Outcome of Obstructed Total Anamalous Pulmonary Venous Connection (TAPVC) Repair Patients with Milrinone Versus Milrinone and Inhaled Nitric Oxide (INO): A Prospective Randomized Observational Study

Background: Obstructed total anomalous pulmonary venous connection (TAPVC) typically present with severe cardiovascular decompensation and requires urgent surgical management. Pulmonary arterial hypertension (PAH) is a major risk factor affecting mortality. Perioperative management focuses on providing inotropic support and managing potential pulmonary hypertensive episodes. Milrinone and inhaled nitric oxide (iNO) efficiently reduce pulmonary artery pressure (PAP) and help to improve the outcome. The aim was to determine the outcome of patients with high PAP with milrinone alone and a combination of iNO and milrinone. Material and Method: After ethical committee approval, the study was conducted over a period of 3 years in 80 patients with obstructed TAPVC repair. A total of 80 patients having severe PAH (supra systemic arterial pressure) randomly divided into two groups with 40 patients in each (M & MN). Group M (milrinone) patients received milrinone and Group MN (milrinone & iNO) patients received both milrinone (after opening aortic cross clamp) and iNO (post operative ICU). Ventilation time, hospital stay, ICU stay, complications, in hospital mortality were compared between both groups. Result: Ventilation time, Intensive Care Unit (ICU) stay, hospital stay for group M was 8.02 � 5.74 days, 11.25 � 7.33 day, 14.92 � 8.55 days, respectively, and for group MN was 5.02 � 1.78 days, 8.27 � 3.24 days, 10.3 � 3.18 days, respectively. In hospital mortality for group M and MN was 10% and 2.5%, respectively. P value for each variable was significant < 0.05 (except mortality). Conclusion: Most of the patients with obstructed TAPVC had severe PAH. Management of severe PAH with a combination of milrinone with iNO had a better outcome than milrinone alone.

The early use of iNO in extremely premature neonates with refractory hypoxic respiratory failure / 中国新生儿科杂志

Objective:To study the early use of inhaled nitric oxide (iNO) as a rescue therapy in extremely premature infants (EPIs) with refractory hypoxic respiratory failure (HRF).Methods:Between January 2021 and December 2021, EPIs with refractory HRF receiving iNO within the first week of life in our NICU were enrolled. Their clinical characteristics and outcomes were retrospectively analyzed.Results:A total of 11 EPIs were included with 5 males and 6 females. The median gestational age (GA) was 24(22.6, 25.2) weeks. The median birth weight (BW) was 580(490, 770) g. The most common primary diagnoses were moderate/severe respiratory distress syndrome (RDS) (5/11) and early-onset sepsis (3/11). The median age starting iNO therapy was 6.5(4.5, 34.0)h and the median duration of iNO was 24(12, 36)h. The median iNO starting dose was 5(5, 8) ppm and the therapeutic range was 5-20 ppm. Therapeutic efficacy was defined as ≥30% FiO 2 reduction after 6 h of iNO treatment. The treatment was effective in 8 cases. The oxygenation index (OI) decreased more than 10% from baseline 1 h after initiation in 9 patients and in all 11 patients after 12 h of iNO. The reduction of OI was more prominent in EPIs with a higher OI at baseline. Of the 11 patients, 8 survived, 1 died and 2 abandoned further treatments. Conclusions:As an early rescue therapy for EPIs with refractory HRF, iNO can improve oxygenation without obvious short-term adverse effects.

Prevalence of oral candidiasis in asthma and COPD patients using inhaled corticosteroids in the Philippine General Hospital Department of out-patient services

Background and Objectives@#Oral candidiasis (OC) is a well-known local side effect of inhaled corticosteroid (ICS) therapy in patients with asthma and chronic obstructive pulmonary disease (COPD). This study aimed to determine the prevalence of OC and its association with ICS-related factors in out-patient asthma and COPD patients of the Departments of Pulmonology and Pediatric Pulmonology of the Philippine General Hospital (PGH).@*Methods@#This is a cross-sectional study conducted from October 2019 to January 2020. Data was collected through a two-part questionnaire accomplished by doctors and patients with asthma or COPD. Results. A total of 67 patients were included in the study. Oral candidiasis was observed in 4 (5.97%) ICS users, and the prevalence was 1.65% to 14.59% (95% CI, SE: 0.028946).@*Conclusion@#This study determined the prevalence of oral candidiasis in asthma and COPD patients and its association with ICS-related factors, including the dosage, medication, device, and duration of therapy. The prevalence of OC in ICS users in PGH cannot be interpreted as high or low due to the small number of respondents, but is consistent with OC prevalence found in related literature. Increased prevalence was observed in adult females with asthma under low dose ICS therapy with Fluticasone/Salmeterol DPI for more than a year. There was no statistically significant correlation among OC prevalence, age, sex, and components of ICS-therapy including dosage, medication, device, frequency, and duration of therapy. A large-scale study is recommended for more accurate assessment of OC prevalence in the population and to determine statistically significant associations among the factors. It is also recommended to quantifiably measure patient compliance, inhalation technique and instruction, and its association to OC prevalence. Findings may be used to strengthen patient education, preventive measures, and disease management to facilitate improved compliance and effective treatment outcomes.

