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Is pulmonary diffusion capacity for nitric oxide (DL,NO) likely to become a routine pulmonary function test?
G Model
ARTICLE IN PRESS
RESPNB-2773; No. of Pages 2
Respiratory Physiology & Neurobiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol
Is pulmonary diffusion capacity for nitric oxide (DL,NO) likely to become a routine pulmonary function test? Irene Steenbruggen 1,∗ , Frans de Jongh 2 1 2
Isala, Lung Function Department, Zwolle, The Netherlands Medisch Spectrum Twente, Lung Function Department, Enschede, The Netherlands
a r t i c l e
i n f o
Article history: Received 8 November 2016 Received in revised form 14 February 2017 Accepted 15 February 2017 Available online xxx
a b s t r a c t DL,CO measurements are often used to evaluate and monitor lung diseases as well as cardiovascular diseases. Whether the combination of DL,CO and DL,NO will improve the management of cardiovascular diseases needs to be investigated. It is hoped that the standardization of the DL,NO measurement will facilitate research. Scientific evidence that DL,NO can provide more accurate information than DL,CO alone, can take away the barriers that prevents DL,NO to become a routine test in pulmonology. © 2017 Elsevier B.V. All rights reserved.
Pulmonary function tests are valuable tools for investigating and evaluating patients with respiratory diseases. Worldwide many pulmonary function laboratories provide several lung function tests. Standardization of tests is crucial in providing high quality care and to harmonize test results across laboratories. The measurement of the single-breath carbon monoxide uptake (DL,CO) is one of the most widely used routine pulmonary function tests. Standards for DL,CO measurements were published in 2005 by the European Respiratory Society (ERS) and the American Thoracic Society (ATS). (MacIntyre et al., 2005) Recently, a joint taskforce, appointed by ERS and ATS published an update to the 2005 DL,CO-standard (Graham et al., 2017). This update is predominantly focused on the use of fast infrared gas analyzers for carbon monoxide and methane. These real-time gas analyzers are currently used in most commercial available DL,CO equipment. In 2015 an ERS task force was created to standardize the measurement on pulmonary diffusing capacity for nitric oxide (DL,NO) (Zavorsky et al., 2017). As pointed out by this task force, the use of DL,NO compared to DL,CO has several practical advantages. No correction is needed for hemoglobin, since DL,NO is just minimally affected by hemoglobin and carboxyhemoglobin. In terms of reproducibility, DL,NO performs better than DL,CO. Another advantage of the DL,NO measurement is it can be measured in conjunction with a DL,CO measurement during one single breath manoeuvre. However, all commercial available sys-
∗ Corresponding author. E-mail address: [email protected] (I. Steenbruggen).
tems with DL,NO option, are equipped with electrochemical cells. These electrochemical cells are slow speed and cannot be used with the real-time analyzers that are currently used in most pulmonary function systems. More sensitive analyzers with fast response times, e.g. chemiluminescence analyzers, could be incorporated in the currently used pulmonary function systems. These chemiluminescence analyzers are accurate and precise, but they are also expensive, quite large and require frequent calibration. Although classical systems which use helium as tracer gas, will still be in use in some pulmonary function laboratories, many laboratories are now equipped with DL,CO systems with rapid responding gas analyzers. No manufacturer has implemented the DL,NO as an option yet in these currently most used systems. Because of the use of an electrochemical cell In the single breath DL,NO test, a breath hold time of 4–6 s is required instead of the 10 s that is used for the DL,CO. This is due to the lower sensitivity of the electrochemical NO analyzer. In healthy individuals, a shorter breath hold time will give more or less equivalent results. However, in patients with airflow obstruction a breath hold time of 4–6 s will be insufficient to allow complete diffusion of the inspired CO, and thus will result in underestimation of DL,CO. In the event that a cheap, rapid NO gas analyzer is added to pulmonary function systems along with the rapid CO gas analyzer, one could measure both gas concentrations during the complete exhalation (after the breath hold time) and even more clinical relevant information might be revealed. Moreover, standard spirometry is more and more performed at primary care offices, so pulmonary function labs shift to more complicated measurements requiring advanced gases and measurement devices. Early and accurate detection of pulmonary diseases like COPD, yet still mainly classified by the fall in FEV1,
http://dx.doi.org/10.1016/j.resp.2017.02.009 1569-9048/© 2017 Elsevier B.V. All rights reserved.
