Imperial College London

DrPeterGeorge

Faculty of MedicineNational Heart & Lung Institute

Honorary Clinical Senior Lecturer
 
 
 
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p.george

 
 
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Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
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158 results found

Shah R, Morgan A, George P, Quint Jet al., 2024, Incidence, prevalence, and mortality of idiopathic pulmonary fibrosis in England from 2008 to 2018: a cohort study, Thorax, ISSN: 0040-6376

Journal article

Devaraj A, Ottink F, Rennison-Jones C, Blé F-X, Joly O, Azim A, Gerry S, Harston G, Ostridge K, George PMet al., 2024, e-Lung CT Biomarker Stratifies Patients at Risk of IPF Progression in a 52-Week Clinical Trial., Am J Respir Crit Care Med

Journal article

Johnson SR, Shaw DE, Avoseh M, Soomro I, Pointon KS, Kokosi M, Nicholson AG, Desai SR, George PMet al., 2024, Diagnosis of cystic lung diseases: a position statement from the UK Cystic Lung Disease Rare Disease Collaborative Network., Thorax

BACKGROUND: Rare cystic lung diseases are increasingly recognised due the wider application of CT scanning making cystic lung disease management a growing part of respiratory care. Cystic lung diseases tend to have extrapulmonary features that can both be diagnostic but also require surveillance and treatment in their own right. As some of these diseases now have specific treatments, making a precise diagnosis is crucial. While Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome, lymphoid interstitial pneumonia and lymphangioleiomyomatosis are becoming relatively well-known diseases to respiratory physicians, a targeted and thorough workup improves diagnostic accuracy and may suggest other ultrarare diseases such as light chain deposition disease, cystic pulmonary amyloidosis, low-grade metastatic neoplasms or infections. In many cases, diagnostic information is overlooked leaving uncertainty over the disease course and treatments. AIMS: This position statement from the Rare Disease Collaborative Network for cystic lung diseases will review how clinical, radiological and physiological features can be used to differentiate between these diseases. NARRATIVE: We highlight that in many cases a multidisciplinary diagnosis can be made without the need for lung biopsy and discuss where tissue sampling is necessary when non-invasive methods leave diagnostic doubt. We suggest an initial workup focusing on points in the history which identify key disease features, underlying systemic and familial diseases and a clinical examination to search for connective tissue disease and features of genetic causes of lung cysts. All patients should have a CT of the thorax and abdomen to characterise the pattern and burden of lung cysts and extrapulmonary features and also spirometry, gas transfer and a 6 min walk test. Discussion with a rare cystic lung disease centre is suggested before a surgical biopsy is undertaken. CONCLUSIONS: We suggest that this focused workup sho

Journal article

Margaritopoulos GA, Proklou A, Trachalaki A, Badenes Bonet D, Kokosi M, Kouranos V, Chua F, George P, Renzoni EA, Devaraj A, Desai S, Nicholson AG, Antoniou KM, Wells AUet al., 2024, Overnight desaturation in interstitial lung diseases: links to pulmonary vasculopathy and mortality, ERJ Open Research, Vol: 10, ISSN: 2312-0541

