The new ERS/ATS standards for DLCO testing were published in the January issue of the European Respiratory Journal. The article was published as open access and can be downloaded from the ERJ website.
The biggest difference between the new standards and those from 2005 is that they are now primarily oriented towards Rapid-response Gas Analyzers (RGA). The authors explicitly state that the new standards do not make older systems that use discrete alveolar sampling and slower gas analyzers obsolete, but many of the new suggestions and requirements for labs and manufacturers require systems with a RGA.
The differences between the 2017 and 2005 standards that I’ve been able to find include:
♦ Flow accuracy was not specified in the 2005 standard but is now required to be ± 2% over a range of ± 10 L/sec.
♦ Volume accuracy is now required to be ± 2.5% (± 75 ml) instead of ± 3.5%. Notably the 2005 standard included a ± 0.5% error in the calibrating syringe. The accuracy of the 3-liter syringe is now stated separately. In the 2005 standard volume accuracy was over an 8-liter range. No volume range is specified in the 2017 standard.
♦ RGA response time (analyzer rise time) had not previously been specified but is now required to be ≤150 milliseconds. Sample transit time was discussed but no specific recommendations were made. Sample transport issues such as Taylor dispersion, gas viscosity and turbulence at gas fittings was also discussed and although it was suggested that manufacturers attempt to minimize these effects no specific recommendations were made.
♦ Analyzer linearity for both RGA and discrete sample systems has been relaxed to ± 1.0% in the 2017 standards from ± 0.5% in the 2005 standards.
♦ CO analyzer accuracy for both RGA and discrete sample systems is now specified as ≤10 ppm (which is ±0.3% of 0.3% CO). It was previously specified as ± 0.0015% (which is ± 0.5% of 0.3% CO).
♦ Interference from CO2 and water vapor for both RGA and discrete sample systems is now specified as ≤10 ppm error in CO (when CO2 and water vapor are ≤5%). Interference was recognized as a problem in the 2005 standard but error limits were not specified.
♦ Digital sampling rate was not discussed or specified in the 2005 standards. It is now specified as a minimum of ≥100 hz with a resolution of 14 bits. A 1000 hz sampling rate is recommended.
♦ Analyzer drift is specified in the 2017 standard as ≤ 10 ppm for CO and 0.5% of full scale for the tracer gas over 30 seconds. The 2005 standard specified drift as 0.5% of full scale over 30 seconds and did not differentiate between CO and tracer gases. The 2017 standards recommends that manufacturers provide a test mode to test drift.
♦ Barometric pressure sensor accuracy is now required to be within ±2.5%. This was not previously specified.
♦ Manufacturers of RGA systems are now required to include the following features:
- Monitor and report end-expiratory tracer gas and carbon monoxide concentrations and to alert the operator if the washout from previous testing is incomplete.
- Compensation for end-expiratory gas concentrations prior to test gas inhalation in the calculation of VA and DLCO.
- Ensure proper alignment of gas concentration signals and the flow signal (although notably specifications for this are not included).
- Measure anatomic dead-space using the Fowler method.
- Display a graph of exhaled gas concentration versus volume (not time) to confirm the point of dead-space washout and to report the amount of manual adjustment if this was done.
- Measure VA using all of the tracer gas data from the entire maneuver in the mass balance equation.
- Report the DLCO adjusted for the change in PAO2 due to barometric pressure.
♦ Further recommended (but not required) RGA options include:
- Ability to input simulated digital test data and compute DLCO, VA, TLC and Vb with ± 2% accuracy expected.
- Report the DLCO adjusted for change in PAO2 due to PACO2 with ± 2% accuracy.
♦ The maximum inspiratory pressure for demand valves has been reduced to <9 cmH2O from <10 cm H2O.
♦ Machine deadspace for adult testing has decreased to 200 ml from 350 ml. There was a further recommendation that machine deadspace should be smaller for children and patients with a VC <2.0 L but no specific requirements were made.
♦ Daily volume calibration must now be performed three time with a 3-liter syringe with using varying flow rates between 0.5 and 12.0 L/sec (injection times 0.5 – 6.0 seconds). Accuracy was not previously specified and now must be <2.5% error.
♦ Timer accuracy was specified in the 2005 standards. There are no timer specifications in the 2017 standards.
♦ Flow sensor zeroing prior to testing is now required.
