N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia
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, su...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12890-018-0599-3 |
| _version_ | 1811305602121465856 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Justin M. Oldham |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T08:29:20Z |
| format | Article |
| id | doaj.art-bf003f0322504d508cdc6520f8130775 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-04-13T08:29:20Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-bf003f0322504d508cdc6520f81307752022-12-22T02:54:19ZengBMCBMC Pulmonary Medicine1471-24662018-02-011811910.1186/s12890-018-0599-3N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumoniaJustin M. Oldham0Leah J. Witt1Ayodeji Adegunsoye2Jonathan H. Chung3Cathryn Lee4Scully Hsu5Lena W. Chen6Aliya Husain7Steven Montner8Rekha Vij9Mary E. Strek10Imre Noth11Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, The University of California at DavisDepartment of Medicine; Division of Geriatrics, University of California at San FranciscoDepartment of Medicine; Section of Pulmonary and Critical Care Medicine, The University of ChicagoDepartment of Radiology, The University of ChicagoDepartment of Medicine; Section of Pulmonary and Critical Care Medicine, The University of ChicagoDepartment of Medicine; Section of Pulmonary and Critical Care Medicine, The University of ChicagoDepartment of Medicine; Section of Pulmonary and Critical Care Medicine, The University of ChicagoDepartment of Pathology, The University of ChicagoDepartment of Radiology, The University of ChicagoDepartment of Medicine; Section of Pulmonary and Critical Care Medicine, The University of ChicagoDepartment of Medicine; Section of Pulmonary and Critical Care Medicine, The University of ChicagoDepartment of Medicine; Section of Pulmonary and Critical Care Medicine, The University of ChicagoAbstract 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.http://link.springer.com/article/10.1186/s12890-018-0599-3Idiopathic pulmonary fibrosisInterstitial lung diseaseInterstitial pneumonia with autoimmune featuresAnti-nuclear autoantibody |
| spellingShingle | 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 N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia BMC Pulmonary Medicine Idiopathic pulmonary fibrosis Interstitial lung disease Interstitial pneumonia with autoimmune features Anti-nuclear autoantibody |
| title | N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia |
| title_full | N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia |
| title_fullStr | N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia |
| title_full_unstemmed | N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia |
| title_short | N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia |
| title_sort | n acetylcysteine exposure is associated with improved survival in anti nuclear antibody seropositive patients with usual interstitial pneumonia |
| topic | Idiopathic pulmonary fibrosis Interstitial lung disease Interstitial pneumonia with autoimmune features Anti-nuclear autoantibody |
| url | http://link.springer.com/article/10.1186/s12890-018-0599-3 |
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