Journal Club Journal Club—COPD2020 Update. Global .

66Journal Club: GOLD 2020 and COPDGene 2019vital capacity (FVC) ratio of less than 70%. In additionto exposure and symptoms, this remains the physiologiccornerstone of GOLD’s definition for the diagnosis ofCOPD despite the recognition in the report that thereare individuals who may have structural changes suchas emphysema or significant small airway diseaseand air trapping and even a reduced FEV1. Yet, if apatient has a preserved FEV1/FVC ratio, he/she is notconsidered for treatment within the GOLD paradigm.The rationale has been that, while these abnormalitiesmay indicate that these individuals are susceptibleto lung injury related to cigarette smoking or otherinjurious inhalants, (biomass fuels for example), thereis little evidence that our current treatment optionshave much impact on their symptoms or progressionof their disease. Further, there is little data as to whethera group of these patients has been fully identified andcharacterized and to know whether or not this group ofindividuals experience significant exacerbations.The COPD Genetic Epidemiology (COPDGene )study includes over 10,000 current or formersmokers in the United States enrolled between 2008and 2011. Baseline evaluations included pre-andpost-bronchodilator spirometry, 6-minute walktest distance, inspiratory and expiratory computedtomography (CT) scans that included a quantitativeassessment of airway wall thickness, emphysemaand gas trapping. Participants also complete 6month interval telephone and web-based follow-ups.In addition, a series of biomarkers were collectedincluding fibrinogen C-reactive protein, surfactantprotein D, soluble receptor for advanced plication andproducts, and Clara cell secretory protein. Mortality isalso being tracked. There were 4615 participants whocompleted a 5-year follow-up with a full set of dataincluding return visits for physiologic and radiographicassessments. With this enormous database ofexposure, symptoms, CT imaging, spirometry andbiomarkers, the COPDGene investigators set outto formulate a unique and new classification schemefor COPD patients by characterizing patients basedon quantitative CT and physiologic and biomarkervariables.Interestingly, 3 papers from the COPDGene studygroup were published in a Special Issue of thisJournal—Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation—in November2019.27-29 The papers present thought-provokingdata compelling us to rethink whether our currentdefinition, diagnostic criteria, and characterizationof patients with COPD is adequate to optimally carefor this patient population. To date, while oxygentherapy and smoking cessation have been shown toprolong survival, there are no medications that havebeen definitively proven to have the ability to improvesurvival or to change the natural course of the diseasein ways that would be considered as disease modifying.With the IMPACT trial data16 bringing into questionwhether or not ICSs may indeed confer an improvedsurvival benefit, we want to make sure we optimallycharacterize the spectrum of COPD patients to identifywho are likely to benefit and whether such interventionshave their greatest impact if they are started early.Further, as we move forward, it is hoped that we willbe able to discover new medications that may betruly disease modifying for patients with COPD. TheCOPDGene study has been following a large cohortof individuals with substantial smoking histories overseveral years and is allowing us to characterize a groupof current and former smokers in a level of detail thathas never been previously attempted. With the datagenerated from this study and the papers that arebeing published, we are able to more clearly phenotypeindividuals who have significant smoking historiesand indeed, pose a compelling argument for revisitingour current GOLD definition of COPD that has beenthe accepted standard for almost 20 years. Ultimately,the goal of such documents is to educate health careproviders and the public about the deleterious effects ofcigarette smoke (and other potential harmful inhalantexposures) and lay out comprehensive strategies toprevent the development and progression of disease.Moving to a definition of COPD that incorporates notonly lung function, but also structural changes notedon CT scans will enable us to select patients withgreater precision for clinical trials to test these newermedicines.The COPDGene articles presented in this JournalClub are thought-provoking and compelling yet thereare a few important issues to put in perspective. TheCOPDGene cohort is highly enriched with heavysmokers (average of approximately 50 pack years) withairflow limitation and therefore the findings, includingassociations and projections, may not be universallyapplicable to those with lower cigarette, (or biomass),exposure or non-smokers who demonstrate airflowlimitation. CT scanning is a high tech and expensivemodality and quantitative CT is not standardized.For personal use only. Permission required for all other uses.journal.copdfoundation.org JCOPDF 2019Volume 7 Number 1 2020

