Clinical significance and measurement of closing capacity

This chapter is most relevant to Section F4(ii) from the 2017 CICM Primary Syllabus, which expects the exam candidates to be able to "define closing capacity, the factors that alter it, its clinical significance and measurement". In the initial version of this chapter, the author had predicted that, because this topic has appeared in the ANZCA primary, it was only a matter of time before CICM appropriate it for their own use. Then, it appeared in Question 7 from the second paper of 2019.

In summary:

In terms of finding respectable-sounding references which one would not need to pay for, there is probably nothing better than the beautiful retrospective by Milic-Emili et al (2007). Its respectability is helped somewhat by the fact that Joseph Milic-Emili is a monolithic institution of respiratory physiology, his career having spanned over sixty years, starting by kicking around with the likes of Jere Mead and Hermann Rahn. 

Definition of closing volume and closing capacity

The ATS/ERS task force has never defined this subdivision of lung space. Nunn's (Ch. 3) defined it as

"The maximal lung volume at which airway closure can be detected in the dependent parts of the lungs"

In other words, the closing capacity is the point in expiration where the lung volume falls enough for small airways to collapse. Any volume above this capacity is therefore characterised by nice open terminal bronchioles and alveolar ducts. When the small airways collapse, they tend to first collapse at the bases of the lung, because that is where the lung is at its most squashed.

The closing capacity is a capacity of the lungs, which by convention means that it is a composite space, created by the combination of residual volume and closing volume. The latter is the volume of gas which represents the difference between closing capacity and residual volume. The best way to represent this is probably by a diagram:

Though there is no convention of what to call the lung space between closing capacity and TLC, Milic-Emili et al (2007)  refer to it as "open capacity", which is probably a logical name for it. 

The physiological basis for closing capacity

If one had to explain closing capacity in some sort of viva scenario, one would probably need to do it a sequence of points which start with the explanation of the factors which hold peripheral airways open. The alveolar shapes and sizes here were photoshopped from a diagram by Gill et al (1979), in order to at least be approximately correct. The original image was a microphotograph of sectioned alveoli at different stages of deflation, from 100% of TLC all the way down to 40%. 

To put this picture into a thousand words:

• The peripheral small airways (terminal bronchioles and alveolar ducts) constantly tend to collapse, partly due to the Law of Laplace and partly because they are largely devoid of rigidity-enhancing cartilage.
• During normal respiration, these airways are kept splinted open by the stretch of alveolar septal elastic tissue
  • As the lung inflates, this stretch increases 
  • This accounts for the decrease in airway resistance associated with increases in lung volume
• Thus, as the lung volume decreases, so the airway diameter decreases
• Therefore there is a lung volume at which the stretch can no longer oppose the forces acting to collapse the airway, and the airway closes, trapping some of the gas.
• Because of the effects of gravity on the lung, the airways in the dependent regions of lung are the smallest, and therefore the most prone to collapse.  

The last point is interesting because it implies that in space the closing capacity should be decreased (i.e. outside of the evil influence of gravity, the dependant airways in the lung bases should stay open for longer, and therefore the closing capacity should be a smaller fraction of the total lung volume.) However, this ts not observed under conditions of actual weightlessness. West et al (1997) measured the closing volumes of NASA astronauts doing short (9-14 day) tours of the Spacelab, and found that they were essentially unchanged when compared to the same subjects standing upright at normal gravity. "This result implies that ... this process is determined by the distribution of mechanical properties of the airways and parenchyma", the authors concluded. The closing capacity was still decreased, as you'd expect, but this was because of an unexpected 18% decrease in residual volume.  

Measurement of closing capacity

Gas bolus method of measuring closing volume

Though realistically you could use any damn gas for this (eg. sarin), one would ideally use something sufficiently distinct from normal respiratory gases that it can be detected easily and in small concentrations. One might also expect the test agent to be sufficiently biologically inert that one might be able to convince healthy volunteers to undergo multiple exposures without fear for their safety. However this last consideration is clearly not essential, as the original description of the method by Dollfuss et al (1967) called for an isotope of xenon (¹³³Xe) which is a radioactive gamma-emitter. To be fair, the authors only irradiated themselves and their lab assistant. 

