Overview of Obstructive Diseases of the Lung, Lung Physiology … · 2006-02-24 · (GOLD)...
Transcript of Overview of Obstructive Diseases of the Lung, Lung Physiology … · 2006-02-24 · (GOLD)...
Jann Mortensen
Final Phil meeting, 29 april 2004
Overview ofObstructive Diseases of the
Lung, Lung Physiology andImaging Modalities
Disposition
Obstructivedisease
• Definition• Epidemiologi• Mechanisms• Natural history• Treatment• Diagnosis
Physiology• Dynamic
spirometry• Lung volumes• Transfer
factor• Reversibility
Imaging•Chest X-ray
•CT
•Nuclear medicine
•V/Q
•MCC
•PET
Change in mortalityUSA 1965 - 1998
3.0
0
2.5
2.0
1.0
1.5
-59% -64% -35% +163% -7%
1965- 1998
www.copdgold.com
Compared to 1965
0.5
1965- 1998 1965- 1998 1965- 1998 1965- 1998
Other reasonsCOPDOther cardio-vascular dis.
StrokeIschemic heart disease
Chronic obstructive disease
AsthmaObstructionFEV1 / FVC < 70 %
Chronicbronchitis
Emphysema
Obstruction is measuredwith Spirometry
FEV1 = Forced expiratory volume in the 1 secondFVC = Forced vital capacity
Obstruction: FEV1 / FVC < 70 %
COPD and asthma definitions
Asthma
Chronicbronchitis
Emphysema
ProductiveCoughMost days>3 months>2 yrsie. Based onsymptoms
Reversible airways-obstructionie. based on objective measures
Destruction ofalveolar walls,resulting inpermanentenlargementof airspacesand loss of lungelasticityie. Based on patoanatomy
COPD and asthmaDestruction ofalveolar walls,resulting inpermanentenlargementof airspaces(and loss of lungElasticity)ie. Based on patoanatomy
Emphysema Normal
Asthma & COPD
Asthma COPD
Ca. 10% have both
NeutrophilsEosinophils*No airwayhyperresponsiveness
Airwayhyperresponsiveness
Bronchodilatorresponse
*No bronchodilatorresponse
*No steroid responseSteroid response
Symptoms episodicNight/early morning
Symptoms progressive
*No < 15%
Onset:Early/Childhood
Onset:mid-lifeSmokinghistory
Pathological airway changes
Normal airwayConstricted airway
in asthma and COPD
Epithelium
Basement membrane
Smooth muscle
Mucus plug
Mucus glandshypertrophy
Inflammation
Airway generations andregional localisation?
Asthma
Chronicbronchitis
Emphysema
Definition of asthma
Global Initiative for Asthma (GINA). WHO/NHLBI, 1995
• A chronic inflammatory disorder of the airway
• Infiltration of mast cells, eosinophils and lymphocytes
• Recurrent episodes of wheezing, coughing and shortness of breath
• Widespread, variable and often reversible airflow limitation
• Airway hyperresponsiveness
(GOLD) Definition of COPD
‘Chronic obstructive pulmonary disease (COPD) is a
disease state characterized by airflow limitation, that is not fully reversible.
The airflow limitation is generally both progressive and associated with an abnormal inflammatory response of the
lungs to noxious particles or gasses.’
http://www.goldcopd.com
This definition does not use the tems chronic bronchitis and emphysema, and excludes asthma (reversible airflow limitation)
What causes COPD
Including passive smokingOther causes: Occupational dust and chemicalsIndoor air pollution to cooking and heatingOutdoor air pollutionRespiratory infections in early childhood increase risk in adulthood
Natural history: Effect of smoking on annual decline in lung function
Adapted from Fletcher & Peto. Br Med J 1977
100
75
50
25
025 50 75
Age (years)
Smoked regularlyand susceptibleto its effects
Disability
Death
Never smoked or notsusceptible to smoke
Stoppedat 45
Stoppedat 65
FE
V1
(% o
f va
lue
at
ag
e 2
5)
† †
20%
Smoking cessation improves decline in FEV1
The Lung Health Study
• 5.887 with mild to moderate COPD
• Multicenter RCT
• Initial improvement & slower decline in FEV1
• Anthonisen et al, JAMA 1994
Screen 2 1 2 3 4 5
Pos
t-br
onch
odil
ator
FE
V1
(L)
2.4
2.5
2.6
2.7
2.8
2.9
"Continuing Smokers"
"Sustained Quitters"
years
Natural history of COPD
Age20 30 40 50 60 70 80
FE
V1
in %
pre
d.
