Economic Burden of Chronic Obstructive Pulmonary Disease (COPD): A Systematic Literature Review

Figures & data

Table 1 Summary of Included Studies (n=73 Studies)

Author, Year	Study Design [Length of Follow-Up], Sample Size	Country and Setting	Groups of Patients with Economic Data Available
AbuDagga, 2013^Citation29	Retrospective cohort [1 year] N=17,382	Country: US Setting: Inpatient and outpatient	Patients with ≥1 ED visit, ≥1 hospitalization or ≥2 physician office visits for chronic bronchitis during follow-up period
Abusaid, 2009^Citation19	Retrospective cohort [2 years] N=139	Country: US Setting: Inpatient	COPD patients (FEV1<80% predicted) with history of exacerbations (who were hospitalized for an exacerbation at the time of enrollment) Subgroup data by the presence of DD
Benzo, 2016^Citation48	Cross-sectional [HRU data were obtained for the 12 months preceding study entry] N=310	Country: US Setting: Outpatient	Moderate-to-very severe COPD (FEV1<80% predicted)
Blasi, 2014^Citation24	Retrospective cohort [29 months] N=15,857	Country: Italy Setting: Inpatient and outpatient	Patients with history of exacerbations prior to a severe exacerbation at enrollment Subgroup data by frequency and severity of COPD exacerbations that occurred over 3-year period prior to the index event
Bu, 2011^Citation59	Prospective cohort [2 years] N=56	Country: Australia Setting: Community	Moderate-to-very severe COPD patients (FEV1<80% predicted; GOLD criteria [2006]) Subgroup data by BODE score
Bustamante-Fermosel, 2007^Citation12	Retrospective cohort [1 year] N=763	Country: Spain Setting: Inpatient	Mild-to-very severe COPD patients (GOLD criteria [2005]) with history of exacerbations
Carrasco Garrido, 2006^Citation60 Publications linked by named source: de Miguel-Diez, 2010^Citation28	Cross-sectional [HRU data provided for 12-month period] N=10,711	Country: Spain Setting: Primary care	Moderate-to-very severe COPD (FEV1<80% predicted)
Chen, 2009^Citation41	Retrospective cohort [1 year] N=108,726	Country: Canada Setting: Inpatient (acute care hospitals)	Patients with history of exacerbations (who were hospitalized for an exacerbation of COPD at enrollment)
Collins, 2012^Citation61	Prospective cohort [median 4.8 years] N=90	Country: US Setting: Outpatient	Moderate-to-severe COPD (self-reported severity)
Dalal, 2010a^Citation62 Publications linked by named data source: Lindenauer, 2006;^Citation63 Silver, 2010;^Citation32 Xu, 2012^Citation21	Retrospective cohort [30–60 days] N=NR [data were reported in terms of healthcare encounters in 2008, N=28,001 inpatient admissions and N=10,322 ED visits]	Country: US Setting: Inpatient and ED	Patients with moderate (ED) and severe (inpatient hospitalizations) exacerbations at enrollment Subgroup data by study year (2005–2008)
Dalal, 2010b^Citation64	Retrospective cohort [data were obtained for 60 days of index admission and the preceding year] N=NR [data were reported in terms of N=85,789 healthcare episodes (inpatient and ED) related to exacerbations]	Country: US Setting: Inpatient and ED	Patients with moderate (ED) and severe (inpatient hospitalizations) exacerbations at enrollment
Dalal, 2015^Citation22 Publications linked by sample: Patel, 2013^Citation65	Retrospective cohort [3 years] N=61,750	Country: US Setting: Inpatient	Patients hospitalized at enrollment Subgroup data by year of study and frequency of exacerbations during hospital admission index year
de Miguel-Diez, 2010^Citation28 Publications linked by named source: Carrasco Garrido, 2006^Citation60	Retrospective cohort [1 year] N=9390	Country: Spain Setting: Outpatient	Moderate-to-severe COPD (FEV1<80% predicted) Subgroup data for patients with or without heart disease
Dhamane, 2016^Citation35 Publications linked by sample: Dhamane, 2015^Citation66	Cross-sectional [data were collected for the 6 months prior to index] N=2497	Country: US Setting: Community (population-based)	Mild-to-severe COPD (self-reported disease severity) Subgroup data by COPD severity
Dushianthan, 2010^Citation67	Retrospective cohort [NR; data collected during ICU stay for exacerbation of COPD, mean 6.8 days] N=64	Country: UK Setting: ICU	Patients with severe COPD (not further defined) admitted to ICU for an exacerbation of COPD
DuVall, 2015^Citation47	Retrospective cohort [30 and 60 days] N=89,502	Country: US Setting: Inpatient	Patients hospitalized at enrollment
Escarrabill, 2015^Citation39	Retrospective cohort [90 days] N=910	Country: Spain Setting: Inpatient	Moderate-to-very severe COPD (FEV1<80% predicted) in patients admitted for an acute exacerbation of COPD at enrollment
Esteban, 2016^Citation68	Prospective cohort [2 years] N=543	Country: Spain Setting: Outpatient	Moderate-to-very severe COPD (FEV1<80% predicted) Subgroup data by disease severity clusters (based on pulmonary function, age, smoking history, comorbidities and other factors)
Foo, 2016^Citation30	Cross-sectional [NA] N=4343	Country: Data reported for UK, US, Mexico, Brazil, France, Germany, Italy, Spain, the Netherlands, Russia, Japan and South Korea separately Setting: Community	COPD patients (costs per exacerbation/hospitalization reported)
Gadre, 2014^Citation69	Retrospective cohort [NR] N=677	Country: US Setting: Inpatient	Patients with severe COPD (based on clinical history and chronic hypercapnia/hypoxia) who were hospitalized for acute respiratory failure requiring mechanical ventilation
Gallego, 2016^Citation34	Prospective cohort [1 year] N=118	Country: Spain Setting: Outpatient	Severe-to-very severe COPD (FEV1<50% predicted; GOLD criteria [2013]) and ≥3 exacerbations in the previous year
Garcia-Aymerich, 2004^Citation70	Cross-sectional [NA] N=346	Country: Spain Setting: Inpatient	Severe COPD (not further defined) who were hospitalized (or remaining in ED for at least 18 hrs) for a COPD exacerbation Subgroup data by energy expenditure in physical activity
Garcia-Aymerich, 2011^Citation33	Retrospective cohort [10 years] N=20,571	Country: US Setting: Community (population-based)	COPD patients Subgroup data by COPD disease severity (based on FEV1% predicted)
García-Polo, 2012^Citation50	Cross-sectional [NA] N=115	Country: Spain Setting: NR [likely to be outpatient because although at least some patients in the high HRU group had been hospitalized in the previous year, the study states that data were from patients monitored by the respiratory services of Spanish public hospitals, suggesting that they were not currently hospitalized]	COPD patients (some were hospitalized at enrollment) Subgroup data by HRU (high vs low)
Gatheral, 2014^Citation45	Retrospective cohort [3.5 years] N=406	Country: UK Setting: Inpatient	Patients hospitalized at enrollment
Gavazzi, 2015^Citation71	Prospective cohort [mean follow-up of 6 (SD: 4) months] N=267	Country: Italy Setting: Outpatient	Patients with advanced heart failure or COPD (likely to be very severe COPD as all patients had to have FEV1<30% predicted, or hypoxemia [PaO2<55 mmHg], or hypercapnia [PaCO2>45 mmHg, ie above the upper threshold of normal], or to be on LTOT for >8 hrs/day)
Huang, 2014^Citation72	Retrospective cohort [mean 2 years] N=756	Country: US Setting: Inpatient	Patients hospitalized at enrollment who were on LTOT
Keilty, 2013^Citation73	Prospective cohort [1 year] N=119	Country: UK Setting: Inpatient	Patients hospitalized at enrollment for an acute exacerbation of COPD requiring NIV
Koleva, 2007^Citation7	Prospective cohort [1 year] N=268	Country: Italy Setting: Outpatient	Moderate-to-very severe COPD (FEV1<80% predicted; GOLD criteria [2006]) Subgroup data by disease severity
Lindenauer, 2006^Citation63 Publications linked by named data source: Dalal, 2010;^Citation62 Silver, 2010;^Citation32 Xu, 2012^Citation21	Retrospective cohort [30 days] N=69,820	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an acute exacerbation of COPD
Lusuardi, 2008^Citation74	Prospective cohort [6 months] N=570	Country: Italy Setting: Inpatient and outpatient	Moderate-to-very severe COPD (stage 2–4; GOLD criteria [2004]) Subgroup data by disease severity and a history of exacerbations
Mahmud, 2015^Citation37	Retrospective cohort [30 days] N=2,723,541	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an acute exacerbation of COPD Subgroup data (for patients with/without reflux esophagitis)
Mapel, 2011^Citation17	Retrospective cohort [1 year] N=51,072	Country: US Setting: Inpatient	Low-to-high complex COPD (based on comorbid respiratory conditions and medical procedures) Subgroup data by type of healthcare coverage and complexity of disease
Martín, 2008^Citation14	Cross-sectional [HRU data provided for a 12-month period] N=9405	Country: Spain Setting: Primary care centers and hospital outpatient clinics	Moderate-to-very severe COPD (FEV1<80% predicted) Subgroup data by disease severity
Matkovic, 2012^Citation75	Prospective cohort [1 month] N=155	Country: Spain Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
