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BPCO: Documenti e linee guida a confronto. Mogliano Veneto (TV ) 3 1 gennaio 2014. Le Comorbilità. 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.

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Dr stefano calabro


Documenti e linee guida a confronto

Mogliano Veneto (TV)

31 gennaio 2014

Le Comorbilità

dr. Stefano Calabro

Dr. Stefano Calabro

REGIONE VENETO – AZIENDA U.L.S.S. n.3Ospedale S. Bassiano - Bassano del GrappaDipartimento di MedicinaStruttura Complessa di Pneumologia

Dr. Rolando Negrin

REGIONE VENETO – AZIENDA U.L.S.S. n.6Ospedale S. Bortolo - VicenzaDipartimento di Area Medica IIUnità Operativa Complessa di Pneumologia

Ultima revisione 28.01.2014.

Dr stefano calabro

Un caso di instabilità terminologica nel vocabolario medico:

comorbidità, comorbilità, comorbosità

Comorbidità e comorbilitàsono 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 comorbilitànegli 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.

Dr stefano calabro

Definizione di comorbidità

“The existence or occurrenceofanydistinctadditionalentityduring the Clinicalcourseof a patientwhohas the indexdisease under study”. “l’esistenza o la presenza di ogni entità patologica distinta addizionale durante il decorso clinico di una patologia oggetto di studio”.

Dr stefano calabro


Valderas JM, Starfield B, Sibbald B, et al.

Defining Comorbidity: Implications for Understanding Health and Health Services.

AnnFamMed 2009;7:357-363. doi:10.1370/afm.983.

Dr stefano calabro

BroncoPneumopatia Cronica Ostruttiva



Dr stefano calabro

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.

Dr stefano calabro

Malattie croniche

Invecchiamento (modificazioni strutturali organo-specifiche, sistemiche e immunologiche in senso proinfiammatorio)

fattori di rischio (es. fumo, inquinamento, iperdislipidemia, obesità)

Invecchiamento, infiammazione sistemica e malattie croniche complesse

Franceschi C, Pauletto P, Incalzi RA, Fabbri LM

Invecchiamento, infiammazione sistemica e malattie cliniche complesse

Italian Journal of Medicine 2011;5S: S3—S13.

Dr stefano calabro

The guideline with the highest coverage of comorbidities was that of the Global Initiative for Chronic Obstructive Lung Disease (GOLD).

Dr stefano calabro


Prevalence in COPD (%)

Patel AR, Hurst JR.

Extrapulmonarycomorbidities in chronic obstructive pulmonary disease: state of the art.

Expert RevRespirMed. 2011; 5:647-62.

Dr stefano calabro


fattori di rischio



Valutazione della gravità

gravità dei sintomi

grado di ostruzione bronchiale

rischio di riacutizzazioni

numero e gravità delle comorbidità

Dr stefano calabro

Relation between lung function and death due to cardiovascular disease, lung cancer, and respiratory failure

Sin DD, Anthonisen NR, Soriano JB, et al.

Mortalityin COPD: roleof comorbidities.

EurRespir J 2006; 28: 1245–57.

Dr stefano calabro

Cardiovasculardiseases (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.

Dr stefano calabro

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 and matched controls
Risk for cardiovascular disease in COPD patients and matched controls

Prevalence of all cardiovascular diseases was higher in the COPD group than in the comparison group.


*P<0.05 for between-group difference

MI = myocardial infarction

CHF = congestive heart failure

CVD = cardiovascular disease







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.

Dr stefano calabro

Cardiovascular disease in COPD patients controls

1200 COPD patients

300 control subjects


Compared with the control group, the COPD group showed a significantly higher prevalence of ischemic heart disease, cerebrovascular disease, and peripheral vascular disease

In the univariate risk analysis, COPD, hypertension, diabetes, obesity, and dyslipidemia were risk factors for ischemic heart disease

In the multivariate analysis adjusted for the remaining factors, COPD was still an independent risk factor (odds ratio: 2.23; 95% confidence interval: 1.18–4.24; P = 0.014)

COPD patients show a high prevalence of cardiovascular disease, higher than expected given their age and the coexistence of classic cardiovascular 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 ChronObstructPulmonDis. 2012;7:679-686.

Dr stefano calabro

The mechanistic links between COPD and controlscardiovascular disease are complex, multifactorial, and not entirelyunderstood

Decramer M, Janssens W.

