Outcomes of Extracorporeal Life Support (ECLS) in Acute Severe Asthma: A Narrative Review.

BACKGROUND: In this narrative review we aimed to explore outcomes of extracorporeal life support (extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R)) as rescue therapy in patients with status asthmaticus requiring mechanical ventilation. METHODS: Multiple databases were searched for studies fulfilling inclusion criteria. Articles reporting mortality and complications of ECMO and ECCO2R in mechanically ventilated patients with acute severe asthma (ASA) were included. Pooled estimates of mortality and complications were obtained by fitting Poisson's normal modeling. RESULTS: Six retrospective studies fulfilled inclusion criteria thus yielding a pooled mortality rate of 17% (13-20%), pooled risk of bleeding of 22% (7-37%), mechanical complications in 26% (21-31%), infection in 8% (0-21%) and pneumothorax rate 4% (2-6%). CONCLUSION: Our review identified a variation between institutions in the initiation of ECMO and ECCO2R in patients with status asthmaticus and discrepancy in the severity of illness at the time of cannulation. Despite that, mortality in these studies was relatively low with some studies reporting no mortality which could be attributed to selection bias. While ECMO and ECCO2R use in severe asthma patients is associated with complication risks, further studies exploring the use of ECMO and ECCO2R with mechanical ventilation are required to identify patients with favorable risk benefit ratio.

Wide Institutional Variability in the Treatment of Pediatric Critical Asthma: A Multicenter Retrospective Study.

OBJECTIVES: Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use. DESIGN: Multicenter retrospective cohort study. SETTING: Administrative data from the Pediatric Health Information Systems (PHIS) database. PATIENTS: All inpatients 2-18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5, p < 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS ( p = 0.81) nor the percentage of encounters with PICU admission ( p = 0.47). CONCLUSIONS: Use of adjunctive therapies for status asthmaticus varies widely among large children's hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs.

Treating asthma patients with probiotics: a systematic review and meta-analysis / Tratamiento de pacientes asmáticos con probióticos: revisión sistemática y metaanálisis

Objective: to evaluate the role of probiotics in the treatment of asthma patients by meta-analysis.Methods: PubMed, Embase, The Cochrane Library, Web of Science, and other databases were searched by computer, and the relevant literature on the treatment of asthma by probiotics that met the inclusion criteria was screened by manual retrieval. Meta-analysis was performed using Revman 5.4 software and the combined effect was evaluated by odds ratio (OR) or mean difference (MD) and 95 % confidence interval (CI). Results: a total of ten references were included, all of which were randomized controlled studies, and a total of 1,101 people were investigated. Fractional exhaled nitric oxide (FeNO) (MD = -7.17, 95 % CI: -12.81, -1.54), asthma symptom severity (MD = -0.07, 95 % CI: -0.10, -0.04), Childhood Asthma Control Test (CACT) (MD = 2.26, 95 % CI: 1.14, 3.39), and the number of acute episodes of asthma (OR = 0.30, 95 % CI: 0.19, 0.47) in the probiotics group were better than those in the control group. There was no significant difference in forced expiratory volume in the first second (FEV1) (MD = 0.11, 95 % CI: -0.05, 0.26) and FEV1/FVC (%) (MD = 0.32, 95 % CI: -1.48, 2.12). Conclusion: the use of probiotics in patients with asthma can improve lung inflammation and asthma symptoms, reduce the number of asthma attacks, and have no effect on lung function.(AU)

Objetivo: evaluar el papel de los probióticos en el tratamiento de pacientes con asma mediante metaanálisis.Métodos: se realizaron búsquedas informáticas en PubMed, Embase, The Cochrane Library, Web of Science y otras bases de datos, y se examinó la literatura relevante sobre el tratamiento del asma con probióticos que cumplía con los criterios de inclusión mediante recuperación manual. El metaanálisis se realizó con el software Revman 5.4 y el efecto combinado se evaluó mediante la razón de probabilidades (OR) o diferencia media (MD) y el intervalo de confianza (IC) del 95 %. Resultados: se incluyó un total de diez referencias, todas ellas estudios controlados aleatorios, y se investigó un total de 1.101 personas. El óxido nítrico exhalado (FeNO) (MD = -7,17, IC 95 %: -12,81, -1,54), la gravedad de los síntomas del asma (MD = -0,07, IC 95 %: -0,10, -0,04), la Prueba de Control del Asma (CACT-ACT) (MD = 2,26, IC 95 %: 1,14, 3,39) y el número de episodios agudos de asma (OR = 0,30, IC 95 %: 0,19, 0,47) en el grupo de probióticos fueron mejores que en el grupo de control. No hubo diferencia significativa en volumen espiratorio forzado en el primer segundo (FEV1) (DM = 0,11, IC 95 %: -0,05, 0,26) y FEV1/FVC (%) (DM = 0,32, IC 95 %: -1,48, 2,12). Conclusión: el uso de probióticos en pacientes con asma puede mejorar la inflamación pulmonar y los síntomas del asma, reducir el número de ataques de asma y no tener efecto sobre la función pulmonar.(AU)