McGhan, 2007^Citation40	Retrospective cohort [up to 6 years] N=51,353	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
Merinopoulou, 2016^Citation8 Publications linked by named data source: Mullerova, 2014;^Citation9 Punekar, 2013a;^Citation76 Punekar, 2013b;^Citation77 Punekar, 2013c;^Citation78 Punekar, 2015;^Citation15 Punekar, 2014^Citation18 Publications linked by sample: Merinopoulou, 2015^Citation79	Retrospective database [accrual years: January 1, 2011–December 31, 2013] N=44,201	Country: UK Setting: Primary and secondary care	Patients with low-to-high risk COPD (A–D; GOLD criteria [2013]) Subgroup data by disease severity and by data accrual year (2011–2013)
Miravitlles, 2006^Citation25	Cross-sectional [HRU data provided for 12-month period] N=1057	Country: Spain Setting: Outpatient	Moderate-to-severe COPD (FEV1<70% predicted) Subgroup data by frequency of exacerbations in the previous year
Mittmann, 2008^Citation20 Publications linked by sample: FitzGerald, 2007^Citation80	Prospective cohort [1 year] N=609	Country: Canada Setting: Primary care	Moderate-to-very severe COPD (FEV1≤65% predicted) Subgroup data by exacerbation severity
Molinari, 2015^Citation81	Retrospective cohort [accrual years: 2007–2012] N=12,751	Country: France Setting: General practice	Patients hospitalized at enrollment due to an exacerbation of COPD Subgroup data by hospitalization severity and hospital admission year
Mullerova, 2014^Citation9 Publications linked by named source: Merinopoulou, 2016;^Citation8 Punekar, 2013a;^Citation76 Punekar, 2013b;^Citation77 Punekar, 2013c;^Citation78 Punekar, 2015;^Citation15 Punekar, 2014^Citation18	Retrospective cohort (mean 2.5 [SD: 1.6] years) N=52,237	Country: UK Setting: Primary care	Patients with low-to-high risk COPD (A–D; GOLD criteria [2011/2013]) Subgroup data by disease severity
Nantsupawat, 2012^Citation46	Retrospective cohort [30 days’ follow-up, mean 16 days] N=81	Country: US Setting: Inpatient	Mild-to-very severe COPD Subgroup data by disease severity
Nguyen, 2014^Citation44	Retrospective cohort [30 days] N=4871	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
Nishi, 2015^Citation49	Retrospective cohort [1 year] N=329,482	Country: US Setting: Inpatient and outpatient	Patients hospitalized at enrollment due to an exacerbation of COPD or who had ≥2 outpatient visits >30 days apart within 1 year of the encounter diagnosis of COPD
Pasquale, 2012^Citation23	Retrospective cohort [2 years] N=8554	Country: US Setting: Inpatient and outpatient	COPD patients Subgroup data by exacerbation frequency
Philip, 2010^Citation82	Retrospective cohort [2 years] N=30,179	Country: Australia Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
Pitassi, 2015^Citation83	Retrospective cohort [accrual years: 2010–2014] N=212	Country: Italy Setting: Inpatient	Moderate-to-severe COPD (GOLD criteria [2011]) in patients hospitalized for an exacerbation of COPD Subgroup data by bronchiectasis
Pretto, 2012^Citation84	Retrospective cohort [3 months] N=203	Country: Australia Setting: Acute care public hospitals	Patients hospitalized at enrollment due to an acute exacerbation of COPD Subgroup data by type of hospital
Punekar, 2014^Citation18 Publications linked by named data source: Punekar, 2013a;^Citation76 Punekar, 2013b;^Citation77 Punekar, 2013c;^Citation78 Punekar, 2015a;^Citation10 Punekar, 2015b^Citation15 Publications linked by sample: Punekar, 2013a;^Citation76 Punekar, 2013c^Citation78	Retrospective cohort [12 months] N=58,589	Country: UK Setting: General practice	Mild-to-very severe COPD (GOLD criteria [2006]) Subgroup data by disease stage (1–4) and frequency of exacerbations
Punekar, 2015a^Citation10 Publications linked by named data source: Punekar, 2013a;^Citation76 Punekar, 2013b;^Citation77 Punekar, 2013c;^Citation78 Punekar, 2014^Citation18 Punekar, 2015b^Citation15	Retrospective cohort [24 months] N=7881	Country: UK Setting: Primary care	Mild-to-very severe COPD (GOLD criteria [2006]) Subgroup data by disease severity
Punekar, 2015b^Citation15 Publications linked by named data source: Punekar, 2013a;^Citation76 Punekar, 2013b;^Citation77 Punekar, 2013c;^Citation78 Punekar, 2014^Citation18 Punekar, 2015a^Citation10 Publications linked by sample: Punekar, 2013b^Citation77	Retrospective cohort [12 months] N=39,639	Country: UK Setting: General practice	Patients on triple therapy (assumed to have moderate-to-very severe COPD) Subgroup data by type of treatment
Quintana, 2014^Citation43	Prospective cohort [2 months] N=2332	Country: Spain Setting: Inpatient including ED	Patients visiting ED at enrollment, of whom a portion were hospitalized
Roberts, 2011a^Citation31 Publications linked by sample: Short, 2013^Citation85	Retrospective cohort [NR] N=6576	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
Roberts, 2011b^Citation86	Retrospective cohort [90 days] N=9716	Country: UK Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
Sharafkhaneh, 2014^Citation87	Retrospective cohort [1 year] N=66,004	Country: US Setting: NR (claims database)	Subgroup data on COPD patients with ≥1.5 doses of SABA per day compared with <1.5 doses
Short, 2013^Citation85	Prospective cohort [30 days] N=1343	Country: UK Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
Silver, 2010^Citation32 Publications linked by named data source: Dalal, 2010;^Citation62 Lindenauer, 2006;^Citation63 Xu, 2012^Citation21	Cross-sectional [NA] N=69,841	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD
Small, 2016^Citation27	Cross-sectional [NA] N=420	Country: Japan Setting: General practice	Subgroup data by dyspnea severity
Stanford, 2006^Citation36	Retrospective cohort [30 days] N=NR [number of hospital encounters, N=59,735]	Country: US Setting: ED and inpatient	Patients hospitalized at enrollment due to an exacerbation of COPD Subgroup data by type of hospital admission
Steer, 2015^Citation88	Prospective cohort [1 year] N=183	Country: UK Setting: Outpatient	Patients hospitalized at enrollment due to an exacerbation of COPD (with data available following discharge from hospital) Subgroup data by ventilation use
Stefan, 2014^Citation89	Prospective cohort [NR] N=3520	Country: US Setting: Inpatient	Patients admitted to ICU at enrollment due to a severe acute exacerbation of COPD
Stefan, 2015^Citation90	Retrospective cohort [1 year] N=NR [number of COPD admissions, N=723,560]	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an acute exacerbation of COPD
Suissa, 2012^Citation42	Retrospective cohort [17 years] N=73,106	Country: Canada Setting: NR (health insurance program database study)	Patients with first-ever hospitalization at enrollment due to a severe exacerbation of COPD
Thomas, 2014^Citation11 Publications linked by sample: Thomas, 2011^Citation91	Retrospective cohort [3 years] N=511	Country: UK Setting: General practice	Mild-to-very severe COPD (mild-to-moderate: FEV1≥50% predicted; severe: FEV1 30–49% predicted; and very severe: FEV1<30% predicted; NICE guideline [2010]). Subgroup data by disease severity and exacerbation frequency
Tran, 2016^Citation51	Retrospective cohort [6 months] N=210	Country: US Setting: Inpatient	Patients hospitalized at enrollment due to an acute exacerbation of COPD
Valido, 2014^Citation13	Retrospective cohort [4 months] N=100	Country: Spain Setting: NR	COPD patients Subgroup data by frequency of exacerbations
Vallabhajosyula, 2015^Citation38	Retrospective cohort [5 years from discharge] N=1145	Country: US Setting: Inpatient	Patients treated for an acute exacerbation at enrollment
Vitacca, 2007^Citation92	Retrospective cohort [1 year] N=289	Country: Italy Setting: Inpatient and outpatient	Patients on home mechanical ventilation (assumed to have severe disease)
Vitacca, 2011^Citation26	Prospective cohort [1 year] N=83	Country: Italy Setting: Outpatient	Very severe COPD (FEV1<30% predicted) Subgroup data by type of home treatment
Wang, 2005^Citation93	Retrospective cohort [phase I/baseline data: 12 months; Phase II/follow-up from hospital discharge: 2.5 years] Phase I: N=282 Phase II/follow-up from hospital discharge: N=54	Country: Canada Setting: Inpatient	Moderate-to-very severe COPD (FEV1<80% predicted) in patients hospitalized for an acute exacerbation of COPD at enrollment to the study
Xu, 2012^Citation21 Publications linked by named data source: Dalal, 2010;^Citation62 Lindenauer, 2006;^Citation63 Silver, 2010^Citation32	Retrospective cohort [NR] N=21,017	Country: US Setting: Inpatient	Patients hospitalized at enrollment into the study due to an acute exacerbation of COPD
Yeo, 2006^Citation16	Cross-sectional [NA] N=27	Country: UK Setting: General practice	Moderate-to-very severe COPD (FEV1<80% predicted; BTS guidelines [1997]) Subgroup data by disease severity
Yu, 2011^Citation94	Retrospective cohort [mean 2.9 (SD: 1.3) years] N=228,978	Country: US Setting: Hospital (healthcare service claims)	Patients with ≥1 COPD exacerbation recorded in the Thomson Reuters MarketScan administrative claims database Subgroup data by severity of exacerbations per patient-quarters