Effects of single nucleotide polymorphism of drug metabolizing enzyme cytochrome P450 on the efficacy of inhaled cortisol hormone in asthmatic children / 中国临床药理学与治疗学

AIM: To elucidate the relationship between childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids (ICS) in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymorphisms (SNPs) of cytochrome P450 enzyme 3A5 (CYP3A5) gene in asthmatic children and healthy children. METHODS: The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 children (Case group) with asthma of Han nationality and 100 healthy children (Control group) who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020, and genotype, allele and linkage analysis were performed. The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months, and lung function and exhaled breath nitric oxide (FeNO) were measured at entry and after treatment, and asthma control score C-ACT/ACT was done after treatment, so as to compare the prevalence of different genotypes and the differences in the above test index scores. RESULTS: There was complete linkage disequilibrium at rs776746 and rs15524 loci. There were three genotypes of T/T, T/C and C/C at rs776746 locus of CYP3A5 gene. There were significant differences in the frequency of different genotypes between the case group and the control group (χ

Analysis of reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products / 中国临床药理学与治疗学

AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.

Safety analysis on bioequivalence studies of orally inhaled drug products in healthy Chinese subjects / 中国临床药理学与治疗学

AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.

The correlation between FCER2 gene polymorphism and the efficacy of inhaled corticosteroids in patients with chronic rhinosinusitis / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the correlation between FCER2（2206A>G） gene polymorphism and the efficacy of inhaled corticosteroids（ICS） in patients with chronic rhinosinusitis（CRS）. Methods:A total of 208 CRS patients were routinely treated with functional endonasal sinus surgery and postoperative ICS. DNA extraction, PCR amplification and gene sequencing were performed to observe the FCER2（2206A>G） gene polymorphism and calculate the allele frequency. The visual analog scale（VAS） score, Lund-Kennedy score, and computed tomography（CT） Lund-Mackay score were determined 6 months after surgery among patients with different genotypes. Moreover, the polymorphism frequency was compared among different subgroups（chronic rhinosinusitis with nasal polyps versus chronic rhinosinusitis without nasal polyps, eosinophilic chronic rhinosinusitis versus non-eosinophilic chronic rhinosinusitis）. Results:There were FCER2（2206A>G） gene polymorphism in patients with CRS, and the phenotypes included 3 genotypes, AA, AG and GG, with distribution frequencies of 68（32.7%）, 116（55.8%） and 24（11.5%） cases, respectively. No significant differences were found in age, VAS score, nasal endoscopic Lund-Kennedy score and CT imaging Lund-Mackay score among patients with CRS of each genotype before surgery. In patients with the AA genotype, the changes in VAS score（5.74±1.10）, Lund Kennedy score（5.92 ± 1.14）, and CT imaging Lund-Mackay score（13.26±4.26） were significantly higher than in patients with the AG（4.37±0.86, 5.37±1.24, 10.82±3.77） and GG（4.26±0.80, 5.18±1.56, 10.10±3.53） genotype（P<0.05）. However, there were no marked difference between patients with the AG genotype and those with the GG genotype（P>0.05）. Compared with patients with non-eosinophilic sinusitis, Among them, the differences between the GG genotype and AG /AA genes were more significant in eosinophilic sinusitis compared to non-eosinophilic sinusitis（P<0.01）. Conclusion:The FCER2（2206A>G） gene in patients with CRS has genetic polymorphism and is associated with the recovery of CRS patients after surgery, individual corticosteroid sensitivity, and subgroup variability.

Localized delivery of nanomedicine and antibodies for combating COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a major health burden in the world. So far, many strategies have been investigated to control the spread of COVID-19, including social distancing, disinfection protocols, vaccines, and antiviral treatments. Despite the significant achievement, due to the constantly emerging new variants, COVID-19 is still a great challenge to the global healthcare system. It is an urgent demand for the development of new therapeutics and technologies for containing the wild spread of SARS-CoV-2. Inhaled administration is useful for the treatment of lung and respiratory diseases, and enables the drugs to reach the site of action directly with benefits of decreased dose, improved safety, and enhanced patient compliance. Nanotechnology has been extensively applied in the prevention and treatment of COVID-19. In this review, the inhaled nanomedicines and antibodies, as well as intranasal nanodrugs, for the prevention and treatment of COVID-19 are summarized.