20
40
60
80
100
Dyspnea
Bothering exacerbationsDisability
Hospital admission
Pulmonary hypertensionHypoxemia
Deconditioning
Systemic disease
Death
290 patienter, parallel design, 3 yr, 800-1200 ug budesonide or placebo
Copenhagen City Lung Study:
No effect of budesonide on ÄFEV1in early COPD
Can steroids modify development of COPD?
EUROSCOPE :
•No effect of budesonide onÄFEV1 in mild COPD
•Initial improvement of FEV1
1.277 patienter, parallel design,
3 yr, 800 ug budesonide eller placebo
ISOLDE
• No effect of fluticasone on ÄFEV1in moderate/severe COPD
• 25 % reduction in no. of exacerbations by fluticasone
• Improved “health status” (SGRQ)
Can steroids modify development of COPD?
751 patients, parallel design,3 yr, 1000 ug fluticasone or placebo
Conclusion on inhaled steroids:
1. Do not change the decline of FEV1 but
2. improve the rate of exacerbations in severe COPD
Guidelines for management of COPD
• Smoking cessation
• Influenza vaccination
• Exercise where possible
• Bronchodilator treatment
• Inhaled steroids
• Pulmonary rehabilitation
• Long-term oxygen therapy
• Lung volume reduction Surgery •Transplantation
SYMPTOMSCoughCoughSputumSputumDyspneaDyspnea
RISK FACTORS
TobaccoTobaccoOccupational exposureOccupational exposure
Air pollutionAir pollution
SPIROMETRISPIROMETRI
Diagnosis: Consider COPDDiagnosis: Consider COPD
èè
Spirometry
Reference values:Age, sex, height, etnic group
Flow rate = driving elastic Pressure / Airway resistance
AsthmaCOPD
Emphysema
Increase inAirway resistance
Low elasticrecoil
Reversibility:spirometric (FEV1) tracings
1 2 3 4 5
Time (seconds)
FEV1
Volume
Normal subject
Asthmatic (after bronchodilator)
Asthmatic (before bronchodilator)
Each FEV1 curve represents the highest of three repeat measurements Global Initiative for Asthma (GINA). WHO/NHLBI, 1995
Establish the diagnosis of COPD
• History• Physical examination
• Lung function tests• Spirometry• Lung volumes• Carbon monoxide diffusing capacity• Arterial blood gases
• Imaging
(slow) Spirometry:Static lung volumes
Body plethysmography = Bodybox
ÄV
ÄP
P P
P x V = (P + ÄP) x (V - ÄV)
BodyboxBodybox
∆P ´0.75
0.50
0.25
0
0.25
0.75
0.50
1.0
1.0
∆ P box
P mouth
Exp
iratio
n
I
nspi
ratio
n
V FRC = x (PFRC – PH20)∆V box
∆ Pmouth
∆Pbox ~∆V
∆P box ~∆V from calibra-Tion with pumped air
BodyboxBodybox
∆P ´0.75
0.50
0.25
0
0.25
0.75
0.50
1.0
1.0
∆ P box
P mouth
Exp
iratio
n
I
nspi
ratio
n
V FRC = x (PFRC – PH20)∆V box
∆ Pmouth
∆Pbox ~∆V
∆P box ~∆V from calibra-Tion with pumped air
Typical Static volumes
Patophysiology• Progressive airways
obstruction->– hyperinflation,
increased work ofbreathing, dyspnea
• Impaired gas exhange– loss of alveoli/airways
obstruction-> disturbedperfusion/ventilation
– hypoxemia and hypercapnia, and eventually acidosis
Carbon monoxide diffusing capacity(mmol/min/Kpa)
= Transfer faktor
Diffusion of gas is proportional with:
The membrane’s AreaThickness
and the difference in concentration over the membrane
Single breath
1) simple2) rapid 3) reproducible 5% (10%)
Inspiration of 0,3% CO og 10% He:
• = CO conc. falls due to dilution + diffusion
• = He conc. falls due todilution only
Alveolus Blood vesselHb
In:
Ex:
Conc.:
Diffusion capacity for CO is low if:
• Small area– Emphysema
– Pulmonary fibrosis
• Thick membrane–Pulmonary fibrosis
• Ventilation / Perfusion disturbancy
V/P V PV/P
• Low Hemoglobin in capillaries (anemia, destruction of vascular tree)
Interpretation:Ventilation and Diffusion Capacity
