A month or two ago in the AARC Diagnostics forum several members noted that their labs had acquired Impulse Oscillometry systems a number of years ago but that their physicians had since stopped ordering oscillometry tests, mostly because nobody understood what it was measuring and didn’t know how to interpret the results. There are a number of reasons why this is probably not an uncommon scenario and why, despite being first described in 1956, oscillometry is not used more widely.
But first, what is oscillometry, and what’s the best way to understand it?
Oscillometry refers to a closely related group of techniques for measuring respiratory impedance by superimposing small pressure waves on top of normal tidal breathing.
There are three main approaches: the Forced Oscillation Technique (FOT), which is sometimes used a blanket term for all oscillometry techniques but more often refers to a single frequency technique, Impulse Oscillometry (IOS) and Pseudo-Random Noise (PRN). Most commercial oscillometry systems use either PRN or IOS because each approach uses multiple oscillation frequencies more or less simultaneously which allows testing to performed relatively quickly. The mono-frequency technique is used mostly in research because although it is slow to scan all frequencies, it is able to resolve rapid changes occurring at a single frequency.
All techniques share a similar equipment configuration:
The oscillatory pressure is usually generated by a loudspeaker, although the actual waveform and the frequency it produces differ for each technique. The peak pressures are usually on the order of +/- 1 to 5 cm H2O (+/- 0.1 to 0.5 kPa). Because patients have to breathe during testing, the system provides a steady flow of fresh air in one manner or another but this has to include a low pass filter of some kind so that the pressure waveform is not significantly diverted or blunted. The key measurements are flow and the pressure at the mouth. Continue reading →
I’ve been interested in ventilation inhomogeneity for a while and as ways to measure it I have looked at VA/TLC ratios, the Lung Clearance Index (LCI) and the phase III slope of the single-breath N2 washout (SIIIN2). All of these tests are able to provide some information about ventilation inhomogeneity but each has their own limitations and just as importantly although their results have a relatively clear relationship with ventilation inhomogeneity it’s not quite as clear what exactly it is they are measuring. A friend recently pointed me to an on-line article in Chest that discusses the dual-tracer single-breath washout test in patients with COPD. The apparent advantage of this test is that it is able to provide information about the site of the ventilation inhomogeneity. Although dual tracer gases have been used to study airway function for over 50 years the limitation of this technique has been the need to use a mass spectrometer. Some recent advances in technology have made it possible for this type of testing to be performed with a significantly less expensive gas analyzer and this has revived an interest in the dual-tracer gas single-breath washout (DTG-SBW).
The two tracer gases in question are Helium and Sulfur Hexaflouride (SF6). Helium has a density of 4 gm/mol and the density of SF6 is 146 gm/mol, and it is the difference in densities between these two inert and insoluble gases that make this test useful. In order to understand why we need to revisit to the anatomy of the terminal airways.
From Osborne S. Airway resistance and airflow through the tracheobronchial tree. www.SallyOsborne.com.
I was reading an article recently that made an off-hand reference to the 100% oxygen shunt fraction test. Results from the test were included in the data analysis but the equations the researchers used were not presented nor were they referenced, nor was the procedure described. This is probably because the shunt fraction test and its equations are very much old-school pulmonary physiology but even if the subject is probably covered at one time or another in physiology classes I suspect that some of the issues involved in the calculation are not as well understood as they should be.
There are some similarities between the deadspace-tidal volume ratio (Vd/Vt) and the shunt fraction but even though they are both are involved in gas exchange (and to some extent they also correlate with each other) they are measuring different things. When blood flows through the lung some blood passes through well ventilated alveoli and becomes fully saturated; some blood passes through poorly ventilated alveoli and is only partially saturated; and some bypasses the alveoli entirely. The resulting arterial oxygen content is the summed average of all of these compartments.
There are two different ways that shunt fraction can be measured and calculated; physiological and anatomical. The physiological shunt equation can be performed at any FiO2 (but usually around the FiO2 of room air) and requires that arterial and mixed venous blood samples be taken more or less simultaneously and then analyzed for PO2 and SaO2. The basic formula is:
I’d spent some time researching single-breath tests a while back and of course ran across the Fowler method for measuring anatomic dead space. It’s a relatively simple test but assessing its results as well as the results of alternate dead space measurement techniques turns out to be more complicated than I had remembered.
