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Table 1. Summary of the Association Between Exacerbation History and Prediction of Future Eventsa
Exacerbation-Related
Author Study Design Outcomes Results
AbuDagga et al.5 Retrospective study of claims- Annual moderate and/or Patients experienced ~29.6% more exacer-
based data (n = 17,382); 1-year severe exacerbation rate bations during follow-up year for each
baseline, 1-year follow-up and exacerbation-related additional exacerbation during the pre-
costs during follow-up vious year (RR, 1.2963; 95% CI,
year 1.2794-1.3134; p < 0.0001)
Hurst et al.18 Observational study (ECLIPSE) Rate of moderate or severe An exacerbation that had been treated
in patients with moderate- exacerbations during the year before study entry was
to-severe COPD (n = 2,138); predictive of an exacerbation within the
3-year study first year of study (OR, 4.30; 95% CI,
3.58-5.17; p < 0.001)
Husebø et al.22 Prospective cohort 3-year study Exacerbation rate ≥2 exacerbations in the previous year were
(n = 403) associated with higher moderate or se-
vere annual exacerbation rate (incidence
rate ratio, 1.65; 95% CI, 1.24-2.21;
p < 0.001)
Kerkhof et al.20 Retrospective analysis of health- Exacerbation frequency Number of exacerbations in year prior to
care database (n = 16,565); COPD diagnosis were predictive of ex-
1-year baseline data, 1-year acerbations during follow-up year: 1 ex-
follow-up acerbation (OR, 2.42; 95% CI, 2.18-2.69);
2 exacerbations (OR, 4.39; 95% CI, 3.89-
4.95); 3 exacerbations (OR, 7.28; 95% CI,
6.25-8.48); ≥4 exacerbations (OR, 17.83;
95% CI, 15.12-21.03)
Müllerovà et al.19 Retrospective medical records Rate of moderate or severe 1 moderate exacerbation in year prior to
study (n = 58,589); 1-year base- exacerbations study vs none was associated with 1 (OR,
line data, 1-year follow-up 1.89; 95% CI, 1.79-1.99) or ≥2 moderate-
to-severe exacerbations during follow-up
year (OR, 3.31; 95% CI, 3.12-3.51)
≥2 moderate exacerbations in the year prior
to study vs none was associated with ≥2
moderate-to-severe exacerbations during
follow-up (OR, 13.64; 95% CI, 12.67-
14.68)
Müllerovà et al.21 Observational study (ECLIPSE) Time to first hospital Patients who had a severe exacerbation
in patients with moderate- admission for an that resulted in hospitalization during the
to-severe COPD (n = 2,138); exacerbation first year of the study were at increased
3-year study risk of being hospitalized for an exacer-
bation during the next 2 years (HR, 2.71;
95% CI, 2.24-3.29; p < 0.001)
Pasquale et al.4 Retrospective analysis of claims Rate of moderate or severe Exacerbations were significantly higher
data from patients with exacerbations during follow-up for patients with ≥1
COPD and chronic bronchitis (mean ± S.D.: 1.26 ± 1.64) or ≥2 (1.77 ±
(n = 8,554); 1-year baseline 1.90) exacerbations during baseline year
data, 1-year follow-up after diagnosis (1.04 ± 1.51)
CI = confidence interval; COPD = chronic obstructive pulmonary disease; HR = hazard ratio; OR = odds ratio; RR = rate ratio.
a
COPD. Similarly, a LAMA/LABA com- COPD exacerbations and increasing up to 1 or at least 1 exacerbation in the
bination of tiotropium/olodaterol pro- the time to first exacerbation in patients previous year.
vided a greater improvement in lung with a history of exacerbations in the A switch from LABA/ICS to LAMA/
function than salmeterol/fluticasone in previous year. Notably, compared with LABA is recommended if patients do
patients with moderate-to-severe COPD LABA/ICS, LAMA/LABA combination not respond to ICS or where risks as-
in the ENERGITO® study.28 In the FLAME therapy significantly reduced the rate of sociated with ICS are a concern.1 If
study,29 glycopyrronium/indacaterol COPD exacerbations by 31%26 and 11%, patients have persistent exacerbations
was more effective than salmeterol/ respectively, in patients with moderate- despite being on the LAMA/LABA or
fluticasone in reducing the rate of to-severe COPD who experienced either LABA/ICS treatment regimens, LAMA/
Figure 1. Updated GOLD classification of COPD severity.1 The GOLD guidelines updated in 2019 use exacerba-
tion history and symptom burden to classify patient’s future exacerbation risk stratification (ABCD tool). However,
the use of spirometry is vital to properly diagnose and gauge a prognosis for the disease. CAT = COPD Assessment
Test, COPD = chronic obstructive pulmonary disease, GOLD = Global Initiative for Chronic Obstructive Lung Disease,
mMRC = modified Medical Research Council, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity.
