Broncopneumopatia cronica ostruttiva (BPCO)

1
Broncopneumopatia cronica ostruttiva (BPCO)
2
COPD

• Definition, Classification
• Burden of COPD
• Risk Factors
• Pathogenesis, Pathology, Pathophysiology
• Practical Considerations

3
COPD
chronic bronchitis
emphysema
unremitting asthma
4
COPD old definition.airflow obstruction due
to emphysema and chronic bronchitis
5
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.

6
Venn diagram illustrating the overlap between
asthma and COPD
COPD
Chronic bronchitis
Asthma
?
Chronic bronchiolitis
Emphysema
reversible
irreversible
Jeffery, AJRCCM 2001
7
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.

8
COPD is a multicomponent disease
Airflow limitation
Cazzola and Dahl, Chest 2004
9
Classification of COPD Severity by Spirometry
Stage I Mild FEV1/FVC lt 0.70
FEV1 gt 80 predicted Stage II Moderate
FEV1/FVC lt 0.70
50 lt FEV1 lt 80 predicted Stage III Severe
FEV1/FVC lt 0.70
30 lt FEV1 lt 50 predicted Stage IV Very
Severe FEV1/FVC lt 0.70 FEV1
lt 30 predicted or FEV1 lt 50 predicted
plus chronic respiratory failure
10
Comparison of ATS 1995 and ATS/ERS 2004 disease
staging systems
11
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).

12
Global Strategy for Diagnosis, Management and
Prevention of COPD

• Definition, Classification
• Burden of COPD
• Risk Factors
• Pathogenesis, Pathology, Pathophysiology
• Practical Considerations

13
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 worlds population

14
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

15
COPD Prevalence Study in Latin America
The prevalence of post-bronchodilator FEV1/FVC lt
0.70 increases steeply with age in 5 Latin
American Cities
Source Menezes AM et al. Lancet 2005
16
FEV1/FVC in asymptomatic, elderly never-smokers
Hardie J, ERJ 2002
17
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.

18
Percent Change in Age-Adjusted Death Rates, U.S.,
1965-1998
Proportion of 1965 Rate
3.0
Coronary Heart Disease
Stroke
Other CVD
COPD
All Other Causes
2.5
2.0
1.5
1.0
0.5
59
64
35
163
7
0
1965 - 1998
1965 - 1998
1965 - 1998
1965 - 1998
1965 - 1998
Source NHLBI/NIH/DHHS
19
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
20
COPD Mortality by Gender,U.S., 1980-2000
Number Deaths x 1000
Source US Centers for Disease Control and
Prevention, 2002
21
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).

22
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
23
Prevalenza

• La BPCO è un problema non trascurabile fin
  dalletà 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 59120-125
24
Global Strategy for Diagnosis, Management and
Prevention of COPD

• Definition, Classification
• Burden of COPD
• Risk Factors
• Pathogenesis, Pathology, Pathophysiology
• Practical Considerations

25
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 Socioecon
omic status Nutrition Comorbidities
26
COPD Natural History
100
75
FEV1 ( predicted at age 25 years)
50
Disability
25
Death
0
25
50
75
Age (years)
Fletcher C Peto R. BMJ 197711645-8
27
Gli italiani secondo labitudine del fumo (stima
su dati Doxa 2006)
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
28
Fumo di sigaretta

• Circa il 30 dei fumatori (gt 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 2331 Lokke
A, et al. Thorax 2006 61935 Shahab L, et al.
Thorax 2006 611043 Pelkonen M, et al. Chest
2006 1301129 Rennard SI, et al. Lancet 2006
3671216
29
Fumo passivo

• Anche lesposizione al fumo passivo
• può contribuire allinsorgenza di sintomi
• respiratori e della malattia, aumentando il
  carico globale di particelle e gas inalati.

de Marco at al Thorax 2004 59120-125
30
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

31
Why case-control association studies for the
genetics of COPD have been so far poorly
informative ?
Silverman Palmer AJRCMB 200022645
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
32
Or is it a matter of a poor definition of the
phenotype ?

COPD
33
Extreme Phenotypes Can Be Determined in the
Minority of COPD subjects
34
Emphysema and cigarette smoking
35
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, l8 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 20022871132-41
36
Inquinamento indoor

• Nei Paesi a basso livello di sviluppo
  economico, lutilizzo 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
37
Basso livello di stato socioeconomico

• E dimostrata una relazione significativa tra
  basso livello di istruzione ed aumento della
  mortalità per BPCO, indipendentemente
  dallabitudine al fumo

Prescott E, Godtfredsen N, VestboJ, Osler M.
Social position and mortality from respiratory
diseases in males and females. Eur Respir j
200321821-6
38
Risk Factors for COPD
Nutrition
Infections
Socio-economic status
Aging Populations
39
Probabilità di contrarre la malattia nei 10 anni
successivi alletà del soggetto, in funzione dei
fattori di rischio (ISS, 2004)
40
Global Strategy for Diagnosis, Management and
Prevention of COPD

