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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2018

Open Access 01-12-2018 | Research article

N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia

Authors: Justin M. Oldham, Leah J. Witt, Ayodeji Adegunsoye, Jonathan H. Chung, Cathryn Lee, Scully Hsu, Lena W. Chen, Aliya Husain, Steven Montner, Rekha Vij, Mary E. Strek, Imre Noth

Published in: BMC Pulmonary Medicine | Issue 1/2018

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Abstract

Background

Mortality is similarly high among individuals with usual interstitial pneumonia (UIP) due to idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF). Circulating anti-nuclear antibodies (ANA) are commonly found in this patient population, suggesting possible aberrant immune activation. Because an environment of oxidative stress can result from immunologic activation, we hypothesized that ANA positive patients with UIP would have improved outcome when exposed to the antioxidant N-acetylcysteine (NAC) compared to ANA negative patients.

Methods

A single center, retrospective cohort analysis was performed. Patients with UIP due to IPF and IPAF were stratified according to ANA status to and NAC exposure. Transplant-free survival (TFS) was assessed using the Kaplan-Meier estimator and multivariable Cox regression adjusted for diagnosis, gender/age/physiology score, immunosuppressant exposure and anti-fibrotic exposure.

Results

Of 293 individuals with UIP due to IPF (74%) or IPAF (26%), NAC exposure was documented in 58 (19.8%). Among NAC exposed individuals, 33 (56.9%) were ANA seropositive and 25 (43.1%) were seronegative. NAC exposure was associated with improved TFS survival among ANA seropositive individuals in unadjusted analysis (plogrank = 0.02) and after multi-variable adjustment (HR 0.51, 95% CI 0.30–0.87; p = 0.01). There was no association between NAC exposure and TFS in ANA seronegative individuals (HR 1.26, 95% CI 0.69–2.32; p = 0.45). Formal interaction testing confirmed NAC*ANA interaction (p = 0.04) and sensitivity analysis demonstrated an increasing effect size associated with NAC therapy as ANA titer increased. Among patients with available genetic data, a marginally higher proportion of ANA positive patients (p = 0.08) carried the rs3750920 (TOLLIP) genotype previously shown to predict favorable outcome in NAC exposed patients.

Conclusion

NAC exposure is associated with improved transplant-free survival ANA positive patients with UIP. These findings support the prospective collection of ANA data in in future NAC clinical trials performed in patients with UIP.
Appendix
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Metadata
Title
N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia
Authors
Justin M. Oldham
Leah J. Witt
Ayodeji Adegunsoye
Jonathan H. Chung
Cathryn Lee
Scully Hsu
Lena W. Chen
Aliya Husain
Steven Montner
Rekha Vij
Mary E. Strek
Imre Noth
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2018
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-018-0599-3

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