1. Increased Risk of Exacerbation and Hospitalization in Subjects With an Overlap Phenotype (COPD-Asthma) Ana Maria B. Menezes, MD ; Maria Montes de Oca, MD ; Rogelio Pérez-Padilla, MD ; Gilbert Nadeau, BSc; Fernando César Wehrmeister, PhD; Maria Victorina Lopez-Varela, MD; Adriana Muiño, MD ; José Roberto B. Jardim, MD ; Gonzalo Valdivia, MD ; and Carlos Tálamo, MD, FCCP ; for the PLATINO Team* R1. 이성곤 /prof. 박명재 CHEST 2014; 145(2):297-304

2. Abstract of COPD & Asthma Most prevalent obstructive airway dz. worldwide. (vary global prevalence) Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) -> 14.3% --stages I to IV, >40 yrs 5 Latin American cities (by GOLD: Global Initiative for Chronic Obstructive Lung Disease) Several COPD phenotypes exist : Overlap COPD-asthma(most recognized) Hardin et al : COPD Gene Study ->13% subjects COPD reported physician-diagnosed asthma.

3. Materials and Methods I PLATINO: Multi-center, population-based survey 1)American Thoracic Society (ATS) criteria : baseline vs 15 min after 200 mg salbutamol(bronchodilator:BD) [Portable spirometer (EasyOne spirometer)] *Definition of asthma [post-BD] ① FEV1 15%↑ ② peak flow variability(PEFR) 20%↑(during 1 week) ③ Physician Dx. of asthma + current symptoms

4. Materials and Methods II 2) Outcomes :self-reported exacerbations in the last year ① Deterioration of breathing Sx. (yes/no) [affected usual daily activities or caused missed work] ② Number of hospitalizations d/t the exacerbations (yes/no), ③ Limitations d/t physical health, & pts’ perception of their GHS [excellent/very good/good/fair/poor by the Short Form-12 questionnaire (SF-12)]

5. Materials and Methods III Definition (1) COPD—based on the ratio of the post-BD FEV 1/FVC < 0.70 +lower limit of normal(LLN) (lower 15th percentile) : as another criterion for COPD (2) Asthma ① Wheezing in the last 12 mo. + post-BD -> FEV 1(200 mL) or FVC(12%) ↑ ② “Medical Dx. of asthma”: also (3) Overlap—the combination of the 2 previous dz.

6. Aim of the study (1) Prevalence of three subgroups: asthma, COPD, and COPD-asthma overlap (PLATINO population) (2) Explore the main characteristics: the 3 subgroups (3) Determine the association btw. -> COPD-asthma overlap: Outcomes ① Exacerbation ② Hospitalization ③ Limitation due do physical health ④ Perception of general health status (GHS).

7. Results I Prevalence - 5,044 subjects -> 767 : COPD group 594 (11.7%) + asthmatic group 84 (1.7%) + overlap group 89 (1.8%)

8. Results II-1

9. Results II-2

10. Results III

11. Results IV

12. Discussion I **Principal finding 1) COPD 12%, Asthma 1.7% Overlap 1.8% 2) Overlap : more respiratory Sx., hospitalization, medication worse Lung function, GHS 3) Adjusting : overlap a/w exacerbation, hospitalization compared with COPD -> prevalence is vary -> Lack of consensus ev)The European Community Respiratory Health Survey : geographical difference :English speaking countries vs Mediterranean & Eastern Europe [eg.Manfreda et al, Arif et al 4.5~16.4%] :Latin America[Brazil, highest prevalence wheezing (24.3%) 6th-highest medical diagnosis of asthma (12%) among 70 countries]

13. Discussion II Asthma and COPD are different dz. But share characteristics : co-exist is recognized but not clearly defined *PLATINO (mainly mild COPD) VS COPDGene(more severe COPD-GOLD stages II-IV) *[In this study] – Denominator N=5,044 1.8% -> 11.6%(N=767) cf) Gene Environment Interactions in Respiratory Diseases study, de Marco et al (total sample size as the denominator) :1.6%(95% CI, 1.3%-2.0%) 20~44-yr-old age group 4.5% (95% CI, 3.2%-5.9%) 60~84-yr-old age group.

14. Discussion III 1) Pul. function? *Overlap syndrome: Lung function↓ & more respiratory Sx. than either dz alone. cf) COPDGene study: did not show difference in lung function btw *This study: worse pulmonary function & more respiratory Sx. in the overlap group. 2) QOL? ① COPDGene cohorts: worse disease-related QOL, severe COPD exacerbation, & experience frequent exacerbations (as also Kauppi et al.) ② Our results : a/w worse GHS, more hospitalization & exacerbations(compared with COPD) Higher risk ~ all the outcomes in the overlap phenotype (<- Definition: medically diagnosed asthma & a post-BD FEV 1 /FVC, <0.70).

15. Discussion IV * The mechanisms are difficult to explain *Some limitations: : ① Asthma: official definition VS GINA (Global Initiative for Asthma) e.g) *Wheezing in the last year? : more sensitive & less specific than physician-diagnosed asthma. *Adding BD response : Specificity↑ vs “medical diagnosis” ② COPD - overdiagnose dz. (in older individuals) cf) LLN ③ Exacerbation: Retrospective report of breathing symptoms->recall bias? ④ Crosssectional study -> underestimate the true rate of COPD exacerbations.