Chronic obstructive pulmonary disease ORIGINAL ARTICLE Thorax: first published as 10.1136/thoraxjnl-2018-211881 on 20 July 2018. Downloaded from Lung volume indices predict morbidity in smokers with preserved spirometry Siyang Zeng,1,2 Andrea Tham,1,3 Bruce Bos,1,4 Joan Jin,1,5 Brian Giang,1,2 Mehrdad Arjomandi1,2 ► Additional material is ABSTRact published online only. To view Background Abnormal lung volumes that reflect Key messages please visit the journal online (http:// dx. doi. org/ 10. 1136/ air trapping are common in COPD. However, their thoraxjnl- 2018- 211881). significance in smokers with preserved spirometry What is the key question? ► Could lung volumes predict progression to overt (normal FEV1 to FVC ratio) is unclear. 1Medical Section, San Francisco Methods Using the Veterans Administration Informatics COPD in smokers without airflow obstruction? Veterans Affairs Medical Center, and Computing Infrastructure database, we identified San Francisco, California, USA What is the bottom line? 2 7479 patients at risk for COPD (ever smokers >40 Department of Medicine, ► This retrospective analysis of the US Veterans years of age without restrictive lung disease) who had University of California, San Affairs electronic health records showed Francisco, California, USA preserved spirometry and concomitant lung volume 3 that abnormal lung volumes representing air School of Medicine, University measurements, and examined their subsequent health of Southern California, Los trapping are common in smokers without COPD records for clinical diagnoses of COPD, healthcare Angeles, USA and are associated with higher healthcare 4 utilisation, follow-up spirometry and mortality. School of Medicine, Radboud utilisation, death and decline in lung function. University Medical Center, Results Air trapping was prevalent, with 31% of Nijmegen, Gelderland, The patients having residual volume to total lung capacity Why read on? Netherlands ratio (RV:TLC) greater than the upper limit of normal 5School of Pharmacy, University ► Understanding the predictors of morbidity and of Illinois at Chicago, Chicago, (ULN). RV:TLC varied widely from 14% to 77% (51% disease progression in smokers without COPD Illinois, USA to 204% of predicted) across the normal ranges of is extremely important for prognostication and FEV1:FVC and FEV1. Patients with RV:TLC greater early intervention. Correspondence to than the ULN were more likely to receive subsequent Dr Mehrdad Arjomandi, Division clinical diagnoses of COPD (HR (95% CI)=1.55 (1.42 of Pulmonary, Critical Care, to 1.70), p<0.001) and had higher all-cause mortality to develop overt disease.4–7 Thus, the ability to Allergy and Immunology, and Sleep Medicine, University (HR (95% CI)=1.41 (1.29 to 1.54), p<0.001). They had identify the smokers with preserved spirometry of California, San Francisco higher rates of respiratory medication prescriptions (GOLD-defined or LLN-defined) who are at risk http://thorax.bmj.com/ Veterans Affairs Medical Center, and hospital and intensive care unit admissions. Other for the development of respiratory problems and San Francisco, CA 94121, USA; air trapping and static hyperinflation indices showed disease progression is of great interest for prognos- mehrdad. arjomandi@ ucsf. edu similar associations with health outcomes. Additionally, tication and intervention purposes. high-normal RV:TLC was associated with intermediate Air trapping, defined as abnormal increase in SZ and AT contributed equally. adverse health outcomes compared with low-normal volume of air remaining in the lungs at the end of Received 30 March 2018 and abnormal RV:TLC. Abnormal RV:TLC predicted exhalation, is a manifestation of obstructive lung Revised 19 June 2018 higher likelihood of progression to spirometric COPD (OR diseases including COPD. Air trapping in people Accepted 25 June 2018 (95% CI)=1.30 (1.03 to 1.65), p=0.027). with COPD is associated with increased dyspnoea, on September 23, 2021 by guest. Protected copyright. Conclusion In this study of the Veterans Affairs reduced functional capacity and higher mortality.8 9 electronic health records, air trapping was common in However, its clinical significance in smokers without smokers with preserved spirometry and predicted adverse COPD (normal FEV1:FVC and FEV1) is unknown. respiratory outcomes and progression to overt COPD. In fact, abnormal lung volumes suggestive of air trapping are routinely ignored in the interpretation of lung function when spirometry is preserved. In this study, we hypothesised that in patients at INTRODUCTION risk for COPD due to smoking but with preserved The Global Initiative on Obstructive Lung Disease spirometry, those with air trapping (and static © Article author(s) (or their (GOLD) defines COPD by an absolute reduction hyperinflation) as measured by residual volume employer(s) unless otherwise in FEV1 to FVC ratio of <0.70 after albuterol (RV), functional residual capacity (FRC), inspiratory stated in the text of thearticle) administration (stage 1), with higher stages of capacity (IC) and their ratios to total