Reproduced with permission from Global Initiative for Chronic Obstructive Lung Disease 2019 report (copyright © 2019
Global Initiative for Chronic Obstructive Lung Disease, Inc.).
Assessment of
Spirometrically Assessment of
symptoms/risk
confirmed diagnosis airflow limitation
of exacerbations
Moderate or Severe
Exacerbation History
Grade FEV1 ≥ 2 or
Post-bronchodilator
FEV1/FVC < 0.7
(% predicted)
≥ 1 leading
to hospital
C D
GOLD 1 ≥ 80 admission
GOLD 2 50-79
0 or 1 A B
GOLD 3 30-49 (not leading
to hospital
GOLD 4 < 30 admission)
mMRC 0-1 mMRC ≥ 2
CAT < 10 CAT ≥ 10
Symptoms
LABA/ICS triple therapy should be con- is recommended in the GOLD strategy of the disease. An individual treatment
sidered. A switch from LAMA/LABA to document for patients who experience approach should always be taken be-
a triple therapy should be guided by further exacerbations on LAMA/LABA cause patients show varied responses
the biomarker assessment (i.e., pa- or LAMA/ICS regardless of their ABCD to available therapies.
tients with eosinophil counts of ≥100 assessment at diagnosis; however, Acute exacerbation. Short-
cells/µL are more likely to benefit from GOLD recommendations note that acting bronchodilators, particularly
the triple therapy). For patients with there is a lack of direct evidence to in- short-acting β2-agonists, are recom-
eosinophil counts of <100 cells/µL, dicate whether triple therapy will offer mended for treatment of exacerbations
roflumilast and azithromycin should any further benefits to LAMA/LABA in and can be combined with short-acting
be considered in patients with chronic absence of a biomarker assessment.1 anticholinergics.1 The addition of a sys-
bronchitis with severe airflow limita- The GOLD guidelines include (since temic corticosteroid to the treatment
tion (FEV1 < 50%) and who are former the 2017 update) guidance for de-es- regimen may be required for moderate-
smokers, respectively.1 calation of treatment should additional to-severe COPD exacerbations or those
Trials assessing LAMA/LABA/ therapies not result in incremental that do not respond to short-acting
ICS triple therapy have shown im- benefits, particularly with regard to re- bronchodilators. European Respiratory
proved bronchodilator effects com- moving ICS from treatment if no ben- Society/American Thoracic Society
pared with LABA/ICS and LAMA efit is seen, if pneumonia is noted, or (ERS/ATS) guidelines recommend oral
alone.30-32 Furthermore, triple therapy if ICS was prescribed for an inappro- corticosteroids over intravenous cor-
was shown to reduce exacerbations priate original indication, as deemed ticosteroids for patients hospitalized
by 23% to 35% in patients who had ex- by a physician.1 This is novel, because with an exacerbation.33 Although oral
perienced exacerbations in the pre- historical approaches to treating COPD corticosteroid therapy is beneficial in
vious year compared with LABA/ICS have tended to be chronic and cumula- resolving exacerbations, duration of
alone.31,32 Escalation to triple therapy tive because of the progressive nature corticosteroid use should be kept to
a minimum to avoid possible side ef- corticosteroids (5 days) were noninferior an additional treatment for patients with
fects, including pneumonia.1 ERS/ to longer courses (14 days) for patients increased sputum purulence that is in-
ATS guidelines recommend treatment experiencing an exacerbation, with dicative of bacterial infection.1 GOLD
with corticosteroids for up to 14 days, both treatments resulting in similar provides little guidance regarding the
whereas GOLD recommends a shorter re-exacerbation rates within 6 months choice of antibiotic other than recom-
time of 5 days.1,33 The REDUCE trial 34 and similar lung-function recovery mending to consider local bacterial re-
found that shorter courses of systemic times. Antibiotics are recommended as sistance patterns.1
Factors that indicate the need for in- mortality rates, whereas higher adher- exacerbation that requires hospitaliza-
patient admission following onset of an ence is associated with reduced hospi- tion can range from $7,000 to $39,200,
exacerbation include patient inability talizations.39 In addition, errors related with costs substantially elevated for pa-
to cope within the home environment, to inhaler handling are associated with tients who require mechanical ventila-
severe dyspnea and/or lack of response an increased rate of severe COPD ex- tion (Table 2). Comorbidities, including
to initial treatment, and acute respira- acerbations.40 Consequently, GOLD cardiovascular disease and lung cancer,
tory failure.1 2019 report, for the first time, highlights are common in patients with COPD and
Opportunities for transitional the importance of assessing inhaler are significantly associated with both
care management. According to technique and adherence in patients higher costs and increased mortality
Hurst and colleagues,35 exacerbations with poor symptom control before following hospitalization for a COPD
in COPD are not random events but adjusting patients’ medications/treat- exacerbation.45 Survival rates at 5 years
