Incidence Of Chronic Lung Disease Research Articles

Provision of bubble continuous positive airway pressure for the stabilisation of extremely and very preterm infants after birth: A single-centre experience.

To describe the effect of resuscitation with bubble CPAP (bCPAP) versus T-piece device at birth on early clinical parameters and hospital outcomes in infants born <32 weeks gestation. This is a single-centre pre- and post-implementation study comparing outcomes in two epochs. In epoch 1 (1 July 2013-31 December 2014), infants were managed with non-humidified gas using Neopuff® T-piece devices to support breathing after birth. In epoch 2 (1 March 2020-31 December 2021), routine application of bCPAP with humidified gas was introduced at birth. Three hundred fifty-seven patients were included (176 epoch 1, 181 epoch 2). The mean gestational age was 28 ± 2 weeks. The demographics of the two epochs were comparable. There were significant improvements in outcomes of infants in epoch 2 with less infants intubated at delivery (16% vs. 4%, P ≤ 0.001), improved 5 min Apgar (7 vs. 8, P ≤ 0.001), reduced need for ventilation (21% vs. 8.8%, P ≤ 0.001), duration of ventilation in the first 72 h (9.6 vs. 4.6 h) and mortality (10.8% vs. 1.7%, P ≤ 0.001). There was, increased incidence of chronic lung disease (30% vs. 55%, P = 0.02) but no increase in infants discharged on oxygen (3.8% vs. 5%, P = 0.25). Similar findings were observed in a subgroup of infants born <25 weeks' gestation with no increase in the incidence of CLD. Introducing application of bCPAP from the first breaths in infants <32 weeks' gestation was associated with better short-term outcomes and mortality, albeit with increased incidence of CLD. The subgroup of infants born <25 weeks' gestation showed similar change in outcomes, with no increase in CLD.

Mechanical power made simple: validating a simplified calculation of mechanical power in preterm lungs.

The incidence of chronic lung disease is increasing, suggesting a need to explore novel ways to understand ventilator induced lung injury (VILI) in preterm infants. Mechanical power (MP) is a unifying measure of energy transferred to the respiratory system and a proposed determinant of VILI. The gold-standard method for calculating MP (geometric method) is not feasible in the clinical setting. This has prompted the derivation of simplified equations for calculating MP. To validate the agreement between a simplified calculation of MP (MPSimple) and the true MP calculated using the geometric method (MPRef). MPSimple and MPRef was calculated in mechanically ventilated preterm lambs (n = 71) and the agreement between both measureswas determined using intraclass correlation coefficients (ICC), linear regression, and Bland-Altman analysis. A strong linear relationship (adjusted R2 = 0.98), and excellent agreement (ICC = 0.99, 95% CI = 0.98-0.99) between MPSimple and MPRef was demonstrated. Bland-Altman analysis demonstrated a negligible positive bias (mean difference = 0.131 J/min·kg). The 95% limits of agreement were -0.06 to 0.32 J/min·kg. In a controlled setting, there was excellent agreement between MPSimple and gold-standard calculations. MPSimple should be validated and explored in preterm neonates to assess the cause-effect relationship with VILI and neonatal outcomes. Mechanical power (MP) unifies the individual components of ventilator induced lung injury (VILI) and providesan estimate of total energy transferred to the respiratory system during mechanical ventilation. As gold-standard calculations of mechanical power at the bedside are not feasible, alternative simplified equations have been proposed. In this study, MP calculated using a simplified equation had excellent agreement with true MP in mechanically ventilated preterm lambs. These results lay foundations to explore the role of MP in neonatal VILI and determine its relationship with short and long term respiratory outcomes.

Non-invasive high-frequency ventilation in newborn infants with respiratory distress.

Non-invasive high-frequency ventilation in newborn infants with respiratory distress.

