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Action plans to reduce hospitalizations for chronic obstructive pulmonary disease exacerbations: focus on oral corticosteroids a
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Timothy H. Self , Shanise J. Patterson , Arthur S. Headley & Christopher K. Finch a
University of Tennessee Health Science Center, Methodist University Hospital Memphis, TNUSA Published online: 26 May 2015.
Click for updates To cite this article: Timothy H. Self, Shanise J. Patterson, Arthur S. Headley & Christopher K. Finch (2014) Action plans to reduce hospitalizations for chronic obstructive pulmonary disease exacerbations: focus on oral corticosteroids, Current Medical Research and Opinion, 30:12, 2607-2615 To link to this article: http://dx.doi.org/10.1185/03007995.2014.934795
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Current Medical Research & Opinion 0300-7995 doi:10.1185/03007995.2014.934795
Vol. 30, No. 12, 2014, 2607–2615
Article ST-0158.R1/934795 All rights reserved: reproduction in whole or part not permitted
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Review Action plans to reduce hospitalizations for chronic obstructive pulmonary disease exacerbations: focus on oral corticosteroids
Timothy H. Self Shanise J. Patterson Arthur S. Headley Christopher K. Finch University of Tennessee Health Science Center, Methodist University Hospital, Memphis, TN, USA Address for correspondence: Dr. Timothy H. Self, University of Tennessee Health Science Center, 881 Madison Ave., Room 235, Memphis, TN 38163, USA. [email protected] Keywords: COPD exacerbations – Hospitalizations – Self-management action plans Accepted: 10 June 2014; published online: 30 June 2014 Citation: Curr Med Res Opin 2014; 30:2607–15
Abstract Objective: Chronic obstructive pulmonary disease (COPD) is associated with a huge burden of suffering and healthcare expenditures. Patients hospitalized due to COPD have increased risk of death. Starting in 2015, reimbursements by the Centers for Medicaid Medicare Services will be significantly reduced to hospitals with excess 30 day readmissions for COPD. Oral corticosteroid (OCS) therapy is established in improving outcomes in COPD patients treated in the emergency department and hospital. The objective of this article is to review the evidence evaluating home OCS treatment of COPD exacerbations as part of a comprehensive self-management action plan. Methods: We reviewed the English literature via PubMed, Embase, and Scopus using the search terms: chronic obstructive pulmonary disease exacerbations AND: oral corticosteroids, prednisone, prednisolone, methylprednisolone, treatment, self-management, disease management, written action plans. When pertinent articles were found, we reviewed the relevant articles cited. Findings: Two randomized trials enrolling 933 patients provide evidence of reduced rates of hospitalization by using comprehensive COPD action plans, including OCS therapy. Three trials with 790 patients enrolled did not reveal reduced rates of hospitalization. Among all five trials together, there were no differences in deaths (76 in the intervention groups [home action plans]; 81 in the usual care groups). Additional studies not assessing hospitalizations have found home use of OCSs increases time to the next exacerbation and decreases recovery time. Conclusion: Further randomized trials are needed to establish that home use of OCS therapy, as part of a comprehensive action plan, reduces the rate of hospitalizations. Such action plans should include structured patient education, early initiation of OCSs, oral antibiotics, and frequent telephone reinforcement and support from case management.
Introduction Chronic obstructive pulmonary disease (COPD) is associated with immense morbidity and economic costs1–3. It is now the third leading cause of death in the US, and hospitalizations due to exacerbations of COPD are associated with increased risk of death1,4. Recent research has shown that the best predictor of a patient having a COPD exacerbation is treatment for an exacerbation in the prior year5. Current evidence demonstrates that roughly 20% of all hospitalized ! 2014 Informa UK Ltd www.cmrojournal.com
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COPD patients get readmitted within 30 days of discharge3. Thus, effective strategies to reduce COPD exacerbations are essential. These data have led to the addition of COPD to the Affordable Care Act core measures6. This change is set to begin in October of 2015 and will significantly reduce payments to hospitals with excess readmissions for this chronic and progressive disease6. The 2014 updated GOLD guidelines point out that 80% of COPD exacerbations can be managed on an outpatient basis1. The purpose of this review article is to focus on the evidence regarding oral corticosteroid (OCS) therapy as one key component of an action plan for home management of COPD exacerbations. A primary goal of such an action plan, as part of a disease-specific self-management intervention, is to reduce hospitalizations. Oral corticosteroid therapy is clearly established as standard drug therapy in patients hospitalized for COPD exacerbations7–9. Because of the efficacy of OCS therapy in the hospitalized patient, including shorter hospital stays7,8, it is logical to assess outcomes of this therapy starting at home at the first sign of a COPD exacerbation. In addition, systemic corticosteroid therapy in the emergency department (ED) or for 10 days after discharge from the ED, is associated with reduced relapse rates10–12. A recent randomized trial found that a 5 day course of prednisone for patients presenting to the ED for treatment of COPD exacerbations was noninferior to a 14 day course13. Noninferiority included time to re-exacerbation over 6 months13. We reviewed the English literature from 1980 to March 2014 via PubMed, Embase, and Scopus using the search terms: chronic obstructive pulmonary disease exacerbations AND: oral corticosteroids, prednisone, prednisolone, methylprednisolone, treatment, selfmanagement, disease management, written action plans. When pertinent articles were found, we reviewed the relevant articles cited. This summary of the literature includes each study found that included oral corticosteroid (OCS) therapy in the home management of COPD exacerbations in an effort to prevent hospitalizations. While we have emphasized randomized controlled trials in this review article, we have included nonrandomized trials and other pertinent literature for completeness. In addition to the subject of our review article, we stress that optimal evidence-based pharmacologic therapy, avoidance of triggers, and appropriate vaccinations are proven to reduce exacerbations1.
