Lung Basic Course: LUNG FUNCTION 12.11.2014 Jie Jia AG: A. Ö. Yildirim

Lung Basic Course: LUNG FUNCTION

12.11.2014Jie 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

Rennard et al., Proc Am Thorac Soc., 2008

Fletcher-Peto curve

Lung connective tissue

CollagenHigh tensile strengthInextensible

ElastinLong tensile strengthExtensible

ShakespeareFan00.

Take home massage: four Vs and four Cs

Lung parameters

•Spirometry

•Gas diffusion test

•Inhalation challenge test

•Exercise stress test

Lung function test is applied for:Cause of breathing problemsLung disease diagnoseBefore surgeryHarmful exposure in work or life

Lung function test

Lung function test measures: volume, speed, and gas exchange.

History of spirometry

Hutchinson determined that the volume of exhaled air (VC) has a linear relationship with height

The first effective spirometer was invented in 1846, by John Hutchinson

http://hardluckasthma.blogspot.de/2012/02/history-of-spirometry.html

Volume and speed

FVC (Forced Vital Capacity)FEV1 (Forced Expiratory Volume in 1 Second)

Highly patient cooperation dependent

Spirometry

Spirometry with Body Plethysmography

Body plethysmography is used to analyze RV, TLC, Raw, etc

Spirometry graph

PEF: Peak of Expiratory FlowFEF: Forced Expiratory Flow

Lung parameters

Obstructive lung diseaseFlow-volume: concave, FEF25%-75% too low, FVC normal; Volume-time curve: FEV1 low, FET high

Restrictive lung diseaseFlow-volume: shape normal, FVC low; Volume-time curve: FEV1 too low, Forced expiratory time (FET) normal

Normal lung

Except TLC, FRC, RV, every parameter dropsRaub et al. Environmental Health Perspectives, 1984

Lung parameters

Every parameter drops

Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage

Gold updated 2014

FEV1 predicted is difined by the average FEV1 in the population for any person of similar age, sex and body composition

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 VolumesSpirometryGas diffusion testInhalation challenge test

Noninvasive and invasive pulmonary function test

Hoymann et al., Frontiers, 2012

Device in lab

Noninvasive and invasive pulmonary function test

• sensitive and specific analysis of pulmonary mechanics

• based on physiological principles

• intact anatomical relationships in the lung

• Ease of BAL sampling

Adv. Dis.

Invasive

Noninvasive

• Quick, easy to handle• Repetitive in the same

animal• No need of anesthesia or

tracheal instrumentation

• Technically demanding• Need of anesthesia and

tracheal instrumentation• Time consuming• No repetitive

measurements in same animals

• Expertise in handing

• 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 complianceResistance 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