Kee H. Pyon

Work of breathing using high-flow nasal cannula in preterm infants

Objective:To compare the work of breathing (WOB) in premature neonates supported with high-flow nasal cannula (HFNC) and nasal continuous positive airway pressure (NCPAP).Study Design:Eighteen preterm neonates <2.0 kg on HFNC or NCPAP support were studied in a random order. A ventilator was used to deliver 6 cm H2O of NCPAP with nasal prongs. High-flow nasal cannula delivered with Vapotherm (VAPO) at 3, 4 and 5 l/min was used. Tidal ventilation was obtained using respiratory inductance plethysmography calibrated with face-mask pneumotachography. An esophageal balloon estimated pleural pressure from which changes in end distending pressure were calculated. Inspiratory, elastic and resistive WOB and respiratory parameters were calculated.Results:No differences were found in the WOB for all settings. Changes in end distending pressure did not vary significantly over all device settings except VAPO at 5 l/min.Conclusion:In these preterm infants with mild respiratory illness, HFNC provided support comparable to NCPAP.

Work of breathing during nasal continuous positive airway pressure in preterm infants : A comparison of bubble vs variable-flow devices

OBJECTIVE:To compare work of breathing and breathing asynchrony during bubble nasal continuous positive airway pressure (NCPAP) vs variable-flow (VF)-NCPAP in premature infants.STUDY DESIGN:We studied 18 premature infants of birth weight <1500 g who required NCPAP for mild respiratory distress. Each infant was studied on bubble and VF-NCPAP at 8, 6, 4, and 0 cmH2O. Tidal volumes were obtained by calibrated respiratory inductance plethysmography. Esophageal pressure estimated intrapleural pressure. Inspiratory and resistive work of breathing were calculated from pressure–volume data. Breathing asynchrony was assessed with phase angle. The results at all NCPAP levels were referenced to VF-NCPAP values at 8 cmH2O.RESULTS:Provision of NCPAP with either device decreased inspiratory work of breathing, tidal volume, and minute ventilation relative to NCPAP of 0 cmH2O. Bubble NCPAP did not decrease resistive work of breathing relative to 0 cmH2O. Resistive work of breathing (p=0.01), respiratory rate (p<0.03), and phase angle (p=0.002) were all greater with bubble compared to VF-NCPAP.CONCLUSION:The more labored and asynchronous breathing seen with bubble NCPAP may lead to higher failure rates over the long term than with VF-NCPAP.

Impact of histological chorioamnionitis on tracheal aspirate cytokines in premature infants.

BACKGROUND Histological chorioamnionitis (CHORIO) may increase inflammatory mediators in the lungs of preterm infants. OBJECTIVE To study the impact of CHORIO on tracheal aspirate (TA) cytokines in ventilated infants. DESIGN/METHODS TA samples collected within 48 hours after birth from 40 ventilated neonates (gestational age [GA] <30 weeks, body weight [BW] <1250 g) were analyzed. Levels of 12 cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, epidermal growth factor [EGF], interferon-γ [IFN-γ], monocyte chemotactic protein-1 [MCP-1], tumor necrosis factor-α [TNF-α], vascular endothelial growth factor [VEGF]) were measured using a biochip multianalyte immunoassay (Randox Laboratories, Antrim, UK). Total protein was measured by the Bradford assay. CHORIO assessment was done by a blinded pathologist. RESULTS Twenty-six infants (GA 26.6 ± 1.4 weeks, BW 852 ± 162 g) had no CHORIO and 14 (GA 25.1 ± 1.0 weeks, BW 776 ± 164 g) had CHORIO. IL-1α, IL-1β, IL-8, and VEGF were significantly higher in TA of infants with CHORIO. After correction for dilution, IL-1α, IL-1β, and IL-8 were significantly elevated. Increased TA total cell count correlated with CHORIO, VEGF, EGF, MCP-1, IL-8, and IL-6 TA levels (all p ≤ 0.02). Ventilator, oxygen supplementation, and hospital days correlated with TA IFN-γ levels (all p ≤ 0.01). CONCLUSION CHORIO is associated with increased specific proinflammatory mediators in TA samples of preterm infants.

High-mobility group box-1 protein in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia and steroid therapy

Objective:High-mobility group box-1 (HMGB1) is a potent inflammatory mediator and contributes to acute lung injury in adults. The role of HMGB1 in neonatal lung injury and the development of bronchopulmonary dysplasia (BPD) is unknown. We studied the association between HMGB1 levels in tracheal aspirates (TAs) and adverse outcomes (BPD/death) in ventilated premature infants (VPIs) and modulation of HMGB1 levels with dexamethasone (Dex) use.Study Design:Infants born before 32 weeks gestation and requiring mechanical ventilation were enrolled. Serial TA samples were collected on days 1, 3, 5 and 7 and HMGB1 levels were measured. HMGB1 levels in TA samples were compared between infants with no BPD and infants who developed BPD or died. HMGB1 TA levels were also compared before and after using Dex.Result:In all, 24 infants (gestational age 26.4±1.9 weeks, birth weight 859±200 g) had no BPD, 60 infants (gestational age 25.4±1.8 weeks, birth weight 749±156 g) developed BPD or died before 36 weeks postmenstrual age. Mean HMGB1 level in first week of life was significantly lower in infants with no BPD (27.3±16.5 ng mg–1) compared with those who developed BPD or died (45.1±30.9 ng mg–1, P=0.004). In total, 29 VPIs received Dex. There was no significant change in HMGB1 levels with steroid therapy (before 47.0±43.9, after 60.1.5±58.8, P=0.3).Conclusion:Our data suggest that higher HMGB1 levels in TA are associated with the development of BPD or death in VPI. Dex use had no effect on HMGB1 levels.

