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Nitric oxide (NO) is one of the most studied molecules in medical science. The role of NO as an endogenous regulator of inflammation, as an antibacterial agent and as an endogenous gasotransmitter is well established. Even so, despite a plethora of excellent wound healing data, hard-to-heal (chronic) wounds are of epidemic proportions, and still growing in number. However, yet to be established and sorely needed is the identification of a single, continuous NO mechanism of action (MoA), where phase-to-phase variance in the complex sequence of cellular and molecular wound healing may elucidate the potential for placing hard-to-heal wounds on positive healing trajectories. Hence, the objectives of this review were to: identify salient MoAs for NO in each phase of skin wound healing; and to select and validate a single MoA that is both ubiquitous and continuous in NO across acute and hard-to-heal wound sequences, and which potentiates the ability to supplementally motivate and guide the recovery of a hard-to-heal wound onto a positive healing trajectory. The search began by selecting a detailed, multipart wound healing model. Next, as guided by the literature, was the identification of salient NO functionalities for each model segment. These modes of action were then be used to identify and validate a single NO MoA that is continuous across the healing spectrum. Finally, by using the principle of 'super position' of two continuous functions, this acute healing NO MoA solution was compared to a similar solution set describing a hard-to-heal or chronic wound. As both solution sets are continuous in a NO function, the resultant 'overlay' then helped to identify and guide the use of a NO MoA capable of placing any hard-to-heal wound on a positive healing trajectory. [ABSTRACT FROM AUTHOR]

Background: Efficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded. Results: All pigs presented airway closure (AOP > 0.5cmH2O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 ± 8 to 42 ± 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13–19] to 9%[IQR:4–12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16–30] to 23%[IQR:14–27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases. Conclusions: In an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation. [ABSTRACT FROM AUTHOR]

Objectives: Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. Methodology: In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). Results: The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive–inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). Conclusion: Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants. [ABSTRACT FROM AUTHOR]

Bacterial infections impede the wound healing process and can trigger local or systemic inflammatory responses. Therefore, there is an urgent need to develop a dressing with antimicrobial and anti-inflammatory properties to promote the healing of infected wounds. In this study, BA/COs/NO-PL/AL hydrogels were obtained by adding brevilin A (BA) camellia oil (CO) submicron emulsion and nitric oxide (NO) to hydrogels consisting of sodium alginate (AL) and Pluronic F127 (PL). The hydrogels were characterized through dynamic viscosity analysis, differential scanning calorimetry, and rheology. They were evaluated through anti-inflammatory, antimicrobial, and wound healing property analyses. The results showed that BA/COs/NO-PL/AL hydrogels were thermo-responsive and had good ex vivo and in vivo anti-inflammatory activity, and they also exhibited strong antimicrobial activity against methicillin-resistant Staphylococcus aureus Pseudomonas aeruginosa (MRPA) and methicillin-resistant Staphylococcus aureus (MRSA). They were able to effectively promote healing of the infected wound model and reduce inflammation and bacterial burden. H&E and Masson's staining showed that BA/COs/NO-PL/AL hydrogels promoted normal epithelial formation and collagen deposition. In conclusion, BA/COs/NO-PL/AL hydrogels are promising candidates for promoting the healing of infected wounds. [ABSTRACT FROM AUTHOR]

Berdazimer topical gel, 10.3% (ZELSUVMI™) is a nitric oxide (NO) releasing topical gel developed by Novan Inc. (a Ligand Pharmaceuticals company) for the treatment of molluscum contagiosum (MC). Novan has used their proprietary NO-based technology platform (NITRICIL™), which stores gaseous NO species on large polymers, in the development of berdazimer topical gel, 10.3%. In January 2024, berdazimer topical gel, 10.3% was approved for the topical treatment of MC in adult and paediatric patients 1 year of age and older in the USA. This article summarizes the milestones in the development of berdazimer topical gel, 10.3% leading to this first approval for the treatment of MC. [ABSTRACT FROM AUTHOR]

Severe pertussis is the leading cause of mortality due to infectious diseases in infants under 2 months old. It is a rare condition with a severe prognosis and a mortality rate of around 70%. The majority of pertussis-related deaths are attributed to this clinical form. Despite therapeutic advancements, such as exchange transfusion, the prognosis remains extremely severe, highlighting the importance of preventive treatment. Indeed, vaccination has significantly reduced the prevalence of the disease. Here, we present a case of a 2-month-old infant admitted to the pediatric intensive care unit for respiratory and hemodynamic distress caused by severe pertussis. [ABSTRACT FROM AUTHOR]

Purpose: Investigate inhaled nitric oxide's influence on mortality rates, mechanical ventilation and cardiopulmonary bypass duration, and length of stay in the intensive care unit and hospital when administered during cardiopulmonary bypass. Methods: Following the PRISMA guidelines, we searched four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) up to 4th March 2023. The protocol was registered in the PROSPERO database with ID: CRD42023423007. Using Review Manager software, we reported outcomes as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs). Results: The meta-analysis included a total of 17 studies with 2897 patients. Overall, there were no significant differences in using nitric oxide over control concerning mortality (RR = 1.03, 95% CI 0.73 to 1.45; P = 0.88) or cardiopulmonary bypass duration (MD = −0.14, 95% CI − 0.96 to 0.69; P = 0.74). The intensive care unit days were significantly lower in the nitric oxide group than control (MD = −0.80, 95% CI − 1.31 to −0.29; P = 0.002). Difference results were obtained in terms of the length of stay in the hospital according to sensitivity analysis (without sensitivity [MD = −0.41, 95% CI − 0.79 to −0.02; P = 0.04] vs. with sensitivity [MD = −0.31, 95% CI − 0.69 to 0.07; P = 0.11]. Subgroup analysis shows that, in children, nitric oxide was favored over control in significantly reducing the duration of mechanical ventilation (MD = −4.58, 95% CI − 5.63 to −3.53; P < 0.001). Conclusion: Using inhaled nitric oxide during cardiopulmonary bypass reduces the length of stay in the intensive care unit, and for children, it reduces the duration of mechanical ventilation. [ABSTRACT FROM AUTHOR]

