardiovascular comorbidity, 3-4 (P ≤ .01). “airways disease” alone female, higher year exposure, .001). rates deaths significantly other .01); despite comparable histology, screen detection (data shown; > .05), surgical comparator arm 2. After CT, (+17%, .03 −32%, .0001, respectively), (+22%, .019; −26%, .002, respectively) even adjustment 2). contrast, no different .05). Healthy accounted most averted (25/28; 89%).Table 2Results Risk Outcomes ArmScreening Effects (CT vs CXR)No SubjectsAirways DiseaseOnlyUndiagnosed COPDDiagnosed COPDaP (12)Outcomes screeningCT CXRCT CXRStage (%)53 (61):25 (39)11 (46): 8 (50)35 (58): 20 (37)21 (60): (49)P .0088P .99P .026P .36Adeno/squamous/other54/15/18 29/17/1812/7/6 5/3/827/17/19 20/11/2312/7/18 17/13/13P .15P .28P .35P .24Screen-detected, (%)55 (63): 25 (39)14 (56): 4 (25)44 (70): (37)25 (68): 16 (37)P .0049P .063P .0004P .008LC rate60/87 33/64aP .01.12/25 8/1636/63 19/54aP .01.18/37 20/43 difference, %+17−2+22+2 valueP .03P .91P .019P .85 Odds (1.07, 4.1)0.92 (0.26, 3.24)2.46 (1.16, 5.19)1.09 (0.45, 2.63) .90P surgery adjusted LC Stage CI)1.00 (0.31, 3.18)1.88 (0.14, 25.1)2.30 (0.80, 6.60)0.56 (0.16, 1.91) .63P .12P .35LC death rate25/87 39/6412/25 8/1623/63 34/54aP .01.15/37 18/43 %−32%−2%−26%−1% .0001P .002P .91LC CT−14NA−11−3 CI)↓36% (23, 52)(+4 LC)↓32% (19, 49)↓17% (6,-39)Odds deathcAdjusted age smoking. CI)0.25 (0.13, 0.50)0.61 (0.15, 2.46)0.33 0.70)0.93 (0.38, 2.30) .49P .0043P .15Odds 1-2 CI)0.29 0.66)0.65 3.29)0.34 (0.11, 1.02)1.32 (0.44, 3.90) .0032P .60P .054P .62Reductions Undiagnosed could attributed arm, adjustment, but differences histology. These can partly shift favoring early-stage cancers screen-detected. Across groups, there differential effects staging interval (unpublished findings). Significant values bold. CXR radiograph; cancer.a Adjusted Reductions cancer. our cohort, 34%, previous investigators.1Balata concur spirometry, context screening, identifies COPD,10Silvestri G.A. Young Strange bedfellows: interaction screening.Ann 17: 810-812Crossref (5) relevant significant reductions randomized concentrated groups. stage, rates, arms respiratory comorbidity found. Of note, function, third 3 NLST.7Young suggests life expectancy important determinants screening11Rivera M.P. Tanner N.T. Silvestri al.Incorporating coexisting illness decisions about selection screening. An Official Thoracic Society Research Statement.Am 198: e3-e13Crossref (30) Scholar,12Cheung L.C. Berg C.D. Castle P.E. al.Life-gained-based versus risk-based Intern 2019; 171: 623-632Crossref (27) exists “sweet spot” optimized.7Young suggest presence severe (GOLD 3-4) may contribute poorer CT-based because rates. conclude might subgroups who Author contributions: R. P. contributed conception design; acquisition, analysis, interpretation; drafting review intellectual content, final approval manuscript. G. A. S. D. biostatistical approval. Role sponsors: sponsor role design study, collection preparation