Publications
69 results found
Nunes A, Desai SR, Semple T, et al., 2021, 3D PATHOLOGICAL SIGNS DETECTION AND SCORING ON CPA CT LUNG SCANS, 18th IEEE International Symposium on Biomedical Imaging (ISBI), Publisher: IEEE, Pages: 82-85, ISSN: 1945-7928
Armstrong-James D, Youngs J, Bicanic T, et al., 2020, Confronting and mitigating the risk of COVID-19 Associated Pulmonary Aspergillosis (CAPA), European Respiratory Journal, Vol: 56, Pages: 1-10, ISSN: 0903-1936
Cases of COVID-19 associated pulmonary aspergillosis (CAPA) are being increasingly reported and physicians treating patients with COVID-19-related lung disease need to actively consider these fungal co-infections.The SARS-CoV-2 (COVID-19) virus causes a wide spectrum of disease in healthy individuals as well as those with common comorbidities [1]. Severe COVID-19 is characterised acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis, treatment of which may require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [2]. Clinicians are alert to the possibility of bacterial co-infection as a complication of lower respiratory tract viral infection; for example a recent review found that 72% of patients with COVID-19 received antimicrobial therapy [3]. However, the risk of fungal co-infection, in particular COVID-19 associated pulmonary aspergillosis (CAPA), remains underappreciated.Fungal disease consistent with invasive aspergillosis (IA) has been observed with other severe Coronaviruses such as Severe Acute Respiratory Syndrome (SARS-CoV-2003) [4, 5] and Middle East Respiratory Syndrome (MERS-CoV) [6]. From the outset of the COVID-19 pandemic, there were warning signs of secondary invasive fungal infection; Aspergillus flavus was isolated from the respiratory tract from one of 99 patients in the first COVID-19 cohort from Wuhan to be reported in any detail [2] and Aspergillus spp. were isolated from 2/52 (3.8%) of a subsequent cohort of critically unwell patients from this region [7]. More recently, retrospective case series from Belgium [8], France [9], The Netherlands [10] and Germany [11] have reported evidence of CAPA in an alarming 20–35% of mechanically ventilated patients.
Wilson MG, Hull JH, Rogers J, et al., 2020, Cardiorespiratory considerations for return-to-play in elite athletes after COVID-19 infection: a practical guide for sport and exercise medicine physicians, BRITISH JOURNAL OF SPORTS MEDICINE, Vol: 54, Pages: 1157-1161, ISSN: 0306-3674
- Author Web Link
- Cite
- Citations: 126
Nwankwo L, McLaren K, Donovan J, et al., 2020, Utilisation of Remote Capillary Blood Testing in an Outpatient Clinic Setting to improve shared decision making and patient and clinician experience: a validation and pilot study, Publisher: Cold Spring Harbor Laboratory
<jats:p>Background In a tertiary respiratory centre, large cohorts of patients are managed in an outpatient setting and require blood tests to monitor disease activity and organ toxicity. This requires either visits to tertiary centres for phlebotomy and physician review or utilisation of primary care services.Objectives This study aims to validate remote capillary blood testing in an outpatient setting and analyse impact on clinical pathways.MethodsA single-centre prospective cross-sectional validation and parallel observational study was performed. Remote finger prick capillary blood testing was validated compared to local standard venesection using comparative statistical analysis: paired t-test, correlation and Bland-Altman. Capillary was considered interchangeable with venous samples if all 3 criteria were met: non-significant paired t-test (i.e. p>0.05), Pearson's correlation coefficient (r) >0.8 and 95% of tests within 10% difference through Bland-Altman (Limits of agreement). In parallel, current clinical pathways including phlebotomy practice was analysed over 4 weeks to review test predictability. A subsequent pilot cohort study analysed potential impact of remote capillary blood sampling on shared decision making and outpatient clinical pathways. Results117 paired capillary and venous blood samples were prospectively analysed. Interchangeability with venous blood was seen with HbA1c (%), total protein and CRP. Further tests, although not interchangeable, are likely useful to enable longitudinal remote monitoring (e.g. liver function, total IgE, and vitamin D). 65% of outpatient clinic blood tests were predictable with 16% of patients requiring further contact due to actions required. Pilot implementation of remote capillary sampling showed patient and clinician-reported improvement in shared decision-making given contemporaneous blood test results.ConclusionsRemote capillary blood sampling can be used accurately for specific tests t