Randomized, controlled trials specifically assessing prevention of hospitalizations Bourbeau and colleagues14 evaluated the effect of a disease-specific self-management intervention on 2608
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hospitalizations in COPD patients. In this randomized study, 95 COPD patients were in the usual care group and 95 patients were in the self-management group. In the prior year, all of these advanced COPD patients had at least one hospitalization for COPD. The self-management group received comprehensive patient education given by trained healthcare professionals via weekly visits over a 2 month period with monthly telephone follow-up. The action plan for exacerbations was customized for each patient, including a contact list and a symptom-monitoring list linked to appropriate actions. Patients had prescriptions to be initiated promptly when at least two of the three following symptom changes were noted: dyspnea, sputum volume, or sputum purulence. Emphasis was placed on starting an antibiotic and OCS for 10 to 14 days for exacerbations with these symptoms associated with infection. Safeguards were included to call the case manager or physician if these symptoms became worse after initiation of therapy at home. Hospital admissions for COPD exacerbations were reduced by 39.8%. In the usual care group, 118 (32.5%) of the 362 total exacerbations resulted in hospital admission versus 71 (23.7%) of the 299 exacerbations in the self-management group. In addition, more patients in the usual care group had at least one hospitalization (50.5%) compared to the intervention group (32.3%, p ¼ 0.01) and 2 admissions (30.5% vs. 15.5%, p ¼ 0.01) during the 1 year study period. Finally, the intervention group had fewer hospital days per patient (12.5 vs. 7.2, p ¼ 0.01). Although it is not known which components of the self-management program had the greatest positive impact, one key feature of the program was stressing the early use of OCS therapy. Sridhar et al.15 studied the effects of a program led by nurses for patients with a history of hospitalization for COPD. Patients were randomized to a control group (n ¼ 61) or an intervention group (n ¼ 61), consisting of pulmonary rehabilitation, self-management education, a written COPD action plan, monthly telephone calls, and three monthly home visits by a nurse specialist for a period of 2 years. The written action plan included advice regarding lifestyle and maintenance medications as well as instructions on when to initiate a course of antibiotics and OCS. The clinicians for these patients were asked to provide reserve supplies of these drugs for the patients. The primary outcome measure was the rate of hospitalizations. There was no difference between the groups in hospitalizations (52.7% in the intervention group vs. 48.9% controls, p ¼ 0.361). More intervention group patients were treated with OCSs plus antibiotics (44% intervention vs. 28.3% controls, p ¼ 0.001) or OCS alone (19.8% vs. 7.7%, p ¼ 0.001). More deaths due to COPD occurred in the control group (8 of 12 deaths) vs. the intervention group (1 of 6 deaths), p ¼ 0.015. Although comorbidities www.cmrojournal.com ! 2014 Informa UK Ltd
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such as a ‘severe heart disease’, cancer, and ethanol-related hepatic disease were among exclusion criteria for this study, not all comorbidities are listed (e.g. the groups could have been different with respect to ‘moderate’ cardiovascular diseases). Effing et al.16 evaluated the effectiveness of self-treatment on the severity of exacerbations in 142 moderate to severe COPD patients. In this 12 month study, patients were randomized to an intervention group (n ¼ 70) or a control group (n ¼ 72). Both groups received four 2 hour COPD patient education sessions regarding overall self-management. The intervention group also received training on self-treatment of exacerbations, including when to start a course of OCSs (prednisolone 30 mg for 7 days) and, if there was a change in sputum color, a course of antibiotics. A respiratory nurse followed up with telephone contact at 4, 12, and 26 weeks after the course. There was a trend to fewer exacerbation days in the intervention group (median 31 vs. 40, p ¼ 0.064), but there was no difference in the exacerbation severity scores or quality of life scores between the groups. Regarding hospitalizations, 14 patients in the intervention group had a hospital admission vs. 24 control patients (p ¼ 0.388). The self-treatment group was cost effective with 154 British pounds saved per patient. Reduced healthcare contacts were found in the intervention group (p ¼ 0.043). Rice and associates17 conducted a randomized controlled trial to assess the effect of a disease management program in reducing hospitalizations and ED visits due to COPD. The study was done at five Veterans Affairs medical centers. In this 1 year study of 743 patients with severe COPD, a usual care group (n ¼ 371) was compared to an intervention group (n ¼ 372), which received individual education sessions (1–1.5 hours), an action plan for self-management of exacerbations, and monthly followup calls from a case manager. The individualized written action plan consisted of refillable prescriptions for OCS (prednisone), an oral antimicrobial agent, contact information for a case manager, and the telephone number of a 24 hour helpline. Patients were to be in possession of action plan medications at all times and were to refill prescriptions immediately after starting the action plan. After 1 year of follow-up, the average number of COPD-related hospitalizations per patient was 30% lower in the disease management group, and the average number of ED visits was 50% lower. Hospitalization and ED visits combined were reduced by 41% in the intervention group (p50.001). Hospitalization rate was 39.8 per 100 patient years in the usual care group vs. 27.6 per 100 patient years in the intervention group (p ¼ 0.08). The percentage of patients who had at least one hospitalization due to COPD was 16.7% in the disease management group and 23.2% in the usual care group (p ¼ 0.03). All cause ! 2014 Informa UK Ltd www.cmrojournal.com
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mortality was assessed with 48 (12.9%) deaths occurring in the usual care group compared to 36 (9.7%) in the intervention group. As with the previously described study13, while the home management plan was multifaceted a key component included emphasizing early initiation of OCS therapy. In a randomized, controlled trial, Fan et al.18 compared a comprehensive care management program to guideline-based usual care in patients who had required hospitalization for COPD in the past year. The intervention group (n ¼ 209) and usual care group (n ¼ 217) were seen in 20 Veterans Affairs hospital-based clinics. The intervention group consisted of four individual COPD education sessions (1.5 hours each) and one group session, an action plan for exacerbations, and scheduled telephone calls from a case manager. The written, individualized action plan for home management of exacerbations included prescriptions for OCSs (prednisone) and an antibiotic. These prescriptions were to be filled and refilled as needed so that medications were always on hand. Patients were taught to initiate the action plan within 48 hours of the onset of exacerbation symptoms. Further, patients were instructed to call their case manager after starting their action plan. If symptoms worsened or failed to respond to therapy, patients were told to call their primary care clinician or 911. Clinicians in both the intervention and usual care groups were advised to manage their patients per evidence-based guidelines, and received a copy of the Global Initiative for Chronic Obstructive Lung Disease19. All usual care group patients received a COPD patient education booklet and had access to a VA 24 hour help line for questions regarding COPD. The primary study outcome was the time from entering the investigation to the first hospitalization for COPD. After 25 months of patient enrollment in the study, the intervention was stopped by the data monitoring committee due to safety concerns. When the investigation was discontinued, the 1 year cumulative incidence of hospitalizations due to COPD was 27% in the intervention group and 24% in the usual care group (p ¼ 0.62). There were 10 deaths from all causes in the usual care group and 28 deaths in the intervention group (p ¼ 0.003). More deaths due to COPD occurred in the intervention group (n ¼ 10) vs. the usual care group (n ¼ 3, p ¼ 0.053). Based on the available data, the investigators could not explain the excess mortality in the intervention group. During a 6 month follow-up period after the intervention was stopped, there were 15 deaths in the intervention group (four due to COPD) and 11 deaths in the usual care group (three due to COPD). Regarding the focus of this review article, an average of 2.5 exacerbations per patient-year were treated with OCS in the intervention group versus 2.1 in the usual care group (p ¼ 0.011). From onset of symptoms, the average delay to COPD action plans and oral corticosteroids Self et al.
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OCS treatment was 6.4 days in the intervention group versus 7.7 days in the usual care group (p ¼ 0.48). Therefore, the educational program for the intervention group did not result in the intended earlier (48 hours) OCS initiation compared to the usual care group. Similarly, there were no differences in use of antibiotics between the groups. The differences in outcomes in the trial by Fan et al.18 and the earlier quite similar studies14–17 is perplexing. The interventions, including educational programs and drug therapy, were comparable. Rice et al.17 enrolled patients from five VA medical centers in one administrative region, whereas Fan et al.18 included patients from 20 VA sites. Cardiovascular disease and unmarried status were more common in the intervention group. Fan et al.18 point out that a potentially relevant difference may have been the number of reinforcement telephone calls from case managers. These calls were scheduled monthly for 1 year in the Bourbeau14, Sridar15, and Rice17 trials, but in the Fan et al.18 study, calls were made on a monthly basis only for the first 3 months and then every 3 months. Effing et al.16 had scheduled calls at weeks 4, 13, and 26. Considering all five trials together, there were 76 deaths in the intervention groups and 81 deaths in the usual care groups (i.e. no difference)14–18. Table 1 summarizes the randomized trials aimed at reducing hospitalizations.