Possibility of using non-invasive modes of respiratory support at the stages of interhospital transportation of newborns

Introduction. Respiratory support remains the most common procedure performed by neonatal transport team specialists. Non-invasive ventilation is a very common method of respiratory support for newborns, reducing the incidence of chronic lung disease. However, the safety and efficacy of this type of support during transportation remain controversial. The aim of the work is to determine the current state of the problem of non-invasive respiratory support in newborns in the initial medical organization, at the stage of pre-transport preparation and during transportation. Materials and methods. Literature sources were searched and selected in PubMed and eLibrary. The following queries were used for the search: nasal continuous positive airway pressure, non invasive ventilation, neonate, newborn, patient transportation, transport, transfer. Types of studies considered: retrospective observational studies, prospective studies (randomized, quasi-randomized, non-randomized), systematic reviews, meta-analyses, clinical protocols. Depth of search − 20 years. The total number of publications included in the review was 61, including 29 studies directly related to the use of noninvasive ventilation in interhospital neonatal transport. Results and discussion. Non-invasive respiratory support is one of the priority and actively used methods of therapy of respiratory disorders of various genesis in neonatology. Nasal CPAP is used both independently and in conjunction with various methods of surfactant administration, reducing the risk of a combined outcome “death or chronic lung disease”. It is recommended both as a method of starting respiratory support and as an intermediate option to increase the probability of successful extubation. There is limited experience with non-invasive respiratory support during interhospital transport of neonates. The available studies suggest that when patients are selected rationally and reasonable criteria are applied to administer nCPAP en route, this method of respiratory support is safe, effective, maintains the benefits of spontaneous breathing, and reduces the duration of intensive care. The small number and poor design quality of studies in this direction do not allow at this stage to form evidence-based recommendations. Conclusion. Medical evacuation of newborns from 1−2 level institutions to level 3 organization with nCPAP is safe and has a number of potential benefits. Existing recommendations are empirical, and there are exceptionally few studies evaluating the validity of such recommendations.

Comparison of conventional mechanical ventilation and high-frequency oscillatory ventilation in congenital diaphragmatic hernias: a systematic review and meta-analysis

Outcomes of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) in patients with congenital diaphragmatic hernia (CDH) were compared through a systematic review and meta-analysis. Outcome measures included mortality and incidence of chronic lung disease (CLD). Odds ratio (OR) and 95% confidence interval (95%CI) were evaluated. Subgroup analyses were performed according to the strategy for applying HFOV in CDH patients. Group A: CMV was initially applied in all CDH patients, and HFOV was applied in unstable patients. Group B: chronologically analyzed. (CMV and HFOV era) Group C: CMV or HFOV was used as the initial MV. Of the 2199 abstracts screened, 15 full-text articles were analyzed. Regarding mortality, 16.7% (365/2180) and 32.8% (456/1389) patients died in CMV and HFOV, respectively (OR, 2.53; 95%CI 2.12–3.01). Subgroup analyses showed significantly worse, better, and equivalent mortality for HFOV than that for CMV in group A, B, and C, respectively. CLD occurred in 32.4% (399/1230) and 49.3% (369/749) patients in CMV and HFOV, respectively (OR, 2.37; 95%CI 1.93–2.90). The evidence from the literature is poor. Mortality and the incidence of CLD appear worse after HFOV in children with CDH. Cautious interpretation is needed due to the heterogeneity of each study.

The association between sarcopenia and incident chronic lung disease in the general population: A longitudinal study based on CHARLS data