Revisión Sistemática Exploratoria sobre Uso de Óxido Nítrico Inhalado para Evaluación de Reactividad Vascular Pulmonar en Laboratorio de Hemodinamia en Sujetos Pediátricos con Hipertensión Pulmonar / Exploratory Systematic Review on the Use of Inhaled Nitric Oxide for Evaluation of Pulmonary Vascular Reactivity in Hemodynamics Laboratory in Pediatric Subjects with Pulmonary Hypertension

Introducción. La hipertensión arterial pulmonar (HAP) es una enfermedad que presenta un elevado índice de mortalidad en la población pediátrica. Para su diagnóstico, el gold standard es la prueba de reactividad vascular pulmonar (PRVP), debido a que permite medir la respuesta vasodilatadora del lecho vascular pulmonar frente a la administración de moléculas con acción terapéutica, como el óxido nítrico inhalado (iNO). Esta prueba al ser positiva se asocia a un mejor pronóstico. En la actualidad existe incertidumbre y falta de consenso sobre la indicación y administración de iNO durante la PRVP. Objetivo. Describir el uso reportado en la literatura sobre iNO en PRVP en sujetos pediátricos con HAP. Métodos. Revisión sistemática exploratoria sensible en bases de datos PubMed, Epistemonikos, Cochrane, Scopus, Lilacs y Scielo, que describen el uso de iNO durante la PRVP en sujetos pediátricos con HAP. Resultados. se identificaron 8.906 artículos, de los cuales se seleccionaron 5 para la revisión cualitativa. La PRVP se realizó durante el cateterismo cardiaco derecho (CCD) en sujetosentre 2 semanas y 18 años de edad. Los diagnósticos fueron HAP primaria, idiopática y asociada a patología cardiaca congénita, cardiomiopatía y enfermedad pulmonar. Esta prueba fue realizada en sujetos sólo con soporte de oxígeno o con sedación profunda en ventilación mecánica invasiva, con dosis variables de oxígeno (21 y 100%) e iNO (3 y 80 ppm), o asociado a otras moléculas como iloprostol®, dilitiazem, sildenafil y/o epoprostenol. La administración de iNO disminuyó presión de arteria pulmonar y la resistencia vascular pulmonar, con mantención de presión arterial sistémica y gasto cardiaco y sin complicaciones asociadas a su uso. Conclusiones. Existen escasos estudios sobre iNO en PRVP pediátrica y con calidad metodológica limitada. El iNO se utiliza como método diagnóstico de vaso reactividad en sujetos pediátricos con HAP asociada a cardiopatía congénita, primaria o secundaria. Los protocolos para su uso son variables con dosis entre 20 y 40 ppm, con o sin uso de oxigeno adicional, con tiempos poco precisos y sin consenso en equipos de administración.

Background. Pulmonary arterial hypertension (PAH) is a disease that has a high mortality rate among the pediatric population. For its diagnosis, the pulmonary vascular reactivity test (PVRT) is considered the "Gold Standard", because it allows to measure the vasodilator response of pulmonary vascular circulation with the administration of molecules with therapeutic action, such as inhaled nitric oxide (iNO). This test, when positive, is associated with a better prognosis of the disease. Currently, there's uncertainty and lack of consensus on the indication and administration of iNO during the PVRT. Objetives. to describe use of iNO in PVRT in pediatric users with PAH reported in the literature. Methods. Scoping review of studies published between 1992 and 2021 in PubMed, Epistemonikos, Cochrane, Scopus, Lilacs and Scielo databases, which describe the use of iNO during PVRT in pediatric users with PAH, in English and Spanish. Primary and secondary studies with a sensitive search strategy were considered. Results. 8,906 articles were identified, 40 were selected by title, 8 by full text, and 5 for final qualitative review. Of the total of articles selected, 3 were primary and 2 secondary studies. PVRT was performed during right heart catheterization (RHC) in a population between 2 weeks and 18 years old. Diagnoses were primary PAH, idiopathic PAH and PAH associated with congenital heart disease, cardiomyopathy and pulmonary disease. This test was carried out in subjects on spontaneous ventilation with oxygen support or with deep sedation in invasive mechanical ventilation, with variable oxygen doses between 21 and 100%, with exclusive use of iNO between 3 and 80 ppm, being more used between 20 and 40 ppm, or associated with other molecules such as iloprostol®, dilithiazim, sildenafil and / or epoprostenol. In all selected studies, administration of iNO decreased PAP (pulmonary artery pressure) and PVR (pulmonary vascular resistance), with maintenance of SBP (systemic arterial blood pressure) and cardiac output. The primary studies were made up of pre and post-test of serial or parallel interventions. The selected studies of iNO in PVRT did not report complications associated with its use. Conclusions. studies on iNO in pediatric PVRT are scarce in number of publications and methodological quality. iNO is used as a diagnostic method of vasoreactivity in pediatric users with PAH associated with congenital, primary, or secondary heart disease. The protocols for its use are variable with recommended doses between 20 and 40 ppm, with or without the use of additional O2, with imprecise times and without consensus in administration equipment. The response to PVRT serves as a guide for the treatment and prognosis of pediatric users with PAH.

