Mogliano Veneto (TV)
31 gennaio 2014
BPCO:
Documenti e linee guida
a confronto
Le Comorbilità
dr. Stefano Calabro
Dr. Stefano Calabro
Dr. Rolando Negrin
REGIONE VENETO – AZIENDA U.L.S.S. n.3
Ospedale S. Bassiano - Bassano del Grappa
Dipartimento di Medicina
Struttura Complessa di Pneumologia
REGIONE VENETO – AZIENDA U.L.S.S. n.6
Ospedale S. Bortolo - Vicenza
Dipartimento di Area Medica II
Unità Operativa Complessa di Pneumologia
Ultima revisione 28.01.2014.
Un caso di instabilità terminologica nel vocabolario medico:
comorbidità, comorbilità, comorbosità
Comorbidità e comorbilità sono due forme lessicali – entrambe attestate negli usi
linguistici medico-scientifici italiani, a volte anche in grafia non univerbata (cioè con
il trattino) – usate dagli specialisti in maniera intercambiabile: negli stessi contesti,
con gli stessi significati, per indicare quindi uno stesso concetto o grappolo di
concetti.
Questa oscillazione fra comorbidità e comorbilità negli usi specialistici si spiega, più
che in termini di sinonimia, come compresenza nel vocabolario medico italiano
attuale di forme alternative e concorrenti, in competizione fra di loro per designare
sostanzialmente la stessa cosa.
Si tratta, dunque, di un caso di instabilità terminologica, accentuata dall’alternanza
con una terza forma, comorbosità, che, sebbene meno frequente – e probabilmente
per questo non menzionata nelle domande – è tuttavia attestata e registrata.
Definizione di comorbidità
“The existence or occurrence of any distinct additional
entity during the Clinical course of a patient who has
the index disease under study”.
“l’esistenza o la presenza di ogni entità patologica
distinta addizionale durante il decorso clinico di una
patologia oggetto di studio”.
Comorbidity constructs
Valderas JM, Starfield B, Sibbald B, et al.
Defining Comorbidity: Implications for
Understanding Health and Health Services.
Ann Fam Med 2009;7:357-363. doi:10.1370/afm.983.
BroncoPneumopatia Cronica Ostruttiva
Complicanze
Comorbilità
Malattie croniche
Number of chronic disorders by age-group
Barnett K, Mercer SW, Norbury M, et al.
Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study.
Published online May 10, 2012 DOI:10.1016/S0140-6736(12)60240-2.
Invecchiamento, infiammazione sistemica e malattie
Malattie
croniche
croniche complesse
Invecchiamento (modificazioni strutturali organospecifiche, sistemiche e immunologiche in senso
proinfiammatorio)
fattori di rischio (es. fumo, inquinamento,
iperdislipidemia, obesità)
Franceschi C, Pauletto P, Incalzi RA, Fabbri LM
Invecchiamento, infiammazione sistemica e malattie cliniche complesse
Italian Journal of Medicine 2011;5S: S3—S13.
The guideline with the highest coverage of
comorbidities was that of the Global Initiative
for Chronic Obstructive Lung Disease (GOLD).
Comorbidity
Prevalence in COPD (%)
Patel AR, Hurst JR.
Extrapulmonary comorbidities in chronic obstructive
pulmonary disease: state of the art.
Expert Rev Respir Med. 2011; 5:647-62.
Diagnosi
fattori di rischio
sintomi
spirometria
Valutazione della gravità
gravità dei sintomi
grado di ostruzione bronchiale
rischio di riacutizzazioni
numero e gravità delle comorbidità
Relation between lung function and death due to
cardiovascular disease, lung cancer, and respiratory failure
Sin DD, Anthonisen NR, Soriano JB, et al.
Mortality in COPD: role of comorbidities.
Eur Respir J 2006; 28: 1245–57.
Cardiovascular diseases (CVD)
Vascular and heart diseases are among the most
important comorbidities observed in COPD, because
they have a direct impact on patient survival.
The pathophysiological mechanisms underlying the
vascular alterations observed in COPD appear to be
mainly mediated by endothelial dysfunction and
coagulopathy.
Relationship Between Reduced Lung Function and Cardiovascular Mortality
There is strong epidemiologic
evidence to indicate that reduced
FEV1 is a marker for cardiovascular
mortality independent of age,
gender, and smoking history.
