PFTech Notes

A]    What's in the Bag?

B]    3 Equation DLCO Technique.

C]    Secrets of the Micro Tach.

D]    Quality Assurance in the PF Lab.

LCO_sb What's in the Bag?

 DLCO_sb      WHAT'S IN THE BAG?

 The single breath test for diffusion capacity (DLCO_SB) has found many clinical uses; identifying gas transfer problems related to occupational or environmental exposures, tracking lung function deterioration associated with chemotherapeutic regimens, disclosing cardiopulmonary anomalies such as mitral stenosis and pulmonary hypertension, and quantifying loss of gas exchange surface area secondary to emphysema, to name a few. However, to take advantage of these diagnostic capabilities, factors that can confuse the results of DLCO_SB must be fully understood. The value of any diagnostic test is founded in its ability to uncover abnormalities at an early stage (sensitivity) and/or describe the precise cause of the abnormality (specificity). This monograph addresses the advantages and disadvantages of single breath DL to afford the clinician better insight as to the value and limitations of this test.

Gas exchange between respiring cells and the atmosphere is a complex process. Under normal conditions a pressure gradient exists between atmosphere and the alveolar spaces. Gases must traverse a complex branching system of conducting airways. This process consists of bulk movement (convection) of atmospheric gases to the terminal airways followed by diffusion of the constituent gases along their individual pressure gradient pathways. Oxygen reaches the alveolar- capillary (AC) membrane with a partial pressure of approximately 110 mmHg at sea level. Its destination, pulmonary capillary blood, has an oxygen partial pressure of about 40 mmHg. The resultant pressure head of 70 mmHg is sufficient to push the oxygen across the membrane in ample time to bind with nearly all of the available hemoglobin.

DLCO_SB closely mimics this process. Carbon monoxide is substituted for oxygen because of similarities in uptake properties with hemoglobin and because under normal conditions there are only trace amounts of CO in pulmonary capillary blood, precluding the need to correct for a CO back pressure factor. The test is simple to perform and requires relatively inexpensive equipment.

Unfortunately and unavoidably, conditions that can alter the transport of oxygen to, and transfer across the AC membrane, also effect the DLCO_SB test gas mixture. Ventilation perfusion mismatch and other conditions that result in arterial hypoxemia can likewise alter DLCO_SB independent of the diffusion process. Thus it is difficult to interpret DLCO_SB in patients with severe obstructive lung disease because it is not clear what process(es), convection through conducting airways, membrane diffusion, pulmonary blood flow, and/or hemoglobin concentration, may be causing a reduced DLCO_SB value. Stated simply "what is the gas in the sample collection bag representing?" The knowledgeable clinician can reconcile these physiologic factors in the interpretation by using the patient’s history and related test parameters.

However, to complete the picture one must add to these factors the difference between the underlying theory of the single breath equation and the reality of actually performing the test. The equation presumes a process in which the test gas is inhaled from residual volume to total lung capacity (vital capacity) with virtually no time expended, is held for 10 seconds, and exhaled with the first portion discarded as dead space gas (again with no time expended) and the last portion collected as a uniformly mixed alveolar sample. The graphical presentation of this ideal procedure would be a square wave.

In reality, the inhalation of test gas and the exhalation of sample gas requires some time to complete. This is the case in normal test subjects as well as those with lung disease. Patients with obstructive lung disease or weakened diaphragmatic function can have greatly prolonged inspiratory/expiratory times. This is an unavoidable nuance of the test and there are varying opinions regarding when the diffusion of CO actually begins and ends. What must be avoided at all costs is any additional impediments to test performance introduced by poorly designed measurement systems.

Measurement systems with high impedance to airflow may cause the test subject to develop excessively negative pleural pressure during inspiration, termed a Muellar maneuver. Pulmonary blood flow would increase, thus falsely increasing DLCO_SB. Conversely, measurements systems that mandate the test subject to hold the inspired breath against a closed shutter may produce a Valsalva maneuver which would falsely reduce DLCO_SB. Furthermore, systems with high impedance to airflow may make it very difficult for patients with low functional vital capacity to discard dead space and fill the sample bag at all.

