Effectiveness and Safety of Albuterol Solutions With and Without Benzalkonium Chloride.

INTRODUCTION: Continuous aerosolized ß2 agonist, namely albuterol, is the most commonly used therapy for critical asthma. Benzalkonium chloride is a preservative present in some formulations of aerosolized albuterol solutions that can induce bronchospasm. Recent studies have shown that inhalation of albuterol containing benzalkonium chloride might induce unintended bronchoconstriction and poor outcomes. This study aimed to investigate whether using albuterol solutions containing benzalkonium chloride results in prolonged hospital length of stay (LOS). METHODS: This was a retrospective cohort study of pediatric subjects admitted to the pediatric ICU (PICU) and treated with continuous albuterol. Data were collected and compared before and after a change to benzalkonium chloride-containing solutions. Subjects who were treated with preservative-free solutions were used as control. The primary outcome was PICU and hospital LOS; secondary outcomes included the duration of continuous albuterol and use of adjunctive therapies. RESULTS: A total of 266 admissions were included in the study. One hundred forty subjects (52.6%) were exposed to benzalkonium chloride. Median age and severity of illness scoring were similar between groups. The initial dose of continuous albuterol was significantly higher in the benzalkonium chloride group (median 15 interquartile range [IQR] 10-20 mg/h) compared to the preservative-free group (median 10 IQR 10-20 mg/h) (P < .001). PICU LOS was longer for the preservative-free group, 2.5 (IQR 1.4-4.6) d vs 1.8 (IQR 1.1-2.9) d for benzalkonium chloride group (P = .002). There was no significant difference in duration of continuous albuterol therapy (P = .16) or need for adjunctive respiratory support (heliox [P = .32], noninvasive ventilation [P = .81], and invasive mechanical ventilation [P = .57]). CONCLUSIONS: In contrast to published literature showing that benzalkonium chloride may be associated with a longer duration of continuous albuterol nebulization and hospital LOS, our study demonstrated that benzalkonium chloride-containing albuterol is safe for continuous nebulization in critically ill children and not associated with worse outcomes.

Rapid Infliximab Biosimilar Infusion in Children With Inflammatory Bowel Disease.

OBJECTIVES: Compare prevalence of infusion reaction (IR) between infliximab (IFX) and infliximab biosimilar (IFX-abda) at standard and rapid rates and measure the impact on health care cost in children with inflammatory bowel disease (IBD). METHODS: Records of subjects receiving IFX and IFX-abda were reviewed over a 21-month period. Demographics and IRs were recorded. Cost analysis utilized average wholesale pricing, infusion duration, nursing time, and infusion center throughput. RESULTS: Fifty-six subjects received 498 infusions. Sixteen subjects received both IFX and IFX-abda. Thirteen IRs occurred for an overall prevalence of 2.6%. One outlier subject accounted for 8 of 13 (62%) of IRs. Data were analyzed with and without the outlier. Standard rate infusion of both IFX and IFX-abda was associated with increased risk of IR compared with rapid rate but only reached significance for IFX when calculated with the outlier removed. Risk of IR was not statistically significant between IFX and IFX-abda for both standard and rapid rates. IFX-abda saved an average of $2,611 per infusion. Rapid infusion saved 70 minutes of infusion time, 20 minutes of estimated nursing time per infusion, and decreased infusion center appointment length by as much as 2 hours per infusion. CONCLUSIONS: Rapid IFX-abda appears safe without increased IRs and decreases cost.

Mistargeting of secretory cargo in retromer-deficient cells.

Intracellular trafficking is a basic and essential cellular function required for delivery of proteins to the appropriate subcellular destination; this process is especially demanding in professional secretory cells, which synthesize and secrete massive quantities of cargo proteins via regulated exocytosis. The Drosophila larval salivary glands are composed of professional secretory cells that synthesize and secrete mucin proteins at the onset of metamorphosis. Using the larval salivary glands as a model system, we have identified a role for the highly conserved retromer complex in trafficking of secretory granule membrane proteins. We demonstrate that retromer-dependent trafficking via endosomal tubules is induced at the onset of secretory granule biogenesis, and that recycling via endosomal tubules is required for delivery of essential secretory granule membrane proteins to nascent granules. Without retromer function, nascent granules do not contain the proper membrane proteins; as a result, cargo from these defective granules is mistargeted to Rab7-positive endosomes, where it progressively accumulates to generate dramatically enlarged endosomes. Retromer complex dysfunction is strongly associated with neurodegenerative diseases, including Alzheimer's disease, characterized by accumulation of amyloid ß (Aß). We show that ectopically expressed amyloid precursor protein (APP) undergoes regulated exocytosis in salivary glands and accumulates within enlarged endosomes in retromer-deficient cells. These results highlight recycling of secretory granule membrane proteins as a critical step during secretory granule maturation and provide new insights into our understanding of retromer complex function in secretory cells. These findings also suggest that missorting of secretory cargo, including APP, may contribute to the progressive nature of neurodegenerative disease.