Il Campionamento Nell'analisi Del Respiro in Tempo Reale

Integriamo idee, persone, tecnologie
per dare anima e valori alle imprese

Enrico Loccioni
NI Medical Innovation Summit Claudio Loccioni Il campionamento del respiro in tempo reale | 15 giugno 2010
Loccioni
PROPRIETA Famiglia LoccionI
STAFF 320 collaboratori

44% laureati
SEDI Moie di Maiolati |General Impianti srl

Angeli di Rosora |AEA srl
Columbia (SC USA) |Loccioni USA Inc.
FATTURATO 50 Milioni di Euro (2009)

Installazioni in oltre 43 Paesi
R&I Research for Innovation Institute

>5% del fatturato 2009 investito
6 laboratori R&D
Laboratorio certificato MIUR
20 brevetti
FORMAZIONE 9% del costo del personale
Research for Innovation
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Applicazioni speciali
Apoteca chemo Sistema automatico per la

preparazione di farmaci citostatici
Medical Gas Tester Sistema mobile per

lanalisi di gas medicali
Breath Sampling Device
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Field of interest_Breath Analysis INTERNAZIONALI
BLUZONE
Place_Johns Hopkins University Baltimore PARTNERS
U-NET
Opinion Leader_ Prof. Terence Risby
Breath analysis
Breath analysis
Dogs able to identify cancer patients breath samples. Response time 10s !!!
McCulloch et al.: Diagnostic Accuracy of Canine Scent Detection
in Early and Late Stage Lung and Breast Cancers.
Integrative Cancer Therapies 5 , 1-10 (2006).
Breath is an instantaneous product of the following sources
molecules originating from inspiratory air

(current or historical exposure)
molecules that are directly or indirectly derived

from foods and beverages
endogenously molecules produced by

biochemical pathways that originate in tissues or VOC
cells throughout the body VOC
VOC VOC
History of breath analysis
400 A.C. Hippocrates

Breath odors provide diagnosis
fruity Diabetis
rotten pulmonary diseases
fish Hepatic diseases
1784 Lavoisier
carbon dioxide as a prodcut of normal respiration
1971 Pauling
Traces of volatile organic compounds in exhaled breath
discovered
2007 More than 500 Volatile Organic compounds in breath are

known
Advantages of breath tests
Breath analysis is non-invasive

Breath can be collected multiple times without risk to the subject
Children give breath samples willingly
Breath can be collected from the neonate to the elderly (a mouse to a elephant)
Breath can be easily collected in field, clinic, in-patient, OR and ICU
Typical concentration of molecules in a single breath of normal humans
Concentration (v/v) Molecules
Percentage (%) oxygen, water, carbon dioxide
parts-per-million (ppm) acetone, carbon monoxide, methane, hydrogen
formaldehyde, acetaldehyde, isoprene ethane,

1-pentane, ethylene, other hydrocarbons, nitric oxide,
parts-per-billion (ppb) carbon disulfide, methanol, carbonyl sulfide,
methanethiol, ammonia, methylamine, dimethyl
sulfide
Part per billion: 0, 000 000 1%
Techniques and methods
Tedlar bags are the most used system to analyze breath. The breath is
than entraped in absorption tubes and successively analyzed by mean of Gas Cromatography
Techniques and methods
Technique Analysis Method Response Time
GC
(Gas offline 1h
Chromatography)
MS
(Mass online <10s
Spectroscopy)
Electronic nose online <10s
Optical
online <1s
spectrometry
Sensors online 10s
Breath research production
Number of Number of
Compound Compound
publications publications
Oxygen 2155 Pulmonary diseases 2983
Carbon dioxide 2027 Asthma 1178
Hydrogen 1722 COPD 417
Emphysema 222
Ethanol 1053
Cystic fibrosis 221
Hydrocarbons 968 104
ARDS
Carbon monoxide 849 1674
Infectious diseases
Water 679 1551
Cardiovascular diseases
Nitric oxide 638 1334
Cancer
Pentane 141 730
Liver diseases
Ethane 128 230
Renal diseases
Acetone 126 221
Organ transplantation
Ammonia 95 81
Gastrointestinal diseases
Acetaldehyde 83 47
Dental diseases
Isoprene 66 4453
Normal physiology
Methanol 51 1858
Alcohol assessment
Methylamine 47 1322
Exercise
Ethylene 38 1142
Exposure assessment
Methanethiol 29 1004
Smoking
Carbon disulfide 23 556
Anesthesia
Carbonyl sulfide 5 445
Nutrition
Library of Medicine computer search (www.ncbi.nlm.nih.gov) :

more than 5000 citations to breath and clinical tests
Helicobacter Pylori detection
Molecules are quantified with spectroscopic methods after administration of a drug

or substrate labelled with carbon
Time of administration of the substrate, ventilation of the pattern must be carefully

controlled
Asthma monitoring by NO measure
Detection of molecules that are produced endogenously as a result

of normal or abnormal physiologies
Careful monitoring of the ventilation of the subject

