Publications by authors named "Louise Wain"

Article Synopsis
  • - The study investigates the relationship between diabetes mellitus (DM) and idiopathic pulmonary fibrosis (IPF) using a Mendelian randomisation approach to determine if there is a causal link between the two.
  • - Analysis of genetic data showed that neither type 1 diabetes (T1D) nor type 2 diabetes (T2D) appeared to directly cause IPF, nor did other diabetes-related factors like HbA1c or fasting insulin levels.
  • - The findings suggest that while DM and IPF often coexist, their relationship may be influenced by common risk factors or complications rather than a direct causal connection.
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Background: People hospitalised for coronavirus disease 2019 (COVID-19) have elevated incidence of diabetes. However, it is unclear whether this is due to shared risk factors, confounding or stress hyperglycaemia in response to acute illness.

Methods: We analysed a multicentre prospective cohort study (PHOSP-COVID) of people ≥18 years discharged from NHS hospitals across the United Kingdom following COVID-19.

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Background: The clinical course of idiopathic pulmonary fibrosis (IPF) is highly variable and unpredictable, with multiple genetic variants influencing IPF outcomes. Notably, rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in these patients. Here we assessed whether rare qualifying variants (QVs) in monogenic adult-onset pulmonary fibrosis (PF) genes are associated with IPF survival.

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Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge.

Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium).

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Article Synopsis
  • Respiratory infections are a major global health issue, but the genetic factors influencing them are not well understood, leading to this study that aimed to investigate genetic determinants through genome-wide association studies (GWAS).
  • The research analyzed data from 19,459 patients with respiratory infections and 101,438 controls in Stage 1, discovering 56 significant genetic signals, including one strong signal related to a gene important for immune response, but the follow-up Stage 2 study did not replicate these findings.
  • Possible reasons for the lack of replication include variations in how the studies were conducted and differences in patient populations, but the research suggests a novel gene may be linked to susceptibility to respiratory infections, warranting further investigation.
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Article Synopsis
  • The study aimed to assess the effectiveness of ECG in detecting cardiac issues in post-hospitalized COVID-19 patients through cardiac magnetic resonance (CMR) imaging.
  • Results showed that these patients had significantly more ECG abnormalities compared to healthy controls, yet both groups had similar levels of CMR abnormalities.
  • Adding additional analyses on repolarization improved ECG's ability to identify patients with CMR abnormalities and reduced the reliance on sex in the diagnostic process.
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Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning.

Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK.

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Article Synopsis
  • Pulmonary embolism (PE) is a serious complication of COVID-19 that can lead to chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH), but the true burden and best screening methods for these conditions are still not clear.
  • During the study from 2017 to 2022, only a small percentage of CTEPH cases were linked to previous COVID-19 infections, with the CTEPH rates returning to pre-pandemic levels after the second year of the pandemic.
  • The findings suggest that while the risk of developing CTEPH after hospitalization for COVID-19 is low, using simple clinical risk scores can help identify patients who may need further evaluation.
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Article Synopsis
  • - The study investigates pulmonary fibrosis, a condition where lung tissue becomes damaged, by classifying patients based on blood biomarkers to identify different disease types, or endotypes.
  • - Researchers used data from the PROFILE study, involving a group of UK patients, to perform cluster analysis and measure 13 specific blood biomarkers related to lung tissue health.
  • - The analysis revealed three distinct patient clusters that correlate with different biomarker levels, providing insights into disease patterns and their associations with mortality and lung function decline.
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Article Synopsis
  • The PHOSP-COVID study examined long-term outcomes in COVID-19 hospitalised patients with pre-existing airway diseases compared to those without.* -
  • Out of 615 participants with airway diseases, many reported lower recovery rates, higher anxiety and depression levels, and greater mobility issues one year post-discharge.* -
  • Overall, individuals with pre-existing airway conditions experienced worse health-related quality of life and more persistent symptoms like breathlessness and fatigue after recovering from COVID-19.*
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Background: Electronic healthcare records (EHRs) are used to document diagnoses, symptoms, tests, and prescriptions. Though not primarily collected for research purposes, owing to the size of the data as well as the depth of information collected, they have been used extensively to conduct epidemiological research. The Clinical Practice Research Datalink (CPRD) is an EHR database containing representative data of the UK population with regard to age, sex, race, and social deprivation measures.

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Fibrosis, driven by fibroblast activities, is an important contributor to morbidity and mortality in most chronic diseases. Endotrophin, a signaling molecule derived from processing of type VI collagen by highly activated fibroblasts, is involved in fibrotic tissue remodeling. Circulating levels of endotrophin have been associated with an increased risk of mortality in multiple chronic diseases.

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Background: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.

Objectives: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.

Methods: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months.

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SARS-CoV-2 infection can result in long COVID, characterized by post-acute symptoms from multiple organs. Current hypotheses on mechanisms underlying long COVID include persistent inflammation and thromboembolism; however, compelling evidence from humans is limited and causal associations remain unclear. Here, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative ( =3,018; =994,582).

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Article Synopsis
  • IPF (idiopathic pulmonary fibrosis) is a lung disease that can also show up in people with rheumatoid arthritis (RA), and researchers wanted to see if one causes the other or if they just happen together.
  • They used special genetic studies to see how RA and IPF relate to each other, finding that IPF seems to increase the risk of developing seropositive RA.
  • However, the opposite (that RA protects against IPF) wasn’t always clear, leading to the conclusion that RA-UIP might be more about how IPF causes RA rather than the two just happening at the same time.
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Background And Aims: Hypertension is a leading risk factor for cardiovascular disease. Electronic health records (EHRs) are routinely collected throughout a person's care, recording all aspects of health status, including current and past conditions, prescriptions and test results. EHRs can be used for epidemiological research.

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Article Synopsis
  • One in ten COVID-19 infections lead to long COVID, characterized by prolonged symptoms, but the underlying mechanisms remain unclear.
  • In a study of 657 individuals, certain inflammatory markers were linked to long COVID symptoms, revealing connections to cardiorespiratory issues, fatigue, anxiety, gastrointestinal problems, cognitive impairments, and potential nerve tissue repair disturbances.
  • Findings suggest that targeting specific inflammatory pathways could offer new therapeutic options for treating different subtypes of long COVID in future clinical trials.*
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Short tandem repeat (STR) variation is an often overlooked source of variation between genomes. STRs comprise about 3% of the human genome and are highly polymorphic. Some cause Mendelian disease, and others affect gene expression.

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Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk.

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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition that is more prevalent in males than females. The reasons for this are not fully understood, with differing environmental exposures due to historically sex-biased occupations, or diagnostic bias, being possible explanations. To date, over 20 independent genetic variants have been identified to be associated with IPF susceptibility, but these have been discovered when combining males and females.

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A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19.

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Objective: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies.

Design/patients: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study).

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