Inhaled nitric oxide (iNO) is an advanced therapy typically managed by physicians and respiratory therapists in order to increase arterial oxygenation and decrease pulmonary arterial pressure. The Johns Hopkins Lifeline Critical Care Transportation Program (Lifeline) initiated a novel nurse-managed iNO protocol in order to optimize the oxygenation of critically ill patients during interfacility transport. This study was a retrospective chart review of adverse events associated with iNO initiation or continuation by Lifeline on patients transported from March 1, 2020, to August 1, 2022. Basic demographic data and adverse events were recorded. Recorded adverse events included hypotension defined as a mean arterial pressure (MAP) < 65 mm Hg, hypoxemia defined as a decrease of ≥ 10% arterial oxygenation saturation measured by pulse oximetry, new bradycardia or tachyarrhythmia, nitrogen dioxide (NO2) levels greater than 1.0 ppm, methemoglobinemia, and cardiac arrest. Fifteen patients were diagnosed with SARS-CoV-2 infection, of which one also had pulmonary emboli, 2 had bacterial pneumonia, 1 suffered cardiogenic shock from occlusive myocardial infarction and were on VA-ECMO, and 2 had significant thoracic trauma resulting in pulmonary contusions and hemopneumothorax. iNO was continued on 10 patients and initiated on 8 patients, 2 of whom were transitioned from inhaled epoprostenol. Hypotension occurred in 3 (16.7%) patients and one (5.56%) of the hypotensive patients subsequently went on to experience new atrial fibrillation with vasopressor titration. No patients developed worsening hypoxemia, elevated NO2 levels, methemoglobinemia, or suffered cardiac arrest. All 3 patients who experienced hypotension were already on vasopressor support and the hypotension resolved with medication titration. This study shows that iNO administration can be safely managed by appropriately trained nurses. [ABSTRACT FROM AUTHOR]

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, is used as a therapeutic modality in infants with hypoxemic respiratory failure (HRF) associated with persistent pulmonary hypertension of the newborn (PPHN). iNO should ideally be initiated following echocardiographic confirmation of PPHN. Use of iNO is recommended in late preterm and term infants who develop HRF despite optimal oxygenation and ventilation strategies. However, routine iNO use in preterm infants on respiratory support is not recommended. iNO may be considered as a rescue modality in preterm infants with early-onset HRF when associated with prolonged rupture of membranes or oligohydramnios, or late-onset HRF in the context of bronchopulmonary dysplasia-associated pulmonary hypertension (PH) with severe right ventricular failure. A trial of iNO may also be considered for infants with congenital diaphragmatic hernia with persistent HRF despite optimal lung recruitment, and with echocardiographic evidence of supra-systemic PH and adequate left ventricular function. [ABSTRACT FROM AUTHOR]

Objective: Optimal care in the delivery room is important to decrease neonatal morbidity and mortality. We aimed to evaluate neonatal resuscitation practices in Turkish centers. Materials and Methods: A cross-sectional survey consisted of a 91-item questionnaire focused on delivery room practices in neonatal resuscitation and was sent to 50 Turkish centers. Hospitals with <2500 and those with ≥2500 births/year were compared. Results: In 2018, approximately 240 000 births occurred at participating hospitals with a median of 2630 births/year. Participating hospitals were able to provide nasal continuous-positive airway-pressure/high-flow nasal cannula, mechanical ventilation, high-frequency oscillatory ventilation, inhaled nitric oxide, and therapeutic hypothermia similarly. Antenatal counseling was routinely performed on parents at 56% of all centers. A resuscitation team was present at 72% of deliveries. Umbilical cord management for both term and preterm infants was similar between centers. The rate of delayed cord clamping was approximately 60% in term and late preterm infants. Thermal management for preterm infants (<32 weeks) was similar. Hospitals had appropriate equipment with similar rates of interventions and management, except continuous-positive-airway-pressure and positive-end-expiratory-pressure levels (cmH2O) used in preterm infants (P = .021, and P = .032). Ethical and educational aspects were also similar. Conclusions: This survey provided information on neonatal resuscitation practices in a sample of hospitals from all regions of Turkey and allowed us to see weaknesses in some fields. Although adherence to the guidelines was high among centers, further implementations are required in the areas of antenatal counseling, cord management, and circulation assessment in the delivery room. [ABSTRACT FROM AUTHOR]

Background: Inhaled nitric oxide (iNO) has been used as a rescue treatment for preterm infants with hypoxemic respiratory failure (HRF). However, its effectiveness remains debatable. Thus, in this study, we aimed to examine the impact of iNO therapy on HRF in extremely preterm infants. Methods: A retrospective observational study was performed. Extremely preterm infants admitted to our neonatal intensive care unit who received iNO therapy later in their postnatal life were included. The oxygen saturation index (OSI) was used as an index of the severity of respiratory failure. Results: In total, 30 extremely preterm infants were included in this study. Oxygenation was enhanced after the administration of iNO in infants with HRF. The OSI decreased by more than 20% in 12 patients (40%, positive responder) and did not decrease in 17 patients (57%, negative responder) within the first 6 h of treatment. The iNO initiation day was the significant independent factor associated with a positive response to iNO therapy in extremely preterm infants with HRF. Conclusions: iNO therapy was effective in enhancing oxygenation in extremely preterm infants with HRF. Earlier use of iNO was the significant factor associated with a positive therapeutic response to iNO, implying that iNO may be more effective in pulmonary vessels which are less damaged by shorter‐term mechanical ventilation. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic disease that affects both adults and children, and that continues to have a high economic burden. Asthma management guidelines were first developed nearly 30 years ago to standardize care, maintain asthma control, improve quality of life, maintain normal lung function, prevent exacerbations, and prevent asthma mortality. The two most common asthma guidelines used today were developed by the National Asthma Education and Prevention Program (NAEPP) Expert Panel Working Group and the Global Initiative for Asthma Science Committee. Both guiding documents use scientific methodology to standardize their approach for formulating recommendations based on pertinent literature. Before the 2020 National Asthma Education and Prevention Program (Expert Panel Report 4), nothing had been released since the 2007 guidelines, whereas the Global Initiative for Asthma publishes updates annually. Although each of these asthma strategies is similar, there are some noted differences. Over the years, the focus of asthma treatment has shifted from acute to chronic management. Frontline respiratory therapists and other health-care providers should have a good understanding of these 2 guiding references and how they can impact acute and chronic asthma management. The primary focus of this narrative is to look at the similarities and differences of these 2 guiding documents as they pertain to the 6 key questions identified by the Expert Panel of the National Asthma Education and Prevention Program. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) results from abnormal development of the diaphragm during fetal life, allowing abdominal organs to herniate through the defect into the thorax. Stunted lung growth is associated with pulmonary hypoplasia and pulmonary hypertension, which are the primary sources of morbidity and mortality for this population. Despite strides in neonatal and surgical care, the management of neonates with CDH remains challenging. Optimal treatment strategies are still largely unknown. Many centers utilize gentle ventilation, permissive hypercapnia, and pulmonary hypertension treatment inclusive of nitric oxide, sildenafil, or epoprostenol, delayed surgical repair, and extracorporeal membrane oxygenation (ECMO). Evidence-based guidelines are needed to enhance CDH care practices and better outcomes. The successful management of CDH is a collaborative team effort from the prenatal to the postnatal period and beyond. [ABSTRACT FROM AUTHOR]