Background: Overnight desaturation predicts poor prognosis across interstitial lung diseases (ILDs). The aim of the present study was to investigate whether nocturnal desaturation is associated with pulmonary vasculopathy and mortality.Methods: A retrospective single centre study of 397 new ILD patients was carried out including patients with idiopathic pulmonary fibrosis (IPF) (n=107) and patients with non-IPF fibrotic ILD (n=290). This is the largest study to date of the effect of significant nocturnal desaturation (SND) (≥10% of total sleep time with oxygen saturation ≤90% measured by pulse oximetry).Results: The prevalence of SND was 28/107 (26.2%) in IPF and 80/290 (27.6%) in non-IPF ILD. The prevalence of SND was higher in non-IPF ILDs than in IPF (p=0.025) in multivariate analysis. SND was associated with noninvasive markers of pulmonary hypertension (PH): tricuspid regurgitation velocity (TRV) (p<0.0001), brain natriuretic peptide (p<0.007), carbon monoxide transfer coefficient (p<0.0001), A–a gradient (p<0.0001), desaturation >4% in 6-min walking test (p<0.03) and pulmonary artery diameter (p<0.005). SND was independently associated with high echocardiographic PH probability in the entire cohort (OR 2.865, 95% CI 1.486–5.522, p<0.002) and in non-IPF fibrotic ILD (OR 3.492, 95% CI 1.597–7.636, p<0.002) in multivariate analysis. In multivariate analysis, SND was associated with mortality in the entire cohort (OR 1.734, 95% CI 1.202–2.499, p=0.003) and in IPF (OR 1.908, 95% CI 1.120–3.251, p=0.017) and non-IPF fibrotic ILD (OR 1.663, 95% CI 1.000–2.819, p=0.041). Separate models with exclusion of each one of the diagnostic subgroups showed that no subgroup was responsible for this finding in non-IPF ILDs. SND was a stronger marker of 5-year mortality than markers of PH.Conclusion: SND was associated with high echocardiographic probability and mortality and was a stronger predictor of mortalit

Journal article

Dixon G, Hague S, Mulholland S, Adamali H, Khin AMN, Thould H, Connon R, Minnis P, Murtagh E, Khan F, Toor S, Lawrence A, Naqvi M, West A, Coker RK, Ward K, Yazbeck L, Hart S, Garfoot T, Newman K, Rivera-Ortega P, Stranks L, Beirne P, Bradley J, Rowan C, Agnew S, Ahmad M, Spencer LG, Aigbirior J, Fahim A, Wilson AM, Butcher E, Chong SG, Saini G, Zulfikar S, Chua F, George PM, Kokosi M, Kouranos V, Molyneaux P, Renzoni E, Vitri B, Wells AU, Nicol LM, Bianchi S, Kular R, Liu H, John A, Barth S, Wickremasinghe M, Forrest IA, Grimes I, Simpson AJ, Fletcher SV, Jones MG, Kinsella E, Naftel J, Wood N, Chalmers J, Crawshaw A, Crowley LE, Dosanjh D, Huntley CC, Walters GI, Gatheral T, Plum C, Bikmalla S, Muthusami R, Stone H, Rodrigues JCL, Tsaneva-Atanasova K, Scotton CJ, Gibbons MA, Barratt SLet al., 2024, Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK., ERJ Open Res, Vol: 10, ISSN: 2312-0541

BACKGROUND: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. METHODS: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. RESULTS: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. CONCLUSION: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD h

Journal article

Desai SR, Sivarasan N, Johannson KA, George PM, Culver DA, Devaraj A, Lynch DA, Milne D, Renzoni E, Nunes H, Sverzellati N, Spagnolo P, Baughman RP, Yadav R, Piciucchi S, Walsh SLF, Kouranos V, Wells AU, Sarcoid Delphi Groupet al., 2023, High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study., Lancet Respir Med

One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis.

Journal article

Barnett JL, Maher TM, Quint JK, Adamson A, Wu Z, Smith DJF, Rawal B, Nair A, Walsh SLF, Desai SR, George PM, Kokosi M, Jenkins G, Kouranos V, Renzoni EA, Rice A, Nicholson AG, Chua F, Wells AU, Molyneaux PL, Devaraj Aet al., 2023, Combination of BAL and computed tomography differentiates progressive and non-progressive fibrotic lung diseases, American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 975-982, ISSN: 1073-449X

