A comparative in vitro study of standard facemask jet nebulization and high-flow nebulization in bronchiolitis.

Aim of Study: The use of a nebulizer paired with high-flow nasal cannulas (HFNC) has been proposed for drug delivery in bronchiolitis. Particle size nebulized is a relevant factor determining the efficacy of the nebulization. We replicated in vitro the theoretical parameters most widely used in bronchiolitis and we compared the size of the droplet nebulized with a standard nebulizer and a nebulizer integrated into HFNC. Materials and Methods: We used laser diffraction to analyze the particle size nebulized (volume median diameter Dv50). The standard system was a jet nebulizer connected to a facemask with a flow rate of 8 L/min (JN). Three designs were used as nebulizers integrated into HFNC: a vibrating mesh nebulizer set 1) before (HFNC-BH) and 2) after (HFNC-AH) the humidifier, and 3) a jet nebulizer connected before the nasal cannula (HFNC-BNC). HFNC was used with neonatal (3-8 L/min) and infant cannulas (8-15 L/min). Results: Droplet size was similar among the three drugs studied. A lower particle size was obtained when using the nebulization system integrated into HFNC compared to the standard nebulizer, regardless of the flow rate and the nasal cannula used when the position of the nebulizer was before the nasal cannula (p < 0.05): 6.89 µm (JN), 2.49 µm (HFNC-BNC 3 L/min), 2.59 µm (HFNC-BNC 5 L/min), 2.44 µm (HFNC-BNC 8 L/min), 3.22 µm (HFNC-BNC 10 L/min), 3.23 µm (HFNC-BNC 13 L/min), 3.16 µm (HFNC-BNC 15 L/min). The particle size was lower in HFNC-BF compared to the HFNC-AH using neonatal nasal cannula (3-8 L/min) (p < 0.05). Conclusion: The use of a nebulizer integrated with HFNC has shown promising results in an experimental scenario of bronchiolitis. The particle size achieved with the nebulizer placed before the humidifier is equivalent to the one obtained via conventional nebulization, and it is even smaller when the integrated nebulizer is placed before the nasal cannulas.

Effectiveness of Two Targeted Temperature Management Methods After Pediatric Postcardiac Arrest: A Multicenter International Study.

OBJECTIVES: It is currently recommended that after return of spontaneous circulation following cardiac arrest, fever should be prevented using TTM through a servo-controlled system. This technology is not yet available in many global settings, where manual physical measures without servo-control is the only option. Our aim was to compare feasibility, safety and quality assurance of servo-controlled system versus no servo-controlled system cooling, TTM protocols for cooling, maintenance and rewarming following return of spontaneous circulation after cardiac arrest in children. DESIGN: Prospective, multicenter, nonrandomized, study. SETTING: PICUs of 20 hospitals in South America, Spain, and Italy, 2012-2014. PATIENTS: Under 18 years old with a cardiac arrest longer than 2 minutes, in coma and surviving to PICU admission requiring mechanical ventilation were included. METHODS: TTM to 32-34°C was performed by prospectively designed protocol across 20 centers, with either servo-controlled system or no servo-controlled system methods, depending on servo-controlled system availability. We analyzed clinical data, cardiac arrest, temperature, mechanical ventilation duration, length of hospitalization, complications, survival, and neurologic outcomes at 6 months. PRIMARY OUTCOME: feasibility, safety and quality assurance of the cooling technique and secondary outcome: survival and Pediatric Cerebral Performance Category at 6 months. MEASUREMENTS AND MAIN RESULTS: Seventy patients were recruited, 51 of 70 TTM (72.8%) with servo-controlled system. TTM induction, maintenance, and rewarming were feasible in both groups. Servo-controlled system was more effective than no servo-controlled system in maintaining TTM (69 vs 60%; p = 0.004). Servo-controlled system had fewer temperatures above 38.1°C during the 5 days of TTM (0.1% vs 2.9%; p < 0.001). No differences in mortality, complications, length of mechanical ventilation and of stay, or neurologic sequelae were found between the two groups. CONCLUSIONS: TTM protocol (for cooling, maintenance and rewarming) following return of spontaneous circulation after cardiac arrest in children was feasible and safe with both servo-controlled system and no servo-controlled system techniques. Achieving, maintaining, and rewarming within protocol targets were more effective with servo-controlled system versus no servo-controlled system techniques.

Incorporating a Nebulizer System Into High-Flow Nasal Cannula Improves Comfort in Infants With Bronchiolitis.