Risk
for cardiovascular
disease in
COPD patients
andin
Prevalence
of all cardiovascular
diseases
was higher
matched
controls
the COPD
group than in the comparison group.
80
Percent of Subjects
70
60
50
40
*
COPD (N=11,493)
Controls (N=22,986)
70,4
*P<0.05 for between-group difference
54
MI = myocardial infarction
CHF = congestive heart failure
CVD = cardiovascular disease
*
31,3
30
*
*
22,8
21,1
20
11,7
10
*
11,2
6,4
9,0
*
5,6
*
9,6
11,2
7,9
3,2
0
Arrhythmia
Angina
Acute MI
CHF
Stroke
Other CVD
CVD
Hospitalisation
Curkendall SM, DeLuise C, Jones JK, et al.
Cardiovascular disease in patients with chronic obstructive pulmonary disease,
Saskatchewan Canada cardiovascular disease in COPD patients.
Am J Epidemiol. 2006;16:63-70.
Cardiovascular disease in COPD patients
1200 COPD patients
300 control subjects
COPD
COPD
group
Control
group
Ischemic
heart disease
12.5%
4.7%;
P <0.0001
Cerebrovascular disease
10%
2%
P <0.0001
16.4%
4.1%
P <0.001
Peripheral
vascular
disease
Compared with the control group, the COPD group showed a significantly higher prevalence
of ischemic heart disease, cerebrovascular disease, and peripheral vascular disease
In theCOPD
univariate
patients
risk analysis,show
COPD, hypertension,
a high prevalence
diabetes, obesity,
of and
cardiovascular
dyslipidemia were
risk factors for ischemic heart disease
disease, higher than expected given their age and the
In the multivariate analysis adjusted for the remaining factors, COPD was still an
independent
risk factor (odds ratio:
2.23; 95%cardiovascular
confidence interval: 1.18–4.24;
P = 0.014)
coexistence
of classic
risk factors
de Lucas-Ramos P, Izquierdo-Alonso JL, Moro JM, et al.
Chronic obstructive pulmonary disease as a cardiovascular risk factor. Results of a case–control study (CONSISTE study)
Int J Chron Obstruct Pulmon Dis. 2012;7:679-686.
The mechanistic links between COPD and cardiovascular disease
are complex, multifactorial, and not entirely understood
Decramer M, Janssens W.
Chronic obstructive pulmonary disease and comorbidities.
Lancet Respir Med. 2013;1:73-83.
Cardiovascular diseases (CVD)
Systemic venous thromboembolism
Pulmonary artery disease : pulmonary hypertension
During COPD exacerbations, VTE is found in 3–29% of cases
Coronary heart disease
Heart failure
Gunen H, Gulbas G, In E, et al.
Venous thromboemboli and exacerbations of COPD.
Eur Respir J 2010; 35: 1243–1248.
Heart arrhythmia
Prevention of Thrombosis
Prevention of VTE in Nonsurgical Patients
Antithrombotic Therapy and Prevention of Thrombosis,
9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines
2012
For acutely ill hospitalized medical patients at increased risk of thrombosis, we
recommend anticoagulant thromboprophylaxis with low-molecular-weight
heparin [LMWH], low-dose unfractionated heparin (LDUH) bid, LDUH tid, or
fondaparinux (Grade 1B).
For acutely ill hospitalized medical patients at low risk of thrombosis, we
recommend against the use of pharmacologic prophylaxis or mechanical
prophylaxis (Grade 1B).
In acutely ill hospitalized medical patients who receive an initial course of
thromboprophylaxis, we suggest against extending the duration of
thromboprophylaxis beyond the period of patient immobilization or acute
hospital stay (Grade 2B).
In chronically immobilized persons residing at home or at a nursing home, we
suggest against the routine use of thromboprophylaxis (Grade 2C).
Increased risk of thrombosis
Prevention of VTE in Nonsurgical Patients
Antithrombotic Therapy and Prevention of Thrombosis,
9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines
2012
Risk Factors for VTE in Hospitalized Medical Patients
Risk Factor
Points
Active cancer
3
Previous VTE (with the exclusion of superfi cial vein thrombosis)
3
Reduced mobility
3
Already known thrombophilic condition
3
Recent (< 1 mo) trauma and/or surgery
2
Elderly age ( > 70 y)
1
Heart and/or respiratory failure
1
Acute myocardial infarction or ischemic stroke
1
Acute infection and/or rheumatologic disorder
1
Obesity (BMI > 30)
1
Ongoing hormonal treatment
1
In the Padua Prediction Score risk assessment model, high risk of VTE is defined by a cumulative score 4 points.
