Tag Archives: COPD

5 days of steroids for COPD exacerbation

A randomised trial showed 5 days of oral steroid therapy (40 mg prednisone) was non-inferior to 14 days’ duration in delaying the next exacerbation.

Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial
JAMA. 2013 Jun 5;309(21):2223-31

IMPORTANCE: International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown.

OBJECTIVE: To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids.

DESIGN, SETTING, AND PATIENTS: REDUCE: (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (≥20 pack-years) without a history of asthma, from March 2006 through February 2011.

INTERVENTIONS: Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%.

MAIN OUTCOME AND MEASURE: Time to next exacerbation within 180 days.

RESULTS: Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently.

CONCLUSIONS AND RELEVANCE: In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.

COPD and heart disease interactions

Ischaemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) often affect the same patient; in fact, more than one-third of patients with angiography-proven IHD also have COPD on spirometry(1).
A recent study suggests COPD exacerbations in patients with IHD were associated with longer (5 more days) recovery times and suffered more severe breathlessness between exacerbations(2).

An accompanying editorial highlights some important points:

  • Patients admitted with COPD exacerbations are more susceptible to myocardial infarction during the admission.
  • Infective COPD exacerbations may contribute to heart failure through systemic inflammation, autonomic activation, and increased fluid in the lung. Lung infection can increase ventilation/perfusion mismatch and increased work of breathing, further straining the heart.
  • Heart failure can be very difficult to diagnose during a COPD exacerbation because cough, dyspnoea and wheeze are common to both disorders. Physical examination may not be discriminatory, and chest radiography is insensitive to milder degrees of heart failure.

The authors recommed a high index of suspicion combined with consideration of biomarkers (BNP or pro-BNP) and imaging such as echocardiography or even nuclear medicine scans, cardiac MRI, and cardiac catheterisation.

So, next time you’re managing a COPD exacerbation, ask yourself:

  • Could there be concomitant heart failure contributing to symptoms?
  • If not, is the patient at risk of cardiac events during this admission, for which we need to be vigilant?
  • Do I need to consider additional laboratory (BNP) or imaging (echo) investigations? Remember BNP may be elevated in pneumonia and other non-cardiac critical illness, although a normal BNP rules out heart failure.
  • Should I add empiric anti-failure therapy to the acute treatment regimen?
  • If there is combined COPD exacerbation and heart failure, are there any conflicting priorities in therapy (eg. the pros and cons of beta-agonists, anticholinergics, and steroids)?

1. The complex relationship between ischemic heart disease and COPD exacerbations
Chest. 2012 Apr;141(4):837-8

2. The impact of ischemic heart disease on symptoms, health status, and exacerbations in patients with COPD
Chest. 2012 Apr;141(4):851-7

BACKGROUND: Comorbid ischemic heart disease (IHD) is a common and important cause of morbidity and mortality in patients with COPD. The impact of IHD on COPD in terms of a patient’s health status, exercise capacity, and symptoms is not well understood.

METHODS: We analyzed stable-state data of 386 patients from the London COPD cohort between 1995 and 2009 and prospectively collected exacerbation data in those who had completed symptom diaries for ≥ 1 year.

RESULTS: Sixty-four patients (16.6%) with IHD had significantly worse health status as measured by the St. George Respiratory Questionnaire (56.9 ± 18.5 vs 49.1 ± 19.0, P = .003), and a larger proportion of this group reported more severe breathlessness in the stable state, with a Medical Research Council dyspnea score of ≥ 4 (50.9% vs 35.1%, P = .029). In subsets of the sample, stable patients with COPD with IHD had a higher median (interquartile range [IQR]) serum N-terminal pro-brain natriuretic peptide concentration than those without IHD (38 [15, 107] pg/mL vs 12 [6, 21] pg/mL, P = .004) and a lower exercise capacity (6-min walk distance, 225 ± 89 m vs 317 ± 85 m; P = .002). COPD exacerbations were not more frequent in patients with IHD (median, 1.95 [IQR, 1.20, 3.12] vs 1.86 (IQR, 0.75, 3.96) per year; P = .294), but the median symptom recovery time was 5 days longer (17.0 [IQR, 9.8, 24.2] vs 12.0 [IQR, 8.0, 18.0]; P = .009), resulting in significantly more days per year reporting exacerbation symptoms (median, 35.4 [IQR, 13.4, 60.7] vs 22.2 [IQR, 5.7, 42.6]; P = .028). These findings were replicated in multivariate analyses allowing for age, sex, FEV(1), and exacerbation frequency where applicable.

CONCLUSIONS: Comorbid IHD is associated with worse health status, lower exercise capacity, and more dyspnea in stable patients with COPD as well as with longer exacerbations but not with an increased exacerbation frequency.

Venous gas in COPD exacerbation

Prolific emergency medicine researcher Anne-Maree Kelly and colleague Dr Lim from Tan Tock Seng Hospital in Singapore have published a systematic review of articles assessing the utility of peripheral venous blood gases (pVBG) in exacerbations of COPD1. Their conclusion:

Available evidence suggests that there is good agreement for pH and HCO3 values between arterial and pVBG results in patients with COPD, but not for pO2 or pCO2. Widespread clinical use is limited because of the lack of validation studies on clinical outcomes

pVBG may however be useful as a screening test for significant arterial hypercarbia; Kelly et al. previously reported2 a cutoff value of 45 mmHg (5.9 kPa).

1. A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department
Eur J Emerg Med. 2010 Oct;17(5):246-8

2. Kelly AM, Kerr D, Middleton P. Validation of venous pCO2 to screen for arterial hypercarbia in patients with chronic obstructive airways disease.
J Emerg Med 2005; 28:377–379

High flow O2 and mortality in COPD

An Australian randomised controlled trial of pre-hospital oxygen therapy in COPD patients compared titrated oxygen therapy with high flow oxygen. The primary outcome was prehospital and in-hospital mortality.

Titrated oxygen treatment was delivered by nasal prongs to achieve arterial oxygen saturations between 88% and 92%, with concurrent bronchodilator treatment administered by a nebuliser driven by compressed air. High flow oxygen was 8-10 l/min administered by a non-rebreather face mask, with bronchodilators delivered by nebulisation with oxygen at flows of 6-8 l/min.
Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. The authors claim: ‘For high flow oxygen treatment in patients with confirmed chronic obstructive pulmonary disease in the prehospital setting, the number needed to harm was 14; that is, for every 14 patients who are given high flow oxygen, one will die.

The authors did not report data on the in-hospital management of the patients.

Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial
BMJ. 2010 Oct 18;341:c5462

Heliox in COPD exacerbation

A 65:35 helium-oxygen mix was compared with 35% oxygen in air in patients with COPD exacerbations requiring non-invasive ventilation. In this RCT there was no difference in intubation rates between the heliox or air/oxygen groups.

A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease
Crit Care Med. 2010 Jan;38(1):145-51