Nonrandomized studies evaluating the effect of action plans on exacerbations In 2000, Seemungal et al.20 studied symptoms and lung function changes associated with COPD exacerbations to determine factors which affected recovery. Over a period of 2.5 years, 101 moderate to severe COPD patients were followed both when stable and during 504 exacerbations (not requiring ED visit or hospitalization). Exacerbations were defined as the presence for at least two consecutive days of increase in any two major symptoms (dyspnea, sputum purulence, sputum amount) or increase in one major and one minor symptom (wheeze, sore throat, cough or nasal congestion/discharge). Patients were asked to contact the clinicians by telephone to schedule a clinic visit if their symptoms worsened, and they were seen within 2 days. This clinic visit included a prescription for 10 days of an antimicrobial agent and/or a 2 week course of OCSs (specific dose not included in this paper) if the physician deemed necessary. Hospitalizations were not assessed in this study. Exacerbations treated with OCSs were more severe, including larger decreases in peak expiratory flow (PEF) and longer PEF recovery time. However, the rate of PEF recovery was quicker with OCS therapy. For the focus of 2610
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this review article, an important finding was that the median time to the next exacerbation was significantly increased with OCS treatment (p ¼ 0.037). Specifically, the median time to the next exacerbation from the onset of initial exacerbation was 84 days in the prednisolone group (n ¼ 36 exacerbations) versus 60 days in the patients not receiving OCS therapy (n ¼ 96 exacerbations). Antibiotic therapy was not associated with increased time to next exacerbation (p40.09). Investigators from the same institution conducted a subsequent study that found early therapy at home reduces exacerbation rates21. Over a period of 6 years, 128 patients with moderate to severe COPD recorded 1099 exacerbations (defined above in the previous study20), including 658 reported to a physician. Among these 1099 exacerbations, 6.4% resulted in hospitalization. Failure to report exacerbations was associated with greater risk of hospitalization (p ¼ 0.04), and earlier therapy was associated with faster recovery. The time between the onset of the exacerbation to treatment was a median of 3.69 days. Among 625 exacerbations that were treated with prescribed oral therapy, a total of 266 exacerbations were treated with OCS. Six hundred of the exacerbations were treated with antibiotics and, of these, 241 had therapy that included both OCSs and antibiotics. Because 93.6% of exacerbations were treated with antimicrobial agents, a meaningful statistical analysis of the effect of antibiotic therapy on exacerbation outcomes was precluded, as the nontreated group was too small. Treatment with OCS hastened recovery by 2.63 days (p ¼ 0.001) compared with exacerbations not treated with OCS. However, the effect of OCS treatment on hospitalizations was not reported. Beaulieu-Genest et al.22 conducted a retrospective cohort study of 89 moderate to severe COPD patients. Prescriptions for OCSs and antibiotics were given to 46 of the patients over a 6 month period. Although no differences were found in unplanned medical visits between the patients who had these prescriptions versus those who did not, more patients given the prescriptions took short courses of OCSs (p ¼ 0.018) and antibiotics (p ¼ 0.006). The authors of this report expressed concern that more use of OCSs and antimicrobial agents did not reduce unplanned medical visits. However, without structured COPD education and case management support, a lack of reduction in unplanned visits is not unexpected. In a retrospective analysis of a randomized trial previously discussed14, Sedeno et al.23 added new findings in terms of patient behavior. The self-management program included structured education (‘Living Well with COPD’), a written action plan, and case manager support. The written action plan included prescriptions for OCSs and antibiotics for initiation by the patient in case of two or more symptoms (dyspnea, sputum volume, sputum purulence) for at least 24 hours. Case-manager reinforcement and www.cmrojournal.com ! 2014 Informa UK Ltd
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142 patients with COPD
122 patients with COPD
Sridhar et al.15 Randomized control trial
Effing et al.16 Randomized control trial
Advanced COPD with 1 hospitalization within the past year 95 patients in self-care management group compared to 95 patients in usual care
Patients
Bourbeau et al.14 Multi-center randomized control trial
Study
To calculate the frequency of exacerbations, the number of exacerbation days and mean daily severity scores
Primary: Rate of hospitalization Secondary: Unscheduled primary care consultations and quality of life
Primary: Number of hospitalizations Secondary: Number of emergency room visits and patients’ health status
Outcome
Table 1. Summary of randomized trials aimed at reducing hospitalizations..
Both groups received four 2 hour COPD patient education sessions regarding overall self-management Intervention group received training on self-treatment of exacerbations (when to start a course of OCS and/or a course of antibiotics) A respiratory nurse followed up via telephone at 4, 12, and 26 weeks after intervention
Pulmonary rehabilitation and self-management education, provision of a written, personalized COPD action plan, monthly telephone calls and 3 monthly home visits by a specialist nurse for a period of 2 years
Self-care management included education with 1 hr teachings for 8 wks followed by weekly phone f/u for 8 wks then monthly phone f/u for remainder of the study of 1 year. Action plan was customized for each patient for the management of infective symptoms (defined as at least two of the following: dyspnea, sputum, or sputum purulence). Patients were instructed to initiate antibiotics and an OCS for 10–14 days
Design
Results Total exacerbations resulted in hospital admission: 23.7% exacerbations in the selfmanagement group vs. 32.5% exacerbations in the usual care group Hospital readmission reduced by 39.8% Patients admitted for acute exacerbations during 1 year: At least 1 hospitalization– 32.3% in selfcare management group compared to 50.5% in the usual care group (p ¼ 0.01) 2 or more hospitalizations – 15.6% in the self-care management group compared to 30.5% in the usual care group (p ¼ 0.01) Self-care management group had fewer hospital days per patient (12.5% vs. 7.2%, p ¼ 0.01) No difference in hospitalizations during 2 year admission (52.7% in the intervention group vs. 48.9% controls, p ¼ 0.361) More intervention group patients were treated with OCS plus antibiotics (44% intervention vs. 28.3% controls, p ¼ 0.001) or OCS alone (19.8% vs. 7.7%, p ¼ 0.001). More deaths due to COPD occurred in the control group (8 of 12 deaths) vs. the intervention group (1 of 6 deaths), p ¼ 0.015 Number of exacerbation days in the intervention group compared to control (median 31 vs. 40, p ¼ 0.064) The difference was significant in the group of patients with a high number of exacerbation days per year (4137 (90th percentile of the whole study population); p¼0.028) No difference in the exacerbation severity scores or quality of life scores between the groups 14 hospitalizations in the intervention group had a hospital admission vs. 24 control patients (p ¼ 0.388) Reduced healthcare contacts in intervention group (p ¼ 0.043)
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(continued )
Self-treatment of exacerbations incorporated in a self-management program leads to fewer exacerbation days
Intermediate care package did not affect the hospital readmission rate
Hospitalizations reduced in the self-care management group compared to usual care group
Conclusions
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f/u: follow-up.
Fan et al.18 Multi-center randomized control trial
Rice et al.17 Multi-center randomized control trial
Study
Table 1. Continued.
743 patients with severe COPD and one or more of the following during the previous year: hospital admission or ED visit for COPD, chronic home oxygen use, or course of systemic corticosteroids for COPD 426 patients hospitalized for COPD in the past year
Patients
Primary outcome: time to first COPD hospitalization Secondary outcome: non-COPD healthcare use, all-cause mortality, health related quality of life, patient satisfaction, disease knowledge, and selfefficacy
To determine whether a simplified disease management program reduces hospital admissions and ED visits due to COPD
Outcome
Intervention group consisted of four individual COPD education sessions (1.5 hours each) and one group session, an action plan for exacerbations, and scheduled telephone calls from a case manager. The written, individualized action plan for home management of exacerbations included prescriptions for OCSs and an antibiotic. Patients were taught to initiate the action plan within 48 hours of the onset of exacerbation symptoms
Intervention group received individual education sessions (1–1.5 hours), an action plan for self-management of exacerbations, and monthly follow-up calls from a case manager. The individualized written action plan consisted of refillable prescriptions for OCS and an oral antimicrobial agent, a case manager’s contact information, and the telephone number of a 24 hour helpline
Design
Results
1 year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (HR 1.13 [95% CI, 0.70 to 1.80]; p ¼ 0.62) 28 deaths from all causes in the intervention group compared to 10 in the usual care group (HR, 3.00 [CI, 1.4 to 6.17]; p ¼ 0.003)
COPD-related hospitalizations intervention group compared to usual care group (39.8 vs. 27.6 per 100 patient-years; RR, 0.69; 95% CI, 0.47–1.01; p ¼ 0.08) COPD-related ED visits intervention group compared to usual care group (42.4 vs. 20.8 per 100 patient-years; RR, 0.49; 95% CI, 0.33–0.72; p50.001)
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Intervention group did not differ in hospitalizations
Disease management program reduced hospitalizations and ED visits compared to usual care group
Conclusions
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monthly telephone follow-ups were part of the action plan. At the end of the 12 month follow-up, 17.2% of exacerbations in the action plan group resulted in hospitalizations vs. the usual care group with 36.3% (p50.001). Among 606 exacerbations, at least one symptom was present, and 67.6% of patients had two or more symptoms. When exacerbations included two or more symptoms, antibiotics and OCS were used together more frequently in the action plan group (54.4%vs. 34.8%, p50.001). Bischoff et al.24 conducted a 12 month prospective cohort study in COPD patients to evaluate the effects of adherence to a written action plan on exacerbation recovery time and unscheduled healthcare utilization. Patients (n ¼ 252 [majority moderate to severe COPD]) were given COPD education, support by case management, and a written action plan for home management of exacerbations. The action plan was to be started within 3 days of the onset of exacerbation (change for at least 24 hours in dyspnea, sputum volume, sputum color), and it included prescriptions for OCS and antibiotics. Among 288 exacerbations reported by 143 patients, dates for initiation of OCSs or antibiotics were recorded for 217 exacerbations by 119 patients. Patients adhered to their written action plans in 40.1% of exacerbations, and this adherence reduced recovery time by a mean of 5.08 days (p ¼ 0.0001) but did not decrease unscheduled healthcare utilization.
