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• Lung volumes measurement for risk stratification in smokers without COPD
  Mehrdad Arjomandi
  Published on: 15 January 2019
• Should lung volumes measurement accompany every spirometry?
  Spyridon Fortis
  Published on: 15 January 2019

• Published on: 15 January 2019

  Lung volumes measurement for risk stratification in smokers without COPD

  • Mehrdad Arjomandi, Associate Professor of Medicine University of California San Francisco; San Francisco Veterans Affairs Medical Center

  We appreciate the points raised by the commentator about our study (Zeng et al.)[1] published in June 2018 issue of Thorax that (1) the prevalence of abnormal residual volume to total lung capacity ratio (RV:TLC) in our study of ever-smokers with preserved spirometry is substantially higher than that observed in the commentator’s past studies,[2-4] and (2) an assumption by the commentator that stringent exclusion of those with abnormally low TLC and those with diagnosis codes of interstitial lung diseases (ILD) in their electronic health records (EHR) may have resulted in overestimation of the prevalence of abnormally high RV:TLC among smokers with preserved spirometry.

  We would like to draw the attention of commentator and readers to the following points:

  1- The studies referenced by the commentator used pulmonary function tests (PFT) data collected from 708 patients in 2013 across 5 clinical sites associated with University of Minnesota Medical Center with inclusion criteria of patients 18 years of age or older with or without history of smoking.[2] They included about 50% women and 3 African Americans. Our study was performed on PFT data obtained from 1985 through 2017 through the United States Veterans Affairs (VA) nationwide EHR from 7,479 patients across 37 VA medical centers in the United States with inclusion criteria of patients 40 years of age or older with an EHR diagnosis code of smoking, which likely suggests heavy smoking for VA patients. Our st...

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  We appreciate the points raised by the commentator about our study (Zeng et al.)[1] published in June 2018 issue of Thorax that (1) the prevalence of abnormal residual volume to total lung capacity ratio (RV:TLC) in our study of ever-smokers with preserved spirometry is substantially higher than that observed in the commentator’s past studies,[2-4] and (2) an assumption by the commentator that stringent exclusion of those with abnormally low TLC and those with diagnosis codes of interstitial lung diseases (ILD) in their electronic health records (EHR) may have resulted in overestimation of the prevalence of abnormally high RV:TLC among smokers with preserved spirometry.

  We would like to draw the attention of commentator and readers to the following points:

  1- The studies referenced by the commentator used pulmonary function tests (PFT) data collected from 708 patients in 2013 across 5 clinical sites associated with University of Minnesota Medical Center with inclusion criteria of patients 18 years of age or older with or without history of smoking.[2] They included about 50% women and 3 African Americans. Our study was performed on PFT data obtained from 1985 through 2017 through the United States Veterans Affairs (VA) nationwide EHR from 7,479 patients across 37 VA medical centers in the United States with inclusion criteria of patients 40 years of age or older with an EHR diagnosis code of smoking, which likely suggests heavy smoking for VA patients. Our study included only 7.5% women but 8.8% African Americans. The populations in our study and that of the commentator’s study are very different. Given the heavier smoking burden at the VA,[5] it is not unexpected to identify higher smoking-related pathology including higher prevalence of air trapping among the VA patients. Of note, through their deployments, veterans are also exposed to high levels of air pollutants,[6] which have been shown to contribute considerably to development of chronic obstructive pulmonary disease (COPD).[7]
  2- As mentioned in our article, a limitation of our study was that spirometries, and specifically full PFT, were likely done due to clinical concerns for respiratory diseases, and given the inclusion of plethysmography, the likely existence of concerns for ILD. This selection bias may then contribute to a higher prevalence of receiving an ILD diagnosis in those patients’ records in our study.
  3- Abnormally low TLC could occur for reasons other than ILD including obesity, which is a common health problem and thus may have resulted in exclusions of many patients from our study.
  4- It is important to note that the assumption of stringent exclusion of those with ILD and abnormally low TLC should result in the remaining included patients to have higher than expected TLC, and should not result in the remaining patients to have high RV; that is, the remaining subjects should have the same level RV but higher TLC, and hence lower RV:TLC ratio. Thus, if the commentator’s assumption that “stringent exclusion criteria resulted in a very small denominator” were correct, then the algorithm of our study indeed would have been biased towards generating lower than expected prevalence of abnormally high RV:TLC, leading to an underestimation, not overestimation, of the prevalence of abnormally high RV:TLC.
  5- Most remarkably, a finding that we would like to emphasize and should not be overlooked is that regardless of whether the RV:TLC ratio was normal or abnormal, it was linearly and directly associated with respiratory morbidity and progression to spirometric COPD. No threshold level was observed.
  6- It is now estimated that approximately 20% of COPD is caused by exposure to air pollutants (including pollutants other than biomass smoke such as the daily air pollution experienced by all across the globe).[8] Given above, the use of “normal” or “abnormal” values and reference equations should be approached cautiously as it is potentially extremely difficult if not impossible to develop a “normal” cohort when all earth inhabitants are being exposed to air pollutants. This is consistent with our related findings in a previous article showing that in never-smokers with history of exposure to air pollutants, all with preserved spirometry AND normal range of RV:TLC, higher RV:TLC ratio was associated with worse physiologic performance.[9]
  7- Finally, the commentator’s statement about lesser reliability and lack of rationale for use of lung volumes in smokers at risk for COPD is fascinating. Spirometry is an extremely important tool in assessment of respiratory diseases including COPD. It is easier to use than plethysmography and more widely available. However, COPD is a complex disease and reducing it to one or two dimensions is unhelpful.[10] As demonstrated in our article, lung volumes, regardless of whether in the normal or abnormal range, provide an additional dimension to help prognosticate in early obstructive lung disease in those at risk for COPD. In their study of 708 patients with normal spirometry,[2] the commentator and colleagues did conclude that their “findings point out the importance of measuring lung volumes in symptomatic patients who have normal spirometry.” We fully agree with them.