Chronic obstructive pulmonary disease and comorbidities.

LancetRespirMed. 2013;1:73-83.

Dr stefano calabro

Cardiovascular controlsdiseases (CVD)

Systemic venous thromboembolism

During COPD exacerbations, VTE is found in 3–29% of cases

GunenH, Gulbas G, In E, et al.

Venousthromboemboli and exacerbations of COPD.

EurRespir J 2010; 35: 1243–1248.

Pulmonary artery disease : pulmonary hypertension

Coronary heart disease



Dr stefano calabro

Prevention controlsof VTE in Nonsurgical Patients

Antithrombotic Therapy and Prevention of Thrombosis,

9th ed: American College of Chest Physicians



Prevention of Thrombosis

For acutely ill hospitalized medical patients at increased risk of thrombosis, we recommend anticoagulantthromboprophylaxis with low-molecular-weightheparin [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).

Dr stefano calabro

Prevention controlsof VTE in Nonsurgical Patients

Antithrombotic Therapy and Prevention of Thrombosis,

9th ed: American College of Chest Physicians



Increasedrisk of thrombosis

Risk Factors for VTE in Hospitalized MedicalPatients

In the Padua Prediction Score risk assessment model, high risk of VTE is defined by a cumulative score 4 points.

Dr stefano calabro

Pulmonary controlshypertension (PH)

Haemodynamicdefinitions of pulmonaryhypertension

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

Dr stefano calabro

Pulmonary controlshypertension (PH)

Moststudieshaveindicatedthat COPD tends to produce relativelymodesthemodynamicalterationsatrest, relative to otherforms of PH, suchasidiopathicpulmonaryarterialhypertension or PH associated with connectivetissuediseases.

Typicalhemodynamicalterations include mildelevations in mPAP, right atrial pressure (RAP), and pulmonaryvascularresistance (PVR).

PH in COPD typicallyoccurs in patients with more advanced compromise in respiratoryfunction (FEV1 < 30% predicted) and low PaO2.

Pulmonary hypertension in COPD: a review of the literature

Minai OA


Dr stefano calabro

Pulmonary controlsHypertension in COPD

PH ismild to moderate butitmay be severe and could be

observedwithout major airflowlimitation


proportion’’ PH

(may be defined by mPAP > 35–40 mmHg and a mild-to-

moderate airflowlimitation)

Meanpulmonaryartery pressure in a hospital-basedcohort of 998 COPD patients with a mild to very severe airflowlimitation

Chaouat A, Bugnet AS, Kadaoui N, et al.

Severe pulmonaryhypertension and chronicobstructivepulmonarydisease

AmJ RespirCrit Care Med 2005; 172: 189–194

Dr stefano calabro

Prognostic controls impact of PH in patients with COPD

Chronicobstructivepulmonarydiseasepatients with a mPAP> 25 mmHg (– – – –) at the beginning of long-termoxygentherapyhave a significantly (p < 0.001) shorter life expectancycompared with patients with mPAP < 25 mmHg (––––)

Oswald-Mammosser M, Weitzenblum E, Quoix E, et al

Prognosticfactors in COPD patientsreceiving long-term

oxygentherapy. Importance of pulmonaryartery pressure

Chest1995; 107: 1193–1198

Dr stefano calabro

CHF & COPD controls

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.

Dr stefano calabro

BPCO e Scompenso cardiaco – mortalità controls


  • primary care patients with COPD ≥ 65

  • years (n=404)

  • follow up for a mean duration of 4.2

  • (SD 1.4) years.

  • HF doubles mortality of patients with

  • COPD: adjusted HR 2.1 (1.2–3.6 C.I.)







COPD + Heart failure


COPD GOLD + Heart Failure









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.

Time (Months)

Dr stefano calabro

Heart controlsfailure (HF)

The combinationofheartfailure and chronicobstructivepulmonarydiseasepresentsmanytherapeuticchallenges.

The cornerstonesoftherapy are beta-blockers and beta-agonists, respectively.


are diametricallyopposed,

and eachispurportedto

adverselyaffect the alternative condition.

