4 Master universitario Pneumologia Interventistica La TC nella valutazione del Fenotipo della BPCO Gianna Camiciottoli Dipartimento di Medicina Sperimentale e Clinica Università degli Studi di Firenze Pneumologia e Fisiopatologia Respiratoria Azienda Ospedaliero-Universitaria Careggi
ENFISEMA POLMONARE DEFINIZIONE: abnorme e permanente dilatazione degli spazi aerei distali al bronchiolo terminale, associata a distruzione dei setti alveolari, senza significativa fibrosi. Centrolobulare Panlobulare Parasettale
ENFISEMA POLMONARE Lobulo secondario di Miller Costituito da 3-5 acini (30/50 lobuli primari) forma poliedrica 1-2,5 cm. Setto interlobulare può talora essere visibile in condizione fisiologiche alla periferia del polmone Acino Porzione di parenchima polmonare distale al bronchiolo terminale; comprende bronchioli respiratori, dotti e sacchi alveolari e alveoli, vasi e connettivo Lobulo primario di Miller Porzione di parenchima polmonare distale al bronchiolo respiratorio
ENFISEMA POLMONARE Enfisema centrolobulare : distruzione di tessuto parenchimale nella regione della porzione prossimale dei bronchioli respiratori
ENFISEMA POLMONARE Segni TC
ENFISEMA POLMONARE Segni TC
ENFISEMA POLMONARE Segni TC
ENFISEMA POLMONARE Valutazione TC Evidente sensibilità e accuratezza della TC nell identificazione delle regioni di parenchima polmonare interessate da enfisema Esigenza di quantificare estensione, gravità e progressione Valutazione soggettiva Scale visive Valutazione oggettiva Analisi densitometrica
ENFISEMA POLMONARE Valutazione TC Scala Visiva di GODDART 0 Nessuna alterazione 1 Alterazioni in meno del 25% del parenchima 2 Alterazioni nel 25-50% del parenchima 3 Alterazioni nel 50-75% del parenchima 4 Alterazioni in più del 75% del parenchima Score di enfisema=(visual score / n scansioni x 4 x 2) x 100 Goddard et al, Clinical Radiology 1982
ENFISEMA POLMONARE Valutazione TC Scala Visiva di GODDART
ENFISEMA POLMONARE Valutazione TC Quantitativa
ENFISEMA POLMONARE Valutazione TC Quantitativa MLA (HU) LAA(%)
ENFISEMA POLMONARE Valutazione TC Quantitativa SPIRO-TC 90%CV 10%CV MLA (HU) LAA(%)
www.clipcopd.com
Classification score <0.56 >0.56 Patients with predominant Chronic Bronchitis (n=51) Patients with predominant Emphysema (n=42) Mean lung density (MLA) -874 HU -893 HU p<.0001 % Lung area with density values<-950 HU (LAA) 16% 30% p<.0001
Classification score 0.33 0.67 Predominant Chronic Bronchitis (GOLD stage III) Predominant Emphysema (GOLD stage I)
ENFISEMA POLMONARE Valutazione TC Quantitativa SPIRO-TC 90%CV 10%CV % Wall Area = WA (%) Thickness/Diameter = TDR D L T
GOLD 1 GOLD 2 GOLD 3-4
Risk (GOLD Classification of Airflow Limitation) COPD classification Risk (Exacerbation history) 4 (C) (D) > 2 3 2 (A) (B) 1 1 0 mmrc 0-1 CAT < 10 mmrc > 2 CAT > 10 Symptoms (mmrc or CAT score)
Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy (Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.) Patient Recommended First choice Alternative choice Other Possible Treatments A SAMA prn or SABA prn LAMA or LABA or SABA and SAMA Theophylline B LAMA or LABA LAMA and LABA SABA and/or SAMA Theophylline C ICS + LABA or LAMA LAMA and LABA or LAMA and PDE4-inh. or LABA and PDE4-inh. SABA and/or SAMA Theophylline D ICS + LABA and/or LAMA ICS + LABA and LAMA or ICS+LABA and PDE4-inh. or LAMA and LABA or LAMA and PDE4-inh. Carbocysteine SABA and/or SAMA Theophylline
COPD Severity and Phenotype CT and pulmonary function Quantitative CT provides accurate information about parenchymal destruction and airways disease Both mechanisms concur to determine the overall severity of COPD Their relative predominance determines the clinical phenotype of COPD Can we predict by clinical and pulmonary function data overall severity and predominant type of lung changes assessed by CT?