  References:

  1. Zeng, S., et al., Lung volume indices predict morbidity in smokers with preserved spirometry. Thorax, 2018.
  2. Fortis, S., E.O. Corazalla, and H.J. Kim, Does normal spirometry rule out an obstructive or restrictive ventilatory defect? Respir Investig, 2017. 55(1): p. 55-57.
  3. Fortis, S., et al., The difference between slow and forced vital capacity increases with increasing body mass index: a paradoxical difference in low and normal body mass indices. Respir Care, 2015. 60(1): p. 113-8.
  4. Fortis, S., et al., Persistent Empiric COPD Diagnosis and Treatment After Pulmonary Function Test Showed No Obstruction. Respir Care, 2016. 61(9): p. 1192-200.
  5. Odani, S., et al., Tobacco Product Use Among Military Veterans - United States, 2010-2015. MMWR Morb Mortal Wkly Rep, 2018. 67(1): p. 7-12.
  6. Falvo, M.J., et al., Airborne hazards exposure and respiratory health of Iraq and Afghanistan veterans. Epidemiol Rev, 2015. 37: p. 116-30.
  7. van Koeverden, I., et al., Secondhand Tobacco Smoke and COPD Risk in Smokers: A COPDGene Study Cohort Subgroup Analysis. COPD, 2015. 12(2): p. 182-9.
  8. Eisner, M.D., et al., An official American Thoracic Society public policy statement: Novel risk factors and the global burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2010. 182(5): p. 693-718.
  9. Arjomandi, M., et al., Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction. BMJ Open Respir Res, 2018. 5(1): p. e000284.
  10. Agusti, A., B. Celli, and R. Faner, What does endotyping mean for treatment in chronic obstructive pulmonary disease? Lancet, 2017. 390(10098): p. 980-987.

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  Conflict of Interest:
  None declared.

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• Published on: 15 January 2019

  Should lung volumes measurement accompany every spirometry?

  • Spyridon Fortis, Pulmonary and Critica Care physician 1Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics

  Should lung volumes measurement accompany every spirometry?
  Spyridon Fortis MD1
  1Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics, Iowa City, IA, USA

  Corresponding Author:
  Spyridon Fortis, MD
  UIHC – Internal Medicine
  200 Hawkins Drive – C33 GH
  Iowa City, IA 52242
  Email: spyridon-fortis@uiowa.edu
  Word Count:
  Author Disclosures: Authors declare that there is no conflict of interest regarding the publication of this paper.
  Running Head: Lung volumes with every spirometry
  Key Words: COPD, diagnosis, lung volumes, RV/TLC, preserved lung function.