♦ Gas analyzer linearity must now be checked monthly. The 2005 standards specified every three months. Manufacturers are urged to automate this process.
♦ A monthly calibration syringe leak test is now required.
♦ Both biological and calibration syringe QC testing are now required weekly. Previously either biological or calibration syringe QC were to be preformed weekly.
♦ Previous calibration syringe QC required the measured inspired volume (VI) to be “~3.30 L”. 2017 standards require accuracy to be ± 300 ml of VI * {STPD to BTPS conversion factor}. [Please note that there is a typo in the paragraph specifying this on page 8, line 8 in the 2017 standards where VA was substituted for VI].
♦ Changes in biological QC requiring action have been relaxed to a >12% change or >3 ml/min/mmHg (whichever is larger) from a simple >10% change. The 2017 standards also state that a mean of 6 prior tests should be used for this while the 2005 standards merely stated “from previous values”. Manufacturers were urged to developed automated QC processes.
♦ Calibration and QC logs can now be kept in a digital file folder.
♦ It was recommended that deep breaths during the pre-test tidal breathing period should be avoided in the 2005 standards but this was not included in the 2017 standards.
♦ The maximum acceptable time for exhalation to RV has been increased from 6 seconds to 12 seconds.
♦ Target VI has changed from ≥85% of the patient’s largest VC to ≥90%. The 2017 standards state however, that a VI of ≥85% of the patient’s largest VC is acceptable if the VA is within 200 ml or 5% (whichever is larger) of the patient’s highest VA from acceptable DLCO maneuvers.
♦ The 2017 standards now recommend that with RGA systems the exhalation following breath-holding should continue to RV in order to calculate VA using a mass-balance equation. Total expiratory time for discrete sample systems (washout and sample collection time) is still ≤4 seconds but is specified as ≤12 seconds in RGA systems.
♦ The DLCO test gas mixture is now required to contain 21% O2. The 2005 standards discussed a range of FIO2’s from 0.17 to 0.21 but only recommended that “inspired oxygen partial pressure values similar to the reference set used in the interpretation” be used.
♦ The required interval between tests (4 minutes minimum, 10 minutes for patients with severe obstruction) now includes the recommendation that the tracer gas concentration at end-exhalation (prior to the inhalation of the test gas mixture) should be ≤ 2% of the inspired concentration.
♦ The 2017 standards now recommend that the end-exhalation concentrations of CO (prior to inhalation of the test gas mixture) be used to adjust DLCO tests for CO back-pressure, to calculate COHb and to compensate for the effects of water vapor and CO2 on gas analyzers.
♦ The 2017 standards discuss the effect that prior testing (spirometry, bronchodilators and N2 washouts) have on DLCO and states that:
- bronchodilators are unlikely to affect DLCO and may therefore be used prior to DLCO testing
- prior spirometry efforts may affect DLCO but this has not been proven and therefore makes no recommendations against performing spirometry prior to DLCO testing
- sufficient time for alveolar O2 levels to return to normal is needed (2 times O2 wash-in time) after performing an N2 washout test. The standard recommends against performing N2 washout tests before DLCO testing but did not make this a requirement.
♦ The 2017 standards recommend that RGA systems calculate VA using mass-balance equations and this is discussed in detail (pages 17-19). This was not previously discussed nor was it an option.
♦ The equation for calculating anatomical deadspace using height (equation 20, page 16) is different from the one suggested in the 2005 standard (equation 10, page 728) but appears to be a restatement rather than being completely different.
♦ The 2017 standards discuss the measurement of anatomical dead space using the Fowler technique in detail. This was not previously discussed.
♦ The 2017 standards discuss flow and gas analyzer signal alignment in detail. This was not previously discussed.
♦ The 2017 standards discuss KCO with significantly more detail than in the 2005 standards. In particular although KCO is calculated from DLCO/VA it should be reported as KCO and not DLCO/VA.
♦ The 2017 standards discuss measuring the Phase III slope during exhalation as an index of ventilation inhomogeneity but does not specifically recommend it (probably a good idea since Phase III slopes during a single-breath N2 washout are usually obtained with low and constant expiratory flow rates which aren’t necessarily congruent with the expiratory flow rates during a DLCO maneuver and the differences between the manner in which these slopes are measured has not been studied).