Introduction: The inducible form of nitric oxide (iNOS) is induced by cytokines and endotoxins. The cardiac-protective effects of nitric oxide (NO) secreted by endothelial NOS are dependent on arginine. Arginine production occurs mainly within the organism, with the kidneys playing a key role in its synthesis and the elimination of asymmetric dimethylarginine (ADM). In the present study the relationship between iNOS, ADMA and left ventricular hypertrophy in chronic kidney disease (CKD) patients and the effect of treatment with angiotensin converting enzyme inhibitor (ACEI) associated with vitamin C (Vit C) were investigated. Material and methods: A longitudinal observational study was conducted on 153 patients with CKD. We studied the correlation between the mean values of iNOS and ADMA in CKD patients and its relationship with left ventricular hypertrophy and the benefit of treating these patients with an associated ACEI and Vit C. Results: The mean age of the patients was 58.85 ±12.75 years. The mean values of iNOS and ADMA were 63.92 ± 0.59 μmol/l and 16.77 ±0.91 μmol/l, respectively. These values increased significantly with the degradation of the renal function (p < 0.05). A significant positive correlation was found between the left ventricular mass index (LVMI) and the two markers, ADMA (0.901 and p = 0001) and iNOS (0.718 and p = 0.0001). After 2 years of treatment with Vit C and ACEI, a significant decrease in LVMI was observed. Conclusions: NO secreted by the iNOS system and ADMAs initiates cardiac remodeling to lead to left ventricular hypertrophy and cardiac fibrosis. ACEIs increase the expression and activity of eNOS and decrease iNOS. Vit C prevents oxidative damage by scavenging ROS species and reagents nitrogen while. iNOS and ADMA accelerate cardiac aging. We conclude that ACEIs combined with Vit C may improve heart health and limite left ventricular hypertrophy in CKD patients. [ABSTRACT FROM AUTHOR]

This study aims to assess the effects of inhaled nitric oxide (iNO) on oxygenation in the management of pulmonary hypertension (PH) secondary to arteriovenous malformations (AVMs) in neonates. This is a matched retrospective cohort study from January 1, 2013, to December 31, 2017. The European inhaled nitric oxide registry from 43 neonatal and pediatric ICUs in 13 countries across Europe was used to extract data. The target population was neonates treated with iNO for the management of PH. The cases (PH secondary to AVMs treated with iNO) were matched (1:4 ratio) to controls (PH without AVMs treated with iNO). The main outcome measure was the absolute change of oxygenation index (OI) from baseline to 60 min after starting iNO in cases and controls. The primary outcome of our study was that the mean absolute change in OI from baseline to after 60 min was higher among cases 10.7 (14), than in controls 6 (22.5), and was not statistically different between the groups. The secondary outcome variable - death before discharge - was found to be significantly higher in cases (55%) than in controls (8%). All the other variables for secondary outcome measures remained statistically insignificant.   Conclusion: Infants with PH secondary to AVMs treated with iNO did not respond differently compared to those presented with PH without AVMs treated with iNO. Right ventricular dysfunction on echocardiography was higher in cases than controls (cases: 66.7% and controls: 28.6%) but was not statistically significant. What is Known: • Arterioenous malformation (AVM) is a well-known cause of persistent pulmonary hypertension in newborns. Inhaled nitric oxide (iNO) is most commonly used as first-line therapy for pulmonary hypertension in newborns. • Around 40-50% of vein of Galen malformations (VOGMs) are found to have congestive heart failure in the neonatal period. What is New: • Neonates may present with an isolated PH of the newborn as the main feature of the VOGMs. A large proportion of cases with AVMs have been associated with right ventricular cardiac dysfunction.  • Results from one of the largest database registries in the world for iNO have been used to answer our research question. [ABSTRACT FROM AUTHOR]

The traditional one-size-fits all approach based on asthma severity is archaic. Asthma is a heterogenous syndrome rather than a single disease entity. Studies evaluating observable characteristics called phenotypes have elucidated this heterogeneity. Asthma clusters demonstrate overlapping features, are generally stable over time and are reproducible. What the identification of clusters may have failed to do, is move the needle of precision medicine meaningfully in asthma. This may be related to the lack of a straightforward and clinically meaningful way to apply what we have learned about asthma clusters. Clusters are based on both clinical factors and biomarkers. The use of biomarkers is slowly gaining popularity, but phenotyping based on biomarkers is generally greatly underutilized even in subspecialty care. Biomarkers are more often used to evaluate type 2 (T2) inflammatory signatures and eosinophils (sputum and blood), fractional exhaled nitric oxide (FeNO) and serum total and specific immunoglobulin (Ig) E reliably characterize the underlying inflammatory pathways. Biomarkers perform variably and clinicians must be familiar with their advantages and disadvantages to accurately apply them in clinical care. In addition, it is increasingly clear that clinical features are critical in understanding not only phenotypic characterization but in predicting response to therapy and future risk of poor outcomes. Strategies for asthma management will need to leverage our knowledge of biomarkers and clinical features to create composite scores and risk prediction tools that are clinically applicable. Despite significant progress, many questions remain, and more work is required to accurately identify non-T2 biomarkers. Adoption of phenotyping and more consistent use of biomarkers is needed, and we should continue to encourage this incorporation into practice. [ABSTRACT FROM AUTHOR]

Objectives: Cardiac surgery using cardiopulmonary bypass frequently provokes a systemic inflammatory response syndrome. This can lead to the development of low cardiac output syndrome (LCOS). Both of these can affect morbidity and mortality. This study is a systematic review of the impact of gaseous nitric oxide (gNO), delivered via the cardiopulmonary bypass (CPB) circuit during cardiac surgery, on post-operative outcomes. It aims to summarise the evidence available, to assess the effectiveness of gNO via the CPB circuit on outcomes, and highlight areas of further research needed to develop this hypothesis. Methods: A comprehensive search of Pubmed, Embase, Web of Science and the Cochrane Library was performed in May 2020. Only randomised control trials (RCTs) were considered. Results: Three studies were identified with a total of 274 patients. There was variation in the outcomes measures used across the studies. These studies demonstrate there is evidence that this intervention may contribute towards cardioprotection. Significant reductions in cardiac troponin I (cTnI) levels and lower vasoactive inotrope scores were seen in intervention groups. A high degree of heterogeneity between the studies exists. Meta-analysis of the duration of mechanical ventilation, length of ICU stay and length of hospital stay showed no significant differences. Conclusion: This systematic review explored the findings of three pilot RCTs. Overall the hypothesis that NO delivered via the CPB circuit can provide cardioprotection has been supported by this study. There remains a significant gap in the evidence, further high-quality research is required in both the adult and paediatric populations. [ABSTRACT FROM AUTHOR]