• Definition, Classification
• Burden of COPD
• Risk Factors
• Pathogenesis, Pathology, Pathophysiology
• Practical Considerations

41
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42
Global Strategy for Diagnosis, Management and
Prevention of COPD

• Definition, Classification
• Burden of COPD
• Risk Factors
• Pathogenesis, Pathology, Pathophysiology
• Practical Considerations

43
Pathogenesis of COPD
Cigarette smoke Biomass particles Particulates
Host factors Amplifying mechanisms
LUNG INFLAMMATION
Anti-oxidants
Anti-proteinases
Oxidative stress
Proteinases
Repair mechanisms
COPD PATHOLOGY
Source Peter J. Barnes, MD
44
Oxidative Stress in COPD
Macrophage
Neutrophil
Anti-proteases
SLPI
?1-AT
NF-?B
Proteolysis
IL-8
TNF-?
? HDAC2 ?Inflammation Steroid resistance
O2-, H202 OH., ONOO-
Neutrophil
recruitment
Bronchoconstriction
Isoprostanes
Plasma leak
? Mucus secretion
Source Peter J. Barnes, MD
45
Fixed effect meta-analysis results of selected
biochemical variables
Franciosi et al, Pulm Pharmacol Ther
200619189-199
46
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
47
Ranked sputum neutrophil data demonstrating
overlap of the ATS FEV1-based disease stages
Franciosi et al, Pulm Pharmacol Ther
200619189-199
48
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
49
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
50
Air Trapping in COPD
Mild/moderateCOPD
Normal
Severe COPD
Inspiration
small airway
alveolar attachments
loss of elasticity
loss of alveolar attachments
Expiration
closure
Dyspnea ? Exercise capacity
Air trapping Hyperinflation
? Health status
Source Peter J. Barnes, MD
51
COPD Small Airway Abnormalities
52
COPD Pulmonary Emphysema
53
Comparison of centrilobular and panacinar
emphysema
54
Changes in Pulmonary Arteries in COPD Patients
Endothelial dysfunction
Intimal hyperplasia
Smooth muscle hyperplasia
? Inflammatory cells (macrophages, CD8
lymphocytes)
Source Peter J. Barnes, MD
55
COPD Pulmonary Vascular Changes
56
COPD Structure Function
Rodríguez-Roisin and MacNee. ERM 19987103-6
57
Pulmonary Hypertension in COPD
Chronic hypoxia
Pulmonary vasoconstriction
Muscularization Intimal hyperplasia Fibrosis Obli
teration
Pulmonary hypertension
Cor pulmonale
Edema
Death
Source Peter J. Barnes, MD
58
Assess for COPDA 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 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 lt 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 lt 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.

61
Diagnosis of COPD
EXPOSURE TO RISK FACTORS
SYMPTOMS
cough
tobacco
sputum
occupation
shortness of breath
indoor/outdoor pollution
è
è
è
SPIROMETRY
62
Spirometry Normal and Patients with COPD
63
COPD Natural History
100
75
FEV1 ( predicted at age 25 years)
50
25
0
25
50
75
Age (years)
64
Assess Physical Examination

• Rarely diagnostic in COPD
• Physical signs of airflow limitation
• rarely present until significant impairment of
  lung function
• low sensitivity and specificity

65
Assess Additional Investigations gt 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

66
Hyperinflated Lungs COPD
67
Computed Tomographic Measurements of Airways
Dimensions and Emphysema in Smokers
Apical bronchus of upper lobe
Luminal area
Wall thickness
68
Assess Additional Investigations gt Stage II
Moderate COPD

• Arterial blood gas measurement
• In advanced COPD FEV1 lt40 predicted or with
  clinical signs suggestive of respiratory failure
  or right heart failure
• central cyanosis, ankle swelling, JVD
• Respiratory failure
• PaO2 lt 60 mm Hg /- PaCO2 gt50 mm Hg at sea level
• Alpha-1 antitrypsin deficiency screening
• COPD at a young age
• strong family history of the disease

69
Relationship between lung function and symptoms
Patients with poor lung function tend to have
worse dyspnoea than those with less severe disease
70
Relationship between symptoms and health status
Health status encompasses respiratory symptoms as
well as their impact on ability to function and
on mood.
71
Relationship between lung function and health
status
Patients with severely impaired lung function
show worse health status than those with more
mild disease.
72
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.
73
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.
74
Polivalent Nature of COPD
J COPD 20052253-62
75
COPD and Co-Morbidities

• COPD patients are at increased risk for
• Myocardial infarction, angina
• Osteoporosis
• Respiratory infection
• Depression
• Diabetes
• Lung cancer

76
SYSTEMIC EFFECTS OF COPD
Circulation
77
COPD and Co-Morbidities

• COPD has significant extrapulmonary
• (systemic) effects including
• Weight loss
• Nutritional abnormalities
• Skeletal muscle dysfunction

78
Target organs
Respiratory system
Systemic inflammation
?
79
Principali comorbidità
Insufficienza cardiaca cronica Coronaropatia e
Infarto miocardico Vasculopatia periferica
Embolia polmonare Aritmie Neoplasia
polmonare Sindrome metabolica Diabete
mellito Osteoporosi Depressione
80
Effetti sistemici della BPCO

• Infiammazione sistemica (aumento di PCR, IL-6,
  IL-8,
• TNF-a 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)

81
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.