♦ Repeatability between DLCO tests is now 2.0 ml/min/mmhg compared to 3.0 ml/min/mmHg in the previous standards.
♦ The 2017 standards include a suggested scoring/grading system for test quality based on inspired volume, breath-holding time and sample collection time (Table 3, page 22).
♦ Although the 2017 standards discusses the use of expired CO2 to estimate PAO2 it does not specifically recommend this.
♦ The 2017 standards have a new equation (38, page 24) used to correct DLCO for end-exhalation CO.
♦ The 2017 standards have new equations for altitude and barometric pressure correction (40 & 41, page 25) that are not a restatement of the previous equation (16, page 730).
♦ The 2017 standards include equations (42 & 43, page 25) to estimate barometric pressure at altitude that were not in the previous standards.
♦ The 2005 standards included equations to correct DLCO for alveolar volume (19 & 20, page 730) that are not discussed and not included in the 2017 standards.
♦ The DLCO results that are reported (Table 4, page 26) are now required to include:
- DLCO adjusted for barometric pressure
- DLCO LLN and/or Z-score
- VA LLN and/or Z-score
- KCO (instead of DLCO/VA)
- KCO LLN and/or Z-score
- Barometric pressure
- Average Breath-hold time
- Fowler anatomical dead space (RGA systems only)
- Single-breath TLC (RGA systems only)
- Test quality grade for acceptable maneuvers
- Reference values source
- Graphs of full maneuver.
- Graphs of exhaled gas concentrations versus volume (RGA systems only).
♦ The 2017 standards do not recommend any specific reference equations but note that many of the equations in use predate the 2005 standards. A short list (Table 5, page 27) of studies that were performed using the 2005 standards was included but it should be noted that the majority of the listed studies are pediatric and not adult.
Overall however, I am pleased that new DLCO standards have finally been released and that they are as comprehensive and forward looking as they are. I am pleased to see that many issues I had raised in previous blog postings have been addressed. I am also pleased that the bar has been raised on technical specifications, including calibration and quality control, and that care that has been taken make the standards as applicable to both old and new test systems.
There are two issues, however that I feel the need to comment on.
One of the biggest new recommendations is for patients on RGA systems to exhale to RV following the breath-hold period and that VA should be calculated with a mass-balance equation using the tracer gas concentrations that occur during the entire exhalation. DLCO is calculated however, using the CO gas concentrations from just the alveolar sample. Although the VA derived using mass balance will more likely approximate TLC, particularly when airway obstruction is present, other than the fact that this would raise the measured DLCO in patients with COPD the overall validity of this approach was not discussed.
I am still hard-pressed to understand why the 2017 standards continue to recommend that hemoglobin correction be performed on the predicted DLCO and not the observed DLCO, particular since the observed DLCO is corrected for PAO2, altitude and end-exhalation back pressures. The logic of this approach not only seems backwards but makes the comparison of trended DLCO results difficult. I read section of the new standards on hemoglobin correction carefully but no particular justification for this was put forward.
In the past I would have taken the release of the new DLCO standards as a sign that new standards for spirometry, lung volumes, methacholine challenge testing(?) and interpretation would also be released soon. The release of the previous standards in 2005 was troubled by confidentiality issues (early release of standards by insiders to some manufacturers) and this time around the ERS and ATS are playing their cards close to their vest. We can only wait and hope.
References:
MacIntyre N, et al. Series ATS/ERS task force: Standardisation of lung function testing. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005; 26: 720-735.
Graham BL, et al. 2017 ERS/ATS standards fir single-breath carbon monoxide uptake in the lung. Eur Respir J 2017; 49: 1600016
PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Richard
Thanks for putting this together – very comprehensive.
Strong work-very helpful.
Wow, great work Richard, thanks!
Thank you, Richard. As always, your work is very helpful. In addition to everything you have detailed, a change I found in the 2017 Standards was the average BHT should now be reported (Table 4 on page 26). I had asked Brian Graham about this, because reporting of BHT had not been specifically addressed in the 2005 document. I am in agreement with reporting the average BHT of acceptably-performed trials.
Jim –
Good catch. I mis-read a section in the 2005 standards and thought BHT was supposed to have been reported then. I will update the posting with this. I can’t think of any reason not to average BHT but the 2017 standards also state that the average VI be reported and there I think it could be argued that the largest VI should be reported instead just in case it’s higher than the FVC or SVC and therefore used in the FEV1/VC ratio.