Objective  The study aimed to evaluate the effects of inhaled iloprost on oxygenation indices in neonates with persistent pulmonary hypertension of the newborn (PPHN). Study Design  We conducted a retrospective chart review of 30 patients with PPHN from January 2014 to November 2018, who did not respond to inhaled nitric oxide (iNO) alone and received inhaled iloprost. Twenty-two patients met the inclusion criteria and eight patients were excluded from the study (complex cardiac disease and extreme prematurity). Patients were categorized as responders or nonresponders (patients who required extracorporeal membrane oxygenation or died). Oxygenation index, mean airway pressure (MAP), and arterial partial pressure of oxygen (PaO 2) were recorded. Results  Among a total of 22 patients who were included in the study, 10 were classified as nonresponders as they required either extracorporeal membrane oxygenation or died. Gestational age and gender did not differ between responders and nonresponders. The median PaO 2 was lower (37 vs. 42 mm Hg; p  < 0.05) and median MAP was higher (20 vs. 17 cm H 2 O; p  < 0.02) in nonresponders compared with responders just prior to initiating iloprost. Iloprost responders had a significant increase in median PaO 2 and decrease in median oxygenation index in the 24 hours after initiating treatment (p  < 0.05), with no significant change in required mean airway pressure over that same period. There was no change in vasopressor use or clinically significant worsening of platelets count, liver, and kidney functions after initiating iloprost. Conclusion  Inhaled iloprost is well tolerated and seems to have beneficial effects in improving oxygenation indices in neonates with PPHN who do not respond to iNO. There is a need of well-designed prospective trials to further ascertain the benefits of using inhaled iloprost as an adjunct treatment in neonates with PPHN who do not respond to iNO alone. Key Points Inhaled iloprost seems to have beneficial effects in improving oxygenation indices in PPHN. Inhaled iloprost is generally well tolerated in newborns with PPHN. There is a need for prospective randomized controlled trials to further ascertain the benefits of using inhaled iloprost. [ABSTRACT FROM AUTHOR]

The article focuses on the evolving field of epigenetics, revealing how environmental factors can alter gene expression over time, potentially leading to unforeseen health risks. Topics include the impact of oxygen exposure in medical settings, the epigenetic effects of chemicals leaching from medical devices, and the long-term consequences of therapeutic interventions like steroids and blood transfusions on gene expression and health outcomes.

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease.Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021.Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685).Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels.Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups.Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery.Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392. [ABSTRACT FROM AUTHOR]

Rationale: Acute changes in cardiopulmonary hemodynamics that include tricuspid regurgitant jet velocity (TRV) elevation measured by Doppler echocardiography are often encountered during sickle cell vasoocclusive pain and acute chest syndrome (ACS). Arginine and nitric oxide depletion develop in patients with these complications. Arginine administration may therefore improve nitric oxide bioavailability and potentiate pulmonary vasodilatation. Objectives: To evaluate effects of l-arginine supplementation on Doppler indices of cardiopulmonary hemodynamics in children with sickle cell anemia experiencing pain. Methods: This was a prospective, double-blinded, randomized placebo-controlled trial of oral arginine in children with sickle cell anemia age 5-17 years hospitalized with severe pain and/or ACS. Measurements and Main Results: Blood biomarkers and Doppler echocardiographic indices of cardiopulmonary hemodynamics were measured before and after supplementation. The mean change in TRV, pulmonary artery systolic pressure, mean pulmonary artery pressure, and other indices of cardiopulmonary hemodynamics were tested with paired Student's t test and correlated with markers of arginine bioavailability using Pearson correlation. Sixty-six children were randomized into arginine versus placebo groups. An elevated TRV ⩾ 2.5 m/s was seen in 40 (61%) patients. A Day 5 Doppler echocardiogram was performed in 47 patients who remained hospitalized. A greater reduction in median TRV occurred in the arginine group than placebo (22.2%, n = 22 vs. 3.8%, n = 25; p < 0.01). A larger percentage increase in global arginine bioavailability was associated with a lower TRV after 5 days of supplementation (r = -0.533; P = 0.001). Significant differences in multiple indices of cardiopulmonary hemodynamics and mean N-terminal pro B-type brain natriuretic peptide were also noted after arginine therapy. Conclusions: Oral arginine supplementation improves cardiopulmonary hemodynamics during sickle cell disease vasoocclusive pain and ACS.Clinical trial registered with Pan African Clinical Trial Registry https://pactr.samrc.ac.za/Search.aspx (PACTR201611001864290). [ABSTRACT FROM AUTHOR]

The article focuses on various topics in neonatology. It discusses a study on the discrepancy between set and delivered pressures using the RAM cannula interface; the relationship between non-invasive ventilation and gastrointestinal issues in micro-premature infants; and the use of dexmedetomidine in improving respiratory stability, ultrasound assessment of diaphragmatic contractility with caffeine administration and the controversy surrounding nitric oxide (iNO) were also discussed.

The administration of exogenous oxygen to support adequate gas exchange is the cornerstone of respiratory care. In the past few years, other gaseous molecules have been introduced in clinical practice to treat the wide variety of physiological derangement seen in critical care patients.Inhaled nitric oxide (NO) is used for its unique selective pulmonary vasodilator effect. Recent studies showed that NO plays a pivotal role in regulating ischemia-reperfusion injury and it has antibacterial and antiviral activity.Helium, due to its low density, is used in patients with upper airway obstruction and lower airway obstruction to facilitate gas flow and to reduce work of breathing.Carbon monoxide (CO) is a poisonous gas that acts as a signaling molecule involved in many biologic pathways. CO's anti-inflammatory and antiproliferative effects are under investigation in the setting of acute respiratory distress and idiopathic pulmonary fibrosis.Inhaled anesthetics are widely used in the operative room setting and, with the development of anesthetic reflectors, are now a valid option for sedation management in the intensive care unit.Many other gases such as xenon, argon, and hydrogen sulfide are under investigation for their neuroprotective and cardioprotective effects in post-cardiac arrest syndrome.With all these therapeutic options available, the clinician must have a clear understanding of the physiologic basis, therapeutic potential, and possible adverse events of these therapeutic gases. In this review, we will present the therapeutic gases other than oxygen used in clinical practice and we will describe other promising therapeutic gases that are in the early phases of investigation. [ABSTRACT FROM AUTHOR]

