Asthma prevalence among US 9th-12th graders who report past 30-day cannabis use in 2019.

INTRODUCTION: Little is known about the relationship between cannabis use and asthma among youth in the US. The aims of this study were to estimate prevalence of asthma among youth who reported any cannabis use in the past 30 days, relative to those who did not, and to investigate the relationship between frequency of cannabis use and prevalence of asthma, adjusting for demographic characteristics and cigarette use. METHODS: Data were drawn from the 2019 Youth Risk Behavior Surveillance System (YRBSS), a CDC national high school survey, which collects data from students in grades 9-12 across the US bi-annually. Logistic regression was used to examine the prevalence of asthma among youth who reported any past 30-day cannabis use, relative to no use, and by frequency of cannabis use, adjusting for demographic characteristics and cigarette use. RESULTS: Asthma was more common among youth who reported any cannabis use, relative to youth who reported no use (29.07% vs. 23.62%; AOR = 1.25 (1.20, 1.30)). Asthma was greater among youth who reported more frequent cannabis use; asthma was highest among youth who reported having used cannabis "40 or more times" in the month (31.38%; AOR = 1.35 (1.25, 1.45)) CONCLUSION: Asthma is more common among youth who use cannabis, relative to those who do not, and the prevalence of asthma increases with frequency of use among 9th-12th graders in the US. More public health and clinical research is needed quickly to produce scientific data that can inform clinical guidelines and public health policy, as well as parents and youth, on the potential relationship between cannabis use and respiratory health among youth.

Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.

BACKGROUND: Most genetic studies of asthma and allergy have focused on common variation in individuals primarily of European ancestry. Studying the role of rare variation in quantitative phenotypes and in asthma phenotypes in populations of diverse ancestries can provide additional, important insights into the development of these traits. OBJECTIVE: We sought to examine the contribution of rare variants to different asthma- or allergy-associated quantitative traits in children with diverse ancestries and explore their role in asthma phenotypes. METHODS: We examined whole-genome sequencing data from children participants in longitudinal studies of asthma (n = 1035; parent-identified as 67% Black and 25% Hispanic) to identify rare variants (minor allele frequency < 0.01). We assigned variants to genes and tested for associations using an omnibus variant-set test between each of 24,902 genes and 8 asthma-associated quantitative traits. On combining our results with external data on predicted gene expression in humans and mouse knockout studies, we identified 3 candidate genes. A burden of rare variants in each gene and in a combined 3-gene score was tested for its associations with clinical phenotypes of asthma. Finally, published single-cell gene expression data in lower airway mucosal cells after allergen challenge were used to assess transcriptional responses to allergen. RESULTS: Rare variants in USF1 were significantly associated with blood neutrophil count (P = 2.18 × 10-7); rare variants in TNFRSF21 with total IgE (P = 6.47 × 10-6) and PIK3R6 with eosinophil count (P = 4.10 × 10-5) reached suggestive significance. These 3 findings were supported by independent data from human and mouse studies. A burden of rare variants in TNFRSF21 and in a 3-gene score was associated with allergy-related phenotypes in cohorts of children with mild and severe asthma. Furthermore, TNFRSF21 was significantly upregulated in bronchial basal epithelial cells from adults with allergic asthma but not in adults with allergies (but not asthma) after allergen challenge. CONCLUSIONS: We report novel associations between rare variants in genes and allergic and inflammatory phenotypes in children with diverse ancestries, highlighting TNFRSF21 as contributing to the development of allergic asthma.

Cannabis use and the prevalence of current asthma among adolescents and adults in the United States.

OBJECTIVES: Cannabis use has increased among adolescents and adults in the United States (US) in recent years. Few data are available on the prevalence of asthma by frequency of cannabis use. This study aimed to estimate the prevalence of asthma by frequency of past 30-day cannabis use among US individuals. METHODS: Data were drawn from the 2020 National Survey on Drug Use and Health (NSDUH), a nationally representative, annual cross-sectional survey of US individuals aged 12 and older in the United States (N = 32,893). Logistic regression models were used to examine the relationship between frequency of any cannabis and/or blunt (i.e., cannabis smoked in a hollowed-out cigar) use in the past 30 days and current asthma, adjusting for demographics and current cigarette smoking. RESULTS: Current asthma was more common among US individuals who reported cannabis use in the past 30-days, relative to those who did not (9.8% vs. 7.4%, p < 0.0001). The odds of asthma was significantly greater among individuals reporting cannabis use 20-30 days/month (Adjusted Odds Ratio [AOR] = 1.67, 95% CI:1.21, 2.31), blunt use 6-15 and 20-30 days/month (AOR = 1.9, 95% CI:1.1, 3.2; AOR = 2.2, 95% CI:1.4, 3.6), respectively, than among those without. A positive linear relationship was observed between frequency of a) cannabis use (p < 0.0001) and b) blunt use (p < 0.0001) and current asthma prevalence. CONCLUSIONS: Findings suggest a dose-response relationship between frequency of current cannabis use and the prevalence of current asthma in the US individuals.