Thanks, Richard
The 2005 Guidelines did state that the average IVC should be reported, but they didn’t address the BHT. My pulmonary equipment vendor and I have some differences of opinion on this, so I had something of a vested interest in what the 2017 Standard said. I see your point in reporting the largest VI; I think I’d still go with reporting the average VI for DLCO, but using the largest VI for VC reporting. Ideally, I think the source of the reported VC would be reported, rather than assuming it’s from the SVC (but perhaps this is making things unnecessarily complex).
Jim –
My lab software doesn’t automatically substitute the highest SVC or IVC in the FEV1/VC ratio and it’s something I have to do manually in the notes. Unless I look at the raw data for the DLCO I won’t know what the individual IVC’s actually are. I’ve seen some lab software that automatically substituted the SVC for the FVC if it was larger, but this was never apparent in the reports and you only knew it had happened if you looked at the raw SVC and FVC data. BTW, the same software would also substitute an FVC for the SVC if it was larger, also not reporting it (and also continuing to use the ERV from the SVC). I’m not against substituting VC’s whenever and wherever it’s appropriate but I’d sure like to see the fact that this was done somewhere on the report.
– Richard
I agree, Richard. It’s sad that vendors aren’t updating their software to be compliant with the latest standards and guidelines. I don’t even remember how long it’s been since the ATS first recommended that the largest VC be reported, regardless of where it’s from. 1995? You (or any other technologist) shouldn’t have to do anything like this manually, and furthermore, reporting these data in the notes doesn’t change the reported values in the database.
The purpose of the ATS/ERS standards is to establish consistent methods that pulmonary measurements should be performed. In a perfect world, if I had repeated pulmonary tests anywhere in the world, my results will be the same from each lab, because each lab would be operating their equipment and performing their measurements with the same procedures and techniques. The ATS/ERS documents can only recommend best practices; it’s up to each technologist and lab to follow them. THIS is why we need accreditation for pulmonary labs.
(climbing down from my soapbox…)
Jim –
[Wild cheering from the crowd while Jim is still on his soapbox. Cries of “right on” and “more” from across the crowd as he steps down.]
I’ll cut the manufacturers a little bit of slack since in the USA the FDA has made it exceedingly difficult and complicated to get even small changes in software approved, and the new standards are a BIG change. For this reason I’m not expecting any software updates concerning the new DLCO standards from my lab’s vendor for at least a year (and that’s being euphorically optimistic). Other than that though, our vendors often put minimal resources into their software and it shows. FYI, a new metabolic cart we got last year has no discernible changes in software from it’s predecessor that we’d bought 12 years ago.
Agree 100% on the need for accreditation, just not sure who has the patience and moxie to see it through the implementation process. I’d like to see the ATS or ACCP step up to the plate with at least a voluntary accreditation program.
– Richard
Thank you! This helps set clear expectations.
Very good!
Just started following your blog as a result of working in a lab, great work!
Richard,
I see that linearity, which is to be done weekly, has changed from +/- 3.5% (105ml) to 2.5% (75ml) now applies to the IVC for the DLCO. Will the volume range change when converting from ATPD to BTPS?
ie) at 21 degrees Celsius and 3.5% the acceptable range is 3.17-3.40 L
Mo –
Linearity is applicable to the gas analyzer, not to flow and volume. Analyzer linearity is to be performed weekly. Flow calibration (and volume accuracy) is to be checked daily and must be within 2.5%. Interestingly, the 2017 standard discusses flow accuracy in two places and puts a +/-2.5% error on the flow sensor and implies this is added to +/- 0.5% error in the calibrating syringe (page 2, paragraph 3). In the section that discusses daily calibration (page 7, paragraph 8) it says that the calibration must be within +/-2.5% and does not include syringe error. Not sure this is contradictory or not since you basically have to assume the syringe is correct and in the daily calibration it is the flow sensor that is in question. In either case, calibration is at ATPD, not BTPS, and assuming that room temperature is less than body temperature the multiplicative correction factor implies that the volume error range when measuring BTPS gases would be slightly larger, however given that the entire volume is also larger this means that the +/-2.5% still applies.