Evaluating the effect of childhood and adolescence asthma on the household economy

Abstract Objective To evaluate the relationship between asthma control, family income and family costs of asthma in a population of children-adolescents; to detail the family costs of asthma in this age range; and to compare asthma costs for the families of children-adolescents and adults. Methods The authors invited asthmatic subjects who attended a scheduled spirometry test at the Jundiaí School of Medicine (FMJ). The FMJ performs all spirometry tests requested by staff physicians who serve at the public healthcare system in the municipality. Volunteers responded to the ACQ, the Asthma Family Costs Questionnaire and underwent a spirometry test. Results The authors included 342 children-adolescents. Families of children-adolescents taking maintenance therapy and families of those reporting uncontrolled asthma symptoms were more likely to report any expenditure with asthma during the preceding month. In this age range, the smallest expenditures were on diagnostic tests and medical consultations, while home expenditures to avoid asthma triggers were the highest ones. As compared to adults' families, the children and adolescents families reported a greater proportion of income committed with asthma. Expenditures with transportation to healthcare facilities for asthma care were greater in the families of children-adolescents as compared to the values reported by the adults' families; in contrast, loss of income due to asthma was smaller in the families of children-adolescents. Conclusions Children-adolescents' asthma affects the household economy. The authors believe researchers should assess this outcome when designing studies about asthma. Finally, the study's data support the necessity of public policies in low-resource communities to minimize the economic impact of children and adolescents' asthma.

Efecto del óxido nítrico inhalado en la mecánica ventilatoria y oxigenación de pacientes con hipoxemia grave refractaria a prono prolongado y bloqueo neuromuscular secundario a infección por SARS-CoV-2 / Effect of inhaled nitric oxide on ventilatory mechanics and oxygenation of patients with severe hypoxemia refractory to prolonged prone and neuromuscular blockade secondary to SARS-CoV-2 / Efeito do óxido nítrico inalado na mecânica ventilatória e oxigenação de pacientes com hipoxemia grave refratária a pronação prolongada e bloqueio neuromuscular secundário à infecção por SARS-CoV-2

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Abstract: Introduction: Among the patients infected with SARS-CoV-2, 14.6% were admitted to intensive care unit. this 29 to 75% required invasive mechanical ventilation with an associated mortality of 12 to 81%. Acute respiratory distress syndrome (ARDS) is the most serious form of presentation. The pathophysiology of ARDS secondary to SARS-CoV-2 differs from conventional causes. It presents dysregulation in hypoxic pulmonary vasoconstriction, secondary acute pulmonary hypertension and microthrombotic phenomena. The development of refractory severe hypoxemia (PaO2 < 60 mmHg or PaO2/FiO2 < 100 mmHg, with FiO2 80 to 100%, with PEEP > 10 to 20 cmH2O for at least 10 to 12 hours) constitutes the scenario of maximum severity with an associated mortality of 71 to 94%. The use of rescue strategies that impact on the specific pathophysiology of this entity such as the use of inhaled nitric oxide, neuromuscular blockade and prone ventilation have emerged as therapeutic targets of interest. Protective mechanical ventilation (plateau pressure [Pplat] < 27 cmH2O and driving pressure [DP] < 15 cmH2O) continues to be the cornerstone of the management. Objectives: To determine whether there is an association between the use of inhaled nitric oxide and prone ventilation with ventilatory mechanics in patients with severe refractory hypoxemia secondary to SARS-CoV-2 infection. Material and methods: A historical, retrospective, descriptive, comparative and retrolective cohort study was carried out. Data from the records of patients admitted to the Respiratory ICU of the ABC Medical Center with a diagnosis of ARDS secondary to SARS-CoV-2 infection who required iNO and mechanical ventilation in prone from April 1 to December 31, 2020 were analyzed. A univariate analysis was performed, the statistical analysis was performed in SPSS v 21, measures of trend, dispersion were analyzed as well as the analysis of risk factors with Student's t test and χ2. Results: A total of 108 patients were analyzed, of which 54 received iNO, neuromuscular blockade and prone and 54 only neuromuscular blockade and prone ventilation. 81.5% (n = 88) were men. The most common comorbidity was diabetes mellitus in 51.9% (n = 56). The increase in oxygenation (delta PaO2/FiO2) was with a median of 31.9 ± 15.2 mmHg in the iNO group and 52.9 ± 16.74 mmHg in the control group (p = 0.001). The postintervention Pplat in the iNO group was 26.3 ± 3 and 34.5 ± 1.9 cmH2O in the control group (p = 0.792). The preintervention DP in the iNO group was 17.2 ± 3.9 and 13.4 ± 2.8 cmH2O in control group vs 13.1 ± 1.29 and 12 ± 1.92 cmH2O after the intervention (p = 0.001). Conclusions: The use of iNO in patients with severe hypoxemia refractory to prone ventilation and neuromuscular blockade did not produce a statistically significant improvement in oxygenation, however it allowed to reprogram the ventilatory support to keep the patient in goals of alveolar protection.