Pulmonary hypertension (PH)
Haemodynamic definitions of pulmonary hypertension
a All values measured at rest.
c High CO can be present in cases of hyperkinetic
conditions such as systemic-to-pulmonary shunts
(only in the pulmonary circulation),anaemia,
hyperthyroidism, etc.
CO = cardiac output;
PAP = pulmonary arterial pressure;
PH = pulmonary hypertension;
PWP = pulmonary wedge pressure;
TPG = transpulmonary pressure gradient (mean PAP –
mean PWP).
ECS/ERS Guidelines 2009
Pulmonary hypertension (PH)
Most studies have indicated that COPD tends to produce relatively
modest hemodynamic alterations at rest, relative to other forms of
PH, such as idiopathic pulmonary arterial hypertension or PH
associated with connective tissue diseases.
Typical hemodynamic alterations include mild elevations in mPAP,
right atrial pressure (RAP), and pulmonary vascular resistance (PVR).
PH in COPD typically occurs in patients with more advanced
compromise in respiratory function (FEV1 < 30% predicted) and low
PaO2.
Pulmonary hypertension in COPD: a review of the literature
Minai OA
www.pvrireview.org
Pulmonary Hypertension in COPD
Mean pulmonary artery pressure in a hospital-based cohort of 998 COPD
patients with a mild to very severe airflow limitation
PH is mild to moderate but it may be severe and could be
observed without major airflow limitation
This latter condition has been termed ‘‘out-of-
proportion’’ PH
(may be defined by mPAP > 35–40 mmHg and a mild-tomoderate airflow limitation)
Chaouat A, Bugnet AS, Kadaoui N, et al.
Severe pulmonary hypertension and chronic obstructive pulmonary
disease
Am J Respir Crit Care Med 2005; 172: 189–194
Prognostic impact of PH in patients with COPD
Chronic obstructive pulmonary disease patients with a mPAP > 25
mmHg (– – – –) at the beginning of long-term oxygen therapy have a
significantly (p < 0.001) shorter life expectancy compared with
patients with mPAP < 25 mmHg (––––)
Oswald-Mammosser M, Weitzenblum E, Quoix E, et al
Prognostic factors in COPD patients receiving long-term
oxygen therapy. Importance of pulmonary artery pressure
Chest 1995; 107: 1193–1198
CHF & COPD
Heart failure is a complex clinical syndrome with many
features in common with COPD, particularly the cardinal
symptoms of dyspnea and fatigue.
Prevalence of COPD ranges from 20-32% in CHF
Risk ratio of developing CHF is 4.5 in COPD
Rutten FH, Cramer MM, Lammers JJ, et al.
Heart failure and chronic obstructive pulmonary disease: an ignored combination.
Eur J Heart Fail 2006;8:706-711.
O'Connor CM, Stough WG, Gallup DS, et al.
Demographics, clinical characteristics, and outcomes of patients hospitalized for
decompensated heart failure: observations from the IMPACT-HF registry.
J Card Fail 2005;11:200-205.
Gustafsson F, Torp-Pedersen C, Burchardt H, et al.
Female sex is associated with a better longterm survival in patients hospitalized with
congestive heart failure.
Eur Heart J. 2004;25:129-315.
BPCO e Scompenso cardiaco – mortalità
1.0
primary care patients with COPD ≥ 65
years (n=404)
Survival
0.9
follow up for a mean duration of 4.2
(SD 1.4) years.
0.8
0.7
COPD
HF doubles mortality of patients with
COPD: adjusted HR 2.1 (1.2–3.6 C.I.)
COPD GOLD
COPD + Heart failure
0.6
COPD GOLD + Heart Failure
0.5
0
12
24
36
48
Time (Months)
60
72
Boudestein LC, Rutten FH, Cramer MJ, et al.
The impact of concurrent heart failure on prognosis in patients with
chronic obstructive pulmonary disease.
Eur J Heart Fail 2009;11:1182–1188.
Heart failure (HF)
The combination of heart failure and chronic obstructive pulmonary
disease presents many therapeutic challenges.
The cornerstones of therapy are beta-blockers and beta-agonists,
respectively.
Their pharmacological effects
are diametrically opposed,
and each is purported to
adversely affect the alternative condition.
