COPD

Broncopneumopatia cronica
ostruttiva (BPCO)
COPD





Definition, Classification
Burden of COPD
Risk Factors
Pathogenesis, Pathology,
Pathophysiology
Practical Considerations
COPD
chronic bronchitis
emphysema
unremitting asthma
COPD: old definition
.…airflow obstruction due to
emphysema and chronic
bronchitis
Definition of COPD



COPD is a preventable and treatable disease with
some significant extrapulmonary effects that may
contribute to the severity in individual patients.
Its pulmonary component is characterized by airflow
limitation that is not fully reversible.
The airflow limitation is usually progressive and
associated with an abnormal inflammatory response
of the lung to noxious particles or gases.
Venn diagram illustrating the overlap
between asthma and COPD
COPD
Chronic
bronchitis ?
Asthma
Chronic
bronchiolitis
Emphysema
reversible
irreversible
Jeffery, AJRCCM 2001
Storia naturale della malattia
•
Tosse e catarro cronici possono precedere
lo sviluppo di BPCO di molti anni
•
Per converso, alcuni pazienti sviluppano
una significativa ostruzione al flusso in assenza
di sintomi respiratori cronici.
COPD is a multicomponent
disease
Airway
obstruction
Inflammation
Structural
changes
Muco-ciliary
dysfunction
Airflow limitation
Cazzola and Dahl, Chest 2004
Classification of COPD Severity
by Spirometry
Stage I: Mild
FEV1/FVC < 0.70
FEV1 > 80% predicted
Stage II: Moderate
FEV1/FVC < 0.70
50% < FEV1 < 80% predicted
Stage III: Severe
FEV1/FVC < 0.70
30% < FEV1 < 50% predicted
Stage IV: Very Severe
FEV1/FVC < 0.70
FEV1 < 30% predicted or
FEV1 < 50% predicted plus
chronic respiratory failure
Comparison of ATS 1995 and ATS/ERS
2004 disease staging systems
“At Risk” for COPD



COPD includes four stages of severity classified by
spirometry.
A fifth category--Stage 0: At Risk--that appeared in the 2001
report is no longer included as a stage of COPD, as there is
incomplete evidence that the individuals who meet the
definition of “At Risk” (chronic cough and sputum production,
normal spirometry) necessarily progress on to Stage I: Mild
COPD.
The public health message is that chronic cough and sputum
are not normal remains important - their presence should
trigger a search for underlying cause(s).
Global Strategy for Diagnosis,
Management and Prevention of COPD