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly used to provide respiratory support in infants with bronchiolitis. The delivery of aerosol therapy through a jet nebulizer is widely indicated despite its controversial efficacy and poor tolerability. METHODS: This randomized cross-over study aimed to evaluate the comfort and satisfaction of the delivery of aerosol therapy using a nebulization system integrated into HFNC compared with the standard practice of using a jet nebulizer with a face mask. The COMFORT-Behavior (COMFORT-B) scale, a visual analog scale, and a numeric rating scale were used by health professionals and caregivers to assess subjects' levels of comfort and satisfaction. RESULTS: A total of 113 nebulizations (64 via nebulizer with HFNC; 49 via jet nebulizer) were delivered to the 6 subjects included in the study. Use of the nebulizer with HFNC showed increased comfort and satisfaction during nebulization compared to use of the jet nebulizer, as measured by the COMFORT-B scale, the visual analog scale, and the numeric rating scale, with the following median (interquartile range) scores: 10.7 (7-16) versus 14.5 (10-20) (P = .006), 8.5 (6-10) versus 7 (4-9) (P = .02), and 3.84 (3.61-4.07) versus 1.83 (1.58-2.08) (P < .001), respectively. Correlation between the COMFORT-B scale and the visual analog scale using Spearman's rho was -0.757 (P < .001). The intraclass correlation coefficient for the COMFORT-B scale, visual analog scale, and numeric rating scale, as measured by 2 different nurses, was between 0.75 and 0.87. CONCLUSIONS: The use of a nebulizer incorporated into HFNC therapy results in an increased level of comfort and satisfaction compared to the use of a conventional jet nebulizer in subjects with bronchiolitis who required HFNC therapy. Further studies are needed to determine whether aerosol therapy delivered through HFNC improves the clinical course of this pathology.

Utilidad de los marcadores de remodelado óseo en la detección de enfermedad mineral ósea en pacientes con fenilcetonuria / Utility of bone turnover markers in metabolic bone disease detection in patients with phenylketonuria

Fundamento y objetivo: La enfermedad mineral ósea (EMO) es más frecuente en pacientes con fenilcetonuria. Los objetivos del estudio son conocer la utilidad de los marcadores de remodelado óseo para identificar a pacientes con fenilcetonuria con EMO y conocer las alteraciones del remodelado óseo subyacentes. Pacientes y método: Estudio observacional transversal de 43 pacientes con fenilcetonuria > 7 años (extremos 7,1-41 años). Se realizó encuesta nutricional, densitometría, determinación de fosfatasa alcalina ósea (FAO), procollagen type 1 N-terminal propeptide (PNP-1, «propéptido aminoterminal del procolágeno tipo 1»), beta-crosslaps y relación calcio/creatinina en orina. Se estratificó a los pacientes por edad y tipo de tratamiento. Resultados: El 20,9% de los pacientes presentaron marcadores de remodelado óseo patológicos; el 90% de ellos eran adultos. La FAO estaba disminuida en el 70% de ellos, y el beta-crosslaps en el 42,8%. Los valores de FAO fueron patológicos con más frecuencia en diagnosticados de fenilcetonuria tardíamente (41,7 frente a 10,7%; p < 0,05) y en pacientes con EMO (60 frente a 14,3%; p < 0,05). Los valores de PNP-1 y calcio/creatinina fueron similares entre todos los pacientes con fenilcetonuria independientemente de presentar EMO, diagnóstico tardío o tratamiento con tetrahidrobiopterina. Los pacientes con disminución de FAO y beta-crosslaps recibieron menor ingesta de proteínas naturales: FAO (media [DE] de 0,21 [0,13] frente a 0,65 [0,65] g/kg; p < 0,05); beta-crosslaps (media de 0,29 [0,23] frente a 0,65 [0,66] g/kg; p < 0,05). Ninguno de los tratados con tetrahidrobiopterina presentó valores alterados de marcadores óseos. Conclusiones: Los pacientes adultos fenilcetonúricos con menor ingesta de proteínas naturales tienden a presentar valores disminuidos de FAO, marcador que puede resultar útil para identificar a los pacientes con riesgo de presentar EMO (AU)

Background and objective: Mineral bone disease is more common in phenylketonuric patients. The objectives of this study were to determine the usefulness of biochemical bone markers to identify phenylketonuric patients with mineral bone disease (MBD) and know the underlying bone remodeling alterations. Patients and method: Cross-sectional study of 43 phenylketonuric patients > 7 years (range: 7.1-41 years). A nutritional survey was performed and bone alkaline phosphatase (BAP), procollagen type 1 N-terminal propeptide (PNP-1), beta-crosslaps and ratio calcium/creatinine in urine were determined. Results: A percentage of 20.9 of patients had pathological biochemical bone markers, 90% of them being adults. BAP was decreased in 70% of them and beta-crosslaps in 42.8%. BAP values were more often pathological in phenylketonuric patients with a late diagnosis (41.7 vs. 10.7%; P < .05) and in patients with MBD (60 vs. 14.3%; P < .05). PNP-1 values and calcium/creatinine were similar among all phenylketonuric patients regardless of presenting MBD, late diagnosis or tetrahydrobipterin treatment (enzyme cofactor). Patients with decreased BAP and beta-crosslaps had lower natural protein intake: BAP (0.21 ± 0.13 vs. 0.65 ± 0.65 g/kg; P < .05); beta-crosslaps (0.29 ± 0.23 vs. 0.65 ± 0.66 g/kg; P < .05). None of the tetrahydrobiopterin treated patients showed altered values of BAP, PNP-1 or calcium/creatinine. Conclusions: Adult phenylketonuric patients with lower natural protein intake tend to have lower values of BAP, which is a marker that may be useful to identify patients at risk for MBD (AU)

New insights in growth of phenylketonuric patients.