Diabetic cutaneous ulcers (DCU) are a chronic and refractory complication of diabetes mellitus, which can lead to amputation or even death in extreme cases. Promoting the early healing of DCU and reducing the disability rate and treatment cost are important research topics in treating with integrated traditional Chinese and Western medicine. Centella asiatica total glycosides are extracted from the traditional Chinese medicine Centella asiatica and have angiogenic, anticancer, antioxidant, and wound healing effects. Nitric oxide (NO) is a critical component of wound healing. During the development of DCU, endogenous NO secretion is insufficient. It has been reported that exogenous nitric oxide can promote wound healing, but it is difficult to adhere to the skin because of its short half-life. Therefore, in this study, we used the polymer excipient hydroxyethyl cellulose as the matrix, combined with Centella asiatica total glycosides and NO, and developed a new type of topical gel that can promote wound healing. At the same time, we made a comprehensive research and evaluation on the preparation technology, quality standard, skin toxicity, reproductive toxicity, and pharmacodynamics against diabetic skin ulcers of the gel. According to our research results, the combination of Centella asiatica total glycosides and nitric oxide can accelerate the healing speed of DCU wounds, and 8% Centella asiatica total glycosides nitric oxide gel (CATGNOG) has the best effect in ulcer wound healing. CATGNOG has the advantages of feasible preparation method, controllable quality, good stability at low temperature, and no apparent skin toxicity and reproductive toxicity. It can effectively inhibit the growth of bacteria on the wound surface, relieve the inflammatory reaction of the wound surface, and promote the healing of ulcer wound, which provides a basis for further research of the preparation in the future. [ABSTRACT FROM AUTHOR]

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Background: Inhaled nitric oxide (iNO) has been in use for several decades now in neonates with hypoxic respiratory failure (HRF) associated with pulmonary hypertension (PH). Its requirement is uncommon, and is considered as an advanced form of support that is not widely available. Analysis of outcomes in specific settings, notably from low-middle income countries, is crucial. Objectives: To evaluate the patient profile and outcomes of neonates treated with iNO in our Level IIIB unit. Methods: This retrospective observational study describes the clinical diagnosis, management strategies and short-term outcomes of all neonates who received iNO in the years between 2013 and 2021. Details were retrieved from Electronic Medical Records and systematically analysed. Observation: Of 35 infants who received iNO during the study period, 31 (88.6%) were >34 weeks. The median and interquartile range (IQR) of oxygenation index at which iNO was started was 28 (20,33). The median (IQR) duration of iNO therapy was 48 (23,95) hours. Overall, 18 neonates (51.4%) survived till hospital discharge. Therapeutic response was best observed in infants with HRF secondary to meconium aspiration syndrome or congenital pneumonia (100% survival). Though the benefits of iNO use in congenital diaphragmatic hernia and bronchopulmonary dysplasia associated with PH are debatable, its use continues as a rescue measure. Conclusion: iNO is used in severe HRF associated with PH in neonates and can improve survival rates in select patient profiles without any major adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence. [ABSTRACT FROM AUTHOR]

This article discusses the pathophysiology, risk factors, clinical manifestations, diagnostics, and pharmacologic treatment of pulmonary arterial hypertension, as well as nursing considerations for caring for patients with this rare disease. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine the action of inhaled nitric oxide in the patients with pulmonary hypertension administered with a face mask before anesthesia induction.Methods: Ten adult patients scheduled for heart surgery with sternotomy were included in this prospective, interventional, single centre study. The inclusion criteria were patients scheduled for heart surgery with sternotomy with cardiopulmonary bypass (CPB), aged >18 years which presents a pulmonary hypertension (PH) (class 2 or 3 according to the Dana Point classification) with systolic pulmonary arterial pressure (PAPS) >40 mmHg diagnosed by preoperative right cardiac catheterization or by transthoracic echocardiography. The exclusion criteria were: heart transplant, PH of type 1, 4, 5, according to the Dana Point classification, methemoglobin reductase deficit, incapacity to understand the protocol and sign the consent.Results: The administration of iNO decrease pulmonary hypertension (P < 0,001 compared to room air; P = 0,01 compared to pure oxygen administration). The iNO administration did not improve arterial blood oxygenation. The hyperoxia, decrease the cardiac index even with right ventricular post charge decrease. The increased blood oxygenation content cause systemic vascular vasoconstriction and decrease the peripheral oxygen extraction showed with VO2 linear increase (P < 0,001).Conclusions: The administration of inhaled nitric oxide with a face mask before anaesthesia induction is safe and effective method to reduce pulmonary hypertension. The oxygen and hyperoxia influences the systemic vascular resistance and peripheral oxygen consumption. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFUs) will affect up to one-third of people with diabetes, and not all ulcers heal despite gold standard management. DFUs carry a very high personal and financial cost, but studies of adjunctive wound healing therapies are sparse. Suggested adjuvant topical agents include sucrose octasulfate, placental membrane allografts and autologous patches containing leucocytes, fibrin and platelets. Systemic options are very limited. Promising treatments needing more study include topical oxygen, honey and nitric oxide, growth factors and other bioengineered skin products. Newer technologies may eventually provide more options. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a powerful mediator with biological activities such as vasodilation and prevention of vascular smooth muscle cell proliferation as well as functional regulation of cardiac cells. Thus, impaired production or reduced bioavailability of NO predisposes to the onset of different cardiovascular (CV) diseases. Alterations in the redox balance associated with excitation–contraction coupling have been identified in heart failure (HF), thus contributing to contractile abnormalities and arrhythmias. For its ability to influence cell proliferation and angiogenesis, NO may be considered a therapeutic option for the management of several CV diseases. Several clinical studies and trials investigated therapeutic NO strategies for systemic hypertension, atherosclerosis, and/or prevention of in stent restenosis, coronary heart disease (CHD), pulmonary arterial hypertension (PAH), and HF, although with mixed results in long-term treatment and effective dose administered in selected groups of patients. Tadalafil, sildenafil, and cinaguat were evaluated for the treatment of PAH, whereas vericiguat was investigated in the treatment of HF patients with reduced ejection fraction. Furthermore, supplementation with hydrogen sulfide, tetrahydrobiopterin, and nitrite/nitrate has shown beneficial effects at the vascular level. [ABSTRACT FROM AUTHOR]

