Long-Term Real-World Outcomes of Mepolizumab and Benralizumab Among Biologic-Naive Patients With Severe Eosinophilic Asthma: Experience of 3 Years' Therapy.

BACKGROUND: Biologic therapies such as mepolizumab and benralizumab offer treatment options for severe eosinophilic asthma (SEA), although long-term real-world data on their use are limited. OBJECTIVES: To evaluate the impact of benralizumab and mepolizumab treatment among biologic-naive patients with SEA over 36 months and describe the incidence of super-response at 12 and 36 months, identifying potential predictive factors. METHODS: We conducted a retrospective, single-center study of patients with SEA who were given mepolizumab or benralizumab from May 2017 to December 2019, and who completed 36 months of therapy. Baseline demographics, comorbidities, and medication use were described. Data on clinical outcomes, including maintenance oral corticosteroid (OCS) use, annual exacerbation rate (AER), mini Asthma Quality of Life Questionnaire, Asthma Control Questionnaire (ACQ-6), and eosinophil count were collected at baseline and at 12 and 36 months. Super-response was evaluated at 12 and 36 months. RESULTS: A total of 81 patients were included. Maintenance OCS use significantly improved from baseline (5.3 mg/d) to 12 months (2.4 mg/d, P < .0001) and 36 months (0.6 mg/d; P < .0001). Annual exacerbation rate decreased from baseline (5.8) to 12 months (0.9; P < .0001) and 36 months (1.2; P < .0001). Mini Asthma Quality of Life Questionnaire, ACQ-6, and eosinophil count significantly improved from baseline to 12 and 36 months. Twenty-nine patients demonstrated super-response at 12 months. Compared with those without a super-response, these patients had better baseline AER (4.7 vs 6.5; P = .009), mini Asthma Quality of Life Questionnaire (3.41 vs 2.54; P = .002), and ACQ-6 (3.38 vs 4.06; P = .03) scores. Most maintained a super-response up to 36 months. CONCLUSIONS: Mepolizumab and benralizumab are associated with significant improvements in OCS use, AER, and asthma control in real-world cohorts for up to 36 months, providing insight into long-term use for SEA.

Dynamic chest radiography: a state-of-the-art review.

Dynamic chest radiography (DCR) is a real-time sequential high-resolution digital X-ray imaging system of the thorax in motion over the respiratory cycle, utilising pulsed image exposure and a larger field of view than fluoroscopy coupled with a low radiation dose, where post-acquisition image processing by computer algorithm automatically characterises the motion of thoracic structures. We conducted a systematic review of the literature and found 29 relevant publications describing its use in humans including the assessment of diaphragm and chest wall motion, measurement of pulmonary ventilation and perfusion, and the assessment of airway narrowing. Work is ongoing in several other areas including assessment of diaphragmatic paralysis. We assess the findings, methodology and limitations of DCR, and we discuss the current and future roles of this promising medical imaging technology.Critical relevance statement Dynamic chest radiography provides a wealth of clinical information, but further research is required to identify its clinical niche.

Surveillance towards preventing paediatric incidence of respiratory syncytial virus attributable respiratory tract infection in primary and secondary/tertiary healthcare settings in Merseyside, Cheshire and Bristol, UK.

INTRODUCTION: Respiratory syncytial virus (RSV) is a common respiratory virus, particularly affecting children, and can cause respiratory infections such as croup and bronchiolitis. The latter is a leading cause of paediatric hospitalisation within the UK. Children <3 years of age and/or with underlying health conditions are more vulnerable to severe RSV infection.There are currently limited data on the incidence of laboratory-confirmed RSV, particularly within primary care settings and outside the typical 'RSV season', which in the Northern hemisphere tends to coincide with winter months. There is also a lack of data on the health economic impact of RSV infection on families and healthcare systems.This observational surveillance study aims to collect data on the incidence of laboratory-confirmed RSV-attributable respiratory tract infection (RTI) in children aged <3 years presenting to primary, secondary or tertiary care; it also aims to estimate the health economic and quality of life impact of RSV-attributable infection in this cohort. Such data will contribute to informing public health strategies to prevent RSV-associated infection, including use of preventative medications. METHODS AND ANALYSIS: Parents/carers of children <3 years of age with RTI symptoms will consent for a respiratory sample (nasal swab) to be taken. Laboratory PCR testing will assess for the presence of RSV and/or other pathogens. Data will be obtained from medical records on demographics, comorbidities, severity of infection and hospitalisation outcomes. Parents will complete questionnaires on the impact of ongoing infection symptoms at day 14 and 28 following enrolment. The primary outcome is incidence of laboratory-confirmed RSV in children <3 years presenting to primary, secondary or tertiary care with RTI symptoms leading to health-seeking behaviours. Recruitment will be carried out from December 2021 to March 2023, encompassing two UK winter seasons and intervening months. ETHICS AND DISSEMINATION: Ethical approval has been granted (21/WS/0142), and study findings will be published as per International Committee of Medical Journal Editors' guidelines.

Comprehensive review of safety in Experimental Human Pneumococcal Challenge.

INTRODUCTION: Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies. METHODS: A single-centre review of all EHPC studies performed 2011-2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation. RESULTS: In 1416 individuals (median age 21, IQR 20-25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28-2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety. DISCUSSION: No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated. CONCLUSION: Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.

Sensitivity of SARS-CoV-2 RNA polymerase chain reaction using a clinical and radiological reference standard.

OBJECTIVES: Diagnostic tests for SARS-CoV-2 are important for epidemiology, clinical management, and infection control. Limitations of oro-nasopharyngeal real-time PCR sensitivity have been described based on comparisons of single tests with repeated sampling. We assessed SARS-CoV-2 PCR clinical sensitivity using a clinical and radiological reference standard. METHODS: Between March-May 2020, 2060 patients underwent thoracic imaging and SARS-CoV-2 PCR testing. Imaging was independently double- or triple-reported (if discordance) by blinded radiologists according to radiological criteria for COVID-19. We excluded asymptomatic patients and those with alternative diagnoses that could explain imaging findings. Associations with PCR-positivity were assessed with binomial logistic regression. RESULTS: 901 patients had possible/probable imaging features and clinical symptoms of COVID-19 and 429 patients met the clinical and radiological reference case definition. SARS-CoV-2 PCR sensitivity was 68% (95% confidence interval 64-73), was highest 7-8 days after symptom onset (78% (68-88)) and was lower among current smokers (adjusted odds ratio 0.23 (0.12-0.42) p < 0.001). CONCLUSIONS: In patients with clinical and imaging features of COVID-19, PCR test sensitivity was 68%, and was lower among smokers; a finding that could explain observations of lower disease incidence and that warrants further validation. PCR tests should be interpreted considering imaging, symptom duration and smoking status.