broncopneumopatia cronica ostruttiva (bpco). copd n definition, classification n burden of copd n...
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Broncopneumopatia cronica ostruttiva (BPCO)
COPDCOPD
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
COPD
unremitting asthma
chronic bronchitis
emphysema
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
Asthma?Chronic
bronchitis
Emphysema
Chronicbronchiolitis
reversible
irreversible
COPD
Jeffery, AJRCCM 2001
• 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.
Storia naturale della malattia
COPD is a multicomponent disease
InflammationAirway
obstructionStructuralchanges
Airflow limitation
Muco-ciliarydysfunction
Cazzola and Dahl, Chest 2004
Classification of COPD Severity
by SpirometryStage 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
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 post-bronchodilator FEV1/FVC < 0.70 increases steeply with age in 5 Latin American Cities
Source: Menezes AM et al. Lancet 2005
45
50
55
60
65
70
75
80
85
90
95
70 75 80 85 90 95 100
Age
FE
V1/F
VC
%
male
female
Regression both sexes
5th and 95th Percentile
FEV1/FVC% in asymptomatic, elderly never-smokers
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
Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998
00
0.50.5
1.01.0
1.51.5
2.02.0
2.52.5
3.03.0
Proportion of 1965 Rate Proportion of 1965 Rate
1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998
–59%–59% –64%–64% –35%–35% +163%+163% –7%–7%
CoronaryHeart
Disease
CoronaryHeart
Disease
StrokeStroke Other CVDOther CVD COPDCOPD All OtherCauses
All OtherCauses
Source: NHLBI/NIH/DHHSSource: 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,U.S., 1980-2000
0
10
20
30
40
50
60
70
1980 1985 1990 1995 2000
Men
Women
Num
ber
Death
s x
100
0N
um
ber
Death
s x
100
0
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 48.685 0.49%
2001 77.264 0.78%
2002 88.083 0.91%
2003 94.829 1.03%
* Dati che, pur sottostimati a causa dei limiti di codifica,evidenziano un trend in netto aumento dei ricoveri
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
Global Strategy for Diagnosis, Management and Prevention of COPD
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
Risk Factors for COPD
Lung growth and development
Oxidative stress
Gender
Age
Respiratory infections
Socioeconomic status
Nutrition
Comorbidities
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
Fletcher C & Peto R. BMJ 1977;1:1645-8
FE
V1
(% p
red
icte
d a
t ag
e 2
5 y
ea
rs)
Age (years)25 50 75
0
25
50
75
100 Never smoked or notsusceptible to smoke
Susceptiblesmoker
Disability
Death
predicted declineif patient stops smoking
COPD: Natural COPD: Natural HistoryHistory
COPD: Natural COPD: Natural HistoryHistory
Totale Maschi Femmine
FUMATORI 12,2 milioni circa 6,9 milioni circa 5,3 milioni circa (24,3%) (28,6%) (20,3%)
EX-FUMATORI 9 milioni circa 5,8 milioni circa 3,3 milioni circa (18,1%) (24%) = (11,2%)
NON FUMATORI 29 milioni circa 11,4 milioni circa 17,5 milioni circa (57,6%) (47,4%) (67,1%)
OSSFAD, Istituto Superiore di Sanità – Indagine DOXA 2006
Gli italiani secondo l’abitudine del fumo (stima su dati Doxa 2006)
• 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: 1645Jyrki-Tapani K, et al.COPD 2005; 2:331Lokke A, et al. Thorax 2006; 61:935Shahab L, et al. Thorax 2006; 61:1043Pelkonen M, et al. Chest 2006; 130:1129Rennard SI, et al. Lancet 2006; 367:1216
Fumo di sigaretta
Fumo passivo
• Anche l`esposizione al fumo passivo
può contribuire all`insorgenza di sintomi
respiratori e della malattia, aumentandoil carico globale di particelle e gas inalati.