Omalizumab rescue therapy in refractory status asthmaticus.

INTRODUCTION: Refractory status asthmaticus (RSA) is a severe, life-threatening form of asthma exacerbation that persists despite aggressive treatment with systemic corticosteroids, bronchodilators, and other supportive measures. Omalizumab, a monoclonal antibody that targets IgE, has been approved for treating severe allergic asthma and is effective in reducing the frequency of exacerbations and improving asthma control. Limited evidence exists regarding the use of Omalizumab in RSA, but some studies have suggested that it may have a role in its management. CASE: A 39-year-old male with a decade-long history of asthma presented to the emergency department intubated and unresponsive to pharmacological therapy. The patient's IgE levels were elevated, and Omalizumab was administered after a comprehensive evaluation. The patient made a dramatic recovery and was successfully weaned off the ventilator within 24 h of receiving Omalizumab. He made an uneventful recovery and was discharged home on Omalizumab once every two weeks with regular follow-ups. DISCUSSION AND CONCLUSION: Per our literature search, only 3 cases have been reported where Omalizumab was administered to patients with RSA to wean them off ventilatory support successfully. This case study adds to the existing data on the potential benefits of Omalizumab in managing RSA. It suggests it may be a valuable treatment option for patients who do not respond to standard therapy. However, further research is needed to determine the efficacy and safety of Omalizumab in this population.

Pediatric extracorporeal life support for refractory status asthmaticus: ELSO Registry trends from the past decade.

BACKGROUND: Extracorporeal life support (ECLS) for status asthmaticus (SA) is rare. Increased safety and experience may increase utilization of ECLS for SA. METHODS: We reviewed pediatric (<18 years old) patients requiring ECLS for SA between 1998 and 2019 within the Extracorporeal Life Support Organization (ELSO) Registry and Nemours Children's Health (NCH) system. We compared patient characteristics, pre-ECLS medications, clinical data, complications, and survival to discharge between Early (1988-2008) and Late (2009-2019) eras. RESULTS: From the ELSO Registry, we identified 173 children, 53 in Early and 120 in Late eras, with primary diagnosis of SA. Pre-ECLS hypercarbic respiratory failure was similar between eras (median pH 7.0 and pCO2 111 mm Hg). Venovenous mode (79% vs. 82%), median ECLS time (116 vs. 99 h), time to extubation (53 vs. 62 h), and hospital survival (89% vs. 88%) also remained similar. Intubation to cannulation time significantly decreased (20 vs. 10 h, p = 0.01). ECLS without complication occurred more in the Late era (19% vs. 39%, p < 0.01), with decreased hemorrhagic (24% vs. 12%, p = 0.05) and noncannula-related mechanical (19% vs. 6%, p = 0.008) complications. Within NCH, we identified six Late era patients. Pre-ECLS medication favored intravenous beta agonists, bronchodilators, magnesium sulfate, and steroids. One patient died from neurological complications following pre-ECLS cardiac arrest. CONCLUSIONS: Collective experience supports ECLS as a rescue therapy for pediatric SA. Survival to discharge remains good, and complication rates have improved. Pre-ECLS cardiac arrest may potentiate neurologic injury and impact survival. Further study is needed to evaluate causal relationships between complications and outcomes.