Connell D, Shah A, 2020, The contribution of Aspergillus fumigatus to COPD exacerbations: a "sensitive" topic, European Respiratory Journal, Vol: 56, ISSN: 0903-1936
Vijayasingam A, Frost E, Wilkins J, et al., 2020, Tablet and web-based audiometry to screen for hearing loss in adults with cystic fibrosis, Thorax, Vol: 75, Pages: 632-639, ISSN: 0040-6376
INTRODUCTION: Individuals with chronic lung disease (eg, cystic fibrosis (CF)) often receive antimicrobial therapy including aminoglycosides resulting in ototoxicity. Extended high-frequency audiometry has increased sensitivity for ototoxicity detection, but diagnostic audiometry in a sound-booth is costly, time-consuming and requires a trained audiologist. This cross-sectional study analysed tablet-based audiometry (Shoebox MD) performed by non-audiologists in an outpatient setting, alongside home web-based audiometry (3D Tune-In) to screen for hearing loss in adults with CF. METHODS: Hearing was analysed in 126 CF adults using validated questionnaires, a web self-hearing test (0.5 to 4 kHz), tablet (0.25 to 12 kHz) and sound-booth audiometry (0.25 to 12 kHz). A threshold of ≥25 dB hearing loss at ≥1 audiometric frequency was considered abnormal. Demographics and mitochondrial DNA sequencing were used to analyse risk factors, and accuracy and usability of hearing tests determined. RESULTS: Prevalence of hearing loss within any frequency band tested was 48%. Multivariate analysis showed age (OR 1.127; (95% CI: 1.07 to 1.18; p value<0.0001) per year older) and total intravenous antibiotic days over 10 years (OR 1.006; (95% CI: 1.002 to 1.010; p value=0.004) per further intravenous day) were significantly associated with increased risk of hearing loss. Tablet audiometry had good usability, was 93% sensitive, 88% specific with 94% negative predictive value to screen for hearing loss compared with web self-test audiometry and questionnaires which had poor sensitivity (17% and 13%, respectively). Intraclass correlation (ICC) of tablet versus sound-booth audiometry showed high correlation (ICC >0.9) at all frequencies ≥4 kHz. CONCLUSIONS: Adults with CF have a high prevalence of drug-related hearing loss and tablet-based audiometry can be a practical, accurate screening tool within integrated ototoxicity monitoring programmes for early detection.
Osborne W, Fernandes M, Brooks S, et al., 2020, Pulsed echinocandin therapy in azole intolerant or multiresistant chronic pulmonary aspergillosis: A retrospective review at a UK tertiary centre, CLINICAL RESPIRATORY JOURNAL, Vol: 14, Pages: 571-577, ISSN: 1752-6981
- Author Web Link
- Cite
- Citations: 3
Hull JH, Schwellnus MP, Pyne DB, et al., 2020, COVID-19 vaccination in athletes: ready, set, go . . ., LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 455-456, ISSN: 2213-2600
- Author Web Link
- Cite
- Citations: 17
Angelini E, Dahan S, Shah A, 2019, Unravelling machine learning: insights in respiratory medicine., European Respiratory Journal, Vol: 54, Pages: 1-4, ISSN: 0903-1936
Waters VJ, Kidd TJ, Canton R, et al., 2019, Reconciling Antimicrobial Susceptibility Testing and Clinical Response in Antimicrobial Treatment of Chronic Cystic Fibrosis Lung Infections, CLINICAL INFECTIOUS DISEASES, Vol: 69, Pages: 1812-1816, ISSN: 1058-4838
- Author Web Link
- Cite
- Citations: 51
Vijayasingam A, Frost E, Wilkins J, et al., 2019, S140 Interim results from a prospective study of tablet and web-based audiometry to detect ototoxicity in adults with cystic fibrosis (vol 73, pg A87, 2018), THORAX, Vol: 74, Pages: 723-723, ISSN: 0040-6376
Periselneris J, Nwankwo L, Schelenz S, et al., 2019, Posaconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis., Journal of Antimicrobial Chemotherapy, Vol: 74, Pages: 1701-1703, ISSN: 0305-7453
OBJECTIVES: Allergic bronchopulmonary aspergillosis (ABPA) can accelerate lung function decline in patients with cystic fibrosis (CF). Antifungal medication can be used in addition to systemic corticosteroid treatment. PATIENTS AND METHODS: We evaluated Aspergillus-specific IgE and the use of therapeutic drug monitoring of triazoles in a retrospective analysis of 32 patients. RESULTS: There was a significant reduction in Aspergillus IgE with posaconazole but not with other triazoles (P = 0.026). Aspergillus IgE levels were inversely correlated with the therapeutic drug level of posaconazole. CONCLUSIONS: These data suggest that posaconazole is better than comparator azoles at decreasing serological response to Aspergillus and that this response was better with therapeutic levels of posaconazole.