de Marco at al Thorax 2004; 59:120-125
Association Studies for Assessment Association Studies for Assessment of Genetics in COPD (1987-2004)of Genetics in COPD (1987-2004)
• alphaalpha11-antitrypsin-antitrypsin• alpha1-antichymotrypsinalpha1-antichymotrypsin• MMPsMMPs• TIMP-2TIMP-2• CFTRCFTR• TNF /TNFRTNF /TNFR• Vit D binding proteinVit D binding protein• Microsomial epoxide hydrolaseMicrosomial epoxide hydrolase• Heme-oxygenase-1Heme-oxygenase-1• GSH S-transferase (M1,T1,P)GSH S-transferase (M1,T1,P)• IL-1IL-1 / IL-1RN / IL-1RN• beta2-adrenoceptorbeta2-adrenoceptor• Cytochrome P450Cytochrome P450
• Association in a given ethnic Association in a given ethnic groupgroup
• Incosistent results when repeated Incosistent results when repeated in different populations of the in different populations of the same ethnic group or tested in same ethnic group or tested in multiple ethnic groupsmultiple ethnic groups
• Negative resultsNegative results
Why case-control association studies for the genetics of COPD have been so far poorly
informative ? Silverman & Palmer AJRCMB 2000;22:645
Issue Key questions Possible solutions
Selection of gene Biologically ? Demonstration
Positionally ? Linkage – Animal
Group stratification Matched ? 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 ?
COPDCOPD
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
NutritionNutrition
InfectionsInfections
Socio-economic Socio-economic statusstatus
Aging PopulationsAging 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
Global Strategy for Diagnosis, Management and Prevention of COPD
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
Global Strategy for Diagnosis, Management and Prevention of COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
Definition, Classification
Burden of COPD Risk Factors Pathogenesis,
Pathology, Pathophysiology
Practical Considerations
LUNG INFLAMMATIONLUNG INFLAMMATION
COPD PATHOLOGYCOPD PATHOLOGY
OxidativeOxidativestressstress ProteinasesProteinases
Repair Repair mechanismsmechanisms
Anti-proteinasesAnti-proteinasesAnti-oxidantsAnti-oxidants
Host factorsAmplifying mechanisms
Cigarette smokeCigarette smokeBiomass particlesBiomass particles
ParticulatesParticulates
Source: Peter J. Barnes, MD
Pathogenesis of COPD
Anti-proteases
SLPI 1-AT
Proteolysis
OO22--, H, H220022
OHOH.., ONOO, ONOO--
Mucus secretion
Plasma leak Bronchoconstriction
NF-NF-BB
IL-8IL-8
NeutrophilNeutrophilrecruitmentrecruitment
TNF-TNF-
IsoprostanesIsoprostanes
↓ ↓ HDAC2HDAC2
↑↑InflammationInflammationSteroidSteroid
resistanceresistance
Macrophage NeutrophilOxidative Stress in COPD
Source: Peter J. Barnes, MD
Fixed effect meta-analysis results of selected biochemical variables
Franciosi et al, Pulm Pharmacol Ther 2006;19:189-199
Mucus gland hyperplasia
Goblet cellhyperplasia
Mucus hypersecretion Neutrophils in sputum
Squamous metaplasia of epithelium
↑ Macrophages
No basement membrane thickening
Little increase in airway smooth muscle
↑ CD8+ lymphocytes
Changes in Large Airways of COPD Patients
Changes in Large Airways of COPD Patients
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
Disrupted alveolar attachments
Inflammatory exudate in lumen
Peribronchial fibrosisLymphoid follicle
Thickened wall with inflammatory cells- macrophages, CD8+ cells, fibroblasts
Changes in Small Airways in COPD Patients
Source: Peter J. Barnes, MD
Alveolar wall destruction
Loss of elasticity
Destruction of pulmonarycapillary bed
↑ Inflammatory cells macrophages, CD8+ lymphocytes
Source: Peter J. Barnes, MD
Changes in Lung Parenchyma in COPD
NormalNormalInspiration
Expiration
alveolar attachments
Mild/moderateMild/moderateCOPD COPD
loss of elasticity
Severe Severe COPD COPD
loss of alveolar attachments
closure
small small airwayairway
Dyspnea↓ Exercise capacity
Air trappingAir trappingHyperinflationHyperinflation
↓ ↓ HealthHealthstatusstatus
Air Trapping in COPD
Source: Peter J. Barnes, MD
COPD: Small AirwayAbnormalities
Normal COPD
COPD: Pulmonary COPD: Pulmonary EmphysemaEmphysema
Comparison of centrilobular and Comparison of centrilobular and panacinar emphysemapanacinar emphysema
Endothelial dysfunction
Intimal hyperplasia
Smooth muscle hyperplasia
↑ Inflammatory cells (macrophages, CD8+ lymphocytes)
Changes in Pulmonary Arteries in COPD Patients
Source: Peter J. Barnes, MD
COPD: Pulmonary Vascular Changes
Normal COPD
COPD: Structure & Function
Alveolar Wall DestructionAir Spaces Enlargement
Alveolar AttachmentsLoss
HIGH VA/Q RATIOS
Capillary Network Reduction
Small AirwaysNarrowing-Distortion
Nonhomogeneous Inspired Air Distribution
LOW VA/Q RATIOS
Reduced Ventilation In Dependent Alveoli
AIR TRAPPING-LUNG HYPERINFLATION
Rodríguez-Roisin and MacNee. ERM 1998;7:103-6
AIRFLOW OBSTRUCTION
AIR TRAPPING
LUNG HYPERINFLATION
AIRFLOWOBSTRUCTION
Chronic hypoxiaChronic hypoxia
Pulmonary vasoconstrictionPulmonary vasoconstriction
MuscularizationMuscularization
Intimal Intimal hyperplasiahyperplasia
FibrosisFibrosis
ObliterationObliteration
Pulmonary hypertensionPulmonary hypertension
Cor pulmonaleCor pulmonale
Death
EdemaEdema
Pulmonary Hypertension in COPD
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
59
Assess and Monitor COPD: Key PointsA 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.
