Lung Basic Course:
LUNG FUNCTION
12.11.2014
Jie Jia
AG: A. Ö. Yildirim
Content
• Basic information
• Lung parameters
• Lung function tests and read-out
• Small animal application
• Equipment in Neuherberg
• Read-out of mouse lung function
Lung diseases you need to know
Restrictive
Obstructive
Why monitoring lung function is important
Fletcher-Peto curve
Rennard et al., Proc Am Thorac Soc., 2008
Lung connective tissue
Collagen
High tensile strength
Inextensible
Elastin
Long tensile strength
Extensible
Lung parameters
Take home massage: four Vs and four Cs
ShakespeareFan00.
Lung function test
Lung function test measures: volume, speed, and gas exchange.
•Spirometry
•Gas diffusion test
•Inhalation challenge test
•Exercise stress test
Lung function test is applied for:
Cause of breathing problems
Lung disease diagnose
Before surgery
Harmful exposure in work or life
History of spirometry
The first effective spirometer was invented in 1846, by John
Hutchinson
Hutchinson determined that the volume of exhaled air (VC) has
a linear relationship with height
http://hardluckasthma.blogspot.de/2012/02/history-of-spirometry.htm
Spirometry
Volume and speed
FVC (Forced Vital Capacity)
FEV1 (Forced Expiratory Volume in
1 Second)
Highly patient cooperation
dependent
Spirometry with Body Plethysmography
Body plethysmography is used to analyze RV, TLC, Raw, etc
Spirometry graph
PEF: Peak of Expiratory Flow
FEF: Forced Expiratory Flow
Lung parameters
Normal lung
Restrictive lung disease
Flow-volume: shape normal, FVC low;
Volume-time curve: FEV1 too low,
Forced expiratory time (FET) normal
Obstructive lung disease
Flow-volume: concave, FEF25%-75%
too low, FVC normal;
Volume-time curve: FEV1 low, FET high
Lung parameters
Every parameter
drops
Except TLC, FRC, RV,
every parameter
drops
Raub et al. Environmental Health Perspectives, 1984
Global Initiative for Chronic Obstructive
Lung Disease (GOLD) stage
FEV1 predicted is difined by the average FEV1 in the
population for any person of similar age, sex and body
composition
Gold updated 2014
Gas diffusion test
Amount of oxygen and other gases that cross the lungs air
sacs per minute
Exhaled gas content is analyzed after one or multiple
times inhalation of target gas, e.g. 100% O2, CO
Darcy D Marciniuk, MD, FCCP
Inhalation challenge test
• Mostly used in asthma diagnosis
• Nebulized methacholine (utilizes the M3 receptor for
bronchoconstriction) or histamine (causes mucus secretion
and bronchoconstriction via the H1 receptor)
Darcy D Marciniuk, MD, FCCP
Small animal lung function test
The measurement can be done also in mouse:
Lung Volumes
Spirometry
Gas diffusion test
Inhalation challenge test
Noninvasive and invasive pulmonary function test
Hoymann et al., Frontiers, 2012
Device in lab
Noninvasive and invasive pulmonary function test
Adv.
Invasive
Noninvasive
Dis.
• sensitive and specific
analysis of pulmonary
mechanics
• based on physiological
principles
• intact anatomical
relationships in the lung
• Ease of BAL sampling
• Technically demanding
• Need of anesthesia and
tracheal instrumentation
• Time consuming
• No repetitive
measurements in same
animals
• Expertise in handing
• Quick, easy to handle
• Repetitive in the same
animal
• No need of anesthesia or
tracheal instrumentation
• No direct assessment of
pulmonary mechanics
• Prone to artifacts
(movements,
temperature)
• Uncertainty about the
bronchoconstriction
Mitzner et al. Resp. Research, 2007
Scripts for Flexivent system
Martin et al., JOVE, 2013
Calculations of lung capacity
Compliance is a measurement of the distensibility of the lung. It
measures how much volume is required to reach certain
pressure in the lung.
Elastance is an inverse of compliance
Changes in lung compliance
http://www.sallyosborne.com/
Loss of connective tissue
http://www.sallyosborne.com/
Induced lung connecting tissue
http://www.sallyosborne.com/
compliance
http://www.sallyosborne.com/
Calculations of lung capacity
Compliance is a measurement of the distensibility
of the lung. It measures how much volume is
required to reach certain pressure in the lung.
Elastance is an inverse of compliance
Resistance is the force of tissue against pressure induced by volume
Questions about lung compliance and elastance
• Lung compliance can be defined as the pressure change required to
achive a unit volume change.
• Elastance is the reciprocal of lug compliance.
• In a healthy individual, alterations in the elastance of the lungs
determines the alterations in the respiratory system.
• Surfactant increases the lung compliance by increasing surface tension.
• Elastance of the lungs filled with air is much lower than that of the lungs
filled with normal saline.
Read-out of mouse lung function analysis
Buxco
Flexivent
Janssens et al., AJRCMB, 2009
Read-out of mouse lung function analysis
Janssens et al., AJRCMB, 2009
Lung function test
• Important for pulmonary disease diagnosis
• Lung parameters: four Vs and four Cs
• Transferred from human to small animal-mouse
• Noninvasive and invasive lung function test
• Relationship between C (Compliance), E (Elastance) and R
(Resistance)
Rennard et al., Proc Am Thorac Soc., 2008
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