Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis.

Background: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day-1, 95% CI -5.24-2.62 mg·day-1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

Association Between Known Close Contact History and Severity of COVID-19 Pneumonia: A Preliminary Evidence Supporting Importance of Filiation.

OBJECTIVE: The role of a known contact history in coronavirus disease 2019 severity in secondary cases is unknown. The study was aimed to investigate the relationship between the close contact history and the severity of the disease in coronavirus disease 2019 pneumonia. MATERIAL AND METHODS: Hospitalized patients diagnosed with coronavirus disease 2019 pneumonia were included. The demo- graphic, clinical, and laboratory data of the patients were collected retrospectively and patients with or without close contact history were analyzed with respect to the severity of pneumonia. RESULTS: In a total of 100 patients with coronavirus disease 2019 pneumonia, 54 (54%) were male and mean age was 42.28 ±17.13 years. Respiratory rate/min (P = .033) was higher, duration of hospitalization (P = .043) was longer, need for oxygen therapy (P < .001), intensive care unit admission (P = .001), and severe pneumonia (P < .001) were higher in the group without a close contact history (n = 50). Male gender (OR, 4.77; 95% CI, 1.06-21.32; P = .041), not having a close contact history (OR, 4.03; 95% CI, 1.00-16.13;P = .049), non-hospital-associated patients (OR, 9.59; 95% CI, 1.47-62.41; P = .018), and dyspnea (OR, 7.58; 95% CI, 1.64-34.93;P = .009) were found to be risk factors for severe pneumonia. CONCLUSION: Known close contact history was associated with non-severe pneumonia and was found to be an independent predic- tor of disease severity in coronavirus disease 2019 pneumonia. The study provides evidence that filiation may prevent severe disease.

Clinical Validation of the Spirohome Clinic Ultrasonic Spirometer in Child and Adolescent Patients.

BACKGROUND: Spirometers are critical devices that reveal the respiratory dynamics caused by respiratory problems and their severity and facilitate their diagnosis and follow-up. Hand-held spirometers have emerged relatively recently and offer several advantages over conventional desktop systems. There remains, however, a need for reassurance of high-quality spirometry testing with next-generation portable spirometers that connect over Bluetooth® to smart device applications. In this study, we examine the accuracy and repeatability of lung function measurements of a novel hand-held ultrasonic spirometer, the Spirohome Clinic and compare its clinical performance to a reference device, the EasyOne Air. METHODS: Benchtop validation of the spirometers was conducted using a lung simulator device according to ATS/ERS guidelines and the ISO 26782 standard waveforms. Subsequently, 48 volunteers (pediatric patients between 6 and 11 years of age and adolescent patients between 12 and 18 years of age) performed spirometry with both the Spirohome Clinic and the EasyOne Air spirometer during their clinic visits. Spirometric data including repeated FEV1, FVC, FEV6, FEF25-75, and PEF measurements were collected. RESULTS: Both the Spirohome Clinic and the EasyOne Air successfully passed requirements for accuracy stated in relevant guidelines and standards for spirometry. The only statistically significant (p<0.05) difference was for FVC measurement accuracy. Clinical comparisons revealed strong correlation between spirometers in the measurement of key pulmonary function parameters including FEV1 and FVC with a Pearson's correlation coefficient of 0.99. Bland-Altman plots showed good agreement between mean differences of FEV1 and FVC with the majority measurements remaining between the limits of 95% agreement for both the entire patient cohort and also in age and gender subsets. CONCLUSION: The present study demonstrated that the Spirohome Clinic spirometer conforms to ATS/ERS performance requirements and validates the clinical comparability of its measurement accuracy and repeatability to the EasyOne Air. These findings support the indicated use of the Spirohome Clinic for high-quality lung function testing in clinical settings.

The course of COVID-19 in patients with severe asthma receiving biological treatment.

OBJECTIVE: In order to decrease the use of systemic corticosteroids and prevent asthma exacerbations, EAACI and GINA made recommendations in favor of severe asthma patients continuing the use of biologicals during the pandemic. However, the course of SARS-CoV-2 infection remains uncertain, especially in patients taking biological therapy for severe asthma. The aim of this study was to demonstrate the clinical course of COVID-19 in severe asthmatic patients receiving biological treatment. METHODS: A total of 75 patients under the care of a tertiary level allergy clinic and receiving omalizumab or mepolizumab, which are the approved biologicals for severe asthma in Turkey, were included in the survey between April 1 and December 31, 2020. A questionnaire was administered via a telephone call by one of the treating physicians. RESULTS: Of the total patients, 46 (61%) were receiving mepolizumab and 29 (39%) omalizumab. Of the patients, 14 (19%) had COVID-19, 9 (64%) had pneumonia, 4 (29%) were hospitalized. A total of 12 (16%) patients interrupted biological treatments because they did not want to attend hospital for injections during the pandemic. The incidence of COVID-19 was higher in patients who have interrupted biological treatment (p < 0.001). In addition, the risk of having COVID-19 was higher in the ones who have interrupted their biological treatment (Relative risk:2.71; 95% Confidence interval:1.21-6.06). Asthma control was better in patients attending regular injections (p = 0.006). CONCLUSION: Severe asthma itself seems to be a risk factor for COVID-19, whether biological treatment has a role in the disease course needs further research.

Effect of COVID-19 on hereditary angioedema activity and quality of life.

Background: The demonstration that severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) enters the cell via the angiotensin-converting enzyme 2 receptor has raised concerns that, in hereditary angioedema (HAE), a disease characterized by bradykinin-mediated angioedema attacks, coronavirus disease 2019 (COVID-19) may trigger angioedema attacks, increase the frequency and/or severity of attacks, or cause more severe symptoms of COVID-19. Objective: The objective was to evaluate the severity of COVID-19 in patients with HAE, the course of HAE attacks, angioedema activity, and the quality-of-life scores during COVID-19 pandemic. Methods: Patients diagnosed with HAE for at least 6 months were included in the study. The 7-day Angioedema Activity Score and the Angioedema Quality of Life (AE-QoL) Questionnaire were first completed at the onset of the pandemic between March 12 and June 1, 2020, then during SARS-CoV-2 infection, and in the third month after recovering from COVID-19. Results: Ten of 67 patients with HAE (14.9%) were diagnosed with COVID-19. The median (interquartile range) age of the 10 patients diagnosed with COVID-19 was 35.5 years (28.0-55.0 years). Six of the 10 patients (60%) were women. During COVID-19, five of the 10 patients (50%) had no angioedema attack. Two patients with severe HAE experienced a significant increase in angioedema activity during COVID-19 compared with their basal activity scores. The remaining three patients had a similar or lower attack frequency than their basal level. Four (40%) of the 10 patients had a relative increase in their attacks during the convalescence period. There was no statistically significant difference among pre-COVID-19, during COVID-19 and post-COVID-19 periods in function, mood, fear and/or shame, nutrition, and total scores of the AE-QoL Questionnaire although the fear dimension was relatively more affected (p = 0.06). Conclusion: Although the sample size was small, analysis of our data supported that the symptoms of COVID-19 were not more severe in HAE. Also, there was no significant difference in the AE-QoL Questionnaire scores, the frequency, and severity of angioedema attacks during the course of COVID-19 in the patients with HAE.