(ERS ATS guidelines)
Summary of clinical breath analysis to date
capnography carbon dioxide

neonatal jaundice carbon monoxide
gastrointestinal diagnoses hydrogen, methane
airway reactivity nitric oxide (FDA approved)
oxidative stress ethane, pentane, ethene
cholesterol biosynthesis isoprene
renal function ammonia, alkylamines
hepatic function ammonia, carbonyl sulfide, methyl sulfide
infection (metabolites, host response to carbon dioxide, carbon monoxide, ethane, pentane,
infection) ethane, nitric oxide
heart transplant rejection branched chain hydrocarbons (FDA approved)
Why is breath analysis still challenging?
Breath sampling
Quintronss device: A-C deisposable tee-mouthpiece assembly, D disposable discard bag,

E single use 750 ml collection bag, F reusable 750 ml collection bag
Breath sampling
Breath sampling
Breath components will change as a function of breathing cycle
Breath molecules originate from cells throughout oral/nasal cavities,

pulmonary system and cells and tissues throughout the organism
Breath composition will change with breathing physiology
Carbon dioxide must be measured as normalizing values
Mouth pressure must be controlled to ensure correct sampling
Real-time breath analysis
Only real time analysis will allow mass screaning and threshold identification
Real-time -- result available within 5-10 min
Based upon sampling single breath
Must be able to be performed by people with limited training
Instruments must be portable/transportable and reliable
Monitoring a single breath in real-time
Measures for each breath

end-tidal CO2 SD
mouth pressure plateau SD
duration of plateau
Critical orifice
Monitor
CO2 monitor
Pressure monitor
Filter
MOUTH
Real-time breath profiling
Real-time breath profiling
From prototype to product: testing and design
GSI/ S Breath Sampler
GSI/ S Breath Sampler
GSI/ S user friendly SW interface
GSI/ S user friendly SW interface
Differential mobility spectrometry
Advantages:
Sensitive from ppb-ppt range

Portable
Relatively low cost
1 cm
No reagents needed
Operates at atmospheric conditions
Rapid sample analysis
Selective tuning capabilities
Useful for volatile organic compounds (VOCs)
Healthy human breath sample
GSI/S sampler + SIONEX ammonia monitor
GSI/S sampler + DAYLIGHT ethanol detection
Contacts
@mail claudio@loccioni.com
Web Loccioni humancare http://humancare.loccioni.com
Web Gruppo Loccioni www.loccioni.com

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Il Campionamento Nell'analisi Del Respiro in Tempo Reale

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Integriamo idee, persone, tecnologie

per dare anima e valori alle imprese

PROPRIETA Famiglia LoccionI

STAFF 320 collaboratori

SEDI Moie di Maiolati |General Impianti srl

FATTURATO 50 Milioni di Euro (2009)

R&I Research for Innovation Institute

FORMAZIONE 9% del costo del personale

Sviluppo di progetti di ricerca a lungo termine

Research for Innovation Institute

Soluzioni di automazione e controllo qualit

Apoteca chemo Sistema automatico per la

Medical Gas Tester Sistema mobile per

Breath Sampling Device

Johns Hopkins Grandi Gruppi

University Health Food CLIENTE

Lab@JHU LABORATORI DI RICERCA

molecules originating from inspiratory air

molecules that are directly or indirectly derived

endogenously molecules produced by

400 A.C. Hippocrates

2007 More than 500 Volatile Organic compounds in breath are

Breath analysis is non-invasive

Concentration (v/v) Molecules

Percentage (%) oxygen, water, carbon dioxide

parts-per-million (ppm) acetone, carbon monoxide, methane, hydrogen

formaldehyde, acetaldehyde, isoprene ethane,

Part per billion: 0, 000 000 1%

Technique Analysis Method Response Time

Electronic nose online <10s

Sensors online 10s

Library of Medicine computer search (www.ncbi.nlm.nih.gov) :

Molecules are quantified with spectroscopic methods after administration of a drug

Time of administration of the substrate, ventilation of the pattern must be carefully

Detection of molecules that are produced endogenously as a result

Careful monitoring of the ventilation of the subject

capnography carbon dioxide

Why is breath analysis still challenging?

Quintronss device: A-C deisposable tee-mouthpiece assembly, D disposable discard bag,

Breath components will change as a function of breathing cycle

Breath molecules originate from cells throughout oral/nasal cavities,

Breath composition will change with breathing physiology

Carbon dioxide must be measured as normalizing values

Mouth pressure must be controlled to ensure correct sampling

Measures for each breath

Sensitive from ppb-ppt range

Web Loccioni humancare http://humancare.loccioni.com

Web Gruppo Loccioni www.loccioni.com

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