Dr stefano calabro

Terapia dell’insufficienza cardiaca controls


Riduzione sintomatologia




Prolungamento sopravvivenza


I b – bloccanti migliorano in modo marcato la sintomatologia e la sopravvivenza dei pazienti con scompenso






Dr stefano calabro

Differenze farmacologiche dei controlsβ-bloccanti approvati per lo scompenso cardiaco

  • BloccoBloccoBlocco ISA ß1ß2 α1

Carvedilolo +++ +++ +++ -

Metoprololo +++ - - -

Bisoprololo +++ - - -

Nebivololo +++ - - -

ISA attività simpaticomimetica intrinseca

Dr stefano calabro

Heart controlsdisease - COPD

Le linee guida della Società Europea di Cardiologia dicono che la BPCO non rappresenta una controindicazione all'utilizzo dei beta-bloccanti.

Dickstein K, Cohen-Solal A, Filippatos G, et al.

ESC guidelines for the diagnosis and treatment of acute and chronicheartfailure 2008: the Task Force for the Diagnosis and Treatment of Acute and ChronicHeartFailure 2008 of the European Society of Cardiology.

EurHeart J 2008;29:2388-442

Dr stefano calabro

Beta-bloccanti – controlsBPCO/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.

Dr stefano calabro

Beta bloccanti e BPCO controls

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.

These data support the use of β blockers in patients with


Kaplan-Meier estimate of probability of survival among patients with COPD by use of β blockers

Adjusted hazard ratios for all cause mortality 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

Dr stefano calabro

Heart failure (HF) controls

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.

Dr stefano calabro

Broncodilatatori – BPCO/scompenso cardiaco controls

Anche se trial clinici randomizzati e controllati hanno stabilito la sicurezza dei beta-agonisti 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.

Dr stefano calabro

Treatment of chronic obstructive pulmonary disease and its controlscomorbidities

Treatmentsfor 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.

Dr stefano calabro

Predictors of controlsEarly and Late Mortality in Hospitalized Patients with Acute Exacerbation of COPD


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.

Dr stefano calabro

Changing paradigms in cardiovascular risk management controls

Volpe M, Erhardt LR, Williams B.

Managing cardiovascular risk: the need for change.

J Hum Hypertens 2008; 22: 154–157.

Dr stefano calabro

Valutazione del rischio cardiovascolare nel paziente BPCO controls


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


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

Valutazione dei fattori di rischio

Dr stefano calabro

Effects of controlsstatins on the cholesterol biosynthesis pathway

De Loecker I and Preiser J-C

Statins in the critically ill

Annals of Intensive Care 2012, 2:19.

Dr stefano calabro

Pleiotropic controlseffectsofstatins

De Loecker I and Preiser J-C

Statins in the critically ill

Annals of Intensive Care 2012, 2:19.

Dr stefano calabro

Effect controlsof statinson 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.

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

Proportion of surviving patients hospitalized with COPD exacerbation by use of statin versus non-use (p < 0.0001).

Dr stefano calabro

Simvastatin controls 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

Dr stefano calabro

BPCO e Diabete mellito controls


Kannel WB and McGee DL

Diabetes and cardiovascular disease.TheFramingham study

Jama1979, 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

EurRespir J 2008; 32: 962–269.

Dr stefano calabro

BPCO e Diabete mellito controls

Mortality in COPD PtsDischargedfrom Hospital (AECOPD) - RoleofComorbidity

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

RespiratoryResearch 2006, 7:109.

Dr stefano calabro

Corticosteroidi controlsinalatori

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, 1.18-2.02; 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.

Dr stefano calabro

Corticosteroidi controlsinalatori

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.

Dr stefano calabro

Ionescu controls AA, Schoon E.

Osteoporosis in chronicobstructivepulmonarydisease.

Eur Respir J Suppl. 2003;46:64s-75s.

Dr stefano calabro

Osteoporosis controls - 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.

Dr stefano calabro

Osteoporosis controls – Fractures – ICS - COPD

Inhaledcorticosteroiduse is associated with a modest but statistically significant increase in the risk of fractures in patients with COPD.

Meta-analysis of inhaled corticosteroids versus controls for fractures in observationalstudies

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.

Dr stefano calabro

Osteoporosis controls - 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.

Dr stefano calabro

Skeletal controlsMuscleAtrophy - COPD

no impairment




Schols AM, Broekhuizen R, Weling-Scheepers CA, et al.

Bodycomposition and mortality in chronic obstructive pulmonary disease.