BackgroundData regarding the association of sarcopenia with chronic lung disease (CLD) has led to inconclusive results. The main goal of this research was to investigate the association between sarcopenia and CLD in middle-aged and elderly individuals in China. MethodsThe study sample consisted of 11,077 individuals without CLD at baseline chosen from the China Health and Retirement Longitudinal Study (CHARLS) data from 2015, followed up until 2018. Sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia (AWGS 2019) in 2019. Individuals were categorized into no-sarcopenia, possible-sarcopenia, and sarcopenia groups. The outcome of the study was considered to be incident CLD, which included chronic bronchitis, emphysema, pulmonary heart disease, and asthma. The association between sarcopenia and the risk of CLD was also examined by employing weighted Cox proportional hazard regression models. ResultsA total of 356 (3.20 %) participants developed CLD during the 3.6-year follow-up period. The cumulative incidence of CLD in the no-sarcopenia, possible-sarcopenia, and sarcopenia groups was 2.80 % (230/8222), 4.37 % (55/1260), and 4.45 % (71/1595), respectively. Individuals with possible sarcopenia {hazard ratio [HR] [95 % confidence interval (CI)]: 1.48 [1.04–2.09]} and sarcopenia [HR (95 % CI): 1.68 (1.12–2.51)] demonstrated a considerably high risk of developing CLD compared to individuals in the no-sarcopenia group. Moreover, individuals diagnosed with sarcopenia, as per the criteria established by the European Working Group on Sarcopenia in Older People (EWGSOP) 2018, were at considerably high risk for developing CLD compared to those in the no-sarcopenia group. ConclusionThis research involving adult Chinese individuals demonstrated a significant association between, possible sarcopenia and sarcopenia with an elevated risk of incident CLD, thereby emphasizing the importance of monitoring respiratory health in this population. Key pointsQuestion: Whether muscle mass and sarcopenia are associated with the development of chronic lung disease (CLD) in Asian middle-aged and elderly individuals.Findings: This longitudinal study encompassing 11,077 adults aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS) data with 3.6 years of follow-up revealed a positive association between sarcopenia at baseline and incidence of CLD.Meaning: The findings suggest that possible sarcopenia and sarcopenia are linked to the development of CLD. Consequently, middle-aged and elderly individuals with possible sarcopenia and sarcopenia can be considered vulnerable regarding the primary prevention strategies for CLD.

Chronic Lung Disease Following Neonatal Extracorporeal Membrane Oxygenation: A Single-Center Experience.

ObjectiveTo assess the incidence and severity of chronic lung disease (CLD) after neonatal extracorporeal membrane oxygenation (ECMO) and to identify factors associated with its development.MethodsA retrospective observational study in a neonatal ECMO center was conducted. All neonates who received support with ECMO in our institution between January 2019 and October 2021 were included and their pulmonary outcome was investigated.ResultsA total of 91 patients [60 with congenital diaphragmatic hernia (CDH), 26 with meconium aspiration syndrome, and 5 with other diagnoses] were included in this study. Sixty-eight (75%) neonates survived. Fifty-two (76%) ECMO survivors developed CLD. There was no statistical difference between patients with and without CLD with regard to gender or gestational age. Patients with CLD had lower birth weight, were younger at the initiation of ECMO, and required longer ECMO runs. Patients with CDH developed CLD more often than infants with other underlying diseases (94 vs. 60%). Seventeen ECMO survivors (25%) developed severe CLD.ConclusionThe incidence of CLD after neonatal ECMO is substantial. Risk factors for its development include CDH as an underlying condition, the necessity for early initiation of ECMO, and the need for ECMO over 7 days.

SM22α cell-specific HIF stabilization mitigates hyperoxia-induced neonatal lung injury.