Terapia dell’insufficienza cardiaca
OBIETTIVI A BREVE TERMINE
Riduzione sintomatologia
DIURETICI
VASODILATATORI
DIGITALE
OBIETTIVI A LUNGO TERMINE
Prolungamento sopravvivenza
ACE- INIBITORI
I b – bloccanti migliorano in modo marcato
NEURO-UMORALI
la INIBITORI
sintomatologia
e la sopravvivenza dei
pazienti con scompenso
b – BLOCCANTI
INIBITORI RECETTORIALI A II
ANTIALDOSTERONICI
Differenze farmacologiche dei β-bloccanti
approvati per lo scompenso cardiaco
Blocco
ß1
Blocco
ß2
Blocco
α1
ISA
+++
-
Carvedilolo
+++
+++
Metoprololo
+++
-
-
-
Bisoprololo
+++
-
-
-
Nebivololo
+++
-
-
-
ISA attività simpaticomimetica intrinseca
Heart disease - COPD
Le linee guida della Società Europea di Cardiologia dicono che la
BPCO non rappresenta una controindicazione all'utilizzo dei betabloccanti.
Dickstein K, Cohen-Solal A, Filippatos G, et al.
ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and
Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology.
Eur Heart J 2008;29:2388-442
Beta-bloccanti – BPCO/scompenso cardiaco
I beta-bloccanti migliorano in maniera altamente
significativa i sintomi e la sopravvivenza nei pazienti con
scompenso cardiaco.
La BPCO (anche se moderata o grave) non costituisce una
controindicazione per i beta-bloccanti.
Va raccomandato un inizio a basso dosaggio e incrementi
progressivi graduali.
Un aspetto fondamentale è la cardioselettività: sono
permessi nella BPCO metoprololo, bisoprololo e nebivololo.
Beta bloccanti e BPCO
What this study adds
β blockers (predominantly cardioselective) reduced mortality
and COPD exacerbations when added to stepwise inhaled
therapy for COPD (including long acting β agonists and
antimuscarinics) in addition to the benefits attributable to
addressing cardiovascular risk.
The benefits observed occurred without adverse effects on
pulmonary function.
estimate ofin
probability
of survival
among patients
These data support the use Kaplan-Meier
of β blockers
patients
with
with COPD by use of β blockers
Adjusted
hazard ratios for all cause mortality
COPD.
among patients with COPD in reference to the
control group (who received only inhaled therapy
with short acting β agonists or antimuscarinics)
Short PM, Lipworth, SIW, Elder DHJ, et al.
Effect of β blockers in treatment of chronic obstructive pulmonary
disease: a retrospective cohort study.
BMJ 2011;342:bmj.d2549
Heart failure (HF)
Are beta2-agonists responsible for increased
mortality in heart failure?
Bermingham M, O'Callaghan E, Dawkins I, et al.
Eur J Heart Fail 2011; 13: 885-891.
Data were available for 1294 patients (age 70.6 ± 11.5 years) of whom 64% were male and
22.2% were taking B2As. β2-Agonist users were older, more likely to be male, to have smoked,
to have chronic obstructive pulmonary disease (COPD) and asthma.
When adjusted for age, sex, medication, co-morbidity, smoking, COPD, and BNP differences,
overall mortality rates were similar [HR 1.043, 95% CI (0.771–1.412), P= 0.783].
Unlike previous reports, this retrospective evaluation of β2-agonist therapy in HF
patients shows no relationship with long-term mortality when adjusted for population
differences including BNP. Large, prospective studies are required to define the
risk/benefit ratio of β2-agonists in patients with heart failure.
Broncodilatatori – BPCO/scompenso cardiaco
Anche se trial clinici randomizzati e controllati hanno stabilito la sicurezza dei betaagonisti a lunga durata d'azione nei pazienti con BPCO, restano zone d'ombra
riguardo la sicurezza nei pazienti con asma.
Nessuno studio prospettico ha valutato la sicurezza dei beta-agonisti a lunga durata
d'azione nei pazienti con BPCO e asma concomitante.
Un broncodilatatore anticolinergico a lunga durata d'azione (tiotropio) si è dimostrato
efficace sia nella BPCO che nell'asma; per tale agente è stata evidenziata una
sicurezza cardiovascolare.
.
