budesonide (Xavin / Pulairmax / Aerosial)

Azathioprine-Induced Pancreatitis in a Patient With Autoimmune Hepatitis: A Case Report.

Oikeh Oikigbeme O, Rathnam Aparna Abhirami AA, Cabrales Jazmin Mexia JM, Abdelghffar Mohamed M

A 67-year-old woman with biopsy-proven autoimmune hepatitis (AIH) developed acute pancreatitis shortly after starting azathioprine (AZA) and budesonide. She presented with abdominal pain, fever, and elevated lipase levels. Imaging confirmed acute interstitial edematous pancreatitis, and common etiologies-including gallstones, alcohol use, and hypertriglyceridemia-were ruled out. AZA was identified as the likely cause and was discontinued, resulting in full clinical recovery with supportive care. The patient was subsequently transitioned to mycophenolate mofetil (MMF) for continued immunosuppression. This case highlights the importance of early recognition of azathioprine-induced pancreatitis (AIP), particularly within the first few weeks of therapy. It also demonstrates the utility of MMF as a viable second-line agent in AZA-intolerant patients with AIH.

Adverse event mining for Breztri and Trelegy Ellipta based on the three international pharmacovigilance databases.

Wang Junyu J, Chen Kexu K, Yun Lu L, Xu Dexiang D

This study aimed to identify adverse drug reaction (ADR) risk signals associated with budesonide/glycopyrrolate/formoterol (Breztri) and fluticasone furoate/umeclidinium/vilanterol (Trelegy Ellipta) to support clinical decision-making and risk management. ADR reports related to Breztri and Trelegy Ellipta from the FDA Adverse Event Reporting System (FAERS) database, Japanese Adverse Drug Event Report (JADER) database and Canada Vigilance Adverse Reaction database (Q3 2004 to Q2 2024) were analyzed. After deduplication, reports were categorized using Medical Dictionary for Regulatory Activities (MedDRA) to obtain System Organ Class (SOC) and preferred terms (PTs). Disproportionality analysis was conducted using reporting odds ratio (ROR) and proportional reporting ratio methods. Analysis of 394 Breztri and 18,866 Trelegy Ellipta FAERS reports (predominantly consumer-submitted, U.S.-originated) identified 47 signals across 11 SOCs for Breztri (e.g., "Drug delivery system issue" ROR = 411.16, "Intentional device misuse" ROR = 410.69) and 160 signals across 15 SOCs for Trelegy (e.g., "Chronic eosinophilic rhinosinusitis" ROR = 187.65, "Foreign body in mouth" ROR = 107.67), revealing unlabeled risks like administration errors and packaging confusion. JADER data reinforced respiratory risks (Breztri: Chronic obstructive pulmonary disease (COPD) ROR = 516.8; Trelegy: gastrointestinal fungal infection ROR = 413.11) and device-independent safety signals (e.g., Trelegy urinary retention ROR = 28.81), while CVARD highlighted region-specific concerns including Trelegy-associated vasculitis (pulmonary vasculitis n = 29) and Breztri hypertension (ROR = 7.82). Cross-database convergence confirmed core anticholinergic/cardiopulmonary risks, yet divergent signals, FAERS' device errors, JADER's infection prominence, and CVARD's immunological events, underscore geographic heterogeneity in adverse reaction profiles, necessitating tailored risk management strategies for inhaler therapies. Inhalation device-related ADRs were observed, with Breztri showing higher incidence than Trelegy Ellipta, likely due to its more complex device usage. These findings highlight the need for enhanced patient education by healthcare providers to ensure proper device use in COPD treatment. Although core respiratory and anticholinergic risks are globally relevant, infection profiles, device complications, and rare immunological events exhibit significant geographic heterogeneity, necessitating tailored risk mitigation strategies aligned with regional pharmacovigilance patterns.

Randomised Controlled Trial Comparing Single Maintenance and Reliever Therapy (SMART) with Inhaled Budesonide-Formoterol Combination, Versus Conventional Budesonide and Additional As-Needed Levo-Salbutamol, in Children with Persistent Bronchial Asthma: Author's Reply.

Mathew Joseph L JL

Respiratory trajectories of infants born before 26 weeks of gestation from birth to discharge: an exploratory analysis of a randomised controlled trial.

Martinez Tugba Alarcon TA, Francis Kate L KL, Kamlin Omar O, Shalish Wissam W et al.

To survive, infants born before 26 weeks' gestation require respiratory assistance immediately after birth. However, the respiratory trajectories of these most preterm infants are not well delineated. We aimed to describe the early respiratory trajectories of infants born before 26 weeks' gestation who received surfactant during their initial neonatal intensive care admission. This study was a post-hoc exploratory analysis of PLUSS, a randomised controlled trial comparing intratracheal budesonide mixed with surfactant versus surfactant alone. Infants were recruited from 21 neonatal intensive care units in Australia, New Zealand, Canada, and Singapore. Infants born before 28 weeks' gestation and aged less than 48 h were eligible if (1) they were mechanically ventilated, or (2) they were receiving non-invasive respiratory support and there was a clinical decision to treat with surfactant. For this analysis, only infants born before 26 weeks' gestation were included, and treatment and control groups were combined. We aimed to describe early respiratory trajectories, including the levels of respiratory support and oxygen administered during the first 14 days, and respiratory outcomes at 28 postnatal days and 36 weeks' and 40 weeks' postmenstrual age. The main in-hospital respiratory outcomes were the timing and success of the first extubation, the durations of respiratory support, including oxygen requirements, and outcomes at hospital discharge, such as duration of hospital stay and discharge home on oxygen. PLUSS is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000322336), and follow-up is ongoing. Between Jan 4, 2018, and March 27, 2023, 1062 infants were recruited to the PLUSS trial, of whom 601 were born before 26 weeks' gestation. 131 (97%) of 135 infants born at 22-23 weeks' gestation were intubated at birth, compared with 163 (74%) of 220 infants born at 24 weeks and 157 (64%) of 246 infants born at 25 weeks. The median postnatal age at first extubation ranged from 15 days (IQR 8-26) in infants born at 22-23 weeks' gestation to 6 days (2-18) in those born at 24 weeks and 3 days (1-10) in those born at 25 weeks. 54 (66%) of 82 infants born at 22-23 weeks' gestation required reintubation, compared with 80 (51%) of 158 infants born at 24 weeks and 72 (38%) of 189 infants born at 25 weeks. The median duration of mechanical ventilation in infants who survived to 36 weeks' postmenstrual age was 36 days (IQR 23-49) in those born at 22-23 weeks' gestation, 26 days (14-39) in those born at 24 weeks, and 12 days (3-27) in those born at 25 weeks. At 40 weeks' postmenstrual age, nine (11%) of 83 surviving infants born at 22-23 weeks' gestation were discharged home, and 63 (85%) of 74 infants still in the hospital were receiving oxygen or respiratory support. By contrast, 36 (23%) of 160 surviving infants born at 24 weeks and 61 (30%) of 204 born at 25 weeks were discharged home, and 97 (78%) of 124 in-hospital infants born at 24 weeks and 79 (55%) of 143 in-hospital infants born at 25 weeks required oxygen or respiratory support. The most preterm infants born at the margins of viability require intensive and prolonged respiratory support. Knowledge of the respiratory trajectories in surfactant-treated infants born before 26 weeks' gestation could assist clinicians in family consultations while also guiding future randomised controlled trials. National Health and Medical Research Council, Australia; Chiesi Farmaceutici.