The use of a poorly designed measurement system compounds the problems inherent in DLCO_SB testing, further magnifying the importance of answering the question "what’s in the sample bag?" Is the collected gas representative of physiologic factors that can be reconciled by the clinician in the interpretation or is the gas contaminated by factors associated with poor system design?

The ideal measuring system for DLCO_SB would employ a rapid response analyzer for real time measure of test gas, dead space gas, and sample gas concentrations. Such an analyzer would obviate the need for a sample collection bag as well as mechanical devices to direct and redirect expired gas flow through the system. Two enormous benefits arise from the use of real time gas analysis; first, the quality control of test results is greatly enhanced by direct visualization of the entire test sequence. Leaks are immediately and clearly visualized; second, the alveolar sample can be inspected for uniform concentration of the inert tracer gas or contamination by dead space gas thus validating the test result before presentation to the physician for interpretation.

Equally important, the system must have minimal impedance to airflow. The use of demand valves commonly employed on flow based (pneumotach) systems introduce the potential for esoteric Muellar maneuvers particularly in patients with reduced inspiratory flow capacity. In addition, some patients will have difficulty with the 10 second breath hold. Systems that employ mandatory shutter valves during breath hold run the risk of premature forced expiratory efforts thus creating Valsalva effects or voluntary test abortion.

The best commercially available demand valve is the volume displacement spirometer. A large reservoir of test gas connected to the patient via a wide bore tube affords any test subject the freedom to inspire to the maximal level of their inspiratory flow capacity without the risk of altering pleural pressure and ultimately the DLCO_SB result. Finally, the use of valves to assist in breath holding should be optional so that their use during testing can be noted and factored into the interpretation of the test results.

Only the Collins CPL_pf offers all of the features of the ideal testing system for DLCO_SB testing. It is the only commercial pulmonary system that employs the rapid response analyzer, a volume displacement spirometer, and has an optional breath hold assist.

3 Equation DLCO Technique

It is widely recognized that there are problems with the single breath method for measuring the diffusion capacity of the lung (DLcoSB). Most significant, there is a fundamental difference between the theory underlining the single breath equation and the practical realities of currently available testing systems. A previous PFTech Note ("What’s in the Bag" Volume II, Issue 1) addressed these problems and how newer technologies have been developed to overcome some of them. This discussion deals with the window of opportunity that this technology has opened and what enhancements to the measurement of lung diffusion are just on the horizon. They are perhaps best appreciated when contrasted with the historical development of the single breath test.

In 1915 Krogh[1] used carbon monoxide (CO) to estimate the diffusion capacity of the lung for oxygen. There are two immediate benefits to the selection of CO as the test gas; there is minimal CO back pressure in venous blood thus simplifying the calculation of CO driving pressure to alveolar CO partial pressure (PACO), and the high affinity of hemoglobin for CO permits its use in very low concentrations. Krogh measured initial PCO by having the patient perform a rapid maximal inhalation immediately followed by a one liter exhalation prior to the breath hold. The fractional concentration of CO (FCO) in the one liter expirate was multiplied by barometric pressure (BP(dry)) to estimate the PCO at the beginning of the test. Alveolar CO concentration was subsequently measured after dead space washout producing the necessary ingredients to compute DLcoSB.

Krogh’s method to compute initial CO concentration contained some errors. First, regardless of how fast the maneuver was performed, some of the CO must have diffused into the blood. Moreover, the flow rates produced by maximal efforts would produce different results in patients with airway obstruction versus normal subjects (at high flow rates distribution of inspired gas is effected primarily by airway resistance). Finally, high flow rates could produce fluctuations in alveolar pressure that might alter right ventricular output, pulmonary capillary blood volume, and consequently DL. Essentially, Krogh’s method did not accurately account for all of the CO used during the test.