I pazienti con SC e BPCO concomitante che hanno bisogno di un'assunzione
regolare di broncodilatatori per via inalatoria a lunga durata d'azione potrebbero
iniziare con un agente anticolinergico piuttosto che con un beta-agonista a lunga
durata d'azione.
Hawkins NM, Petrie MC, MacDonald MR, et al.
Heart Failure and Chronic Obstructive Pulmonary Disease: The Quandary of Beta-Blockers and Beta-Agonists.
J Am Coll Cardiol.2011; 57: 2127-2138.
Chowdhury BA, Dal PG.
The FDA and safe use of long-acting betaagonists in the treatment of asthma.
N Engl J Med 2010;362:1169-71.
Treatment of chronic obstructive pulmonary disease and
its comorbidities
Treatments for COPD may positively affect morbidity
and mortality linked to comorbidities of COPD
Treatments for comorbidities may positively affect
morbidity and mortality linked to COPD
Luppi F, Franco F, Beghé B, et al.
Treatment of chronic obstructive pulmonary disease and its comorbidities
Proc Am Thorac Soc 2008;5:848-856.
Predictors of Early and Late Mortality in Hospitalized Patients
with Acute Exacerbation of COPD
Adapted from
Singanayagam A, Schembri S, Chalmers JD.
Predictors of mortality in hospitalized adults with acute exacerbation of chronic
obstructive pulmonary disease.
Ann Am Thoracic Soc 2013, 10:81–89.
Changing paradigms in cardiovascular risk management
Volpe M, Erhardt LR, Williams B.
Managing cardiovascular risk: the need for change.
J Hum Hypertens 2008; 22: 154–157.
Valutazione del rischio cardiovascolare nel paziente BPCO
Età
Valutazione dei fattori di rischio
Sesso (prima della menopausa)
Familiarità per coronaropatia o morte improvvisa: positiva se coronaropatia o morte improvvisa
Attività fisica: livello di attività sia al lavoro che extra
Fumo:
1) numero di sigarette fumate al giorno e durata della abitudine al fumo
2) se ex fumatore, da quando ha smesso e per quanto tempo ha fumato
3) esposizione passiva
Peso corporeo e distribuzione del grasso:
1) anamnesi familiare/personale
2) peso, altezza con calcolo dell’IMC( > 25 Kg/m2 sovrappeso, > 30 Kg/m2 obesità)
3) circonferenza vita (adiposità addominale > 102cm per uomo, > 88cm per donna, adiposità addominale borderline > 94
cm per uomo e > 80 cm per donna)
Pressione arteriosa
Sindrome metabolica, intolleranza glucidica, diabete,
Lipidi plasmatici (colesterolo, HDL colesterolo, LDL colesterolo, trigliceridi)
Sindrome delle apnee ostruttive nel sonno
Malattie renali croniche
Effects of statins on the cholesterol biosynthesis pathway
De Loecker I and Preiser J-C
Statins in the critically ill
Annals of Intensive Care 2012, 2:19.
Pleiotropic effects of statins
De Loecker I and Preiser J-C
Statins in the critically ill
Annals of Intensive Care 2012, 2:19.
Effect of statins on mortality and exacerbation in COPD
1,687 patients (mean age 70.6 years)
596 statin users - 1,091 non-users
Hazard ratios calculated for statin users versus statin non-users for all-cause mortality over follow-up of up to 4 years.
Statin use is associated with a 30% reduction in all-cause mortality at 3-4 years after first
admission for COPD, irrespective of a past history of cardiovascular disease and diabetes.
Lawes CM, Thornley S, Young R,et al.
Statin use in COPD patients is associated with a reduction in mortality: a national cohort study.
Prim Care Respir J 2012, 21:35–40.
Proportion of surviving patients hospitalized with COPD
exacerbation by use of statin versus non-use (p < 0.0001).
Mortensen EM, Copeland LA, Pugh MJ, et al.
Impact of statins and ACE inhibitors on mortality after COPD
exacerbations.
Respiratory Research 2009, 10:45 doi:10.1186/1465-9921-10-45
Simvastatin Therapy for Moderate and Severe
COPD (STATCOPE)
To determine the effect of daily administration of 40 mg simvastatin
taken for at least 12 months (range 12-36 months) on the frequency of
exacerbations of chronic obstructive lung disease (COPD) in patients
with moderate to severe COPD who are prone to exacerbations and do
not have other indications for statin treatment.
