One of the hallmarks of chronic asthma is airway inflammation. This frequently causes an increase in the perfusion of the airways which in turn can appear as an increased DLCO in routine PFTs. A number of investigators have noted that this inflammation can also cause an increase in exhaled air temperature. This increase in exhaled air temperature is not due to an increase in body temperature but to increase in the rate of heat exchange between the airways and respired air due to the increased airway perfusion.

Because the increase in exhaled air temperature also correlates reasonably well with exhaled Nitric Oxide (NO) levels it would seem that measuring exhaled air temperature as part of spirometry or other pulmonary function testing could either act as a substitute for exhaled NO measurements or at least indicate which patients would benefit the most from exhaled NO measurements. It turns out however, that making these measurements is a lot more complicated than it would appear at first glance.

The most important factor that makes exhaled temperature difficult to measure is that it varies throughout exhalation. This has lead to two different approaches to measuring exhaled air temperature. First by measuring the rate at which exhaled air temperature changes during a slow exhalation. Second, by measuring the plateau temperature (PLET) which usually occurs near the end of exhalation and also usually from a slow, controlled exhalation.

One of the early group of researchers noted that exhaled air temperature increased exponentially during exhalation. For mathematical reasons, they determined that the temperature slope from the beginning of exhalation to 63% of the plateau temperature best characterized the rate of increase. In this and related studies exhalation was standardized with a mouth pressure of 10 cm H2O and at a flow rate of 10-11 LPM and results were expressed as degrees centigrade per second.

 

Other researchers have noted more significant differences in plateau temperatures than in the temperature slope although the definition of plateau temperature is open to interpretation. One study defined it as a 2 second period where the exhaled temperature did not change more than 0.5 degree centigrade. Another as the average temperature in the last 20% of exhalation and occurring more than 6 seconds after the start of the maneuver. Several others simply stated it was the “end-expiratory plateau” temperature without any further explanation.

Although there is general agreement that asthmatics have higher exhaled air temperatures than patients with normal lungs there are discrepancies when the results from different studies are compared. Part of the reason for this is that expiratory flow has varied between ~5 and ~10 L/min in different studies when the measurements were made from a single expiratory maneuver. Another reason is that there has been no standardization in the equipment used to measure exhaled air temperature. More than one investigator has noted that both the slope and the plateau temperatures decrease the further the measurements are made from the subject’s mouth. Temperature measurement have been made anywhere from ~1 cm to ~15 cm away from the subject’s mouth but in several studies the distance was not noted.

Another factor is that thermistors and thermocouples have their own thermal mass and therefore take a finite time period to respond to changes in temperature. Researchers from different studies have noted response times of between 1 and 64 milliseconds but it some cases is not clear to me what is meant by response time. The speed of a response to a change in temperature is usually characterized by what is called the time constant and it usually takes a period of approximately 5 time constants to reach at least 95% of the final response. Some studies attempted to carefully characterize their thermisters or thermocouples while other studies just reported the device’s specified “response time” which likely  came from a manufacturer’s data sheet.

Finally there is a certain amount of noise in the temperature signal. This noise can be a significant fraction of degree centigrade. Where noted there were a couple of different approaches used towards averaging this noise but in some cases this signal noise was not even acknowledged.

Study results:

Slope: (degrees centigrade per second)

Study	Normal	Asthma	COPD
D	4.12 +/- 0.41	8.17 +/- 0.83
E	4.00 +/- 0.26		1.86 +/- 0.15
F	4.23 +/- 0.41	7.27 +/- 0.6
H	1.93 +/- 0.21	2.43 +/- 0.23
I	120.90 +/- 95.90	116.43 /- 87.05

PLET (degrees centigrade)

Study	Normal	Asthma	BPD	COPD
A	26.97 (26.58-27.38)	29.60 (29.20-30.02	26.72 (25.11-27.57)
D	34.45 +/- 0.8	35.75 +/- 0.6
E	34.45 +/- 0.8			34.55 +/- 0.6
G		31.1 +/- 0.3
H	27.47 +/- 0.24	30.18 +/- 0.14
I	30.27 +/- 1.25	31.15 +/- 1.19
J	34.84 (32.29-35.84)	35.45 (34.12-36.09)

One very interesting question these results bring up is whether PFT results are being properly corrected for temperature. Spirometer and pneumotach results are routinely corrected using the BTPS factor which assumes that exhaled air is at body temperature (nominally 37 degrees). The maximum exhaled temperature that was observed in all of these studies for normal subjects was less than 35 degrees. Research from several decades ago showed temperatures in the middle bronchi was pretty much at body temperature during normal tidal breathing so the question is why is there a discrepancy of at least 2.5 degrees between this and exhaled air temperature. Although this is probably due in part to heat recovery within the airways during exhalation it is also true that during a forced vital capacity maneuver the rate at which inspired air comes to equilibrium with body temperature depends on the inspiratory flow rate, inspiratory volume and how long the breath is held at TLC before exhaling. Expiratory flow rates can affect the rate of heat recovery by the airways as well. It is possible, therefore, that during an FVC maneuver inspired air does not always reach body temperature before being exhaled.