occur in a high-risk period for recur- ment regimen.1 Community, clinical, after a hospitalization for a COPD exac-
rent exacerbation in the 8-week period and hospital pharmacists can provide erbation are estimated to be only 45%.24
following an initial exacerbation. This medication-related education for pa- Hospital readmissions within
finding presents a therapeutic window tients with COPD, including the pur- 30 days of discharge after an acute
for healthcare providers for preven- pose and value of taking maintenance COPD exacerbation occur in ~20% of
tative interventions. Reduction in the medications, the importance of adher- patients.8 Studies have shown that fac-
risk of future exacerbations is a key goal ence, proper inhaler technique, and tors associated with re-exacerbation
of COPD management, and patients how to troubleshoot and maintain their and readmission include longer du-
should be started on appropriate main- inhalers. A review of studies conducted ration of hospital stay, low FEV1,
tenance therapy following an exacer- during a 10-year period showed that comorbidities, high modified Medical
bation.1 Follow-up appointments after inhaler training education and medi- Research Council dyspnea score, and
hospitalization for acute exacerba- cation adherence by community phar- previous admissions.50,51 A study of
tion are recommended for all patients macists had a positive impact, resulting 90-day readmission rates following
within 1 to 4 weeks and 12 to 16 weeks in significant reduction in inhalation acute exacerbations found that read-
postdischarge. These appointments errors, improvement in the choice of mission was ~35% and was significantly
should focus on areas including treat- inhalers, and better adherence to in- associated with increased mortality
ment regimen, inhaler technique, and haled medication.41 (13.4% in readmitted versus 2.3% in
measurement of symptoms. nonreadmitted patients).50
Inhaler technique is often poor Implications for the health Patients who experience numerous
among patients with COPD, a factor system and managed care readmissions may have a phenotype
that is associated with increased risk community known as the “frequent exacerbator.” 52
of ED visits and hospitalization.36 Thus, Exacerbations of COPD are a major It is hypothesized that patients with this
initial and repeated reinforcement of cause of healthcare resource use be- phenotype have an altered adaptive
patient education on inhaler technique cause they increase physician office (CD4 and CD8 T cell) immune system
is critical for COPD management.1,36 visits, ED visits, hospitalizations, and that attenuates an inflammatory re-
Selection of an appropriate inhaler is pharmacy use compared with stable sponse, facilitating COPD exacerba-
also important for managing COPD, COPD.4-7 Data from large prospective tions.53 However, this phenotype is not
because patient satisfaction with the and retrospective studies suggest that only seen in patients with the most se-
inhaler is thought to influence adher- ~37% to 71% of patients with COPD ex- vere airflow obstruction. The ECLIPSE
ence.37 Follow-up visits and patient ed- perience at least 1 exacerbation annu- study found that 22%, 33%, and 47%
ucation should also cover adherence to ally.4,6,17,42 Exacerbations can also occur of patients with moderate, severe, and
medication.1 Poor adherence to main- in patients with mild COPD but are very severe airflow obstruction, respec-
tenance therapies is common among underreported.43 Among patients who tively, were frequent exacerbators.18
patients with COPD and is often mul- experience a COPD exacerbation, ~9% This high prevalence of the frequent-
tifactorial. As the disease progresses, to 31% require an ED visit and ~14% to exacerbator phenotype, even among
COPD typically requires more than 35% require hospitalization.4,6,7,17,42 patients with moderate airflow obstruc-
1 medication, which may not be de- Milder exacerbations can often tion, is particularly concerning because
livered with similar inhalers. The use of be treated on an outpatient basis, but of the detrimental effects that exacer-
multiple inhalers can be confusing to those which are moderate to severe in bations exert, including accelerating
patients and lead to poor inhaler tech- nature may prompt ED visits or hospi- lung-function decline, reducing quality
nique.38 Also, the lack of generic inhaled talization, leading to higher treatment of life, and increasing hospitalizations
options can affect cost, which also can costs with increased exacerbation fre- and mortality.52 These factors, together
negatively influence adherence. Poor quency and severity (Table 2).4,6,18,42,44-49 with implementation of the Afford
adherence is associated with increased Mean cost of treatment for a severe able Care Act Hospital Readmissions
Table 2. Estimates of the Costs of Treating COPD Exacerbations in the United Statesa
Authors Study Design Findings
Dalal et al.46 Retrospective, claims based Cost per visit for exacerbation, mean ± S.D.