Other related studies One small randomized trial evaluated the long-term effects of pulmonary rehabilitation on factors such as dyspnea and quality of life as well as hospitalizations25. Both the pulmonary rehabilitation (e.g. breathing retraining; exercise) group and the usual care group had home use of OCSs and antibiotics as part of routine home management for exacerbations. There was no statistical difference between the groups in hospitalizations. We note that two additional small studies have used OCS and antibiotics as part of an action plan at home, and while this intervention revealed no difference with the usual care groups, the studies did not assess hospitalizations or ED visits26,27. These studies evaluated other parameters such as quality of life, symptom scores, walking distance, and pulmonary function tests26,27.
Discussion OCSs are very effective in treating patients hospitalized for COPD exacerbations, including reducing length of hospital stay7,8. Therefore, it is logical to evaluate whether, as part of a comprehensive action plan, starting OCS therapy at home early in the exacerbation may decrease ! 2014 Informa UK Ltd www.cmrojournal.com
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the need for unscheduled office visits, ED visits, or hospitalizations. A very similar approach is effective for home management of asthma exacerbations and is recommended in national guidelines28,29. Further randomized trials are needed to establish that action plans, including OCS therapy, reduce hospitalizations for COPD exacerbations. However, the trials by Bourbeau et al.14 and Rice et al.17 provide compelling evidence that comprehensive action plans are effective. It is potentially a pertinent point that these investigators included closer (monthly) telephone follow-up than Fan et al.18 and Effing et al.16. Sridar et al.15 also provided monthly telephone follow-up and found reduced deaths in the action plan group. Based on studies to date, it is certainly reasonable that further investigations should include monthly telephone follow-up as a component of the home action plan. In an editorial response to the trial by Fan et al.18, Pocock30 points out that there is no convincing evidence that harm was caused by the comprehensive intervention. Yeatts et al.31 reported in 2013 on the population-based burden of COPD-related visits in the ED, including return ED visits and hospitalizations. In this 2 year study in North Carolina, 97,511 ED visits occurred due to COPD. Return ED visits were found in 7% of patients within 30 days, and 28% of patients had a return ED visit within 365 days. Among COPD patients with an ED visit, 51% were admitted to the hospital from the ED31. This very recent study further emphasizes the need for strategies to reduce ED visits and hospitalizations associated with COPD exacerbations. Because oral antibiotic therapy is combined with OCSs in most studies of COPD action plans, the recent study by Miravitlles et al.32 is important to note briefly. Among the three standard (Anthonisen) criteria of increased dyspnea, increased sputum volume, and increased sputum purulence, only increase in sputum purulence was associated with risk of failure in COPD patients without antibiotics. Clinical failure was observed in 9.5% of mild to moderate COPD patients with exacerbations seen in a primary care clinic and prescribed amoxicillin/clavulanate therapy versus 19.9% of patients without antibiotic treatment (p ¼ 0.022). A second predictor of clinical failure was a point-of-care serum C-reactive protein32. Therefore, if further study validates the investigation by Miravitlles et al.32, oral antibiotics may routinely be needed as part of home action plans only in patients with mild to moderate COPD who have increase in sputum purulence. Another important factor in predicting hospitalization is the physical capacity of COPD patients. A recent study by Garcia-Rio et al.33 evaluated 173 patients with moderate to very severe COPD. The daily physical activity in these patients was an independent prognostic factor for mortality and hospitalization due to severe exacerbations. Zanoria and ZuWallack34 confirmed this observation, and COPD action plans and oral corticosteroids Self et al.
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reported that a 6 minute walk distance test of5350 m significantly predicted subsequent all-cause and respiratoryrelated hospitalizations. Consequently, this aspect of home management of COPD exacerbations must be absolutely considered. Of interest, in the negative study by Fan et al.18, no data were reported on the physical capacity of patients. Therefore, it is possible that an unbalanced distribution of patients with poor physical capacity favored the control group. Because increased sputum production (and possibly mucus plugging) is commonly seen in COPD exacerbations, we note a very recent exhaustive review of nonpharmacologic airway clearance techniques in hospitalized patients35. Unfortunately, data from several studies in acutely ill COPD patients revealed no significant short term benefit from nonpharmacologic airway clearance modalities35. Future investigations should include evaluations of inner city COPD patients. For example, strict adherence to comprehensive action plans and ability to maintain monthly telephone follow-up in disadvantaged populations would be challenging. Nevertheless, with comprehensive care including patient education, and frequent telephone follow-up by case managers, many patients who receive prompt initiation of OCS and oral antibiotics at home will likely have reduced rates of hospitalization for COPD exacerbations. Beyond a reduction in human suffering, there is obvious potential for achieving a marked decreased in healthcare costs associated with early intervention in COPD exacerbation at home.
Conclusion More randomized trials are needed to clearly establish that home use of OCS therapy, as part of a comprehensive action plan, reduces the rate of hospitalizations for COPD. Such action plans should include structured patient education, early initiation of OCS, oral antibiotics, and frequent telephone reinforcement and support from case management.
Transparency Declaration of funding This study was not funded. Declaration of financial/other relationships C.K.F. has disclosed that he is a speaker for GlaxoSmithKline. T.H.S., S.J.P. and A.S.H. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose. 2614
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References 1. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2014. Global Initiative for Chronic Obstructive Lung Disease. Available at: www.goldcopd.org [Last accessed 21 February 2014] 2. American Lung Association. Available at: www.lung.org/lung-disease/ [Last accessed 21 February 2014] 3. Guarascio AJ, Ray SM, Finch CK, et al. The clinical and economic burden of chronic obstructive pulmonary disease in the USA. ClinicoEconomics Outcomes Research 2013;5:235-45 4. Garcia-Aymerich J, Pons IS, Mannino DM, et al. Lung function impairment COPD hospitalizations and subsequent mortality. Thorax 2011;66:585-90 5. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbations in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128-38 6. Centers for Medicare and Medicaid Services. Readmissions Reduction Program. Available at: http://www.cms.gov/Medicare/Medicare-Fee-forService-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html [Last accessed 27 November 2013] 7. Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1999;340:1941-7 8. Davies L, Angus RM, Calverley PMA. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomized trial. Lancet 1999;354:456-60 9. Albert RK, Martin TR, Lewis SW. Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Ann Intern Med 1980;92:753-8 10. Murata GH, Gorby MS, Chick TW, et al. Intravenous and oral corticosteroids for the prevention and relapse after treatment of decompensated COPD: effect of patients with a history of multiple relapses. Chest 1990;98:845-9 11. Aaron SD, Vandemheen KL, Hebert P, et al. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 2003;348:2618-25 12. Thompson WH, Nielson CP, Carvalho P, et al. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med 1996;154:407-12 13. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: The REDUCE randomized clinical trial. JAMA 2013;309:2223-31 14. Bourbeau J, Julien M, Maltais F, et al. Reduction of hospital utilization in patients with chronic obstructive pulmonary disease. Arch Intern Med 2003;163:585-91 15. Sridhar M, Taylor R, Dawson S, et al. A nurse led intermediate care package in patients who have been hospitalized with an acute exacerbation of chronic obstructive pulmonary disease. Thorax 2008;63:194-200 16. Effing T, Kerstjens H, van der Valk P, et al. Cost-effectiveness of self-treatment of exacerbations on the severity of exacerbations in patients with COPD: the COPE II study. Thorax 2009;64:956-62 17. Rice KL, Dewan N, Bloomfield HE, et al. Disease management program for chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med 2010;182:890-6 18. Fan VS, Gaziano JM, Lew R, et al. A comprehensive care management program to prevent chronic obstructive pulmonary disease hospitalizations. Ann Intern Med 2012;156:673-83 19. Rabe KF, Hurd S, Anzueto A, et al; Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007;176:532-55 20. Seemungal TA, Donaldson GC, Bhowmik A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1608-13 21. Wilkinson TMA, Donaldson GC, Hurst JR, et al. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;169:1298-303