Though survival rates for preterm infants are improving, the incidence of chronic lung disease of infancy, or bronchopulmonary dysplasia (BPD), remains high. Histologically, BPD is characterized by larger and fewer alveoli. Hypoxia-inducible factors (HIFs) may be protective in the context of hyperoxia-induced lung injury, but the cell-specific effects of HIF expression in neonatal lung injury remain unknown. Thus, we sought to determine whether HIF stabilization in SM22α-expressing cells can limit hyperoxia-induced neonatal lung injury. We generated SM22α-specific HIF-1α-stabilized mice (SM22α-PHD1/2-/- mice) by cross-breeding SM22α-promotor-driven Cre recombinase mice with prolyl hydroxylase PHD1flox/flox and PHD2flox/flox mice. Neonatal mice were randomized to 21% O2 (normoxia) or 80% O2 (hyperoxia) exposure for 14 days. For the hyperoxia recovery studies, neonatal mice were recovered from normoxia for an additional 10 wk. SM22α-specific HIF-1α stabilization mitigated hyperoxia-induced lung injury and preserved microvessel density compared with control mice for both neonates and adults. In SM22α-PHD1/2-/- mice, pulmonary artery endothelial cells (PAECs) were more proliferative and pulmonary arteries expressed more collagen IV compared with control mice, even under hyperoxic conditions. Angiopoietin-2 (Ang2) mRNA expression in pulmonary artery smooth muscle cells (PASMC) was greater in SM22α-PHD1/2-/- compared with control mice in both normoxia and hyperoxia. Pulmonary endothelial cells (PECs) cocultured with PASMC isolated from SM22α-PHD1/2-/- mice formed more tubes and branches with greater tube length compared with PEC cocultured with PASMC isolated from SM22α-PHD1/2+/+ mice. Addition of Ang2 recombinant protein further augmented tube formation for both PHD1/2+/+ and PHD1/2-/- PASMC. Cell-specific deletion of PHD1 and 2 selectively increases HIF-1α expression in SM22α-expressing cells and protects neonatal lung development despite prolonged hyperoxia exposure. HIF stabilization in SM22α-expressing cells preserved endothelial cell proliferation, microvascular density, increased angiopoietin-2 expression, and lung structure, suggesting a role for cell-specific HIF-1α stabilization to prevent neonatal lung injury.

Implementation of Bubble Continuous Positive Airway Pressure in the Delivery Room and NICU.

Implementation of Bubble Continuous Positive Airway Pressure in the Delivery Room and NICU.

Effect of Prophylactic Caffeine on Noninvasive Respiratory Support in Preterm Neonates Weighing 1250-2000 g: A Randomized Controlled Trial.

Caffeine is commonly used to prevent or treat apnea in preterm neonates. The present trial was designed to determine the effect of caffeine on reducing the time required for nasal continuous positive airway pressure (NCPAP) in neonates with respiratory distress syndrome (RDS). In a randomized controlled trial, a total of 90 neonates (birth weight between 1250 and 2000 g) who were clinically diagnosed with RDS were subjected to random assignment to one of the two groups of caffeine (n=45) or control (n=45). Infants in the caffeine group received 20 mg/kg caffeine as the initial dose, and then 10 mg/kg daily as the maintenance dose. Infants in the control group did not receive any placebo or similar drugs. The primary outcome was the duration time of respiratory support with NCPAP. The mean (SD) duration of NCPAP differed significantly and was shorter among the infants in the caffeine group than those assigned to the control group (41.53 (43.25) versus 78.48 (114.25) hours, respectively; mean difference: -36.95; 95%CI: -73.14, -0.76; P = 0.04). Apnea of prematurity (AOP) occurred in 2 (4.4%) newborns in the caffeine group and in 9 (20%) of the infants in the control condition [proportion difference: -15.6% (-29.8,-1.8); (P = 0.02)]. The incidence of intraventricular hemorrhage (IVH) was higher in the control group than in the caffeine group after one week (P = 0.03). The incidence of chronic lung disease (CLD), infection, necrotizing enterocolitis (NEC), seizure, vomiting and pneumothorax was similar in the two groups. The results suggest that preventative caffeine can reduce the duration of NCPAP support in neonates with RDS.