Somayaji R, Parkins MD, Shah A, et al., 2019, Antimicrobial susceptibility testing (AST) and associated clinical outcomes in individuals with cystic fibrosis: a systematic review, Journal of Cystic Fibrosis, Vol: 18, Pages: 236-243, ISSN: 1569-1993
BackgroundAntimicrobial susceptibility testing (AST) is a cornerstone of infection management. Cystic fibrosis (CF) treatment guidelines recommend AST to select antimicrobial treatments for CF airway infection but its utility in this setting has never been objectively demonstrated.MethodsWe conducted a systematic review of primary published articles designed to address two PICO (patient, intervention, comparator, outcome) questions: 1) “For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection predictable from AST results available at treatment initiation?” and 2) “For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection affected by the method used to guide antimicrobial selection?” Relationships between AST results and clinical response (changes in pulmonary function, weight, signs and symptoms of respiratory tract infection, and time to next event) were assessed for each article and results were compared across articles when possible.ResultsTwenty-five articles describing the results of 20 separate studies, most of which described Pseudomonas aeruginosa treatment, were identified. Thirteen studies described pulmonary exacerbation (PEx) treatment and seven described ‘maintenance’ of chronic bacterial airways infection. In only three of 16 studies addressing PICO question #1 was there a suggestion that baseline bacterial isolate antimicrobial susceptibility was associated with clinical response to treatment. None of the four studies addressing PICO question #2 suggested that antimicrobial selection methods influenced clinical outcomes.ConclusionsThere is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment, suggesting a need for careful consideration of current AST use by the CF community.
Shteinberg M, Shah A, Elborn JS, 2019, New insights into immunological responses to infection in bronchiectasis, European Respiratory Journal, Vol: 53, Pages: 1-4, ISSN: 0903-1936
Zusag M, Desai SR, Di Paolo M, et al., 2019, SAPSAM - SPARSELY ANNOTATED PATHOLOGICAL SIGN ACTIVATION MAPS - A NOVEL APPROACH TO TRAIN CONVOLUTIONAL NEURAL NETWORKS ON LUNG CT SCANS USING BINARY LABELS ONLY, 16th IEEE International Symposium on Biomedical Imaging (ISBI), Publisher: IEEE, Pages: 298-302, ISSN: 1945-7928
- Author Web Link
- Cite
- Citations: 2
Abdolrasouli A, Scourfield A, Rhodes J, et al., 2018, High prevalence of triazole resistance in clinical Aspergillus fumigatus isolates in a specialist cardiothoracic centre, International Journal of Antimicrobial Agents, Vol: 52, Pages: 637-642, ISSN: 0924-8579
OBJECTIVES: To evaluate the prevalence of triazole-resistant Aspergillus fumigatus and common molecular cyp51A polymorphisms amongst clinical isolates in a specialised cardiothoracic centre in London, UK. METHODS: All A. fumigatus isolates were prospectively analysed from April 2014 to March 2016. Isolates were screened with a four-well VIPcheck™ plate to assess triazole susceptibility. Resistance was confirmed with a standard microbroth dilution method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Triazole-resistant A. fumigatus isolates were subjected to a mixed-format real time polymerase chain reaction (RT-PCR) assay (AsperGenius®) to detect common cyp51A alterations. RESULTS: We identified 167 clinical A. fumigatus isolates from 135 patients. Resistance to at least one azole antifungal drug was confirmed in 22/167 (13.2%) of isolates from 18/135 (13.3%) patients, including 12/74 (16.2%) patients with cystic fibrosis (CF). The highest detection rate of azole-resistant A. fumigatus was among the 11- to 20-y age group. All triazole-resistant isolates (n = 22) were resistant to itraconazole, 18 showed cross-resistance to posaconazole and 10 displayed reduced susceptibility to voriconazole. No pan-azole-resistant A. fumigatus was identified. TR34/L98H was identified in 6/22 (27.3%) of azole-resistant isolates and detectable in 5/12 (42%) patients with CF. CONCLUSIONS: In our specialist cardiothoracic centre, the prevalence of triazole-resistant A. fumigatus is alarmingly high (13.2%). The majority of azole-resistant isolates were from patients with CF. We found a higher prevalence of the environmentally driven mutation TR34/L98H in our A. fumigatus isolates than in published UK data from other specialist respiratory centres, which may reflect differing patient populations managed at these institutions.