Rendimiento clínico de espirometría y oscilometría respiratoria para predecir crisis graves en escolares con asma / Clinical performance of spirometry and respiratory oscillometry for prediction of severe exacerbations in schoolchildren with asthma

Objetivo: Determinar el rendimiento de espirometría y oscilometría respiratoria (RO) para predecir crisis de asma graves (CAG) en niños. Métodos: En un estudio prospectivo, 148 niños (6-14 años) con asma realizaron RO, espirometría y prueba broncodilatadora. Se clasificaron en fenotipos de atrapamiento aéreo (ATA), limitación del flujo aéreo (LFA) y normal, según la espirometría y prueba broncodilatadora. A las 12 semanas fueron revalorados respecto a aparición de CAG. Se analizó el rendimiento de los parámetros de RO, espirometría y fenotipos ATA/LFA para predecir la aparición de CAG con cocientes de probabilidad positivos y negativos (LR+/LR−), área bajo la curva de curvas ROC y análisis multivariante ajustado por posibles factores de confusión. Resultados: Un 7,4% tuvo CAG en el seguimiento, con diferencias según fenotipo (Normal 2,4%; LFA 17,9%; ATA 22,2%; p=0,005). La mejor área bajo la curva fue del flujo espiratorio forzado 25-75% (FEF25-75): 0,787; intervalo de confianza 95%: 0,600-0,973. También tuvieron áreas bajo la curva significativas el área de reactancia (AX), el volumen espiratorio forzado en el primer segundo (FEV1), el cambio post-broncodilatador en capacidad vital forzada (FVC), y FEV1/FVC. Todas las variables tenían una baja sensibilidad para predecir CAG. La mejor especificidad correspondía al fenotipo ATA: 93,8% (intervalo de confianza del 95% 87,9-97,0), pero solo FEF25-75 tenía tanto LR+ como LR− significativos. En el análisis multivariante, solo algunos parámetros de espirometría fueron significativos para predecir CAG (fenotipo ATA, FEF25-75 y FEV1/FVC). Conclusiones: La espirometría tiene un rendimiento superior a la RO para predecir CAG a medio plazo en escolares con asma. (AU)

Objective: To determine the performance of spirometry and respiratory oscillometry (RO) in the prediction of severe asthma exacerbations (SAEs) in children. Methods: In a prospective study, 148 children (age 6–14 years) with asthma were assessed with RO, spirometry and a bronchodilator test. Based on the findings of spirometry and the bronchodilator test, they were classified into 3 phenotypes: air trapping (AT), airflow limitation (AL) and normal. Twelve weeks later, they were re-evaluated in relation to the occurrence of SAEs. We analysed the performance of RO, spirometry and AT/AL phenotypes for prediction of SAEs by means of positive and negative likelihood ratios (LR+/LR–), ROC curves with the corresponding areas under the curve and a multivariate analysis adjusted for potential confounders. Results: During the followup, 7.4% of patients had SAEs, and there were differences between phenotypes (normal, 2.4%; AL, 17.9%; AT, 22.2%, P=.005). The best area under the curve corresponded to the forced expiratory flow between 25% and 75% of vital capacity (FEF25–75): 0.787; 95% confidence interval, 0.600-0.973. Other significant areas under the curve were those for the reactance area (AX), forced expiratory volume in the first second (FEV1), the post- bronchodilator change in forced vital capacity (FVC), and the FEV1/FVC ratio. All of the variables had a low sensitivity for prediction of SAEs. The AT phenotype had the best specificity (93.8%; 95% confidence interval, 87.9-97.0), but LR+ and LR– were both significant only for the FEF25–75. In the multivariate analysis, only some spirometry parameters were significative for prediction of SAEs (AT phenotype, FEF25–75 and FEV1/FVC). Conclusions: Spirometry performed better than RO for prediction of SAEs in the medium term in schoolchildren with asthma. (AU)

Assessment and therapeutic management of acute asthma: The approaches of nursing staff in patient care.

Acute severe asthma describes serious asthmatic attacks, which remain a major treatment challenge and a significant source of morbidity in adults. It places the patient in danger of developing respiratory failure, a condition known as status asthmaticus. It is often fatal if not recognized and treated early. Many patients are at risk for numerous reasons; thus, the key issues are early detection, assessment and management. A multidisciplinary and collaborative approach is needed to effectively treat acute respiratory failure (ARF). Considerable research has investigated the range of opportunities available for treating asthma. Current treatment options include conventional agents, such as inhalational corticosteroids, â-agonists, leukotriene modulators, monoclonal antibodies, and oral corticosteroids (OCS). Nurses are in a perfect position to assess patients' risk of developing respiratory failure, monitor them, evaluate their care, and coordinate a multidisciplinary approach. In this review, we discuss acute asthma and the role of the nursing officer (NO) in the management of the illness. The review will also emphasize various current treatment approaches available for the NO that can effectively target and prevent respiratory failure. This review provides nurses and other healthcare workers with updated information on timely, effective and safe supportive management of patients with asthma.