(n = 71,493), 2005-2009 ED visit: $647 ± $445
Simple admissions (no ICU/intubation): $7,242 ± $7,987
Complex admissions (general/surgical/medical ICU and/or intubation):
$20,757 ± $41,370 (5.8% of all admissions)
Dalal et al.49 Retrospective, claims Per visit COPD-related healthcare costs (2009), mean
based on commercial ED visit (commercial): $345
(n = 51,210) and Medicare ED visit (Medicare): $429
plans (n = 42,166), 2006- Standard hospitalization (commercial): $10,170
2009 Standard hospitalization (Medicare): $7,430
Intensive care hospitalization (commercial): $39,229
Intensive care hospitalization (Medicare): $14,112
Dhamane et al.6 Retrospective, claims based Mean COPD-related total costs over 24 months
(n = 52,459), 2007-2012 No exacerbations: $1,605
≥1 exacerbation: $3,707
≥2 exacerbations: $6,712
≥3 exacerbations: $12,257
Ke et al.42 Retrospective, claims based Annual COPD-related healthcare costs for all patients,b mean ± S.D. (median)
(n = 754), ED visits: $257 ± $1,039 ($0)
2011-2014 Hospitalizations: $7,625 ± $21,785 ($0)
Pasquale et al.4 Retrospective, claims COPD-related annual total costs, mean (95% CI)
based. Patients with No exacerbations: $1,425 (1,404-1,447)
COPD and chronic bron- ≥1 moderate or severe exacerbation: $7,022 (6,926-7,119)
chitis on maintenance
medications (n = 8,554),
2007-2011
Perera et al.45 Retrospective study of Cost per hospitalization for acute exacerbation, mean ± S.D.
U.S. inpatient discharge Overall (COPD or chronic bronchitis ICD-9 code with pneumonia or procedure code
records (n = 1,254,703), for mechanical ventilation): $9,545 ± $12,700
2006 Principal diagnosis of COPD: $7,015 ± $8,289
With mechanical ventilation: $24,374 ± $26,608
Without mechanical ventilation: $7,569 ± $7,434
Yu et al.47 Retrospective, claims based Total healthcare cost per patient quarter (90 days), mean ± S.D.
(n = 228,978), 2004-2009 No exacerbations: $4,762 ± $13,082
Mild-to-moderate exacerbation: $6,628 ± $18,188
Severe exacerbation: $17,016 ± $24,675
COPD-related total cost per patient quarter (90 days), mean ± S.D.
No exacerbation: $658 ± $3,336
Mild-to-moderate exacerbation: $,1522 ± $11,505
Severe exacerbation: $7,014 ± $13,278
Wallace et al.48 Retrospective, claims based Annual COPD-related healthcare costs for all patients,b mean ± S.D.