Abdolrasouli A, Bercusson AC, Rhodes JL, et al., 2018, Airway persistence by the emerging multi-azole-resistant Rasamsonia argillacea complex in cystic fibrosis, Mycoses, Vol: 61, Pages: 665-673, ISSN: 0933-7407
Infections caused by Rasamsonia argillacea complex have been reported in various clinical settings. Cystic fibrosis (CF) is one of the main underlying conditions. An observational cohort study of CF patients with Rasamsonia in respiratory samples was conducted. Eight isolates from six patients were identified as R. argillacea complex and tested for antifungal susceptibility. All isolates had high MICs to voriconazole and posaconazole and low MECs to echinocandins. Four patients experienced lung function decline in the year preceding first Rasamsonia isolation. This continued in the year following first isolation in three out of four cases. Antifungal therapy was initiated in two patients, to which only one exhibited a clinical response. Three out of six patients died within three years of isolating Rasamsonia. Genotyping suggests that similar genotypes of Rasamsonia can persist in CF airways. Consistent with other fungi in CF, the clinical impact of airway colonization by Rasamsonia is variable. In certain patients, Rasamsonia may be able to drive clinical decline. In others, though a clear impact on lung function may be difficult to determine, the appearance of Rasamsonia acts as a marker of disease severity. In others it does not appear to have an obvious clinical impact on disease progression.
Armstrong-James DPH, Bercusson A, Colley T, et al., 2018, Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis, Blood, Vol: 132, Pages: 1985-1988, ISSN: 1528-0020
Dennis BB, Rinaldi G, Housley G, et al., 2018, The utility of drug reaction assessment trials for inhaled therapies in patients with chronic lung diseases, RESPIRATORY MEDICINE, Vol: 140, Pages: 122-126, ISSN: 0954-6111
- Author Web Link
- Cite
- Citations: 1
Dave K, Di Paolo M, Vijayasingam A, et al., 2018, P075 Anti-fungal therapeutic drug monitoring in adults with cystic fibrosis, Journal of Cystic Fibrosis, Vol: 17, Pages: S80-S80, ISSN: 1569-1993
Eades CP, Armstrong-James DPH, Periselneris J, et al., 2018, Improvement in Exophiala dermatitidis airway persistence and respiratory decline in response to interferon-gamma therapy in a patient with cystic fibrosis, Journal of Cystic Fibrosis, Vol: 17, Pages: e32-e34, ISSN: 1569-1993
Wrench C, Belchamber K, Bercusson A, et al., 2018, Reduced Clearance of Fungal Spores by Chronic Obstructive Pulmonary Disease GM-CSF- and M-CSF-derived Macrophages, Publisher: American Thoracic Society, Pages: 271-273, ISSN: 1044-1549
Armstrong-James D, de Boer L, Bercusson A, et al., 2018, From phagocytosis to metaforosis: calcineurin's deadly role in innate processing of fungi, PLoS Pathogens, Vol: 14, Pages: e1006627-e1006627, ISSN: 1553-7366
Shah A, 2018, Respiratory fungal infection, Essentials of Clinical Pulmonology, Pages: 400-417, ISBN: 9781498715799
Fungal respiratory disease causes significant mortality and morbidity.1, 2 With increasing use of immunosuppressive therapeutics and an aging population with chronic disease, the incidence of fungal infections continues to rise.3 Pulmonary complication is the most frequent cause of morbidity and mortality following fungal infection in the immunocompromised state.2, 4 In this chapter, we review the spectrum of respiratory fungal disease. Largely, this constitutes invasive fungal infection in the setting of systemic immunocompromise; however, the prevalence of chronic semi-invasive disease is rising with better recognition. The diagnosis of fungal infection remains challenging due to the low sensitivity of conventional cultural and microscopic methods, and consensus international recommendations utilizing clinical, microbiological, and radiological criteria are currently utilized.5 Histological confirmation remains the gold standard in themajority of respiratory fungal infections; however, this is often impractical and associated with considerable risk. Nevertheless, delay in diagnosis is associated with poor outcome, and advances in novel diagnostics and therapeutics for invasive fungal diagnostics are discussed alongside research into the role of immunotherapy. Lastly, the emergence of novel fungal pathogens and fungal resistance causing significant morbidity are reviewed alongside the respiratory complications of endemic mycoses.