Please cite this article in press as: Steenbruggen, I., de Jongh, F., Is pulmonary diffusion capacity for nitric oxide (DL,NO) likely to become a routine pulmonary function test? Respir. Physiol. Neurobiol. (2017), http://dx.doi.org/10.1016/j.resp.2017.02.009
G Model RESPNB-2773; No. of Pages 2 2
ARTICLE IN PRESS I. Steenbruggen, F. de Jongh / Respiratory Physiology & Neurobiology xxx (2017) xxx–xxx
might be improved with diffusion measurements, especially since often in the first stage the alveolar-capillary membrane is affected. In the far future adding extra analyzers for instance for detecting volatile organic compounds, present in the exhaled breath, might improve clinical value. DL,CO measurements are often used to evaluate and monitor lung diseases as well as cardiovascular diseases. Whether the combination of DL,CO and DL,NO will improve the management of cardiovascular diseases needs to be investigated. At this moment most physicians do not seem to be very interested in DL,NO measurements since present studies did not yet prove sufficient evidence that the additional value is clinically relevant enough to outweigh the costs. As a result, manufacturers will not be interested to implement DL,NO to the DL,CO systems which use rapid analyzers. To facilitate the use of DL,NO, prediction equations are included in the ERS task force document on standardization of technique and application of single-breath DL,NO (Zavorsky et al., 2017).
It is hoped that the standardization of the DL,NO measurement will facilitate research. Scientific evidence that DL,NO can provide more accurate information than DL,CO alone, can take away the barriers that prevents DL,NO to become a routine test in pulmonology. References Graham, B.L., Brusasco, V., Burgos, F., Cooper, B.G., Jensen, R., Kendrick, A.R., MacIntyre, N.R., Thompson, B.R., Wanger, J., 2017. Summary: 2016 ERS/ATS Standards for single-breath carbon monoxide uptake in the lung. Eur. Respir. J. 49, 1600016. MacIntyre, N., Crapo, R., Viegi, G., Johnson, D., et al., 2005. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur. Respir. J. 26, 720–735. Zavorsky, G.S., Hsia, C.C.W., Hughes, J.M.B., Borland, C.D.R., Guenard, H.J., Van der Lee, I., Steenbruggen, I., Naeije, R., Cao, J., Dinh-Xuan, A.T., 2017. Standardization and application of the single-breath determination of nitric oxide uptake in the lung. Eur. Respir. J. 49, 1600962.
Please cite this article in press as: Steenbruggen, I., de Jongh, F., Is pulmonary diffusion capacity for nitric oxide (DL,NO) likely to become a routine pulmonary function test? Respir. Physiol. Neurobiol. (2017), http://dx.doi.org/10.1016/j.resp.2017.02.009
ARTICLE IN PRESS
RESPNB-2773; No. of Pages 2
Respiratory Physiology & Neurobiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol
Is pulmonary diffusion capacity for nitric oxide (DL,NO) likely to become a routine pulmonary function test? Irene Steenbruggen 1,∗ , Frans de Jongh 2 1 2
Isala, Lung Function Department, Zwolle, The Netherlands Medisch Spectrum Twente, Lung Function Department, Enschede, The Netherlands
a r t i c l e
i n f o
Article history: Received 8 November 2016 Received in revised form 14 February 2017 Accepted 15 February 2017 Available online xxx
a b s t r a c t DL,CO measurements are often used to evaluate and monitor lung diseases as well as cardiovascular diseases. Whether the combination of DL,CO and DL,NO will improve the management of cardiovascular diseases needs to be investigated. It is hoped that the standardization of the DL,NO measurement will facilitate research. Scientific evidence that DL,NO can provide more accurate information than DL,CO alone, can take away the barriers that prevents DL,NO to become a routine test in pulmonology. © 2017 Elsevier B.V. All rights reserved.
Pulmonary function tests are valuable tools for investigating and evaluating patients with respiratory diseases. Worldwide many pulmonary function laboratories provide several lung function tests. Standardization of tests is crucial in providing high quality care and to harmonize test results across laboratories. The measurement of the single-breath carbon monoxide uptake (DL,CO) is one of the most widely used routine pulmonary function tests. Standards for DL,CO measurements were published in 2005 by the European Respiratory Society (ERS) and the American Thoracic Society (ATS). (MacIntyre et al., 2005) Recently, a joint taskforce, appointed by ERS and ATS published an update to the 2005 DL,CO-standard (Graham et al., 2017). This update is predominantly focused on the use of fast infrared gas analyzers for carbon monoxide and methane. These real-time gas analyzers are currently used in most commercial available DL,CO equipment. In 2015 an ERS task force was created to standardize the measurement on pulmonary diffusing capacity for nitric oxide (DL,NO) (Zavorsky et al., 2017). As pointed out by this task force, the use of DL,NO compared to DL,CO has several practical advantages. No correction is needed for hemoglobin, since DL,NO is just minimally affected by hemoglobin and carboxyhemoglobin. In terms of reproducibility, DL,NO performs better than DL,CO. Another advantage of the DL,NO measurement is it can be measured in conjunction with a DL,CO measurement during one single breath manoeuvre. However, all commercial available sys-
∗ Corresponding author. E-mail address: [email protected] (I. Steenbruggen).