Rationale: Identifying patients with pulmonary fibrosis (PF) at risk of progression can guide management. Objectives: To explore the utility of combining baseline BAL and computed tomography (CT) in differentiating progressive and nonprogressive PF. Methods: The derivation cohort consisted of incident cases of PF for which BAL was performed as part of a diagnostic workup. A validation cohort was prospectively recruited with identical inclusion criteria. Baseline thoracic CT scans were scored for the extent of fibrosis and usual interstitial pneumonia (UIP) pattern. The BAL lymphocyte proportion was recorded. Annualized FVC decrease of >10% or death within 1 year was used to define disease progression. Multivariable logistic regression identified the determinants of the outcome. The optimum binary thresholds (maximal Wilcoxon rank statistic) at which the extent of fibrosis on CT and the BAL lymphocyte proportion could distinguish disease progression were identified. Measurements and Main Results: BAL lymphocyte proportion, UIP pattern, and fibrosis extent were significantly and independently associated with disease progression in the derivation cohort (n = 240). Binary thresholds for increased BAL lymphocyte proportion and extensive fibrosis were identified as 25% and 20%, respectively. An increased BAL lymphocyte proportion was rare in patients with a UIP pattern (8 of 135; 5.9%) or with extensive fibrosis (7 of 144; 4.9%). In the validation cohort (n = 290), an increased BAL lymphocyte proportion was associated with a significantly lower probability of disease progression in patients with nonextensive fibrosis or a non-UIP pattern. Conclusions: BAL lymphocytosis is rare in patients with extensive fibrosis or a UIP pattern on CT. In patients without a UIP pattern or with limited fibrosis, a BAL lymphocyte proportion of ⩾25% was associated with a lower likelihood of progression.

Journal article

Stock CJW, Bray WG, Kouranos V, Jacob J, Kokosi M, George PM, Chua F, Wells AU, Sestini P, Renzoni EAet al., 2023, Serum C-reactive protein is associated with earlier mortality across different interstitial lung diseases, RESPIROLOGY, ISSN: 1323-7799

Journal article

Morgan A, Shah R, George P, Quint Jet al., 2023, Validation of the recording of idiopathic pulmonary fibrosis in routinely collected electronic healthcare records in England, BMC Pulmonary Medicine, Vol: 23, Pages: 1-12, ISSN: 1471-2466

BackgroundRoutinely-collected healthcare data provide a valuable resource for epidemiological research. Validation studies have shown that for most conditions, simple lists of clinical codes can reliably be used for case finding in primary care, however, studies exploring the robustness of this approach are lacking for diseases such as idiopathic pulmonary fibrosis (IPF) which are largely managed in secondary care.MethodUsing the UK’s Clinical Practice Research Datalink (CPRD) Aurum dataset, which comprises patient-level primary care records linked to national hospital admissions and cause-of-death data, we compared the positive predictive value (PPV) of eight diagnostic algorithms. Algorithms were developed based on the literature and IPF diagnostic guidelines using combinations of clinical codes in primary and secondary care (SNOMED-CT or ICD-10) with/without additional information. The positive predictive value (PPV) was estimated for each algorithm using the death record as the gold standard. Utilization of the reviewed codes across the study period was observed to evaluate any change in coding practices over time.ResultA total of 17,559 individuals had a least one record indicative of IPF in one or more of our three linked datasets between 2008 and 2018. The PPV of case-finding algorithms based on clinical codes alone ranged from 64.4% (95%CI:63.3–65.3) for a “broad” codeset to 74.9% (95%CI:72.8–76.9) for a “narrow” codeset comprising highly-specific codes. Adding confirmatory evidence, such as a CT scan, increased the PPV of our narrow code-based algorithm to 79.2% (95%CI:76.4–81.8) but reduced the sensitivity to under 10%. Adding evidence of hospitalisation to the standalone code-based algorithms also improved PPV, (PPV = 78.4 vs. 64.4%; sensitivity = 53.5% vs. 38.1%). IPF coding practices changed over time, with the increased use of specific IPF codes.ConclusionHigh diagnostic validi

