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OBJECTIVE: In the UK, asthma deaths are at their highest level this century. Increased recognition of at-risk patients is needed. This study phenotyped frequent asthma exacerbators and used machine learning to predict frequent exacerbators. METHODS: Patients admitted to a district general hospital with an asthma exacerbation between 1st March 2018 and 1st March 2020 were included. Patients were organized into two groups: "Infrequent Exacerbators" (1 admission in the previous 12 months) and "Frequent Exacerbators" (≥2 admissions in the previous 12 months). Patient data were retrospectively collected from hospital and primary care records. Machine learning models were used to predict frequent exacerbators. RESULTS: 200 patients admitted for asthma exacerbations were randomly selected (73% female; mean age 47.8 years). Peripheral eosinophilia was uncommon in either group (21% vs 19%). More frequent exacerbators were being treated with high-dose ICS than infrequent exacerbators (46.5% vs 23.2%; P < 0.001), and frequent exacerbators used more SABA inhalers (10.9 vs 7.40; P = 0.01) in the year preceding the current admission. BMI was raised in both groups (34.2 vs 30.9). Logistic regression was the most accurate machine learning model for predicting frequent exacerbators (AUC = 0.80). CONCLUSIONS: Patients admitted for asthma are predominately female, obese and non-eosinophilic. Patients who require multiple admissions per year have poorer asthma control at baseline. Machine learning algorithms can predict frequent exacerbators using clinical data available in primary care. Instead of simply increasing the dose of corticosteroids, multidisciplinary management targeting Th2-low inflammation should be considered for these patients.
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Asma , Asma/tratamento farmacológico , Asma/epidemiologia , Progressão da Doença , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fenótipo , Estudos RetrospectivosRESUMO
BACKGROUND: Pneumothorax (PTX) and pneumomediastinum (PM), collectively termed here "air leak", are now well described complications of severe COVID-19 pneumonia across several case series. The incidence is thought to be approximately 1% but is not definitively known. OBJECTIVES: To report the incidence and describe the demographic features, risk factors and outcomes of patients with air leak as a complication of COVID-19. METHODS: A retrospective observational study on all adult patients with COVID-19 admitted to Watford General Hospital, West Hertfordshire NHS Trust between March 1st 2020 and Feb 28th 2021. Patients with air leak were identified after reviewing both chest radiographs (CXRs) and axial imaging (CT Thorax) with confirmatory radiology reports inclusive of the terms PTX and/or PM. RESULTS: Air leak occurred with an incidence of 0.56%. Patients with air leak were younger and had evidence of more severe disease at presentation, including a higher median CRP and number of abnormal zones affected on chest radiograph. Asthma was a significant risk factor in the development of air leak (OR 13.4 [4.7-36.4]), both spontaneously and following positive pressure ventilation. CPAP and IMV were also associated with a greater than six fold increase in the risk of air leak (OR 6.4 [2.5-16.6] and 9.8 [3.7-27.8] respectively). PTX, with or without PM, in the context of COVID-19 pneumonia was almost universally fatal whereas those with alone PM had a lower risk of death. CONCLUSION: Despite the global vaccination programme, patients continue to develop severe COVID-19 disease and may require respiratory support. This study demonstrates the importance of identifying that deterioration in such patients may be resultant from PTX or PM, particularly in asthmatics and those managed with positive pressure ventilation.
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COVID-19 , Enfisema Mediastínico , Pneumotórax , Adulto , COVID-19/complicações , Humanos , Incidência , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/epidemiologia , Enfisema Mediastínico/etiologia , Pneumotórax/diagnóstico por imagem , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Fatores de RiscoRESUMO
Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.
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COVID-19/complicações , Pressão Positiva Contínua nas Vias Aéreas , Intubação Intratraqueal , Ventilação não Invasiva/métodos , Oxigenoterapia/métodos , Insuficiência Respiratória/terapia , Adulto , COVID-19/mortalidade , Cânula , Feminino , Mortalidade Hospitalar , Humanos , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologiaRESUMO
INTRODUCTION: Risk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking. METHODS: Multivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290). RESULTS: 983 patients (median age 70, IQR 53-83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0-1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%). CONCLUSION: The SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.
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COVID-19/mortalidade , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Monitorização Ambulatorial/estatística & dados numéricos , Pneumonia Viral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Mosaic attenuation on computed tomography (CT) has been identified in international guidelines as an important diagnostic feature of fibrotic hypersensitivity pneumonitis (FHP) as opposed to idiopathic pulmonary fibrosis (IPF). However, mosaic attenuation comprises several different radiological signs (low-density lobules, preserved lobules, air trapping and the so-called "headcheese sign") which may have differing diagnostic utility. Furthermore, the extent of mosaic attenuation required to distinguish these two diagnoses is uncertain and thresholds of mosaic attenuation from international guidelines have not been validated. METHODS: Inspiratory and expiratory CT scans were evaluated by two readers in 102 patients (IPF n=57; FHP n=45) using a semiquantitative scoring system for mosaic attenuation. Findings were validated in an external cohort from a secondary referral institution (IPF n=34; FHP n=28). RESULTS: Low-density lobules and air trapping were a frequent finding in IPF, present in up to 51% of patients. A requirement for increasing extent of low-density lobules and air trapping based on guidelines (American Thoracic Society and Fleischner Society) was associated with increased specificity for the diagnosis of FHP (0.96 and 0.98, respectively) but reduced sensitivity (0.16 and 0.20, respectively). The headcheese sign was found to be highly specific (0.93) and moderately sensitive (0.49) for a high-confidence diagnosis of FHP. The high specificity of the headcheese sign was maintained in the validation cohort and when patients with other CT features of FHP were excluded. CONCLUSION: Mosaic attenuation is a frequent finding in IPF. However, the headcheese sign can be confidently considered as being inconsistent with a diagnosis of IPF and specific for FHP.