60
Assess and Monitor COPD: Spirometry
Spirometry should be performed after the administration of an adequate dose of a short-
acting 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.
SYMPTOMScoughcough
sputumsputumshortness of breathshortness of breath
EXPOSURE TO RISKFACTORS
tobaccotobaccooccupationoccupation
indoor/outdoor pollutionindoor/outdoor pollution
SPIROMETRYSPIROMETRY
Diagnosis of COPDDiagnosis of COPD
Spirometry: Normal and Patients with COPD
Age (years)
25 50 750
25
50
75
100
COPD: Natural COPD: Natural HistoryHistory
Dyspnea
Exercise Intolerance
Exacerbations
Hospitalizations
FE
V1
(% p
red
icte
d a
t ag
e 2
5 y
ea
rs)
Systemic Effects Respiratory Failure
Pulm Hypertension
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
Apical bronchus of upper lobe
Luminal area Wall thickness
Computed Tomographic Measurements of Airways Dimensions
and Emphysema in Smokers
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 Relationship between lung function and health statuslung 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.
AIRFLOWLIMITATION
AirwayObstruction
StructuralChanges
MucociliaryDysfunction
Polivalent Nature of COPD
J COPD 2005;2:253-62
SystemicEffects
COPD and Co-MorbiditiesCOPD and Co-Morbidities
COPD patients are at increased risk for: • Myocardial infarction, angina• Osteoporosis• Respiratory infection• Depression• Diabetes• Lung cancer
COPD patients are at increased risk for: • Myocardial infarction, angina• Osteoporosis• Respiratory infection• Depression• Diabetes• Lung cancer
LiverLiverIL-6, TNF-IL-6, TNF-αα, IL-1, IL-1ββIL-6IL-6
CRPCRP
Cardiovascular diseaseCardiovascular disease Muscle wastingMuscle wasting
Skeletal Skeletal musclemuscle
OtherOtherInflammatory Inflammatory diseasesdiseases
CirculationCirculation
SYSTEMIC EFFECTS OF COPDSYSTEMIC EFFECTS OF COPD
COPD and Co-MorbiditiesCOPD and Co-Morbidities
COPD has significant extrapulmonary
(systemic) effects including:
• Weight loss
• Nutritional abnormalities
• Skeletal muscle dysfunction
COPD has significant extrapulmonary
(systemic) effects including:
• Weight loss
• Nutritional abnormalities
• Skeletal muscle dysfunction
Respiratory system
Target organs
Systemic inflammation
?
Insufficienza cardiaca cronicaCoronaropatia e Infarto miocardico
Vasculopatia periferica Embolia polmonare
Aritmie
Neoplasia polmonare
Sindrome metabolicaDiabete mellito
Osteoporosi
Depressione
Principali comorbidità
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.