Purpose: Several reports have demonstrated similar effects on oxygenation between inhaled epoprostenol (iEPO) compared to inhaled nitric oxide (iNO) for acute respiratory distress syndrome (ARDS). Previous studies directly comparing oxygenation and clinical outcomes between iEPO and iNO exclusively in an adult ARDS patient population utilized a weight-based dosing strategy. The purpose of this study was to compare the clinical and economic impact between iNO and fixed-dosed iEPO for ARDS in adult intensive care unit (ICU) patients. Methods: This retrospective cohort study was conducted at a major academic medical center between January 1, 2014, and October 31, 2018. Patients ≥18 years of age with moderate-to-severe ARDS were included. The primary end point was to compare the mean change in partial arterial oxygen pressure to fraction of inspired oxygen (PaO2: FIO2) at 4 hours from baseline between iEPO and iNO. Other secondary aims were total acquisition drug costs, in-hospital mortality, ICU and hospital length of stay, and duration of mechanical ventilation. Results: A total of 239 patients were included with 139 (58.2%) and 100 (41.8%) in the iEPO and iNO groups, respectively. The mean change in PaO2: FIO2 at 4 hours from baseline in the iEPO and iNO groups were 31.4 ± 54.6 and 32.4 ± 42.7 mm Hg, respectively (P = .88). The responder rate at 4 hours was similar between iEPO and iNO groups (64.7% and 66.0%, respectively, P = .84). Clinical outcomes including mortality, overall hospital and ICU length of stay, and mechanical ventilation duration were similar between iEPO and iNO groups. Estimated annual cost-savings realized with iEPO was USD1 074 433. Conclusion: Fixed-dose iEPO was comparable to iNO in patients with moderate-to-severe ARDS for oxygenation and ventilation parameters as well as clinical outcomes. Significant cost-savings were realized with iEPO use. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the chief micro-vascular aggravation of diabetes, and it is accountable for about 10,000 new cases of blindness every year in the USA and affects about 100 million people worldwide. Nitric oxide synthase oxide is family of enzymes catalysing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signalling molecule. It helps modulate vascular tone, insulin secretion, airway tone, peristalsis and is involved in angiogenesis and neural development. By utilizing an ELISA kit for the measurement of the level of NOS in serum, the serum level of NOS was measured in one hundred Iraqi subjects: 30 patients, who have diabetes without DR, 30 patients with diabetic retinopathy (DR), 30 patients who have no diabetes or retinopathy as control group. S. NOS had a significant increase in T2DM and DR patients when related to not diabetic subjects (P<0.001). Glycated Hb revealed a higher significant level in T2DM group and DR group when related to the not-diabetic group (P<0.001) Total Cholesterol revealed Non- significant level in T2DM, DR groups than in non-diabetic controls (P=0.001). Regarding R.B.S level in T2DM, DR groups was high significant when compared with non-diabetic control groups. the serum level of NOS was higher in patients with the NDR than those in DR also it was higher in diabetic patients with retinopathy when compared to control. [ABSTRACT FROM AUTHOR]

The soil of crop fields is composed of various types of elements, which are vital for the proper functioning of the cellular activities of plants. However, the presence of these components above the permissible limit in soil causes toxicity and poses negative impact on crop productivity worldwide. NaCl is one of the such components which causes ion toxicity and stunts the growth of the plants. Therefore, there is need of strategies which may reduce NaCl induced toxicity in crop plants for better yield. Recently, the exogenous application of signalling molecule such as nitric oxide in mitigating negative impact of abiotic stress has gained wider attention. Moreover, the potential signalling mediated effect of NO in plants exposed to NaCl stress is not much known. Therefore, the present study was undertaken to evaluate the ameliorative effect of NO in NaCl induced decline in growth, pigment contents, nitrogen metabolism. NaCl stress (30 mM) considerably declined the growth, photosynthetic pigments and nitrogen metabolism as a result of direct effect or by disturbing the redox homeostasis of vegetable bottle gourd. Further, the application of NO (25µM SNP) successfully alleviated the NaCl induced toxicity on these parameters by regulating the adjustment of redox homeostasis, thereby leading bottle gourd seedlings to sustainably adapt to salinity stress. The potent role of NO as signalling agent was also ascertained by application of different modulators: cPTIO (25µM), LNAME (300 µM) and ST (300 µM) [ABSTRACT FROM AUTHOR]

The article discusses the consideration of surfactant redosing in preterm infants based on increased oxygen requirements, with a case illustrating the decision-making process involving physical examination and echocardiography. It highlights studies on surfactant redosing in infants born to mothers with hypertension and those small for gestational age, emphasizing the importance of recognizing persistent pulmonary hypertension and the potential use of inhaled nitric oxide as a treatment option.

Pulmonary arterial hypertension (PAH) is a severe disease with poor prognosis and shortened life expectancy. Treatment has traditionally involved the sequential use of endothelin receptor agonists, prostacyclin therapies, and nitric oxide pathway modulators, which each have distinct mechanisms of action leading to pulmonary vasodilation, and improvement in exercise capacity, hemodynamic measures, and clinical outcomes for patients with PAH. This article provides a review of goals of therapy in PAH, determinants of prognosis and levels of patient risk, and additional factors that guide treatment decision making. Recent research in combination therapies has created a paradigm shift in the treatment of PAH and will be reviewed. Additionally, recent updates to the American College of Chest Physicians guidelines will be reviewed along with the updated evidence-based treatment algorithm. Finally, trial data will be evaluated for the recently developed agent selexipag and improved treprostinil delivery formulations that may provide enhanced convenience. [ABSTRACT FROM AUTHOR]

The role of inhaled nitric oxide in the treatment of shock remains controversial and further translational research is needed. Long-term observation studies using a model of endotoxin-induced shock to assess the effect of inhaled nitric oxide on platelet aggregation have not yet been reported. The tests were carried out in an animal model of shock in two 10-h periods. During the first 10 h, endotoxin was infused and the inhibition of platelet aggregation was evaluated; following the termination of endotoxin infusion, the restoration of platelet aggregation was assessed for 10 h. A total of 30 pigs were used (NO group, N = 14; control, N = 16). In the NO group, nitric oxide inhalation (30 ppm) was started 3 h after endotoxin infusion and continued until the end of the study. Treatment with NO selectively decreased pulmonary artery pressure at 4 (p = 0.002) and 8 h (p = 0.05) of the experiment as compared to the control. Endotoxin significantly reduced platelet aggregation, as indicated by the decreased activity of platelet receptors: ASPI, ADP, collagen, and TRAP during the experiment (p < 0.001). Endotoxin had no significant effect on changes in the response of the receptor after ristocetin stimulation. After stopping endotoxin infusion, a significant restoration of receptor activity was observed for collagen and TRAP, while ASPI and ADP remained partially depressed. Inhaled nitric oxide did not cause additional inhibition of platelet aggregation, either during or after endotoxin challenge. A profound reduction in platelet aggregation was observed during endotoxic shock. After stopping endotoxin infusion a restoration of platelet receptor activity was seen. The inhibition of platelet aggregation induced by endotoxin infusion was not intensified by nitric oxide, indicating there was no harmful effect of inhaled nitric oxide on platelet aggregation. • Endotoxin significantly reduces platelet aggregation, as indicated by the decreased activation of platelet receptors. • Inhaled nitric oxide does not cause any deterioration of platelet aggregation either during or after endotoxin challenge. • After stopping endotoxin infusion a restoration of platelet receptor activity was seen. [ABSTRACT FROM AUTHOR]

