Contemporary Management of Acute Exacerbations of COPD: A Systematic Review and Metaanalysis

doi:10.1378/chest.07-1207

Chest

Volume 133, Issue 3, March 2008, Pages 756-766

https://doi.org/10.1378/chest.07-1207 Get rights and content

Background

Systemic corticosteroids, antibiotics, and noninvasive positive pressure ventilation (NPPV) are recommended for patients with acute exacerbation of COPD. However, their clinical benefits in various settings are uncertain. We undertook a systematic review and metaanalysis to systematically evaluate the effectiveness of these therapies.

Methods

MEDLINE and EMBASE were searched to identify relevant randomized controlled clinical trials published from January 1968 to November 2006. We identified additional studies by searching bibliographies of retrieved articles.

Results

Compared with placebo, systemic corticosteroids reduced treatment failure by 46% (95% confidence interval [CI], 0.41 to 0.71), length of hospital stay by 1.4 days (95% CI, 0.7 to 2.2), and improved FEV₁ by 0.13 L after 3 days of therapy (95% CI, 0.04 to 0.21). Meanwhile, the risk of hyperglycemia significantly increased (relative risk, 5.88; 95% CI, 2.40 to 14.41). Compared with placebo, antibiotics reduced treatment failure by 46% (95% CI, 0.32 to 0.92) and in-hospital mortality by 78% (95% CI, 0.08 to 0.62). Compared with standard therapy, NPPV reduced the risk of intubation by 65% (95% CI, 0.26 to 0.47), in-hospital mortality by 55% (95% CI, 0.30 to 0.66), and the length of hospitalization by 1.9 days (95% CI, 0.0 to 3.9).

Conclusions

For acute COPD exacerbations, systemic corticosteroids are effective in reducing treatment failures, while antibiotics reduce mortality and treatment failures in those requiring hospitalization and NPPV reduces the risk of intubation and in-hospital mortality, especially in those who demonstrate respiratory acidosis.

Section snippets

Methods and Materials

We decided a priori to examine the published evidence for systemic corticosteroids, antibiotics, and NPPV in the treatment of acute COPD exacerbations. For each of these therapies, we conducted a literature search by using MEDLINE and EMBASE. We limited the search to English-language articles published from January 1968 to November 2006, conducted in adults (> 19 years of age) using a randomized, controlled trial design. To limit the studies to COPD, we used the following terms: chronic

Systemic Corticosteroids

A total of 10 studies¹⁰¹¹¹²¹³¹⁴¹⁵¹⁶¹⁷¹⁸¹⁹ involving 959 patients (Table 2) were identified that examined the effects of systemic corticosteroids during acute COPD exacerbations. The mean age of patients of these studies was 67 years. The patients at the time of presentation to the hospital demonstrated an average arterial pH of 7.40 and Paco₂ of 42 mm Hg. Most of the patients were active smokers with a mean smoking history of 63 pack-years. The treatment was initiated in hospital in eight of

Discussion

Acute exacerbations of COPD are an increasing cause of morbidity, mortality, and economic burden in the United States and elsewhere. Despite the widespread promulgation of clinical guidelines by various expert committees and professional societies over the past decade, there continues to be considerable heterogeneity in the way in which acute exacerbations are managed between physicians.³¹ For instance, a large survey³¹ found that < 3% of patients with acute COPD exacerbations were treated with

References (56)

SullivanSD et al.
The economic burden of COPD
Chest
(2000)
JadadAR et al.
Assessing the quality of reports of randomized clinical trials: is blinding necessary?
Control Clin Trials
(1996)
BullardMJ et al.
Early corticosteroid use in acute exacerbations of chronic airflow obstruction
Am J Emerg Med
(1996)
DaviesL et al.
Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial
Lancet
(1999)
EmermanCL et al.
A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD
Chest
(1989)
FearEC et al.
Antibiotic regimes in chronic bronchitis
Br J Dis Chest
(1962)
ManresaF et al.
Antibiotics for exacerbations of chronic bronchitis
Lancet
(1987)
NouiraS et al.
Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trial
Lancet
(2001)
PinesA et al.
Antibiotic regimens in moderately ill patients with purulent exacerbations of chronic bronchitis
Br J Dis Chest
(1972)
DewanNA et al.
Acute exacerbation of COPD: factors associated with poor treatment outcome
Chest
(2000)

BottJ et al.

Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease

Lancet

(1993)

CelikelT et al.

Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure

Chest

(1998)

PlantPK et al.

Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial

Lancet

(2000)

ConnorsAF et al.

Outcomes following acute exacerbation of severe chronic obstructive lung disease: the SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments)

Am J Respir Crit Care Med

(1996)

SeneffMG et al.

Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease

JAMA

(1995)

ManninoDM et al.

Chronic obstructive pulmonary disease surveillance–United States, 1971–2000

MMWR Surveill Summ

(2002)

FabbriL et al.

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary updated 2003

COPD

(2004)

SeemungalTA et al.

Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

(1998)

SethiS et al.

New strains of bacteria and exacerbations of chronic obstructive pulmonary disease

N Engl J Med

(2002)

SeemungalTA et al.

Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease

Eur Respir J

(2000)

AaronSD et al.

Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease

N Engl J Med

(2003)

AlbertRK et al.

Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency

Ann Intern Med

(1980)

MaltaisF et al.

Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

Am J Respir Crit Care Med

(2002)

NiewoehnerDE et al.

Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease: department of Veterans Affairs Cooperative Study Group

N Engl J Med

(1999)

RostomR et al.

The long term efficacy of methylprednisolone in the treatment of acute exacerbation of COPD [abstract]

Chest

(1994)

ThompsonWH et al.

Controlled trial of oral prednisone in outpatients with acute COPD exacerbation

Am J Respir Crit Care Med

(1996)

Wood-BakerR et al.

A double-blind, randomised, placebo-controlled trial of corticosteroids for acute exacerbations of chronic obstructive pulmonary disease

Aust N Z J Med

(1998)

AnthonisenNR et al.

Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease

Ann Intern Med

(1987)

