Comparison of Efficacy and Pharmacoeconomic Outcomes Between Calfactant and Poractant Alfa in Preterm Infants With Respiratory Distress Syndrome.

OBJECTIVES: In order to evaluate the impact of the surfactant of choice selection, primary end points were to compare the average number of doses per patient, need for mechanical ventilation on day 3, hospital length of stay, and in-hospital mortality between calfactant and poractant alfa in preterm infants with respiratory distress syndrome (RDS). Secondary outcomes included administration complications, development of bronchopulmonary dysplasia (BPD), and estimated average per patient cost among the study population. METHODS: A retrospective chart review was performed at a level IV neonatal intensive care unit between January 2020 and December 2021 to compare the efficacy, safety, and pharmacoeconomic outcomes -following a surfactant of choice switch from calfactant to poractant alfa in preterm infants with RDS. RESULTS: Final analysis included 253 premature infants with gestational age (GA) between 22 and 36 weeks who met inclusion criteria. A total of 118 patients who received calfactant required higher average number of doses, 1.5 vs 1.3 doses (p = 0.031), and had more administration complications than 135 patients who received poractant alfa (10.2 vs 2.2%, p = 0.008). The need for redosing, mechanical ventilation on day 3, hospital length of stay, in-hospital mortality, and development of BPD were comparable between both groups. However, the estimated average per patient cost for poractant alfa was 32% higher than calfactant ($1,901 vs $1,439, p <0.001). CONCLUSIONS: Despite the pharmacoeconomic disadvantage, preterm infants who received poractant alfa needed fewer doses and were less likely to have administration complications compared with those who received calfactant.

Comparison of the Pharmacoeconomics of Calfactant and Poractant Alfa in Surfactant Replacement erapy.

OBJECTIVE: To compare the pharmacy costs of calfactant (Infasurf, ONY, Inc.) and poractant alfa (Curosurf, Chiesi USA, Inc., Cary, NC). METHODS: The University of South Alabama Children's and Women's Hospital switched from calfactant to poractant alfa in 2013 and back to calfactant in 2015. Retrospectively, we used deidentified data from pharmacy records that provided type of surfactant administered, gestational age, birth weight, and number of doses on each patient. We examined differences in the number of doses by gestational ages and the differences in costs by birth weight cohorts because cost per dose is based on weight. RESULTS: There were 762 patients who received calfactant and 432 patients who received poractant alfa. The average number of doses required per patient was 1.6 administrations for calfactant-treated patients and 1.7 administrations for poractant alfa-treated patients, p = 0.03. A higher percentage of calfactant patients needed only 1 dose (53%) than poractant alfa patients (47%). The distribution of the number of doses for calfactant-treated patients was significantly lower than for the poractant alfa-patients, p < 0.001. Gestational age had no consistent effect on the number of doses required for either calfactant or poractant alfa. Per patient cost was higher for poractant alfa than for calfactant in all birth weight cohorts. Average per patient cost was $1160.62 for poractant alfa, 38% higher than the average per patient cost for calfactant ($838.34). Using poractant alfa for 22 months is estimated to have cost $202,732.75 more than it would have cost if the hospital had continued using calfactant. CONCLUSION: Our experience showed a strong pharmacoeconomic advantage for the use of calfactant compared to the use of poractant alfa because of similar average dosing and lower per patient drug costs.

Electronic cigarette vapor alters the lateral structure but not tensiometric properties of calf lung surfactant.

BACKGROUND: Despite their growing popularity, the potential respiratory toxicity of electronic cigarettes (e-cigarettes) remains largely unknown. One potential aspect of e-cigarette toxicity is the effect of e-cigarette vapor on lung surfactant function. Lung surfactant is a mixture of lipids and proteins that lines the alveolar region. The surfactant layer reduces the surface tension of the alveolar fluid, thereby playing a crucial role in lung stability. Due to their small size, particulates in e-cigarette vapor can penetrate the deep lungs and come into contact with the lung surfactant. The current study sought to examine the potential adverse effects of e-cigarette vapor and conventional cigarette smoke on lung surfactant interfacial properties. METHODS: Infasurf®, a clinically used and commercially available calf lung surfactant extract, was used as lung surfactant model. Infasurf® films were spread on top of an aqueous subphase in a Langmuir trough with smoke particulates from conventional cigarettes or vapor from different flavors of e-cigarettes dispersed in the subphase. Surfactant interfacial properties were measured in real-time upon surface compression while surfactant lateral structure after exposure to smoke or vapor was examined using atomic force microscopy (AFM). RESULTS: E-cigarette vapor regardless of the dose and flavoring of the e-liquid did not affect surfactant interfacial properties. In contrast, smoke from conventional cigarettes had a drastic, dose-dependent effect on Infasurf® interfacial properties reducing the maximum surface pressure from 65.1 ± 0.2 mN/m to 46.1 ± 1.3 mN/m at the highest dose. Cigarette smoke and e-cigarette vapor both altered surfactant microstructure resulting in an increase in the area of lipid multilayers. Studies with individual smoke components revealed that tar was the smoke component most disruptive to surfactant function. CONCLUSIONS: While both e-cigarette vapor and conventional cigarette smoke affect surfactant lateral structure, only cigarette smoke disrupts surfactant interfacial properties. The surfactant inhibitory compound in conventional cigarettes is tar, which is a product of burning and is thus absent in e-cigarette vapor.