Consider:Lung Disease –(other than airways disorders)Pulmonary embolismPleural effusionsLobar collapseDiaphragm weakness(Guillain Barre)
• Heart Disease –Myocardial infarctionCardiac rhythm disturbanceDissecting aneurysmLeft ventricular failure
• Systemic Disease –Blood loss/anaemia
• Foreign Body Aspiration
Patient presents with cough, wheeze,chest tightness or breathlessness
SUDDEN / RECENT Consider:Lung Disease -(other than airways disorders)Infiltration (Malignancy, Sarcoidosis)Fibrosing/allergic alveolitisEosinophilic pneumoniaDiaphragm Weakness(Motor Neurone Disease)Chest wall deformityAsbestosis
•Heart Disease -Chronic heart failure, valve disease,cardiomyopathy
•Systemic Disorders -Anaemia, obesity, hyperthyroidism
CHRONIC
Consider: Blood Tests or Chest X-Ray or ECG
www.theipcrg.org/guidelines/index.php
ERS Sep 2006 www.consultmarklevy.com
COPD: Making a diagnosis - Spirometry
YYYYYY
Mast cellMast cell
CD4+ cellCD4+ cell(Th2)(Th2)
EosinophilEosinophil
AllergensAllergens
Ep cellsEp cells
ASTHMAASTHMA
BronchoconstrictionBronchoconstrictionAHRAHR
Alv macrophageAlv macrophage Ep cellsEp cells
CD8+ cellCD8+ cell(Tc1)(Tc1)
NeutrophilNeutrophil
Cigarette smokeCigarette smoke
Small airway narrowingSmall airway narrowingAlveolar destructionAlveolar destruction
COPDCOPD
Reversible IrreversibleAirflow LimitationAirflow Limitation
Source: Peter J. Barnes, MD
Overlap between COPD and asthma
COPD ASTHMA–Neutrophils–No airway hyperreactivity–No bronchodilator response–No corticosteroid response
–Eosinophils–Airway
hyperreactivity–Bronchodilator
response–Corticosteroid
response
“Wheezy bronchitis”
~10%
Barnes, Chest 2000
Modifiche patologiche nelle vie aeree di pazienti con BPCO e asma
Modifiche patologiche nelle vie aeree di pazienti con BPCO e asma
eosinofili
membranabasale
Fabbri et al, AJRCCM 2003
Bronchite eosinofilica 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.
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
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 +++
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 asmaDonna di 38 anni, morta per assunzione di barbiturici, con una
lunga storia di ripetuti attacchi asmatici
Iperinflazione del polmone in asmaDonna 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 panlobulareUomo di 62 anni deceduto per occlusione coronarica ma che aveva sintomi di malattia polmonare ostruttiva da 10 anni
prima di morire.
Enfisema panlobulareUomo di 62 anni deceduto per occlusione coronarica ma che aveva sintomi di malattia polmonare ostruttiva da 10 anni
prima di morire.
Gli spazi aerei dell’intero acino e del lobulo sono allargati con solo occasionali alveoli rimasti intatti
I bronchioli appaiono attenuati ecollassati e le strutture alveolari
non sono presenti
Differential Diagnosis: Differential Diagnosis: COPD and AsthmaCOPD and Asthma
COPD ASTHMA
• Onset in mid-life
• Symptoms slowly progressive
• Long smoking history
• Dyspnea during exercise
• Largely irreversible airflow limitation
• Onset early in life (often childhood)
• Symptoms vary from day to day
• 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?
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?
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
6470362130
90/39*1181
7580826795909630
AcetylcholineMethacholineHistamine PropranololSO2
AMP Hyperventilation§
Fog
COPD Asthma Stimulus
* 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
Hospers et al, Lancet 2000
0
20
40
60
80
>32 32 16 8 4 1
histamine threshold (g/L)
% C
OP
D d
ea
ths
Heavy smokers Light smokers Never smokers
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 testinghttp://www.nice.org.uk/
Other Diff Dx to ConsiderOther Diff Dx to Consider Bronchiectasis
Large volumes of purulent sputum bacterial infection CXR/CT shows bronchial dilation, bronchial wall
thickening TB
History with the usual suspects BOO and BOOP
nonsmokers environmental exposures CT on expiration shows hypodense areas
Bronchiectasis Large volumes of purulent sputum bacterial infection CXR/CT shows bronchial dilation, bronchial wall
thickening TB
History with the usual suspects BOO and BOOP
nonsmokers environmental exposures CT on expiration shows hypodense areas
Congestive Heart FailureCongestive Heart Failure
Fine basilar crackles on auscultation Chest x-ray shows dilated heart,
pulmonary edema PFTs indicate restriction- not obstruction BNP can help
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)