67Journal Club: GOLD 2020 and COPDGene 2019This will need to be further studied and standardizedas far as automated algorithms for calculation ofemphysema and small airway disease and its practicalapplication globally. Studies will need to examinewhether there may be other less expensive means toacquire similar information regarding small airwaydisease, particularly for parts of the world where theremay not be access to such technology.Since 2007 the COPD Foundation has produced aPocket Consultant Guide to assist health care providersin caring for patients with COPD. They launched amobile version in 2013 that was then updated in 2018and in June of 2019 released the latest iteration thatis a mobile app with a significant health care providertrack and a patient track with an interactive dailyaction plan, activity monitoring and exercise videos.Considering the COPD Foundation endorsement ofmoving to a new definition of COPD, the next iterationof the COPD Foundation pocket guide is likely to reflectthis transition to the COPDGene 2019 definition.Bottom LineThe GOLD Committee has provided an abundance ofsound evidence-based recommendations for over 18years and will continue to be a global leader and aninvaluable source of information. Hopefully, they willfind the work of the COPDGene group compellingenough to incorporate their findings into an updateddefinition of COPD going forward. Of course, the bigquestion that future studies will need to address iswhether suggesting that a screening CT scan (withspecial quantitative measurement capabilities, as yetnot standardized) on smokers with a certain smokinghistory (yet to be determined) leads to interventionsthat will provide significant positive outcomes thatwill justify the added expense to incorporate suchscreening. It has been proven for lung cancer; it isquite plausible it will also be found for COPD. Indeed,there will certainly be overlap and insights to gainfrom the lung cancer screening program to date. It willalso be instructive to review how many lung cancersare serendipitously found on CT evaluations as part ofCOPDGene and what are the characteristics of thatcohort.Abstract 1COPDGene 2019: Redefining theDiagnosis of Chronic ObstructivePulmonary DiseaseLowe KE, Regan EA, Anzueto A, et al. Chronic ObstrPulm Dis. 2019;6(5):384-399.doi: kground: Chronic obstructive pulmonarydisease (COPD) remains a major cause of morbidityand mortality. Present-day diagnostic criteriaare largely based solely on spirometric criteria.Accumulating evidence has identified a substantialnumber of individuals without spirometric evidenceof COPD who suffer from respiratory symptomsand/or increased morbidity and mortality. There isa clear need for an expanded definition of COPDthat is linked to physiologic, structural (computedtomography [CT]) and clinical evidence of disease.Using data from the COPD Genetic Epidemiologystudy (COPDGene ), we hypothesized that anintegrated approach that includes environmentalexposure, clinical symptoms, chest CT imaging andspirometry better defines disease and captures thelikelihood of progression of respiratory obstructionand mortality.Methods: Four key disease characteristics environmental exposure (cigarette smoking), clinicalsymptoms (dyspnea and/or chronic bronchitis),chest CT imaging abnormalities (emphysema,gas trapping and/or airway wall thickening), andabnormal spirometry - were evaluated in a groupof 8784 current and former smokers who wereparticipants in COPDGene Phase 1. Using these 4disease characteristics, 8 categories of participantswere identified and evaluated for odds of spirometricdisease progression (FEV1 350 ml loss over 5years), and the hazard ratio for all-cause mortalitywas examined.Results: Using smokers without symptoms, CTimaging abnormalities or airflow obstruction as thereference population, individuals were classified asPossible COPD, Probable COPD and Definite COPD.Current Global initiative for obstructive Lung DiseaseFor personal use only. Permission required for all other uses.journal.copdfoundation.org JCOPDF 2019Volume 7 Number 1 2020

68Journal Club: GOLD 2020 and COPDGene 2019(GOLD) criteria would diagnose 4062 (46%) of the8784 study participants with COPD. The proposedCOPDGene 2019 diagnostic criteria would addan additional 3144 participants. Under the newcriteria, 82% of the 8784 study participants wouldbe diagnosed with Possible, Probable or DefiniteCOPD. These COPD groups showed increased riskof disease progression and mortality. Mortalityincreased in patients as the number of their COPDcharacteristics increased, with a maximum hazardratio for all cause-mortality of 5.18 (95% confidenceinterval [CI]: 4.15-6.48) in those with all 4 diseasecharacteristics.Conclusions: A substantial portion of smokers withrespiratory symptoms and imaging abnormalitiesdo not manifest spirometric obstruction as definedby population normals. These individuals are atsignificant risk of death and spirometric diseaseprogression. We propose to redefine the diagnosisof COPD through an integrated approach usingenvironmental exposure, clinical symptoms, CTimaging and spirometric criteria. These expandedcriteria offer the potential to stimulate both currentand future interventions that could slow or haltdisease progression in patients before disability orirreversible lung structural changes develop.CommentsIt has been appreciated that there are smokers withsignificant symptoms of cough, shortness of breath, andmucous production who may demonstrate evidenceof emphysema and/or small airways disease, (notedby gas trapping and airway wall thickening), despitehaving normal FEV1 and a preserved FEV1/ FVC ratioof greater than 70%. In the initial iterations of theGOLD guidelines such patients were considered to beGOLD 0 but this Grade was dropped in subsequentiterations of the GOLD report. There is also the groupof individuals who have an FEV1 that is reduced below80% of predicted but have a normal FEV1/FVCand have been labeled as preserved ratio-impairedspirometry (PRISm). This study demonstrates the utilityof incorporating the 4 significant features of exposure,symptoms, CT scan characterization of emphysemaand airway wall thickening and physiological measuresof lung function. The study identifies that a substantialnumber already would meet GOLD criteria for a COPDdiagnosis and a

Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation Journal Club—COPD2020 Update. Global Initiative for Chronic Obstructive Lung Disease 2020 Report and the Journal of the COPD Foundation Special Edition, Moving to a New Definition for COPD: “COPDGene 2019” Ron Balkissoon, MD, MSc, DIH, FRCPC1