  In their study published in the June 2018 issue of Thorax, Zeng et al showed that RV/TLC ratio in smokers with preserved lung function is associated with clinical diagnosis of COPD, higher rates of respiratory medications prescriptions, emergency room visits, hospitalizations, and all cause-mortality[1]. The findings strongly support that patients with respiratory symptoms and normal spirometry who have air trapping in lung volume measurements have worse outcomes than those with no air trapping. Those patients at risk for COPD may suffer early obstructive lung disease which has not yet met the spirometric criteria for COPD diagnosis.
  I congratulate the authors for their study as they address a very clinically relevant topic. Further studies are neede...

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  Should lung volumes measurement accompany every spirometry?
  Spyridon Fortis MD1
  1Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics, Iowa City, IA, USA

  Corresponding Author:
  Spyridon Fortis, MD
  UIHC – Internal Medicine
  200 Hawkins Drive – C33 GH
  Iowa City, IA 52242
  Email: spyridon-fortis@uiowa.edu
  Word Count:
  Author Disclosures: Authors declare that there is no conflict of interest regarding the publication of this paper.
  Running Head: Lung volumes with every spirometry
  Key Words: COPD, diagnosis, lung volumes, RV/TLC, preserved lung function.

  In their study published in the June 2018 issue of Thorax, Zeng et al showed that RV/TLC ratio in smokers with preserved lung function is associated with clinical diagnosis of COPD, higher rates of respiratory medications prescriptions, emergency room visits, hospitalizations, and all cause-mortality[1]. The findings strongly support that patients with respiratory symptoms and normal spirometry who have air trapping in lung volume measurements have worse outcomes than those with no air trapping. Those patients at risk for COPD may suffer early obstructive lung disease which has not yet met the spirometric criteria for COPD diagnosis.
  I congratulate the authors for their study as they address a very clinically relevant topic. Further studies are needed to examine whether treatment of those patients improve their outcomes. The prevalence of this specific pulmonary function test pattern, though, may be much less than 30%. Using more stringent exclusion criteria, authors excluded 15,236 patients for low TLC. They also excluded 16,904 patients with interstitial lung disease to ensure that the high-risk for COPD sample is not contaminated by other lung diseases like interstitial lung disease. These numbers appear extremely high given that the prevalence of ILD is much less than 1%. The stringent exclusion criteria (120,461 of 127,940) have resulted in a very small denominator which led to overestimation of the prevalence of this PFT pattern. In previous studies, including only PFTs that met the American Thoracic Society standards from one single health system, we have shown that only 4.9% of all PFTs had TLC, RV and/or RV/TLC above the upper limit of normal[2 , 3]. Of those PFTs with normal spirometry, 12.4% of them had TLC, RV and/or RV/TLC above the upper limit of normal and 10.4% of them had RV and/or RV/TLC above the upper limit of normal[3].
  Using lung volumes like RV/TLC in every day practice should be exercised with caution, in particular, in the presence of normal spirometry. The reference values determine whether a spirometric or lung volume value of an individual is normal or abnormal. Spirometric reference values are derived from large cohorts[4] while lung volume measurement values are derived from small cohort and often from samples that are not representative of our population[5]. Thus, lung volume measurements are less reliable than spirometry.
  Although, lung volume measurement may offer additional prognostic information, it is still unclear whether they should be routinely performed in every patient with respiratory symptoms.

  References
  1. Zeng S, Tham A, Bos B, Jin J, Giang B, Arjomandi M. Lung volume indices predict morbidity in smokers with preserved spirometry. Thorax 2018 doi: 10.1136/thoraxjnl-2018-211881[published Online First: Epub Date]|.
  2. Fortis S, Corazalla EO, Jacobs DR, Jr., Kim HJ. Persistent Empiric COPD Diagnosis and Treatment After Pulmonary Function Test Showed No Obstruction. Respiratory care 2016;61(9):1192-200 doi: 10.4187/respcare.04647[published Online First: Epub Date]|.
  3. Fortis S, Corazalla EO, Kim HJ. Does normal spirometry rule out an obstructive or restrictive ventilatory defect? Respiratory investigation 2017;55(1):55-57 doi: 10.1016/j.resinv.2016.07.005[published Online First: Epub Date]|.
  4. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. American journal of respiratory and critical care medicine 1999;159(1):179-87 doi: 10.1164/ajrccm.159.1.9712108[published Online First: Epub Date]|.
  5. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. The European respiratory journal. Supplement 1993;16:5-40

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  Conflict of Interest:
  None declared.

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