Journal article

Nolan CM, Schofield SJ, Maddocks M, Patel S, Barker RE, Walsh JA, Polgar O, George PM, Molyneaux PL, Maher TM, Cullinan P, Man WD-Cet al., 2023, Change in gait speed and adverse outcomes in patients with idiopathic pulmonary fibrosis: a prospective cohort study, Respirology, Vol: 28, Pages: 649-658, ISSN: 1323-7799

BACKGROUND AND OBJECTIVE: Gait speed is associated with survival in individuals with idiopathic pulmonary fibrosis (IPF). The extent to which four-metre gait speed (4MGS) decline predicts adverse outcome in IPF remains unclear. We aimed to examine longitudinal 4MGS change and identify a cut-point associated with adverse outcome. METHODS: In a prospective cohort study, we recruited 132 individuals newly diagnosed with IPF and measured 4MGS change over 6 months. Death/first hospitalization at 6 months were composite outcome events. Complete data (paired 4MGS plus index event) were available in 85 participants; missing 4MGS data were addressed using multiple imputation. Receiver-Operating Curve plots identified a 4MGS change cut-point. Cox proportional-hazard regression assessed the relationship between 4MGS change and time to event. RESULTS: 4MGS declined over 6 months (mean [95% CI] change: -0.05 [-0.09 to -0.01] m/s; p = 0.02). A decline of 0.07 m/s or more in 4MGS over 6 months had better discrimination for the index event than change in 6-minute walk distance, forced vital capacity, Composite Physiologic Index or Gender Age Physiology index. Kaplan-Meier curves demonstrated a significant difference in time to event between 4MGS groups (substantial decline: >-0.07 m/s versus minor decline/improvers: ≤-0.07 m/s; p = 0.007). Those with substantial decline had an increased risk of hospitalization/death (adjusted hazard ratio [95% CI] 4.61 [1.23-15.83]). Similar results were observed in multiple imputation analysis. CONCLUSION: In newly diagnosed IPF, a substantial 4MGS decline over 6 months is associated with shorter time to hospitalization/death at 6 months. 4MGS change has potential as a surrogate endpoint for interventions aimed at modifying hospitalization/death.

Journal article

Shah R, 2023, Incidence and prevalence of interstitial lung diseases worldwide: a systematic literature review, BMJ Open Respiratory Research, Vol: 10, Pages: 1-11, ISSN: 2052-4439

Interstitial lung disease (ILD) is a collective term representing a diverse group of pulmonary fibrotic and inflammatory conditions. Due to the diversity of ILD conditions, paucity of guidance and updates to diagnostic criteria over time, it has been challenging to precisely determine ILD incidence and prevalence. This systematic review provides a synthesis of published data at a global level and highlights gaps in the current knowledge base. Medline and Embase databases were searched systematically for studies reporting incidence and prevalence of various ILDs. Randomised controlled trials, case reports and conference abstracts were excluded. 80 studies were included, the most described subgroup was autoimmune-related ILD, and the most studied conditions were rheumatoid arthritis (RA)-associated ILD, systemic sclerosis associated (SSc) ILD and idiopathic pulmonary fibrosis (IPF). The prevalence of IPF was mostly established using healthcare datasets, whereas the prevalence of autoimmune ILD tended to be reported in smaller autoimmune cohorts. The prevalence of IPF ranged from 7 to 1650 per 100 000 persons. Prevalence of SSc ILD and RA ILD ranged from 26.1% to 88.1% and 0.6% to 63.7%, respectively. Significant heterogeneity was observed in the reported incidence of various ILD subtypes. This review demonstrates the challenges in establishing trends over time across regions and highlights a need to standardise ILD diagnostic criteria.PROSPERO registration number: CRD42020203035.

