ArticleAmerican journal of respiratory and critical care medicine2015
TOLLIP, MUC5B, and the Response to N-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis.
Article in American journal of respiratory and critical care medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05537220 (NAC Attack, A Phase III, Multicenter, Randomized, Parallel, Double Masked, Placebo-Controlled Study Evaluating the Efficacy and Safety of Oral N-Acetylcysteine in Patients With Retinitis Pigmentosa), which is not on this map. Cited by 168 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NAC Attack, A Phase III, Multicenter, Randomized, Parallel, Double Masked, Placebo-Controlled Study Evaluating the Efficacy and Safety of Oral N-Acetylcysteine in Patients With Retinitis Pigmentosa
Who cites it
168 citing papers in PubMed, 4 syntheses or guidelines pooled it, 352 citations in OpenAlex.
- Associations between genetic variants of Toll-interacting proteins and interstitial lung diseases: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2024Pooled it
- Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.BMC pulmonary medicine · 2023Pooled it
- Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: a systematic review and meta-analysis.BMC pulmonary medicine · 2020Pooled it
- Evaluation of oxidative stress biomarkers in idiopathic pulmonary fibrosis and therapeutic applications: a systematic review.Respiratory research · 2018Pooled it
- Telomere Length and Use of Immunosuppressive Medications in Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2019Trial
- Next-Generation Sequencing in Pulmonary Fibrosis: Translational Promise and Current Clinical Limitations.Current issues in molecular biology · 2026Review
- The Genetic Landscape of Fibrotic Interstitial Lung Diseases: Clinical Implications and Diagnostic Challenges in Familial Pulmonary Fibrosis.Journal of clinical medicine · 2026Review
- Toll interacting protein (TOLLIP) serum concentration in patients with systemic sclerosis (SSc), with and without interstitial lung disease (ILD).BMJ open respiratory research · 2026Article
- Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).International journal of molecular medicine · 2026Review
- Immunological mechanisms and therapeutic approaches in pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Prospective study of fibrosis in the lung endpoints (PROFILE): characteristics of an incident cohort of patients with idiopathic pulmonary fibrosis.BMJ open respiratory research · 2026Observational
- The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress.Antioxidants (Basel, Switzerland) · 2026Review
- Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine.Frontiers in pharmacology · 2026Review
- N-acetylcysteine: evidence based consensus document on the therapeutic advantages in respiratory diseases (NECTAR).Frontiers in medicine · 2026Review
- Familial interstitial lung disease: emerging insights into screening and genetic risk.Frontiers in medicine · 2026Review
- Article
- Idiopathic Pulmonary Fibrosis: A Comprehensive Review of Risk Factors, Genetics, Diagnosis, and Therapeutic Approaches.Biomedicines · 2026Review
- Genetic Determinants of Progressive Pulmonary Fibrosis: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Precision Medicine Advances in Chronic Lung Diseases.International journal of molecular sciences · 2025Article
- Moving past multidisciplinary discussions and Gender-Age-Physiology model: precision medicine through biological phenotyping in interstitial lung disease.Current opinion in pulmonary medicine · 2025Review
108 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
rationaleIdiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. The genes TOLLIP and MUC5B play important roles in lung host defense, which is an immune process influenced by oxidative signaling. Whether polymorphisms in TOLLIP and MUC5B modify the effect of immunosuppressive and antioxidant therapy in individuals with IPF is unknown.
objectivesTo determine whether single-nucleotide polymorphisms (SNPs) within TOLLIP and MUC5B modify the effect of interventions in subjects participating in the Evaluating the Effectiveness of Prednisone, Azathioprine, and N-Acetylcysteine in Patients with Idiopathic Pulmonary Fibrosis (PANTHER-IPF) clinical trial.
methodsSNPs within TOLLIP (rs5743890/rs5743894/rs5743854/rs3750920) and MUC5B (rs35705950) were genotyped. Interaction modeling was conducted with multivariable Cox regression followed by genotype-stratified survival analysis using a composite endpoint of death, transplantation, hospitalization, or a decline of ≥ 10% in FVC. MEASUREMENTS AND MAIN
resultsSignificant interaction was observed between N-acetylcysteine (NAC) therapy and rs3750920 within TOLLIP (P interaction = 0.001). After stratifying by rs3750920 genotype, NAC therapy was associated with a significant reduction in composite endpoint risk (hazard ratio, 0.14; 95% confidence interval, 0.02-0.83; P = 0.03) in those with a TT genotype, but a nonsignificant increase in composite endpoint risk (hazard ratio, 3.23; 95% confidence interval, 0.79-13.16; P = 0.10) was seen in those with a CC genotype. These findings were then replicated in an independent IPF cohort.
conclusionsNAC may be an efficacious therapy for individuals with IPF with an rs3750920 (TOLLIP) TT genotype, but it was associated with a trend toward harm in those with a CC genotype. A genotype-stratified prospective clinical trial should be conducted before any recommendation regarding the use of off-label NAC to treat IPF.
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