Definition, Classification
Burden of COPD
Risk Factors
Pathogenesis, Pathology,
Pathophysiology
Practical Considerations
Burden of COPD: Key Points
• COPD is a leading cause of morbidity and
mortality worldwide and results in an economic
and social burden that is both substantial and
increasing
• COPD prevalence, morbidity, and mortality vary
across countries and across different groups
within countries
• The burden of COPD is projected to increase in
the coming decades due to continued exposure
to COPD risk factors and the changing age
structure of the world’s population
Burden of COPD: Prevalence
• Many sources of variation can affect estimates of
COPD prevalence, including e.g., sampling methods,
response rates and quality of spirometry.
• Data are emerging to provide evidence that
prevalence of Stage I: Mild COPD and higher is
appreciably higher in:
- smokers and ex-smokers
- people over 40 years of age
- males
COPD Prevalence Study in Latin
America
The prevalence
of postbronchodilator
FEV1/FVC < 0.70
increases steeply
with age in 5
Latin American
Cities
Source: Menezes AM et al. Lancet 2005
FEV1/FVC% in asymptomatic, elderly neversmokers
95
90
FEV1/FVC %
85
80
75
70
65
60
55
male
female
50
Regression both sexes
5th and 95th Percentile
45
70
75
80
85
90
95
100
Age
Hardie J, ERJ 2002
Burden of COPD: Mortality
 COPD is a leading cause of mortality worldwide and
projected to increase in the next several decades.
 COPD mortality trends generally track several
decades behind smoking trends.
 In the US and Canada, COPD mortality for both
men and women have been increasing.
 In the US in 2000, the number of COPD deaths was
greater among women than men.
Percent Change in Age-Adjusted
Death Rates, U.S., 1965-1998
Proportion of 1965 Rate
3.0
3.0
2.5
2.5
Coronary
Heart
Disease
Stroke
Other CVD
COPD
All Other
Causes
–59%
–64%
–35%
+163%
–7%
2.0
2.0
1.5
1.5
1.0
1.0
0.5
0.5
0.0 0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
Source: NHLBI/NIH/DHHS
Of the six
leading causes
of death in the
United States,
only COPD has
been increasing
steadily since
1970
Source: Jemal A. et al. JAMA 2005
COPD Mortality by Gender,
Number Deaths x 1000
U.S., 1980-2000
70
60
Men
50
40
Women
30
20
10
0
1980
1985
1990
1995
2000
Source: US Centers for Disease Control and Prevention, 2002
Morbidità
•
La morbidità è prevista in notevole aumento
nel mondo con uno spostamento
dal 12 ° al 6° posto.
•
In termini di ricoveri ospedalieri in Italia
i casi di BPCO risultano al 7° posto
(fonte ISTAT 2003).
Bronchite cronica ostruttiva,
con riacutizzazione icd9cm 491.21
Ricoveri in Regime Ordinario
(FONTE SDO – MINISTERO DELLA SALUTE)
% sul totale dei ricoveri
2000
2001
2002
2003
48.685
77.264
88.083
94.829
* Dati che, pur sottostimati a causa dei limiti di codifica,
evidenziano un trend in netto aumento dei ricoveri
0.49%
0.78%
0.91%
1.03%
Prevalenza
• La BPCO è un problema non trascurabile
fin dall’età giovanile.
•
Studi epidemiologici hanno evidenziato che,
nei soggetti tra 20 e 44 anni, il 10% presenta
tosse ed espettorato senza segni di ostruzione
bronchiale ed il 3.6% sintomi di ostruzione
bronchiale (Stadi I - III).
de Marco at al Thorax 2004; 59:120-125
Global Strategy for Diagnosis,
Management and Prevention of COPD





Definition, Classification
Burden of COPD
Risk Factors
Pathogenesis, Pathology,
Pathophysiology
Practical Considerations
Risk Factors for COPD
Genes
Exposure to particles
● Tobacco smoke
● Occupational dusts, organic
and inorganic
● Indoor air pollution from
heating and cooking with
biomass in poorly ventilated
dwellings
● Outdoor air pollution
Lung growth and development
Oxidative stress
Gender
Age
Respiratory infections
Socioeconomic status
Nutrition
Comorbidities
FEV1 (% predicted at age 25 years)
COPD: Natural History
Never smoked or not
susceptible to smoke
100
75
Susceptible
smoker
50
Disability
25
predicted decline
if patient stops
smoking
Death
0
25
50
75
Age (years)
Fletcher C & Peto R. BMJ 1977;1:1645-8
Gli italiani secondo l’abitudine del fumo
(stima su dati Doxa 2006)
Totale
FUMATORI
EX-FUMATORI
NON FUMATORI
Maschi
12,2 milioni circa 
(24,3%)
9 milioni circa
(18,1%)

