Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

BACKGROUND: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals. METHODS: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care. The primary end point was the annualized rate of exacerbations at 52 weeks. Secondary end points, which were analyzed in a hierarchical manner to adjust for multiplicity, included the change from baseline in the score on the St. George's Respiratory Questionnaire (SGRQ), the forced expiratory volume in 1 second, and asthma symptom reports at 52 weeks. RESULTS: Across the two trials, 792 patients underwent randomization and 762 were included in the full analysis; 502 were assigned to receive depemokimab and 260 to receive placebo. The annualized rate of exacerbations was 0.46 (95% confidence interval [CI]), 0.36 to 0.58) with depemokimab and 1.11 (95% CI, 0.86 to 1.43) with placebo (rate ratio, 0.42; 95% CI, 0.30 to 0.59; P<0.001) in SWIFT-1 and 0.56 (95% CI, 0.44 to 0.70) with depemokimab and 1.08 (95% CI, 0.83 to 1.41) with placebo (rate ratio, 0.52; 95% CI, 0.36 to 0.73; P<0.001) in SWIFT-2. No significant between-group difference in the change from baseline in the SGRQ score was observed in either trial, so no statistical inference was drawn on subsequent secondary end points. The proportion of patients with any adverse event was similar in the two groups in both trials. CONCLUSIONS: Depemokimab reduced the annualized rate of exacerbations among patients with severe asthma with an eosinophilic phenotype. (Funded by GSK; SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.).

[Laryngopharyngeal Reflux (LPR) in patients with persistent hoarseness]. / Refluks krtaniowo-gardlowy (LPR) u pacjentów z przewlekla chrypka

INTRODUCTION: In 2006 The Global Consensus Group in Montreal pointed out that chronic laryngitis is highly associated with gastroesophageal reflux disease (GERD). AIM OF THE STUDY: To evaluate the frequency of LPR in a selected group of patients with chronic hoarseness. We were also interested in assessment of the relationship between Reflux Symptoms Index (RSI) scores, Ryan scores from the pharyngeal pH monitoring and the morphological changes in the larynx according to Reflux Findings Score (RFS). In addition, we wanted to assess the frequency of various clinical symptoms included in the RSI questionnaire among patients with LPR. MATERIALS AND METHODS: 42 patients from an outpatient ENT clinic with chronic hoarseness and RSI ≥ 13. All subjects underwent pharyngeal pH monitoring with the Dx-pH System Restech ™ and laryngoscopy. RESULTS: Among 42 patients with chronic hoarseness, LPR was confirmed in 35 patients (83.33%). In 7 subjects pharyngeal pH monitoring was normal. Among all patients with confirmed LPR, only 5 out of 8 elements of RFS laryngoscopic changes were observed. The most frequent inflammatory changes noticed included erythema of the arytenoids and interarytenoid regions (posterior laryngitis). These findings were found in 30 out of 35 patients with LPR. Median value of RFS in patients with LPR was 4.45, which is lower than the cut off value of 7 necessary for recognition of LPR. There is statistically significant positive correlation between Ryan scores and the RFS scale results (correlation coefficient 0.91, p<0.001). CONCLUSIONS: Pharyngeal pH monitoring confirmed LPR in 83.33% selected group of patients with chronic hoarseness and RSI ≥ 13. Isolated erythema of arytenoid and interarytenoid region was the most frequent inflammatory abnormality found in the larynx. RFS values below 7 do not exclude the diagnosis of LPR. We can use RFS scales as a prognostic test of severity of LPR - due to statistically significant positive correlation between Ryan score and RFS values. The use of RSI scale revealed that the most frequent symptom among patient with LPR was throat clearing followed by hoarseness.

[Spirometric tests in school-age children with past bronchopulmonary dysplasia]. / Ocena wybranych parametrów spirometrycznych u dzieci szkolnych z przebyta dysplazja oskrzelowo-plucna.

The aim of the paper was to estimate 9 spirometric parameters in 38 children aged 8-12, among them in16 with past bronchopulmonary dysplasia and in 22 healthy ones. Mean values of VC, FEV1, FVC Ex, PEF, MEF 75, MEF 50 and MEF 25 in children with past bronchopulmonary dysplasia were significantly lower than in healthy children. In children with past bronchopulmonary dysplasia VC was decreased comparing to normal values in 94% of cases, FVC Ex and MEF 50 in 75% and FEV1 in 63% of subjects. Tiffeneau coefficient and value of FEV1% FVC Ex were normal. Inhaled salbutamol increased significantly the mean values of VC and MEF 25 in children with dysplasia. The increase of FEV1 > 15% in 56% and VC > 15% only in 25% of these children was observed. It was found, that past bronchopulmonary dysplasia induces ventilatory disorders, mainly restriction changes with obstruction component in airways of school-age children.