The official definition of anatomic dead space is that it is that part of the inhaled volume that remains in the airways at the end of inhalation and does not participate in gas exchange. An accurate estimate of this volume is important because respiratory dead space (Vd/Vt, discussed previously) is composed of both anatomical and physiological dead space. The physiological component of the respiratory dead space cannot be determined without knowing the anatomical dead space.
Anatomic dead space is usually considered to be the physical volume of the airways but static measurements of airway volume do not take into consideration the dynamic aspects of respiration. The most commonly used method for measuring anatomic dead space in a research setting is the single-breath technique developed by Fowler in 1948. In this method, after an inhalation of oxygen, the nitrogen concentration in an individual’s exhalation is plotted against exhaled volume.
Oxygen transport between the lungs and the body depends on numerous complex factors. Ventilation and the alveolar-capillary surface area are of course important but a critical component is hemoglobin. Oxygen is poorly soluble in water (which is what blood is mostly made of) and the transportation of oxygen throughout the body would not happen without hemoglobin’s ability to absorb and release oxygen on demand. Although it is possible to measure the diffusing capacity of oxygen (DLO2) the process is technically difficult and not at all suited to routine clinical testing.
There are a number of gases that are able to diffuse across the alveolar-capillary membrane and can be used in a variety of physiological measurements but in order for a particular gas to act as a substitute for oxygen it must be able to interact with hemoglobin. Carbon monoxide (CO) has an affinity for hemoglobin approximately 220 times greater than oxygen and was the first gas used to measure diffusing capacity (DLCO). DLCO has been a routine test for well over 50 years and has been measured by single-breath, steady-state and rebreathing techniques.
Nitric Oxide (NO) has an affinity for hemoglobin about 400 times greater than carbon monoxide (it is generally an irreversible process since the end product is methemoglobin whereas hemoglobin’s binding with CO is more reversible) and for this reason it can also be used to measure diffusing capacity. DLNO can also be measured by single-breath, steady-state and rebreathing techniques. Because of its high affinity and the speed at which the binding of NO to hemoglobin occurs numerous researchers have assumed that DLNO is equivalent to DMNO (the membrane component of diffusing capacity). This is not really true, but it can be a useful fiction and in order to understand why it’s necessary to look at the basic physiology of diffusing capacity tests.
Roughton and Forster’s seminal 1957 paper showed that diffusion is the sum of two resistances. I’ve discussed this previously but specifically:
DMCO = membrane component
θCO = the rate at which CO binds to hemoglobin
Vc = pulmonary capillary blood volume
The first resistance (1/DMCO) is the resistance to the diffusion of CO through the alveolar-capillary membrane and blood plasma to the surface of the stagnant plasma boundary layer around a red blood cell. The second resistance refers to the diffusion rate of CO through the plasma boundary layer, then the wall and interior of the red blood cell and finally the rate of reaction with hemoglobin.
Recently I was trying to explain the effect of altitude on blood oxygenation to somebody with IPF. They had observed that their oxygen saturation was fairly normal at sea level but that they needed to use their supplemental O2 when they went up to 2000 feet and didn’t understand why such a low altitude made that much of a difference. I don’t think I did very well with the explanation since at the time I was limited to only text and I much prefer pulling out diagrams and waving my hands in the air.
The place to start is with the alveolar air equation.
PAO2 = partial pressure of O2 in the alveoli
FiO2 = fractional concentration of O2
PB = barometric pressure
PH20 = partial pressure of water vapor in the alveoli
PaCO2 = partial pressure of CO2 in the arteries
RER = respiratory exchange ratio (VCO2/VO2)
When normal values are plugged into the alveolar air equation it looks like this:
An important point is that when air is inhaled into the lung oxygen is diluted by the water vapor and carbon dioxide that are already there. The partial pressure of oxygen will vary with atmospheric pressure but the partial pressure of water vapor and carbon dioxide are relatively fixed values. Atmospheric pressure of course decreases with altitude.
While reviewing a CPET I noticed the patient had a low PETCO2 throughout exercise and an elevated Ve-VCO2 slope. In addition the patient’s minute ventilation was on the high side (75% of predicted) at peak exercise. This is something you might expect to see in association with pulmonary vascular disease but the subject had a normal DLCO; normal spirometry; their oxygen saturation was normal at all times; and they had a normal maximum VO2 and a normal VO2 at anaerobic threshold. Since there didn’t seem to be any clinical reason for the low PETCO2 I had to wonder whether it was due to hyperventilation syndrome (HVS).