Estimated Study Completion Date: January 2014
Simvastatin therapy for moderate and severe COPD
(STSTCOPE).: United States National Institute of Health;
http://clinicaltrials.gov/ct2/show/NCT01061671
BPCO e Diabete mellito
Kannel WB and McGee DL
Diabetes and cardiovascular disease.The Framingham study
Jama 1979, 241:2035-2038
Large population studies show that there is an increased prevalence of
diabetes among COPD patients (relative risk 1.5– 1.8), even in patients with
mild disease.
Mannino DM, Thorn D, Swensen A, Holguin F.
Prevalence and outcomes of diabetes, hypertension, and cardiovascular disease in
chronic obstructive pulmonary disease
Eur Respir J 2008; 32: 962–269.
BPCO e Diabete mellito
Mortality in COPD Pts Discharged from Hospital
(AECOPD) - Role of Comorbidity
416 patients
Follow-up 24 months
122 (29.3%) of the 416 patients died
Kaplan-Meier survival curve in patients with and without diabetes
Patients with diabetes had an increased mortality rate [HR = 2.25 (1.28–3.95)]
Gudmundsson G, Gislason T, Lindberg E, et al.
Mortality in COPD patients discharged from hospital: the role of
treatment and co-morbidity
Respiratory Research 2006, 7:109.
Corticosteroidi inalatori
Effetti collaterali
Inhaled corticosteroids and the risk of diabetes
Current use of inhaled corticosteroids was associated with a 34% increase in the rate of
diabetes (rate ratio [RR] 1.34; 95% confidence interval [CI], 1.29-1.39) and in the rate of
diabetes progression (RR 1.34; 95% CI, 1.17-1.53).
The risk increases were greatest with the highest inhaled corticosteroid doses, equivalent to
fluticasone 1000 μg per day or more (RR 1.64; 95% CI, 1.52-1.76 and RR 1.54; 95% CI, 1.182.02; respectively).
*Individuals who entered the cohort after the age of 55 years and without mention of asthma during a hospitalization.
Suissa S, Kezouh A, Ernst P.
Inhaled corticosteroids and the risks of diabetes onset and progression
Am J Med 2010;123:41001-1006.
Corticosteroidi inalatori
Effetti collaterali
Inhaled corticosteroids and the risk of diabetes
388,584 patients
30,167 had diabetes onset during 5.5
years of follow-up (incidence rate
14.2/1000/year), and 2099 subsequently
progressed from oral hypoglycemic
treatment to insulin (incidence rate
19.8/1000/year).
Adjusted rate ratio of diabetes incidence associated with inhaled corticosteroid use, as a function of the current
dose converted to fluticasone equivalents (in g), along with the corresponding 95% confidence limits for the
fitted dose-response curve.
Suissa S, Kezouh A, Ernst P.
Inhaled corticosteroids and the risks of diabetes onset and Progression
Am J Med 2010;123:41001-1006.
List of potential risk factors of osteoporosis
Smoking
Increased alcohol intake
Vitamin D levels
Genetic factors
Treatment with corticosteroids
Reduced skeletal muscle mass and strength
Low BMI and changes in body composition
Hypogonadism
Reduced levels of insulin-like growth factors
Chronic systemic inflammation
Ionescu AA, Schoon E.
Osteoporosis in chronic obstructive pulmonary disease.
Eur Respir J Suppl. 2003;46:64s-75s.
Osteoporosis - COPD
Osteoporosis is highly prevalent in patients with COPD, irrespective of gender.
Langhammer A, Forsmo S, and Syversen U. Long-term therapy in COPD: any
evidence of adverse effect on bone?
Int J Chron Obstruct Pulmon Dis. 2009; 4: 365–380.
Osteoporosis – Fractures – ICS - COPD
Inhaled corticosteroid use is associated with a modest but statistically
significant
increase
in the riskversus
of fractures
in patients
with
COPD.
Meta-analysis
of inhaled corticosteroids
controls for fractures
in observational
studies
Loke YK, Cavallazzi R, Singh S.
Risk of fractures with inhaled corticosteroids in COPD: systematic review and
meta-analysis of randomised controlled trials and observational studies.
Thorax 2011;66:699-708.
Osteoporosis - Prednisolone
Adjusted odds ratio for fracture risk at different sites by daily dose of prednisolone in UK General Practice Research
Database (GPRD) and Danish large register studies.
