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N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia.
BMC Pulm Med ; 18(1): 30, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422061
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.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Acetilcisteína / Depuradores de Radicais Livres / Fibrose Pulmonar Idiopática Tipo de estudo: Estudo de coorte / Incidence_studies Aspecto clínico: Diagnóstico / Etiologia / Predição / Prognóstico / Terapia Limite: Idoso / Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: BMC Pulm Med Ano de publicação: 2018 Tipo de documento: Artigo País de afiliação: Estados Unidos