Analysis of COPD Patient's Exhaled Breath Using Sensor Array

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Journal of Sensor Science and Technology Vol. 22, No. 3 (2013) pp. 219-222

http://dx.doi.org/10.5369/JSST.2013.22.3.219 pISSN 1225-5475/eISSN 2093-7563

J. Sensor Sci. & Tech. Vol. 22, No. 3, 2013

1. ≠ –

Œº°≠ ™¿¬ ºÎ¶ ÃÎ— «≠ Û¬¶ ¯‹œ¬ Ê˝∫ ¿

° ¸ŒÕ œŒ ∞Î«˙∏™ «≠« Ø≠° ˚• ∏º˚Œ ˆÛ«

ıÌ˙ ¸√ÿ≠¬ π∫ ¨∏° ¯‡«ˆ “Ÿ. ^{÷Ÿ° –Æ‚˙}

« ﬂﬁŒGC-MSª ÁÎœ© Œº« Ë‚«¬ °, ^“Ø, ^{ßª –}

Æœ© ≥Œ« ØÃ— ∫–˙ ∫˚Œ ˜Ã° ˚• ∫–° Î— ¨∏

° ÃÁÓ≥Ÿ. «— £‚¶ Îœ© Ë‚«¬ ∫–∫ ÷ﬂ∫ Ø‚≠

’∞(volatile organic compounds)^{∫ ‡}3000^{© æÃ ÷∏Á Ã}

È ∫–∫ ‹Œ°≠ ÛŒ Ø‘«≈™ Û°≠ ˝∫… ˆ ÷¬ ∫–°

Î— ≈¯ÎÁ« μ‚ª ﬁª ˆ ÷Ÿ[1, 2].Ø˜ Û¬ ºª« Í“

Ó›˙ ˜◊ ª ﬂ˝œ¬ °∫« œŒ¶ Ë‚œ¬ ‚¸ÃŸ. ^{Û ˙}

ØÃ ﬂ˝œÈ ÃØ— ≈¯ÎÁ° ¯∞œˆ ¯œ«Œ Û°≠ Ë‚

«¬ °∫¶ –Æœ© Û˙Øª ÆŒ“ ˆ ÷ª Õ∏Œ ∏Ì ÷∏

Á, ÷Ÿ°¬ Ûœ Ø⁄« £‚° Î— π∫ ¨∏° ÃÁÓˆÌ ÷ Ÿ. Ø˜ £‚° ˜‘«Ó ÷¬VOC ^{∫–« À‚ª ß—}GC-MS

¶ ÁÎ— ¨∏° ¯‡«Ó ‘∏Á, ¨∏¯∫ °∫æ≠¶ ÃÎ—Û œØ⁄Õ«≠—Á˜«∏∞ªß—¨∏°¯‡«˙Ÿ[3-7].

∏∫Û‚∫ Û˙Ø(chronic obstructive pulmonary disease)

¬ Û°≠ ∞ıÃ ˝‚È≠ ¯‚« Ãø ÎŒ° ºΔÆ≠ Í“ ¯ﬁ Ã ¯∞œˆ ¯œ© ∏∫¥∏Œ «≠«ÓÆÛ ﬂ¤(lung attack)^Ø

ª œ∏≤Ÿ. Û ﬂ¤Ã œÓ™È ⁄÷ ˚Ã °¸ˆÌ ∏∫‚ß, ^°

◊–Ò, ÿμ« «Œ ÓÃ ™∏≠Ÿ. COPD¬ Á¡¸« ÷‰ ¯ Œ ﬂ« œ™ÛÌ ºË ∏« ‚∏°≠¬ ﬁœÌ ÷Ÿ. ^˚Û≠

COPD¯‹°≠μ ∂‚¯‹ª ß— ¨∏Ê˝∏Œ Û°≠ ¿ßø»

‡˚«≈™ ﬂ˝œ¬ °∫° Î— –Æª ¯‡œ© ‘Ÿ[8].