lung capacity 2018. All rights reserved. No COPD defined by a concomitant reduction in FEV1 (TLC) have increased respiratory morbidity and commercial use is permitted 1 unless otherwiseexpressly as a per cent predicted. Other criteria empha- mortality. To test this, we identified 7479 patients granted. sise a lower-limit-of-predicted normal (LLN) from the Veterans Administration Informatics and approach rather than a standard fixed cut-point in Computing Infrastructure (VINCI) database at risk To cite: Zeng S, Tham A, FEV1:FVC, but nonetheless rely on the same basic for COPD due to smoking who ever had a pulmonary Bos B, et al. Thorax Epub 2 3 ahead of print: [please metrics of spirometry. Many current and former function test (PFT) with concomitant lung volume include Day Month Year]. smokers without GOLD-defined (or LLN-defined) measurements that showed preserved spirometry doi:10.1136/ COPD have similar acute and chronic respiratory (defined by FEV1:FVC and FEV1≥LLN). We then thoraxjnl-2018-211881 symptoms as those with COPD and may proceed reviewed their subsequent electronic health records Zeng S, et al. Thorax 2018;0:1–11. doi:10.1136/thoraxjnl-2018-211881 1 Chronic obstructive pulmonary disease (EHR) and determined whether patients with air trapping were defined by those who were >40 years of age and had diagnosis Thorax: first published as 10.1136/thoraxjnl-2018-211881 on 20 July 2018. Downloaded from more likely to have adverse health outcomes compared with of tobacco use at the time of their full PFT. Smoking status was those without air trapping. assigned by documented diagnosis of ICD-9 or ICD-10 codes or diagnosis of smoking on PFT report. Accordingly, 52 668 METHODS patients who were not considered to be at risk for COPD were Study design excluded. Patients were further excluded if they had evidence of This was a retrospective study of EHR available from the nation- restrictive lung disease on PFT as determined by TLC ≤80% or wide Veterans Health Administration (VHA) VINCI database <LLN, diagnoses of interstitial lung diseases, or allergic lung with patients at risk for COPD (current or former smokers >40 diseases (except for asthma). Patients with a diagnosis of asthma years of age) who ever had a full PFT between 1985 and 2017. who were considered to be at risk for COPD were not excluded Medical records of eligible patients were interrogated to quan- to avoid exclusion of those with overlap disease. A further tify the frequency of acute and chronic respiratory outcomes 35 286 patients were excluded who had abnormal spirometry and mortality subsequent to their very first PFT that included (FEV1:FVC or FEV1<LLN). Overall, data were available from prealbuterol and postalbuterol administration spirometry and 7479 patients at risk for COPD but with preserved spirom- lung volume measurement by plethysmography. The latest etry from 37 Veterans Affairs Medical Centers across the USA postbronchodilator spirometry that was available in their EHR (figure 1). Data from other Veterans Affairs Medical Centers was also examined. Mortality data were extracted from docu- were not used due to lack of availability of coded PFT data that mented death notes, and patients were considered to be alive would be obtainable through VINCI. up to the date of their last medical encounter, after which they were considered as lost to follow-up. The utility of lung volume Statistical analysis indices from the first PFT to predict the subsequent occurrence Data management of the above outcomes was assessed in those with preserved Predicted values and ranges for PFT measurements were calcu- spirometry. lated using Crapo predicted formulas,10–12 except for FRC:TLC, The University of California San Francisco Institutional IC and IC:TLC for which data from Quanjer et al and Francisco Review Board and the Veterans Health Administration Research et al were used.2 13 Patients were categorised to have air trapping and Development Committee approved this study. Detailed if they had abnormal RV:TLC (greater than the upper limit of inclusion and exclusion algorithm and the International Classifi- normal (ULN)). Those with normal RV:TLC were further cate- cation of Diseases (ICD)-9 and ICD-10 diagnosis codes used are gorised into low-normal and high-normal groups relative to the available in the online supplementary appendix. median value of the distribution of normal RV:TLC. Study population Outcomes From 1985 to 2017, 127 940 patients from the VHA were docu- Healthcare outcomes including clinical diagnoses, respiratory mented to have received full PFT including postbronchodilator medication prescribed, outpatient office visits, emergency room spirometry and lung volume measurements by plethysmog- (ER) visits, hospital admissions and intensive care unit (ICU) http://thorax.bmj.com/ raphy. Our study aimed to focus on patients at risk for COPD as admissions with a COPD diagnosis and all-cause mortality on September 23, 2021 by guest. Protected copyright. Figure 1 Subject flow. LLN, lower limit of normal; PFT, pulmonary function test; TLC, total lung capacity.