tems with DL,NO option, are equipped with electrochemical cells. These electrochemical cells are slow speed and cannot be used with the real-time analyzers that are currently used in most pulmonary function systems. More sensitive analyzers with fast response times, e.g. chemiluminescence analyzers, could be incorporated in the currently used pulmonary function systems. These chemiluminescence analyzers are accurate and precise, but they are also expensive, quite large and require frequent calibration. Although classical systems which use helium as tracer gas, will still be in use in some pulmonary function laboratories, many laboratories are now equipped with DL,CO systems with rapid responding gas analyzers. No manufacturer has implemented the DL,NO as an option yet in these currently most used systems. Because of the use of an electrochemical cell In the single breath DL,NO test, a breath hold time of 4–6 s is required instead of the 10 s that is used for the DL,CO. This is due to the lower sensitivity of the electrochemical NO analyzer. In healthy individuals, a shorter breath hold time will give more or less equivalent results. However, in patients with airflow obstruction a breath hold time of 4–6 s will be insufficient to allow complete diffusion of the inspired CO, and thus will result in underestimation of DL,CO. In the event that a cheap, rapid NO gas analyzer is added to pulmonary function systems along with the rapid CO gas analyzer, one could measure both gas concentrations during the complete exhalation (after the breath hold time) and even more clinical relevant information might be revealed. Moreover, standard spirometry is more and more performed at primary care offices, so pulmonary function labs shift to more complicated measurements requiring advanced gases and measurement devices. Early and accurate detection of pulmonary diseases like COPD, yet still mainly classified by the fall in FEV1,
http://dx.doi.org/10.1016/j.resp.2017.02.009 1569-9048/© 2017 Elsevier B.V. All rights reserved.
Please cite this article in press as: Steenbruggen, I., de Jongh, F., Is pulmonary diffusion capacity for nitric oxide (DL,NO) likely to become a routine pulmonary function test? Respir. Physiol. Neurobiol. (2017), http://dx.doi.org/10.1016/j.resp.2017.02.009
G Model RESPNB-2773; No. of Pages 2 2
ARTICLE IN PRESS I. Steenbruggen, F. de Jongh / Respiratory Physiology & Neurobiology xxx (2017) xxx–xxx
might be improved with diffusion measurements, especially since often in the first stage the alveolar-capillary membrane is affected. In the far future adding extra analyzers for instance for detecting volatile organic compounds, present in the exhaled breath, might improve clinical value. DL,CO measurements are often used to evaluate and monitor lung diseases as well as cardiovascular diseases. Whether the combination of DL,CO and DL,NO will improve the management of cardiovascular diseases needs to be investigated. At this moment most physicians do not seem to be very interested in DL,NO measurements since present studies did not yet prove sufficient evidence that the additional value is clinically relevant enough to outweigh the costs. As a result, manufacturers will not be interested to implement DL,NO to the DL,CO systems which use rapid analyzers. To facilitate the use of DL,NO, prediction equations are included in the ERS task force document on standardization of technique and application of single-breath DL,NO (Zavorsky et al., 2017).
It is hoped that the standardization of the DL,NO measurement will facilitate research. Scientific evidence that DL,NO can provide more accurate information than DL,CO alone, can take away the barriers that prevents DL,NO to become a routine test in pulmonology. References Graham, B.L., Brusasco, V., Burgos, F., Cooper, B.G., Jensen, R., Kendrick, A.R., MacIntyre, N.R., Thompson, B.R., Wanger, J., 2017. Summary: 2016 ERS/ATS Standards for single-breath carbon monoxide uptake in the lung. Eur. Respir. J. 49, 1600016. MacIntyre, N., Crapo, R., Viegi, G., Johnson, D., et al., 2005. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur. Respir. J. 26, 720–735. Zavorsky, G.S., Hsia, C.C.W., Hughes, J.M.B., Borland, C.D.R., Guenard, H.J., Van der Lee, I., Steenbruggen, I., Naeije, R., Cao, J., Dinh-Xuan, A.T., 2017. Standardization and application of the single-breath determination of nitric oxide uptake in the lung. Eur. Respir. J. 49, 1600962.
Please cite this article in press as: Steenbruggen, I., de Jongh, F., Is pulmonary diffusion capacity for nitric oxide (DL,NO) likely to become a routine pulmonary function test? Respir. Physiol. Neurobiol. (2017), http://dx.doi.org/10.1016/j.resp.2017.02.009