Approximately 40 years later, Oglivie and Forster [1] attempted to correct for some of Krogh’s errors by using helium (He) to better estimate the initial CO concentration and calculate alveolar volume (VA), and by using a standardized breath hold time (BHT). Problems persisted because the BHT in the single breath equation assumes instantaneous inhalation of the test gas, instantaneous washout of the dead space and instantaneous collection of the alveolar sample. In practice none of these conditions are met. Failure to account for these elements in the BHT results in overestimation of DLcoSB. Still later, Jones and Meade [3] further refined the test protocol by introducing an algorithm to minimize the effects of inhalation, dead space washout and sample collection on the BHT. Modifications of their method (ATS, ESP) are widely used in pulmonary labs today.

Jones and Meade determined the onset of BHT by extrapolating the exponential disappearance of CO measured during the actual breath hold period back through the inhalation time. They concluded that CO uptake and thus the start of BHT begins after three-tenths of the inhalation time. They also recommended the collection of a very small expired sample (85ml) immediately after washout of the dead space to minimize the effect of expiratory delays on BHT. These modifications and ideas for standardization made by other investigators have certainly contributed to the precision of DLcoSB measurements. Accuracy is another matter.

It is also widely appreciated that the DLcoSB test performed using conventional methods and technology is difficult for many patients to perform correctly. Patients with COPD and other obstructive defects present a particular challenge. Prolonged inspiratory and expiratory times, increased dead space and reduced vital capacity can further confound the estimate of BHT and the point at which the alveolar sample should be collected. The size of the alveolar sample is a "catch 22"; in obstructive lung disease small samples may only represent regional areas of the lung characterized by fast emptying units.Aalternatively, large samples will further prolong expiratory time thus widening the difference between the true and estimated BHT.

Poor equipment design can also contribute to the problem. High resistance breathing circuits may result in inadvertent Muellar maneuvers during inspiration, and similarly mandatory breath holding against a shutter and/or resistance to exhalation may result in Valsalva maneuvers. Both of these are known to alter pulmonary capillary blood flow and DL. The problem is further compounded by the requirement to reach maximal lung volume and hold it for ten seconds. What happens if maximal lung volume and/or the ten second BHT are not achieved? Unfortunately, results of these poorly performed tests are reported and interpreted.

In most of the above circumstances the problem is the same as that encountered by Krogh 80 years ago, i.e. the inability to account for all of the test gas at every point in the procedure. Since then technologies e.g. rapid response analyzers (RRA), have been developed that permit a greater understanding of the diffusion process through continuous real time sampling, and offer solutions to the pitfalls associated with its measurement.

The 3-GAS DLcoSB module currently offered by Collins is one such solution. Clinicians can now clearly visualize the demarcation point for alveolar sample collection. This point can be moved and the size of the sample adjusted to produce the best testing condition for a given patient. By using a volume displacement spirometer, wide bore tubing, an optional breath hold assist shutter and excluding high resistance demand valves, Collins has developed the most state of the art, patient friendly DLcoSB module on the market today. And this is only the beginning!

In 1980, Graham et al [4] described a mathematical formulation that accounts for all of the test gas used at every point in the testing process. This algorithm (DLcoSB -3EQ), based upon the mass balance equation, applies a differential equation to each of the three portions of the single breath test; inspiration, breath hold and expiration. Rather than assigning an empirically derived and thus somewhat arbiter point to the beginning and end of the BHT, the three equations express CO concentration as a function of the variables that interact to produce it, namely, volume, time, and DL.

Extensive studies including modeling and clinical trials have demonstrated that the DLcoSB -3EQ results compare precise! With Jones and Meade’s technique when the test was performed by well trained normal subjects. More important

the DLcoSB -3EQ technique has been shown to be unaffected by variations in the single breath test maneuver e.g. flow rates, BHTs, the size and collection time of expired gas samples, and nonuniform distribution of DL. The clinical ramifications of this technique are significant; accuracy and precision will be improved and patients will not have to perform the test as stringently as required by conventional techniques.