Even if it is assumed that inhaled air does reach body temperature this also brings into question how different systems correct for BTPS. Some test systems measure the temperature of their spirometer or pneumotach and even perform a “dynamic” BTPS correction but fact is that there are many that do not. I’d be curious what assumptions are being made in some of these test systems in order to make the BTPS correction, particularly since it is apparent that exhaled air temperature varies throughout exhalation.

Researchers have shown that exhaled air temperature is higher in asthmatics than in normal subjects. Exhaled air temperature has been shown to correlate highly with airway perfusion and this has been confirmed by measuring airway perfusion more or less directly. It has also been confirmed by seeing a decrease in exhaled air temperature when asthmatics are treated with inhaled steroids and an increase when normal subjects receive an inhaled bronchodilator. One study also showed, not surprisingly, that exhaled air temperatures in patients with COPD were lower than normal subjects. Exhaled air temperature has also been shown to correlate reasonably well with exhaled Nitric Oxide levels.

Exhaled air temperature has the potential to be a simple and inexpensive screening tool, both in the presumptive diagnosis of asthma and in determining which patients could benefit from nitric oxide measurements. Exhaled air temperature measurements however, lack standardization both in how they are analyzed (slope versus plateau) and in the hardware used to measure it. This makes it difficult to determine the range of normal values and means that it is not yet ready for routine clinical use.

Since an elevated DLCO is often seen in asthmatic patients, I would be interested to see if it also correlates with an elevated exhaled air temperature. I would not be surprised to find that exhaled air temperature, exhaled NO and DLCO all correlated with each other since they are all dependent to one extent or another on airway perfusion.

References:

[A] Carraro S, Piacentin S, Lusiani M, Uayan ZS, Filippone M, Schiavon M, Boner AL, Baraldi E. Exhaled air temperature in children with bronchopulmonary dysplasia. Ped Pulmonlology 2010; article ID PPUL-10-007.R1.

[B] Madan I, Bright P, Miller MR. Expired air temperature at the mouth during a maximal forced expiratory maneuver. Eur Respir J 1993; 6: 1556-1562.

[C] McFadden ER, Denison DM, Waller JF, Assoufi B, Peacock A. Direct recordings of the temperatures in the tracheobronchial tree in normal man. J Clin Invest 1982; 69:700-705.

[D] Paredi P, Kharitonov SA, Barnes PJ. Fasther rise of exhaled breath temperature. A novel marker of airway inflammation? Amer J Respir Crit Care Med 2002; 165: 181-184.

[E] Paredi P, Caramori G, Cramer D, Ward S, Ciacci A, Papi A, Kharitonov SA, Barnes PJ. Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease. Eur Respir J 2003; 21: 439-443.

[F] Paredi P, Kharitonov SA, Barnes PJ. Correlation of exhaled breath temperature with bronchial blood flow in asthma. Respiratory Research 2006; 6:15

[G] Piacentini GL, Bodini A, Zerman L, Costella S, Zanolla L, Peroni DG, Boner AL. Relationship between exhaled air temperature and exhaled nitric oxide in childhood asthma. Eur Respir J 2002; 20: 108-111.

[H] Piacentini GL, Peroni D, Crestani E, Zardini F, Bodini A, Costella S, Boner AL. Exhaled air temperature in asthma: methods and relationshipo with markers of disease. Clin Exp Allergy 2007; 37: 415-419.

[I] Pifferi M, Ragazzo V, Previti A, Pioggia G, Ferro M, Macchia P, Piacentini GL, Boner AL. Exhaled air temperature in asthmatic children: a mathematical evaluation. Pediat Allerg Immunol 2008; DOI: 10.1111|j.1399-2027.2008.00742

[J] Popov TA, Dunev S, Kralimarkova TZ, Kraeva S, Dubuske LM. Evaluation of a simple, potentially individual device for exhaled breath temperature measurement. Respiratory Medicine 2007; 101: 2044-2050.

[K] Popov TA. Human exhaled breath analysis. Ann Allergy Asthma Immunol 2011; 106: 451-456.

[L] Zawadski DK, Lenner KA, McFadden ER. Comparison of intraairway temperature in normal and asthmatic subjects after hyperpnea with cold, cold and ambient air. Amer Rev Resp Dis 1988; 138: 1553-1558.

PFT Blog by Richard Johnston is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.