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Treatment with systemic corticosteroid versus placebo for exacerbations of COPD: A systematic review and meta-analysis: Meta-analysis of systemic corticosteroid treatment for COPD exacerbations
2024, Respiratory Investigation
For the treatment of COPD exacerbations, systemic corticosteroids are recommended in addition to short-acting bronchodilators. Although there have been several systemic reviews, many of the included studies were conducted before 2007 and a re-evaluation has not been performed since 2014. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of systemic corticosteroids in patients with COPD during exacerbations.
We searched relevant randomized control trials (RCTs) and analyzed the treatment failure, relapse, lung function, improvement in PaO₂ and PaCO₂, dyspnea, quality of life (QOL), length of stay in hospital and adverse events including hyperglycemia and mortality as the outcomes of interest.
We identified a total of 12 RCTs (N = 1336). Systemic corticosteroids significantly reduced the treatment failure (odds ratios; OR 0.41, 95% confidence intervals; CI 0.25 to 0.67) and hospital length of stay (mean difference; MD -1.57 days, 95% CI -2.36 to −0.78) and improved FEV₁ (MD 0.18 L, 95% CI 0.08 to 0.28) and dyspnea (transitional dyspnea index; MD 1.90, 95% CI 0.26 to 3.54) in COPD exacerbations compared to placebo. However, systemic corticosteroids were associated with a significantly higher incidence of adverse events (OR 1.83, 95% CI 1.25 to 2.69) and hyperglycemia (OR 2.94, 95% CI 1.68 to 5.14).
In patients with moderate and severe COPD and severe obstructive impairment during exacerbations, systemic corticosteroids cause more adverse events, including hyperglycemia, than placebo but significantly reduce the treatment failure and hospital length of stay and improve FEV₁ and dyspnea.
Is PM<inf>2.5</inf> associated with emergency department visits for mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease?
2021, American Journal of Emergency Medicine
Citation Excerpt :
Patients with COPD tend to have recurrent exacerbations and ARF triggered by air pollution [15,22,43-45]. Ventilators are essential equipment for the care of AECOPD patients who experience ARF [16-21,24]; however, ED ventilator demand/capacity mismatch may occur due to a peak in AECOPD development during air pollution and climate change. For the needs of the study, predicting and monitoring ventilator need may help manage AECOPD patients with ARF and the necessary ancillary equipment in advance [1,44,46].
Patients with chronic obstructive pulmonary disease (COPD) can have recurrent exacerbations and acute respiratory failure (ARF) triggered by particulate matter with a diameter of ≤2.5 μm (PM_2.5). To prevent ventilator shortages, this study investigated the short-term association between PM_2.5 concentration and emergency department visits (EDVs) among patients with acute exacerbation of COPD (AECOPD) requiring mechanical ventilation (MV).
We conducted a time-series study to predict the PM_2.5 concentration and number of ventilators needed. Daily counts of EDVs among AECOPD patients requiring ventilation from 2015 to 2019 were obtained from a hospital. Generalized linear models extending Poisson regression were used to explore the association of AECOPD with PM_2.5 after controlling for the time trend, seasonal variations, and meteorological variables.
Eight hundred seventy-five AECOPD patients receiving MV were recorded, of whom 734 received noninvasive ventilation and 141 received invasive ventilatory support. EDVs for AECOPD patients with ARF significantly increased by 3.5% (95% confidence interval [CI]: 2.51%–4.42%) per 10 μg m⁻³ increase in PM_2.5 concentration. Among seasons, PM_2.5 concentration had the strongest effect on AECOPD patients with ARF in spring (<24.5 °C), with a 1.64% (95% CI: −0.56% to 3.83%) increase in admissions per 10 μg m⁻³ increase in same-day PM_2.5 concentration. The interquartile range increase of 20 μg m⁻³ between winter and spring was associated with an average EDV increase of 48.66%.
This is the first study to predict the number of ventilators required by calculating quantitative estimates of the short-term effects of PM_2.5 on EDVs for AECOPD patients with ARF. Adverse effects of PM_2.5 on AECOPD patients requiring MV are evident, especially in the spring. Establishing protective standards and reducing the PM_2.5 concentration to below various thresholds are urgently needed.
Adequacy and prognostic impact of treatment for severe exacerbation of chronic obstructive pulmonary disease
2020, Revista Clinica Espanola
Definir las características clínicas de los pacientes hospitalizados en servicios de medicina interna (MI) y neumología por exacerbaciones de la EPOC, evaluar la adecuación a las recomendaciones de las guías de práctica clínica y conocer su impacto en el pronóstico de los pacientes.
Estudio longitudinal retrospectivo. Se incluyeron aleatoriamente pacientes ingresados por exacerbación de EPOC en un hospital de tercer nivel. Se registraron variables demográficas, clínicas (grado de disnea y de obstrucción, exacerbaciones previas, comorbilidades), criterios de adecuación a las guías clínicas GOLD y GesEPOC y datos de reingresos y mortalidad. Se realizó un análisis univariante, multivariante y de supervivencia.
Se incluyeron 108 pacientes y la edad media fue de 71,48±11,65 años. Los reingresos a los 3 meses fueron un 26,4% y al año un 43,4%. La mortalidad intrahospitalaria fue del 3,9%, a los 3 meses del 21,9%, y al año del 27,4%. Los pacientes ingresados en MI tuvieron una mortalidad más elevada durante el ingreso (p = 0,043), a los tres meses (p = 0,028) y al año (p = 0,007) respecto a los de neumología. La adecuación global a las guías clínicas en la evaluación clínica fue del 63% (menor en los pacientes de MI: 56,1% vs. 73,8%, p = 0,063), y en el tratamiento del 26,9% para la GOLD, y del 28,7% para GesEPOC. La adecuación en el uso de corticoides según GOLD se asoció a menor tasa de reingresos al año (p = 0,041) y mortalidad intrahospitalaria (p = 0,007) y a los 3 meses (p = 0,05).
El perfil clínico de los pacientes es actualmente similar al descrito previamente pero su evolución clínica fue peor. La adecuación global del tratamiento farmacológico a las guías clínicas es baja, y solo el uso adecuado de esteroides sistémicos se asocia a una reducción de la mortalidad precoz y de los reingresos a medio plazo.
To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease (COPD) exacerbation, to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients’ prognosis.
We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital. We collected demographic and clinical variables (degree of dyspnoea and obstruction, previous exacerbations, comorbidities), readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and the Spanish COPD guidelines (GesEPOC). We performed a univariate, multivariate and survival analysis.
The study included 108 patients, and the mean age was 71.48±11.65 years. The readmission rate was 26.4% at 3 months and 43.4% at 1 year. The hospital mortality rate was 3.9%, the mortality rate at 3 months was 21.9%, and the mortality rate at 1 year was 27.4%. The patients hospitalised in the internal medicine department had higher mortality during hospitalisation (p = .043), at 3 months (p = .028) and at 1 year (p = .007) compared with the rates for the pneumology department. Overall compliance with the clinical guidelines was 63% for the clinical evaluation (less for the patients in internal medicine: 56.1% vs. 73.8%, p = .063). For the treatment, the compliance was 26.9% for GOLD and 28.7% for GesEPOC. Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions (p = .041) and hospital mortality (p = .007) and 3-month mortality (p = .05).
The clinical profile of the patients is currently similar to that previously reported, but their clinical progression was poorer. Overall compliance with the clinical guidelines for drug treatment was low, and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions.
The obese patient and acute respiratory failure, a challenge for intensive care
2019, Revue des Maladies Respiratoires
Du fait d’une épidémie toujours croissante, l’obésité morbide est devenue une maladie courante en soins critiques. Ses conséquences sur l’appareil respiratoire sont multiples, à la fois sur la mécanique et l’échangeur pulmonaire, et impactent considérablement la prise en charge et le pronostic. Les caractéristiques anatomiques et physiologiques respiratoires particulières du patient avec une obésité morbide posent des problématiques techniques et posturales spécifiques qui doivent être connues car elles peuvent causer de très graves complications. Cet article passe en revue la prise en charge du patient obèse en insuffisance respiratoire aiguë de la ventilation non invasive à la trachéotomie, en passant par le positionnement et les difficultés techniques, et explique la stratégie de ventilation fondée sur la physiologie appliquée à la fois pour la ventilation non invasive et la ventilation mécanique invasive jusqu’au sevrage du support ventilatoire.
As a result of the constantly increasing epidemic of obesity, it has become a common problem in the intensive care unit. Morbid obesity has numerous consequences for the respiratory system. It affects both respiratory mechanics and pulmonary gas exchange, and dramatically impacts on the patient's management and outcome. With the potential for causing devastating respiratory complications, the particular anatomical and physiological characteristics of the respiratory system of the morbidly obese subject should be carefully taken into consideration. The present article reviews the management of obese patients in respiratory failure, from noninvasive ventilation to tracheostomy, including postural and technical issues, and explains the physiologically based ventilatory strategy both for NIV and invasive mechanical ventilation up to the weaning from the ventilatory support.
Impact of Outpatient Prescribing of Antibiotics for Acute Exacerbation of Chronic Obstructive Pulmonary Disease on 30-Day Re-exacerbation Rates
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Noninvasive positive pressure in acute exacerbations of chronic obstructive pulmonary disease
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View all citing articles on Scopus