Langhammer A, Forsmo S, and Syversen U. L
ong-term therapy in COPD: any evidence of adverse effect on bone?
Int J Chron Obstruct Pulmon Dis. 2009; 4: 365–380.
Skeletal Muscle Atrophy - COPD
no impairment
muscle atrophy
semistarvation
cachexia
Schols AM, Broekhuizen R, Weling-Scheepers CA, et al.
Bodycomposition and mortality in chronic obstructive pulmonary disease.
Am J Clin Nutr 2005; 82: 53–59.
Proposed Mechanisms of Skeletal Muscle Dysfunction in COPD
Kim HC, Mofarrahi M, Hussain SN.
Skeletal muscle dysfunction in patients with chronic
obstructive pulmonary disease.
Int J Chron Obstruct PulmonDis 2008, 3:637–658.
Targets of Exercise Training as Part of a Pulmonary Rehabilitation
Program for Patients with COPD
Casaburi R, ZuWallack R.
Pulmonary rehabilitation for management of chronic obstructive
pulmonary disease.
N Engl J Med 2009;360:1329-1335.
Variables Associated With Depression and Anxiety in
Patients With COPD
Physical disability
Long-term oxygen therapy
Low body mass index
Severe dyspnea
Percentage of predicted FEV1 50%
Poor quality of life
Presence of comorbidity
Living alone
Female gender
Current smoking
Low social class status
Maurer J, Rebbapragada V, Borson S, et al.
Anxiety and depression in COPD: current understanding, unanswered questions, and
research needs.
Chest 2008; 134: 43S–56S.
Anaemia
Anaemia is defined by a haemoglobin concentration of < 13 g.dL-1
for males and 12 g.dL-1 for females.
Anaemia was recently identified as a comorbidity of COPD.
Hypoxaemic smokers would actually be expected to exhibit
polycythaemia, but studies that have reported haematological
values show that anaemia is more common than polycythaemia,
with a prevalence ranging from 12.3% to 23% for anaemia and of
6% for polycythaemia.
Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ.
Comorbidities in chronic obstructive pulmonary disease.
Proc Am Thorac Soc 2008;5:549–555.
Epstein AA.
A Contribution to the study of the chemistry of blood serum.
J Exp Med. 1912;16:719–731.
Weber FP.
The prognostic significance of secondary polycythaemia in cardiopulmonary cases.
Proc R Soc Med. 1913;6:83–98.
COPD has long been recognized as an important cause of secondary polycythemia.
Early reports include that of Epstein in 1912, which described polycythemia
occurring in cases of “respiratory embarrassment”, including emphysema, while
an association between the presence of polycythemia and increased risk of
mortality was observed by Weber in 1913.
Anaemia in COPD and chronic respiratory failure (CRF)
185 patients with CRF;
18.4% anaemia
*Potential contributions for anaemia: low folic acid or vitamin B12 levels (two patients);
GFR< 60 ml/min (three patients); uncontrolled diabetes (two patients); toxic causes (two
patients); missing values of TSAT (two patients).
ACD, anaemia of chronic disease; IDA, iron deficiency anaemia
Schneckenpointner R, Jörres RA, Meidenbauer N, et al.
The clinical significance of anaemia and disturbed iron homeostasis in chronic respiratory failure.
Int J Clin Pract 2014;68:130-138.
In 1978, Bernice Cohen, discussing her findings on familial
aggregation of chronic obstructive pulmonary disease (COPD)
and lung cancer, stated that “a common predisposition to
pulmonary dysfunction in families of COPD and lung cancer
probably precedes, rather than merely accompanies, both
neoplastic and non neoplastic disease”.
Following such a hypothesis, she proposed a model in which
impaired pulmonary function, irrespective of its causation
(either genetically or environmentally mediated), could lead to
many disorders including COPD and lung cancer.
Cohen BH.
Is pulmonary dysfunction the common denominator for the multiple effects
of cigarette smoking?
Lancet 1978 ;2 (8098 ): 1024 – 1027.
Lung cancer
COPD is associated with a lung cancer risk that is two to six times
Theoflung
cancer
risk COPD.
seems to be greater in patients
that
smokers
without
with mild to moderate COPD than in those with more
Moreover, COPD was associated with lung cancer in neversmokers;
hence, the association is not solely due to smoking.
severe disease.
Proportion of chronic smokers with COPD and
healthy lung function who will get lung cancer
Lung cancer
Young RP, Hopkins RJ, Christmas T, et al.
