WARFARIN USE IS ASSOCIATED WITH INCREASED MORTALITY AT ONE YEAR IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS

Abstract Background: We aimed to investigate whether dextromethorphan (DM), an antitussive agent, could improve the antifibrotic efficacy of pirfenidone in treating idiopathic pulmonary fibrosis, a fatal interstitial lung disease characterized by progressive and irreversible respiratory failure.Methods: A bleomycin-induced mouse pulmonary fibrosis model study and an open-label randomized clinical trial were performed to evaluate the effectiveness of pirfenidone combined with DM.Results: In the animal study, pirfenidone combined with DM protected the mice against bleomycin-induced pulmonary fibrosis with better capabilities than pirfenidone or DM alone, as indicated by lung histologic analysis and hydroxyproline levels. In the clinical study, pirfenidone plus DM markedly mitigated pulmonary function (FEV1 and FVC) decline and ameliorated chest HRCT imaging scores (ground glass opacities and reticulation) of patients with IPF compared with pirfenidone alone at one year after administration. There were no significant differences in adverse reactions between the pirfenidone-DM group and the pirfenidone group.Conclusions: Pirfenidone plus DM may be a better strategy to modify IPF than pirfenidone alone. The efficacy and safety of the combination of pirfenidone and DM for patients with IPF warrants further verification by a double-blind randomized controlled trial (RCT).

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Biomarker signatures for progressive idiopathic pulmonary fibrosis

European Respiratory Journal ◽

10.1183/13993003.01181-2021 ◽

2021 ◽

pp. 2101181

Author(s):

Britt Clynick ◽

Tamera J. Corte ◽

Helen E. Jo ◽

Iain Stewart ◽

Ian N. Glaspole ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Progression Free Survival ◽

Intercellular Adhesion Molecule ◽

Lasso Regression ◽

Intercellular Adhesion Molecule 1 ◽

Clinical Endpoints ◽

Proteomic Data ◽

Proteomic Approach ◽

One Year

RationaleIdiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers has the potential for guiding management in clinical practice.ObjectivesWe assessed the prognostic role of serum biomarkers in three independent IPF cohorts, the Australian IPF Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE).MethodsIn the AIPFR, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. Least absolute shrinkage and selection operator (LASSO) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at one-year in AIPFR, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in PROFILE. Four significantly replicating biomarkers were aggregated into a progression index (PI) model based on tertiles of circulating concentrations.Main ResultsOne-hundred and eighty-nine participants were included in the AIPFR cohort, 205 participants from the TLF, and 122 participants from the PROFILE cohorts. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at one-year. Proteomic data did not replicate. The PI in the AIPFR, TLF and PROFILE predicted risk of progression, mortality and progression-free survival. A statistical model incorporating PI demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP model alone in all cohorts, and significantly so within incidence based TLF and PROFILE cohorts.ConclusionA panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.

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Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

Cells ◽

10.3390/cells11010143 ◽

2022 ◽

Vol 11 (1) ◽

pp. 143

Author(s):

Kazutaka Takehara ◽

Yasuhiko Koga ◽

Yoshimasa Hachisu ◽

Mitsuyoshi Utsugi ◽

Yuri Sawada ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Adverse Events ◽

Disease Progression ◽

Continuous Treatment ◽

Discontinuation Rate ◽

Antifibrotic Therapy ◽

Significant Difference ◽

One Year ◽

Observation Period

Antifibrotic agents have been widely used in patients with idiopathic pulmonary fibrosis (IPF). Long-term continuation of antifibrotic therapy is required for IPF treatment to prevent disease progression. However, antifibrotic treatment has considerable adverse events, and the continuation of treatment is uncertain in many cases. Therefore, we examined and compared the continuity of treatment between pirfenidone and nintedanib in patients with IPF. We retrospectively enrolled 261 consecutive IPF patients who received antifibrotic treatment from six core facilities in Gunma Prefecture from 2009 to 2018. Among them, 77 patients were excluded if the antifibrotic agent was switched or if the observation period was less than a year. In this study, 134 patients treated with pirfenidone and 50 treated with nintedanib were analyzed. There was no significant difference in patient background, discontinuation rate of antifibrotic treatment over time, and survival rate between the two groups. However, the discontinuation rate due to adverse events within one year of antifibrotic treatment was significantly higher in the nintedanib group than in the pirfenidone group (76% vs. 37%, p < 0.001). Furthermore, the discontinuation rate due to adverse events in nintedanib was higher than that of pirfenidone treatment throughout the observation period (70.6% vs. 31.2%, p = 0.016). The pirfenidone group tended to be discontinued due to acute exacerbation or transfer to another facility. The results of this study suggest that better management of adverse events with nintedanib leads to more continuous treatment that prevents disease progression and acute exacerbations, thus improving prognosis in patients with IPF.