29 milioni circa 
(57,6%)
OSSFAD, Istituto Superiore di Sanità – Indagine DOXA 2006
Femmine
6,9 milioni circa 
(28,6%)
5,3 milioni circa
(20,3%) 
5,8 milioni circa
(24%) =
3,3 milioni circa
(11,2%) 
11,4 milioni circa
(47,4%) 
17,5 milioni circa
(67,1%) 
Fumo di sigaretta
• Circa il 30% dei fumatori (> 10 pack-year)
oltre i 40 anni presenta una limitazione
al flusso aereo.
• Circa il 40-50% dei fumatori
sviluppa BPCO.
Fletcher C, Peto R. BMJ 1977; 1: 1645
Jyrki-Tapani K, et al.COPD 2005; 2:331
Lokke A, et al. Thorax 2006; 61:935
Shahab L, et al. Thorax 2006; 61:1043
Pelkonen M, et al. Chest 2006; 130:1129
Rennard SI, et al. Lancet 2006; 367:1216
Fumo passivo
•
Anche l`esposizione al fumo passivo
può contribuire all`insorgenza di sintomi
respiratori e della malattia, aumentando
il carico globale di particelle e gas inalati.
de Marco at al Thorax 2004; 59:120-125
Association Studies for Assessment
of Genetics in COPD (1987-2004)
•
•
•
•
•
•
•
•
•
•
•
•
•
alpha1-antitrypsin
alpha1-antichymotrypsin
MMPs
TIMP-2
CFTR
TNF /TNFR
Vit D binding protein
Microsomial epoxide hydrolase
Heme-oxygenase-1
GSH S-transferase (M1,T1,P)
IL-1b / IL-1RN
beta2-adrenoceptor
Cytochrome P450
•
•
•
Association in a given ethnic
group
Incosistent results when repeated
in different populations of the
same ethnic group or tested in
multiple ethnic groups
Negative results
Why case-control association studies for the
genetics of COPD have been so far poorly
informative ?
Silverman & Palmer AJRCMB 2000;22:645
Issue
Selection of gene
Key questions
Biologically ?
Positionally ?
Group stratification Matched ?
Possible solutions
Demonstration
Linkage – Animal
Ethnicity
Family-based ass.
Unlinked markers
Hardy-Weinberg e. Control in H-W e.? Calculation
Multi.comparisons How many alleles? Bonferroni
How many loci ?
Empirical p value
Or is it a matter of a poor definition of
the phenotype ?
COPD
Extreme Phenotypes Can Be
Determined in the Minority of COPD
subjects
Emphysema and cigarette
smoking
Inquinamento outdoor
•
Ogni incremento di 10 µg/m3 di particelle fini
è associato a circa il 4% di aumento
del rischio di mortalità per qualsiasi causa,
il 6% per cause cardiopolmonari,
l’8% per cancro al polmone
Pope CA 3 rd, Burnett RT, Thum MJ, Calle EE, et all. Lung cancer, cardiopulmonary mortality, and
tong –term exposure to fine particulate air pollution. JAMA 2002;287:1132-41
Inquinamento indoor

Nei Paesi a basso livello di sviluppo
economico, l’utilizzo di combustibili biologici
in ambienti con scarsa ventilazione
è un fattore causale di BPCO
Warwick H, et al. ITDG Publishing, 2004: 103; http://www.idgpublishing.org.uk;
Ezzati M. Lancet 2005; 336: 104; Oroczo-Levi M, et al. Eur Respir J 2006; 27: 542
Basso livello di stato socioeconomico
•
E’ dimostrata una relazione significativa tra basso livello
di istruzione ed aumento della mortalità per BPCO,
indipendentemente dall’abitudine al fumo
Prescott E, Godtfredsen N, VestboJ, Osler M. Social position and mortality from respiratory diseases
in males and females. Eur Respir j 2003;21:821-6
Risk Factors for COPD
Nutrition
Infections
Socio-economic
status
Aging Populations
Probabilità di contrarre la malattia nei
10 anni successivi all’età del soggetto,
in funzione dei fattori di rischio (ISS, 2004)
Global Strategy for Diagnosis,
Management and Prevention of COPD





Definition, Classification
Burden of COPD
Risk Factors
Pathogenesis, Pathology,
Pathophysiology
Practical Considerations
Global Strategy for Diagnosis,
Management and Prevention of COPD