(n = 1,505), 2011-2015 ED visits:
GOLD 1: $186 ± $1,100
GOLD 2: $144 ± $588
GOLD 3: $193 ± $651
GOLD 4: $534 ± $1,059
Hospitalizations:
GOLD 1: $3,853 ± $12,462
GOLD 2: $4,449 ± $12,728
GOLD 3: $6,277 ± $12,970
GOLD 4: $12,139 ± $15,599
a
CI = confidence interval, COPD = chronic obstructive pulmonary disease, ED = emergency department, GOLD = Global Initiative for Chronic
Obstructive Lung Disease, ICD-9 = International Classification of Diseases 9th revision, ICU = intensive care unit, S.D. = standard deviation.
b
Costs calculated from whole population including patients who did not use the service. GOLD airflow limitation severity classification: GOLD 1
(mild), forced expiratory volume in 1 second (FEV1) ≥80% predicted; GOLD 2 (moderate), FEV1 50% to 79% predicted; GOLD 3 (severe), FEV1 30%
to 49% predicted; GOLD 4 (very severe), FEV1 < 30% predicted.
Reduction Program, whereby hospitals a care bundle that included smoking maintenance therapy within the first
with higher-than-expected 30-day re- cessation counseling, patient educa- 30 days of discharge resulted in signifi-
admission rates for COPD are finan- tion, and telephone follow-up did not cantly reduced COPD-related ED visits
cially penalized, have highlighted the reduce 30- and 60-day readmission (36.7%), office visits (12.1%), and outpa-
need for strategies to reduce readmis- rates.56 Similarly, a Medicare Bundled tient costs (39.0%) in the following year.61
sions and improve overall patient care.8 Payments for Care Improvement A large retrospective study of claims
Several studies have assessed re- Initiative, in which patients were data found that after a moderate exac-
admission characteristics and trialed more likely to receive telephone fol- erbation requiring a prescription for an
ways to reduce readmissions following low-up, pulmonary rehabilitation, oral corticosteroid, only 25% of patients
discharge after acute exacerbation. pulmonologist appointments, and were prescribed maintenance therapy.62
A disease-management program for home care, did not significantly reduce Based on data from the TORCH trial, ad-
COPD, which provided follow-up in the 30- or 90-day readmissions and was herence to maintenance medication is
community after hospital discharge, found not to be cost-effective.57 also vitally important in reducing hospi-
was found to reduce COPD-related and Pulmonary rehabilitation programs talizations and mortality.39
all-cause 60- and 90-day readmission that involve a multidisciplinary ap-
rates.54 This program included home proach, including exercise therapy and Conclusion
visits, clinical assessment, medication patient education, have been shown to COPD exacerbations, particularly
review, inhaler technique training, and improve health-related quality of life in those that require ED visits or hospital-
disease-education components. Care patients with COPD.58 A 5-year study ization, lead to substantial economic
team members typically included a of the use of a pulmonary rehabilita- burden. Patients who have frequent
nurse practitioner, a registered nurse, tion program with negative pressure exacerbations have reduced quality of
and a respiratory therapist.53 Patients ventilation found that during the first life and accelerated disease progres-
discharged to skilled nursing facilities 4 years, patients with pulmonary reha- sion. Appropriate therapy with mainte-
were found to be less likely to be re- bilitation and negative pressure venti- nance bronchodilators has been shown
admitted to a hospital within 30 days of lation had increased exercise capacity to reduce exacerbation frequency but is
discharge than those discharged home, and reduced lung-function decline.59 underused, highlighting a need for in-
with or without home care (18.8%, Furthermore, in patients who received creased awareness of treatment recom-
27.7%, and 31.1% readmission rates, pulmonary rehabilitation and negative mendations among treating physicians,
respectively).8 In a prospective, obser- pressure ventilation, risk of exacerba- prescribers, and healthcare organiza-
vational study, a COPD care bundle, tions requiring ED visit or hospitali- tions in which patient care could be
involving a multidisciplinary team of zation was reduced by 66% and 54%, improved. Several studies have found
respiratory therapists, pulmonologists, respectively, and annual total medical that COPD aftercare programs that in-
pharmacists, critical care physicians, costs were reduced when compared crease patient support are beneficial
general internists, and nurses, was also with patients who were assigned to an in improving outcomes and reducing
found to improve care of patients with exercise program alone ($3,274 ± $1,604 hospitalizations. Programs that include
COPD exacerbations.55 This bundle versus $4,335 ± $3,269). ERS/ATS referrals to pulmonologists, patient ed-
included standard nursing protocols, guidelines recommend starting pul- ucation and inhaler technique training,
patient education on inhaler use and monary rehabilitation within 3 weeks and pulmonary rehabilitation have
medication, and postdischarge refer- of hospital discharge.33 Limited access been shown to be successful and, in
rals to pulmonologists and was found to pulmonary rehabilitation remains an combination with appropriate mainte-
to significantly reduce 30- and 60-day issue for many patients who could oth- nance therapy, could improve the lives
readmissions compared with con- erwise benefit from this resource.1 of patients with frequent exacerbations.
