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Pharmacologic and Non-pharmacologic Therapies in Adult Patients with Acute Exacerbation of COPD: A Systematic Review

Systematic Review Draft

Open for comment through Apr 25, 2019

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Purpose of Review

This systematic review evaluated the effectiveness and harms of pharmacologic and nonpharmacologic treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD).

Key Messages

  • Antibiotic therapy increases the clinical cure rate and reduces the clinical failure rate.
  • Oral and intravenous corticosteroids improve dyspnea and reduce the clinical failure rate.
  • Antibiotics and corticosteroids are not associated with significant increase in serious adverse events.
  • The evidence is insufficient to support the effect of aminophyllines, magnesium sulfate, mucolytics, inhaled corticosteroids, inhaled antibiotics, 5-lipoxygenase inhibitor and statins on mortality, dyspnea, need for intubation, clinical failure, or hospital admission.
  • Titrated oxygen reduces mortality compared with high flow oxygen.
  • The Evidence suggests benefits of some nonpharmacological interventions such as chest physiotherapy using vibration/percussion or using breathing technique (on dyspnea), resistance training (on dyspnea and quality of life), early pulmonary rehabilitation during AECOPD (on dyspnea) and whole body vibration training (on quality of life).
  • Vitamin D supplementation may improve quality of life.
  • The evidence is insufficient for comparative effectiveness of different regimens of antibiotics and corticosteroids, based on type of agents, delivery modes, and duration of treatments.
  • The evidence is insufficient for effectiveness of combinations of treatments that each individually is effective.
  • Serious adverse events were not statistically significantly different between most evaluated interventions.

Structured Abstract

Objectives. To synthesize existing knowledge about the effectiveness and harms of pharmacologic and nonpharmacologic treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD).

Data sources. Embase, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Daily, MEDLINE, Cochrane Central Registrar of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from database inception to April 11, 2018.

Review methods. We included randomized controlled trials (RCTs) that evaluated pharmacologic intervention or non-pharmacologic interventions for AECOPD. The strength of evidence (SOE) was graded for critical final health outcomes.

Results. We included 95 RCTs (13,022 patients, mean treatment duration 9.9 days, mean followup 3.5 months). Final health outcomes including mortality, resolution of exacerbation, hospital readmissions, repeat exacerbations and need for intubation were infrequently evaluated and often showed no difference between groups. Moderate SOE suggests that antibiotic therapy increases the clinical cure rate and reduces the clinical failure rate regardless of the severity of AECOPD including in patients with only mild AECOPD treated as outpatients. We were unable to demonstrate a difference based on antibiotic regimen. Low SOE suggests that oral and intravenous corticosteroids improve dyspnea and reduce the clinical failure rate. Very limited information on AECOPD phenotypes (e.g. infective versus non-infective, high versus low eosinophil count) has been included in trials of intervention. In particular, whether a response to systemic corticosteroids depends on the blood eosinophil level remains unexplored. Despite the ubiquitous use of SABAs, SAMAs, LABAs and LAMAs in AECOPD, we only found a small number of trials that assessed lung function, and not final health outcomes. The evidence is insufficient to support the effect of aminophyllines, magnesium sulfate, mucolytics, inhaled corticosteroids, inhaled antibiotics, 5-lipoxygenase inhibitor and statins on final health outcomes. Low SOE suggests that titrated oxygen reduces mortality compared with high flow oxygen. Low SOE suggests benefits of some nonpharmacological interventions such as chest physiotherapy using vibration/percussion or breathing technique (on dyspnea), resistance training (on dyspnea and quality of life), early pulmonary rehabilitation during AECOPD (on dyspnea) and whole body vibration training (on quality of life). Vitamin D supplementation may improve quality of life (Low SOE).

Conclusions. Despite a proliferation of the COPD literature, the evidence base for most interventions in AECOPD remains limited.

Systemic antibiotics and corticosteroids are associated with improved outcomes in mild and moderate/severe AECOPD. Titrated oxygen reduces mortality. Future research is required to assess the effectiveness of several emerging nonpharmacological and dietary treatments.