Resumo: Introdução: 14.6% dos pacientes infectados com SARS-CoV-2 são internados em terapia intensiva. Destes, 29 a 75% necessitam de ventilação mecânica invasiva com mortalidade associada de 12 a 81%. A síndrome do desconforto respiratório agudo (SDRA) é a forma mais grave de apresentação. A fisiopatologia da SDRA secundária ao SARS-CoV-2 difere das causas convencionais. Apresenta desregulação na vasoconstrição pulmonar hipóxica, hipertensão pulmonar aguda secundária e fenômenos microtrombóticos. O desenvolvimento de hipoxemia grave refratária (PaO2 < 60 mmHg ou PaO2/FiO2 < 100 mmHg, com FiO2 de 80 a 100%, PEEP > 10 a 20 cmH2O por pelo menos 10 a 12 horas) constitui o cenário mais grave com mortalidade associada de 71 a 94%. O uso de estratégias de resgate que impactam na fisiopatologia específica dessa entidade, como o uso de óxido nítrico inalatório (NOi), bloqueio neuromuscular e ventilação prona, surgiram como alvos terapêuticos de interesse. A ventilação mecânica protetora (Pressão de Platô [PPLAT] < 27 cmH2O e Pressão de Condução [CP] < 15 cmH2O) continua sendo a base de seu manejo. Objetivo: Determinar se existe associação entre o uso de óxido nítrico inalatório e ventilação prona prolongada com mecânica ventilatória em pacientes com hipoxemia refratária grave secundária à infecção por SARS-CoV-2. Material e métodos: Realizou-se um estudo de coorte histórico, retrospectivo, descritivo, comparativo e retroletivo. Analisaram-se dados dos prontuários de pacientes internados na UTI Respiratória do Centro Médico ABC com diagnóstico de SDRA secundária à infecção por SARS-CoV-2 que necessitaram de óxido nítrico inalatório e ventilação mecânica prona no período de 1o de abril a 31 de dezembro de 2020. Realizou-se uma análise univariada , a análise estatística foi realizada no SPSS v 21, foram analisadas as medidas de tendência e dispersão, assim como a análise dos fatores de risco com teste t de Student e χ2. Resultados: Analisaram-se 108 pacientes, dos quais 54 receberam NOi, bloqueio neuromuscular e prono e 54 apenas bloqueio neuromuscular e ventilação prona. 81.5% (n = 88) eram homens. A comorbidade mais comum foi diabetes mellitus em 51.9% (n = 56). O aumento da oxigenação (Delta PaO2/FiO2) foi com mediana de 31.9 ± 15.2 mmHg no grupo NOi e 52.9 ± 16.74 mmHg no grupo controle (p = 0.001). A PPLAT após a intervenção no grupo NOi foi de 26.3 ± 3 e 34.5 ± 1.9 cmH2O no grupo controle (p = 0.792). A PC antes da intervenção no grupo NOi foi de 17.2 ± 3.9 e 13.4 ± 2.8 cmH2O no grupo controle vs 13.1 ± 1.29 e 12 ± 1.92 cmH2O após a intervenção (p = 0.001). Conclusões: O uso de NOi em pacientes com hipoxemia grave refratária à ventilação em pronação e bloqueio neuromuscular não produziu melhora estatisticamente significativa na oxigenação, porém permitiu que o suporte ventilatório fosse reprogramado para manter as metas de proteção alveolar do paciente.

A prospective and observational study on the variation in Hemoglobin A1c levels among asthmatic children using inhaled corticosteroids

Background: The studies in children regarding the effects of inhaled corticosteroids (ICS) on the carbohydrate metabolism are scant in India. This study was undertaken to determine if there is any effect of inhaled steroids on the glycemic control. Aims and Objectives: The aim of the study was to analyze the pattern of glycated hemoglobin (HbA1c) levels in children with persistent asthma, before and after using prophylactic doses of ICS and to evaluate and compare HbA1c levels separately in those taking budesonide and in those taking fluticasone or other steroids. Materials and Methods: It was a prospective and observational study, based on a study proforma. Children of 2–12 years of age, diagnosed with mild-to-moderate persistent asthma, attending the Asthma Clinic at Paediatrics Department of SAT Hospital, Government Medical College, Thiruvananthapuram were included in the study. The diagnosis of asthma and the severity was recorded according to Global Initiative for Asthma guidelines. The sample size was calculated to be 40. Type, dose, and frequency of administration of ICS and other coprescribed drugs were recorded on an asthma diary and entered into the study proforma. HbA1c levels were measured in children before they were started on ICS, on the same day of visit using high perfusion liquid chromatography technique and repeated after 6 months. Student’s t-test was used to compare mean values between two groups. Results: Mean age of patients is 5.75. About 62.5% of patients were males. About 72.5% of the patients had a diagnosis of moderate persistent asthma. The mean HbA1c before the treatment with ICS was 5.36 and after the treatment is 5.37 and the difference was not significant. Conclusions: There was no significant change in HbA1c levels with the use of ICS.