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22. Beaulieu-Genest L, Chretien D, Maltais F, et al. Self-administered prescriptions of oral steroids and antibiotics in chronic obstructive pulmonary disease: are we doing more harm than good? Chron Respir Dis 2007;4:143-7 23. Sedeno MF, Nault D, Hamd DH, et al. A self-management education program including an action plan for acute COPD exacerbation. COPD 2009;6:352-8 24. Bischoff EWMA, Hamd DH, Sedeno M, et al. Effects of written action plan adherence on COPD exacerbation recovery. Thorax 2011;66:26-31 25. Guell R, Casan P, Belda J, et al. Long-term effects of outpatient rehabilitation of COPD: a randomized trial. Chest 2000;117:976-83 26. Watson PB, Town GI, Holbrook N, et al. Evaluation of a self-management plan for chronic obstructive pulmonary disease. Eur Respir J 1997;10:1267-71 27. Monninkhof E, van der Valk P, vander Palen J, et al. Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease. Eur Respir J 2003;22:815-20 28. Self TH, Chrisman CR, Jacobs AR, et al. Preventing emergency department visits and hospitalizations for asthma by use of oral corticosteroids at home: are we adhering to national guidelines? J Asthma 2010;47:1123-7
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29. Expert Panel Report 3. Guidelines for the Diagnosis and Management of Asthma. National Asthma Education and Prevention Program. Bethesda, MD: National Institutes of Health, 2007 30. Pocock SJ. Ethical dilemmas and malfunctions in clinical trials research. Ann Intern Med 2012;156:746-7 31. Yeatts KB, Lippmann SJ, Waller AE, et al. Population-based burden of COPDrelated visits in the ED: return ED visits, hospital admissions, and comorbidity risks. Chest 2013;144:784-93 32. Miravitlles M, Moragas A, Hernandez S, et al. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment. Chest 2013;144:1571-7 33. Garcia-Rio F, Rojo B, Casitas R, et al. Prognostic value of the objective measurement of daily physical activity in patients with COPD. Chest 2012;142:338-46 34. Zanoria SJ, ZuWallack R. Directly measured physical activity as a predictor of hospitalizations in patients with chronic obstructive pulmonary disease. Chron Respir Dis 2013;10:207-13 35. Andrews J, Sathe NA, Krishnaswami S, et al. Nonpharmacologic airway clearance techniques in hospitalized patients: a systematic review. Respir Care 2013;58:2160-86
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Action plans to reduce hospitalizations for chronic obstructive pulmonary disease exacerbations: focus on oral corticosteroids a
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Timothy H. Self , Shanise J. Patterson , Arthur S. Headley & Christopher K. Finch a
University of Tennessee Health Science Center, Methodist University Hospital Memphis, TNUSA Published online: 26 May 2015.
Click for updates To cite this article: Timothy H. Self, Shanise J. Patterson, Arthur S. Headley & Christopher K. Finch (2014) Action plans to reduce hospitalizations for chronic obstructive pulmonary disease exacerbations: focus on oral corticosteroids, Current Medical Research and Opinion, 30:12, 2607-2615 To link to this article: http://dx.doi.org/10.1185/03007995.2014.934795
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Review Action plans to reduce hospitalizations for chronic obstructive pulmonary disease exacerbations: focus on oral corticosteroids
Timothy H. Self Shanise J. Patterson Arthur S. Headley Christopher K. Finch University of Tennessee Health Science Center, Methodist University Hospital, Memphis, TN, USA Address for correspondence: Dr. Timothy H. Self, University of Tennessee Health Science Center, 881 Madison Ave., Room 235, Memphis, TN 38163, USA. [email protected] Keywords: COPD exacerbations – Hospitalizations – Self-management action plans Accepted: 10 June 2014; published online: 30 June 2014 Citation: Curr Med Res Opin 2014; 30:2607–15
Abstract Objective: Chronic obstructive pulmonary disease (COPD) is associated with a huge burden of suffering and healthcare expenditures. Patients hospitalized due to COPD have increased risk of death. Starting in 2015, reimbursements by the Centers for Medicaid Medicare Services will be significantly reduced to hospitals with excess 30 day readmissions for COPD. Oral corticosteroid (OCS) therapy is established in improving outcomes in COPD patients treated in the emergency department and hospital. The objective of this article is to review the evidence evaluating home OCS treatment of COPD exacerbations as part of a comprehensive self-management action plan. Methods: We reviewed the English literature via PubMed, Embase, and Scopus using the search terms: chronic obstructive pulmonary disease exacerbations AND: oral corticosteroids, prednisone, prednisolone, methylprednisolone, treatment, self-management, disease management, written action plans. When pertinent articles were found, we reviewed the relevant articles cited. Findings: Two randomized trials enrolling 933 patients provide evidence of reduced rates of hospitalization by using comprehensive COPD action plans, including OCS therapy. Three trials with 790 patients enrolled did not reveal reduced rates of hospitalization. Among all five trials together, there were no differences in deaths (76 in the intervention groups [home action plans]; 81 in the usual care groups). Additional studies not assessing hospitalizations have found home use of OCSs increases time to the next exacerbation and decreases recovery time. Conclusion: Further randomized trials are needed to establish that home use of OCS therapy, as part of a comprehensive action plan, reduces the rate of hospitalizations. Such action plans should include structured patient education, early initiation of OCSs, oral antibiotics, and frequent telephone reinforcement and support from case management.
Introduction Chronic obstructive pulmonary disease (COPD) is associated with immense morbidity and economic costs1–3. It is now the third leading cause of death in the US, and hospitalizations due to exacerbations of COPD are associated with increased risk of death1,4. Recent research has shown that the best predictor of a patient having a COPD exacerbation is treatment for an exacerbation in the prior year5. Current evidence demonstrates that roughly 20% of all hospitalized ! 2014 Informa UK Ltd www.cmrojournal.com
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COPD patients get readmitted within 30 days of discharge3. Thus, effective strategies to reduce COPD exacerbations are essential. These data have led to the addition of COPD to the Affordable Care Act core measures6. This change is set to begin in October of 2015 and will significantly reduce payments to hospitals with excess readmissions for this chronic and progressive disease6. The 2014 updated GOLD guidelines point out that 80% of COPD exacerbations can be managed on an outpatient basis1. The purpose of this review article is to focus on the evidence regarding oral corticosteroid (OCS) therapy as one key component of an action plan for home management of COPD exacerbations. A primary goal of such an action plan, as part of a disease-specific self-management intervention, is to reduce hospitalizations. Oral corticosteroid therapy is clearly established as standard drug therapy in patients hospitalized for COPD exacerbations7–9. Because of the efficacy of OCS therapy in the hospitalized patient, including shorter hospital stays7,8, it is logical to assess outcomes of this therapy starting at home at the first sign of a COPD exacerbation. In addition, systemic corticosteroid therapy in the emergency department (ED) or for 10 days after discharge from the ED, is associated with reduced relapse rates10–12. A recent randomized trial found that a 5 day course of prednisone for patients presenting to the ED for treatment of COPD exacerbations was noninferior to a 14 day course13. Noninferiority included time to re-exacerbation over 6 months13. We reviewed the English literature from 1980 to March 2014 via PubMed, Embase, and Scopus using the search terms: chronic obstructive pulmonary disease exacerbations AND: oral corticosteroids, prednisone, prednisolone, methylprednisolone, treatment, selfmanagement, disease management, written action plans. When pertinent articles were found, we reviewed the relevant articles cited. This summary of the literature includes each study found that included oral corticosteroid (OCS) therapy in the home management of COPD exacerbations in an effort to prevent hospitalizations. While we have emphasized randomized controlled trials in this review article, we have included nonrandomized trials and other pertinent literature for completeness. In addition to the subject of our review article, we stress that optimal evidence-based pharmacologic therapy, avoidance of triggers, and appropriate vaccinations are proven to reduce exacerbations1.
