Delmedica Investments (Singapore) Pte Ltd
7 Temasek Boulevard
#06-01, Suntec Tower 1
Singapore 038987
Phone: +65 6415 3102
Fax: +65 6415 3108

Background
Airway inflammation is considered to be the hallmark of asthma and is also playing a role in COPD and other lung diseases [1,2]. Its assessment by non-invasive methods has proven useful in asthma management [3], but no easy and affordable methods to this end are available in everyday practice. We have developed a device to measure the temperature of the exhaled breath (exhaled breath temperature, EBT) as a surrogate marker of the inflammation in the intrathoracic airways [4]. The high level of precision of the instrument allows picking the signal attributable to the input from the airway wall to the overall temperature of the exhaled air.

Most studies on EBT so far have been done in asthmatic patients and have suggested the utility of this approach to assess non-invasively changes in the degree of airway inflammation [5-9]. Our portable device makes this method much more applicable in everyday clinical practice as it makes possible individual measurements possible in the home of those suffering. The option with the newest third generation devices to have a succession of measurements accessible to the treating physicians could make decision making about treatment modalities more objective. We have demonstrated the association between the daily course of EBT, PEF and symptoms [10].

The method holds particular promise in pediatric practices, as children at the age of 3 and above are able to cope with the requirements of the measurement. Actually, most of the initial work to prove the feasibility of the method was done by Giorgio Piacentini and co-workers in children [6, 8, 9]. In a recent study the team of Nikos Papadopoulos found an association between viral exacerbations of asthma and EBT in paediatric patients [11].

EBT measurements appear to hold promise also in other lung diseases. There are reports that EBT is shifting downwards in patients with chronic obstructive pulmonary disease, in whom airways and pertaining vasculature are reduced [12, 13]. We have preliminary yet unpublished data of increased EBT (but not axillary temperature) in cases with viral infections, tuberculosis and bronchopneumonia.

Advantages
- Simplicity of use.
- Few consumables.
- Immediate results.
- Possibility to use X-halo at the patient’s home.

Areas of application
1. Research:
a. Field epidemiological studies.
b. Clinical trials comparing anti-inflammatory drugs.
c. Pilot studies in areas beyond asthma and COPD.
d. Pilot studies in areas beyond pulmonary medicine.
   
2. Patient care:
a. To assess asthma / COPD control on subsequent visits in the physician’s office.
b. Day-to-day assessment of asthma / control at the patients’ homes (like PEF-meter).
c. To predict onset of respiratory viral infections in patients at risk.

Limitations
- At this point of development of the device it is not possible to use it to discriminate asthmatics from non asthmatics on the basis of one time measurement of EBT.
- No reference values in relation to age, gender, height, weight and ethnicity are available thus far.

EBT and Nitric Oxide measurement (FeNO)
FeNO has been established as a non-invasive marker of airway inflammation in eosinophilic asthma [14]. It has been demonstrated useful in monitoring asthma control [15] and in assessing the anti-inflammatory effect of inhaled corticosteroids [16]. Most of the intital work has been done with sophisticated NO-analyzers using the principle of chemiluminescence. Recently, a handheld device (NIOX MINO; Aerocrine) using electrochemical sensors for NO assessment has been introduced to the market [17, 18] which is more affordable for use in physicians’ offices. However, the initial and maintenance costs of this portable NO device still limit its use. There are also issues related to the repeatability of the results [19, 20]. Correlations have been found between FeNo and EBT [6, 8, 9]. EBT ranges fall within a narrower band, but their repeatability is quite high. Measuring EBT also captures the signal of non-eosinophilic inflammation.
T. Popov

References

1. National Heart, Lung and Blood Institute. 1995. Global Initiative for Asthma. National Institutes of Health, Bethesda, MD. Publication No. 95-3659.
2. The global strategy for diagnosis, management and prevention of COPD (updated 2008). GOLD website <www.goldcopd.org>.
3. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715-21.
4. 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.
5. Paredi P, Kharitonov SA, Barnes PJ. Faster rise of EBT in asthma: a novel marker of airway inflammation? Am J Respir Crit Care Med 2002; 165: 181–184.
6. Piacentini GL, Bodini A, Zerman L, et al. Relationship between exhaled air temperature and exhaled nitric oxide in childhood asthma. Eur Respir J 2002; 20: 108–111.
7. Paredi P, Kharitonov SA, Barnes PJ. Correlation of exhaled breath temperature with bronchial blood flow in asthma. Respiratory Research 2005; 6, 15: 1-10.
8. Piacentini GL, Peroni D,.Crestani E, Zardini F, Bodini A, Costellaw S, Boner AL. Exhaled air temperature in asthma: methods and relationship with markers of disease. Clin Exper Allergy 2007; 37: 415–419.
9. Pifferi M, Ragazzo V, Previti, Pioggia AG, Ferro M, Macchia P, Piacentini GL, Boner AL. Exhaled air temperature in asthmatic children: a mathematical evaluation. Pediatr Allergy Immunol 2008, online: Mar 10 2008; DOI: 10.1111/j.1399-3038.2008.00742.x.
10. Popov TA, Kralimarkova TZ, Lazarova C, Tzachev CT, Dimitrov,VD.. Daily monitoring of asthmatics by means of individual devices for exhaled breath. IEEE Sensors Journal, 2009 (in press).
11. Xepapadaki P, Xatziioannou A, Chatzicharalambous M, Makrinioti H, Papadopoulos NG.  Exhaled breath temperature increases during mild exacerbations in children with virus-induced asthma.  Int Arch Allergy Immunol 2010;153:70–74.
12. Paredi P, Caramori G, Cramer D, Ward S, Ciaccia A, Papi A, Kharitonov SA, Barnes PJ. Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease. Eur Respir J. 2003 Mar;21(3):439-43.
13. Schuermans D, Verbanck S, Vincken W. Is exhaled breath temperature a useful marker of pulmonary inflammation? Abstract Book ERS Congress Berlin 2008, A4066.
14. Jones SL, Kittelson J, Cowan JO, Flannery EM, Hancox RJ, McLachlan CR, et al. The Predictive value of exhaled nitric oxide measurements in assessing changes in asthma control.  Am J Respir Crit Care Med 2001; 164: 738-43.
15. Jones SL, Herbison P, Cowan JO, Flannery EM, Hancox RJ, McLachlan CR, et al. Exhaled NO and assessment of anti-inflammatory effects of inhaled steroid: doseresponse  relationship. Eur Respir J 2002; 20: 601-8.
16. American Thoracic Society, European Respiratory Society.  ATS/ERS Recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Resp Crit Care Med 2005; 171: 912-30.
17. Alving K, Janson C, Nordvall L. Performance of a new hand-held device for exhaled nitric oxide measurement in adults and children. Respir Res 2006; 7: 67.
18. McGill C, Malik G, Turner SW. Validation of a hand-held exhaled nitric oxide analyzer for use in children. Pediatr Pulmonol 2006; 41: 1053-7.
19. Khalili B, Boggs PB, L. BS. Reliability of a new hand-held device for the measurement of exhaled nitric oxide. Allergy 2007; 62: 1171-4.
20. Menzies D, Nair A, Lipworth BJ. Portable exhaled nitric oxide measurement: comparison with the "gold standard" technique. Chest 2007; 131: 410-4.