Increased incidence of chronic lung disease and respiratory sequelae in growth restricted versus appropriately grown preterms

Background: Fetal growth restriction (FGR) affects 5–10% term gestational age pregnancies. When accompanied by prematurity, FGR infants have significantly greater risk of perinatal morbidity and/or mortality compared to non-growth restricted preterm infants. Aim: Current study aimed to ascertain the incidence FGR among premature infants and its association with respiratory morbidity. Methods: Institution database for preterm infants of 23–31+6 weeks of gestation was accessed. FGR infants were compared with gestation/sex matched appropriately grown infants. Results: During the period 2016–2018, 973 infants between 23 and 31+6 weeks gestation were admitted amongst whom, 206 (27%) were FGR. Between 28 and 31+6 weeks gestation, approximately 1/3rd were FGR. Gestation and birth weight of the FGR and appropriately grown cohorts were 30.2±0.2 versus 30.1±0.2 weeks (p=0.8) and 1132±43 versus 1499±54 g (p&lt;0.0001), respectively. While antenatal steroids, surfactant, mechanical ventilation, sepsis, and ductal therapy were comparable, respiratory outcomes were significantly worse in the FGR cohort (duration of respiratory support: 37±10 vs. 23±5 days [p=0.016], home oxygen: 24 [11.6%] vs. 8 [3.8%]; [p=0.005] and chronic lung disease [CLD]: 53 [25.7%] vs. 28 [13.6%], [p=0.002], respectively). The odds ratio (95% confidence intervals) for developing CLD and for home oxygen when born FGR were 2.2 (1.3–3.6) and 3.2 (1.4–7.4), respectively. Conclusions: In spite of comparable postnatal variables, FGR infants had significantly greater respiratory morbidity.

VIP/PACAP signaling as an alternative target during hyperoxic exposure in preterm newborns.

The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways. In addition, the relaxation pathway of the vasoactive intestinal peptide (VIP) and/or pituitary adenylate cyclase activating peptide (PACAP) is another part of this system that plays an important role in the airway caliber. Peptide, which activates VIP cyclase and pituitary adenylate cyclase, has prolonged airway smooth muscle activity. It has long been known that VIP inhibits airway smooth muscle cell proliferation in a mouse model of asthma, but there is no data about its role in the regulation of airway and tracheal smooth muscle contractility during hyperoxic exposure of preterm newborns.

Symptomatic Response to Transcatheter Mitral Valve Repair According to Baseline Left Atrial Pressure

ABSTRACT Background: Prior studies have demonstrated that patients with low left atrial pressure (LAP) undergoing transcatheter mitral valve repair (TMVr) have a high incidence of chronic lung disease, and it is unknown whether they symptomatically benefit from repair. The goal of this study was to compare the degree of symptomatic improvement following TMVr in patients according to baseline LAP. Methods: We retrospectively reviewed patients who underwent TMVr with continuous LAP monitoring from May 1, 2014 to January 14, 2020. Patients were grouped according to mean LAP below (group 1) or above (group 2) the median (< or ≥ 18 mmHg, respectively) and symptoms were assessed by New York Heart Association (NYHA) functional class. One-year mortality and symptomatic improvement were compared between groups. Results: In 302 patients, age, sex, left ventricular ejection fraction and mitral regurgitation severity were similar between groups. Patients in group 2 had larger left atrial volume index (73.0 ± 32.2 cc/m2 vs. 67.0 ± 26.0 cc/m2, p = 0.008) and higher baseline mean NYHA class compared to group 1 (3.2 ± 0.5 vs. 3.0 ± 0.6, p = 0.003), but both had significant improvements in NYHA at 1-month (1.9 ± 0.9 vs. 1.8 ± 0.8, both p < 0.0001) and 12-months (1.9 ± 0.8 vs. 2.2 ± 0.9, both p < 0.0001). The predicted one-year survival free of severe class 3 or 4 heart failure symptoms was also similar (58.7% vs. 66.0%, p = 0.33) and there was no difference in estimated one-year survival between groups (77.5% vs. 72.7%, p = 0.89). Conclusion: Patients with severe mitral regurgitation experience a similar symptomatic improvement following TMVr regardless of baseline LAP.

HIV-1 Productively Infects and Integrates in Bronchial Epithelial Cells.