Outcomes of children with life-threatening status asthmaticus requiring isoflurane therapy and extracorporeal life support.

BACKGROUND: Severe, refractory asthma is a life-threatening emergency that may be treated with isoflurane and extracorporeal life support. The objective of this study was to describe the clinical response to isoflurane and outcomes after discharge of children who received isoflurane and/or extracorporeal life-support for near-fatal asthma. METHODS: This was a retrospective descriptive study using electronic medical record data from two pediatric intensive care units within a single healthcare system in Atlanta, GA. RESULTS: Forty-five children received isoflurane, and 14 children received extracorporeal life support, 9 without a trial of isoflurane. Hypercarbia and acidosis improved within four hours of starting isoflurane. Four children died during the index admission for asthma. Twenty-seven percent had a change in Functional Status Score of three or more points from baseline to PICU discharge. Patients had median percent predicted FEV1 and FEV1/FVC ratios pre- and post-bronchodilator values below normal pediatric values. CONCLUSION: Children who received isoflurane and/or ECLS had a high frequency of previous PICU admission and intubation. Improvement in ventilation and acidosis occurred within the first four hours of starting isoflurane. Children who required isoflurane or ECLS may develop long-lasting deficits in their functional status. Children with near-fatal asthma are a high-risk group and require improved follow-up in the year following PICU discharge.

Early Intravenous Magnesium Sulfate Administration in the Emergency Department for Severe Asthma Exacerbations.

BACKGROUND: Severe asthma exacerbations in pediatric patients occur frequently and can require pediatric intensive care unit (PICU) admission. OBJECTIVE: To determine if early administration of intravenous magnesium sulfate (IVMg) to pediatric patients experiencing severe asthma exacerbations, defined as a respiratory clinical score (RCS) of 9 to 12, resulted in fewer PICU admissions. METHODS: Retrospective chart review of pediatric patients aged from 2 to 17 years presenting with a severe asthma exacerbation to a single tertiary care pediatric emergency department. Univariable and multivariable logistic regression analyses were used to determine if admission to the PICU was associated with early IVMg treatment, within 60 minutes of registration. RESULTS: A total of 1911 patients were included in the study, of which 1541 received IVMg. The average time to IVMg was 79 minutes, with 35% of the patients receiving it within 60 minutes of arrival. Two hundred forty-eight (13%) were admitted to the PICU, 641 (34%) were admitted to the general inpatient floor, and 1022 (53%) were discharged home. Factors associated with increased odds ratio (OR) of PICU admission were: early IVMg (OR, 1.63; 95% CI: 1.16-2.28), arrival mode to the emergency department via ambulance (OR, 2.23; 95% CI: 1.45-3.43), history of PICU admission for asthma (OR, 1.73; 95% CI: 1.22-2.44), and diagnosis of status asthmaticus (OR, 8.88; 95% CI: 3.49-30.07). Calculated OR of PICU admission subcategorized by RCS for early IVMg patients, after controlling for PICU risk factors, are as follows: RCS 9 (reference), RCS 10 (OR, 2.52; 95% CI: 0.89-2.23), RCS 11 (OR, 2.19; 95% CI: 1.3-3.70), and RCS 12 (OR, 4.12; 95% CI: 2.13-7.95). CONCLUSIONS: Early administration of IVMg to pediatric patients experiencing severe asthma exacerbations does not result in fewer PICU admissions.

Adolescents' practical knowledge of asthma self-management and experiences in the context of acute asthma: a qualitative content analysis.