Am J ClinNutr 2005; 82: 53–59.

Dr stefano calabro

Proposed Mechanisms of Skeletal Muscle Dysfunction in COPD controls

Kim HC, Mofarrahi M, HussainSN.

Skeletalmuscledysfunction in patientswith chronic obstructive pulmonary disease.

IntJ Chron Obstruct PulmonDis2008, 3:637–658.

Dr stefano calabro

Targets of Exercise Training as Part of a controlsPulmonary Rehabilitation Program for Patients with COPD

Casaburi R, ZuWallack R.

Pulmonaryrehabilitationfor management ofchronicobstructivepulmonarydisease.

N Engl J Med 2009;360:1329-1335.

Dr stefano calabro

Variables Associated With Depression and Anxiety in Patients With COPD



Low body mass index

Severe dyspnea

Percentage of predicted FEV1 50%

Poorqualityof life


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.

Dr stefano calabro

Anaemia With COPD

Anaemia is defined by a haemoglobin concentration of < 13 g.dL-1for males and 12 g.dL-1for females.

Anaemiawas 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 ThoracSoc 2008;5:549–555.

Dr stefano calabro

Epstein AA. With COPD

A Contribution to the study of the chemistry of blood serum.

J ExpMed. 1912;16:719–731.

Weber FP.

The prognostic significance of secondary polycythaemiain cardio-pulmonary cases.

ProcR 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.

Dr stefano calabro

Anaemia With COPD 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 ClinPract 2014;68:130-138.

Dr stefano calabro

In 1978, With COPDBernice Cohen, discussingher findings on familial aggregation ofchronicobstructivepulmonarydisease (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 environmentallymediated), could lead to many disorders including COPD and lungcancer.

Cohen BH.

Is pulmonary dysfunction the common denominator for the multiple effects

of cigarette smoking?

Lancet 1978 ;2 (8098 ): 1024 – 1027.

Dr stefano calabro

Lung With COPDcancer

COPD is associated with a lung cancer risk that is two to six times that of smokers without COPD.

Moreover, COPD was associated with lung cancer in never-smokers; hence, the association is not solely due to smoking.

The lung cancer risk seems to be greater in patients with mild to moderate COPD than in those with more severe disease.

Proportion of chronic smokers with COPD and healthy lung function who will get 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.

Dr stefano calabro

Recent With COPDdata 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.

Dr stefano calabro

U.S. Preventive Services Task Force With COPD

La USPSTF raccomanda:


Dr stefano calabro

COTE Index With COPD

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 non-survivors. Of those, 12 predicted mortality:

  • Oncologic(lung, pancreatic, esophageal, and breastcancers)

  • Pulmonary(pulmonaryfibrosis)

  • Cardiac(atrialfibrillation/flutter, congestive heartfailure, and coronaryarterydisease)

  • Gastrointestinal(gastric/duodenalulcer, livercirrhosis)

  • Endocrine(diabetes with neuropathy)

  • Psychiatric(anxiety)

  • Divo M, Cote C, de Torres JP, et al.

    Comorbidities and risk of mortality in patients with chronicbstructivepulmonarydisease

    Am. J. Respir. Crit. Care Med. 2012;186:155 -161.

Dr stefano calabro

COTE Index With COPD



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 chronicbstructivepulmonarydisease

    Am. J. Respir. Crit. Care Med. 2012;186:155 -161.

Dr stefano calabro

William Osler (1849 – 1919) With COPD

«Itismuch more important to knowwhatsort of patienthas a diseasethan to knowwhatkind of a disease a patienthas»

Dr stefano calabro

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.

FamPract 2010, 27:1-2.

Dr stefano calabro

Grazie per l’attenzione guideline for each disease

dr. Stefano Calabro

Dr. Stefano Calabro

REGIONE VENETO – AZIENDA U.L.S.S. n.3Ospedale S. Bassiano - Bassano del GrappaDipartimento di MedicinaStruttura Complessa di Pneumologia

Dr. Rolando Negrin

REGIONE VENETO – AZIENDA U.L.S.S. n.6Ospedale S. Bortolo - VicenzaDipartimento di Area Medica IIUnità Operativa Complessa di Pneumologia

Dr stefano calabro

Corticosteroidi guideline for each diseaseinalatori

$ confronto basato sui dati di efficacia