High Oxygen Concentrations Adversely Affect the Performance of Pulmonary Surfactant.

BACKGROUND: Although effective in the neonatal population, exogenous pulmonary surfactant has not demonstrated a benefit in pediatric and adult subjects with hypoxic lung injury despite a sound physiologic rationale. Importantly, neonatal surfactant replacement therapy is administered in conjunction with low fractional FIO2 while pediatric/adult therapy is administered with high FIO2 . We suspected a connection between FIO2 and surfactant performance. Therefore, we sought to assess a possible mechanism by which the activity of pulmonary surfactant is adversely affected by direct oxygen exposure in in vitro experiments. METHODS: The mechanical performance of pulmonary surfactant was evaluated using 2 methods. First, Langmuir-Wilhelmy balance was utilized to study the reduction in surface area (δA) of surfactant to achieve a low bound value of surface tension after repeated compression and expansion cycles. Second, dynamic light scattering was utilized to measure the size of pulmonary surfactant particles in aqueous suspension. For both experiments, comparisons were made between surfactant exposed to 21% and 100% oxygen. RESULTS: The δA of surfactant was 21.1 ± 2.0% and 35.8 ± 2.0% during exposure to 21% and 100% oxygen, respectively (P = .02). Furthermore, dynamic light-scattering experiments revealed a micelle diameter of 336.0 ± 12.5 µm and 280.2 ± 11.0 µm in 21% and 100% oxygen, respectively (P < .001), corresponding to a ∼16% decrease in micelle diameter following exposure to 100% oxygen. CONCLUSIONS: The characteristics of pulmonary surfactant were adversely affected by short-term exposure to oxygen. Specifically, surface tension studies revealed that short-term exposure of surfactant film to high concentrations of oxygen expedited the frangibility of pulmonary surfactant, as shown with the δA. This suggests that reductions in pulmonary compliance and associated adverse effects could begin to take effect in a very short period of time. If these findings can be demonstrated in vivo, a role for reduced FIO2 during exogenous surfactant delivery may have a clinical benefit.

Calf Lung Surfactant Recovers Surface Functionality After Exposure to Aerosols Containing Polymeric Particles.

BACKGROUND: Recent studies have shown that colloidal particles can disrupt the interfacial properties of lung surfactant and thus key functional abilities of lung surfactant. However, the mechanisms underlying the interactions between aerosols and surfactant films remain poorly understood, as our ability to expose films to particles via the aerosol route has been limited. The aim of this study was to develop a method to reproducibly apply aerosols with a quantifiable particle dose on lung surfactant films and investigate particle-induced changes to the interfacial properties of the surfactant under conditions that more closely mimic those in vivo. METHODS: Films of DPPC and Infasurf® were exposed to aerosols containing polystyrene particles generated using a Dry Powder Insufflator™. The dose of particles deposited on surfactant films was determined via light absorbance. The interfacial properties of the surfactant were studied using a Langmuir-Wilhelmy balance during surfactant compression to film collapse and cycles of surface compression and expansion at a fast cycling rate within a small surface area range. RESULTS: Exposure of surfactant films to aerosols led to reproducible dosing of particles on the films. In film collapse experiments, particle deposition led to slight changes in collapse surface pressure and surface area of both surfactants. However, longer interaction times between particles and Infasurf® films resulted in time-dependent inhibition of surfactant function. When limited to lung relevant surface pressures, particles reduced the maximum surface pressure that could be achieved. This inhibitory effect persisted for all compression-expansion cycles in DPPC, but normal surfactant behavior was restored in Infasurf® films after five cycles. CONCLUSIONS: The observation that Infasurf® was able to quickly restore its function after exposure to aerosols under conditions that better mimicked those in vivo suggests that particle-induced surfactant inhibition is unlikely to occur in vivo due to an aerosol exposure.