Risk Factors for Pneumothorax and Its Association with Ventilation in Neonates.

OBJECTIVE: The mode of ventilation that is implicated in pneumothorax is the one at the time of its diagnosis. Although there is evidence that air leak starts many hours before it is clinically evident, there are no prior studies that have investigated the association of pneumothorax with the mode of ventilation few hours before rather than at the time of its diagnosis. STUDY DESIGN: A retrospective case-control study was conducted in the neonatal intensive care unit (NICU) between 2006 and 2016 where cases of neonates with pneumothorax were compared with gestational age-matched control neonates without pneumothorax. Respiratory support associated with pneumothorax was classified as the mode of ventilation 6 hours before the clinical diagnosis of pneumothorax. We investigated the factors that were different between cases and controls, and between cases of pneumothorax on bubble continuous positive airway pressure (bCPAP) and invasive mechanical ventilation (IMV). RESULT: Of the 8,029 neonates admitted in the NICU during the study period, 223 (2.8%) developed pneumothorax. Among these, 127 occurred among 2,980 (4.3%) neonates on bCPAP, 38 among 809 (4.7%) neonates on IMV, and the remaining 58 among 4,240 (1.3%) neonates on room air. Those with pneumothorax were more likely to be male, have higher body weight, require respiratory support and surfactant administration, and have bronchopulmonary dysplasia (BPD). Among those who developed pneumothorax, there were differences in the gestational age, gender, and use of antenatal steroids between those who were on bCPAP as compared to those on IMV. IMV was associated with increased odds of pneumothorax as compared to those on bCPAP in a multivariable regression analysis. Cases on IMV had higher incidence of intraventricular hemorrhage, retinopathy of prematurity, BPD, and necrotizing enterocolitis, as well as longer length of stay as compared to those on bCPAP. CONCLUSION: Neonates who require any respiratory support have higher incidence of pneumothorax. Among those on respiratory support, those on IMV had higher odds of pneumothorax and worse clinical outcomes as compared to those on bCPAP. KEY POINTS: · The process of air leak leading to pneumothorax in majority of neonates starts much before it is clinically diagnosed.. · It is possible to detect the air leak early in the process by subtle changes in the signs, symptoms and changes in lung function.. · True association of the ventilation associated with pneumothorax is not at the time of diagnosis of pneumothorax but few hours before it is diagnosed.. · There is higher incidence of pneumothorax in neonates on any respiratory support.. · There is significantly higher incidence of pneumothorax among neonates on invasive ventilations as compared to noninvasive ventilation after correction for all other clinical factors..

Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings.

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; ßz = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV1-associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV1 risk alleles (p = 1.3x10-5; ß = 0.12, 95% CI = 0.06-0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure.

Crosstalk between CD4+ T Cells and Airway Smooth Muscle in Pediatric Obesity-related Asthma.

Rationale: Pediatric obesity-related asthma is a nonatopic asthma phenotype with high disease burden and few effective therapies. RhoGTPase upregulation in peripheral blood T helper (Th) cells is associated with the phenotype, but the mechanisms that underlie this association are not known. Objectives: To investigate the mechanisms by which upregulation of CDC42 (Cell Division Cycle 42), a RhoGTPase, in Th cells is associated with airway smooth muscle (ASM) biology. Methods: Chemotaxis of obese asthma and healthy-weight asthma Th cells, and their adhesion to obese and healthy-weight nonasthmatic ASM, was investigated. Transcriptomics and proteomics were used to determine the differential effect of obese and healthy-weight asthma Th cell adhesion to obese or healthy-weight ASM biology. Measurements and Main Results: Chemotaxis of obese asthma Th cells with CDC42 upregulation was resistant to CDC42 inhibition. Obese asthma Th cells were more adherent to obese ASM compared with healthy-weight asthma Th cells to healthy-weight ASM. Compared with coculture with healthy-weight ASM, obese asthma Th cell coculture with obese ASM was positively enriched for genes and proteins involved in actin cytoskeleton organization, transmembrane receptor protein kinase signaling, and cell mitosis, and negatively enriched for extracellular matrix organization. Targeted gene evaluation revealed upregulation of IFNG, TNF (tumor necrosis factor), and Cluster of Differentiation 247 (CD247) among Th cell genes, and of Ak strain transforming (AKT), Ras homolog family member A (RHOA), and CD38, with downregulation of PRKCA (Protein kinase C-alpha), among smooth muscle genes. Conclusions: Obese asthma Th cells have uninhibited chemotaxis and are more adherent to obese ASM, which is associated with upregulation of genes and proteins associated with smooth muscle proliferation and reciprocal nonatopic Th cell activation.