This project is supported by the Canadian Institutes of Health Research. Dr. Sin is a Canada Research Chair in COPD and a senior scholar with the Michael Smith Foundation for Health Research.

The authors have no conflicts of interest to disclose.

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Chest

SPECIAL FEATURESContemporary Management of Acute Exacerbations of COPD: A Systematic Review and Metaanalysis

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

Systemic Corticosteroids

Discussion

Chest

Control Clin Trials

Am J Emerg Med

Lancet

Chest

Br J Dis Chest

Lancet

Lancet

Br J Dis Chest

Chest

Lancet

Chest

Lancet

Outcomes following acute exacerbation of severe chronic obstructive lung disease: the SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments)

Am J Respir Crit Care Med

Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease

JAMA

Chronic obstructive pulmonary disease surveillance–United States, 1971–2000

MMWR Surveill Summ

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary updated 2003

COPD

Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

New strains of bacteria and exacerbations of chronic obstructive pulmonary disease

N Engl J Med

Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease

Eur Respir J

Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease

N Engl J Med

Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency

Ann Intern Med

Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

Am J Respir Crit Care Med

Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease: department of Veterans Affairs Cooperative Study Group

N Engl J Med

The long term efficacy of methylprednisolone in the treatment of acute exacerbation of COPD [abstract]

Chest

Controlled trial of oral prednisone in outpatients with acute COPD exacerbation

Am J Respir Crit Care Med

A double-blind, randomised, placebo-controlled trial of corticosteroids for acute exacerbations of chronic obstructive pulmonary disease

Aust N Z J Med

Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease

Ann Intern Med

SPECIAL FEATURES
Contemporary Management of Acute Exacerbations of COPD: A Systematic Review and Metaanalysis