PMID- 29422061
OWN - NLM
STAT- MEDLINE
DCOM- 20190325
LR  - 20210520
IS  - 1471-2466 (Electronic)
IS  - 1471-2466 (Linking)
VI  - 18
IP  - 1
DP  - 2018 Feb 8
TI  - N-acetylcysteine exposure is associated with improved survival in anti-nuclear 
      antibody seropositive patients with usual interstitial pneumonia.
PG  - 30
LID - 10.1186/s12890-018-0599-3 [doi]
LID - 30
AB  - 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 (p(logrank) = 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.
FAU - Oldham, Justin M
AU  - Oldham JM
AD  - Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep 
      Medicine, The University of California at Davis, Sacramento, CA, USA. 
      joldham@ucdavis.edu.
FAU - Witt, Leah J
AU  - Witt LJ
AD  - Department of Medicine; Division of Geriatrics, University of California at San 
      Francisco, San Francisco, USA.
FAU - Adegunsoye, Ayodeji
AU  - Adegunsoye A
AD  - Department of Medicine; Section of Pulmonary and Critical Care Medicine, The 
      University of Chicago, Chicago, USA.
FAU - Chung, Jonathan H
AU  - Chung JH
AD  - Department of Radiology, The University of Chicago, Chicago, USA.
FAU - Lee, Cathryn
AU  - Lee C
AD  - Department of Medicine; Section of Pulmonary and Critical Care Medicine, The 
      University of Chicago, Chicago, USA.
FAU - Hsu, Scully
AU  - Hsu S
AD  - Department of Medicine; Section of Pulmonary and Critical Care Medicine, The 
      University of Chicago, Chicago, USA.
FAU - Chen, Lena W
AU  - Chen LW
AD  - Department of Medicine; Section of Pulmonary and Critical Care Medicine, The 
      University of Chicago, Chicago, USA.
FAU - Husain, Aliya
AU  - Husain A
AD  - Department of Pathology, The University of Chicago, Chicago, USA.
FAU - Montner, Steven
AU  - Montner S
AD  - Department of Radiology, The University of Chicago, Chicago, USA.
FAU - Vij, Rekha
AU  - Vij R
AD  - Department of Medicine; Section of Pulmonary and Critical Care Medicine, The 
      University of Chicago, Chicago, USA.
FAU - Strek, Mary E
AU  - Strek ME
AD  - Department of Medicine; Section of Pulmonary and Critical Care Medicine, The 
      University of Chicago, Chicago, USA.
FAU - Noth, Imre
AU  - Noth I
AD  - Department of Medicine; Section of Pulmonary and Critical Care Medicine, The 
      University of Chicago, Chicago, USA.
LA  - eng
GR  - K23 HL138190/HL/NHLBI NIH HHS/United States
GR  - T32 HL007605/HL/NHLBI NIH HHS/United States
GR  - K23HL138190/National Heart, Lung, and Blood Institute (US)/
PT  - Journal Article
DEP - 20180208
PL  - England
TA  - BMC Pulm Med
JT  - BMC pulmonary medicine
JID - 100968563
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Free Radical Scavengers)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*therapeutic use
MH  - Aged
MH  - Antibodies, Antinuclear/immunology
MH  - Cohort Studies
MH  - Female
MH  - Free Radical Scavengers/*therapeutic use
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/*drug therapy/immunology/mortality
MH  - Kaplan-Meier Estimate
MH  - Lung Transplantation/statistics & numerical data
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Proportional Hazards Models
MH  - Retrospective Studies
MH  - Survival Rate
PMC - PMC5806226
OTO - NOTNLM
OT  - Anti-nuclear autoantibody
OT  - Idiopathic pulmonary fibrosis
OT  - Interstitial lung disease
OT  - Interstitial pneumonia with autoimmune features
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the 
      University of Chicago Institutional Review Board (protocol #14163). All patients 
      provided written informed consent for this study. CONSENT FOR PUBLICATION: Not 
      applicable COMPETING INTERESTS: JMO has received grants from the American 
      Thoracic Society, Boehringer Ingelheim and the American Lung Association, and has 
      received consulting and speaking fees from Genentech and Boerhinger Ingelheim, 
      outside the submitted work. LJW, AA, KL, AH, SM, SH and LC have nothing to 
      disclose. JHC has received consulting and speaking fees from Genentech outside 
      the submitted work. RV has received a grant from Genentech outside the submitted 
      work. MES has institutional grants from the NIH and Boehringer Ingelheim for the 
      conduct of clinical trials in IPF. She has received honoraria for serving on a 
      Data Monitoring Committee for Boehringer Ingelheim and an advisory board for 
      Boehringer Ingelheim and Genentech outside the submitted work. IN has received 
      honoraria for advisory boards with Boehringer Ingelheim, InterMune, Anthera 
      outside the submitted work. He has also received speaking honoraria from GSK and 
      receives consulting fees for Immuneworks outside the submitted work. He also has 
      study contracts with the NIH, Stromedix, Sanofi, and BI for the conduct of 
      clinical trials in IPF. PUBLISHER'S NOTE: Springer Nature remains neutral with 
      regard to jurisdictional claims in published maps and institutional affiliations.
EDAT- 2018/02/10 06:00
MHDA- 2019/03/26 06:00
PMCR- 2018/02/08
CRDT- 2018/02/10 06:00
PHST- 2017/07/24 00:00 [received]
PHST- 2018/01/30 00:00 [accepted]
PHST- 2018/02/10 06:00 [entrez]
PHST- 2018/02/10 06:00 [pubmed]
PHST- 2019/03/26 06:00 [medline]
PHST- 2018/02/08 00:00 [pmc-release]
AID - 10.1186/s12890-018-0599-3 [pii]
AID - 599 [pii]
AID - 10.1186/s12890-018-0599-3 [doi]
PST - epublish
SO  - BMC Pulm Med. 2018 Feb 8;18(1):30. doi: 10.1186/s12890-018-0599-3.