Hyperventilation syndrome is something that everybody “knows” about but is still somewhat ill-defined and this is at least partly because it is most often diagnosed solely by patient-reported symptoms. My lab does not have any diagnostic criteria for hyperventilation syndrome and for this reason I decided to review the literature on the subject.
Hyperventilation syndrome is usually suspected when a patient has rapid, shallow breathing with an irregular breathing frequency and with frequent sigh breaths. Common complaints are dizziness, dry mouth, tingling sensations in the hands and feet and often in combination with chest pain. These symptoms may raise the suspicion that a patient has hyperventilation syndrome and the classic way to diagnose HVS is has to have the patient perform a Hyperventilation Provocation Test (HVPT). During this test a patient voluntarily hyperventilates for three minutes and is then asked whether they felt the symptoms they had been complaining of occurred while they were hyperventilating.
The causes of HVS are considered to be primarily psychosomatic and the majority of articles written on the subject primarily explore this aspect. There are surprisingly few articles on the physiology of HVS and for this reason the physiological causes and consequences of HVS are poorly understood. Of note, I reviewed a couple dozen textbooks on pulmonary function testing and pulmonary diseases that I have on hand and found hyperventilation syndrome to be mentioned in only one (Cotes) where it merited one relatively small paragraph.
Recently I reviewed a set of completely irreproducible spirometry results. The patient had made eight attempts and the FVC, FEV1 and Peak Flow were different every time. In particular, there were frequent stops and starts during exhalation. I’ve always wondered why some patients have so much difficulty with what should be a simple test and although in this particular case it could simply be glottal closure I wondered if it could be Vocal Cord Dysfunction (VCD). For this reason I spent some time reviewing the literature.
Vocal Cord Dysfunction is defined as the paradoxical closure of the vocal cords with variable airflow obstruction that often mimics asthma and in fact VCD is often mistaken for refractory asthma. Unfortunately, for this reason individuals with VCD are often treated with corticosteroids and bronchodilators for years without any improvement of their symptoms.
The gold standard for diagnosing VCD is direct visualization of the vocal cords with a laryngoscope. Characteristically, the anterior (frontal) two-thirds of the vocal cords are closed with a narrow posterior glottal chink. The difficulty with this is that VCD symptoms are often transitory and a large number of patients that are suspected to have VCD are asymptomatic when a laryngoscopy is performed.
Since most PFT labs are not equipped with laryngoscopes nor are they prepared to perform a laryngoscopy at a moment’s notice we have to rely on the tests that measure airflow. Although the wheeze and shortness of breath that accompanies VCD mimics asthma the most common problem associated with VCD is inspiratory obstruction. The flow-volume loop pattern is therefore that of a variable extrathoracic airway obstruction.
Obesity has become far more commonplace than it was a generation ago. The reasons for this are unclear and have been attributed at one time or another to hormone-mimicking chemicals in our environment, altered gut biomes, sedentary lifestyles or the easy availability of high calorie foods. Whatever the cause, obesity affects lung function through a variety of mechanisms although not always in a predictable manner.
Many investigators have shown a relatively linear relationship between an increase in BMI and decreases in FVC and FEV1. These decreases are small however, and FVC and FEV1 tend to remain within normal limits even in extreme obesity. The decreases in FEV1 and FVC tend to be symmetrical which is shown by the fact that the FEV1/FVC ratio is usually preserved in obese subjects without lung disease. Several studies have shown that the decreases in FVC and FEV1 are reversible since a decrease in weight showed a corresponding increase in FVC and FEV1.
In one study a 1 kg increase in weight correlated with a decrease in FEV1 of approximately 13 ml in males and 5 ml in females. The same increase in weight correlated with a decrease in FVC of approximately 21 ml in males and 6.5 ml in females. The greater change in FVC and FEV1 in males than females has been attributed to the fact that males tend to accumulate extra weight primarily in the abdomen.
The notion that abdominal weight has a disproportionate effect on lung function is seconded to some extent by studies that have shown that decreases in FVC and FEV1 correlated better with increases in waist circumference and the waist to hip ratio than with BMI. One study showed a 1 cm increase in waist circumference caused a 13 ml reduction in FVC and an 11 ml reduction in FEV1 across a range of elevated BMI’s.