Journal article

Massen G, Morgan AD, George PM, Quint JKet al., 2023, Does Antacid Therapy in Idiopathic Pulmonary Fibrosis Patients Increase Risk of Pneumonia? An Observational Cohort Study, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

George PM, Rennison-Jones C, Bellot P, Joly O, Gerry S, Schwartz LA, Thiele A, Harston G, Devaraj Aet al., 2023, Performance and Reproducibility of a Deep-learning Derived Automated Algorithm to Detect, Segment and Measure Lung Cancer Lesions on Computed Tomography Scans, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

George PM, Rennison-Jones C, Benvenuti G, Gupta G, Joly O, Gerry S, Rajan S, Jankharia B, Fernandez C, Harston G, Devaraj Aet al., 2023, The Automated E-ILD CT Algorithm Is More Prognostic Than FVC in the Serial Assessment of Patients With Non-IPF Fibrotic Interstitial Lung Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

George PM, Rennison-Jones C, Benvenuti G, Gupta G, Joly O, Gerry S, Fernandez C, Harston G, Devaraj Aet al., 2023, In the Serial Assessment of Patients With Idiopathic Pulmonary Fibrosis, the Automated E-ILD CT Algorithm Outperforms Lung Function; a Validation Study, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Morgan AD, Massen GM, George PM, Quint JKet al., 2023, Use of Inhaled Corticosteroids and the Risk of Mortality and Hospitalisation for Pneumonia in a UK Cohort of Patients With Idiopathic Pulmonary Fibrosis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Shah R, Morgan AD, George PM, Quint JKet al., 2023, Validation of Coding of Idiopathic Pulmonary Fibrosis in Primary and Secondary Health Records in the UK, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Stewart I, Molyneaux PL, Fabbri L, Quint JK, Walsh SLF, Weeks M, Jenkins RGet al., 2023, Residual lung abnormalities following COVID-19 hospitalization: interim analysis of the UKILD Post-COVID study, American Journal of Respiratory and Critical Care Medicine, Vol: 207, Pages: 693-703, ISSN: 1073-449X

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage.Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post–COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata.Methods: The PHOSP–COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP–COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up.Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83–155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05–1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00–1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07–1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6–9.5), rising to 11.7% (95% CrI, 10.3–13.1) in the sensitivity analysis.Conclusions: Residual lung abnormalities were estimated in up to 11% of

Journal article

Dawes TJW, McCabe C, Dimopoulos K, Stewart I, Bax S, Harries C, Samaranayake CB, Kempny A, Molyneaux PL, Seitler S, Semple T, Li W, George PM, Kouranos V, Chua F, Renzoni EA, Kokosi M, Jenkins G, Wells AU, Wort SJ, Price LCet al., 2023, Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: A Bayesian retrospective observational cohort study, Respirology, Vol: 28, Pages: 262-272, ISSN: 1323-7799

Background and ObjectivePulmonary 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.MethodsConsecutive 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.ResultsThe 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).ConclusionPDE5i treatment in ILD-PH should be investigated by a prospective randomized trial.

Journal article

Mikolasch TA, George PM, Sahota J, Nancarrow T, Barratt SL, Woodhead FA, Kouranos V, Cope VSA, Creamer AW, Fidan S, Ganeshan B, Hoy L, Mackintosh JA, Shortman R, Duckworth A, Fallon J, Garthwaite H, Heightman M, Adamali HI, Lines S, Win T, Wollerton R, Renzoni EA, Steward M, Wells AU, Gibbons M, Groves AM, Gooptu B, Scotton CJ, Porter JCet al., 2023, Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis, ECLINICALMEDICINE, Vol: 55

Journal article

Raman L, Stewart I, Barrett S, Chua F, Chaudhuri N, Crawshaw A, Gibbons M, Hogben C, Hoyles R, Kouranos V, Martinovic J, Mulholland S, Myall K, Naqvi M, Renzoni E, Saunders P, Stewart M, Suresh D, Thillai M, Wells A, West A, Mitchell J, George Pet al., 2022, Nintedanib for non-IPF progressive pulmonary fibrosis: 12-month outcome data from a real-world multicentre observational study, European Respiratory Journal, Vol: 9, Pages: 1-12, ISSN: 0903-1936

