Faculty Opinions recommendation of Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. Methods Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not. Results Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics. Conclusion Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

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Switching antifibrotics in patients with idiopathic pulmonary fibrosis: a multi-center retrospective cohort study

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01587-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuzo Suzuki ◽

Kazutaka Mori ◽

Yuya Aono ◽

Masato Kono ◽

Hirotsugu Hasegawa ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Survival Times ◽

Antifibrotic Therapy ◽

Median Period

Abstract Background Currently, there are two antifibrotics used to treat idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. Antifibrotics slow disease progression by reducing the annual decline of forced vital capacity (FVC), which possibly improves outcomes in IPF patients. During treatment, patients occasionally switch antifibrotic treatments. However, prognostic implication of changing antifibrotics has not yet been evaluated. Methods This multi-center retrospective cohort study examined 262 consecutive IPF patients who received antifibrotic therapy. Antifibrotic agents were switched in 37 patients (14.1%). The prognoses were compared between the patient cohort that switched antifibrotics (Switch-IPF) and those without (Non-Switch-IPF) using propensity-score matched analyses. Results The median period between the initiation of antifibrotic therapy and the drug switch was 25.8 (12.7–35.3) months. The most common reasons for the switch were disease progression (n = 17) followed by gastrointestinal disorders (n = 12). Of the 37 patients that switched antifibrotics, only eight patients disrupted switched antifibrotics by their adverse reactions. The overall prognosis of the Switch-IPF cohort was significantly better than the Non-Switch-IPF cohort (median periods: 67.2 vs. 27.1 months, p < 0.0001). In propensity-score matched analyses that were adjusted to age, sex, FVC (%), history of acute exacerbation, and usage of long-term oxygen therapy, the Switch-IPF cohort had significantly longer survival times than the Non-Switch-IPF group (median 67.2 vs. 41.3 months, p = 0.0219). The second-line antifibrotic therapy showed similar survival probabilities than those in first-line antifibrotic therapy in multistate model analyses. Conclusion Switching antifibrotics is feasible and may improve prognosis in patients with IPF. A further prospective study will be required to confirm clinical implication of switching the antifibrotics.

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Efficacy of early antifibrotic treatment for idiopathic pulmonary fibrosis

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01595-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Keishi Sugino ◽

Hirotaka Ono ◽

Natsumi Watanabe ◽

Masahiro Ando ◽

Eiyasu Tsuboi ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Vital Capacity ◽

Early Stage ◽

Japanese Patients ◽

Oxygen Desaturation ◽

Stage I ◽

Relative Decline ◽

Antifibrotic Drugs

Abstract Background Although antifibrotic drugs, including nintedanib and pirfenidone, slow the progression of idiopathic pulmonary fibrosis (IPF), there is little data about the timing of start of antifibrotic treatment in real-world clinical practice. The present study aimed to clarify the efficacy of nintedanib and pirfenidone in patients with early-stage IPF. Methods We compared survival and disease progression between patients with IPF with Japanese Respiratory Society (JRS) disease severity system stage I with and without oxygen desaturation on the 6-min walk test (6MWT) and increased the gender–age–physiology (GAP) staging. We examined the efficacy of antifibrotic drugs in patients with early-stage IPF. Results The severity of stage I IPF (n = 179) according to the JRS criteria consisted of the following GAP staging criteria: stage I, 111 cases; stage II, 58 cases; stage III, 10 cases. The duration from the initial visit to disease progression and survival time was significantly shorter in JRS stage I patients with oxygen desaturation on the 6MWT or with increased GAP staging (unfavorable group) compared with patients without those factors. In the unfavorable group, the relative decline in percentage predicted forced vital capacity (%FVC) over 6 months was significantly lower in patients undergoing antifibrotic treatment compared with non-treated patients. Conclusion Antifibrotic drugs have a beneficial effect on the decline in %FVC in Japanese patients with early-stage IPF who have oxygen desaturation on the 6MWT or increased GAP staging.

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Longitudinal serological assessment of neutrophil activity is related to disease progression in idiopathic pulmonary fibrosis

10.1183/13993003.congress-2021.pa2252 ◽

2021 ◽

Author(s):

Henrik Jessen ◽

Nils Hoyer ◽

Thomas Prior ◽

Peder Frederiksen ◽

Morten Karsdal ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Neutrophil Activity

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Quantitative CT analysis using functional imaging is superior in describing disease progression in idiopathic pulmonary fibrosis compared to forced vital capacity

Respiratory Research ◽

10.1186/s12931-018-0918-5 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 8

Author(s):

J. Clukers ◽

M. Lanclus ◽

B. Mignot ◽

C. Van Holsbeke ◽

J. Roseman ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Functional Imaging ◽

Forced Vital Capacity ◽

Vital Capacity ◽

Quantitative Ct ◽

Ct Analysis ◽

Quantitative Ct Analysis

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Disease Progression Events in Trials of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a4548 ◽

2020 ◽

Author(s):

S.D. Nathan ◽

U. Costabel ◽

L.H. Lancaster ◽

T.J. Corte ◽

H. Nunes ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression

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Effects of Nintedanib on Quantitative Lung Fibrosis Score in Idiopathic Pulmonary Fibrosis

The Open Respiratory Medicine Journal ◽

10.2174/1874306402014010022 ◽

2020 ◽

Vol 14 (1) ◽

pp. 22-31

Author(s):

Lisa Lancaster ◽

Jonathan Goldin ◽

Matthias Trampisch ◽

Grace Hyun Kim ◽

Jonathan Ilowite ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Lung Fibrosis ◽

Open Label ◽

High Resolution Computed Tomography ◽

Double Blind ◽

Phase Iiib ◽

Exploratory Data ◽

Relative Change

Background: Nintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied. Objective: We conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF. Methods: 113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory. Results: Adjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: −9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: −1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were −14.2 mL and −83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: −8.7, 146.8]). Conclusion: Exploratory data suggest that in patients with IPF, 6 months’ treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF.

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