Sedación con sistema AnaConDa en pacientes COVID-19 crítico y su impacto en días de ventilación mecánica / Sedation with AnaConDa system in critical COVID-19 and its impact on mechanical ventilation length / Sedação com o sistema AnaConDa em pacientes em estado crítico com COVID-19 e seu impacto nos dias de ventilação mecânica

Resumen La sedación en el paciente crítico es esencial para asegurar un desenlace óptimo. El desabasto de medicamentos ha sido un reto frecuente durante la pandemia por COVID-19, repercutiendo principalmente en aquellos medicamentos empleados para la sedación y la analgesia. Esto ha llevado a buscar alternativas para la sedación intravenosa, siendo una de ellas la administración de anestésicos volátiles. La evidencia respecto a uso de sedación volátil en el paciente crítico apoya a su empleo en el síndrome de dificultad respiratoria aguda pues se ha demostrado que mejora el intercambio gaseoso, reduce el edema alveolar y la inflamación pulmonar. Asimismo, se ha reportado disminución del tiempo de destete de la ventilación mecánica posterior a la suspensión del medicamento. Se realizó un estudio de cohorte retrospectivo, comparativo y longitudinal en una Unidad de Terapia Intensiva mediante la búsqueda intencionada en el expediente electrónico y el análisis de los datos de aquellos pacientes con diagnóstico de COVID-19 crítico que ameritaron el uso de ventilación mecánica e inicio de sedación intravenosa y volátil con sevoflurano durante el periodo comprendido desde el 01 de enero al 30 de junio de 2021. Estos datos se compararon con un grupo de pacientes seleccionados aleatoriamente que estuvieron internados en ese mismo periodo y que recibieron ventilación mecánica y sedación intravenosa exclusiva. Se analizó como desenlace primario si existía una diferencia significativa en el número de días de ventilación mecánica y como objetivos secundarios la presencia de diferencia significativa en los días de hospitalización, días de estancia en terapia intensiva, incidencia de neumonía intrahospitalaria y en la incidencia de mortalidad. Se identificaron 43 pacientes que recibieron sedación volátil e intravenosa, de los cuales 36 cumplían con las características necesarias para ser incluidos en el estudio. Los pacientes recibieron en promedio seis días de sedación con sevoflurano. Se compararon con 42 pacientes que recibieron sedación intravenosa exclusiva. En el análisis poblacional se encontró una diferencia significativa de edad en la población que recibió sedación volátil. Dentro de los desenlaces estudiados se encontró una diferencia significativa en los días de hospitalización, favoreciendo el empleo de sevoflurano. Ninguno de los otros desenlaces estudiados mostró diferencia significativa. La sedación volátil es una herramienta útil que puede ofrecer múltiples beneficios a los pacientes de terapia intensiva con necesidad de ventilación mecánica. El presente estudio demostró una disminución significativa del tiempo de estancia hospitalaria, aunque se limita por un sesgo de edad en el subgrupo de sevoflurano. Es necesario realizar estudios con muestras más grandes, aleatorizadas y con criterios estandarizados para la aplicación de la terapia con el fin de validar estos hallazgos.

Abstract Sedation is essential for an optimal outcome in the critical care patient with mechanical ventilation. Drug shortages have been common during the COVID-19 pandemic, mainly in those medications employed for sedation and analgesia. This has led to a search for alternatives to traditional intravenous sedation, one of which is volatile sedation. Evidence around volatile sedation in the critical care patient supports its employment in ARDS. Multiples studies have shown a positive effect on the gaseous exchange, and a diminishment in both alveolar edema and lung inflammation. A significant decrease in awakening time from sedation has also been reported. We conducted a retrospective, comparative, longitudinal cohort study in a single intensive care unit, retrieving the medical records of critical COVID-19 patients which needed mechanical ventilation, and which were administered volatile sedation alongside intravenous sedation. This group was compared to a randomly selected group of critical COVID-19 patients with mechanical ventilation which were administered exclusively intravenous sedation. The analyzed trial period comprised from January 01, to June 30, 2021. The main outcome was number of days on mechanical ventilation, with secondary outcomes of length of stay on the ICU, length of stay in the hospital, incidence of ventilation associated pneumonia and both 30-day and overall mortality. The medical records of 43 patients which received mixed sedation were identified, with 36 fulfilling the inclusion criteria. The average time of administration of sevoflurane was six days in the population studied. This group was compared to 42 patients with exclusive intravenous sedation. Baseline characteristics were similar among the two groups, except for a significant trend towards younger age in the sevoflurane group. There was a significant difference on length of stay in the hospital, with sevoflurane being associated with a shorter stay compared to exclusive intravenous sedation. None of the other analyzed outcomes showed a significant difference. Volatile sedation is a useful tool with multiple benefits for the critical care patients with a need for mechanical ventilation. The current study demonstrates a significant difference in the length of stay in the hospital, but more studies are needed with a greater sample size, randomization, and standardized criteria for the administration of the intervention to reduce the risk of bias and validate these findings.