Abbreviations: BODE, Body mass index, airflow Obstruction, Dyspnea and Exercise capacity; BTS, British Thoracic Society; COPD, chronic obstructive pulmonary disease; DD, diastolic dysfunction; ED, emergency department; FEV₁, forced expiratory volume in 1 s; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HRU, healthcare resource utilization; ICU, intensive care unit; LTOT, long-term oxygen therapy; NA, not applicable; NICE, National Institute for Health and Care Excellence; NIV, non-invasive ventilation; NR, not reported; PaCO₂, arterial partial pressure of carbon dioxide; PaO₂, arterial partial pressure of oxygen; SABA, short-acting β₂-agonist; SD, standard deviation; UK, United Kingdom; US, United States.

Figure 1 Identification of studies for inclusion in the systematic literature review (following systematic processes outlined in PRISMA guidelines).

Note: Adapted from Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.⁶
Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2 Location of included studies.

Notes: Australia (n=3), Canada (n=4), France (n=2), Germany (n=1), Italy (n=8), Japan (n=2), Spain (n=14), UK (n=14), US (n=31). Some publications reported data from multiple countries.
Abbreviations: UK, United Kingdom; US, United States.

Figure 3 Number of studies reporting on each outcome.

Abbreviation: HRU, healthcare resource utilization.