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.

BACKGROUND: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. METHODS: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. RESULTS: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. CONCLUSIONS: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases.

The airway epithelium during infancy and childhood: A complex multicellular immune barrier. Basic review for clinicians.

The airway epithelium is a complex multicellular layer that extends from the nasopharynx to the small airways. It functions as an immune respiratory barrier during early life that develops, matures, and regenerates to adapt to the changes in the environment. While airway epithelial abnormalities have been identified in several clinical disorders, there is increasing interest in understanding its basic regulation and structure in humans. Indeed, recent advances in technology (e.g. single-cell analysis and new human airway epithelial cell models) have allowed us to identify additional cellular subtypes and functions that overall have greatly improved our understanding of the airway epithelium during health and disease. In this review we summarize key features of the airway epithelium including: 1) multilayer structure and cell heterogeneity; 2) adaptability to different environmental and developmental stimuli; 3) innate recognition; and 4) orchestration of immune responses. We discuss these features with a translational and clinical prospective focusing on the development of human respiratory immunity, particularly during early life.

Association between asthma and dental caries in US (United States) adult population.

OBJECTIVE: To investigate the associations of asthma with dental-caries-experience (DFT: decayed and filled teeth) and untreated-dental-caries (DT: decayed teeth) in the US adult population. METHODS: Data from the National Health and Nutritional Examination Survey, 2009-2014 were analyzed. Study-participants were classified into current, former and never asthmatics based on their asthma-status. Former-asthmatics were excluded. Both the outcomes, dental-caries-experience and untreated-dental-caries were dichotomized as being either present or absent, and were also categorized into tertiles based on their distributions in our study-sample. Logistic regression analyses were performed to determine the associations of asthma with dichotomized outcomes. The generalized logit model was applied for multilevel categorical outcomes. Multivariable models were developed to control for common demographic, clinical, and lifestyle factors. RESULTS: Total study-participants were 13,135, representing 175.26 million US adults. In the adjusted models, current-asthmatics, when compared to the reference group of never-asthmatics, were more likely to have dental-caries-experience (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.13-1.66) and untreated-dental-caries (OR, 1.38; 95% CI, 1.10-1.73) in ≥1 tooth. Asthma was associated with all three categories of dental-caries-experience in our study-sample. We observed a positive gradient in the OR with an increasing extent of untreated-dental-caries. Relative to never-asthmatics, asthma doubled the odds of having untreated dental caries in the subgroup of current-smokers. CONCLUSION: Current-asthmatic adults had higher odds of dental-caries-experience and untreated-dental-caries as compared to never-asthmatic adults in the US. Based on the observations from this study, interprofessional collaboration should be recommended to institute caries control and health promotion in current-asthmatic adult population.

Airway Inflammation and Lung Function in Sickle Cell Disease.