Utility of performing routine head ultrasounds in preterm infants with gestational age 30-34 weeks

Background. The American Academy of Neurology and Child Neurology Society recommend performing routine screening head ultrasounds (HUS) on preterm infants of less than 30 weeks gestation. Objective. To study the incidence of intraventricular hemorrhage (IVH) and evaluate the need for screening HUS in preterm infants with gestational age (GA) of 30–34 weeks. Design/Methods. Preterm infants (GA; 30–34 weeks) admitted to the neonatal intensive care unit (NICU) between January 1997 and September 2007 were included in this study. Grades of IVH were defined as per the Papile classification. Results. Screening HUS were performed on 463 infants with GA of 30–34 weeks. Twenty-seven (5.8%) infants had abnormal cranial ultrasound (US) (IVH or periventricular leucomalacia [PVL]). The incidence of IVH ranged from 3.3% to 6.3% at various GA. Seven (1.5%) infants had severe abnormalities on HUS (grades III/IV or PVL). Conclusions. A significant number of infants born between 30 and 34 weeks of gestation have abnormalities on screening cranial US. Since not all infants born at 30–34 weeks of gestation received a HUS, the incidence of HUS abnormalities might have been overestimated due to a possible ‘selection bias’. Additional studies are needed to examine the adverse neurodevelopmental outcomes in this group of preterm infants with mild abnormalities (IVH grades I or II) on cranial US before recommending routine screenings for IVH.

Detection of pepsin in mouth swab: correlation with clinical gastroesophageal reflux in preterm infants.

Abstract Objective: To study the relationship between pepsinogen/pepsin in a mouth swab and clinical gastroesophageal reflux (GER) in preterm infants. Methods: Preterm infants (birth weight ≤ 2000 g) on full enteral feeds were enrolled. Mouth swabs from cheek and below the tongue were collected one, two and three hours after feeding. An enzymatic assay with substrate fluorescein isothiocyanate-casein was used to detect pepsin A and C activities with further confirmation by western blot. Blinded investigators reviewed the infant’s medical record to clinically diagnose GER. Results: A total of 101 premature infants were enrolled. Pepsinogen/pepsin was detected in 45/101 (44.5%) infants in at least one sample. A clinical diagnosis of GER was made in 36/101 (35.6%) infants. Mouth swabs were positive in 26/36 (72%) infants with clinical GER and only 19/65 (29%) infants without GER (p < 0.001). Similarly, the levels of pepsinogen/pepsin A and C were higher in the mouth swabs of infants with clinical GER. Conclusion: The detection of pepsinogen/pepsin in a mouth swab correlates with clinical GER in premature infants.

Twice-weekly fluconazole prophylaxis in premature infants: association with cholestasis.

Background:  Fluconazole prophylaxis is effective in preventing invasive candidiasis in extremely low‐birthweight (ELBW) infants. The authors previously reported an increased incidence of cholestasis with fluconazole prophylaxis in ELBW infants, which led to fluconazole prophylaxis being changed to a less frequent dosing (LFD) schedule of twice a week at their institution. The purpose of the present study was therefore to evaluate the effectiveness and safety of LFD fluconazole prophylaxis in preventing invasive candidiasis in ELBW infants.

IFN-γ and IP-10 in tracheal aspirates from premature infants: Relationship with bronchopulmonary dysplasia†‡

Interferon‐gamma (IFN‐γ) and interferon‐inducible protein of 10 kDa (IP‐10) are potent inflammatory mediators and contribute to acute lung injury in adults. Recently, a potential role for IFN‐γ and IP‐10 in the pathogenesis of bronchopulmonary dysplasia (BPD) has been reported in animal models.

Sirtuin1 in tracheal aspirate leukocytes: possible role in the development of bronchopulmonary dysplasia in premature infants.

Objective: To study the association between Sirtuin1 (Sirt1), a class III histone deacetylator, in tracheal aspirate (TA) leukocytes and the development of bronchopulmonary dysplasia (BPD) in premature infants and modulation of Sirt1 with dexamethasone (Dex) use. Design/methods: Serial TA samples were collected on days 1, 3, 5 and 7 from ventilated premature neonates. Sirt1 was localized by immunocytochemistry and quantified on a scale of 0–4 by blinded observers. BPD was defined as the need of supplemental oxygen at 36 weeks postmenstrual age (PMA). Results: A total of 130 TA samples were collected from 51 infants (mean ± SD: GA 25.5 ± 1.4 w, BW 762 ± 174 g). Eleven infants survived without BPD and 40 infants died before 36 weeks PMA or developed BPD. Sirt1 was localized in the cytoplasm and nuclei of mononuclear (MONO) as well as polymorphonuclear cells. Sirt1 was significantly more localized in the nuclei of MONO cells in infants without BPD compared to infants who developed BPD or died before 36 weeks PMA. Twenty six infants received Dex. There was no significant change in Sirt1 localization with steroid therapy. Conclusions: Lower Sirt1 in TA leukocytes is associated with the development of BPD or death in premature infants. Dex use had no effect on Sirt1.

Inspiratory Work of Breathing (WOB) with a Demand Flow Vs Constant Flow Nasal Continuous Positive Airway Pressure (NCPAP) Device in Preterm Neonates

Inspiratory Work of Breathing (WOB) with a Demand Flow Vs Constant Flow Nasal Continuous Positive Airway Pressure (NCPAP) Device in Preterm Neonates