Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone

Ikeda, Kimiyuki; Shiratori, Masanori; Chiba, Hirofumi; Nishikiori, Hirotaka; Yokoo, Keiki; Saito, Atsushi; Hasegawa, Yoshihiro; Kuronuma, Koji; Otsuka, Mitsuo; Yamada, Gen; Takahashi, Hiroki

doi:10.1016/j.rmed.2017.08.021

Cited by 25 publications

(13 citation statements)

References 37 publications

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“…On the other hand, our study indicated the changes in serum levels of SP-A and KL-6 correlated signi cantly with changes in respiratory function, which re ects disease activity. These results are also consistent with other reports [6,10,11,26,28,32,33,[35][36][37][38]. Because of the di culty of respiratory function tests for patients of ILD, this evidence strongly supports the value of biomarkers in monitoring the activity of ILDs.…”

Section: Discussionsupporting

confidence: 92%

“…In the present study, pretreatment serum levels of SP-A and KL-6 did not relate to disease prognosis. It was reported that pretreatment KL-6 levels was signi cantly different depending on the response of pirfenidone therapy for IPF [32]. In the present study, pirfenidone was used on only 6 patients; the difference of treatment may affect this discrepancy.…”

Section: Discussionmentioning

confidence: 68%

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The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease 

Zheng¹,

Zheng²,

Hasegawa³

et al. 2020

Preprint

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Background The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to determine patients’ prognoses. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) were known biomarkers as a monitor of the prognoses. However, the clinical or pathophysiological differences of those biomarkers are not well evaluated. Therefore, through the comparison of the changes of SP-A and KL-6 levels before and after treatment, we investigated the clinical or pathophysiological differences which are embodied by those markers. Methods This study included retrospective data for 71 patients treated for ILD at the First Affiliated Hospital of Guangzhou Medical University between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed for at least 3 months. Results Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were significantly correlated (rS = 0.482, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (P < 0.05). In a cluster analysis of delta SP-A and KL-6 levels, patients were classified into three groups. In the cluster analysis, in the group in which only SP-A levels decreased after treatment, 50.0% of patients recovered respiratory function and had a significant reduction of serum LDH levels.Conclusions Reduced serum SP-A and/or KL-6 levels were associated with improved lung function in patients with ILD. However, there were patients who showed only a reduction of SP-A levels after treatment. Thus, for proper disease monitoring, measuring both markers are important.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 68%

The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease 

Zheng¹,

Zheng²,

Hasegawa³

et al. 2020

Preprint

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“…The daily dose of pirfenidone was increased in a stepwise manner from 600 mg to 1200-1800 mg every 2 weeks, as previously described [15]. The median maximum dose was 1500 mg (inter-quartile range [IQR], 1200-1800 mg), and the median final dose was 1200 mg (IQR, 1200-1800 mg).…”

Section: Pirfenidone and Nintedanib Treatmentmentioning

confidence: 99%

Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis

et al. 2020

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Background Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with poor prognosis. Pirfenidone and nintedanib are anti-fibrotic drugs used for patients with IPF. These drugs reduce the rate of decline in forced vital capacity (FVC). Serum surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) are monitoring and prognostic biomarkers in patients with IPF; however, their relationship with the therapeutic outcomes of anti-fibrotic drugs has not been investigated. We aim to clarify whether serum SP-A, SP-D, and KL-6 reflect therapeutic outcomes of pirfenidone and nintedanib administration in patients with IPF. Methods We retrospectively investigated patients with IPF who were initiated on pirfenidone or nintedanib administration between January 2014 and June 2018 at our hospital. Changes in clinical parameters and serum SP-A, SP-D, and KL-6 levels were evaluated. Patients with ≥10% decline in FVC or ≥ 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as progression group, while the other patients were classified as stable group. Results Forty-nine patients were included (pirfenidone, 23; nintedanib, 26). Stable group comprised 32 patients, while progression group comprised 17 patients. In the stable group, changes in SP-A and KL-6 from baseline to 3 and 6 months significantly decreased compared with the progression group (SP-A: 3 months − 6.0% vs 16.7%, 6 months − 10.2% vs 20.2%, KL-6: 3 months − 9.2% vs 6.7%, 6 months − 15.0% vs 12.1%, p < 0.05). Changes in SP-A and SP-D levels showed significant negative correlations with the change in %FVC (r = − 0.46 and r = − 0.39, p < 0.01, respectively) and %DLco (r = − 0.67 and r = − 0.54, p < 0.01, respectively). Similar results were also seen in subgroup analysis for both pirfenidone and nintedanib groups. On logistic regression analysis, decrease in SP-A from baseline to 3 months and 6 months was found to predict the outcomes at 6 months (odds ratios: 0.89 and 0.88, respectively). Conclusions Changes in serum SP-A reflected the outcomes of anti-fibrotic drug therapy. Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs.

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“…13 In fact, it is reported that serum SP-D levels may predict the effectiveness of antifibrotic therapy. 14 In this study, a potent antifibrotic efficacy by RTX may be indicated as rapid decrease of SP-D in the good responder group. Meanwhile, baseline SP-D levels did not correlate with %FVC.…”

Section: Discussionmentioning

confidence: 88%

Rapid decrease of serum surfactant protein‐D levels predicts the reactivity of rituximab therapy in systemic sclerosis‐associated interstitial lung disease

Ebata

Yoshizaki

Fukasawa

et al. 2020

The Journal of Dermatology

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Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage and excessive fibrosis. SSc-associated interstitial lung disease (ILD) is a leading cause of death in SSc. Several studies have shown the efficacy of rituximab (RTX) in SSc-ILD, but no study has examined the relation between RTX reactivity and change of serum marker levels. In this study we examined the relation between change of serum surfactant protein-D (SP-D) levels and change of percentage forced vital capacity (FVC) in 11 SSc-ILD patients with antitopoisomerase I antibody treated by RTX. Serum SP-D levels were significantly decreased compared with baseline at 2 weeks after first RTX infusion in good responders (P = 0.04), while not in poor responders (P = 0.77). Moreover, DSP-D at 2 weeks negatively correlated with D%FVC at 24 weeks (P = 0.001). In conclusion, we suggested that the rapid decrease of SP-D levels may be a predictive marker of RTX effect against SSc-ILD.

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Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone

Cited by 25 publications

References 37 publications

The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease

The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease

Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis

Rapid decrease of serum surfactant protein‐D levels predicts the reactivity of rituximab therapy in systemic sclerosis‐associated interstitial lung disease

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Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone

Cited by 25 publications

References 37 publications

The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease&nbsp;

The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease&nbsp;

Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis

Rapid decrease of serum surfactant protein‐D levels predicts the reactivity of rituximab therapy in systemic sclerosis‐associated interstitial lung disease

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The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease

The Difference Between SP-A and KL-6 Levels Responses for Treatment of Interstitial Lung Disease