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Alveolite Alérgica Extrínseca/diagnóstico por imagem , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Prospectively validate prognostication scores, SOARS and 4C Mortality Score, derived from the COVID-19 first wave, for mortality and safe early discharge in the evolving pandemic with SARS-CoV-2 variants (B.1.1.7 replacing D614) and healthcare responses altering patient demographic and mortality. DESIGN: Protocol-based prospective observational cohort study. SETTING: Single site PREDICT and multisite ISARIC (International Severe Acute Respiratory and Emerging Infections Consortium) cohorts in UK COVID-19 second wave, October 2020 to January 2021. PARTICIPANTS: 1383 PREDICT and 20 595 ISARIC SARS-CoV-2 patients. PRIMARY OUTCOME MEASURES: Relevance of SOARS and 4C Mortality Score determining in-hospital mortality and safe early discharge in the evolving UK COVID-19 second wave. RESULTS: 1383 (median age 67 years, IQR 52-82; mortality 24.7%) PREDICT and 20 595 (mortality 19.4%) ISARIC patient cohorts showed SOARS had area under the curve (AUC) of 0.8 and 0.74, while 4C Mortality Score had AUC of 0.83 and 0.91 for hospital mortality, in the PREDICT and ISARIC cohorts respectively, therefore, effective in evaluating safe discharge and in-hospital mortality. 19.3% (231/1195, PREDICT cohort) and 16.7% (2550/14992, ISARIC cohort) with SOARS of 0-1 were candidates for safe discharge to a virtual hospital (VH) model. SOARS implementation in the VH pathway resulted in low readmission, 11.8% (27/229) and low mortality, 0.9% (2/229). Use to prevent admission is still suboptimal, as 8.1% in the PREDICT cohort and 9.5% in the ISARIC cohort were admitted despite SOARS score of 0-1. CONCLUSIONS: SOARS and 4C Mortality Score remains valid, transforming complex clinical presentations into tangible numbers, aiding objective decision making, despite SARS-CoV-2 variants and healthcare responses altering patient demographic and mortality. Both scores, easily implemented within urgent care pathways for safe early discharge, allocate hospital resources appropriately to the pandemic's needs while enabling normal healthcare services resumption.
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COVID-19 , Humanos , Idoso , SARS-CoV-2 , Estudos Prospectivos , Alta do Paciente , Mortalidade Hospitalar , Reino Unido/epidemiologiaRESUMO
We report a case of a 74-year-old male patient who was referred to the respiratory clinic with an incidental finding of a left sided pleural effusion. He was initially being treated by the general practitioner for chest infection with productive cough that had limited resolution after course of oral antibiotics. At the pleural clinic, 1.5 L of serosanguineous fluid was drained and sent for diagnostics. However, the diagnosis only reached as far as idiopathic exudative effusion with lymphocytes and plasma cells. He was then referred for video-assisted thoracoscopic surgery pleural biopsy and pleurodesis. It revealed black pleura with abundant IgG4 positive cells. He is followed up in respiratory clinic where further discussion and treatment has commenced.
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Derrame Pleural , Idoso , Exsudatos e Transudatos , Humanos , Masculino , Pleura/diagnóstico por imagem , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Pleurodese , Cirurgia Torácica VídeoassistidaRESUMO
OBJECTIVES: To investigate whether calcium derangement was a specific feature of COVID-19 that distinguishes it from other infective pneumonias, and its association with disease severity. DESIGN: A retrospective observational case-control study looking at serum calcium on adult patients with COVID-19, and community-acquired pneumonia (CAP) or viral pneumonia (VP). SETTING: A district general hospital on the outskirts of London, UK. PARTICIPANTS: 506 patients with COVID-19, 95 patients with CAP and 152 patients with VP. OUTCOME MEASURES: Baseline characteristics including hypocalcaemia in patients with COVID-19, CAP and VP were detailed. For patients with COVID-19, the impact of an abnormally low calcium level on the maximum level of hospital care, as a surrogate of COVID-19 severity, was evaluated. The primary outcome of maximal level of care was based on the WHO Clinical Progression Scale for COVID-19. RESULTS: Hypocalcaemia was a specific and common clinical finding in patients with COVID-19 that distinguished it from other respiratory infections. Calcium levels were significantly lower in those with severe disease. Ordinal regression of risk estimates for categorised care levels showed that baseline hypocalcaemia was incrementally associated with OR of 2.33 (95% CI 1.5 to 3.61) for higher level of care, superior to other variables that have previously been shown to predict worse COVID-19 outcome. Serial calcium levels showed improvement by days 7-9 of admission, only in survivors of COVID-19. CONCLUSION: Hypocalcaemia is specific to COVID-19 and may help distinguish it from other infective pneumonias. Hypocalcaemia may independently predict severe disease and warrants detailed prognostic investigation. The fact that decreased serum calcium is observed at the time of clinical presentation in COVID-19, but not other infective pneumonias, suggests that its early derangement is pathophysiological and may influence the deleterious evolution of this disease. TRIAL REGISTRATION NUMBER: 20/HRA/2344.
