Efficacy and safety of inhaled N-acetylcysteine in idiopathic pulmonary fibrosis: A prospective, single-arm study

Okuda, Ryo; Matsushima, Hidekazu; Oba, Tomohiro; Kawabe, Rie; Matsubayashi, Minako; Amano, Masashi; Nishizawa, Tomotaka; Honda, Kojiro

doi:10.1016/j.resinv.2015.10.001

Cited by 11 publications

(18 citation statements)

References 21 publications

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“…1). Eight studies were conducted in Japan (Bando et al, 2010[3]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Okuda et al, 2016[22]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]), three in multi-countries (Behr et al, 2009[6], 2016[5]; Raghu et al, 2012[24]) and one in United States (Martinez et al, 2014[20]). Only two types of antioxidants (N-Acetylcysteine (NAC) (Bando et al, 2010[3]; Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Martinez et al, 2014[20]; Okuda et al, 2016[22]; Raghu et al, 2012[24]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]) and lecithinized superoxide dismutase (PC-SOD) (Kamio et al, 2014[17]) were reported in these studies.…”

Section: Resultsmentioning

confidence: 99%

“…Eight studies were conducted in Japan (Bando et al, 2010[3]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Okuda et al, 2016[22]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]), three in multi-countries (Behr et al, 2009[6], 2016[5]; Raghu et al, 2012[24]) and one in United States (Martinez et al, 2014[20]). Only two types of antioxidants (N-Acetylcysteine (NAC) (Bando et al, 2010[3]; Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Martinez et al, 2014[20]; Okuda et al, 2016[22]; Raghu et al, 2012[24]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]) and lecithinized superoxide dismutase (PC-SOD) (Kamio et al, 2014[17]) were reported in these studies. Six studies (Bando et al, 2010[3]; Homma et al, 2012[14], Okuda et al, 2016[22]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]) had inhalation as a route of administration of NAC whereas five studies (Behr et al, 2009[6], 2016[5]; Huang et al, 2015[15]; Martinez et al, 2014[20]; Raghu et al, 2012[26]) indicated NAC as an oral treatment and in only one study (Kamio et al, 2014[17]) PC-SOD was administered intravenously.…”

Section: Resultsmentioning

confidence: 99%

“…There was a total of 1,062 enrolled patients, of which 530 (49.9 %) patients received antioxidant treatment, whereas remaining were on placebo. Eight studies were randomized controlled trials (seven were double blinded (Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Martinez et al, 2014[20]; Raghu et al, 2012[24]) and one was open arm (Tomioka et al, 2005[36])); while three were retrospective studies (Bando et al, 2010[3]; Sakamoto et al, 2013[30]), one had a single-arm prospective clinical trial (Okuda et al, 2016[22]) and case-control trial study (Sakamoto et al, 2015[31]), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Various clinical studies have reported the efficacy of antioxidant treatment (such as N-acetylcysteine (NAC) and lecithinized superoxide dismutase (PC-SOD)) for IPF (Bando et al, 2010[3]; Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Martinez et al, 2014[20]; Okuda et al, 2016[22]; Raghu et al, 2012[24]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]). Several studies found that NAC treatment had a beneficial effect on lung function in IPF patients and significantly delayed disease progression (Behr et al, 2009[6]; Homma et al, 2012[14]; Huang et al, 2015[15]; Okuda et al, 2016[22]; Sakamoto et al, 2013[30], 2015[31]) whereas few studies reported that NAC treatment had no benefit and did not significantly improve the lung function of patients with IPF (Bando et al, 2010[3]; Behr et al, 2016[5]; Martinez et al, 2014[20]; Raghu et al, 2012[24]). A study by Tomioka et al (Tomioka et al, 2005[36]) showed that N-acetylcysteine aerosol treatment might delay disease progression, but did not improve pulmonary function or quality of life (QoL).…”

Section: Introductionmentioning

confidence: 99%

“…However, PC-SOD treatment had a beneficial effect on serum markers in IPF patients with severe respiratory dysfunction (Kamio et al, 2014[17]). As low statistical power may limit the interpretability of the findings, the results of all of these trials (Bando et al, 2010[3]; Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Martinez et al, 2014[20]; Okuda et al, 2016[22]; Raghu et al, 2012[24]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]) should be interpreted with caution. In view of this conflicting evidence landscape, it is important to create an empirical evidence framework to underline the degree of therapeutic benefit of antioxidant therapy in IPF patients.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Efficacy of antioxidant in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Kandhare

Mukherjee

Ghosh

et al. 2016

EXCLI Journal; 15:Doc636; ISSN 1611-2156

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Efficacy of antioxidant in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Kandhare

Mukherjee

Ghosh

et al. 2016

EXCLI Journal; 15:Doc636; ISSN 1611-2156

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Redox Imbalance in Idiopathic Pulmonary Fibrosis: A Role for Oxidant Cross-Talk Between NADPH Oxidase Enzymes and Mitochondria

Veith

Boots

Idris

et al. 2019

Antioxidants & Redox Signaling

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N-acetylcysteine for adults with acute respiratory distress syndrome: A meta-analysis of randomized controlled trials

et al. 2019

Hong Kong Journal of Emergency Medicine

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Background: Acute respiratory distress syndrome is regarded as a formidable clinical challenge due to its high prevalence and mortality. The treatment of acute respiratory distress syndrome is very complex and difficult. As an adjuvant therapy, the antioxidant N-acetylcysteine has been investigated for several years but the benefit is controversial. Objectives: We performed the systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy of N-acetylcysteine on patients with acute respiratory distress syndrome. Methods: We searched PubMed, CENTRAL, and CBM databases. Randomized controlled trials comparing the effects of N-acetylcysteine and control were included. Overall mortality was the primary outcome; length of intensive care unit stay, duration of mechanical ventilation, glutathione levels, and PaO2/FiO2 were the secondary outcomes. Results: Eight trials with a total of 289 patients were included. Compared to the control group, the N-acetylcysteine group did not lower the overall mortality (risk ratio: 0.83; 95% confidence interval: 0.62 to 1.11; P = 0.21; I2 = 0%). However, N-acetylcysteine significantly shortened intensive care unit stay in the random-effects model (mean difference: –4.47 days; 95% confidence interval: –8.79 to −0.14; P = 0.04; I2 = 46%). Due to substantial heterogeneity and limited number of studies, the data of duration of mechanical ventilation, glutathione levels, and PaO2/FiO2 could not be pooled in the meta-analysis. Conclusion: N-acetylcysteine is ineffective in reducing mortality but beneficial for intensive care unit stay. Nonetheless, the effectiveness of N-acetylcysteine for acute respiratory distress syndrome is limited and further research is required before strong recommendations can be made.

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Efficacy and safety of inhaled N-acetylcysteine in idiopathic pulmonary fibrosis: A prospective, single-arm study

Cited by 11 publications

References 21 publications

Efficacy of antioxidant in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Efficacy of antioxidant in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Redox Imbalance in Idiopathic Pulmonary Fibrosis: A Role for Oxidant Cross-Talk Between NADPH Oxidase Enzymes and Mitochondria

N-acetylcysteine for adults with acute respiratory distress syndrome: A meta-analysis of randomized controlled trials

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