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P088 Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis (IPF): one-year data from post-marketing surveillance in the United States

QJM ◽

10.1093/qjmed/hcw127.024 ◽

2016 ◽

Keyword(s):

United States ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

The United States ◽

Post Marketing Surveillance ◽

Post Marketing ◽

One Year

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Functional improvement in patients with idiopathic pulmonary fibrosis undergoing single lung transplantation

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37132015000000057 ◽

2015 ◽

Vol 41 (4) ◽

pp. 299-304 ◽

Cited By ~ 6

Author(s):

Adalberto Sperb Rubin ◽

Douglas Zaione Nascimento ◽

Letícia Sanchez ◽

Guilherme Watte ◽

Arthur Rodrigo Ronconi Holand ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Transplantation ◽

Functional Improvement ◽

First Year ◽

Single Lung Transplantation ◽

The Third ◽

The Mean ◽

One Year

AbstractObjective: To evaluate the changes in lung function in the first year after single lung transplantation in patients with idiopathic pulmonary fibrosis (IPF).Methods: We retrospectively evaluated patients with IPF who underwent single lung transplantation between January of 2006 and December of 2012, reviewing the changes in the lung function occurring during the first year after the procedure.Results: Of the 218 patients undergoing lung transplantation during the study period, 79 (36.2%) had IPF. Of those 79 patients, 24 (30%) died, and 11 (14%) did not undergo spirometry at the end of the first year. Of the 44 patients included in the study, 29 (66%) were men. The mean age of the patients was 57 years. Before transplantation, mean FVC, FEV1, and FEV1/FVC ratio were 1.78 L (50% of predicted), 1.48 L (52% of predicted), and 83%, respectively. In the first month after transplantation, there was a mean increase of 12% in FVC (400 mL) and FEV1 (350 mL). In the third month after transplantation, there were additional increases, of 5% (170 mL) in FVC and 1% (50 mL) in FEV1. At the end of the first year, the functional improvement persisted, with a mean gain of 19% (620 mL) in FVC and 16% (430 mL) in FEV1.Conclusions: Single lung transplantation in IPF patients who survive for at least one year provides significant and progressive benefits in lung function during the first year. This procedure is an important therapeutic alternative in the management of IPF.

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Mean Nocturnal Baseline Impedance on Multichannel Intraluminal Impedance Monitoring Predicts One-Year Pulmonary Function Decline in Patients with Idiopathic Pulmonary Fibrosis

Gastroenterology ◽

10.1016/s0016-5085(17)30771-0 ◽

2017 ◽

Vol 152 (5) ◽

pp. S131

Author(s):

Lawrence F. Borges ◽

Kelly Hathorn ◽

Sravanya Gavini ◽

Wai-Kit Lo ◽

Robert Burakoff ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Pulmonary Function ◽

Multichannel Intraluminal Impedance ◽

Intraluminal Impedance ◽

Impedance Monitoring ◽

One Year

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CHANGE IN COPD ASSESSMENT TEST SCORE IS SIGNIFICANTLY ASSOCIATED WITH CHANGE OF DISEASE STATUS IN IDIOPATHIC PULMONARY FIBROSIS IN ONE-YEAR FOLLOW-UP

Respirology ◽

10.1111/resp.13207_442 ◽

2017 ◽

Vol 22 ◽

pp. 253-253

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Test Score ◽

Disease Status ◽

Copd Assessment Test ◽

One Year

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The Value of the Surprise Question to Predict One-Year Mortality in Idiopathic Pulmonary Fibrosis: A Prospective Cohort Study

Respiration ◽

10.1159/000516291 ◽

2021 ◽

pp. 1-6

Author(s):

Catharina C. Moor ◽

Nelleke C. Tak van Jaarsveld ◽

Catherine Owusuaa ◽

Jelle R. Miedema ◽

Sara Baart ◽

...

Keyword(s):

Palliative Care ◽

Cohort Study ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Positive Predictive Value ◽

Predictive Value ◽

Prospective Cohort ◽

C Statistic ◽

One Year ◽

Surprise Question

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease with a heterogeneous disease course. Timely initiation of palliative care is often lacking. The surprise question “Would you be surprised if this patient died within the next year?” is increasingly used as a clinical prognostic tool in chronic diseases but has never been evaluated in IPF. Objective: We aimed to evaluate the predictive value of the surprise question for 1-year mortality in IPF. Methods: In this prospective cohort study, clinicians answered the surprise question for each included patient. Clinical parameters and mortality data were collected. The sensitivity, specificity, accuracy, negative, and positive predictive value of the surprise question with regard to 1-year mortality were calculated. Multivariable logistic regression analysis was performed to evaluate which factors were associated with mortality. In addition, discriminative performance of the surprise question was assessed using the C-statistic. Results: In total, 140 patients were included. One-year all-cause mortality was 20% (n = 28). Clinicians identified patients with a survival of <1 year with a sensitivity of 68%, a specificity of 82%, an accuracy of 79%, a positive predictive value of 49%, and a negative predictive value of 91%. The surprise question significantly predicted 1-year mortality in a multivariable model (OR 3.69; 95% CI 1.24–11.02; p = 0.019). The C-statistic of the surprise question to predict mortality was 0.75 (95% CI 0.66–0.85). Conclusions: The answer on the surprise question can accurately predict 1-year mortality in IPF. Hence, this simple tool may enable timely focus on palliative care for patients with IPF.

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