COPD Severity and Phenotype Subjects and Methods In 473 outpatients with COPD in stable condition we assessed the following clinical and functional data: Cough: absent, occasional, chronic Sputum: absent/occasional, chronic non purulent, chronic purulent mmrc dyspnea score (0 to 4) Dynamic lung volumes: FEV1, FEV1/FVC, FEV1/VC (airway obstruction) Static lung volumes: TLC, FRC, RV (hyperinflation) Diffusing capacity: DLCO (parenchymal destruction) In 100 of these patients (learning set) we measured by CT the % low attenuation area and airway wall thickness to develop predictive models to classify the remaining 373 patients (testing set) according to overall severity and predominant phenotype of COPD. Camiciottoli G, et al. Eur Respir J 2013, in press
CT scan in COPD Quantitative evaluation %LAA-950 AWT-Pi10 (mm) Vida Diagnostics, Coralville, Iowa, http://www.vidadiagnostics.com/
COPD severity and phenotype LAA-950 HU and AWT-Pi10 Principal Component Analysis n=100 learning set (mm) Camiciottoli G, et al. Eur Respir J 2013, in press
COPD severity and phenotype LAA-950 HU and AWT-Pi10 Principal Component Analysis n=100 learning set (mm) Camiciottoli G, et al. Eur Respir J 2013, in press
COPD severity and phenotype CT1 and CT2 Principal Component Analysis Camiciottoli G, et al. Eur Respir J 2013, in press
COPD severity and phenotype severity CT1 and CT2 Principal Component Analysis CT2 is proportional to the sum of the original variables (%LAA-950 plus AWT-Pi10) and reflects then the overall CT severity of COPD Camiciottoli G, et al. Eur Respir J 2013, in press
COPD severity and phenotype severity CT1 and CT2 Principal Component Analysis CT2 is proportional to the sum of the original variables (%LAA-950 plus AWT-Pi10) and reflects then the overall CT severity of COPD phenotype Camiciottoli G, et al. Eur Respir J 2013, in press CT1 is proportional to the difference of the original variables (%LAA-950 minus AWT-Pi10) and reflects then the prevalent mechanism of airflow obstruction (airways or emphysema CT phenotype)
COPD severity and phenotype Predictive models of CT1 and CT2 Predictive models of CT1 and CT2 by multivariate analysis of clinical and pulmonary function variables n=100 Predictors Coefficients R Prediction errors mean mode CT1 phenotype CT2 severity DLCO% purulent sputum TLC% intercept FEV1/VC purulent sputum FRC% intercept -0.018-0.580 0.011 0.324-0.030 0.775 0.013-0.575 0.64 6.7% 2.3% 0.77 6.2% 2.1% The models derived from the learning set of 100 patients were ten fold cross-validated and trained to estimate CT1 and CT2 in the prospective set of 373 patients.
COPD severity and phenotype Prospective validation n=373 testing set (patients who did not undergo CT) C D A B Camiciottoli G, et al. Eur Respir J 2013, in press
COPD severity and phenotype Prospective validation C n=373 testing set n=80 FEV1/VC: 45% FRC: 132% DLCO: 78% n=73 FEV1/VC: 36% FRC: 162% DLCO: 49% D A n=143 FEV1/VC: 60% FRC: 100% DLCO: 88% n=77 FEV1/VC: 52% FRC: 118% DLCO: 61% B Camiciottoli G, et al. Eur Respir J 2013, in press
n=373 testing set C D (patients who did not undergo CT) chronic/ purulent -0.41 chronic/ non purulent 0.07 absent/ occasional 0.30 A B Camiciottoli G et al. Eur Respir J 2013, in press
COPD severity and phenotype severity Prospective validation n=373 prospective set C D purulent sputum FEV1/VC TLC% FRC% DLCO% A phenotype B
Predominant airway disease mixed Predominant emphysema very severe C D very severe severe severe moderate moderate mild A B mild Predominant airway disease mixed Predominant emphysema
COPD: classifications Risk (GOLD Classification of Airflow Limitation) C A D B 4 3 2 1 (C) (A) mmrc 0-1 CAT < 10 (D) (B) mmrc > 2 CAT > 10 Symptoms > 2 1 0 Risk (Exacerbation history) Purulent sputum FEV1/VC TLC% FRC% DLCO% mmrc/cat FEV1 Exacerbation history
4 Master universitario Pneumologia Interventistica COPD: classifications C D A B CT classification GOLD 2013 classification
CT2 (severity) 4 Master universitario Pneumologia Interventistica COPD: classifications CT classification versus GOLD 2013 classification GOLD 2013 GOLD 2013 The GOLD 2013 classification reflects COPD severity, but not the COPD phenotype as assessed by quantitative CT
Risk (GOLD Classification of Airflow Limitation) 4 Master universitario Pneumologia Interventistica COPD: classifications C A CT classification D B 4 3 2 1 (C) (A) mmrc 0-1 CAT < 10 Symptoms GOLD 2013 classification ( (D) (B) mmrc > 2 CAT > 10 2 1 0 Risk -Exacerbation history)
severity 4 Master universitario Pneumologia Interventistica C D A B C D A B phenotype
severity 4 Master universitario Pneumologia Interventistica C D GOLD D GOLD D A B C D GOLD A GOLD C A B phenotype
severity 4 Master universitario Pneumologia Interventistica C D A B C D A phenotype B
severity 4 Master universitario Pneumologia Interventistica C D GOLD D GOLD D A B C D GOLD A GOLD C A phenotype B
Conclusions COPD is a heterogeneous disorder with different clinical manifestations or phenotypes, and with various degrees of severity Quantitative CT depicts accurately both phenotypes and severity of COPD in vivo Multivariate models including lung function and sputum characteristics allow patients classification of phenotype and severity in agreement with quantitative CT findings A simple method to phenotype COPD and graduate severity could be useful in biological and epidemiological studies and in pharmacological trials.