Benefits of High-Dose N-Acetylcysteine to Exacerbation-Prone Patients With COPD

Tse, Hoi Nam; Raiteri, Luca; Wong, King Ying; Ng, Lai Yun; Yee, Kwok Sang; Tseng, Cee Zhung Steven

doi:10.1378/chest.13-2784

Cited by 53 publications

(34 citation statements)

References 35 publications

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“…A recent retrospective analysis of the High-dose N-acetylcysteine in Stable COPD -a 1-year, Double-Blind, Randomized, Placebo-Controlled Trial (HIACE) study suggests that high-dose NAC is mainly effective in the frequent exacerbator phenotype, regardless of symptoms [35]. The lack of specific information on the topic in the individual papers and our lack of access to the original data did not allow us a specific meta-analysis aimed at confirming this point.…”

Section: Figurementioning

confidence: 99%

“…one linked to genetic, environmental and/or dietary factors) that explains the apparently specific effectiveness of NAC in Chinese patients [1,20]. However, as correctly stressed by TSE et al [35], current international guidelines for COPD do not distinguish treatment options (including dosages) for any drug class based on potential racial or cultural differences.…”

Section: Figurementioning

confidence: 99%

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Influence ofN-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

et al. 2015

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In order to clarify the possible role of N-acetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD), we have carried out a metaanalysis testing the available evidence that NAC treatment may be effective in preventing exacerbations of chronic bronchitis or COPD and evaluating whether there is a substantial difference between the responses induced by low (⩽600 mg per day) and high (>600 mg per day) doses of NAC.The results of the present meta-analysis (13 studies, 4155 COPD patients, NAC n=1933; placebo or controls n=2222) showed that patients treated with NAC had significantly and consistently fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75, 95% CI 0.66-0.84; p<0.01), although this protective effect was more apparent in patients without evidence of airway obstruction. However, high doses of NAC were also effective in patients suffering from COPD diagnosed using spirometric criteria (relative risk 0.75, 95% CI 0.68-0.82; p=0.04). NAC was well tolerated and the risk of adverse reactions was not dose-dependent (low doses relative risk 0.93, 95% CI 0.89-0.97; p=0.40; high doses relative risk 1.11, 95% CI 0.89-1.39; p=0.58).The strong signal that comes from this meta-analysis leads us to state that if a patient suffering from chronic bronchitis presents a documented airway obstruction, NAC should be administered at a dose of ⩾1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient. @ERSpublications Evidence that high doses of NAC protect against COPD exacerbations with a favourable riskbenefit ratio http://ow.ly/NeSbl

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Influence ofN-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

et al. 2015

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“…Accordingly, one study showed that NAC (600 mg b.i.d.) was more effective than placebo in reducing exacerbation risk and prolonging time to first exacerbation in high-risk patients (GOLD Groups C and D, according to the 2011 GOLD recommendations), but not low-risk patients [102]. …”

Section: Other Pharmacological Treatments In the Prevention Of Exacermentioning

confidence: 99%

Optimizing bronchodilation in the prevention of COPD exacerbations

2017

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The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments. The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention. ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy. In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations. We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS. In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA.

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“…In both these studies, NAC was not beneficial in low risk or mild COPD patients, again emphasizing need to tailor COPD management based on heterogeneous subgroups. [112] A meta-analysis suggests that higher doses (>1200mg per day) may be required to prevent AECOPD among individuals with chronic bronchitis and COPD. [113]…”

Section: Oral Agentsmentioning

confidence: 99%

Bringing Stability to the Chronic Obstructive Pulmonary Disease Patient: Clinical and Pharmacological Considerations for Frequent Exacerbators

Gulati

Wells

2017

Drugs

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Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A “frequent exacerbator” is a sub-phenotype of COPD that is defined as an individual who experiences ≥2 moderate to severe exacerbations per year. This distinct subgroup has higher mortality and account for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for utilizing combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: 1) maximizing bronchodilation, 2) reducing inflammation, and 3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies include combination long acting muscarinic agents (LAMA) plus long acting beta agonists (LABA) show promising results compared to monotherapy or LABA inhaled corticosteroid (ICS) combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase (PDE4) inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on identification of various subtypes or “endotypes” and targeting therapies based on their pathophysiology. This review aims to describe the impact of AECOPD, challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these individuals.

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Benefits of High-Dose N-Acetylcysteine to Exacerbation-Prone Patients With COPD

Cited by 53 publications

References 35 publications

Influence ofN-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

Influence ofN-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

Optimizing bronchodilation in the prevention of COPD exacerbations

Bringing Stability to the Chronic Obstructive Pulmonary Disease Patient: Clinical and Pharmacological Considerations for Frequent Exacerbators

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