Randomized, controlled trials specifically assessing prevention of hospitalizations Bourbeau and colleagues14 evaluated the effect of a disease-specific self-management intervention on 2608
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hospitalizations in COPD patients. In this randomized study, 95 COPD patients were in the usual care group and 95 patients were in the self-management group. In the prior year, all of these advanced COPD patients had at least one hospitalization for COPD. The self-management group received comprehensive patient education given by trained healthcare professionals via weekly visits over a 2 month period with monthly telephone follow-up. The action plan for exacerbations was customized for each patient, including a contact list and a symptom-monitoring list linked to appropriate actions. Patients had prescriptions to be initiated promptly when at least two of the three following symptom changes were noted: dyspnea, sputum volume, or sputum purulence. Emphasis was placed on starting an antibiotic and OCS for 10 to 14 days for exacerbations with these symptoms associated with infection. Safeguards were included to call the case manager or physician if these symptoms became worse after initiation of therapy at home. Hospital admissions for COPD exacerbations were reduced by 39.8%. In the usual care group, 118 (32.5%) of the 362 total exacerbations resulted in hospital admission versus 71 (23.7%) of the 299 exacerbations in the self-management group. In addition, more patients in the usual care group had at least one hospitalization (50.5%) compared to the intervention group (32.3%, p ¼ 0.01) and 2 admissions (30.5% vs. 15.5%, p ¼ 0.01) during the 1 year study period. Finally, the intervention group had fewer hospital days per patient (12.5 vs. 7.2, p ¼ 0.01). Although it is not known which components of the self-management program had the greatest positive impact, one key feature of the program was stressing the early use of OCS therapy. Sridhar et al.15 studied the effects of a program led by nurses for patients with a history of hospitalization for COPD. Patients were randomized to a control group (n ¼ 61) or an intervention group (n ¼ 61), consisting of pulmonary rehabilitation, self-management education, a written COPD action plan, monthly telephone calls, and three monthly home visits by a nurse specialist for a period of 2 years. The written action plan included advice regarding lifestyle and maintenance medications as well as instructions on when to initiate a course of antibiotics and OCS. The clinicians for these patients were asked to provide reserve supplies of these drugs for the patients. The primary outcome measure was the rate of hospitalizations. There was no difference between the groups in hospitalizations (52.7% in the intervention group vs. 48.9% controls, p ¼ 0.361). More intervention group patients were treated with OCSs plus antibiotics (44% intervention vs. 28.3% controls, p ¼ 0.001) or OCS alone (19.8% vs. 7.7%, p ¼ 0.001). More deaths due to COPD occurred in the control group (8 of 12 deaths) vs. the intervention group (1 of 6 deaths), p ¼ 0.015. Although comorbidities www.cmrojournal.com ! 2014 Informa UK Ltd
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such as a ‘severe heart disease’, cancer, and ethanol-related hepatic disease were among exclusion criteria for this study, not all comorbidities are listed (e.g. the groups could have been different with respect to ‘moderate’ cardiovascular diseases). Effing et al.16 evaluated the effectiveness of self-treatment on the severity of exacerbations in 142 moderate to severe COPD patients. In this 12 month study, patients were randomized to an intervention group (n ¼ 70) or a control group (n ¼ 72). Both groups received four 2 hour COPD patient education sessions regarding overall self-management. The intervention group also received training on self-treatment of exacerbations, including when to start a course of OCSs (prednisolone 30 mg for 7 days) and, if there was a change in sputum color, a course of antibiotics. A respiratory nurse followed up with telephone contact at 4, 12, and 26 weeks after the course. There was a trend to fewer exacerbation days in the intervention group (median 31 vs. 40, p ¼ 0.064), but there was no difference in the exacerbation severity scores or quality of life scores between the groups. Regarding hospitalizations, 14 patients in the intervention group had a hospital admission vs. 24 control patients (p ¼ 0.388). The self-treatment group was cost effective with 154 British pounds saved per patient. Reduced healthcare contacts were found in the intervention group (p ¼ 0.043). Rice and associates17 conducted a randomized controlled trial to assess the effect of a disease management program in reducing hospitalizations and ED visits due to COPD. The study was done at five Veterans Affairs medical centers. In this 1 year study of 743 patients with severe COPD, a usual care group (n ¼ 371) was compared to an intervention group (n ¼ 372), which received individual education sessions (1–1.5 hours), an action plan for self-management of exacerbations, and monthly followup calls from a case manager. The individualized written action plan consisted of refillable prescriptions for OCS (prednisone), an oral antimicrobial agent, contact information for a case manager, and the telephone number of a 24 hour helpline. Patients were to be in possession of action plan medications at all times and were to refill prescriptions immediately after starting the action plan. After 1 year of follow-up, the average number of COPD-related hospitalizations per patient was 30% lower in the disease management group, and the average number of ED visits was 50% lower. Hospitalization and ED visits combined were reduced by 41% in the intervention group (p50.001). Hospitalization rate was 39.8 per 100 patient years in the usual care group vs. 27.6 per 100 patient years in the intervention group (p ¼ 0.08). The percentage of patients who had at least one hospitalization due to COPD was 16.7% in the disease management group and 23.2% in the usual care group (p ¼ 0.03). All cause ! 2014 Informa UK Ltd www.cmrojournal.com
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mortality was assessed with 48 (12.9%) deaths occurring in the usual care group compared to 36 (9.7%) in the intervention group. As with the previously described study13, while the home management plan was multifaceted a key component included emphasizing early initiation of OCS therapy. In a randomized, controlled trial, Fan et al.18 compared a comprehensive care management program to guideline-based usual care in patients who had required hospitalization for COPD in the past year. The intervention group (n ¼ 209) and usual care group (n ¼ 217) were seen in 20 Veterans Affairs hospital-based clinics. The intervention group consisted of four individual COPD education sessions (1.5 hours each) and one group session, an action plan for exacerbations, and scheduled telephone calls from a case manager. The written, individualized action plan for home management of exacerbations included prescriptions for OCSs (prednisone) and an antibiotic. These prescriptions were to be filled and refilled as needed so that medications were always on hand. Patients were taught to initiate the action plan within 48 hours of the onset of exacerbation symptoms. Further, patients were instructed to call their case manager after starting their action plan. If symptoms worsened or failed to respond to therapy, patients were told to call their primary care clinician or 911. Clinicians in both the intervention and usual care groups were advised to manage their patients per evidence-based guidelines, and received a copy of the Global Initiative for Chronic Obstructive Lung Disease19. All usual care group patients received a COPD patient education booklet and had access to a VA 24 hour help line for questions regarding COPD. The primary study outcome was the time from entering the investigation to the first hospitalization for COPD. After 25 months of patient enrollment in the study, the intervention was stopped by the data monitoring committee due to safety concerns. When the investigation was discontinued, the 1 year cumulative incidence of hospitalizations due to COPD was 27% in the intervention group and 24% in the usual care group (p ¼ 0.62). There were 10 deaths from all causes in the usual care group and 28 deaths in the intervention group (p ¼ 0.003). More deaths due to COPD occurred in the intervention group (n ¼ 10) vs. the usual care group (n ¼ 3, p ¼ 0.053). Based on the available data, the investigators could not explain the excess mortality in the intervention group. During a 6 month follow-up period after the intervention was stopped, there were 15 deaths in the intervention group (four due to COPD) and 11 deaths in the usual care group (three due to COPD). Regarding the focus of this review article, an average of 2.5 exacerbations per patient-year were treated with OCS in the intervention group versus 2.1 in the usual care group (p ¼ 0.011). From onset of symptoms, the average delay to COPD action plans and oral corticosteroids Self et al.