Definition, Classification
Burden of COPD
Risk Factors
Pathogenesis, Pathology,
Pathophysiology
Practical Considerations
Cigarette smoke
Biomass particles
Particulates
Pathogenesis of
COPD
Host factors
Amplifying mechanisms
LUNG INFLAMMATION
Anti-oxidants
Oxidative
stress
Anti-proteinases
Proteinases
Repair
mechanisms
COPD PATHOLOGY
Source: Peter J. Barnes, MD
Oxidative Stress in COPD
Macrophage Neutrophil
Anti-proteases
SLPI 1-AT
NF-B
Proteolysis
IL-8
↓ HDAC2
O2-, H202
OH., ONOO-
↑Inflammation
Steroid
resistance
Isoprostanes
Plasma leak
TNF-
Neutrophil
recruitment
Bronchoconstriction
 Mucus secretion
Source: Peter J. Barnes, MD
Fixed effect
meta-analysis
results of
selected
biochemical
variables
Franciosi et al, Pulm Pharmacol Ther 2006;19:189-199
Changes in Large Airways of COPD Patients
Mucus hypersecretion
Neutrophils in sputum
Squamous metaplasia of epithelium
No basement membrane thickening
Goblet cell
hyperplasia
↑ Macrophages
↑ CD8+ lymphocytes
Mucus gland hyperplasia
Little increase in
airway smooth muscle
Source: Peter J. Barnes, MD
Ranked sputum neutrophil data demonstrating
overlap of the ATS’ FEV1-based disease stages
Franciosi et al, Pulm Pharmacol Ther 2006;19:189-199
Changes in Small Airways in COPD Patients
Inflammatory exudate in lumen
Disrupted alveolar attachments
Thickened wall with inflammatory cells
- macrophages, CD8+ cells, fibroblasts
Peribronchial fibrosis
Lymphoid follicle
Source: Peter J. Barnes, MD
Changes in Lung Parenchyma in COPD
Alveolar wall destruction
Loss of elasticity
Destruction of pulmonary
capillary bed
↑ Inflammatory cells
macrophages, CD8+ lymphocytes
Source: Peter J. Barnes, MD
Air Trapping in COPD
Mild/moderate
COPD
Normal
Inspiration
Severe
COPD
small
airway
alveolar attachments
loss of elasticity
loss of alveolar attachments
Expiration
closure
↓ Health
status
Dyspnea
↓ Exercise capacity
Air trapping
Hyperinflation
Source: Peter J. Barnes, MD
COPD: Small Airway
Abnormalities
Normal
COPD
COPD: Pulmonary
Emphysema
Comparison of centrilobular and
panacinar emphysema
Changes in Pulmonary Arteries in COPD Patients
Endothelial dysfunction
Intimal hyperplasia
Smooth muscle hyperplasia
↑ Inflammatory cells
(macrophages, CD8+ lymphocytes)
Source: Peter J. Barnes, MD
COPD: Pulmonary Vascular
Changes
Normal
COPD
COPD: Structure & Function
Attachments
AIRFLOWAlveolar
OBSTRUCTION
Loss
AIRFLOW
LUNG HYPERINFLATION
AIR TRAPPING OBSTRUCTION
Alveolar Wall Destruction
AIR Air
TRAPPINGSpaces Enlargement
Small Airways
LUNG HYPERINFLATION
Capillary Network
Reduction
Narrowing-Distortion
Nonhomogeneous
Inspired Air Distribution
HIGH VA/Q RATIOS
Reduced Ventilation
In Dependent Alveoli
LOW VA/Q RATIOS
Rodríguez-Roisin and MacNee. ERM 1998;7:103-6
Pulmonary Hypertension in COPD
Chronic hypoxia
Pulmonary vasoconstriction
Muscularization
Pulmonary hypertension
Intimal
hyperplasia
Fibrosis
Cor pulmonale
Obliteration
Edema
Death
Source: Peter J. Barnes, MD
Assess for COPD:
A Common Story
• Cough
– intermittent or daily
– present throughout day- seldom only nocturnal
• Sputum
– Any pattern of chronic sputum production
• Dyspnea
– Progressive and Persistent
– "increased effort to breathe" "heaviness" "air hunger"
or "gasping"
– Worse on exercise
– Worse during respiratory infections
• Exposure to risk factors
– Tobacco smoke
– Occupational dusts and chemicals
– Smoke from home cooking and heating fuels
Assess and Monitor COPD: Key Points
 A clinical diagnosis of COPD should be considered
in any patient who has dyspnea, chronic cough or
sputum production, and/or a history of exposure
to risk factors for the disease.
 The diagnosis should be confirmed by spirometry.
A post-bronchodilator FEV1/FVC < 0.70 confirms
the presence of airflow limitation that is not fully
reversible.
 Comorbidities are common in COPD and should be
actively identified.
59
Assess and Monitor COPD: Spirometry
 Spirometry should be performed after the
administration of an adequate dose of a shortacting inhaled bronchodilator to minimize
variability.
 A post-bronchodilator FEV1/FVC < 0.70 confirms
the presence of airflow limitation that is not fully
reversible.
 Where possible, values should be compared to
age-related normal values to avoid overdiagnosis
of COPD in the elderly.
60
Diagnosis of COPD
SYMPTOMS
cough
sputum
shortness of breath
EXPOSURE TO RISK
FACTORS
tobacco
occupation
indoor/outdoor pollution