OBJECTIVE: To characterize adolescents' practical knowledge of asthma self-management and experiences during acute asthma episodes, and compare practical knowledge between minority and non-minority groups. METHODS: We conducted a secondary analysis using a qualitative descriptive design of textual data collected from 126 adolescents that participated in a randomized controlled trial of an asthma self-management program. Directed content analysis was conducted using four constructs of asthma self-management including symptom prevention, symptom monitoring, acute symptom management, and symptom communication. RESULTS: Most of the adolescents knew how to prevent exercised-induced bronchoconstriction, but had limited understanding about how to assess and monitor the severity of acute symptoms, appropriately use bronchodilators, seek timely medical help, and communicate acute symptoms to caregivers or healthcare providers during a slow-onset and rapid-onset asthma attack. More minority participants monitored asthma using peak expiratory flow than non-minority participants, who often relied on symptom-based monitoring. Minority adolescents more frequently mentioned bronchodilator use to manage asthma attacks, while non-minority adolescents often reported use of complementary and alternative approaches. Minority youth mentioned accessing healthcare services for acute episodes more often than their non-minority counterparts. Minority participants mentioned communicating acute symptoms to their providers, or family members less frequently than non-minority youth. CONCLUSIONS: Adolescents have insufficient practical knowledge about ways to prevent and manage acute asthma. Periodic assessment of learning needs related to asthma attacks should be considered a routine part of clinical visits for adolescents to provide targeted information support to address their identified needs.

Nebulizer versus metered dose inhaler with space chamber (MDI spacer) for acute asthma and chronic obstructive pulmonary disease exacerbation: attitudes of patients and healthcare providers in the COVID-19 era.

OBJECTIVE: Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults. METHODS: Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods. RESULTS: Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only. CONCLUSIONS: Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.

Antibiotic use among admitted pediatric patients in the United States with status asthmaticus before and during the COVID-19 pandemic.

OBJECTIVE: Hospital admission trends of children with status asthmaticus diminished during the Coronavirus-19 (COVID-19) pandemic of 2020, possibly secondary to several factors such as school closures and use of face masks. What effect this had on antibiotic prescribing practices has yet to be described. The objective of our study was to evaluate the use of antibiotics in hospitalized children with a diagnosis of status asthmaticus before and during the COVID pandemic.Methods: A retrospective cross-sectional analysis was conducted using the TriNetX® cloud-based program with a national and institutional database. Each database was queried for all inpatient pediatric encounters from 3 to 18 years old, admitted with a diagnosis of status asthmaticus in the spring seasons of 2017-2019. Admission data and antibiotic usage were queried during the COVID-19 pandemic year of 2020 from both databases and compared amongst all study years.Results: In 2020, there was an overall decrease in the number of admissions as compared to the average number from 2017-2019, by 76.9% in the national database (p < 0.05) and 91.2% in the institutional database. The rates of antibiotic prescriptions significantly dropped among the national database (p < 0.001, z = 3.39) and remained non-significantly changed among the institutional database (p = 0.944 and z = 0.073).Conclusions: Our study demonstrates that the COVID-19 pandemic year of 2020 coincided with a significant decrease in hospital admissions and antibiotic prescribing prevalence among children with status asthmaticus on a national level. Nonetheless, our reported trends in antibiotic prescribing are still grossly similar to that of pre-pandemic times and may demonstrate a continued need for antimicrobial stewardship.

Status Asthmaticus Gravidus: Emergency and Critical Care Management of Acute Severe Asthma During Pregnancy.

One-third of women with asthma have deterioration of their asthma during pregnancy, and one-fourth of pregnant women with asthma will experience severe exacerbations necessitating emergency department (ED) visits or hospitalizations. Early recognition of acute severe asthma, including life-threatening status asthmaticus, and aggressive medical interventions with ß2-agonists, anticholinergic agents, and systemic corticosteroids are necessary to treat maternal airway bronchoconstriction, support maternal and fetal oxygenation, and avoid adverse fetal outcomes. This review describes management of acute severe asthma in pregnancy, including status asthmaticus, in the ED and intensive care unit.

Role of IL-22 in acute asthma mouse model.