Rationale: Asthma is a common comorbid condition in sickle cell disease (SCD). However, obstructive lung disease is prevalent in SCD, independent of a diagnosis of asthma. It is speculated that the heightened state of inflammation in SCD, involving pathways distinct from allergic asthma, may underlie the SCD-specific obstructive disease. Objective: The objective of the study was to compare airway and systemic inflammatory markers between SCD patients with pulmonary manifestations and patients with allergic asthma, and correlate the discriminating inflammatory markers with clinical measures of pulmonary disease. Materials and Methods: In a pilot translational study conducted at the Children's Hospital at Montefiore, 15 patients with SCD, and history of asthma, airway obstruction, or airway hyper-reactivity, and 15 control patients with allergic asthma 6-21 years of age were recruited. Inflammatory markers, including peripheral blood T helper cell subsets, serum and exhaled breath condensate (EBC) cytokines and chemokines of the Th-1/Th-17, Th-2, and monocytic pathways, and serum cysteinyl leukotrienes B4 (LTB4), were quantified, compared between the study groups, and correlated with atopic sensitization, pulmonary function tests, and markers of hemolysis. Results: White blood cells (P < 0.05) and monocytes (P < 0.001) were elevated in the SCD group, while atopic characteristics were higher in the control asthma group. Tumor necrosis factor-alpha (P < 0.01), interferon gamma inducible protein (IP)-10 (P < 0.05), and interleukin-4 (P < 0.01) in serum and monocyte chemotactic protein (MCP)-1 in EBC were higher in the SCD group (P ≤ 0.05). Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in patients with SCD inversely correlated with serum IP-10 and LTB4 levels. Conclusions: Compared with atopic asthmatic patients, inflammatory markers involving Th-1, Th-2, and monocytic pathways were higher in the SCD group, among which Th-1 measures correlated with pulmonary function deficits.

Trends in epidemiology and outcomes of respiratory distress syndrome in the United States.

BACKGROUND: The management practices of Respiratory Distress Syndrome (RDS) in the newborn have changed over time. We examine the trends in the epidemiology, resource utilization, and outcomes (mortality and bronchopulmonary dysplasia [BPD]) of RDS in preterm neonates ≤34 weeks gestational age (GA) in the United States. METHODS: In this retrospective serial cross-sectional study, we used ICD-9 codes to classify preterm infants GA ≤34 weeks between 2003 and 2014 from the National Inpatient Sample as having RDS or not. Trends in the prevalence of infants defined as RDS by ICD-9 code (ICD9-RDS), length of stay, BPD, and mortality were analyzed using Cochran-Armitage and Jonckheere-Terpstra tests and multivariable logistic regression. RESULTS: Of 1 526 186 preterm live births with GA ≤34 weeks, 554 409 had ICD9-RDS (260 cases per 1000 live births) with the prevalence increasing from 170 to 361 (Ptrend < 0.001) and associated decrease in all-cause mortality (7.6% to 6.1%; Ptrend < 0.001) from 2003 to 2014. Increased utilization of non-invasive mechanical ventilation (NIMV) (69.5% to 74.3%; Ptrend < 0.001) was associated with decreased invasive mechanical ventilation (IMV) use >96 h (60.4 to 56.6%; Ptrend < 0.001). Exclusive NIMV use increased from 16.8% to 29.1% (Ptrend < 0.0001). BPD incidence decreased from 14% to 12.5% (Ptrend < 0.001). LOS increased from 32 days to 38 days (Ptrend < 0.001) and cost increased from $49,521 to $55,394 (Ptrend < 0.001). CONCLUSION: From 2003 to 2014, the assigned ICD9-RDS diagnosis, and utilization of NIMV increased and mortality among infants assigned the ICD9-RDS diagnosis decreased. With higher survival, hospital cost increased incrementally, indicating the importance of ongoing analysis of appropriate reimbursement for the care provided at tertiary centers for preterm infants.

Association of systemic inflammation, adiposity, and metabolic dysregulation with asthma burden among Hispanic adults.

RATIONALE: Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood. OBJECTIVE: To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics. METHODS: Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV1, and FVC) while adjusting for demographic and clinical covariates. RESULTS: Of the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV1 and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (ß -138 ml (95%CI -27 ml, -249 ml)) and FEV1 (ß -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (ß -111 ml (-22 ml, -201 ml) and FEV1 (ß -100 ml (-12 ml, -188 ml)). Results were similar in men and women. CONCLUSIONS: Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

Drop in platelet counts in extremely preterm neonates and its association with clinical outcomes.