Copyright of Parasite (1252607X) is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: We sought to evaluate the institutional use of inhaled nitric oxide (INO) and to create a pathway to reduce waste using the Institute for Healthcare Improvement's model for improvement. Our aim was to reduce the use of INO by 20% within 8 months. METHODS: This was a prospective, respiratory therapist-driven, quality improvement project. We implemented a hospital-wide INO utilization protocol that was developed by neonatology, pediatric critical care, cardiac critical care, and respiratory therapy. INO use and respiratory therapist input for protocol failures were derived from the electronic medical record and were used to generate improvement opportunities. Monthly total hospital use of INO (in hours) was used as the primary outcome measure. Median hourly use per subject (evaluated in groups of 7 subjects) was used as a secondary outcome measure. New sildenafil dosing was tabulated for pre- and post-INO weaning protocol intervention as a balancing measure. Subjects included all patients in the hospital who were given INO therapy during the specified timeframe. RESULTS: Hospital-wide total hours were reduced from 1,515 h/month to 930 h/month. This hospital-wide reduction of 39% equates to a costavoidance of approximately $912,000 per year based on 2018 costs of INO of $130 per hour. Median hours of INO per subject decreased from 88 h to 50 h. Sildenafil was started in 18 of 98 subjects (18%) in the pre-intervention period and in 12 of 109 subjects (11%) in the post-intervention period (P = .27). CONCLUSIONS: A hospital-wide, multi-professional initiative led to a reduction in unnecessary INO use, resulting in decreased subject exposure and associated cost avoidance. [ABSTRACT FROM AUTHOR]

Importance: Asthma is a major public health problem worldwide and is associated with excess morbidity, mortality, and economic costs associated with lost productivity. The National Asthma Education and Prevention Program has released the 2020 Asthma Guideline Update with updated evidence-based recommendations for treatment of patients with asthma.Objective: To report updated recommendations for 6 topics for clinical management of adolescents and adults with asthma: (1) intermittent inhaled corticosteroids (ICSs); (2) add-on long-acting muscarinic antagonists; (3) fractional exhaled nitric oxide; (4) indoor allergen mitigation; (5) immunotherapy; and (6) bronchial thermoplasty.Evidence Review: The National Heart, Lung, and Blood Advisory Council chose 6 topics to update the 2007 asthma guidelines based on results from a 2014 needs assessment. The Agency for Healthcare Research and Quality conducted systematic reviews of these 6 topics based on literature searches up to March-April 2017. Reviews were updated through October 2018 and used by an expert panel (n = 19) that included asthma content experts, primary care clinicians, dissemination and implementation experts, and health policy experts to develop 19 new recommendations using the GRADE method. The 17 recommendations for individuals aged 12 years or older are reported in this Special Communication.Findings: From 20 572 identified references, 475 were included in the 6 systematic reviews to form the evidence basis for these recommendations. Compared with the 2007 guideline, there was no recommended change in step 1 (intermittent asthma) therapy (as-needed short-acting β2-agonists [SABAs] for rescue therapy). In step 2 (mild persistent asthma), either daily low-dose ICS plus as-needed SABA therapy or as-needed concomitant ICS and SABA therapy are recommended. Formoterol in combination with an ICS in a single inhaler (single maintenance and reliever therapy) is recommended as the preferred therapy for moderate persistent asthma in step 3 (low-dose ICS-formoterol therapy) and step 4 (medium-dose ICS-formoterol therapy) for both daily and as-needed therapy. A short-term increase in the ICS dose alone for worsening of asthma symptoms is not recommended. Add-on long-acting muscarinic antagonists are recommended in individuals whose asthma is not controlled by ICS-formoterol therapy for step 5 (moderate-severe persistent asthma). Fractional exhaled nitric oxide testing is recommended to assist in diagnosis and monitoring of symptoms, but not alone to diagnose or monitor asthma. Allergen mitigation is recommended only in individuals with exposure and relevant sensitivity or symptoms. When used, allergen mitigation should be allergen specific and include multiple allergen-specific mitigation strategies. Subcutaneous immunotherapy is recommended as an adjunct to standard pharmacotherapy for individuals with symptoms and sensitization to specific allergens. Sublingual immunotherapy is not recommended specifically for asthma. Bronchial thermoplasty is not recommended as part of standard care; if used, it should be part of an ongoing research effort.Conclusions and Relevance: Asthma is a common disease with substantial human and economic costs globally. Although there is no cure or established means of prevention, effective treatment is available. Use of the recommendations in the 2020 Asthma Guideline Update should improve the health of individuals with asthma. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the survival and neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants at 18 to 26 months with early hypoxemic respiratory failure (HRF). We also assessed whether African American infants with early HRF had improved outcomes after exposure to inhaled nitric oxide (iNO). METHODS: ELBW infants ≤1000 g and gestational age ≤26 weeks with maximal oxygen ≥60% on either day 1 or day 3 were labeled as "early HRF" and born between 2007 and 2015 in the Neonatal Research Network were included. Using a propensity score regression model, we analyzed outcomes and effects of exposure to iNO overall and separately by race. RESULTS: Among 7639 ELBW infants born ≤26 weeks, 22.7% had early HRF. Early HRF was associated with a mortality of 51.3%. The incidence of moderate-severe NDI among survivors was 41.2% at 18 to 26 months. Mortality among infants treated with iNO was 59.4%. Female sex (adjusted odds ratio [aOR]: 2.4, 95% confidence interval [CI]: 1.8-3.3), birth weight ≥720 g (aOR: 2.3, 95% CI: 1.7-3.1) and complete course of antenatal steroids (aOR: 1.6, 95% CI: 1.1-2.2) were associated with intact survival. African American infants had a similar incidence of early HRF (21.7% vs 23.3%) but lower exposure to iNO (16.4% vs 21.6%). Among infants with HRF exposed to iNO, intact survival (no death or NDI) was not significantly different between African American and other races (aOR: 1.5, 95% CI: 0.6-3.6). CONCLUSIONS: Early HRF in infants ≤26 weeks' gestation is associated with high mortality and NDI at 18 to 26 months. Use of iNO did not decrease mortality or NDI. Outcomes following iNO exposure were not different in African American infants. [ABSTRACT FROM AUTHOR]

