Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study

Jenkins, Gisli; Simpson, Juliet K.; Saini, Gauri; Bentley, Johanne; Russell, Anne-Marie; Braybrooke, Rebecca; Molyneaux, Philip L.; McKeever, Tricia M.; Wells, Athol U.; Flynn, AA; Hubbard, Richard; Leeming, Diana Julie; Marshall, Richard P.; Karsdal, Morten A.; Lukey, Pauline T.; Maher, Toby M.

doi:10.1016/s2213-2600(15)00048-x

Cited by 261 publications

(235 citation statements)

References 33 publications

Supporting

Mentioning

218

Contrasting

Unclassified

Order By: Relevance

“…Subjects with a consensus diagnosis of IPF [made in accordance with current international criteria (13)] were recruited as a subgroup of the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study (14), from the interstitial lung disease unit at Royal Brompton Hospital, London. The study was approved by the Royal Free Hospital and Medical School Research Ethics Committee (10/H0720/12), and all subjects provided signed, informed consent.…”

Section: Study Subjectsmentioning

confidence: 99%

Daily Home Spirometry: An Effective Tool for Detecting Progression in Idiopathic Pulmonary Fibrosis

Russell

Adamali

Molyneaux

et al. 2016

Am J Respir Crit Care Med

Self Cite

143

120

View full text Add to dashboard Cite

Rationale: Recent clinical trial successes have created an urgent need for earlier and more sensitive endpoints of disease progression in idiopathic pulmonary fibrosis (IPF). Domiciliary spirometry permits more frequent measurement of FVC than does hospital-based assessment, which therefore affords the opportunity for a more granular insight into changes in IPF progression.Objectives: To determine the feasibility and reliability of measuring daily FVC in individuals with IPF.Methods: Subjects with IPF were given handheld spirometers and instruction on how to self-administer spirometry. Subjects recorded daily FEV 1 and FVC for up to 490 days. Clinical assessment and hospital-based spirometry was undertaken at 6 and 12 months, and outcome data were collected for 3 years.Measurements and Main Results: Daily spirometry was recorded by 50 subjects for a median period of 279 days (range, 13-490 d). There were 18 deaths during the active study period. Home spirometry showed excellent correlation with hospital-obtained readings. The rate of decline in FVC was highly predictive of outcome and subsequent mortality when measured at 3 months (hazard ratio [HR], 1.040; 95% confidence interval [CI], 1.021-1.062; P < 0.001), 6 months (HR, 1.024; 95% CI, 1.014-1.033; P , 0.001), and 12 months (HR, 1.012; 95% CI, 1.007-1.016; P = 0.001).Conclusions: Measurement of daily home spirometry in patients with IPF is highly clinically informative and is feasible to perform for most of these patients. The relationship between mortality and rate of change of FVC at 3 months suggests that daily FVC may be of value as a primary endpoint in short proof-of-concept IPF studies.

show abstract

Section: Study Subjectsmentioning

confidence: 99%

Daily Home Spirometry: An Effective Tool for Detecting Progression in Idiopathic Pulmonary Fibrosis

Russell

Adamali

Molyneaux

et al. 2016

Am J Respir Crit Care Med

Self Cite

143

120

View full text Add to dashboard Cite

show abstract

“…In PROFILE, the largest IPF biomarker cohort studied globally, JENKINS et al [36] showed changes in serum concentrations of proteolytically cleaved protein fragments/neopitopes. Levels of fragmented proteins generated by MMP activity and collagen synthesis in the serum of IPF patients were associated with IPF progression, as well as survival rate [36].…”

Section: Peripheral Blood Phenotypingmentioning

confidence: 99%

“…Levels of fragmented proteins generated by MMP activity and collagen synthesis in the serum of IPF patients were associated with IPF progression, as well as survival rate [36]. Immune cell type dysfunction has also been implicated in IPF.…”

Section: Peripheral Blood Phenotypingmentioning

confidence: 99%

Systems medicine advances in interstitial lung disease

2017

View full text Add to dashboard Cite

Fibrotic lung diseases involve subject-environment interactions, together with dysregulated homeostatic processes, impaired DNA repair and distorted immune functions. Systems medicine-based approaches are used to analyse diseases in a holistic manner, by integrating systems biology platforms along with clinical parameters, for the purpose of understanding disease origin, progression, exacerbation and remission.Interstitial lung diseases (ILDs) refer to a heterogeneous group of complex fibrotic diseases. The increase of systems medicine-based approaches in the understanding of ILDs provides exceptional advantages by improving diagnostics, unravelling phenotypical differences, and stratifying patient populations by predictable outcomes and personalised treatments. This review discusses the state-of-the-art contributions of systems medicine-based approaches in ILDs over the past 5 years.

show abstract

“…Thus, it is challenging to identify matrikines that can exert a specific phenotype in diseases where the ECM undergoes continuous remodeling, as is seen in interstitial lung diseases including idiopathic pulmonary fibrosis, ARDS, and COPD. To our knowledge, the largest characterization of ECM turnover in lung disease was in the longitudinal monitoring of collagen protein turnover by neoepitope analysis in the PRO-FILE cohort of pulmonary fibrosis patients (108). This study used ELISA to detect and characterize collagen breakdown products and showed that patients with increased collagen breakdown products have worse outcomes from lung fibrosis in idiopathic pulmonary fibrosis.…”

Section: Hyaluronan-derived Matrikinesmentioning

confidence: 99%