Resumo A sedação é essencial para um resultado ideal no paciente de cuidados intensivos com ventilação mecânica. A escassez de medicamentos tem sido um desafio frequente durante a pandemia de COVID-19, afetando principalmente os medicamentos usados para sedação e analgesia. Isso levou à busca de alternativas à sedação intravenosa, sendo uma delas a administração de anestésicos voláteis. As evidências sobre o uso de sedação volátil em pacientes críticos apoiam seu uso na síndrome do desconforto respiratório agudo, uma vez que demonstrou melhorar as trocas gasosas, reduz o edema alveolar e a inflamação pulmonar. Da mesma forma, foi relatada uma diminuição no tempo de desmame da ventilação mecânica após a descontinuação da droga. Realizou-se um estudo de coorte retrospectivo, comparativo e longitudinal em unidade de terapia intensiva por meio de busca deliberada no arquivo eletrônico e análise dos dados daqueles pacientes com diagnóstico de COVID-19 crítico que necessitaram do uso de ventilação mecânica e iniciação de sedação intravenosa e volátil com sevoflurano durante o período de 1o de janeiro a 30 de junho de 2021. Esses dados foram comparados com um grupo de pacientes selecionados aleatoriamente que foram internados no mesmo período e que receberam ventilação mecânica e sedação. Analisou-se o desfecho primário se houve diferença significativa no número de dias de ventilação mecânica e como objetivos secundários a presença de diferença significativa nos dias de internação, dias de permanência em terapia intensiva, incidência de pneumonia hospitalar e na incidência da mortalidade. Foram identificados 43 pacientes que receberam sedação volátil e intravenosa, dos quais 36 preencheram as características necessárias para serem incluídos no estudo. Os pacientes receberam em média 6 dias de sedação com sevoflurano. Eles foram comparados com 42 pacientes que receberam sedação intravenosa exclusiva. Na análise populacional, foi encontrada diferença significativa de idade na população que recebeu sedação volátil. Entre os desfechos estudados, foi encontrada diferença significativa nos dias de internação, favorecendo o uso do sevoflurano. Nenhum dos outros desfechos estudados apresentou diferença significativa. A sedação volátil é uma ferramenta útil que pode oferecer múltiplos benefícios aos pacientes de terapia intensiva que necessitam de ventilação mecânica. O presente estudo demonstrou uma diminuição significativa no tempo de internação, mais se limitada por um viés de idade no subgrupo sevoflurano. É necessário realizar estudos com amostras maiores, aleatórias e com critérios padronizados para a aplicação da terapia para validar esses achados.

Clinical trials of inhalation in pediatric population in China / 中国临床药理学与治疗学

AIM: To investigate the characteristics of clinical trials of inhalation in pediatric population in China. METHODS: The pediatric clinical trials of inhaled drugs in China registered on the www.Chinadrugtrials.org.cn and Clinical Trials in USA respectively until November 20, 2021 were reviewed. The characteristics of pediatric clinical trials of inhaled drugs including the clinical trial phases, drug indications and classificatio etc. were analyzed. RESULTS: There were 21 pediatric clinical trials of inhaled drugs registered on the www.Chinadrugtrials.org.cn, accounted for 8.9%(21/235) of inhalation clinical trials in all populations. 47.6% of them were generic drugs, mainly focusing on expectorants for Phlegm symptoms and inhaled preparations for asthma, which accounting for 71.4%(15/21). There were 34 pediatric clinical trials of inhaled drugs registered on the Clinical Trials in USA, the drug indications of which were mainly asthma and anesthesia, accounting for 76.5%(26/34). CONCLUSION: The pediatric clinical trials of inhalations in China started later, and the total number is small compared to adults, mainly focusing on generic drugs. We should pay attention to the research and development of new inhalation drugs, standardizing and promoting the clinical trials of inhaled drugs in pediatric population actively.