In short, the technique works like this:

• The subject exhales maximally, i.e. they are at their residual volume
• The subject then starts inhaling slowly up to TLC (over 5-10 seconds)
• As they start doing this, you quickly give them a small bolus of tracer gas (Dollfuss et al only needed about 2-4ml of radioactive xenon, or about 37 megabequerels, deliver over less than 1 second)
• Because at RV the small distal airways in the dependent lung regions are closed, the upper alveoli get all the tracer gas.
• After filling their lungs, the subject then exhales slowly, back down to RV.
• As the subject exhales, the tracer gas concentration comes out in four distinct phases:
  • First, dead space gas comes out, which has no tracer gas in it (Phase I)
  • Next, tracer gas concentration increases as alveolar gas comes out (Phase II)
  • Then, a plateau of tracer concentration is reached, as the tracer content of these "middle" alveoli will be relatively even (Phase III)
  • Finally, as closing capacity is reached, the dependent (tracerless) alveoli close, and only the open tracer-rich alveoli continue with the exhalation. As this happens, the tracer concentration being exhaled is no longer diluted by the air of these dependent alveoli. The effect of this is an increase in the measured tracer concentration. This is conventionally referred to as Phase IV.

This last stage of the measurement process can then be used to describe closing capacity. The exact point where tracer concentration begins to increase may be somewhat difficult to pinpoint, but lines of best fit can be drawn through the tracer concentration curve. The image below is from the original paper by Dollfuss et al (1967), lightly molested with Illustrator. Notice the erratic zigzag of xenon count measurements, introduced into the process by the random nature of radioactive decay.

To be completely and nerdishly precise, the closing volume is what ends up being measured here, as the method does not contain any provision for the measurement of residual volume (which would need to be added in order for the closing capacity to be reported). Just so you're aware.

Resident gas method of measuring closing volume

The resident gas method is essentially the same as the gas bolus method, except without the radiation exposure or the need to procure an expensive and short-lived isotope of xenon (its half-life is only five days, and then it breaks down into caesium).  This method relies on the presence of a "naturally resident" gas in the alveoli.  This "resident gas" referred to here is in fact nitrogen, which makes all the more baffling that people should call it the "resident gas method".  This appears to be an anachronism dating back to the 1970s (see Make & Lapp, 1975) which has propagated through textbooks presumably because textbook-writers are of the same sort of vintage. More modern sources (eg. Robinson et al, 2013) tend to refer to "inert gas washout measurement".

In summary:

• The subject exhales to RV
• At this volume, the upper lobe alveoli are well-open and full of nitrogen-rich air, and the dependent lung should be fairly collapsed.
• Pure oxygen is then inhaled until the subject can inhale no more (i.e. up to TLC)
• This fills the lung with pure oxygen, except for the upper lobe alveoli, where some nitrogen still remains and therefore dilutes the inspired oxygen
• The subject then exhales through a nitrogen sensor
• As with the gas bolus method, initially there is no nitrogen in the exhaled gas (this represents Phase I, the dead space volume)
• Then, nitrogen begins to leak out, and the nitrogen concentration detected by the sensor increases. At this stage, both the nitrogen-rich upper alveoli and the nitrogen-poor dependent alveoli are emptying into the airway, and the nitrogen concentration detected by the sensor remains relatively stable.
• At the end of expiration, as closing capacity is encountered, the dependent airways close and now the only gas being exhaled comes from the nitrogen-rich upper lobe alveoli, which increases the expired concentration of nitrogen.
• On a N₂ concentration/volume graph, the point at which the expired concentration of nitrogen suddenly increases is therefore the closing volume.

The resulting graphic closely resembles the xenon bolus measurement. Here, a single-breath nitrogen washout of a 60 year old smoker can be seen (it is stolen shamelessly from Robinson et al, 2013 and modified only to help illustrate the point better)

If one thinks that this single breath nitrogen washout technique looks a lot like Fowler's method for determining dead space, one would be essentially correct. Both methods involve a single breath of pure oxygen. However,  Fowler (1948) never intended to use his single-breath method for the purpose of measuring the closing volume, and the original Fowler method does not include exhaling until Phase IV can be seen. The closing volume concept wasn't even a thing until Dollfuss et al (1967).  Fowler's original nitrogen washout technique was modified by Antonisen et al in 1969 for the purpose of cheaply and safely measuring closing capacities in a large group of subjects (xenon doesn't grow on trees you know). Unfortunately, nobody ended up calling it the Antonisen method. 