Table 2 Multivariate Analyses of HRU (n=24 Studies)

Type of HRU	Independent Drivers (Positive)	Independent Drivers (Negative)
Hospitalization
For a COPD exacerbation  or respiratory cause	Restricted lung function;^Citation33 GOLD stages 0–4 (vs normal lung function);^Citation33 baseline hypercapnia;^Citation34 C-reactive protein concentration (47.8–100 mg/L; >100 mg/L)^Citation34	NR
For any cause	Use of LTOT;^Citation25 increasing number of previous exacerbations;^Citation25 use of SABA;^Citation25 SGRQ total score;^Citation25 incomplete primary education;^Citation25 disease severity^Citation35	NR
Length of hospital stay for  a COPD exacerbation	Level of hospital (number of discharges for acute COPD exacerbations);^Citation39 diagnosis of reflux esophagitis;^Citation37 cor pulmonale;^Citation31 stroke;^Citation31 left ventricular failure;^Citation31 cardiac arrhythmia/dysrhythmia;^Citation31,Citation32 other malignant disease;^Citation31 thromboembolic disease;^Citation31 locomotor problems;^Citation31 number of comorbid conditions (vs none);^Citation31 congestive heart failure;^Citation32 pulmonary vascular disease;^Citation32 pneumonia;^Citation32 intrathoracic malignancies;^Citation32 anemia;^Citation32 renal failure;^Citation32 weight loss;^Citation32 anxiety/depression;^Citation32 age;^Citation36 female (vs male);^Citation36 CCI;^Citation36 East/South US-based (vs North-based);^Citation36 hospital size;^Citation36 referral, transfer or routine admission (vs ED admission);^Citation36 ICU treatment;^Citation36 intubation;^Citation36 severe COPD;^Citation38 BNP level^Citation38	No diagnosis of reflux disease;^Citation37 chronic airway obstruction (vs chronic bronchitis);^Citation36 West US-based (vs North-based);^Citation36 Medicaid plan (vs Medicare);^Citation36 Blue Cross/Blue Shield (vs Medicare);^Citation36 health maintenance organization (vs Medicare);^Citation36 commercial (vs Medicare);^Citation36 other plan (vs Medicare);^Citation36 teaching hospital (vs non-teaching);^Citation36 other route of admission (vs ED admission)^Citation36
ICU
Admission	Congestive heart failure;^Citation32 cardiac dysrhythmia;^Citation32 pulmonary vascular disease;^Citation32 pneumonia;^Citation32 anemia;^Citation32 renal failure;^Citation32 weight loss;^Citation32 anxiety/depression^Citation32	NR
Length of stay	Severe COPD;^Citation38 BNP level^Citation38	NR
GP/traditional healthcare provider visits	Female gender;^Citation10 obesity;^Citation10 depression;^Citation10 anxiety;^Citation10 presence of ≥1 comorbidity^Citation10	NR
Ventilation	Year (annual change);^Citation90 age-by-year interaction, ≥85 years (vs <65 years);^Citation90 Gagne Comorbidity score (vs ≤1);^Citation90 presence of concomitant pneumonia (vs no pneumonia);^Citation90 previous admissions for COPD;^Citation90 BNP level^Citation38	Female (vs male);^Citation90 age-by-year interaction, 65–74 years, 75–84 years (vs <65 years);^Citation90 race-by-year interaction, Hispanic, black or other race (vs white race)^Citation90
Readmission
For a COPD  exacerbation or  respiratory cause	History of coronary artery disease;^Citation46 unilateral pulmonary infiltrates on admission;^Citation46 hospitalizations in previous year;^Citation43,Citation44 anemia;^Citation44 ≥3 chronic conditions;^Citation44 new oxygen prescription at discharge;^Citation44 baseline FEV1% predicted <30% (vs ≥50%);^Citation43 baseline dyspnea (MRC score 5 vs 1);^Citation43 dyspnea 1 week post-index ED visit;^Citation43 ischemic heart disease (women only);^Citation41 congestive heart disease;^Citation41 arrhythmia (women only);^Citation41 pulmonary heart disease;^Citation41 CCI;^Citation41 male gender;^Citation40,Citation42 modified chronic disease score (vs first quartile);^Citation42 pulmonary hypertension;^Citation40 prior hospitalization;^Citation40 asthma;^Citation40 age;^Citation40 no inclusion in a hospital-at-home program;^Citation39 severity of bronchiectasis^Citation45	Age (per 10 years);^Citation42 cohort entry after year 2000;^Citation42 previous COPD diagnosis;^Citation39 LTOT use;^Citation39 better FEV1% predicted;^Citation39 regular physical activity;^Citation39,Citation44 diabetes (complicated or uncomplicated);^Citation40 hypertension (complicated or uncomplicated);^Citation40 Hispanic race^Citation40
For any cause^a	Previous hospitalization;^Citation47 moderate/severe liver disease;^Citation47 paraplegia;^Citation47 pulmonary hypertension;^Citation47 substance abuse;^Citation47 heart failure;^Citation47 cor pulmonale;^Citation31 lung cancer;^Citation31 neurologic condition;^Citation31 left ventricular failure;^Citation31 alcohol-related condition;^Citation31 ischemic heart disease;^Citation31 diabetes;^Citation31 number of conditions^Citation31	Other cardiovascular disease^Citation31
ED visits^b	COPD severity;^Citation35 emotional intelligence^Citation48	NR
LTOT	Low socioeconomic status;^Citation49 Elixhauser Comorbidity score (vs 0);^Citation49 study recruitment years 2002–2008 (vs 2001);^Citation49 US region (vs New England)^Citation49	Age ≥85 years (vs 66–74 years);^Citation49 male gender;^Citation49 black or other race (vs white race);^Citation49 study recruitment year 2009–2010 (vs 2001)^Citation49
High HRU^c	London Chest Activity of Daily Living Scale score;^Citation50 leukocyte count;^Citation50 fibrinogen level^Citation50	Hemoglobin oxygen saturation^Citation50

Notes: ^aLiving alone, COPD exacerbation frequency and not having a family doctor were also described as drivers through multivariate analysis, but inconsistencies in data reporting rendered these results difficult to interpret in terms of the nature of their association.⁹³ bAge, comorbidity, FEV₁% predicted, SGRQ total score, COPD exacerbation frequency, LTOT and not having a family doctor were also described as drivers through multivariate analysis, but inconsistencies in data reporting rendered these results difficult to interpret in terms of the nature of their association.⁹³ cDefined as admission for a COPD exacerbation, ≥2 ED visits for COPD exacerbations or ≥2 unscheduled outpatient visits related to COPD.

Abbreviations: BNP, B-type natriuretic peptide; CCI, Charlson Comorbidity Index; COPD, chronic obstructive pulmonary disease; ED, emergency department; GOLD, Global Initiative for Chronic Obstructive Lung Disease; FEV₁, forced expiratory volume in 1 s; GP, general practitioner; HRU, healthcare resource utilization; ICU, intensive care unit; LTOT, long-term oxygen therapy; MRC, Medical Research Council; NR, not reported; SABA, short-acting β₂-agonist; SGRQ, St. George’s Respiratory Questionnaire; US, United States.