trol (9.1% versus 54.4% for 30-day and Maintenance medication therapy This highlights that continuing the
22.7% versus 77.0% for 60-day). Length remains a key strategy to reduce hospi- move toward integrated care of COPD
of hospital stay was also reduced fol- talizations due to acute COPD exacer- is the way to achieve better outcomes.
lowing implementation of the care bations. The timing of maintenance
bundle, as were the total aggregate therapy initiation following an acute Disclosures
hospital costs at 90 days postdischarge, exacerbation in naive patients can sig- Editorial support and/or formatting assis-
which were reduced from $19,954 to nificantly affect outcomes, with pa- tance was provided by Suchita Nath-Sain,
$7,652. tients who started maintenance more Ph.D.; Saurabh Gagangras, Ph.D.; Dhananjay
In contrast, others have found that than 30 days postdischarge having sig- Arankale, B.N.Y.S., PGDPH; and Vidula Bhole,
use of care bundles did not result in nificantly higher risk (43%) of COPD- M.D., M.H.Sc., of Cactus Communications,
which was contracted and compensated by
reduced readmission rates in patients related hospitalization or ED visit in the Boehringer Ingelheim Pharmaceuticals Inc.
with acute exacerbations of COPD.56,57 following year.60 Others have agreed with The authors have declared no potential con-
In a single-center randomized study, these findings and found that initiating flicts of interest.
Management of COPD exacerba- 44. Punekar YS, Shukla A, Müllerova H. exacerbator” COPD phenotype. Respir
tions: a European Respiratory Society/ COPD management costs according to Res. 2016; 17:140.
American Thoracic Society guideline. the frequency of COPD exacerbations 54. Alshabanat A, Otterstatter MC, Sin DD
Eur Respir J. 2017; 49:1600791. in UK primary care. Int J Chron Obstruct et al. Impact of a COPD comprehensive
34. Leuppi JD, Schuetz P, Bingisser R et al. Pulmon Dis. 2014; 9:65-73. case management program on hospital
Short-term vs conventional glucocorti- 45. Perera PN, Armstrong EP, Sherrill DL, length of stay and readmission rates.
coid therapy in acute exacerbations of Skrepnek GH. Acute exacerbations of Int J Chron Obstruct Pulmon Dis. 2017;
chronic obstructive pulmonary disease: COPD in the United States: inpatient 12:961-71.
the REDUCE randomized clinical trial. burden and predictors of costs and 55. Parikh R, Shah TG, Tandon R. COPD
JAMA. 2013; 309:2223-31. mortality. COPD. 2012; 9:131-41. exacerbation care bundle improves
35. Hurst JR, Donaldson GC, Quint JK et al. 46. Dalal AA, Shah M, D’Souza AO, standard of care, length of stay, and
Temporal clustering of exacerbations Rane P. Costs of COPD exacerbations readmission rates. Int J Chron Obstruct
in chronic obstructive pulmonary di- in the emergency department and Pulmon Dis. 2016; 11:577-83.
sease. Am J Respir Crit Care Med. 2009; inpatient setting. Respir Med. 2011; 56. Jennings JH, Thavarajah K, Mendez MP
179:369-74. 105:454-60. et al. Predischarge bundle for patients
36. Melani AS, Bonavia M, Cilenti V 47. Yu AP, Yang H, Wu EQ et al. Incremental with acute exacerbations of COPD to
et al., for the Gruppo Educazionale third-party costs associated with COPD reduce readmissions and ED visits:
Associazione Italiana Pneumologi exacerbations: a retrospective claims a randomized controlled trial. Chest.