Inhaled pulmonary vasodilators are a powerful tool in the arsenal of therapies designed to treat pulmonary hypertension in pediatrics. Yet only 1 inhaled vasodilator, inhaled nitric oxide (INO), has been approved by the Food and Drug Administration for use in neonates > 34 weeks gestational age with persistent pulmonary hypertension of the newborn. Off-label use of inhaled vasodilators is common in the neonatal and pediatric population despite a lack of evidence. Growing focus on providing evidence-based therapies combined with the increasing cost of INO has led to the exploration of other inhaled pulmonary vasoactive agents. Advancements in technology have led to the creation of nitric oxide generation devices that do not require tanks. This review evaluates the current evidence regarding the use of inhaled vasodilators and INO delivery devices in the neonatal and pediatric intensive care population. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can vary from asymptomatic to severe symptoms. It can lead to respiratory failure and acute respiratory distress syndrome requiring intubation and mechanical ventilation. Triaging patients is key to prevent spread, conserving medical resources, and providing appropriate care. The treatment of these patients remains supportive. Respiratory failure due to the virus should be managed by providing supplemental oxygen and early intubation. Some patients develop acute respiratory distress syndrome and refractory hypoxemia. In this article, we review the 2 phenotypes of respiratory failure, mechanical ventilation and the management of refractory hypoxemia. [ABSTRACT FROM AUTHOR]

The article highlights the role of home nitric oxide therapy for COVID-19. It also mentions about infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes a range of cardiopulmonary and vascular complications, ranging from upper respiratory tract symptoms to severe acute respiratory distress syndrome (ARDS), as well as shock, acute kidney injury, and thromboembolic complications.

Currently, there are no approved treatments for infants with acute bronchiolitis, the leading cause for hospitalization of infants worldwide, and thus the recommended approach is supportive. Inhaled Nitric oxide (iNO), possesses anti-viral properties, improves oxygenation, and was shown to be safe in infants with respiratory conditions. Hospitalized infants with acute bronchiolitis were therefore recruited to a prospective double-blinded, multi-center, randomized controlled pilot study. They received intermittent high dose iNO (160 ppm) plus oxygen/air for 30 min or oxygen/air alone (control), five times/day, up to 5 days. Sixty-nine infants were enrolled. No difference was observed in frequencies of subjects with at least one Adverse Event (AE) in iNO (44.1%) vs. control (55.9%); neither was Methemoglobin >7% safety threshold. No drug-related serious AEs (SAEs) were reported. Analysis of Per-Protocol population revealed that length of stay (LOS), time to SpO2 ≥92%, and time to mTal clinical score ≤5 improved by 26.7 ± 12.7 (Welch's t-test p = 0.04), 20.8 ± 8.9 (p = 0.023), and 14.6 ± 9.1 (p = 0.118) hours, respectively, in the iNO group compared to the control. Overall, high dose iNO (160ppm) was safe, well-tolerated, reduced LOS and showed rapid improvement of oxygen saturation, compared to the standard therapy. Further investigation in larger cohorts is warranted to validate these encouraging efficacy outcomes. (Trial registration: NCT03053388) [ABSTRACT FROM AUTHOR]

Aim: Pulmonary hypertension (PH) frequently complicates neonatal hypoxaemic respiratory failure, but is inconsistently defined. We aimed to describe the variation among randomised controlled trials (RCTs) of inhaled nitric oxide (iNO), in relation to the definition of PH and/or hypoxaemic respiratory failure used to select patients for trial inclusion.Methods: PubMed, Cochrane Library and ClinicalTrials.gov were systematically searched for RCTs of iNO in neonates. Included studies were assessed for clinical and/or echocardiography criteria used to define PH/hypoxaemic respiratory failure.Results: Thirty-two trials were included in this review, of which 23 enrolled infants ≥34 weeks' gestation. Echocardiographic diagnosis was used in 21 studies, but there was considerable variation in the echocardiographic parameters used to diagnose PH. The most commonly used indices included markers of tricuspid regurgitation and extrapulmonary shunt.Conclusion: There is wide variation in the definition of PH used to select infants for inclusion into RCTs of iNO therapy in neonates. We recommend that an international consensus be reached on which parameters should be used and the thresholds defining severity of disease. [ABSTRACT FROM AUTHOR]

Aim: The aim of our review was to describe the clinical response to inhaled nitric oxide (iNO) in a series of preterm babies in respiratory failure during uplift transfers to a neonatal intensive care unit.Methods: We performed a retrospective review of critical newborns with gestational age <34+0  weeks transferred from January 2013 to December 2018. Data were extracted from our Clinical Information System for transport. The primary measure of this review was to assess whether a significant improvement in the oxygenation saturation index (OSI) occurred following the use of iNO.Results: Thirty preterm babies <34+0  weeks were included in our review. OSI, as a measure of oxygenation, did not statistically improve as an immediate response to iNO from referral to receiving hospital (17.1 vs 16.4; P = .7). We found that pH (7.15 vs 7.29; P = .004) and pCO2 (8.1 vs 6.3; P = .05) significantly improved probably based on ventilation management.Conclusion: Following the recommendations of the American Academy of Paediatrics and other organizations, iNO should not routinely be used during the neonatal transfer of preterm babies <34+0 in respiratory failure. We need to conduct further studies to establish which selected preterm patients would benefit from being treated with iNO. [ABSTRACT FROM AUTHOR]

Increased plasma nitrate concentrations from dietary sources of nitrate have proven to benefit exercise performance. Beetroot (BR) contains relatively high levels of nitrate (NO3–), which increases nitric oxide stores. This study investigated whether dietary nitrate supplementation, in the form of a BR beverage, would improve rowing performance during ergometer repetitions. In a randomized crossover design, 14 well-trained junior male rowers consumed 500 ml of either BR or placebo (PL) daily for 6 d. After supplementation, rowers completed 6 maximal 500-m ergometer repetitions and times were recorded. A 7-d washout period separated the 2 trials. Blood pressure, oxygen saturation, maximum heart rate, urine (specific gravity, pH, and nitrites), and lactates were collected for analysis at baseline and pre- and postperformance. Changes in the mean with 95%confidence limits were calculated. There was a likely benefit to average repetition time in the BR condition, compared with PL (0.4%, 95% confidence limits, ± 1.0%). In particular, Repetitions 4–6 showed an almost certain benefit in rowing time on BR (1.7%, 95% CL, ± 1.0%). The underlying mechanism for the observed results remains unknown, as differences observed in rowers’ physiological measures between the 2 conditions were unclear. Conclusively, nitrate supplementation in the form of BR juice resulted in improved maximal rowing-ergometer repetitions, particularly in the later stages of exercise. [ABSTRACT FROM AUTHOR]