Regards, Richard
Hi richard
So on the rga systems we dont need to worry about a discard volume??just collect the virtual sample within 12 sec .how much sample we need to collect? Min 85ml to max 500ml
Gilbert –
By discard volume I assume you mean the washout volume. In one sense you’re right in that you don’t have to pre-set the washout volume, you can identify it and the alveolar plateau after the test. The defaults for these volumes remain the same as they were in the 2005 standards, however; 0.75 L washout and 0.75 alveolar sample. But the 2017 standard wants the exhalation to continue long past the washout and sample volumes and this is so VA can be calculated using a mass balance equation rather than just using the tracer gas in the alveolar sample. This is one point that bothers me a bit because KCO is being calculated using the CO in the alveolar sample but VA is being calculated using pretty much the entire exhalation. This has implications mostly for patients with ventilation inhomogeneities and will reduce the difference between the VA and the TLC measured by different methods but whether it’s correct to extrapolate the rate of CO uptake in the alveolar sample to the entire VA is not as clear to me as I’d like. But that was also a problem with calculating VA from the alveolar sample too.
– Richard
Richard,
I still have question regarding the new DLCO standards.
Flow accuracy
RGA response time
CO analyzer accuracy
Interference
Digital sampling rate
Analyzer drift
Barometric pressure sensor accuracy
Is this all up to the manufacturer to update as needed? I couldn’t find this info in the manual to verify compliance. Called Jaeger/Carefusion tech support and they did not know. Said they would get back to me, but didn’t. Is there a time period in which updates have to be made and implemented?
Mass balance equation for VA and Fowler method for anatomic dead-space. Are these software updates?
How is gas analyzer linearity checked?
Syringe leak test was unclear. How is it performed?
How is the calibration syringe QC performed?
Your response is greatly appreciated and keep the blogs coming!
Thanks,
Sue
Sue –
Although many of the current DLCO tests systems already in use have the potential to meet the 2017 DLCO standards, the standards are largely aimed at the next generation of test systems. Current systems that are physically capably of meeting the 2017 standards will need software updates for the mass balance VA equation and Fowler dead space. How soon manufacturers provide a software update and what they include in it (or if they do at all) is up to each individual manufacturer. I will point out that even for manufacturers who intend to update their software the FDA 510K approval process for even simple software changes is a long and convoluted process that can easily take up to a year and that’s on top of whatever time it takes to update the software. Having said that, manufacturers will need to produce the required specifications for their current test systems at some point.
The calibration syringe leak test is straightforward. Fill the syringe to the 3.00 liter mark, cork the outlet, and push in the syringe handle to the 2.95 liter mark for 10 seconds, release the handle and if it does not return to at least 2.99 liters the syringe is leaking.
To do the DLCO calibration check with a 3 L syringe just perform a DLCO test with the syringe rather than a person. The inspired volume must not be more than +/- 0.3 L of 3.00 liters time the correction factor (863/(Pb-47)) and the calculated DLCO needs to be less than 0.5 ml/min/mmhg.
I still have some significant reservations about calculating VA using the mass balance equation and DLCO from the change in CO in the alveolar sample. On the one hand the mass balance equation using the tracer gas from the entire exhalation should more accurately reflect TLC but on the other hand, using it to calculate DLCO makes the assumption that CO uptake is homogeneous for both the alveolar and non-alveolar sample portion of the exhalation and this isn’t necessarily true.
I also am concerned that the issue of software manipulation of gas analyzer response times wasn’t addressed. Most CO/CH4 gas analyzers do not actually meet the specifications for rise/fall times and to get around this the software takes the known characteristics of the gas analyzer and uses an algorithm to “predict” the actual gas concentrations. To my knowledge how well this actually works (i.e. comparing with a mass spectrometer) has never been studied.
Regards, Richard
All good points, Richard. When the 2017 recommendations were released, not one system marketed in the United States could meet every one of them. Some of the standards can be met by software updates, but if a lab’s existing hardware cannot meet the new specs, then they’re left with either continuing with the 2005 recommendations or purchasing new equipment.
I’ve long felt that the rapid-response DLco technology that was released in the early 1990’s was not fully developed, and when we needed to update our equipment in 2007, we went back to a bag-in-box system, which has worked very well for us. If gas transit time and analyzer response time were being measured on these systems, it wasn’t being reported on the systems I’d worked with, nor did I ever see an error message regarding these. The speed of the expiration after the breath-hold remains a critical issue with rapid-response gas measurements, and I don’t know how this will be successfully resolved. At this point, though, I think the rapid-response technology has matured enough that we’ll look into it for our next upgrade. I think this maturation is reflected in the 2017 recommendations, which address many of the issues that were not apparent during the time leading up to the 2005 statement.