SPIROMETRY
Spirometry: Normal and
Patients with COPD
FEV1 (% predicted at age 25 years)
COPD: Natural History
100
Dyspnea
Exercise Intolerance
75
Exacerbations
Hospitalizations
50
Systemic Effects
Respiratory Failure
Pulm Hypertension
25
0
25
50
Age (years)
75
Assess:
Physical Examination
• Rarely diagnostic in COPD
• Physical signs of airflow limitation
– rarely present until significant impairment of
lung function
– low sensitivity and specificity
Assess: Additional Investigations
> Stage II: Moderate COPD
• Bronchodilator reversibility testing
–
–
–
–
rule out asthma
establish best attainable lung function
gauge a patient's prognosis
guide treatment decisions
• Chest x-ray
– seldom diagnostic unless obvious bullous disease
– valuable in excluding alternative diagnoses
– CT not routinely recommended
Hyperinflated Lungs : COPD
Computed Tomographic Measurements
of Airways Dimensions and Emphysema
in Smokers
Apical bronchus of
upper lobe
Luminal area
Wall thickness
Assess: Additional Investigations
> Stage II: Moderate COPD
• Arterial blood gas measurement
– In advanced COPD: FEV1 <40% predicted or with
clinical signs suggestive of respiratory failure or right
heart failure
– central cyanosis, ankle swelling, JVD
– Respiratory failure
• PaO2 < 60 mm Hg +/- PaCO2 >50 mm Hg at sea level
• Alpha-1 antitrypsin deficiency screening
– COPD at a young age
– strong family history of the disease
Relationship between
lung function and symptoms
Patients with poor lung
function tend to have
worse dyspnoea than
those with less severe
disease
Relationship between
symptoms and health status
Health status
encompasses
respiratory
symptoms as well as
their impact on
ability to function
and on mood.
Relationship between
lung function and health status
Patients with severely
impaired lung function
show worse health
status than those with
more mild disease.
Relationship between
lung function and mortality
The risk of dying from
COPD is higher in
patients with poor lung
function than in those
with more mild disease.
Relationship between
health status and mortality
Poor health status is
associated with
increased risk of death
from COPD and small
improvements may be
associated with
important differences in
prognosis.
Polivalent Nature of COPD
Mucociliary
Structural
Dysfunction
Changes
Airway
Obstruction
Systemic
Effects
AIRFLOW
LIMITATION
J COPD 2005;2:253-62
COPD and Co-Morbidities
COPD patients are at increased risk
for:
•
Myocardial infarction, angina
Osteoporosis
Respiratory infection
•
Depression
•
Diabetes
•
Lung cancer
•
•
SYSTEMIC EFFECTS OF COPD
IL-6
IL-6, TNF-α, IL-1β
Liver
CRP
Circulation
Skeletal
muscle
Cardiovascular disease
Muscle wasting
Other
Inflammatory
diseases
COPD and Co-Morbidities
COPD has significant extrapulmonary
(systemic) effects including:
•
Weight loss
•
Nutritional abnormalities
•
Skeletal muscle dysfunction
Target organs
Respiratory system
Systemic
inflammation
?
Principali comorbidità
Insufficienza cardiaca cronica
Coronaropatia e Infarto miocardico
Vasculopatia periferica
Embolia polmonare
Aritmie
Neoplasia polmonare
Sindrome metabolica
Diabete mellito
Osteoporosi
Depressione
Effetti sistemici della BPCO



Infiammazione sistemica (aumento di PCR, IL-6, IL-8,
TNF-α; cellule infiammatorie circolanti; stress ossidativo sistemico)
Alterazioni nutrizionali e cachessia (aumento del dispendio energetico
e del catabolismo, alterata composizione del corpo)
Alterazioni muscolo-scheletriche (perdita di massa muscolare;
alterazioni della struttura e funzione, ridotta tolleranza allo sforzo)

Aspetti cardiovascolari (malattia aterosclerotica)

Alterazioni del metabolismo osseo (osteopenia, osteoporosi)