Amarsaikhan N, Sands EM, Shah A, et al., 2017, Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis., Journal of Immunology, Vol: 199, Pages: 624-632, ISSN: 1550-6606
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA.
Shah A, Donovan J, Marino P, et al., 2017, A lesson in plasticity: a 74-year-old man with plastic bronchitis., Thorax, Vol: 72, Pages: 1055-1057, ISSN: 0040-6376
Shah A, Armstrong-James D, 2016, Opportunist Turns Allergen: Double Life of Pneumocystis jirovecii in Asthma., American Journal of Respiratory and Critical Care Medicine, Vol: 194, Pages: 779-780, ISSN: 1535-4970
Shah A, Shoemark A, MacNeill SJ, et al., 2016, A longitudinal study characterising a large adult primary ciliary dyskinesia population, European Respiratory Journal, Vol: 48, Pages: 441-450, ISSN: 1399-3003
Primary ciliary dyskinesia (PCD) in adults has not been well described. In this retrospective observational study we aimed to characterise a large adult population and identify features associated with disease progression.We retrospectively analysed 151 adult patients at a single tertiary centre at baseline and longitudinally for a median of 7 years.We found significant variation in age at diagnosis (median 23.5 years; range <1-72 years). Older age at diagnosis was associated with impaired baseline forced expiratory volume in 1 s (FEV1) (r= -0.30, p=0.01) and increased Pseudomonas aeruginosa colonisation (difference in medians 17 years (95% CI 4.5-20 years); p=0.002). Lung function decline was estimated at FEV1 decline of 0.49% predicted per year. Lung function decline was associated with ciliary ultrastructure, with microtubular defect patients having the greatest decline (p=0.04). High-resolution computed tomography (HRCT) scores of severity of bronchial wall dilatation (p<0.001) and extent of bronchiectasis (p=0.03) additionally showed evidence of modifying FEV1 decline with age.Our study reveals that a large proportion of adult PCD patients are diagnosed late, with impaired FEV1 and increased P. aeruginosa colonisation. Increased disease burden on HRCT and ciliary ultrastructure may predict progressive lung function decline. This study characterises a large adult PCD population, identifies features associated with disease progression and highlights the need for prospective trials to determine whether early diagnosis of high-risk subgroups alongside optimal management can modify disease progression.
Armstrong-James DPH, 2016, Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death, American Journal of Respiratory and Critical Care Medicine, Vol: 194, Pages: 1127-1139, ISSN: 1535-4970
Rationale: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis.Objectives: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants.Methods: We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies.Measurements and Main Results: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell–cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape.Conclusions: These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.
Henderson SR, Shah A, Copley SJ, et al., 2015, Occam's razor or Hickam's dictum? Allergic bronchopulmonary aspergillosis and eosinophilic granulomatosis with polyangiitis, Thorax, Vol: 71, Pages: 193-195, ISSN: 1468-3296
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.