Table 3 Multivariate Analyses of Direct Costs (n=7 Studies)

Measure of Direct Costs	Independent Drivers (Positive)	Independent Drivers (Negative)
Costs per patient	MRC dyspnea scale score;^Citation27 receipt of appropriate pharmacotherapy with an inhaled bronchodilator (vs no receipt);^Citation51 older age (vs younger age);^Citation51 higher pre-index costs;^Citation51 longer length of stay at baseline admission;^Citation51 black or other race (vs white race);^Citation23 income (high vs not high^a);^Citation23 cardiovascular disease (vs no cardiovascular disease);^Citation23 diabetes (vs no diabetes);^Citation23 ICS + LABA maintenance medication;^Citation23 LAMA maintenance medication;^Citation23 LABA maintenance medication;^Citation23 LTOT use;^Citation23 exacerbation severity;^Citation23 health plan type (vs preferred provider organization);^Citation29 Deyo-Charlson Comorbidity Index;^Citation29 prescription fills for SAMA rescue medications;^Citation29 exacerbation frequency^Citation29	Age;^Citation23 Northeast US geographical region (vs South);^Citation29 prescription fills for fixed-dose ICS + LABA rescue medication^Citation29
Costs per hospitalized exacerbation^b	Hispanic race (vs white race);^Citation31 age;^Citation36 CCI;^Citation36 female gender (vs male);^Citation36 emphysema (vs chronic bronchitis);^Citation36 ICU treatment (vs no ICU treatment);^Citation36 intubation;^Citation36 East or West US geographical location (vs North);^Citation36 hospital size (medium or large vs small);^Citation36 congestive heart failure;^Citation32 ischemic heart disease;^Citation32 cardiac dysrhythmia;^Citation32 pulmonary vascular disease;^Citation32 pneumonia;^Citation32 intrathoracic malignancies;^Citation32 anemia;^Citation32 renal failure;^Citation32 weight loss/cachexia;^Citation32 anxiety and depression^Citation32	South US geographical location (vs North);^Citation36 transfer, routine or other admission (vs ED admission);^Citation36 Medicaid or Blue Cross/Blue Shield (vs Medicare);^Citation36 health maintenance organization or commercial cover (vs Medicare)^Citation36

Notes: ^aHigh income was defined as income ≥$52,480 (USD). ^bCOPD severity, length of hospital stay, number of days in the ICU and treatment in an urban hospital or teaching hospital were also identified as significant drivers of direct costs, but the direction of the association was not clearly reported.³¹

Abbreviations: CCI, Charlson Comorbidity Index; COPD, chronic obstructive pulmonary disease; ED, emergency department; ICS, inhaled corticosteroid; ICU, intensive care unit; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; LTOT, long-term oxygen therapy; MRC, Medical Research Council; SAMA, short-acting muscarinic antagonist; US, United States; USD, United States dollars.

AbudaggaA, SunSX, TanH, SolemCT. Exacerbations among chronic bronchitis patients treated with maintenance medications from a US managed care population: an administrative claims data analysis. Int J Chron Obstruct Pulmon Dis. 2013;8:175–185. doi:10.2147/COPD.S4043723589684

 PubMed Web of Science ®Google Scholar

AbusaidGH, BarbagelataA, TueroE, MahmoodA, SharmaG. Diastolic dysfunction and COPD exacerbation. Postgrad Med. 2009;121(4):76–81. doi:10.3810/pgm.2009.07.203319641273

 PubMed Web of Science ®Google Scholar

BenzoRP, KirschJL, DuloheryMM, Abascal-BoladoB. Emotional intelligence: a novel outcome associated with wellbeing and self-management in chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2016;13(1):10–16. doi:10.1513/AnnalsATS.201508-490OC26501370

 PubMed Web of Science ®Google Scholar

BlasiF, CesanaG, ContiS, et al. The clinical and economic impact of exacerbations of chronic obstructive pulmonary disease: a cohort of hospitalized patients. PLoS One. 2014;9(6):e101228. doi:10.1371/journal.pone.010122824971791

 PubMed Web of Science ®Google Scholar

BuXN, YangT, ThompsonMA, HutchinsonAF, IrvingLB. Changes in the BODE index, exacerbation duration and hospitalisation in a cohort of COPD patients. Singapore Med J. 2011;52(12):894–900.22159933

 PubMed Web of Science ®Google Scholar

Bustamante-FermoselA, De Miguel-yanesJM, Duffort-FalcóM, MunozJ. Mortality-related factors after hospitalization for acute exacerbation of chronic obstructive pulmonary disease: the burden of clinical features. Am J Emerg Med. 2007;25(5):515–522. doi:10.1016/j.ajem.2006.09.01417543654

 PubMed Web of Science ®Google Scholar

Carrasco GarridoP, de Miguel DíezJ, Rejas GutiérrezJ, et al. Negative impact of chronic obstructive pulmonary disease on the health-related quality of life of patients. Results of the EPIDEPOC study. Health Qual Life Outcomes. 2006;4:31. doi:10.1186/1477-7525-4-3116719899

 PubMed Web of Science ®Google Scholar

de Miguel-díezJ, Carrasco-GarridoP, Rejas-GutierrezJ, et al. The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings. BMC Cardiovasc Disord. 2010;10:8. doi:10.1186/1471-2261-10-820167091

 PubMed Web of Science ®Google Scholar

ChenY, LiQ, JohansenH. Age and sex variations in hospital readmissions for COPD associated with overall and cardiac comorbidity. Int J Tuberc Lung Dis. 2009;13(3):394–399.19275803

 PubMed Web of Science ®Google Scholar

CollinsEG, HalabiS, LangstonM, SchnellT, TobinMJ, LaghiF. Sexual dysfunction in men with COPD: impact on quality of life and survival. Lung. 2012;190(5):545–556. doi:10.1007/s00408-012-9398-422752718

 PubMed Web of Science ®Google Scholar

DalalAA, ShahM, D’SouzaAO, RaneP. Costs of inpatient and emergency department care for chronic obstructive pulmonary disease in an elderly Medicare population. J Med Econ. 2010a;13(4):591–598. doi:10.3111/13696998.2010.52173420854113

 PubMedGoogle Scholar

LindenauerPK, PekowP, GaoS, CrawfordAS, GutierrezB, BenjaminEM. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2006;144(12):894–903. doi:10.7326/0003-4819-144-12-200606200-0000616785478

 PubMed Web of Science ®Google Scholar

SilverH, BlanchetteCM, RobertsM, PetersenH, StCharlesME. Prevalence of comorbidities in patients hospitalized for COPD exacerbations and impact on impatient mortality and hospital expenditures. Am J Respir Crit Care Med. 2010;181:A5943. doi:10.1164/rccm.200904-0493OC

 Web of Science ®Google Scholar

XuX, KnightT, BaikR, TuX, ParkerJM. Patient characteristics, health resource utilization (HRU) and treatment costs of chronic obstructive pulmonary disease (COPD) patients treated in hospital facilities for exacerbations. Am J Respir Crit Care Med. 2012;185:A3047.