Factors which alter closing capacity

One day, one might need to list these in some sort of SAQ or viva, as the college curriculum document specifically asks for "the factors that alter it". In brief:

• Expiratory airflow: closing capacity increases significantly with increased expiratory flow. Rodarte et al (1975) found that closing capacity almost doubled when expiratory flow increased from 30L/min to 60L/min.
• Expiratory effort:  the pressure of the chest wall on inflated alveoli is transmitted to the small airways, i.e. the alveolar pressure might exceed airway pressure so much that airway closure occurs. Closing capacity will therefore be higher during forceful expiratory manoeuvres.
• Small airways disease, eg. asthma or COPD, gives rise to an increased closing capacity by increasing the muscularity and mucus content of peripheral airways, making them more narrow and therefore making their collapse earlier, at higher lung volumes
• Increased pulmonary blood volume: this is supposed to be related purely to the weight of all that extra blood, which basically puts pressure on dependent lung regions and causes them to remain collapsed at higher lung volumes. As such, any condition which increases pulmonary blood volume (eg. left ventricular failure) is said to increase the closing capacity. Or so it is repeated in many textbooks because wisened elders (Collins et al, 1975, for example) have previously demonstrated it. Perhaps modern CCF patients are better fluid-managed; Torchio et al (2006) were unable to find any significant difference in closing capacity between their CCF patients and healthy controls.
• Decreased pulmonary surfactant: anything that increases the propensity of the alveoli to collapse will lead to an increase in the closing capacity. Those collapsed alveolar septa no longer provide traction on the walls of small airways because they are folded and flaccid. 
• Parenchymal lung disease: given the reliance of the small airways on the elastic pull of neighbouring alveolar septa, one might conclude that closing capacity increases when lung elastic tissue is lacking.
• Age - increasing age results in an increased closing capacity, a matter which is discussed at length below

Influence of age on closing capacity

With increasing age, closing capacity increases, largely as the consequence of an increase in residual volume. The closing volume does not change substantially. This is generally viewed as the consequence of a deterioration of lung elasticity, a loss of stretchy recoil pressure which main the patency of smaller airways.  This delightful feature of old age is important to mention because it is relevant to a famous diagram, which in its most basic form looks like this:

A somewhat more evolved version of this image can be sometimes found in authoritative monographs on the topic of age-related changes in respiratory function. Probably the best example is Figure 3 from the excellent paper by Zaugg & Lucinetti (2000). With the exception of added colour, it is reproduced here in its intact form, without any permission whatsoever:

The CICM primary exam candidate may wish to commit this thing to memory, as it might one day be asked about in some sort of written SAQ. Important elements to label on this graph would be the age at which the closing capacity exceeds supine FRC (44 years) and erect FRC (66 years). These are probably numbers worth repeating because they seem to occur frequently in textbooks. The origin of these values appears to be a paper by F.Ruff (1974), whose mean ages are derived from a population of Scandinavian subjects (Ruff's numbers are 44 and 65).  Nunn's differs slightly (the 8th edition gives 75 years as the age at which the erect man will have a closing capacity greater than their FRC), and no reference is given for this. Overall, given the variability in the structure and function of elderly people, one could probably come out with just about any number, and stand a reasonable chance of successfully bamboozling a sleepy viva examiner. 

Clinical significance of closing capacity

After all this explanatory work, one might fairly ask the question, what is the point? Why do we care? Is this an abstract lung volume which nobody will ever need to know about after they finish their primary exams? The answer is probably yes, but closing capacity does have some physiological relevance to the intensivist, and is probably worth knowing about.

• It influences denitrogenation of the FRC.  Collapsed lung units will not have nice fresh oxygen wafting into them while you preoxygenate your patient prior to induction. Factors which decrease the FRC (obesity, etc) or increase the closing capacity (old age) increase this effect, whereas techniques which increase the FRC (eg. the use of PEEP) ameliorates it.
• It influences atelectasis. Airway closure leads to the absorption of alveolar gas, loss of alveolar volume, and ultimately collapse of those alveoli. Rothen et al (1998) were able to demonstrate that airway closure and shunt are closely matched in anaesthetised patients, and that their combination accounts for 75% of the hypoxia during anaesthesia.
• It is responsible for the age-related decrease in oxygenation, because the elderly, i.e. anybody over 66 according to F.Ruff (1974), have some degree of dependent atelectasis under normal circumstances and even when upright. The resulting shunt produces the observed downward drift of PaO₂ which is associated with increasing age.
• It aggravates lung injury through cyclic atelectasis. When one's tidal ventilation volume includes the closing volume, the end of every breath is punctuated by the collapse of small airways, and every inspiration drags them open again. The outcome is biotrauma, most often discussed in the context of ventilator-induced lung injury.  Milic-Emili et al (2007) spend about four pages on this specific issue, which makes one think that it must have some importance.