SPME (Solid-Phase Microextraction)ƒÃˆ¬ ÷Ÿ° ≥ﬂ»

GC –Æª ß— ˘√μ ‚˙Œ Ìº, ^◊º, «¬ ‚º √·¶ ±Ì

¸£‘ ˘√μ “ ˆ ÷¬ ø≤˚Œ ‚˙ÃŸ. SPME ^{ƒÃˆ¶ Á}

ÎœÈ √·« ˘√μª ß— Î≈ «¬ π‚— Â°° ‰ ¯∏

Á, π∫ æ˘« °∫¶ –∫ Ûμ ¸ß° Îœ© ±¸˚Œ ·˙¶

™∏ΩŸ. SPME¬ Ì–⁄ Ì§Ûª °¯ «Æ´¶ Ÿ√ •È° ⁄

æ≠ ÓπÃ¶ ÁÎ— COPD ^{Ø⁄« £‚–Æ}

ØÿŒ1^• Ã≈±2^• ¸¯μ3^• Ø¸‚3^• ”§¡1,+

Analysis of COPD Patient's Exhaled Breath Using Sensor Array

Joon-Boo Yu¹, Shin-Yup Lee², Jin-Young Jeon³, Hyung-Gi Byun³, and Jeong-Ok Lim^1,+

Abstract

The exhaled breath contains gases generated from human body. When disease occurs in the body, exhaled breath may include gas components released from disease metabolism. If we can find specific elements through analysis of the exhaled gases, this approach is an effective way to diagnose the disease. The lung function has a close relationship with exhalation. Exhaled gases from COPD (Chronic Obstructive Pulmonary Disease) patients can be analyzed by gas chromatography-mass spectroscopy (GC-MS) and a gas sensor system.

The exhaled breath for healthy person and COPD patients had different components. Significantly more benzendicarboxylic acid was detected from COPD patients than in healthy persons. In addition, patients had a variety of decane. Phosphorous compounds with different isomers were detected from patients. The results obtained by gas sensor system were processed by PCA (Principal Component Analysis). The PCA results revealed distinct difference between the patients and healthy people.

Keywords : GC-MS, COPD, Sensor array, Exhaled breath

1ÊœÎ–≥ ˝Ì«–¨∏“(Bio-Medical Research Institute, Kyungpook National Unversity)

135 Dongdeukro, Junggu, Daegu, 700-721, Korea

2ÊœÎ–≥¥¯(Department of Internal Medicine, School of Medicine, Kyungpook National University)

807 Hongukno, Bukgu, Daegu, 702-210, Korea

3≠¯Î–≥ ¸⁄§∏Î≈¯–Œ(Department of Electronic, Information

& Communication Engineering, Kangwon National University) Joongangro, Samcheok, Kangwon, 245-711, Korea

+Corresponding author : [email protected] (Received : May. 6, 2013, Accepted : May. 20, 2013)

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License(http://creativecommons.org/licenses/by- nc/3.0)which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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J. Sensor Sci. & Tech. Vol. 22, No. 3, 2013 -220-

Joon-Boo Yu§Shin-Yup Lee§Jin-Young Jeon§Hyung-Gi Byun§Jeong-Ok Lim

√— ƒÃˆ¶ Ø∞˜ Ì»» ¸Î ”° ÷Ó ∏ÈÓÆ ÷Ÿ. ^ƒÃ

ˆ¬ ◊º «¬ ‚º° ˜¢ Î‚œ© √·¶ Ì¯√∞ÌGC-MS

« ÷‘∏° ÷Ó Ì¯» °∫¶ ª¯√— √·¶ –Æ“ ˆ ÷Ÿ[9].