 Google Scholar

DalalAA, ShahM, D’SouzaAO. Economic burden of health care admissions related to chronic obstructive pulmonary disease exacerbations: data from inpatient administrative database. Am J Respir Crit Care Med. 2010b;181:A1492.

 Web of Science ®Google Scholar

DalalAA, PatelJ, D’SouzaA, FarrellyE, NagarS, ShahM. Impact of COPD exacerbation frequency on costs for a managed care population. J Manag Care Spec Pharm. 2015;21(7):575–583. doi:10.18553/jmcp.2015.21.7.57526108382

 PubMed Web of Science ®Google Scholar

PatelJ, DalalAA, NagarS, D’SouzaAO, ShahM, FarrellyE. Economic burden of frequently and infrequently exacerbating patients with a diagnosis of COPD. Am J Respir Crit Care Med. 2013;187:A1437.

 Web of Science ®Google Scholar

DhamaneAD, WittEA, SuJ. Associations between COPD severity and work productivity, health-related quality of life, and health care resource use: a cross-sectional analysis of national survey data. J Occup Environ Med. 2016;58(6):e191–e197. doi:10.1097/JOM.000000000000073527206123

 PubMed Web of Science ®Google Scholar

DhamaneA, WittEA, HernandezG, SuJ. Association between COPD severity and work productivity, quality of life and healthcare resource use. Am J Respir Crit Care Med. 2015;191:A4447.

 Web of Science ®Google Scholar

DushianthanA, TemblettP, BhattaA. Outcome of a cohort of older population with COPD, admitted with hypercapnaeic respiratory failure and acidosis. Am J Respir Crit Care Med. 2010;181:A1506. doi:10.1164/rccm.200904-0493OC

 Web of Science ®Google Scholar

DuVallS, BrownK, NiciL, et al. Incidence and predictors of hospital readmission among patients with chronic obstructive pulmonary disease in the Department of Veterans Affairs. Chest. 2015;148(4 Suppl):684A. doi:10.1378/chest.2223166

 Web of Science ®Google Scholar

EscarrabillJ, TorrenteE, EsquinasC, et al. Clinical audit of patients hospitalized due to COPD exacerbation. MAG-1 Study. Arch Bronconeumol. 2015;51(10):483–489. doi:10.1016/j.arbres.2014.06.02325447590

 PubMed Web of Science ®Google Scholar

EstebanC, ArosteguiI, AburtoM, et al. Chronic obstructive pulmonary disease subtypes. Transitions over time. PLoS One. 2016;11(9):e0161710. doi:10.1371/journal.pone.016171027611911

 PubMed Web of Science ®Google Scholar

FooJ, LandisSH, MaskellJ, et al. Continuing to Confront COPD International Patient Survey: economic impact of COPD in 12 countries. PLoS One. 2016;11(4):e0152618. doi:10.1371/journal.pone.015261827092775

 PubMed Web of Science ®Google Scholar

GadreS, DuggalA, GuzmanJ. Epidemiological characteristics and outcomes of patients with severe COPD requiring mechanical ventilation. Chest. 2014;146(4 Suppl 2):58A. doi:10.1378/chest.199191124652410

 PubMed Web of Science ®Google Scholar

GallegoM, PomaresX, CapillaS, et al. C-reactive protein in outpatients with acute exacerbation of COPD: its relationship with microbial etiology and severity. Int J Chron Obstruct Pulmon Dis. 2016;11:2633–2640. doi:10.2147/COPD27799762

 PubMed Web of Science ®Google Scholar

Garcia-AymerichJ, FélezMA, EscarrabillJ, et al. Physical activity and its determinants in severe chronic obstructive pulmonary disease. Med Sci Sports Exerc. 2004;36(10):1667–1673. doi:10.1249/01.MSS.0000142378.98039.5815595285

 PubMed Web of Science ®Google Scholar

Garcia-AymerichJ, Serra PonsI, ManninoDM, MaasAK, MillerDP, DavisKJ. Lung function impairment, COPD hospitalisations and subsequent mortality. Thorax. 2011;66(7):585–590. doi:10.1136/thx.2010.15287621515553

 PubMed Web of Science ®Google Scholar

Garciía-PoloC, Alcázar-NavarreteB, Ruiz-IturriagaLA, et al. Factors associated with high healthcare resource utilisation among COPD patients. Respir Med. 2012;106(12):1734–1742. doi:10.1016/j.rmed.2012.09.00923058483

 PubMed Web of Science ®Google Scholar

GatheralT, KumarN, SansomB, et al. COPD-related bronchiectasis; independent impact on disease course and outcomes. COPD. 2014;11(6):605–614. doi:10.3109/15412555.2014.92217424983298

 PubMedGoogle Scholar

GavazziA, De MariaR, ManzoliL, et al. Palliative needs for heart failure or chronic obstructive pulmonary disease: results of a multicenter observational registry. Int J Cardiol. 2015;184:552–558. doi:10.1016/j.ijcard.2015.03.05625767016

 PubMed Web of Science ®Google Scholar

HuangH, LinI, GoldsteinB, RosielloR, MenzinJ. Rehospitalization rates and mortality among patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy in a managed-care setting. Am J Respir Crit Care Med. 2014;189:A3058. doi:10.1164/rccm.201306-1150OC

 Web of Science ®Google Scholar

KeiltyS, MurphyP, HartN. 1 year UK survival readmission rate in chronic obstructive pulmonary disease (COPD) survivors following acute non-invasive ventilation (NIV). Thorax. 2013;68(Suppl. 3):A47–A48. doi:10.1136/thoraxjnl-2013-204457.95

 Web of Science ®Google Scholar

KolevaD, MotterliniN, BanfiP, GarattiniL. Healthcare costs of COPD in Italian referral centres: a prospective study. Respir Med. 2007;101(11):2312–2320. doi:10.1016/j.rmed.2007.06.02017681461

 PubMed Web of Science ®Google Scholar

LusuardiM, LucioniC, De BenedettoF, MazziS, SanguinettiCM, DonnerCF. GOLD severity stratification and risk of hospitalisation for COPD exacerbations. Monaldi Arch Chest Dis. 2008;69(4):164–169. doi:10.4081/monaldi.2008.37819350838

 PubMedGoogle Scholar

MahmudN, McNabb-BalterJ, ChanWW. The impact of gastroesophageal reflux on the length of hospital stay for COPD exacerbations: a report of the nationwide inpatient sample. Gastroenterology. 2015;148(4Suppl. 1):S606. doi:10.1016/S0016-5085(15)32044-8