82
Comorbidità prospettive future

• Nel programmare la gestione del paziente è
  indispensabile tener conto di possibili
  condizioni morbose concomitanti, molto comuni nei
  pazienti di età gt65 anni.
• Non è noto se lapplicazione contemporanea di
  linee guida rivolte a differenti patologie
  interferisca con il raggiungimento degli
  obiettivi terapeutici di ciascuna condizione.
• In futuro la formulazione e limplementazione di
  specifiche linee guida dovrà avvalersi di un
  contributo multidisciplinare comprendente in
  particolare il medico di medicina generale.

83
Translating COPD Guidelines into Primary CareKEY
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 patients health status, and
  can complicate the management of COPD.

84
Patient presents with cough, wheeze,chest
tightness or breathlessness

• 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

• 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

CHRONIC
SUDDEN / RECENT
Consider Blood Tests or Chest X-Ray or ECG
www.theipcrg.org/guidelines/index.php
85
COPD Making a diagnosis - Spirometry
86
ASTHMA
Allergens
Mast cell
Ep cells
CD4 cell (Th2)
Eosinophil
Bronchoconstriction AHR
Airflow Limitation
Reversible
Irreversible
Source Peter J. Barnes, MD
87
Overlap between COPD and asthma
COPD
ASTHMA

• Neutrophils
• No airway hyperreactivity
• No bronchodilator response
• No corticosteroid response

• Eosinophils
• Airway hyperreactivity
• Bronchodilator response
• Corticosteroid response

10
Wheezy bronchitis
Barnes, Chest 2000
88
Modifiche patologiche nelle vie aeree di pazienti
con BPCO e asma
Fabbri et al, AJRCCM 2003
89
Bronchite eosinofilica

• Una percentuale di pazienti con BPCO mostra un
  certo grado di eosinofilia nellespettorato.
• E possibile che la presenza di eosinofili nelle
  vie aeree sia correlata allintensità 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 leosinofilia
  nellespettorato sono più intense, con una
  relazione diretta fra i numeri di neutrofili ed
  eosinofili.

Maestrelli et al, Thorax 2001
90
Differenze nelle risposte infiammatorie fra asma
e BPCO
91
Iperinflazione del polmone in asmaDonna di 38
anni, morta per assunzione di barbiturici, con
una lunga storia di ripetuti attacchi asmatici
Gli spazi aerei sono allargati, senza distruzione
del tessuto
Il muco occlude i lumi bronchiolari
92
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 dellintero acino e del lobulo
sono allargati con solo occasionali alveoli
rimasti intatti
I bronchioli appaiono attenuati e collassati e le
strutture alveolari non sono presenti
93
Differential Diagnosis COPD and Asthma
COPD
ASTHMA

• 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

• Onset in mid-life
• Symptoms slowly progressive
• Long smoking history
• Dyspnea during exercise
• Largely irreversible airflow
• limitation

94
Come distinguere lasma dalla BPCO in base alla
funzione polmonare?

• Un valore post BD FEV1/FVC lt70 suggerisce
  fortemente una BPCO
• Una risposta al BD gt12 (post BD FEV1-pre BD
  FEV1/pre-BD FEV1x 100) suggerisce fortemente
  unasma
• Che cosa ci dice una risposta positiva alla
  metacolina?

95
Prevalence of hyperresponsiveness to different
stimuli in asthma and COPD
90 in smokers, 39 in non-smokers.
Hyperventilation of cold air.
Postma and Kerstjens, AJCCRM 1998
96
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
97
Problemi con i criteri funzionali polmonari

• Il rimodellamento nellasma può causare
  unostruzione fissa.
• I CSI riducono linfiammazione, quindi riducono
  la risposta al BD, e ciò pone seri dubbi sul
  concetto di considerare solo una risposta post BD
  gt12 come significativa.

98
Reversibilità e patologia sofferta
Sitkauskiene et al, Respir Med 2003
99
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 lasma quanto per la BPCO.

Hansen et al, AJRCCM 1999
100
Reversibility testing
http//www.nice.org.uk/
101
Other 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

102
Congestive Heart Failure

• Fine basilar crackles on auscultation
• Chest x-ray shows dilated heart, pulmonary edema
• PFTs indicate restriction- not obstruction
• BNP can help

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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 lt40 predicted or clinical signs of
  respiratory failure or right heart failure
  (JVD/edema)