UNLABELLED: Treatment of phenylketonuria involves a restriction in the intake of natural proteins. This can lead to growth impairment. Weight, height and body mass index of 109 hyperphenylalaninemic patients (mild hyperphenylalaninemia (HPA) and phenylketonuria (PKU)) were determined from birth until 18 years, every 6 months, and differences to the healthy population, depending on the age, sex and phenotype, were analyzed. Data collection was longitudinal retrospective during 31 years. Statistical analysis of z-score values was performed by advanced statistical tools. Long-term evolution of anthropometric z-scores showed no significant statistical differences between PKU and mild HPA individuals, according to the general population. For PKU individuals, height is slightly lower and weight slightly higher than in the healthy population, but differences are smaller than one standard deviation. Nevertheless, over-time evolutions of female height z-scores are different in each type of pathology, with a crossover between 8 and 12 years (p = 0.0186). CONCLUSIONS: It is nowadays possible to achieve a long-term normal growth in PKU patients with appropriate dietary treatment. There is however an acceleration of growth up to 8 years old for PKU female patients that leads to a slightly lower final height. Detection of this behaviour was possible by using nonlinear mixed effects models.

[Utility of bone turnover markers in metabolic bone disease detection in patients with phenylketonuria]. / Utilidad de los marcadores de remodelado óseo en la detección de enfermedad mineral ósea en pacientes con fenilcetonuria.

BACKGROUND AND OBJECTIVE: Mineral bone disease is more common in phenylketonuric patients. The objectives of this study were to determine the usefulness of biochemical bone markers to identify phenylketonuric patients with mineral bone disease (MBD) and know the underlying bone remodeling alterations. PATIENTS AND METHOD: Cross-sectional study of 43 phenylketonuric patients>7 years (range: 7.1-41 years). A nutritional survey was performed and bone alkaline phosphatase (BAP), procollagen type 1 N-terminal propeptide (PNP-1), beta-crosslaps and ratio calcium/creatinine in urine were determined. RESULTS: A percentage of 20.9 of patients had pathological biochemical bone markers, 90% of them being adults. BAP was decreased in 70% of them and beta-crosslaps in 42.8%. BAP values were more often pathological in phenylketonuric patients with a late diagnosis (41.7 vs. 10.7%; P<.05) and in patients with MBD (60 vs. 14.3%; P<.05). PNP-1 values and calcium/creatinine were similar among all phenylketonuric patients regardless of presenting MBD, late diagnosis or tetrahydrobipterin treatment (enzyme cofactor). Patients with decreased BAP and beta-crosslaps had lower natural protein intake: BAP (0.21 ± 0.13 vs. 0.65 ± 0.65 g/kg; P<.05); beta-crosslaps (0.29 ± 0.23 vs. 0.65 ± 0.66 g/kg; P<.05). None of the tetrahydrobiopterin treated patients showed altered values of BAP, PNP-1 or calcium/creatinine. CONCLUSIONS: Adult phenylketonuric patients with lower natural protein intake tend to have lower values of BAP, which is a marker that may be useful to identify patients at risk for MBD.

Risk factors for developing mineral bone disease in phenylketonuric patients.

There is a compromised bone mass in phenylketonuria patients compared with normal population, but the mechanisms responsible are still a matter of investigation. In addition, tetrahydrobiopterin therapy is a new option for a significant proportion of these patients and the prevalence of mineral bone disease (MBD) in these patients is unknown. We conducted a cross-sectional observational study including 43 phenylketonuric patients. Bone densitometry, nutritional assessment, physical activity questionnaire, biochemical parameters, and molecular study were performed in all patients. Patients were stratified by phenotype, age and type of treatment. The MBD prevalence in phenylketonuria was 14%. Osteopenic and osteoporotic (n=6 patients) had an average daily natural protein intake significantly lower than the remaining (n=37) patients with PKU (14.33 ± 8.95 g vs 21.25 ± 20.85 g). Besides, a lower body mass index was found. There were no statistical differences in physical activity level, calcium, phosphorus and fat intake, and in phenylalanine, vitamin D, paratohormone, docosahexaenoic and eicosapentaenoic acid blood levels. Mutational spectrum was found in up to 30 different PAH genotypes and no relationship was established among genotype and development of MBD. None of the twelve phenylketonuric patients treated with tetrahydrobiopterin (27.9%), for an average of 7.1 years, developed MBD. Natural protein intake and blood levels of eicosapentaenoic acid were significantly higher while calcium intake was lower in these patients. This study shows that the decrease in natural protein intake can play an important role in MBD development in phenylketonuric patients. Therapy with tetrahydrobiopterin allows a more relaxed protein diet, which is associated with better bone mass.