BackgroundThe role of lung epithelial cells in HIV-1-related lung comorbidities remains unclear, and the major hurdle in curing HIV is the persistence of latent HIV reservoirs in people living with HIV (PLWH). The advent of combined antiretroviral therapy has considerably increased the life span; however, the incidence of chronic lung diseases is significantly higher among PLWH. Lung epithelial cells orchestrate the respiratory immune responses and whether these cells are productively infected by HIV-1 is debatable.MethodsNormal human bronchial epithelial cells (NHBEs) grown on air–liquid interface were infected with X4-tropic HIV-1LAV and examined for latency using latency-reversing agents (LRAs). The role of CD4 and CXCR4 HIV coreceptors in NHBEs were tested, and DNA sequencing analysis was used to analyze the genomic integration of HIV proviral genes, Alu-HIVgag-pol, HIV-nef, and HIV-LTR. Lung epithelial sections from HIV-infected humans and SHIV-infected macaques were analyzed by FISH for HIV-gag-pol RNA and epithelial cell-specific immunostaining.Results and DiscussionNHBEs express CD4 and CXCR4 at higher levels than A549 cells. NHBEs are infected with HIV-1 basolaterally, but not apically, by X4-tropic HIV-1LAV in a CXCR4/CD4-dependent manner leading to HIV-p24 antigen production; however, NHBEs are induced to express CCR5 by IL-13 treatment. In the presence of cART, HIV-1 induces latency and integration of HIV provirus in the cellular DNA, which is rescued by the LRAs (endotoxin/vorinostat). Furthermore, lung epithelial cells from HIV-infected humans and SHIV-infected macaques contain HIV-specific RNA transcripts. Thus, lung epithelial cells are targeted by HIV-1 and could serve as potential HIV reservoirs that may contribute to the respiratory comorbidities in PLWH.

Ventilatory management in extremely low birth weight infants

The improvement in survival in premature infants associated with the evolution of mechanical ventilation has been accompanied by an increase in ventilator induced lung injury. High frequency ventilation has been shown to reduce the incidence of ventilator induced lung injury and hence chronic lung disease in the very low birth weight infant. The evolution in understanding how to best use high frequency ventilation in this population has prompted us to ask whether similar strategies to optimize lung volumes on conventional mechanical ventilation can minimize chronic lung disease in the neonate. We retrospectively reviewed the medical charts of 51 extremely low birth weight infants born in Kingston, Ontario in two epochs, 1990 to 1991 and 1999 to 2000, for ventilatory strategy and outcome. From our review, it is clear that surfactant therapy rapidly changes lung mechanics by improving pulmonary compliance and that lung damage may result if there are not changes in the ventilatory management to reflect the altered compliance. Early ventilation strategies during the apparently stable "honeymoon period" in a patient with respiratory distress syndrome (RDS) has significant implications on long term morbidity. In the era prior to the use of surfactant, 30% of infants died and 40% developed chronic lung disease (CLD). Immediately following the use of surfactant , mortality was reduced to 18%, however, the incidence of CLD increased to 78%. In the most recent era, following 10 years of experience with surfactant and mechanical ventilation, morbidity was 17% and CLD 21%. This study demonstrates that a particularly crucial time is in the immediate period following surfactant administration. The use of lower peak inspiratory pressure (PIP) and mean airway pressure (MAP) over the first 24 hours and an increase in the use of synchronous intermittent mandatory ventilation (SIMV) was associated with an improved outcome. The challenge remaining is to determine how to best utilize a conventional mode of ventilation to best optimize lung volume and protect the immature lung.