 Google Scholar

MapelDW, DutroMP, MartonJP, WoodruffK, MakeB. Identifying and characterizing COPD patients in US managed care. A retrospective, cross-sectional analysis of administrative claims data. BMC Health Serv Res. 2011;11:43. doi:10.1186/1472-6963-11-4321345188

 PubMed Web of Science ®Google Scholar

MartínA, Rodríguez-González MoroJM, IzquierdoJL, GobarttE, de LucasP. Health-related quality of life in outpatients with COPD in daily practice: the VICE Spanish Study. Int J Chron Obstruct Pulmon Dis. 2008;3(4):683–692. doi:10.2147/COPD.S479119283915

 PubMedGoogle Scholar

MatkovicZ, HuertaA, SolerN, et al. Predictors of adverse outcome in patients hospitalised for exacerbation of chronic obstructive pulmonary disease. Respiration. 2012;84(1):17–26. doi:10.1159/00033546722327370

 PubMed Web of Science ®Google Scholar

McGhanR, RadcliffT, FishR, SutherlandER, WelshC, MakeB. Predictors of rehospitalization and death after a severe exacerbation of COPD. Chest. 2007;132(6):1748–1755. doi:10.1378/chest.06-301817890477

 PubMed Web of Science ®Google Scholar

MerinopoulouE, Raluy-CalladoM, RamagopalanS, MacLachlanS, KhalidJM. COPD exacerbations by disease severity in England. Int J Chron Obstruct Pulmon Dis. 2016;11:697–709. doi:10.2147/COPD.S10025027099486

 PubMed Web of Science ®Google Scholar

MullerovaH, HanMK, BaxterR, GOLDDK. 2013 COPD classification: a comparison with GOLD 2011 and COPD outcomes in the UK Clinical Practice Research Datalink (CPRD) COPD cohort. Am J Respir Crit Care Med. 2014;189:A5965. doi:10.1164/rccm.201306-1150OC

 Web of Science ®Google Scholar

PunekarYS, ShuklaA, MuellerovaH. Comparing COPD costs by exacerbation frequency and dyspnoea level in a primary care setting in the United Kingdom. Value Health. 2013;16(7):A723. doi:10.1016/j.jval.2013.08.2259

 Web of Science ®Google Scholar

PunekarYS, WurstK, ShuklaA. COPD management costs among newly diagnosed COPD patients in the UK primary care setting. Am J Respir Crit Care Med. 2013;187:A4373.

 Web of Science ®Google Scholar

PunekarYS, ShuklaA, MuellerovaH. Disease management costs associated with COPD patients with infrequent exacerbations in the UK primary care setting. Am J Respir Crit Care Med. 2013;187:A4374.

 Web of Science ®Google Scholar

PunekarYS, LandisSH, BonarK, LeH. Health care utilisation and costs among COPD patients newly prescribed maintenance therapy in the United Kingdom (UK). Thorax. 2015b;70:A142–A143. doi:10.1136/thoraxjnl-2015-207770.269

 Web of Science ®Google Scholar

PunekarYS, ShuklaA, MüllerovaH. COPD management costs according to the frequency of COPD exacerbations in UK primary care. Int J Chron Obstruct Pulmon Dis. 2014;9:65–73. doi:10.2147/COPD24426781

 PubMed Web of Science ®Google Scholar

MerinopoulouE, Raluy-CalladoM, RamagopalanS, MacLachlanS, KhalidJM. Resource use and exacerbations of chronic obstructive pulmonary disease (COPD) by GOLD categories. Value Health. 2015;18(7):A506–A507. doi:10.1016/j.jval.2015.09.1449

 Web of Science ®Google Scholar

MiravitllesM, CalleM, Alvarez-GutierrezF, GobarttE, LópezF, MartinA. Exacerbations, hospital admissions and impaired health status in chronic obstructive pulmonary disease. Qual Life Res. 2006;15(3):471–480. doi:10.1007/s11136-005-3215-y16547786

 PubMed Web of Science ®Google Scholar

MittmannN, KuramotoL, SeungSJ, HaddonJM, Bradley-KennedyC, FitzgeraldJM. The cost of moderate and severe COPD exacerbations to the Canadian healthcare system. Respir Med. 2008;102(3):413–421. doi:10.1016/j.rmed.2007.10.01018086519

 PubMed Web of Science ®Google Scholar

FitzGeraldJM, HaddonJM, Bradley-KennedyC, KuramotoL, FordGT, RUSIC Study GroupT. The RUSIC Study Group. Resource Use Study in COPD (RUSIC): a prospective study to quantify the effects of COPD exacerbations on health care resource use among COPD patients. Can Respir J. 2007;14(3):145–152. doi:10.1155/2007/92191417464378

 PubMed Web of Science ®Google Scholar

MolinariN, BriandC, VachierI, et al. Hospitalizations for COPD exacerbations: trends and determinants of death. COPD. 2015;12(6):621–627. doi:10.3109/15412555.2015.100793126263032

 PubMedGoogle Scholar

NantsupawatT, LimsuwatC, NugentK. Factors affecting chronic obstructive pulmonary disease early rehospitalization. Chron Respir Dis. 2012;9(2):93–98. doi:10.1177/147997231243870322399574

 PubMed Web of Science ®Google Scholar

NguyenHQ, ChuL, Liu I-LA, et al. Higher level of regular physical activity is associated with lower risk of 30-day readmissions in patients with COPD. Am J Respir Crit Care Med. 2014;189:A2452. doi:10.1164/rccm.201306-1150OC

 Web of Science ®Google Scholar

NishiSP, ZhangW, KuoYF, SharmaG. Oxygen therapy use in older adults with chronic obstructive pulmonary disease. PLoS One. 2015;10(3):e0120684. doi:10.1371/journal.pone.012068425785586

 PubMed Web of Science ®Google Scholar

PasqualeMK, SunSX, SongF, HartnettHJ, StemkowskiSA. Impact of exacerbations on health care cost and resource utilization in chronic obstructive pulmonary disease patients with chronic bronchitis from a predominantly medicare population. Int J Chron Obstruct Pulmon Dis. 2012;7:757–764. doi:10.2147/COPD.S3699723152680

 PubMed Web of Science ®Google Scholar

PhilipJ, LoweA, GoldM, et al. Using administrative datasets to assist prognostication in chronic obstructive pulmonary disease (COPD). Palliat Med. 2010;24:S25.

 Google Scholar

PitassiM, VitaleC, D’AmatoM, StanziolaA, MormileM, MolinoA. Impact of bronchiectasis on duration of hospitalization in patients with exacerbations of COPD. Eur Respir J. 2015;46:PA4701.