COPD prevalence is increased in lung cancer,
independent of age, sex and smoking history.
Eur Respir J 2009; 34: 380–86.
Recent data from the American National Lung Screening Trial showed a 20%
reduction in death due to lung cancer in the group screened using computed
tomography compared to the group screened by radiography, among smokers or
former smokers aged between 55 years and 74 years with a smoking history of o30
pack-years.
The patients’ lung function was not reported in the trial.
These epidemiological data suggest that targeted lung cancer screening for COPD
patients could be worthwhile.
The National Lung Screening Trial Research Team, Aberle DR, Adams AM.
Reduced lung-cancer mortality with low-dose computed tomographic screening.
N Engl J Med 2011; 365: 395–409.
U.S. Preventive Services Task Force
La USPSTF raccomanda:
LO SCREENING ANNUALE CON LDCT NEGLI ADULTI DI ETÀ COMPRESA
TRA I 55 E GLI 80 ANNI CHE HANNO UNA STORIA DI FUMO DI
ALMENO 30 PACCHETTI-ANNO, E CHE CONTINUANO A FUMARE O
HANNO SMESSO DA MENO DI 15 ANNI.
COTE Index
1664 patients with COPD in 5 centers were observed for a median of 51 months,
and 79 comorbidities were recorded.
Fifteen of 79 comorbidities differed in prevalence between survivors and nonsurvivors. Of those, 12 predicted mortality:
Oncologic (lung, pancreatic, esophageal, and breast cancers)
Pulmonary (pulmonary fibrosis)
Cardiac (atrial fibrillation/flutter, congestive heart failure, and coronary
artery disease)
Gastrointestinal (gastric/duodenal ulcer, liver cirrhosis)
Endocrine (diabetes with neuropathy)
Psychiatric (anxiety)
Divo M, Cote C, de Torres JP, et al.
Comorbidities and risk of mortality in patients with chronic bstructive pulmonary disease
Am. J. Respir. Crit. Care Med. 2012;186:155 -161.
COTE Index
COMORBIDITIES AND POINT VALUES USED FOR THE COMPUTATION
OF COTE INDEX
Increases in the BODE and COTE were
independently associated with an
increased risk for death.
A COTE of 4 points or more increased
the risk for death by 2.2-fold (HR, 2.26 2.68; P < .001) in all BODE quartiles.
Increases in the COTE index were associated with an increased risk for death from both
COPD (HR, 1.13; 95% CI, 1.08 - 1.18; P < .001) and causes not related to COPD (HR, 1.18;
95% CI, 1.15 - 1.21; P < .001).
Divo M, Cote C, de Torres JP, et al.
Comorbidities and risk of mortality in patients with chronic bstructive
pulmonary disease
Am. J. Respir. Crit. Care Med. 2012;186:155 -161.
William Osler (1849 – 1919)
«It is much more important
to know what sort of
patient has a disease than
to know what kind of a
disease a patient has»
Co-morbidity: we need a guideline for each
patient not a guideline for each disease
Dawes M.
Co–morbidity: we need a guideline for each patient not a guideline for
each disease.
Fam Pract 2010, 27:1-2.
Grazie per l’attenzione
dr. Stefano Calabro
Dr. Stefano Calabro
REGIONE VENETO – AZIENDA U.L.S.S. n.3
Ospedale S. Bassiano - Bassano del Grappa
Dipartimento di Medicina
Struttura Complessa di Pneumologia
Dr. Rolando Negrin
REGIONE VENETO – AZIENDA U.L.S.S. n.6
Ospedale S. Bortolo - Vicenza
Dipartimento di Area Medica II
Unità Operativa Complessa di Pneumologia
Corticosteroidi inalatori
DOSI QUOTIDIANE (in mcg) COMPARATIVE DI CORTICOSTEROIDI PER VIA
INALATORIA
FARMACO
ADULTI $
Dose bassa
Dose intermedia
Dose Alta
Beclometasone
Dipropionato HFA
100 – 200
>200 – 400
>400 – 800
Budesonide
200 – 400
>400 – 800
>800 – 1600
Ciclesonide
80-160
160-320
320-1280
Flunisolide
500 – 1000
>1000 – 2000
>2000
Fluticasone
Propionato
100 – 250
>250 – 500
>500 – 1000
Mometasone furoato
200-400
400-800
800-1200
$ confronto basato sui dati di efficacia