Application and progress of pharmacodynamics study in bioequivalence evaluation of orally inhaled drug products / 中国临床药理学与治疗学

Orally inhaled drug products (OIDPs) play a great role in the pharmacological treatment of chronic obstructive pulmonary disease (COPD) and asthma. There is an unmet clinical need for OIDPs. Pharmacodynamics-Bioequivalence studies (PD-BE) are recommended by several national guidelines as important research methods for bioequivalence study of OIDPs. It can effectively bridge the gap between in vitro studies and PK-BE studies in evaluating the efficacy and safety consistency of generic drugs with the original drugs. There are two research methods for PD-BE, using a diastolic model or an excitation model. The different methods use different metrics to evaluate efficacy. The more commonly used metrics include Forced Expiratory Volume in the First Second (FEV1), Specific Airway Conductance (sGaw), Peripheral Airway Resistance (R5-20), and stimulant concentration/dose (PC20/PD20). PD-BE studies using FEV1 as an efficacy metric is also recommended by the FDA (Food and Drug Administration), EMA (European Medicines Agency) and NMPA (National Medical Products Administration) guidelines and is widely accepted by investigators. In such PD-BE studies, the trial protocols for different OIDPs drugs are relatively consistent in terms of trial design, trial data processing, and equivalence evaluation criteria, while there are detailed differences in terms of target population, single/multiple dosing, dose administration, and collection site design. This paper reviews the progress of PD-BE studies in the bioequivalence evaluation of OIDPs by combining national guidelines and PD-BE-related studies of OIDPs published in the last five years, with a view to providing important theoretical information for PD-BE studies of OIDPs.

Clinical application and research progress of inhaled methoxyflurane / 中国临床药理学与治疗学

As a fluorinated hydrocarbon anesthetic, methoxyflurane may cause serious adverse reactions such as renal damage under anesthetic doses, but its analgesic effect at sub-anaesthetic doses is safe, high tolerability, and short-term acute Good choice for analgesia. This article describes the pharmacokinetics, clinical validity, adverse reactions and clinical application of methoxyflurane, and explores the feasibility of methoxyflurane as an analgesic in clinical application. Methoxyflurane is convenient to use as an inhaled analgesic. It can provide patients with emergency analgesia without intravenous administration. It is a good choice for emergency analgesia in pre-hospital and emergency settings.

Anesthetics, analgesics and cognitive function / 中国临床药理学与治疗学

Cognitive dysfunction has become a pivotal factor affecting the quality of life of elderly patients. The existing literatures can not explain the factors causing cognitive decline. Many researchers believe that anesthetics and analgesics may play important roles in cognitive dysfunction. This review will discuss the effects of different anesthetics and analgesics on cognitive function and briefly describe their mechanisms, so as to provide reference for the rational choice of medications in clinical practice.

TRALI as a Cause of Massive Tracheal Secretions during Cardiac Surgery / 日本心臓血管外科学会雑誌

A 46 year-old man underwent double valve replacement for valve insufficiency due to infective endocarditis. Upon withdrawal from extracorporeal circulation and administration of 8 units of fresh frozen plasma, a large amount of yellow serous secretion was aspirated from the trachea, and rapid and exacerbated oxygenation was observed. We determined that the patient was not congested, based on his hemodynamics; instead, he appeared to have acquired transfusion-related acute lung injury (TRALI). The patient was given a steroid infusion. By the time the patient returned to the intensive care unit, his oxygenation capacity improved and the secretions from his trachea decreased. The patient was weaned off the ventilator on the second post-operative day. Inhaled nitric oxide was very effective in improving oxygenation. We conjectured that TRALI should be recognized as a differential diagnosis for poor oxygenation after withdrawal from extracorporeal circulation.

New progress of airway management in children with cystic fibrosis / 中华实用儿科临床杂志

Cystic fibrosis (CF) is a multisystem disease mainly caused by pathogenic mutation of the cystic fibrosis transmembrane conduction regulator gene.In recent years, with the deepened understanding of the disease and the popularization of gene detection technology, an increasing number of children are diagnosed with CF in China.Lung involvement is reported to affect the prognosis of the disease.Lung involvement is closely related to the airway, and good airway management can prolong the life of children.In this paper, the selection of airway clearance techniques and inhaled drugs were expounded, so as to improve the long-term airway management of children with CF in China.

Relationship between gene polymorphism of inhaled glucocorticosteroids budesonide and efficacy in asthma / 中国临床药理学与治疗学

AIM: To investigate the relationship among the rs37973 polymorphism of glucocorticoid induced transcription factor 1 (GLCCI1) gene, the rs1876828 polymorphism of corticotropin-hormone receptor 1 (CRHR1) gene, the rs28364072 polymorphism of Fc fragment of IgE receptor II (FCER2) gene and the response to inhaled corticosteroids (ICS) budesonide in patients with asthma. METHODS: 152 blood samples of patients with asthma were collected. The DNA were studied by blood samples. Fluorescence in situ hybridization method was used to detect the polymorphism of GLCCI1, CRHR1, FCER2. Lung function index of the ICS before and after treatment, such as forced vital capacity (FVC), first second forced breath volume (FEV