ª ¨∏°≠¬COPD Ø⁄Õ «≠— Á˜ª ÎÛ∏Œ œ© £‚

« ˜Ã°ªGC-MSŒ ≠’∞ª Ò≥œÌ, æ≠ ÓπÃ¶ ÁÎœ

2. «Ë Ê˝

2.1 ^{£‚°∫« ˆ˝}

COPDØ⁄« £‚¶ –Æœ‚ ß— £‚ §Î ÎÛ∫60~70^º

« ¨…ÎŒ COPDÕ Î∂∫∏Œ Ì¨ Ê¬Ã ÷¬ «≠— Á˜ª

±§ œ¥Ÿ. £‚ §Î√ ÛÕ ‚μ° Δ— ‘»°≠ ﬂ˝— °∫

¶ ¶≈œ‚ ßœ© ÎÛ⁄¬2√£ Ã¸° ƒÁ¶ œ·— Û¬Œ Á˜∏Œ ±§œ¥Ì, £‚§Î ÎÛ⁄¬ ©÷∏∏Œ Á°¶ œÌ

˝ˆŒ ‘ »ª Û∏Ó ªμœ œ¥Ÿ. £‚°∫« ˆ˝∫ ß Ó«

ˆ–ª ¶≈œ‚ ßœ© Æ¶ª ◊ÈØÈ(tedlar bag) ^{’° ¨·œ}

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¸œ© §≠–›¿Ã ÷“≠ «μœ œ¥Ÿ. 2.2 ^£‚°∫«GC-MS ^–Æ

£‚ °∫« –Æ∫GC-MS (HP5890, HP 5972)^{¶ ÁÎœ©}

¯‡œ¥Ÿ. GC-MS° ÁÎ» Æ≥ ÊÃ¬30 m^{ÃÌ ∫√¥Æ∫}

(splitless) ÂŒ ¿Ï« ¬μ¬60^…°≠ 7 ^…/min ^{Œ ı°œ©}

300^…°≠20^{–£ Øˆœ¥Ÿ}. ^¯§—mass ^¸ß¬50-600 m/z

ÃŸ.

£‚°∫« –Æª ßÿSPME ƒÃˆ¶ ÁÎœ© °∫¶ Ì¯

œ¬ ¸≥Æ¶ œ¥∏Á, 65 um PDMS/DVB (polydimethylsilox ane/divinylbenzene) ƒÃˆ¶ ÁÎ œ¥Ÿ. PDMS/DVB ^ƒÃˆ

¬ ¿‚ «¬ ÃÍ≠∫“« μ‚ª ÷“≠“ ˆ ÷∏Á, VOC ^À‚

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2.3 ^{æ≠√∫¤ ◊ ¯§}

æ≠ ¯§√∫¤ ∏∫∫ ›”Í≠∞ æ≠ŒTGS 2600, 2610, 2601, 2620^{ª ¢¢}2^{≥ø ÁÎœ©}3 ml« ˆ° Œ¯œ¥Ÿ.

ˆ« ’ ‹°¬ ¿∞» ¯‚¶ ¶≈œ‚ ß— Õ¶ Œ¯œÌ ƒ‹

°¬ ﬂ¡¶ ¨·œ¥Ÿ. ˆ° £‚ ˘√Ã Ì¯»SPME^ƒÃˆ

¶ ÷‚ ß— πœ˙ ·› Â°¶ Œ¯œ¥Ÿ. ^{æ≠« ≈£¬}DAQ (National Instrument) ∏Â¶ ÁÎœ© πÊ“ ˆ ÷μœ œ¥∏

Á Fig. 1^{˙ ∞Ã ∏∫«˙Ÿ}.

æ≠ ÓπÃ √∫¤°≠ £‚ ¯§ª œ‚ ßœ©SPME^ƒÃˆ

¬200^…°≠20–£ ˙“°∫¶ ¯ﬁœÁ º¥œ¥Ÿ. SPME ^ƒ

Ãˆ¬ £‚°∫¶ §˝— ◊ÈØ È° ‘œ©20^{–£ Î‚œ©}

£‚ ˘√ª ƒÃˆ° Ì¯√◊Ÿ. ƒÃˆ¬ æ≠ √∫¤° Â¯œ

« ›¿ª ≈£Œ ‚¬—Ÿ. Ã ß ¯§— ™∫ æ≠« ˙◊Ø≠≤

Œ ØØœ© ¯§™∏Œ ÁÎœ¥Ÿ.