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COVID-19 , Hipocalcemia , Adulto , Estudos de Casos e Controles , Humanos , Hipocalcemia/diagnóstico , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: Identify predictors of clinical deterioration in a virtual hospital (VH) setting for COVID-19. DESIGN: Real-world prospective observational study. SETTING: VH remote assessment service in West Hertfordshire NHS Trust, UK. PARTICIPANTS: Patients with suspected COVID-19 illness enrolled directly from the community (postaccident and emergency (A&E) or medical intake assessment) or postinpatient admission. MAIN OUTCOME MEASURE: Death or (re-)admission to inpatient hospital care during VH follow-up and for 2 weeks post-VH discharge. RESULTS: 900 patients with a clinical diagnosis of COVID-19 (455 referred from A&E or medical intake and 445 postinpatient) were included in the analysis. 76 (8.4%) of these experienced clinical deterioration (15 deaths in admitted patients, 3 deaths in patients not admitted and 58 additional inpatient admissions). Predictors of clinical deterioration were increase in age (OR 1.04 (95% CI 1.02 to 1.06) per year of age), history of cancer (OR 2.87 (95% CI 1.41 to 5.82)), history of mental health problems (OR 1.76 (95% CI 1.02 to 3.04)), severely impaired renal function (OR for eGFR <30=9.09 (95% CI 2.01 to 41.09)) and having a positive SARS-CoV-2 PCR result (OR 2.0 (95% CI 1.11 to 3.60)). CONCLUSIONS: These predictors may help direct intensity of monitoring for patients with suspected or confirmed COVID-19 who are being remotely monitored by primary or secondary care services. Further research is needed to confirm our findings and identify the reasons for increased risk of clinical deterioration associated with cancer and mental health problems.
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COVID-19/diagnóstico , Deterioração Clínica , Consulta Remota , Adulto , Idoso , COVID-19/patologia , Estudos de Coortes , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
INTRODUCTION: COPD exacerbation phenotypes have been defined in research populations by predominantly infective or inflammatory aetiology. We sought to characterise this in patients admitted to our centre. MATERIALS AND METHODS: Case-notes of consecutive patients discharged alive after treatment for acute COPD exacerbations between December 2012 and January 2017 were analysed. Data were collected on treatment, length of stay, C-reactive protein (CRP), eosinophil count and bacterial sputum culture positivity for potentially pathogenic microorganisms (PPM). RESULTS: 1029 exacerbations were included. There was an inverse correlation between CRP and eosinophil count (rho = -0.277, p < 0.01). The proportion of eosinophilic exacerbations (eosinophils ≥0.3 × 109/L) was low (157, 15%). Median length of stay was longer in patients with a CRP >100 mg/L (4d [3,8] vs 4d [2,7], p < 0.01) or when given antibiotics (4d [2,8] vs 3d [1,6], p < 0.001) and shorter if receiving corticosteroids (4d [2,6] vs 6d [3,7], p < 0.001). Being sputum culture positive on first exacerbation was associated with sputum culture positivity in subsequent exacerbations. Patients with PPM in sputum culture had a significantly higher median CRP than culture negative patients (38 mg/L [18.75, 57] v 18 mg/L [8.5,45.5] p < 0.05). Length of stay, eosinophil count and CRP were significantly correlated between exacerbation pairs. CONCLUSIONS: This real-world population found eosinophilic and high CRP exacerbations to be distinct and significantly stereotyped within individual patients across recurrent exacerbations. High CRP exacerbations are associated with greater healthcare utilisation and chance of sputum positivity with PPM. Eosinophilic exacerbations were associated with lower rate of readmission. Phenotype-driven treatment warrants further investigation in this population.
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Hospitalização , Fenótipo , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Coortes , Progressão da Doença , Eosinófilos , Tempo de Internação , Contagem de Leucócitos , Aceitação pelo Paciente de Cuidados de Saúde , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/microbiologia , Recidiva , Escarro/microbiologiaAssuntos
Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Reino Unido/epidemiologiaRESUMO
RATIONALE: New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. OBJECTIVES: To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. METHODS: We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. MEASUREMENTS AND MAIN RESULTS: An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. CONCLUSIONS: Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.