Irreversible obstructive lung functionlow FEV1/FVC, FVC, FEV1, and
high RV, FRC, TLC
&
Low diffusion ~ COPD with emphysema
Normal diffusion ~ COPD without emphysema
Establishing the diagnosis of COPD
• Imaging
• Chest X-ray
• CT of chest
• Nuclear medicine
• V/Q
• MCC
• PET
1 choice: Chest x-rayMild COPD:•Normal
Advanced COPD:•Hyperinflation •Flat diagfragm•Vaskular markings•Thin heart shadow
•Complications•Infiltrates if pneumonia•Cor pulmonale
•Alternative diagnosis: nodules, pleural disease, interstitial disease
Computerised tomographySuperior to demonstrate (type, distribution and severity of) emphysema:
Findings:•Low attenuation areas•Bullae•Attenuation and abnormal vascular tree
Monitoring:•the progress through lung density measurements
•Centriacinar•Involves primarily the respiratory bronchiole •The distal acinus or alveoli are unchanged.•Occurs more commonly in the upper lobes. •Most common type.•Seen in cigarette smokers
•Panacinar•Involves entire respiratory acinus, •commonly in the lower lobes. •1/20 as rare as centricular emphysema.• in alpha 1 - antitrypsin deficiency
•Paraseptal•The distal respiratory acinus, includingalveolar duct and alveoli, is expanded.•primarily adjacent to the pleura and connective tissue septa,• especially in the upper lobes.
Emphysema types demonstrated on CT:
Monitoring the progress throughlung density measurements
A
B
The gray area represent the relativ area (RA) of emphysematic lung, (threshold value of –910 HU)
A) RA 10%, 15th percentile –894 HU
B) RA 31%, 15th percentile –946 HU.
Computerised tomography
If complications aresuspected:
•Lung cancer
•Pulmonary embolism
•Confirm alternative diagnosis
Positron emission Tomography (PET)
65 yrs female COPD, CT: 13 mm nodule in Right apex
18 F-flouro-deoxy-glucose (FDG)
Single pulmonary nodule: Lung Cancer ?
Diagnostics in single pulmonary nodules
57 yr male COPD, 9 mm nodule
9 mm nodule
(Nucl Med Comm 2004)
Major indications for PETin lung cancer
• ”Diagnostical use”(Tumor)– indeterminate SPN on CT
• Staging in NSCLC
Relatively good evidence: class B
55 studies 1500 patients
Good evidence: class A
Lancet Oncol 2001;2:659-66
CT+PETCT PET
Integrated PET-CT improves the diagnostic accuracy of the staging of NSCLC. N Engl J Med 2003; 348: 2500-7
Gamma camera
Perfusion Ventilation
Perfusion / Ventilation scintigraphy: Pulmonary embolism ?
Emphysema: is LVRS possible ?
After
lg/jm
Before
Anterior/posterior projections
LVRS in severe COPD
Special Genetic types of COPD:a1-antitrypsin deficiency emphysema
a1-antitrypsin deficiency causes proteolytic damage of the lungs and emphysema
TLC
FRC
RV
Homozygotic PiZZ, blod a1-antitrypsin test, 1 % of COPD cases, Early onset: 30-40 yrs
Panlobular:
Special Genetic types of COPD:Primary ciliary dyskinesia
Ultrastructural defects in cilia impairs mucus transport in the airways and results in infections and
chronic sinusitis/otitis, bronchiectasis and (mild) COPD
Homozygotic, Mucociliary function test; Rare:1 in 15.000 subjects; Very early onset: from 0 yrs
Impaired mucociliary clearance inPrimary Ciliary Dyskinesia
start
2 h
1 h
24 h
Markers
Stomach
Unresolved questions ?Unresolved questions ?
• Why do only 15-20 % of smokers develop COPD?
• Why do some develop bronchitis and others emphysema?
• Are asthma and COPD different entities or interconnected ?
• The patogenesis of COPD (genes and molecular biology)?
• How do we improve treatment?
• How do we identify pre-clinical (early) COPD?– PHIL ?