Future enhancements derived from the DLcoSB -3EQ technique are under development. These include the virtual elimination of breath holding, the use of submaximal lung volumes, and the inclusion of volume history in the maneuver. These adjustments are directed towards the development of a test that more closely mimics the actual physiologic conditions under which lung diffusion takes place, i.e. tidal breathing interspersed with sigh breaths that results in reestablishment of the diffusion pathway, release of neutrophils from pulmonary capillaries, and reduction of alveolar surface tension secondary to surfactant release that in turn augments transmembrane potential. The sensitivity and specificity as well as the accuracy and precision of DLcoSB will be improved.

Also, by focusing elements of the DLcoSB -3EQ technique on the expiratory period, a more precise analysis of the inert tracer gas (methane, CH4) during phase III and IV could result in lung volume determinations comparable to multiple breath He dilution and plethysmography, an assessment of the inhomogeneity of diffusion, and possibly information related to small airways disease (closing volume). Perhaps most important from the patient’s perspective, the DLcoSB -3EQ technique promises to culminate in a test maneuver that every patient, no matter how badly compromised, will be able to perform without difficulty..

References:

1. Krogh M, "The diffusion of gases through the lungs of man,"J. Physiol. London, vol. 49, pp. 271-300, 1915.

2. Ogilvie CM, Forster RE, Blakemore RS, and Morton JW, "A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide,"J. Clin. Invest., vol. 36, pp. 1-17, 1957.

3. Jones RS and Meade F. "Pulmonary diffusing capacity. An improved single breath method," Lancer, vol. 1, pp. 95-95, 1960

4. Graham BL, Dosman JA, and Cotton DJ, "A theoretical analysis of the single breath diffusing capacity for carbon monoxide," IEEE Transactions on Biomed. Engin., vol. 27 pp. 221-227, 1980.

 

Secrets Of The MicroTach

Validation of ATS Standards

Q. Can you give a basic description of the design characteristics of the Collins microTach?

A. The Collins microTach is a single screen, Silverman type (extremely low thermal mass) pneumotachometer that can be  used directly at the mouth, permitting the measurement of both inspiratory and expiratory flow, which is programmatically integrated to derive volume.

Q. With only a single screen, how can the microTach be linear?

A. Linearization is done dynamically by the software.

Q. Why was linearization handled this way? Isn't it easier to place screens in front and back of the main resistive screen to laminarize the flow?

A. This approach has been used in the past, but the extensive evaluation of multiscreen type pneumotachs as the first step in designing the microTach showed that they were linear throughout their full flow range; tests of several manufacturers multiscreen devices on our flow-bench showed that virtually all of them had one or more irregularities in the supposed linearized device. On this basis we elected to use a single, low thermal mass screen and accomplish linearization in software. This approach provides us with other benefits.

Q. For instance?

A. If you depend on the physical characteristics of a device to provide linearity, you always run the risk of having that device become alinear because of changes/damage to the screens during handling, such as cleaning. The device may become significantly alinear before results begin to be questioned and someone thinks to check the linearity. Checking linearity requires special equipment, expertise, and time to be repeatedly checking the linearity of pneumotachs. The microTach is designed to allow the user to verify the linearity in about a minute or less with nothing more than a calibration syringe. Thus, if the verification procedure is performed after a pneumotach calibration or, if a complete calibration is not done prior to each test the verification is quickly run, you know that the microTach is in good working order and linear.

Q. How does the software actually linearize the microTach?

A. In many flow-based pulmonary systems, the linearization is approximated by depending on algorithms than manipulate the average of several syringe strokes, often requiring each stroke to be performed at some specific flow-rate. Other approaches rely on some type of convergence algorithm to shift a generic software linearization table back and forth until some approximate fit with the current flow envelope occurs. The microTach is linearized dynamically by use of specialized curve fitting. Thus, each time a calibration is performed, a new linearization table is generated, specific for the microTach currently being used. The beauty of this approach is that calibration/linearization becomes a simple stroke in, stroke out.