Back in 2005, there were rumors (I don’t know if they were ever substantiated or not) that one company was given access to the 2005 DLCO recommendations prior to the official release. This company was then able to say that their equipment met all of the new standards from day one. True or not, perhaps all of the manufacturers should be given a heads-up if new recommendations will require significant hardware changes. I don’t know if the manufacturers have any input regarding new equipment standards; it would seem appropriate for them to have at least an advisory role. I would think that the manufacturers would be more qualified than the physicians on the ATS/ERS board to state what can and cannot be realistically done with existing and future hardware. That said, you need the clinical people to specify how to obtain the greatest clinical yield from a pulmonary test, so the current ATS/ERS leadership should still be behind the wheel; they ought to occasional stop to ask for directions, though.
Does anyone use the DLCO with 3EQ? I realize it’s really a lung volume + DLCO measurement and therefore betwixt and between. However, I’ve not found where ERS or ATS address it.
Cheryl –
The 3EQ DLCO is actually much more than that. It uses different sets of equations to determine CO uptake during the inspiratory phase and the expiratory phase, as well as the breath-holding period. One of the limitations of the standard single-breath DLCO equation is that it makes no allowance for inspiratory or expiratory time, and in fact basically assumes that both are instantaneous. The various methods of determining breath-holding time (Ogilvie, ESP, Jones-Meade) all attempt to mitigate this to one degree or another (with varying degrees of success) but are at best empirical approximations. My only criticism of the 3EQ method is that it is based on theoretical (although probably fairly accurate) estimations of what occurs to alveolar surface area during inspiration and expiration in normal subjects and how well this applies to subjects with significant lung disease is unclear.
Regards, Richard
Hi, Richard.
You stated that there’s an error on page eight, line eight of the 2017 ERS/ATS DLco statement, where Va was entered instead of Vi. I’ve not been able to find any references about this. Could you provide them?
Thanks – Jim Sullivan
Jim –
The line states “Secondly, a DLCO test should be performed with a calibrated 3-L syringe by attaching the syringe to the instrument in the normal patient test mode. The syringe should then be emptied, filled with 3 L of test gas and emptied into the mouthpiece after the 10 s breath-hold. The calculation of VA must be within 300 mL of 3 L times the STPD to BTPS…”
After re-reading this and doing the math it’s apparent that this is my error. Since VA is = inspired volume x (inhaled tracer gas / exhaled tracer gas) then VA should be equal to 3 liters plus a bit for the syringe deadspace. Didn’t think it through when I read it the first time.
Regards, Richard
Thanks, Richard. I find it difficult to believe the ATS/ERS is stating a system is functioning normally if the VA with a 3.0 L syringe returns values between 2.70 L and 3.30 L. This is so wide, it’s useless.
I’ve been working on a method of DLco syringe QA which measures the VA using both the CO and the tracer gases. I’ve gotten results far, far closer than +/- 10%. Instead of saying the CO analyzer if functioning correctly if the DLco is about zero, which the ATS/ERS is doing, this method uses both analyzers to measure VA, plus the flow measurement accuracy is assessed with all calculations. There are a few more issues I need to work out, but once these are resolved, I hope to prepare this work for publication.
Hi Richard,
Now that we have been using the 2017 DLCO guidelines, I have a hard time grasping the “VA’s within 200ml or 5%.”
ATS-ERS have tightened the repeatability from 3 units or 10% to within 2 units. Increased the IVC to 90%.
If a patient produces 2 trials, where the IVC’s are both above 85% and the DLCO’s are repeatable within 2 units, but the VA’s are outside the 200ml or 5%, where does doing another trial, just to match up VA’s help or change the interpretation?
Even if I produce another trial, with an IVC above 85% and now the VA’s meet, yet the DLCO value is still reproducible with the other 2 trials produced, was there really any benefit to do the third DLCO, other than criteria met?
I do understand that one more trial to meet acceptability is easily done, but I fail to see how that changes final interpretation. Not sure why they added the IVC’s of at least 85% and VA’s with 200ml or 5%.
Your thoughts are greatly appreciated.
Mo