3. ·˙ ◊ Ì˚

3.1 GC-MS ^–Æ

£‚°∫¶GC-MS^{Œ –Æ— ·˙¬}Fig. 2 ^{Õ ∞Ã ™∏μ∏}

Á, ^°Œ, ºŒ‡∫ ¢¢ √£‡˙ °∫ ∫–« ∏Á Ò≤ª ™∏ª Ì ÷Ÿ. 5≥« «©° ÷» Æª ÃÁÌ ÷∏Á, ^{ÃÈ ∞˙∫ Δº}

∏∂ÃÂ(acetamide), ^‰Ó(phenol)^˙3^{æ« «œÍ}(siloxane)^˘

° –˘«˙Ÿ. Δº∏∂ÃÂ¬ ø“ «¬ Ã˝∞° «ÿ≠ ’∫…

ˆ ÷¬ ∞˙ÃÁ, ‰Ó∫ ∂∫Ã ÷¬ ∞˙Œ Ωƒ∞Œ ∑Î» Ø Á∫–« Ø¸ «¬ ‹ŒØÊ ‰Œ° ‚Œ— Õ œ ˆ ÷Ÿ. ^{ÃÈ ∫}

– ‹ ÃÆ« °∫È∫Table 1^°COPDØ⁄Õ «≠— Á˜« £

‚°≠ À‚» ∫–È˙ È˚ Ò¶ ™∏ª˙Ÿ.

Benzendicarboxylic acid^∫–∫COPD Ø⁄« £‚°≠ «≠

— Á˜∏Ÿ Ù‘ ™∏μŸ. ^{«— Œ}(P)∫–Ã ˜‘» ’∫∞∫ «

≠— Á˜˙ Ø⁄« ÊÏ ◊ ∏∂° Ÿ• phosphoric acid^Õ triphenyl phosphate^{Œ À‚«˙Ÿ}. Triphenyl phosphate^{¬ •}

Ã ŸÓ÷¬ ∏∂ÃÁ, cyclohexanol^{μ •°}-OH^{° ∑°«Ó}

÷¬ ∏∂ÃŸ. ◊ ‹°μ •« Ø¸» ∫–È˙ ∫“Õ ˆ“Œ

∏∫» •≠(decane)« Ã∫˙º° πÃ ™∏μŸ.

Fig. 1. The measurement sensor system with metal oxide sensor.

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Analysis of COPD Patient's Exhaled Breath Using Sensor Array

3.2 æ≠ ÓπÃ¶ ÁÎ— £‚ ¯§

«≠— Á˜˙COPD Ø⁄°‘≠ §˝— £‚°∫¬ Û¬°≠

˜§ª œ© Ãøœ¥∏Á, ^{§Î ƒ}24√£ Ãª ¯§œ¥Ÿ. ^£‚

°∫ ¯§— ·˙¬Fig. 3 ^{˙ ∞Ã ™∏μŸ}.

¯§·˙¶ ÃÎœ© ÷∫––Æ(principal component analysis)^{ª ˚Î— ·˙¬}Fig. 4^{Õ ∞Ã ™∏μŸ}. ^{Î∂∫˙ Ø⁄}

« £‚¬ œ¸˜ ∏∞«Ó ™∏™Ì ÷Ÿ. COPD ^{Ø⁄ £« ·˙}

μ ≥Ó¯ ¸¬¶ ØˆœÌ ÷˙∏Á, ^{ÃØ— ·˙¬}COPD^{˙¥ ‹}

Ë°GOLD I ^˙GOLD III« ˜Ã° ¯ŒÃ … ˆ ÷Ÿ. ^{˙¥« ‹}

Ë° ˚Û1^{£ Î¬∫ £‚Æ}(FEV1)^ÃGOLD III^{Œ Ø⁄« ÊÏ}

°¬47% ^¥∏Á, GOLD I ^{« Ø⁄¬}84%Œ Î∂∫˙ ‡£« ˜Ã

¶ ∏ÃÌ ÷˙Ÿ. ^{˚Û≠ Ø⁄° ˚Û}FEV1Ã ∑∫ ÊÏ°¬ Û

”« ¯‚¶ Ê–˜ ¯Ó √Æˆ ¯œ© Û ª° ˝∫» °∫¶ À

‚œ‚ Ó¡Ô ˆ ÷Ÿ.

