Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial

Our plain-English summary of Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial, by H. Alfonso, P. Franklin, S. Ching, et al (Respirology, 2015).

The study

• Authors: H. Alfonso, P. Franklin, S. Ching, K. Croft, P. Burcham, N. Olsen, A. Reid, D. Joyce, N. de Klerk, A.B. Musk
• Journal: Respirology
• Published: 2015;20(7):1102-7
• Type of article: Randomized trial
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background And Objective: Many of the pathological consequences in the lung following inhalation of asbestos fibres arise as a consequence of persistent oxidative stress and inflammation. Inflammatory responses can be observed in asymptomatic asbestos-exposed individuals. There are currently no interventions to reduce inflammatory or oxidative responses to asbestos before disease develops. We investigated the effects of oral N-acetylcysteine (NAC) on indicators of inflammation or oxidative stress in asymptomatic people previously exposed to asbestos.

Methods: A double-blind, randomized, placebo-controlled study was conducted to assess the effectiveness and safety of 1800 mg of NAC given orally over a period of 4 months. This was a proof of principle study. Effectiveness was assessed using indicators of inflammation or oxidation as primary end-points. Serum levels of total combined thiols (cysteine, cysteinylglycine, glutathione and homocysteine) were used to monitor the NAC supplementation.

Results: Thirty-four subjects were randomly allocated to NAC and 32 to placebo. Serum levels of total combined thiols were similar between the groups after intervention. There were no differences in levels of inflammatory or oxidative stress end-points between the groups. No adverse effects were identified.

Conclusions: No evidence was found that NAC supplementation replenishes total combined thiols in the blood of healthy subjects with a history of asbestos exposure. There was also no evidence of reduced indicators of inflammation or oxidative stress. Further studies should determine the conditions required to increase levels of total anti-oxidant capacity in the blood and in the lungs of subjects with either asbestos-related diseases or subclinical lung inflammation.

© 2015 Asian Pacific Society of Respirology.

In plain English

This double-blind, randomized, placebo-controlled trial tested whether the antioxidant N-acetylcysteine (NAC) lowered markers of oxidative stress and inflammation in men aged 40 to 70 who had been exposed to asbestos. None had asbestos-related disease other than hyaline pleural plaques, and none were current smokers. The men came from Western Australia's Asbestos Review Program, which covers former Wittenoom workers, former Wittenoom residents and other asbestos workers. They were recruited between April 2010 and August 2011. Of 66 men randomized, 34 were assigned to 1800 mg of NAC daily and 32 to a placebo for 4 months, and 25 and 29 completed the study. Blood thiol levels did not differ between the groups. Changes in serum F2-isoprostane and protein carbonyl did not differ significantly. Neither did lung-fluid IL-8, measured in 21 men. None of these 21 men had TNF-alpha above the detection limit in lung fluid. No adverse events were attributed to NAC. The authors concluded that this dose did not raise antioxidant capacity or change these markers. They said this could reflect the dose, the length of treatment, or the choice of healthy subjects.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Double-blind, randomized, placebo-controlled trial with a 4-month intervention period, described by the authors as a proof of principle study
• Who was studied: Men aged 40 to 70 attending the Asbestos Review Program in Western Australia. This included former Wittenoom asbestos workers, former Wittenoom residents, and other workers exposed to asbestos for at least 3 months. The study excluded men with any asbestos-related disease (except hyaline pleural plaques) or chronic respiratory disease, current smokers, and men on certain medications. Recruitment ran from April 2010 to August 2011. Of 66 men randomized, 34 were allocated to NAC and 32 to placebo. Of these, 25 in the NAC group and 29 in the placebo group completed the study.
• Exposure: Intervention: NAC 1800 mg per day (two 900 mg tablets) or a look-alike placebo for 4 months. Prior asbestos exposure was as Wittenoom workers, Wittenoom residents or other asbestos workers. Among completers, median cumulative exposure was 4.23 (IQR 0.51 to 9.88) in the NAC group and 3.04 (IQR 1.46 to 7.88) in the placebo group; units were not stated. Fiber types were not named.
• Main results:
  • Serum cysteine, cysteinylglycine, glutathione and homocysteine did not differ between the NAC and placebo groups when measured as changes from the first visit (t = 0.41, P = 0.69). Combined thiols also did not differ significantly (t = 0.80, P = 0.43).
  • Median change in serum F2-isoprostane was 176 μmol/L (IQR -176 to 489) in the NAC group versus 45 μmol/L (IQR -299 to 388) in the placebo group (t = -0.42, P = 0.67).
  • Very few exhaled breath condensate samples had detectable F2-isoprostane, so this marker was not analysed further.
  • Median change in serum protein carbonyl was 0.033 μmol/L (IQR -0.208 to 0.221) in the NAC group and -0.013 μmol/L (IQR -0.316 to 0.231) in the placebo group (t = -1.16, P = 0.26).
  • Twenty-one men had bronchoalveolar lavage (10 NAC, 11 placebo). In them, IL-8 did not differ significantly between groups: median 0.135 pg/mL (IQR 0.08 to 0.39) with NAC versus 0.125 pg/mL (IQR 0.05 to 0.37) with placebo (t = 0.13, P = 0.90).
  • Among the 21 men who had lavage, no subject had TNF-alpha above the limit of detection.
  • There were no significant differences between groups in general serum markers (protein, albumin, C-reactive protein, uric acid, bilirubin).
  • Symptoms were reported similarly in both groups. Three adverse events required reporting: two occurred in the placebo group and one resulted from the end-of-study bronchoscopy. None was attributed to the treatment.
  • Twelve men withdrew before completion: 9 in the NAC group and 3 in the placebo group. The authors reported no obvious pattern or single cause.
• The authors' conclusion: The authors concluded that 1800 mg of daily NAC did not increase total antioxidant capacity or affect markers of inflammation and oxidation in asymptomatic people previously exposed to asbestos. They said future studies should determine how to reach therapeutic antioxidant levels in people with asbestos-related disease or evidence of lung inflammation.
• Limitations the authors state:
  • The lack of difference may reflect the NAC dose given not being effective.
  • Inflammation and oxidative stress in these healthy subjects may not have been high enough to detect an anti-inflammatory effect.
  • High variability in the outcome measurements decreased statistical power to detect differences.
  • With the current data, the authors could not separate a true lack of efficacy from a failure to replenish antioxidant capacity.
  • Testing individual chemical end-products cannot capture activity in all oxidation pathways in all tissues.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Wittenoom, Western Australia

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Oxidative Stress, Inflammation, Clinical Trial, Glutathione (GSH), Asbestos Exposure.

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