Q. But you only appear to linearize the microTach at ± 2-liters/second. How do I know it's linear at all flows?

A. The ± 2-liters/second flow is only a target for the computer algorithm to work with. The nature of the specialized curve fitting is such that the dynamic linearization curve generated for a specific microTach is independent of the specific flow rate. If you doubt this, perform a one-stroke calibration and save the results. Then select the <V>erify option on the calibration menu. During verification, there are no target flow lines on the graph; any flow up to the maximum range of the microTach is okay. Push the plunger of the syringe in or pull is out as quickly (without exceeding the microTach maximum of 16-liters/Second) or as slowly as desired. Vary the speed of the syringe piston throughout the stroke to get a variety of flows. Each of the sample points (every few milliseconds) will be read by the computer and linearized. If the linearization is not within the specified limits, the individual samples will not sum up to the 3-liter volume of the calibration syringe. While we specify the accuracy of the microTach to be within ± 3 % in keeping with the American Thoracic Society (ATS) recommendations, in general the microTach is very close to being a 1% device. And best of all, you can determine this prior to each test so you are assured that your test results are accurate.

 

Quality Assurance in the PF Lab

In a departure from strictly technical content, this edition of PFTech Notes deals with a subject that clinicians encounter on a daily basis, one which will become more prominent as healthcare reform continues to evolve. The subject is quality assurance (QA). Specifically, this issue discusses how the data management power of Collins’ PLUS^sql software can help in the development of an effective QA program for the pulmonary function laboratory.

Most clinicians have had some exposure to regulatory oversight; the Joint Commission on the accreditation of Healthcare Organizations (JCAHO), the College of American Pathologists (CAP), and state departments of public health are examples of regulatory entities that make periodic inspections of hospitals to evaluate the quality of the services provided. In the past such inspections were scheduled with ample advance warning and typically focused on retrospective audits.

More recently, regulatory agencies, the JCAHO in particular, have refocused their efforts to evaluate quality using techniques adopted from industry. Despite different terms used to describe these QA initiatives, Total Quality Management (TQM) and Continuous Quality Improvement (CQI) for example, they all describe essentially the same process, a formalized measure of the quality of healthcare services using three criteria; access to care, clinical outcome, and cost. In short, give the patient what they need, when they need it and as cost effectively as possible.

QA is not quality control (QC). QC is a systematic measure of instrument performance using control media with the results expressed statistically. QC is one component of QA. Certainly validating the accuracy and precision of test results via QC contributes to forming the correct diagnosis and assessing the effectiveness of interventional therapies. But the value of any test result, no matter how accurate, is diminished if the report is mishandled, misplaced, mislabeled or misinterpreted. The quality of test results is more comprehensively validated using a QA cycle which evaluates each component of the test event. Arterial blood gas samples, for example, must be collected in a specific way, labeled, placed in ice, transported to the lab, analyzed, and the results recorded and transmitted back to the clinician, all within a relatively short time frame. Any deficiency in the process could invalidate the test result and potentially place the patient in jeopardy.

The QA cycle can be relatively small and self contained as in the example above, or it can encompass the patient’s entire healthcare experience. In order to make the evaluation process more manageable, each component of the QA cycle can be defined by a statement called a clinical indicator. Clinical indicators are at the center of the JCAHO’s current regulatory initiatives.

Clinical indicators are statements that describe discrete healthcare processes. They are applied to patient populations to determine if certain standards of care are being met. These standards, called rationales, include the appropriateness, effectiveness, and timeliness of care provided to patients. Recently, the cost of care has been added to the list of standards. Accordingly, once a patient is granted access to the healthcare system, the quality of his/her experience will be judged solely on the final outcome and its associated cost. The use of expensive technology to produce a favorable clinical outcome can no longer be justified if a less costly alternative would product the same result.