4. ·–

Œº ª°≠ Ë‚«¬ °, £‚ Ó∫ ºª°≠ œÓ™ ˝ÆˆÛ ª ›μœ«Œ «≠ Û¬¶ ÆŒœ¬ ‰“Œ≠ ¤Î“ ˆ ÷Ÿ. ^£

‚¬ Û° Í“¶ ¯ﬁœ¬ ÎŒŒ≠ ª¨¬ Ø˚°¬ Û ”° ÷¬

°∫∫– «¬ ˜◊ ª° ÏΔ÷¯ °∫ ∫–μ Ë‚… ˆ ÷∏Á,

Ã¶ ÃÎ— ÛÕ ¸√— «≠Û¬¶ ¯‹œ¬ ¨∏¶ ¯‡œ¥Ÿ. COPD¬ Û« ‚… Â÷Œ ﬂ˝««Œ Û°≠ ﬂ˝œ≈™ ‡˚«

Fig. 2.The GC-MS result of exhaled breath of COPD and control

; (a) M/54 smoker of control and (b) M/72 smoker of

COPD. Fig. 3. Test results for healthy subjects and patients with COPD;

Control 1: 59 years healthy man with exsmoker; Control 2: 54 years man with emphysema, smoker; COPD1: 72 years man with COPD, smoker; COPD 2: 63 years man with exsmoker.

Fig. 4. PCA to COPD patient's and control exhaled breath

Table 1. Comparison of patient with COPD and healthy Person

Cyclohexanol 0.11 0.44 0.14 0.68 Hentriacontane 0.03 0.04 0.03 0.03

Octadecane 0.03 0.04 0.03 0.03

Benzenedicarboxylic acid 0.32 0.15 0.08 0.08 Octahydro-4bbeta.,

8,10a.beta.-trimethyl-1 0.05 0.02 0.02 0.04 -phenanthrenol

Heptacosane 0.01 0.01 0.01 0.01

Tridecane 0.02 0.02 0.02 0.02

Phosoporic acid 0.11 0.44 0.04 0.04 Triphenyl phosphate 0.05 0.06 0.14 0.68 Chemical Components Area %

COPD Control

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Joon-Boo Yu§Shin-Yup Lee§Jin-Young Jeon§Hyung-Gi Byun§Jeong-Ok Lim

COPD Ø⁄« ÊÏ Î∂∫˙ ØÁ— ∫–« °∫ÈÃ πÃ À‚

«˙ˆ∏Benzendicarboxylic acid^∫–∫COPD ^{Ø⁄« £‚°}

≠ Î∂∫ ∏Ÿ Ù‘ ™∏μŸ. •≠˘« ∫–μ πÃ ™∏μ∏Á,

Œ(P)∫–Ã ˜‘» ’∫∞« Ã∫˙ºμ ≠Œ Ÿ• ¸¬Œ ∏∫«

Ó ÷˙Ÿ.

£‚¶ Îÿ≠ Ë‚«¬ ≠’∞« ∫–Ã Ÿ£Ÿ¬ ﬂ§° «—

∫ £« ∏∞Ã ÃÁÓ¸ª ÆŒœ¥Ÿ. COPD ^{Ø⁄£°μ ∏∞«}

Ó ™∏™Ì ÷˙∏Á, COPD ‹Ë° ˚Û £ÌÆ« ˜Ã¶ ∏Ã Ì ÷∏«Œ Û˜« ¯‚¶ Ê–˜ ¯Ó√Æˆ ¯ ‘∏Œ≠ ˙¥˙

¨¸» ∫–ª ˜‘«ˆ ª ˆ ÷Ÿ. ˚Û≠ Û˜« ¯‚¶ ˜‘

“ ˆ ÷¬ £‚¶ §Î“ ˆ ÷¬ ‚∏ «¬ Ê˝Ã ﬂ‰— ‚ÿÃ

… ˆ ÷ª ÕÃŸ.

Á« ¤

Ã ÌÆ∫2012^{‚ §Œ}(^{≥∞˙–‚˙Œ})« Á¯∏Œ ﬁ’ ŒˆØ Ê Á˜ªŒ-≈‚˙ ∂’¸ ∫Âø¬ Á˜« ˆ¯ª ﬁΔ ˆ‡»

¨∏”(2012K001351).

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