Ospedalieri. Inhaler mishandling analysis. J Med Econ. 2011; 14:315-23. 2015; 147:1227-34.
remains common in real life and is as- 48. Wallace AE, Kaila S, Zubek V et al. 57. Bhatt SP, Wells JM, Iyer AS et al. Results
sociated with reduced disease control. Healthcare resource utilization, costs, of a Medicare bundled payments for
Respir Med. 2011; 105:930-8. and exacerbation rates in patients care improvement initiative for chronic
37. Hodder R, Price D. Patient preferences with COPD stratified by GOLD airflow obstructive pulmonary disease re-
for inhaler devices in chronic obstruc- limitation classification in a US com- admissions. Ann Am Thorac Soc. 2017;
tive pulmonary disease: experience with mercially insured population. Poster 14:643-8.
Respimat® Soft Mist™ Inhaler. Int J Chron presented at the Academy of Managed 58. Puhan MA, Gimeno-Santos E,
Obstruct Pulmon Dis. 2009; 4:381-90. Care Pharmacy Nexus. Dallas, Texas, Cates CJ, Troosters T. Pulmonary re-
38. Van der Palen J, Klein JJ, USA; October 16–19, 2017. habilitation following exacerbations
van Herwaarden CL et al. Multiple 49. Dalal AA, Liu F, Riedel AA. Cost trends of chronic obstructive pulmonary
inhalers confuse asthma patients. Eur among commercially insured and disease. Cochrane Database Syst Rev.
Respir J. 1999; 14:1034-7. Medicare Advantage-insured patients 2016; 12:CD005305.
39. Vestbo J, Anderson JA, Calverley PM with chronic obstructive pulmonary 59. Huang HY, Chou PC, Joa WC et al.
et al. Adherence to inhaled therapy, disease: 2006 through 2009. Int J Chron Pulmonary rehabilitation coupled with
mortality and hospital admission in Obstruct Pulmon Dis. 2011; 6:533-42. negative pressure ventilation decreases
COPD. Thorax. 2009; 64:939-43. 50. Engel B, Schindler C, Leuppi JD, decline in lung function, hospital-
40. Molimard M, Raherison C, Lignot S Rutishauser J. Predictors of izations, and medical cost in COPD:
et al. Chronic obstructive pulmonary re-exacerbation after an index ex- A 5-year study. Medicine (Baltimore).
disease exacerbation and inhaler acerbation of chronic obstructive 2016; 95(41):e5119.
device handling: real-life assessment pulmonary disease in the REDUCE ran- 60. Dalal AA, Shah MB, D’Souza AO et al.
of 2935 patients. Eur Respir J. 2017; domised clinical trial. Swiss Med Wkly. Outcomes associated with timing of
49:pii1601794. 2017; 147:w14439. maintenance treatment for COPD
41. Hesso I, Gebara SN, Kayyali R. Impact 51. Hartl S, Lopez-Campos JL, Pozo- exacerbation. Am J Manag Care. 2012;
of community pharmacists in COPD Rodriguez F et al. Risk of death and re- 18(9):e338-45.
management: inhalation technique admission of hospital-admitted COPD 61. Coutinho AD, Lokhandwala T, Boggs RL
and medication adherence. Respir Med. exacerbations: European COPD audit. et al. Prompt initiation of maintenance
2016; 118:22-30. Eur Respir J. 2016; 47:113-21. treatment following a COPD exacerba-
42. Ke X, Marvel J, Yu TC et al. Impact of 52. Wedzicha JA, Brill SE, Allinson JP, tion: outcomes in a large insured popu-
lung function on exacerbations, health Donaldson GC. Mechanisms and lation. Int J Chron Obstruct Pulmon Dis.
care utilization, and costs among pa- impact of the frequent exacerbator 2016; 11:1223-31.
tients with COPD. Int J Chron Obstruct phenotype in chronic obstructive 62. Dalal AA, Shah MB, D’Souza AO et al.
Pulmon Dis. 2016; 11:1689-703. pulmonary disease. BMC Med. 2013; Observational study of the outcomes
43. Welte T, Vogelmeier C, Papi A. COPD: 11:181. and costs of initiating maintenance
early diagnosis and treatment to slow 53. Geerdink JX, Simons SO, Pike R et al. therapies in patients with moderate
disease progression. Int J Clin Pract. Differences in systemic adaptive im- exacerbations of COPD. Respir Res. 2012;
2015; 69:336-49. munity contribute to the “frequent 13:41.