 Web of Science ®Google Scholar

PrettoJJ, McDonaldVM, WarkPA, HensleyMJ. Multicentre audit of inpatient management of acute exacerbations of chronic obstructive pulmonary disease: comparison with clinical guidelines. Intern Med J. 2012;42(4):380–387. doi:10.1111/j.1445-5994.2011.02475.x21395962

 PubMed Web of Science ®Google Scholar

PunekarYS, WurstK, ShuklaA. Resource use and costs up to two years post diagnosis among newly diagnosed COPD patients in the UK primary care setting: a retrospective cohort study. COPD. 2015;12(3):267–275. doi:10.3109/15412555.2014.93395325093809

 PubMedGoogle Scholar

QuintanaJM, EstebanC, Garcia-GutierrezS, et al. Predictors of hospital admission two months after emergency department evaluation of COPD exacerbation. Respiration. 2014;88(4):298–306. doi:10.1159/00036599625228470

 PubMed Web of Science ®Google Scholar

RobertsMH, BorregoM, PetersenH, KharatA, BlanchetteC. Estimating the burden and course of severe COPD exacerbations in the U.S. Hispanic population. Am J Respir Crit Care Med. 2011a;183:A1496.

 Web of Science ®Google Scholar

ShortPM, WilliamsonPA, SinganayagamA, AkramA, ChalmersJD, SchembriS. Guideline adherent therapy and reduced mortality and length of stay in adults hospitalised with exacerbations of COPD. Thorax. 2013;68(Suppl. 3):A136. doi:10.1136/thoraxjnl-2013-204457.283

 Web of Science ®Google Scholar

RobertsCM, StoneRA, LoweD, PurseyNA, BuckinghamRJ. Co-morbidities and 90-day outcomes in hospitalized COPD exacerbations. COPD. 2011b;8(5):354–361. doi:10.3109/15412555.2011.60036221864116

 PubMedGoogle Scholar

SharafkhanehA, AltanAE, ColiceGL, et al. A simple rule to identify patients with chronic obstructive pulmonary disease who may need treatment reevaluation. Respir Med. 2014;108(9):1310–1320. doi:10.1016/j.rmed.2014.07.00225130680

 PubMed Web of Science ®Google Scholar

SmallM, HolbrookT, WoodR, MullerovaH, NayaI, PunekarYS. Prevalence and burden of dyspnoea among COPD patients in Japan. Int J Clin Pract. 2016;70(8):676–681. doi:10.1111/ijcp.2016.70.issue-827396989

 PubMed Web of Science ®Google Scholar

StanfordRH, ShenY, McLaughlinT. Cost of chronic obstructive pulmonary disease in the emergency department and hospital: an analysis of administrative data from 218 US hospitals. Treat Respir Med. 2006;5(5):343–349. doi:10.2165/00151829-200605050-0000516928147

 PubMedGoogle Scholar

SteerJ, GibsonGJ, BourkeSC. Longitudinal change in quality of life following hospitalisation for acute exacerbations of COPD. BMJ Open Respir Res. 2015;2(1):e000069. doi:10.1136/bmjresp-2014-000069

 PubMed Web of Science ®Google Scholar

StefanMS, NathansonB, LindenauerP, HigginsT, SteingrubJ. Characteristics, ventilation strategies, and outcomes of patients hospitalized in intensive care units with an acute exacerbation of COPD. Am J Respir Crit Care Med. 2014;189:A1632. doi:10.1164/rccm.201306-1150OC

 Web of Science ®Google Scholar

StefanMS, ShiehMS, PekowPS, HillN, RothbergMB, LindenauerPK. Trends in mechanical ventilation among patients hospitalized with acute exacerbations of COPD in the United States, 2001 to 2011. Chest. 2015;147(4):959–968. doi:10.1378/chest.14-121625375230

 PubMed Web of Science ®Google Scholar

SuissaS, Dell’AnielloS, ErnstP. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957–963. doi:10.1136/thoraxjnl-2011-20151822684094

 PubMed Web of Science ®Google Scholar

ThomasM, RadwanA, StonhamC, MarshallS. COPD exacerbation frequency, pharmacotherapy and resource use: an observational study in UK primary care. COPD. 2014;11(3):300–309. doi:10.3109/15412555.2013.84167124152210

 PubMedGoogle Scholar

ThomasM, RadwanA, StonhamC, MarshallS. Exacerbation frequency and maintenance treatment of COPD in UK clinical practice. Thorax. 2011;66(Suppl 4):A153. doi:10.1136/thoraxjnl-2011-201054c.211

 Web of Science ®Google Scholar

TranM, XiangP, RascatiKL, et al. HEDIS quality measure performance and other factors predictive of health care costs following COPD-related admission. Value Health. 2016;19:A122.

 Web of Science ®Google Scholar

ValidoA, Gomez-BasteroA, AlmadanaV, LuqueE, MontemayorT. Clinical and functional differences, exercise capacity and physical activity among frequent and not frequent exacerbators in COPD patients. Eur Respir J. 2014;44(Suppl 58):P4883. doi:10.1183/09031936.00003814

 Web of Science ®Google Scholar

VallabhajosyulaS, HaddadTM, SundaragiriPR, et al. Role of B-type natriuretic peptide in predicting in-hospital outcomes in acute exacerbation of chronic obstructive pulmonary disease: a five-year retrospective analysis. Am J Respir Crit Care Med. 2015;191:A2938.

 Web of Science ®Google Scholar

VitaccaM, EscarrabillJ, GalavottiG, et al. Home mechanical ventilation patients: a retrospective survey to identify level of burden in real life. Monaldi Arch Chest Dis. 2007;67(3):142–147. doi:10.4081/monaldi.2007.48518018753

 PubMedGoogle Scholar

VitaccaM, BianchiL, BazzaA, CliniEM. Advanced COPD patients under home mechanical ventilation and/or long term oxygen therapy: italian healthcare costs. Monaldi Arch Chest Dis. 2011;75(4):207–214. doi:10.4081/monaldi.2011.20822462308

 PubMedGoogle Scholar

WangQ, BourbeauJ. Outcomes and health-related quality of life following hospitalization for an acute exacerbation of COPD. Respirology. 2005;10(3):334–340. doi:10.1111/res.2005.10.issue-315955146

 PubMed Web of Science ®Google Scholar

YeoJ, KarimovaG, BansalS. Co-morbidity in older patients with COPD–its impact on health service utilisation and quality of life, a community study. Age Ageing. 2006;35(1):33–37. doi:10.1093/ageing/afj00216364931

 PubMed Web of Science ®Google Scholar

YuAP, YangH, WuEQ, SetyawanJ, MocarskiM, BlumS. Incremental third-party costs associated with COPD exacerbations: a retrospective claims analysis. J Med Econ. 2011;14(3):315–323. doi:10.3111/13696998.2011.57629521500975

 PubMedGoogle Scholar

MoherD, LiberatiA, TetzlaffJ, AltmanDG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.100009719621072

 PubMed Web of Science ®Google Scholar