Background: Nintedanib slows lung function decline for patients with non-IPF progressive pulmonary fibrosis (PPF) in clinical trials, but the real-world safety and efficacy are not known.Methods: In this retrospective cohort study, standardised data was collected across 8 UK centres from patients in whom nintedanib was initiated for PPF between 2019 and 2020 through an early access programme. Rate of lung function change in the 12 months pre- and post-nintedanib initiation was the primary analysis. Symptoms, drug safety, tolerability, and stratification by interstitial lung disease (ILD) subtype and CT pattern were secondary analyses.Results: 126 patients were included; 67(53%) females, mean age 60(±13) years. At initiation of nintedanib, mean FVC was 1.87 L (58%) and DLco 32.7% predicted. 68% of patients were prescribed prednisolone (median dose 10 mg) and 69% prescribed a steroid sparing agent. In the 12 months after nintedanib initiation, lung function decline was significantly lower than in the preceding 12 months; FVC −88.8 ml versus −239.9 ml respectively, (p=0.004) and absolute decline in DLco −2.1% versus −6.1% respectively; (p=0.004). Response to nintedanib was consistent in sensitivity and secondary analyses. 89/126 (71%) of patients reported side effects but 86 of the surviving 108 patients (80%) were still taking nintedanib at 12 months with patients reporting a reduced perception of symptom decline. There were no serious adverse events.Conclusion: In PPF, the real-world efficacy of nintedanib replicated that of clinical trials, significantly attenuating lung function decline. Despite the severity of disease, nintedanib was safe and well tolerated in this real-world multicentre study

Journal article

Raman L, Stewart I, Barratt S, Chua F, Chaudhuri N, Crawshaw A, Gibbons M, Hogben C, Hoyles R, Kouranos V, Martinovic J, Mulholland S, Myall K, Naqvi M, Renzoni EA, Saunders P, Steward M, Suresh D, Thillai M, Wells AU, West A, Mitchell JA, George PMet al., 2022, Nintedanib for progressive pulmonary fibrosis: 12-month outcome data from a multicentre observational study, Publisher: SPRINGER LONDON LTD, Pages: S139-S139, ISSN: 0021-1265

Conference paper

George PM, Reed A, Desai SR, Devaraj A, Faiez TS, Laverty S, Kanwal A, Esneau C, Liu MKC, Kamal F, Man WD-C, Kaul S, Singh S, Lamb G, Faizi FK, Schuliga M, Read J, Burgoyne T, Pinto AL, Micallef J, Bauwens E, Candiracci J, Bougoussa M, Herzog M, Raman L, Ahmetaj-Shala B, Turville S, Aggarwal A, Farne HA, Dalla Pria A, Aswani AD, Patella F, Borek WE, Mitchell JA, Bartlett NW, Dokal A, Xu X-N, Kelleher P, Shah A, Singanayagam Aet al., 2022, A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae., Science Translational Medicine, Vol: 14, Pages: 1-16, ISSN: 1946-6234

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

Journal article

Heriot DA, Stock CJW, Mumtaz Z, Jenkins RG, Chua F, Molyneaux PL, Devaraj A, Kouranos V, Wells AU, Renzoni EA, Wells AU, Renzoni EA, Padley SPG, Desai SR, George PMet al., 2022, IMPACT OF HIATUS HERNIA IN HYPERSENSITIVITY PNEUMONITIS - EXPERIENCE AT A TERTIARY CENTRE, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A94-A94, ISSN: 0040-6376

Conference paper

Stock CJW, Bray W, Kokosi M, Kouranos V, George PM, Molyneaux PL, Chua F, Jenkins GR, Wells AU, Renzoni EAet al., 2022, PROGNOSTIC VALUE OF ROUTINE PERIPHERAL BLOOD MARKERS IN FIBROTIC HYPERSENSITIVITY PNEUMONITIS, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A95-A95, ISSN: 0040-6376