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants\u2014\u201cThe OPTTIMMAL-Trial\u201d\u2014Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial

BackgroundNasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants.MethodsIn this randomized multicenter trial, 216 preterm infants born at 26 + 0–29 + 6 gestational weeks will be allocated to receive a higher (6–8 cmH2O) or a lower (3–5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart).DiscussionBased on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4–8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants.Trial registrationdrks.de DRKS00019940. Registered on March 13, 2020

Ventilator-associated pneumonia in neonates: the role of point of care lung ultrasound

No consensus exists regarding the definition of ventilator-associated pneumonia (VAP) in neonates and reliability of chest X-ray (CXR) is low. Lung ultrasound (LU) is a potential alternative diagnostic tool. The aim was to define characteristics of VAP in our patient population and propose a multiparameter score, incorporating LU, for VAP diagnosis. Between March 25, 2018, and May 25, 2019, infants with VAP were identified. Clinical, laboratory and microbiology data were collected. CXRs and LU scans were reviewed. A multiparameter VAP score, including LU, was calculated on Day 1 and Day 3 for infants with VAP and for a control group and compared with CXR. VAP incidence was 10.47 episodes/1000 ventilator days. LU and CXR were available for 31 episodes in 21 infants with VAP, and for six episodes in five patients without VAP. On Day 1, a VAP score of > 4, and on Day 3 a score of > 5 showed sensitivity of 0.94, and area under the curve of 0.91 and 0.97, respectively. AUC for clinical information only was 0.88 and for clinical and CXR 0.85.Conclusion: The multiparameter VAP score including LU could be useful in diagnosing VAP in neonates with underlying lung pathology.What is Known:• Ventilator associated pneumonia (VAP) is common in infants on the neonatal unit and is associated with increased use of antibiotics, prolonged ventilation and higher incidence of chronic lung disease.• Commonly used definitions of VAP are difficult to apply in neonates and interpretation of chest X-ray is challenging with poor inter-rater agreement in patients with underlying chronic lung disease.What is New:• The multiparameter VAP score combining clinical, microbiology and lung ultrasound (LU) data is predictive for VAP diagnosis in preterm infants with chronic lung disease.• LU findings of VAP in neonates showed high inter-rater agreement and included consolidated lung areas, dynamic bronchograms and pleural effusion.

Effect of Fluid Bolus on Clinical Outcomes in Very Low Birth Weight Infants.

Administration of fluid bolus in very low birth weight (VLBW) infants is a common practice in the NICU, but one without clear evidence demonstrating benefits in clinical outcomes. On the contrary, recent observational studies have suggested a potential detrimental effect of empiric fluid bolus in preterm infants, especially in the absence of clear indications. The aim of this study was to assess the impact of fluid bolus on various clinical outcomes in VLBW infants. Retrospective cohort study of VLBW infants born at ≤34 weeks' gestation and/or ≤1500-g birth weight at a single level III NICU from January 1, 2008, to December 31, 2013, and who received at least one fluid bolus within the first 48 hours of life. Outcomes studied were in-hospital mortality, need for home oxygen, incidence of chronic lung disease (CLD), prevalence of patent ductus arteriosus (PDA), and intraventricular hemorrhage (IVH). Of 516 infants, 112 (21.7%) received a fluid bolus within the first 48 hours of life for various indications. Propensity models suggested no statistical difference for CLD or mortality, but exposed infants had an increased incidence of home on oxygen (p = 0.018), PDA prevalence (p = 0.008), and IVH prevalence (p = 0.038). Fluid bolus in the first 48 hours of life may be associated with increased incidence of need for home oxygen and higher prevalence of PDA and IVH in VLBW infants. Future studies are needed to address these important adverse outcomes.

SUN-296 Acromegaly Significantly Impacts Employees’ Health Benefit Costs and Increases Work Absenteeism