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OCS treatment was 6.4 days in the intervention group versus 7.7 days in the usual care group (p ¼ 0.48). Therefore, the educational program for the intervention group did not result in the intended earlier (48 hours) OCS initiation compared to the usual care group. Similarly, there were no differences in use of antibiotics between the groups. The differences in outcomes in the trial by Fan et al.18 and the earlier quite similar studies14–17 is perplexing. The interventions, including educational programs and drug therapy, were comparable. Rice et al.17 enrolled patients from five VA medical centers in one administrative region, whereas Fan et al.18 included patients from 20 VA sites. Cardiovascular disease and unmarried status were more common in the intervention group. Fan et al.18 point out that a potentially relevant difference may have been the number of reinforcement telephone calls from case managers. These calls were scheduled monthly for 1 year in the Bourbeau14, Sridar15, and Rice17 trials, but in the Fan et al.18 study, calls were made on a monthly basis only for the first 3 months and then every 3 months. Effing et al.16 had scheduled calls at weeks 4, 13, and 26. Considering all five trials together, there were 76 deaths in the intervention groups and 81 deaths in the usual care groups (i.e. no difference)14–18. Table 1 summarizes the randomized trials aimed at reducing hospitalizations.
Nonrandomized studies evaluating the effect of action plans on exacerbations In 2000, Seemungal et al.20 studied symptoms and lung function changes associated with COPD exacerbations to determine factors which affected recovery. Over a period of 2.5 years, 101 moderate to severe COPD patients were followed both when stable and during 504 exacerbations (not requiring ED visit or hospitalization). Exacerbations were defined as the presence for at least two consecutive days of increase in any two major symptoms (dyspnea, sputum purulence, sputum amount) or increase in one major and one minor symptom (wheeze, sore throat, cough or nasal congestion/discharge). Patients were asked to contact the clinicians by telephone to schedule a clinic visit if their symptoms worsened, and they were seen within 2 days. This clinic visit included a prescription for 10 days of an antimicrobial agent and/or a 2 week course of OCSs (specific dose not included in this paper) if the physician deemed necessary. Hospitalizations were not assessed in this study. Exacerbations treated with OCSs were more severe, including larger decreases in peak expiratory flow (PEF) and longer PEF recovery time. However, the rate of PEF recovery was quicker with OCS therapy. For the focus of 2610
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this review article, an important finding was that the median time to the next exacerbation was significantly increased with OCS treatment (p ¼ 0.037). Specifically, the median time to the next exacerbation from the onset of initial exacerbation was 84 days in the prednisolone group (n ¼ 36 exacerbations) versus 60 days in the patients not receiving OCS therapy (n ¼ 96 exacerbations). Antibiotic therapy was not associated with increased time to next exacerbation (p40.09). Investigators from the same institution conducted a subsequent study that found early therapy at home reduces exacerbation rates21. Over a period of 6 years, 128 patients with moderate to severe COPD recorded 1099 exacerbations (defined above in the previous study20), including 658 reported to a physician. Among these 1099 exacerbations, 6.4% resulted in hospitalization. Failure to report exacerbations was associated with greater risk of hospitalization (p ¼ 0.04), and earlier therapy was associated with faster recovery. The time between the onset of the exacerbation to treatment was a median of 3.69 days. Among 625 exacerbations that were treated with prescribed oral therapy, a total of 266 exacerbations were treated with OCS. Six hundred of the exacerbations were treated with antibiotics and, of these, 241 had therapy that included both OCSs and antibiotics. Because 93.6% of exacerbations were treated with antimicrobial agents, a meaningful statistical analysis of the effect of antibiotic therapy on exacerbation outcomes was precluded, as the nontreated group was too small. Treatment with OCS hastened recovery by 2.63 days (p ¼ 0.001) compared with exacerbations not treated with OCS. However, the effect of OCS treatment on hospitalizations was not reported. Beaulieu-Genest et al.22 conducted a retrospective cohort study of 89 moderate to severe COPD patients. Prescriptions for OCSs and antibiotics were given to 46 of the patients over a 6 month period. Although no differences were found in unplanned medical visits between the patients who had these prescriptions versus those who did not, more patients given the prescriptions took short courses of OCSs (p ¼ 0.018) and antibiotics (p ¼ 0.006). The authors of this report expressed concern that more use of OCSs and antimicrobial agents did not reduce unplanned medical visits. However, without structured COPD education and case management support, a lack of reduction in unplanned visits is not unexpected. In a retrospective analysis of a randomized trial previously discussed14, Sedeno et al.23 added new findings in terms of patient behavior. The self-management program included structured education (‘Living Well with COPD’), a written action plan, and case manager support. The written action plan included prescriptions for OCSs and antibiotics for initiation by the patient in case of two or more symptoms (dyspnea, sputum volume, sputum purulence) for at least 24 hours. Case-manager reinforcement and www.cmrojournal.com ! 2014 Informa UK Ltd
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142 patients with COPD
122 patients with COPD
Sridhar et al.15 Randomized control trial
Effing et al.16 Randomized control trial
Advanced COPD with 1 hospitalization within the past year 95 patients in self-care management group compared to 95 patients in usual care
Patients
Bourbeau et al.14 Multi-center randomized control trial
Study
To calculate the frequency of exacerbations, the number of exacerbation days and mean daily severity scores
Primary: Rate of hospitalization Secondary: Unscheduled primary care consultations and quality of life
Primary: Number of hospitalizations Secondary: Number of emergency room visits and patients’ health status
Outcome
Table 1. Summary of randomized trials aimed at reducing hospitalizations..
Both groups received four 2 hour COPD patient education sessions regarding overall self-management Intervention group received training on self-treatment of exacerbations (when to start a course of OCS and/or a course of antibiotics) A respiratory nurse followed up via telephone at 4, 12, and 26 weeks after intervention
Pulmonary rehabilitation and self-management education, provision of a written, personalized COPD action plan, monthly telephone calls and 3 monthly home visits by a specialist nurse for a period of 2 years
Self-care management included education with 1 hr teachings for 8 wks followed by weekly phone f/u for 8 wks then monthly phone f/u for remainder of the study of 1 year. Action plan was customized for each patient for the management of infective symptoms (defined as at least two of the following: dyspnea, sputum, or sputum purulence). Patients were instructed to initiate antibiotics and an OCS for 10–14 days
Design
Results Total exacerbations resulted in hospital admission: 23.7% exacerbations in the selfmanagement group vs. 32.5% exacerbations in the usual care group Hospital readmission reduced by 39.8% Patients admitted for acute exacerbations during 1 year: At least 1 hospitalization– 32.3% in selfcare management group compared to 50.5% in the usual care group (p ¼ 0.01) 2 or more hospitalizations – 15.6% in the self-care management group compared to 30.5% in the usual care group (p ¼ 0.01) Self-care management group had fewer hospital days per patient (12.5% vs. 7.2%, p ¼ 0.01) No difference in hospitalizations during 2 year admission (52.7% in the intervention group vs. 48.9% controls, p ¼ 0.361) More intervention group patients were treated with OCS plus antibiotics (44% intervention vs. 28.3% controls, p ¼ 0.001) or OCS alone (19.8% vs. 7.7%, p ¼ 0.001). More deaths due to COPD occurred in the control group (8 of 12 deaths) vs. the intervention group (1 of 6 deaths), p ¼ 0.015 Number of exacerbation days in the intervention group compared to control (median 31 vs. 40, p ¼ 0.064) The difference was significant in the group of patients with a high number of exacerbation days per year (4137 (90th percentile of the whole study population); p¼0.028) No difference in the exacerbation severity scores or quality of life scores between the groups 14 hospitalizations in the intervention group had a hospital admission vs. 24 control patients (p ¼ 0.388) Reduced healthcare contacts in intervention group (p ¼ 0.043)
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(continued )
Self-treatment of exacerbations incorporated in a self-management program leads to fewer exacerbation days
Intermediate care package did not affect the hospital readmission rate
Hospitalizations reduced in the self-care management group compared to usual care group
Conclusions
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f/u: follow-up.
Fan et al.18 Multi-center randomized control trial
Rice et al.17 Multi-center randomized control trial
Study
Table 1. Continued.