BACKGROUND: Thrombocytopenia is a common finding among preterm neonates and has been associated with mortality and morbidities. In recent studies in adults, the drop in platelet numbers has been shown to be a predictor of clinical outcomes. Although drop in the platelet counts with or without thrombocytopenia has also been observed in neonates, its association with mortality and morbidity has not been investigated in the preterm population. OBJECTIVE: To study the prevalence of a ≥ 30% drop in platelet counts in preterm neonates and its association with clinical outcomes. METHODS: Retrospective chart review was done on neonates born at gestational age ≤ 28 weeks and survived for ≥ 7 days. As with the adult studies, a ≥30% drop in platelet numbers were identified at 7 days and 28 days of age and their association with mortality, morbidities, and length of stay (LOS) was investigated. RESULTS: Two hundred eighty-six patients included in the study had a mean gestational age of 26.3 weeks (range, 23 to 28 wk) and birth weight of 899 ± 215 grams. A ≥ 30% drop in platelet counts occurred in 68.1% neonates. It was significantly associated with mortality (P < 0.001), morbidities at both 7 and 28 days [intraventricular bleed (P < 0.01)], retinopathy of prematurity (P<0.01), necrotizing enterocolitis (P < 0.05) and gram-positive infections (P < 0.05), and LOS (P < 0.01). Only those neonates who had a ≥ 30% drop in the platelet numbers developed gram negative and fungal infections. These associations of clinical morbidities and mortality with a ≥ 30% drop in platelet counts were independent of thrombocytopenia. CONCLUSIONS: A ≥ 30% drop in platelet counts is associated with increased mortality, morbidities, and LOS in preterm neonates, independent of thrombocytopenia. As the drop occurs before the onset of clinical morbidity, one potential application is its use to predict the onset of morbidities including necrotizing enterocolitis, intraventricular hemorrhage, and retinopathy of prematurity, and a prolonged LOS and mortality.

NCI classification of thrombocytopenia in extremely preterm neonates and its association with mortality and morbidity.

BACKGROUND: Thrombocytopenia (TP) is a common finding among preterm neonates and has been associated with mortality and morbidities. Yet, there is no consistent classification for neonatal TP. TP in adults has recently been graded by the National Cancer Institute (NCI) Common Toxicity Criteria and has been shown to predict clinical outcomes. OBJECTIVE: To use the NCI classification for TP in preterm neonates and elucidate its association with clinical outcomes. METHODS: Retrospective chart review was done on neonates born at gestational age (GA) ≤28 weeks and survived for ≥7 days. TP was classified as per NCI guidelines at 7 days and 28 days of age and their association with mortality, major morbidities and hospital length of stay (LOS) were investigated. RESULTS: A total of 286 patients were included in the study with a mean GA of 26.3±1.5 weeks and birth weight of 899±215 g. NCI TP grades at 7 days were significantly (P<0.001) associated with mortality, LOS, intraventricular hemorrhage and Gram negative infections. In addition to these outcomes, necrotizing enterocolitis, Gram positive and fungal infections were also significantly associated with NCI TP grades at 28 days. CONCLUSIONS: Classification of TP using the NCI criteria in extreme preterm neonates is clinically applicable. This grading system of platelet counts is significantly associated with mortality, morbidity and LOS in preterm neonates.

Inhaled nitric oxide and gentle ventilation in the treatment of pulmonary hypertension of the newborn--a single-center, 5-year experience.

OBJECTIVE: To evaluate the effect of inhaled nitric oxide (INO) in pulmonary hypertension of the newborn (PH) in a single center over 5 years using gentle ventilation (GV), without hyperventilation or induced alkalosis. METHODS: Data from 229 consecutive infants with PH of varied etiology treated with INO and GV, and from 67 infants with meconium aspiration syndrome (MAS) and primary PH (PPHN) treated with GV alone were reviewed over a 5-year period (86% outborn). INO was initiated at 25 ppm when PH and severe hypoxemia persisted despite maximal optimal ventilation. Hyperventilation or systemic alkalosis were not attempted. RESULTS: Mean duration of ventilation was 9.9 +/- 14 days (median 6.5 days). Average mean airway pressure (MAP) dropped from 17.7 +/- 4.3 cm H(2)O at the referral hospital to 13.2 +/- 2.5 cm H(2)O (p < 0.001) following admission to our unit using conventional settings and GV, before starting INO. Mean oxygenation index (OI) dropped from 46.8 +/- 24.5 to 22.7 +/- 21.4 within 24 hours of INO therapy (p < 0.001). Infants with higher baseline pH and lower baseline OI responded better to INO (p < 0.02). Overall survival was 72%. Patients with MAS and PPHN had the best response, 92% survived and there was a 46% reduction in need for extracorporeal membrane oxygenation (ECMO) compared to historical pre-INO period controls (23.9% vs. 12.8%, p < 0.01). In the infants treated with GV alone, the MAP dropped from 17.2 +/- 4.3 cm H2O at the referral hospital to 12.6+/-2.4 after GV was started in our unit. CONCLUSIONS: We conclude that INO is an effective and well-tolerated therapy for PH in infants receiving GV.