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 Chronic bronchiolitis ?

Emphysema Asthma 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 Stage II: Moderate Stage III: Severe Stage IV: Very Severe FEV 1 /FVC < 0.70 FEV 1 > 80% predicted FEV 1 /FVC < 0.70

50% < FEV 1 < 80% predicted FEV 1 /FVC < 0.70

30% < FEV 1 < 50% predicted FEV 1 /FVC < 0.70

FEV 1 FEV 1 < 30% predicted < 50% predicted or 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 post bronchodilator FEV 1 Cities /FVC < 0.70 increases steeply with age in 5 Latin American Source : Menezes AM et al. Lancet 2005

75 70 65 60 55 50 45 FEV 1 /FVC% in asymptomatic, elderly never smokers 95 90 85 80

male female Regression both sexes 5th and 95th Percentile

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

Coronary Heart Disease Stroke Other CVD COPD All Other Causes

–59% –64% –35% +163% –7%

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,

U.S., 1980-2000

70 60 50 40 30 20 10 0 1980 Men Women 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 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

     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

COPD: Natural History

100

Never smoked or not susceptible to smoke

75

Susceptible smoker

50 Disability 25 0 25 Death

predicted decline if patient stops smoking

50

Age (years)

75

Fletcher C & Peto R. BMJ 1977;1:1645-8

Gli italiani secondo l’abitudine del fumo (stima su dati Doxa 2006) Totale FUMATORI 12,2 milioni circa (24,3%)



EX-FUMATORI 9 milioni circa (18,1%)



NON FUMATORI 29 milioni circa



(57,6%) Maschi 6,9 milioni circa



(28,6%) 5,8 milioni circa (24%) = 11,4 milioni circa (47,4%)



Femmine 5,3 milioni circa (20,3%)



3,3 milioni circa (11,2%)



17,5 milioni circa (67,1%)



OSSFAD, Istituto Superiore di Sanità – Indagine DOXA 2006

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)

• alpha 1 -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-1 b / 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 ? Issue Selection of gene

Silverman & Palmer AJRCMB 2000;22:645

Key questions Biologically ?

Positionally ?

Possible solutions Demonstration 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 ?

COPD

Extreme Phenotypes Can Be Determined in the Minority of COPD subjects

Emphysema and cigarette smoking

Inquinamento outdoor

• Ogni incremento di 10 µg/m 3 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 Anti-proteinases Oxidative stress Proteinases Repair mechanisms COPD PATHOLOGY Source : Peter J. Barnes, MD

Oxidative Stress in COPD

Macrophage Neutrophil

Anti-proteases SLPI



1 -AT Proteolysis ↓ HDAC2 ↑Inflammation Steroid resistance O 2 OH .

, H 2 0 2 , ONOO NF-



B IL-8 TNF-



Neutrophil recruitment Isoprostanes



Mucus secretion Plasma leak Bronchoconstriction 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 Goblet cell hyperplasia Mucus gland hyperplasia Neutrophils in sputum Squamous metaplasia of epithelium No basement membrane thickening ↑ Macrophages ↑ CD8 + lymphocytes Little increase in airway smooth muscle Source : Peter J. Barnes, MD

Ranked sputum neutrophil data demonstrating overlap of the ATS’ FEV 1 -based disease stages Franciosi et al, Pulm Pharmacol Ther 2006;19:189-199

Changes in Small Airways in COPD Patients

Lymphoid follicle Inflammatory exudate in lumen Disrupted alveolar attachments Thickened wall with inflammatory cells - macrophages, CD8 + cells, fibroblasts Peribronchial fibrosis 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

Inspiration Normal

small airway

Air Trapping in COPD

Mild/moderate COPD Severe COPD

alveolar attachments

Expiration

loss of elasticity loss of alveolar attachments 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

Alveolar Wall Destruction AIR TRAPPING Loss AIR TRAPPING AIRFLOW OBSTRUCTION LUNG HYPERINFLATION Reduction Small Airways Narrowing-Distortion Nonhomogeneous Inspired Air Distribution Reduced Ventilation In Dependent Alveoli HIGH V A /Q RATIOS LOW V A /Q RATIOS Rodríguez-Roisin and MacNee. ERM 1998;7:103-6

Pulmonary Hypertension in COPD

Chronic hypoxia Pulmonary vasoconstriction Pulmonary hypertension Cor pulmonale Edema Muscularization Intimal hyperplasia Fibrosis Obliteration 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 FEV reversible.

1 /FVC < 0.70 confirms the presence of airflow limitation that is not fully 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 short acting inhaled bronchodilator to minimize variability.

A post-bronchodilator FEV reversible.

1 /FVC < 0.70 confirms the presence of airflow limitation that is not fully 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

COPD: Natural History

100 75 50 25 0 25

Dyspnea Exercise Intolerance Exacerbations Hospitalizations Systemic Effects Respiratory Failure Pulm Hypertension

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 Dysfunction Structural 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

Liver

CRP IL-6 IL-6, TNF α, IL-1β Circulation Cardiovascular disease

Skeletal muscle

Muscle wasting Other Inflammatory diseases

COPD and Co-Morbidities

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

Respiratory system ?

Systemic inflammation Target organs

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 Lung Disease – (other than airways disorders) Pulmonary embolism Pleural effusions Lobar collapse Diaphragm weakness (Guillain Barre) 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 – Myocardial infarction Cardiac rhythm disturbance Dissecting aneurysm Left ventricular failure

•

Heart Disease Chronic heart failure, valve disease, cardiomyopathy

•

Systemic Disease – Blood loss/anaemia

•

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

ASTHMA

Allergens

COPD

Cigarette smoke Ep cells Mast cell Alv macrophage Ep cells CD4+ cell (Th2) Eosinophil

Bronchoconstriction AHR Reversible

CD8+ cell (Tc1) Neutrophil

Small airway narrowing Alveolar destruction Airflow Limitation Irreversible Source : Peter J. Barnes, MD

Overlap between COPD and asthma COPD – Neutrophils – – – No airway hyperreactivity No bronchodilator response No corticosteroid response ~10% ASTHMA – 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 FEV eosinofili.

1 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 Maestrelli et al, Thorax 2001

Differenze nelle risposte infiammatorie fra asma e BPCO Infiammazione Asma Mediatori infiammatori BPCO LTD 4 , istamina IL-4, IL-5, IL-13 LTB 4 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 Long smoking history Dyspnea during exercise Largely irreversible airflow limitation • • •

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

Come distinguere l’asma dalla BPCO in base alla funzione polmonare?



Un valore post BD FEV 1 /FVC <70% suggerisce fortemente una BPCO



Una risposta al BD >12% (post BD FEV 1 -pre BD FEV 1 /pre-BD FEV 1 x 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 SO 2 AMP Hyperventilation § Fog Asthma 75 80 82 67 95 90 96 30 COPD 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 80 60 40 20 0 >32 32 16 8 histamine threshold (g/L) 4 Heavy smokers Light smokers 1 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  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 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)