743 patients with severe COPD and one or more of the following during the previous year: hospital admission or ED visit for COPD, chronic home oxygen use, or course of systemic corticosteroids for COPD 426 patients hospitalized for COPD in the past year
Patients
Primary outcome: time to first COPD hospitalization Secondary outcome: non-COPD healthcare use, all-cause mortality, health related quality of life, patient satisfaction, disease knowledge, and selfefficacy
To determine whether a simplified disease management program reduces hospital admissions and ED visits due to COPD
Outcome
Intervention group consisted of four individual COPD education sessions (1.5 hours each) and one group session, an action plan for exacerbations, and scheduled telephone calls from a case manager. The written, individualized action plan for home management of exacerbations included prescriptions for OCSs and an antibiotic. Patients were taught to initiate the action plan within 48 hours of the onset of exacerbation symptoms
Intervention group received individual education sessions (1–1.5 hours), an action plan for self-management of exacerbations, and monthly follow-up calls from a case manager. The individualized written action plan consisted of refillable prescriptions for OCS and an oral antimicrobial agent, a case manager’s contact information, and the telephone number of a 24 hour helpline
Design
Results
1 year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (HR 1.13 [95% CI, 0.70 to 1.80]; p ¼ 0.62) 28 deaths from all causes in the intervention group compared to 10 in the usual care group (HR, 3.00 [CI, 1.4 to 6.17]; p ¼ 0.003)
COPD-related hospitalizations intervention group compared to usual care group (39.8 vs. 27.6 per 100 patient-years; RR, 0.69; 95% CI, 0.47–1.01; p ¼ 0.08) COPD-related ED visits intervention group compared to usual care group (42.4 vs. 20.8 per 100 patient-years; RR, 0.49; 95% CI, 0.33–0.72; p50.001)
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Intervention group did not differ in hospitalizations
Disease management program reduced hospitalizations and ED visits compared to usual care group
Conclusions
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monthly telephone follow-ups were part of the action plan. At the end of the 12 month follow-up, 17.2% of exacerbations in the action plan group resulted in hospitalizations vs. the usual care group with 36.3% (p50.001). Among 606 exacerbations, at least one symptom was present, and 67.6% of patients had two or more symptoms. When exacerbations included two or more symptoms, antibiotics and OCS were used together more frequently in the action plan group (54.4%vs. 34.8%, p50.001). Bischoff et al.24 conducted a 12 month prospective cohort study in COPD patients to evaluate the effects of adherence to a written action plan on exacerbation recovery time and unscheduled healthcare utilization. Patients (n ¼ 252 [majority moderate to severe COPD]) were given COPD education, support by case management, and a written action plan for home management of exacerbations. The action plan was to be started within 3 days of the onset of exacerbation (change for at least 24 hours in dyspnea, sputum volume, sputum color), and it included prescriptions for OCS and antibiotics. Among 288 exacerbations reported by 143 patients, dates for initiation of OCSs or antibiotics were recorded for 217 exacerbations by 119 patients. Patients adhered to their written action plans in 40.1% of exacerbations, and this adherence reduced recovery time by a mean of 5.08 days (p ¼ 0.0001) but did not decrease unscheduled healthcare utilization.
Other related studies One small randomized trial evaluated the long-term effects of pulmonary rehabilitation on factors such as dyspnea and quality of life as well as hospitalizations25. Both the pulmonary rehabilitation (e.g. breathing retraining; exercise) group and the usual care group had home use of OCSs and antibiotics as part of routine home management for exacerbations. There was no statistical difference between the groups in hospitalizations. We note that two additional small studies have used OCS and antibiotics as part of an action plan at home, and while this intervention revealed no difference with the usual care groups, the studies did not assess hospitalizations or ED visits26,27. These studies evaluated other parameters such as quality of life, symptom scores, walking distance, and pulmonary function tests26,27.
Discussion OCSs are very effective in treating patients hospitalized for COPD exacerbations, including reducing length of hospital stay7,8. Therefore, it is logical to evaluate whether, as part of a comprehensive action plan, starting OCS therapy at home early in the exacerbation may decrease ! 2014 Informa UK Ltd www.cmrojournal.com
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the need for unscheduled office visits, ED visits, or hospitalizations. A very similar approach is effective for home management of asthma exacerbations and is recommended in national guidelines28,29. Further randomized trials are needed to establish that action plans, including OCS therapy, reduce hospitalizations for COPD exacerbations. However, the trials by Bourbeau et al.14 and Rice et al.17 provide compelling evidence that comprehensive action plans are effective. It is potentially a pertinent point that these investigators included closer (monthly) telephone follow-up than Fan et al.18 and Effing et al.16. Sridar et al.15 also provided monthly telephone follow-up and found reduced deaths in the action plan group. Based on studies to date, it is certainly reasonable that further investigations should include monthly telephone follow-up as a component of the home action plan. In an editorial response to the trial by Fan et al.18, Pocock30 points out that there is no convincing evidence that harm was caused by the comprehensive intervention. Yeatts et al.31 reported in 2013 on the population-based burden of COPD-related visits in the ED, including return ED visits and hospitalizations. In this 2 year study in North Carolina, 97,511 ED visits occurred due to COPD. Return ED visits were found in 7% of patients within 30 days, and 28% of patients had a return ED visit within 365 days. Among COPD patients with an ED visit, 51% were admitted to the hospital from the ED31. This very recent study further emphasizes the need for strategies to reduce ED visits and hospitalizations associated with COPD exacerbations. Because oral antibiotic therapy is combined with OCSs in most studies of COPD action plans, the recent study by Miravitlles et al.32 is important to note briefly. Among the three standard (Anthonisen) criteria of increased dyspnea, increased sputum volume, and increased sputum purulence, only increase in sputum purulence was associated with risk of failure in COPD patients without antibiotics. Clinical failure was observed in 9.5% of mild to moderate COPD patients with exacerbations seen in a primary care clinic and prescribed amoxicillin/clavulanate therapy versus 19.9% of patients without antibiotic treatment (p ¼ 0.022). A second predictor of clinical failure was a point-of-care serum C-reactive protein32. Therefore, if further study validates the investigation by Miravitlles et al.32, oral antibiotics may routinely be needed as part of home action plans only in patients with mild to moderate COPD who have increase in sputum purulence. Another important factor in predicting hospitalization is the physical capacity of COPD patients. A recent study by Garcia-Rio et al.33 evaluated 173 patients with moderate to very severe COPD. The daily physical activity in these patients was an independent prognostic factor for mortality and hospitalization due to severe exacerbations. Zanoria and ZuWallack34 confirmed this observation, and COPD action plans and oral corticosteroids Self et al.
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reported that a 6 minute walk distance test of5350 m significantly predicted subsequent all-cause and respiratoryrelated hospitalizations. Consequently, this aspect of home management of COPD exacerbations must be absolutely considered. Of interest, in the negative study by Fan et al.18, no data were reported on the physical capacity of patients. Therefore, it is possible that an unbalanced distribution of patients with poor physical capacity favored the control group. Because increased sputum production (and possibly mucus plugging) is commonly seen in COPD exacerbations, we note a very recent exhaustive review of nonpharmacologic airway clearance techniques in hospitalized patients35. Unfortunately, data from several studies in acutely ill COPD patients revealed no significant short term benefit from nonpharmacologic airway clearance modalities35. Future investigations should include evaluations of inner city COPD patients. For example, strict adherence to comprehensive action plans and ability to maintain monthly telephone follow-up in disadvantaged populations would be challenging. Nevertheless, with comprehensive care including patient education, and frequent telephone follow-up by case managers, many patients who receive prompt initiation of OCS and oral antibiotics at home will likely have reduced rates of hospitalization for COPD exacerbations. Beyond a reduction in human suffering, there is obvious potential for achieving a marked decreased in healthcare costs associated with early intervention in COPD exacerbation at home.
Conclusion More randomized trials are needed to clearly establish that home use of OCS therapy, as part of a comprehensive action plan, reduces the rate of hospitalizations for COPD. Such action plans should include structured patient education, early initiation of OCS, oral antibiotics, and frequent telephone reinforcement and support from case management.
Transparency Declaration of funding This study was not funded. Declaration of financial/other relationships C.K.F. has disclosed that he is a speaker for GlaxoSmithKline. T.H.S., S.J.P. and A.S.H. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose. 2614
COPD action plans and oral corticosteroids Self et al.
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