ORCID Profile
0000-0002-1340-2688
Current Organisations
Cochrane
,
Imperial College London
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Publisher: American Thoracic Society
Date: 15-03-2023
Publisher: Wiley
Date: 29-09-2022
DOI: 10.1111/RESP.14378
Abstract: Pulmonary hypertension is a life‐limiting complication of interstitial lung disease (ILD‐PH). We investigated whether treatment with phosphodiesterase 5 inhibitors (PDE5i) in patients with ILD‐PH was associated with improved survival. Consecutive incident patients with ILD‐PH and right heart catheterisation, echocardiography and spirometry data were followed from diagnosis to death, transplantation or censoring with all follow‐up and survival data modelled by Bayesian methods. The diagnoses in 128 patients were idiopathic pulmonary fibrosis ( n = 74, 58%), hypersensitivity pneumonitis ( n = 17, 13%), non‐specific interstitial pneumonia ( n = 12, 9%), undifferentiated ILD ( n = 8, 6%) and other lung diseases ( n = 17, 13%). Final outcomes were death ( n = 106, 83%), transplantation ( n = 9, 7%) and censoring ( n = 13, 10%). Patients treated with PDE5i ( n = 50, 39%) had higher mean pulmonary artery pressure (median 38 mm Hg [interquartile range, IQR: 34, 43] vs. 35 mm Hg [IQR: 31, 38], p = 0.07) and percentage predicted forced vital capacity (FVC median 57% [IQR: 51, 73] vs. 52% [IQR: 45, 66], p= 0.08) though differences did not reach significance. Patients treated with PDE5i survived longer than untreated patients (median 2.18 years [95% CI: 1.43, 3.04] vs. 0.94 years [0.69, 1.51], p = 0.003) independent of all other prognostic markers by Bayesian joint‐modelling (HR 0.39, 95% CI: 0.23, 0.59, p 0.001) and propensity‐matched analyses (HR 0.38, 95% CI: 0.22, 0.58, p 0.001). Survival difference with treatment was significantly larger if right ventricular function was normal, rather than abnormal, at presentation (+2.55 years, 95% CI: −0.03, +3.97 vs. +0.98 years, 95% CI: +0.47, +2.00, p = 0.04). PDE5i treatment in ILD‐PH should be investigated by a prospective randomized trial.
Publisher: Wiley
Date: 15-05-2023
DOI: 10.1002/ART.42491
Abstract: In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD). We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF‐controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc‐ILD, and its association with lung function, disease extent on radiography, and patient health–related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc‐ILD from IPF‐controls were identified. A composite biomarker index, comprising surfactant protein D (SP‐D), Ca15‐3, and intercellular adhesion molecule 1 (ICAM‐1), was strongly associated with SSc‐ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59–35.21) ( P 0.001). The composite index strengthened the performance of in idual biomarkers for SSc‐ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (for biomarker index score 3 relative to biomarker index score 0, the adjusted absolute change in forced vital capacity percent predicted was −17.84% and the diffusing capacity for carbon monoxide percent predicted was −20.16% both P 0.001). A composite serum biomarker index, comprising SP‐D, Ca15‐3, and ICAM‐1, may improve the identification and risk stratification of ILD in SSc patients at baseline.
Publisher: Microbiology Society
Date: 10-2021
DOI: 10.1099/JMM.0.001420
Abstract: Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways. Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load. Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live P. aeruginosa load in adults with CF. Methodology. Seventy-five sputum s les at clinical stability and 48 paired sputum s les obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative P. aeruginosa polymerase chain reaction (qPCR). Live P. aeruginosa qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine. Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live P. aeruginosa qPCR load in sputum, compared to culture. Following systemic antibiotics live P. aeruginosa qPCR load decreased significantly ( P .001) and was correlated with a reduction in plasma NHQ (plasma: r=0.463, P =0.003). Conclusion. In adults with CF, AQ concentrations correlated more strongly with live P. aeruginosa bacterial load measured by qPCR compared to traditional culture. Prospective studies are required to assess the potential of systemic AQs as biomarkers of P. aeruginosa bacterial burden.
Publisher: European Respiratory Society (ERS)
Date: 21-10-2021
DOI: 10.1183/13993003.01181-2021
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE). In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations. 189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. 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 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts. A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.
Publisher: Cold Spring Harbor Laboratory
Date: 14-12-2022
DOI: 10.1101/2022.12.13.22283391
Abstract: Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. Sleep parameters were assessed in a prospective cohort of patients (n=2,468) hospitalised for COVID-19 in the United Kingdom in 39 centres using both subjective and device-based measures. Results were compared to a matched UK biobank cohort and associations were evaluated using multivariable linear regression. 64% (456/714) of participants reported poor sleep quality 56% felt their sleep quality had deteriorated for at least 1-year following hospitalisation. Compared to the matched cohort, both sleep regularity (44.5 vs 59.2, p .001) and sleep efficiency (85.4% vs 88.5%, p .001) were lower whilst sleep period duration was longer (8.25h vs 7.32h, p .001). Overall sleep quality (effect estimate 4.2 (3.0–5.5)), deterioration in sleep quality following hospitalisation (effect estimate 3.2 (2.0–4.5)), and sleep regularity (effect estimate 5.9 (3.7–8.1)) were associated with both dyspnoea and impaired lung function (FEV 1 and FVC). Depending on the sleep metric, anxiety mediated 13–42% of the effect of sleep disturbance on dyspnoea and muscle weakness mediated 29-43% of this effect. Sleep disturbance is associated with dyspnoea, anxiety and muscle weakness following COVID-19 hospitalisation. It could have similar effects for other causes of hospitalisation where sleep disturbance is prevalent. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Iain Stewart.