Conference paper

Hewitt RJ, Bartlett EC, Ganatra R, Butt H, Kouranos V, Chua F, Kokosi M, Molyneaux PL, Desai SR, Wells AU, Jenkins RG, Renzoni EA, Kemp S, Devaraj A, George PMet al., 2022, Lung cancer screening provides an opportunity for early diagnosis and treatment of interstitial lung disease, Thorax, Vol: 77, Pages: 1149-1151, ISSN: 0040-6376

Interstitial lung abnormalities (ILA) can be incidentally detected in patients undergoing low-dose CT screening for lung cancer. In this retrospective study, we explore the downstream impact of ILA detection on interstitial lung disease (ILD) diagnosis and treatment. Using a targeted approach in a lung cancer screening programme, the rate of de novo ILD diagnosis was 1.5%. The extent of abnormality on CT and severity of lung function impairment, but not symptoms were the most important factors in differentiating ILA from ILD. Disease modifying therapies were commenced in 39% of ILD cases, the majority being antifibrotic therapy for idiopathic pulmonary fibrosis.

Journal article

Gerovasili V, Shah A, Singanayagam A, George PM, Njafuh R, Prendecki M, Carby M, Willicombe M, Kelleher P, Reed Aet al., 2022, Impaired humoral and cellular responses to COVID-19 vaccine in heart and lung transplant recipients, American Journal of Respiratory and Critical Care Medicine, Vol: 205, Pages: 1476-1479, ISSN: 1073-449X

Journal article

Koteci A, Morgan A, Portas L, Whittaker H, Kallis C, George P, Quint Jet al., 2022, Left-sided heart failure burden and mortality in idiopathic pulmonary fibrosis: a population-based study, BMC Pulmonary Medicine, Vol: 22, Pages: 1-11, ISSN: 1471-2466

BackgroundCardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data.MethodsClinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression.ResultsFrom 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2–34.6) in 2010 to 20.9% (20.0–21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9–4.8) in 2017 to 3.4 (3.0–3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03–1.14) for all-cause mortality; 1.32 (1.09–1.59) for cardiovascular mortality).ConclusionLeft-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors.

Journal article

Nolan CM, Polgar O, Schofield SJ, Patel S, Barker RE, Walsh JA, Ingram KA, George PM, Molyneaux PL, Maher TM, Man WD-Cet al., 2022, Pulmonary rehabilitation in idiopathic pulmonary fibrosis and COPD: a propensity matched real-world study, Chest, Vol: 161, Pages: 728-737, ISSN: 0012-3692

BACKGROUND: The adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison to people with chronic obstructive pulmonary disease (COPD), remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program, and to determine whether pulmonary rehabilitation is associated with survival in IPF. RESEARCH QUESTION: Do people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are non-completion of and/or non-response to pulmonary rehabilitation associated with one-year all-cause mortality in IPF? STUDY DESIGN AND METHODS: Using propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred to pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over one-year following pulmonary rehabilitation discharge. Cox proportional-hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality. RESULTS: Similar pulmonary rehabilitation completion rates (IPF: 69%; COPD: 63%; p=0.24) and improvements in exercise response were observed in both groups with no significant mean (95% confidence interval (CI)) between-group differences in incremental shuttle walk (ISW) change (2 (-18 to 22) meters). Pulmonary rehabilitation non-completion (hazard ratio (HR) (95%CI) 5.62 (2.24 to 14.08)) and non-response (HR (95%CI) 3.91 (1.54 to 9.93)) were independently associated with increased one-year all-cause mortality in IPF. INTERPRETATION: Compared with a matched group of patients with COPD, this real-word study demonstrates that patients with IPF have similar completion rates and magnitude of response to pul

Journal article

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