Background: Acromegaly (ACRO) is a rare, chronic disorder of growth hormone hypersecretion associated with increased morbidity that can affect work productivity. Data on ACRO employees’ health costs and work absenteeism are limited. Aims: To assess the impact of ACRO on employees’ health benefit costs and absenteeism. Methods: A US employee database of prescription (Rx) drug, medical claims, and absenteeism (payment and time) from Jan 2010 to Apr 2019 was analyzed. Employees with the diagnosis (Dx) of ACRO were identified based on claims with ICD-9/-10 codes 253.0x/E22.0. A 12 month study period followed each employee’s first ACRO Dx in the database (the index date). ACRO patients in the study had ≥ 2 ACRO Dxs > 30 days apart, or 1 ACRO Dx plus either a pituitary adenoma Dx or a pituitary surgery or radiosurgery claim during the study period. Controls were matched to each ACRO employee on demographic, job-related variables, region, and Charlson comorbidity index (CCI) score. Costs were adjusted using the general Consumer Price Index (CPI), medical CPI, and Rx cost CPI. Outcomes included direct costs (medical and Rx), indirect costs (absence payments by benefit type), and lost time (absences by benefit type). Outcomes were analyzed using two-part regression models (logistic followed by generalized linear) for each outcome, controlling for demographic and job-related variables, region, and CCI scores. Data are shown as likelihood or mean ± standard error. Findings are significant at P < 0.05. Results: Participants were 18–65 yr old with continuous eligibility for medical and Rx benefits for the study period. Forty seven ACRO patients and 940 controls were identified. ACRO employees were similar to the controls in most demographic (age, gender, race) and job-related variables (tenure, full-/part-time status, exempt status, salary), but had a higher CCI (0.60 ± 0.15 vs 0.30 ± 0.03; P = 0.029) and a higher incidence of chronic lung disease (31.9 vs 17.4%; P = 0.012), hyperlipidemia (27.7 vs 16.0%, P = 0.035), arthritis (19.1 vs 3.7%), diabetes (31.9 vs 8.3%), hypertension (40.4 vs 13.6%), and thyroid disease (31.9 vs 8.9%) (P < 0.0001). Patients with ACRO were 64.3% more likely to have undergone an MRI (P < 0.0001).Total indirect costs (including sick leave and disability) were higher for ACRO patients ($10,530 vs $1,157; P < 0.05) with both short-term and long-term disability comprising 96% of the difference. Compared with employees without ACRO, employees with ACRO used more short-term disability (10.9 vs 0.9 days; P = 0.0076) and had more total days absent from work (12.7 vs 3.3 days; P < 0.05). Conclusions: Our findings indicate that ACRO has far-reaching implications on direct and indirect employee health benefit costs and increased work absenteeism. Awareness by employers of ACRO-induced increased absenteeism is important to tailor working conditions and to prevent unrealistic work expectations.

Reduced 25(OH) Vitamin D Association with Lower Alpha-1-Antitrypsin Blood Levels in Type 2 Diabetic Patients

Introduction: Reduced circulating levels of 25(OH)VD are associated with an increased incidence of chronic lung diseases. Alpha-1-antitrypsin (AAT) is needed to maintain healthy lung function.Objective: This study examined the hypothesis that circulating levels of AAT are lower in adult type 2 diabetic patients and that a positive association exists between circulating AAT levels and 25(OH)VD levels in these patients.Methods: Fasting blood was obtained after written informed consent from type 2 diabetic patients (n = 80) and normal siblings or volunteers (n = 22) attending clinics at LSUHSC according to the protocol approved by the Institutional Review Board for Human studies. Plasma AAT and 25(OH)VD levels were determined using ELISA kits. HbA1c levels and chemistry profiles were analyzed at the clinical laboratory of LSUHSC hospital.Results: ATT and 25(OH)VD levels were significantly lower in type 2 diabetic patients compared with those of age-matched healthy controls. There was a significant positive correlation between 25(OH)VD and ATT deficiency. AAT levels showed significant positive correlation with HDL cholesterol levels in type 2 diabetic patients. There was no correlation between AAT levels and those of HbA1c or with the duration of diabetes of T2D patients.Conclusions: These results suggest that 25(OH)VD deficiency may predispose type 2 diabetic patients to AAT deficiency. Whether reduced levels of circulating AAT indeed contribute to the increased risk for lung dysfunction in subjects with type 2 diabetes needs further investigation.