Alterazioni ematologiche (anemia normocitica, normocromica)
Relazione fra prognosi e comorbidità
(BPCO - Malattie cardiovascolari)
•
•
•
Le comorbidità hanno un importante effetto sulla prognosi del paziente con BPCO.
La coesistenza delle due malattie è condizione di peggioramento della prognosi.
L'insufficienza respiratoria progressiva spiega solo un terzo circa
della mortalità legata alla BPCO; quindi fattori diversi dalla progressione
della malattia polmonare devono avere un ruolo di rilievo.
•
I decessi dei pazienti con BPCO avvengono prevalentemente
a causa delle comorbidità piuttosto che per la BPCO.
•
Nei pazienti affetti da BPCO il 40-50% dei casi di morte è imputabile
a cause cardiovascolari.
•
Circa 1/3 dei pazienti affetti da cardiopatie è affetto anche da BPCO
che ne aumenta il rischio di morte.
•
La riduzione del VEMS è un fattore di rischio di mortalità per tutte le cause.
Comorbidità: prospettive future
•
Nel programmare la gestione del paziente
è indispensabile tener conto di possibili condizioni
morbose concomitanti, molto comuni nei pazienti
di età >65 anni.
•
Non è noto se l’applicazione contemporanea
di linee guida rivolte a differenti patologie interferisca
con il raggiungimento degli obiettivi terapeutici
di ciascuna condizione.
•
In futuro la formulazione e l’implementazione
di specifiche linee guida dovrà avvalersi di un contributo
multidisciplinare comprendente in particolare il medico
di medicina generale.
Translating COPD Guidelines into Primary Care
KEY POINTS


Spirometric confirmation is a key
component of the diagnosis of COPD and
primary care practitioners should have
access to high quality spirometry.
Older patients frequently have multiple
chronic health conditions. Comorbidities
can magnify the impact of COPD on a
patient’s health status, and can
complicate the management of COPD.
Patient presents with cough, wheeze,
chest tightness or breathlessness
SUDDEN / RECENT
Consider:
Lung Disease –
(other than airways disorders)
Pulmonary embolism
Pleural effusions
Lobar collapse
Diaphragm weakness
(Guillain Barre)
• Heart Disease –
Myocardial infarction
Cardiac rhythm disturbance
Dissecting aneurysm
Left ventricular failure
• Systemic Disease –
Blood loss/anaemia
CHRONIC
Consider:
Lung Disease (other than airways disorders)
Infiltration (Malignancy, Sarcoidosis)
Fibrosing/allergic alveolitis
Eosinophilic pneumonia
Diaphragm Weakness
(Motor Neurone Disease)
Chest wall deformity
Asbestosis
• Heart Disease Chronic heart failure, valve disease,
cardiomyopathy
• Systemic Disorders Anaemia, obesity, hyperthyroidism
• Foreign Body Aspiration
Consider: Blood Tests or Chest X-Ray or ECG
www.theipcrg.org/guidelines/index.php
COPD: Making a diagnosis Spirometry
ERS Sep 2006
www.consultmarklevy.com
COPD
ASTHMA
Cigarette smoke
Allergens
Ep cells
Mast cell
CD4+ cell
(Th2)
Eosinophil
Bronchoconstriction
AHR
Reversible
Alv macrophage Ep cells
CD8+ cell
(Tc1)
Neutrophil
Small airway narrowing
Alveolar destruction
Airflow Limitation
Irreversible
Source: Peter J. Barnes, MD
Overlap between COPD and asthma
COPD
ASTHMA
–Neutrophils
–No airway
hyperreactivity
~10%
–No bronchodilator
response
–No corticosteroid
response
–Eosinophils
–Airway
hyperreactivity
–Bronchodilator
response
–Corticosteroid
response
“Wheezy bronchitis”
Barnes, Chest 2000
Modifiche patologiche nelle vie aeree di
pazienti con BPCO e asma
eosinofili
membrana
basale
Fabbri et al, AJRCCM 2003
Bronchite eosinofilica