The JCAHO is committed to the clinical indicator format. It has beta tested several indicators in various hospital departments with the intent of developing a list that will help promote standardization and intrahospital comparisons. None as yet have been developed for respiratory care. However, several sources exist from which clinical indicators can be developed; clinical experience, practice guidelines published by the American Association of Respiratory Care (AARC), therapist driven protocols (TDPs) and information compiled by state and local chapters of respiratory care. When and wherever possible the JCAHO encourages interdepartmental QA studies.

The use of clinical indicators in the pulmonary function laboratory can provide many benefits including some that are self serving. Healthcare reform has forced many hospitals to downsize and/or consolidate clinical departments. Some respiratory departments have used cross training to help preserve a full complement of patient care services. In many cases respiratory care practitioners (RCPs) are required to administer pulmonary function tests in between performing duties in critical care areas. In other cases, respiratory departments have attempted to increase testing volume to underwrite the expense of maintaining requisite level of personnel. Neither solution is viable without capturing significant productivity gains. Clinical indicators can be used to identify and quantify such gains.

As an example, consider a hypothetical situation in which a pulmonary function lab, as directed by protocol, administers complete tests to every patient (spirometry, lung volumes, single breath diffusion capacity [DLCO_SB], bronchodilator challenge, and arterial blood gas analysis). Each test takes one hour to complete and the patient volume requires the exclusive deployment of one RCP per shift to the PFT laboratory. The laboratory director surmises that some of this testing may be clinically unnecessary and is searching for a way to recoup some of the personnel time spent performing PFTs for use in other clinical areas. This is a QA issue because valuable hospital resources may be consumed in the process of collecting test data with minimal clinical relevance.

A QA study is created around the clinical indicator, "patients with normal spirometry receiving complete PFTs". The population is all patients who receive complete PFTs and the rationale for the study is the appropriateness of care. In other words, is a complete PFT what the patient needs at this point in time? Implicit in this rationale is the unwarranted cost of administering more tests than the patient needs. The laboratory’s medical director provides the criteria for normal spirometry.

The QA study can be greatly facilitated if the PFT system uses a relational database for data management and a structured query language (SQL) to allow its data files to be queried. Queries are questions posed to a database that produce filtered views of the data. Relational database management using Informix and the SQL language are standard features of Collins PLUS^sql software package. In this example, the query statement would ask to find (count) the complete PFTs with normal FVC and FEV₁. Because the intent is to preclude lung volumes and DLCO_SB in patients with normal spirometry, a higher level of confidence could be attained if the query were amended to find those PFTs with normal spirometry but abnormal lung volumes or DLCO_SB. Adding diagnosis and pertinent demographic data to the query may provide further sophistication and minimize the possibility that important clinical information is missed due to a revised testing policy.

With SQL, an analysis of this type can be performed in a matter of minutes. The results of the query provide the foundation for the QA study. By simply placing the results in clinical indicator format, the laboratory would be well on the way to satisfying the JCAHO’s requirement for QA (two indicator studies per year are required). More importantly, this hypothetical QA study would have either validated the laboratory testing policy or potentially identified a less than optimal use of RCP time. The results of the QA study could have helped the laboratory director ward off further staff reductions by demonstrating the need to commit personnel to the pulmonary lab or, alternatively, a parcel of REP time could have been recovered for use in other clinical areas.

There are many uses of SQL related to QA. Queries can be formulated to measure compliance with American Thoracic Society (ATS) testing standards, e.g. how often inspiratory volume performed with the DLCO_SB maneuver falls within 10% of vital capability, or whether the washout volume is appropriate for patients diagnosed with COPD. These queries and those described above demonstrate the capability of a well designed data management system to positively influence the overall quality of the pulmonary function laboratory.

 

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