Introduction: Allergic asthma is often associated with eosinophilic inflammation, which is related to the T-helper cell type 2 (Th2) cytokines and responsive to corticosteroids. However, there are also phenotypes of non-Th2-mediated asthma, which have poor responsivity to corticosteroids. The leading phenotype of non-Th2-mediated asthma is neutrophilic asthma, which is considered difficult to treat. Recently, IL-22 has been found to be involved in neutrophilic inflammation in asthma. However, studies on the role of IL-22 in asthma are still controversial as IL-22 has both pro-inflammatory and anti-inflammatory roles in asthma. This study examined whether the IL-22 level increased in acute neutrophilic asthma in the mouse model. Herein, we aimed to demonstrate increased IL-22 levels in neutrophilic asthma and elucidate the pathways leading to elevated neutrophil counts.Methods: Six-week old female BALB/c mice were sensitized and challenged with PBS, ovalbumin (OVA) or OVA + lipopolysaccharide (LPS). The mice were then assigned to one of the following five groups: (1) control (PBS/ PBS), (2) OVA/PBS, (3) OVA/OVA, (4) OVA+LPS/PBS, (5) OVA+LPS/OVA+LPS.Results: The levels of Th2 cytokines, IL-17, and IL-22 were assessed, with investigation of the neutrophil chemokines. This study showed that in the acute neutrophilic asthma, the levels of IL-17 and IL-22 were significantly higher than those in the OVA/OVA group, which represents acute eosinophilic asthma. Moreover, the level of CCL20 increased in the neutrophilic asthma group.Conclusion: Thus, this study suggests that in the acute neutrophilic asthma mouse model, IL-17 and IL-22 may increase with CCL20, resulting in neutrophilic inflammation.

Optimising intravenous salbutamol in children: a phase 2 study.

OBJECTIVE: The ß2-agonists such as salbutamol are the mainstay of asthma management. Pharmacokinetic-pharmacodynamic (PKPD) models to guide paediatric dosing are lacking. We explored the relationship between salbutamol dose, serum concentration, effectiveness and adverse effects in children by developing a PKPD model. DESIGN: A prospective cohort study of children admitted to hospital with acute asthma, who received intravenous salbutamol. SETTING: Children were recruited in two cohorts: the emergency departments of two London hospitals or those retrieved by the Children's Acute Transport Service to three London paediatric intensive care units. PATIENTS: Patients were eligible if aged 1-15 years, admitted for acute asthma and about to receive or receiving intravenous salbutamol. INTERVENTIONS: Treatment was according to local policy. Serial salbutamol plasma levels were taken. Effectiveness measurements were recorded using the Paediatric Asthma Severity Score (PASS). Toxicity measurements included lactate, pH, glucose, heart rate, blood pressure and arrhythmias. PKPD modelling was performed with non-linear mixed-effect models. MAIN OUTCOMES: Fifty-eight children were recruited with 221 salbutamol concentration measurements from 54 children. Median (range) age was 2.9 (1.1-15.2) years, and weight was 13.6 (8-57.3) kg. Ninety-five PASS measurements and 2078 toxicity measurements were obtained. RESULTS: A two-compartment PK model adequately described the time course of salbutamol-plasma concentrations. An EMAX (maximum drug effect) concentration-effect relationship described PASS and toxicity measures. PKPD simulations showed an infusion of 0.5 µg/kg/min (maximum 20 µg/min) for 4 hours after bolus achieves >90% maximal bronchodilation for 12 hours. CONCLUSIONS: A paediatric PKPD model for salbutamol is described. An infusion of 0.5 µg/kg/min after bolus achieves effective bronchodilation. Higher rates are associated with greater tachycardia and hyperglycaemia.

COVID-19, rinovirus y asma... ¿Una mala combinación? / COVID-19, rhinovirus and asthma... a bad conmbination?

La pandemia de COVID-19 enfrentó a la humanidad a un gran desafío y hemos ido aprendiendo a medida que avanzó. La aparición de este virus, su comportamiento por si solo y en conjunto con los otros virus nos mantuvo alerta.. Los pacientes pediátricos asmáticos, a pesar de lo que se pensó en un principio, son menos afectados y hacen un cuadro clínico más leve. Objetivo: presentar un caso clínico de un paciente asmático, con una evolución tortuosa por co-infección SARS-CoV-2 y Rinovirus (RV) y revisión de la litaratura. Se trata de un escolar de 6 años, asmático con mal control, con 2 dosis de vacuna anti SARS-CoV-2, que presento un estado asmático por rinovirus y posterior evolución con neumonía grave por SARS-CoV-2, requiriendo ventilación mecánica invasiva y estadía en UCI Pediátrica. Es probable que la gravedad del caso presentado se deba al mal control del asma antes de la infección, ya que se ha visto que los niños asmáticos alérgicos presentan un factor protector para infección grave por SARS-CoV-2, lo cual esta supeditado a un buen control de su enfermedad basal.