Una percentuale di pazienti con BPCO mostra
un certo grado di eosinofilia nell’espettorato.
E’ possibile che la presenza di eosinofili nelle
vie aeree sia correlata all’intensità del
processo infiammatorio nella BPCO, che porta
ad un reclutamento non specifico di queste
cellule e alla loro attivazione.
Il maggiore impatto sul FEV1 avviene nei casi in
cui sia la neutrofilia sia l’eosinofilia
nell’espettorato sono più intense, con una
relazione diretta fra i numeri di neutrofili ed
eosinofili.
Maestrelli et al, Thorax 2001
Differenze nelle risposte infiammatorie fra
asma e BPCO
Infiammazione
Asma
BPCO
Mediatori
infiammatori
LTD4, istamina
LTB4
IL-4, IL-5, IL-13
TNF-
Eotaxina, RANTES
IL-8
Stress ossidativo
+
Stress ossidativo
+++
Iperinflazione del polmone in asma
Donna di 38 anni, morta per assunzione di barbiturici, con una
lunga storia di ripetuti attacchi asmatici
Il muco occlude i lumi bronchiolari
Gli spazi aerei sono allargati, senza
distruzione del tessuto
Enfisema panlobulare
Uomo di 62 anni deceduto per occlusione coronarica ma che
aveva sintomi di malattia polmonare ostruttiva da 10 anni prima di
morire.
I bronchioli appaiono attenuati e
collassati e le strutture alveolari
non sono presenti
Gli spazi aerei dell’intero acino e
del lobulo sono allargati con solo
occasionali alveoli rimasti intatti
Differential Diagnosis:
COPD and Asthma
COPD
• Onset in mid-life
•
Symptoms slowly
progressive
ASTHMA
• Onset early in life (often
childhood)
• Symptoms vary from day to day
•
• Long smoking history
• Dyspnea during exercise •
• Largely irreversible airflow
•
limitation
•
Symptoms at night/early morning
Allergy, rhinitis, and/or eczema
also present
Family history of asthma
Largely reversible airflow
limitation
Come distinguere l’asma dalla BPCO
in base alla funzione polmonare?
 Un
valore post BD FEV1/FVC <70%
suggerisce fortemente una BPCO
 Una
risposta al BD >12% (post BD
FEV1-pre BD FEV1/pre-BD FEV1x 100)
suggerisce fortemente un’asma
 Che
cosa ci dice una risposta
positiva alla metacolina?
Prevalence of hyperresponsiveness to
different stimuli in asthma and COPD
Stimulus
Acetylcholine
Methacholine
Histamine
Propranolol
SO2
AMP
Hyperventilation§
Fog
Asthma
COPD
75
80
82
67
95
90
96
30
64
70
36
21
30
90/39*
11
81
* 90% in smokers, 39% in non-smokers.
§Hyperventilation
of cold air.
Postma and Kerstjens, AJCCRM 1998
Percentage of deaths with COPD as primary or
secondary diagnosis according to the histamine
threshold in light, heavy, and never smokers
% COPD deaths
80
60
40
20
0
>32
32
16
4
8
1
histamine threshold (g/L)
Heavy smokers
Light smokers
Never smokers
Hospers et al, Lancet 2000
Problemi con i criteri funzionali
polmonari

Il rimodellamento nell’asma può
causare un’ostruzione fissa.

I CSI riducono l’infiammazione,
quindi riducono la risposta al BD, e
ciò pone seri dubbi sul concetto di
considerare solo una risposta post
BD >12% come significativa.
Reversibilità e patologia sofferta
Sitkauskiene et al, Respir Med 2003
Ostruzione bronchiale reversibile e
irreversibile quale predittore della
mortalità complessiva in asma e BPCO
 La massima funzione polmonare
ottenibile è il miglior indice
spirometrico nella predizione della
sopravvivenza a prescindere dai
farmaci necessari per ottenerlo.
 Ciò è vero tanto per l’asma quanto per
la BPCO.
Hansen et al, AJRCCM 1999
Reversibility testing
http://www.nice.org.uk/
Other Diff Dx to Consider

Bronchiectasis




TB


Large volumes of purulent sputum
bacterial infection
CXR/CT shows bronchial dilation, bronchial wall
thickening
History with the usual suspects
BOO and BOOP



nonsmokers
environmental exposures
CT on expiration shows hypodense areas
Congestive Heart Failure




Fine basilar crackles on auscultation
Chest x-ray shows dilated heart,
pulmonary edema
PFTs indicate restriction- not obstruction
BNP can help
Monitoring: This is a progressive
disease
• Lung function worsens over time- even with best
care
• Monitor symptoms and objective measures of airflow
limitation for development of complications and to
determine when to adjust therapy
• Spirometry should be performed if there is a
substantial increase in symptoms or a complication
• ABG should be considered in all patients with an
FEV1 <40% predicted or clinical signs of respiratory
failure or right heart failure (JVD/edema)