The COVID-19 pandemic presented a great challenge and we have been learning as it has progressed. The appearance of this virus, its behavior by itself and in conjunction with the other viruses kept us alert. Pediatric asthmatic patients, despite what was initially thought, are less affected and present a milder clinical picture. Objective: to present a clinical case of an asthmatic patient, with a tortuous evolution due to SARS-CoV-2 and Rhinovirus (RV) co-infection and a literature review. This is a 6-year-old schoolboy, asthmatic with poor control, with 2 doses of the SARS-CoV-2 vaccine, who presents asthmatic status due to rhinovirus and subsequent evolution with severe pneumonia due to SARS-CoV-2, requiring invasive mechanical ventilation and stay in Pediatric ICU. It is likely that the severity of the case presented is due to poor asthma control before infection, since it has been seen that allergic asthmatic children present a protective factor for severe infection by SARS-CoV-2, which is subject to good control of his basal disease.

Safety and efficacy of tezepelumab vs. placebo in adult patients with severe uncontrolled asthma: a systematic review and meta-analysis.

Patients with severe uncontrolled asthma still experience acute asthma symptoms and exacerbations, particularly those with non-eosinophilic inflammation who take the maximum amount of standard drug therapy. Tezepelumab, a human monoclonal antibody, can improve lung function and enhance control of asthma symptoms in those patients, regardless of the disease's baseline characteristics. This study aims to investigate the safety and efficacy of using tezepelumab in controlling severe symptoms of uncontrolled asthma. We performed a comprehensive literature search in several databases, including PubMed, Scopus, Web of Science, Cochrane Library, and clinicaltrial.gov, using a well-established search strategy to include all relevant publications. According to our inclusion criteria, we searched for randomized controlled trials comparing tezepelumab versus placebo in patients with severe, uncontrolled asthma. We analyzed the data using The Revman 5.4 program software. The search identified 589 potential articles. After excluding studies inconsistent with selection criteria, four studies were included and analyzed qualitatively and quantitatively. The pooled effect demonstrated the better performance of tezepelumab over the placebo regarding the decrease in annualized asthma exacerbation rate (MD = - 0.74, (95% CI [- 1.04, - 0.44], p < 0.00001)), asthma control questionnaire-6 (ACQ-6) Score MD = - 0.32, (95% CI [- 0.43, - 0.21], p < 0.00001)), blood eosinophil count (MD = - 139.38 cells/mcL, (95% CI [- 150.37, - 128.39], p < 0.00001)), feNO (MD = - 10 ppb, (95% CI [- 15.81, - 4.18], p = 0.0008)) and serum total IgE (MD = - 123.51 UI/ml, (95% CI [- 206.52, - 40.50], p = 0.004)). All tezepelumab groups had higher pre-bronchodilator forced expiratory volume in 1 s than the placebo group (MD = 0.16, (95% CI [0.10, 0.21], p < 0.00001)). Higher efficacy and safety profile was detected for tezepelumab to control the exacerbations of severe uncontrolled adult asthmatics.

Functional immunophenotyping of children with critical status asthmaticus identifies differential gene expression responses in neutrophils exposed to a poly(I:C) stimulus.

The host immune response to a viral immune stimulus has not been examined in children during a life-threatening asthma attack. We determined whether we could identify clusters of children with critical asthma by functional immunophenotyping using an intracellular viral analog stimulus. We performed a single-center, prospective, observational cohort study of 43 children ages 6-17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021. Neutrophils were isolated from children, stimulated overnight with LyoVec poly(I:C), and mRNA was analyzed using a targeted Nanostring immunology array. Network analysis of the differentially expressed transcripts for the paired LyoVec poly(I:C) samples was performed. We identified two clusters by functional immunophenotyping that differed by the Asthma Control Test score. Cluster 1 (n = 23) had a higher proportion of children with uncontrolled asthma in the four weeks prior to PICU admission compared with cluster 2 (n = 20). Pathways up-regulated in cluster 1 versus cluster 2 included chemokine receptor/chemokines, interleukin-10 (IL-10), IL-4, and IL-13 signaling. Larger validation studies and clinical phenotyping of children with critical asthma are needed to determine the predictive utility of these clusters in a larger clinical setting.