Heliox for Pediatric Critical Asthma: A Multicenter, Retrospective, Registry-Based Descriptive Study.

BACKGROUND: In cases of critical asthma (CA), heliox may be applied as an adjunctive rescue therapy to avoid invasive mechanical ventilation (MV), improve deposition of aerosolized medications, and enhance laminar airflow through obstructed airways. Using the Pediatric Health Information System (PHIS) registry, we evaluate heliox prescribing and explored for differences in MV rates and hospital length of stay (LOS) among children with and without heliox exposure. METHODS: We performed a retrospective cohort study using PHIS data from 42 pediatric intensive care units among children 5-17 years of age admitted for CA from 2010 through 2019. Primary outcomes were heliox prescribing rates and trends. Secondary outcomes were invasive MV rates and LOS assessed in a subgroup of children receiving ≥ 1 adjunctive intervention(s). RESULTS: Of the 19,780 studied, heliox was prescribed in 12.5% and linearly declined from 16.1% in 2010 to 5.6% in 2019. The overall MV rate was 12.8% and was lower in subjects receiving heliox alone (4.9%) compared to heliox plus alternative adjunctive therapies [31.2%] or children receiving non-heliox adjunctive therapies [22.1%], P < .01). Accounting for MV, no difference in LOS was observed. In exploratory adjusted models, MV free hospitalization was associated with heliox-only exposure (OR: 0.33, 95% CI: 0.17-0.63, P < .01) and exposure to multiple adjunctive therapies was associated with MV (OR: 2.48, 95% CI: 1.56-3.94, P < .01). CONCLUSIONS: In this multicenter retrospective study from 42 children's hospitals, heliox prescribing for CA declined over the last decade. Subjects receiving multiple adjunctive therapies more commonly required invasive MV perhaps indicating a greater severity of illness. At this time, prospective trials needed to identify the role of heliox for pediatric CA.

Volatile anesthetic agents for life-threatening pediatric asthma: A multicenter retrospective cohort study and narrative review.

BACKGROUND: Volatile anesthetic agents are described as rescue therapy for children invasively ventilated for critical asthma. Yet, data are currently limited to case series. AIMS: Using the Virtual Pediatric Systems database, we assessed children admitted to a pediatric intensive care unit invasively ventilated for life-threatening asthma and hypothesized ventilation duration and mortality rates would be lower for subjects exposed to volatile anesthetics compared with those without exposure. METHODS: We performed a multicenter retrospective cohort study among nine institutions including children 5-17 years of age invasively ventilated for asthma from 2013 to 2019 with and without exposure to volatile anesthetics. Primary outcomes were ventilation duration and mortality. Secondary outcomes included patient characteristics, length of stay, and anesthetic-related adverse events. A subgroup analysis was performed evaluating children intubated ≥2 days. RESULTS: Of 203 children included in study, there were 29 (14.3%) with and 174 (85.7%) without exposure to volatiles. No differences in odds of mortality (1.1, 95% CI: 0.3-3.9, p > .999) were observed. Subjects receiving volatiles experienced greater median difference in length of stay (4.8, 95% CI: 1.9-7.8 days, p < .001), ventilation duration (2.3, 95% CI: 1-3.3 days, p < .001), and odds of extracorporeal life support (9.1, 95% CI: 1.9-43.2, p = .009) than those without volatile exposure. For those ventilated ≥2 days, no differences were detected in mortality, ventilation duration, length of stay, arrhythmias, or acute renal failure. However, the odds of extracorporeal life support remained greater for those receiving volatiles (7.6, 95% CI: 1.3-44.5, p = .027). No children experienced malignant hyperthermia or hepatic failure after volatile exposure. CONCLUSIONS: For intubated children for asthma, no differences in mechanical ventilation duration or mortality between those with and without volatile anesthetic exposure were observed. Although volatiles may represent a viable rescue therapy for severe cases of asthma, definitive, and prospective trials are still needed.

Blood eosinophil count correlates with severity of respiratory failure in life-threatening asthma and predicts risk of subsequent exacerbations.

BACKGROUND: An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation. AIM: To elucidate the relationship between a spot blood eosinophil count-measured at the onset of a life-threatening asthma exacerbation-with indices of exacerbation severity and risk of subsequent exacerbations. METHODS: Real-world, retrospective review of all life-threatening asthma cases admitted at 4 public hospitals in Singapore between 2011-2015. We assessed the trends and correlations between blood eosinophil count on admission with arterial blood gas values, duration of mechanical ventilation, and risk of death, hypoxic ischemic encephalopathy or respiratory arrest. Risk of future exacerbations among survivors was modelled using Cox regression and survival curves. RESULTS: There were 376 index life-threatening exacerbations with median blood eosinophil count (5-95th percentiles) of 0.270 × 109 /L (0-1.410 × 109 /L). Arterial pH decreased and PCO2 increased with increasing eosinophil count. Duration of mechanical ventilation and risk of death, hypoxic ischaemic encephalopathy or respiratory arrest did not vary with eosinophils. Among 329 survivors who were followed-up over a median of 52 months, blood eosinophils ≥1.200 × 109 /L was associated with an increased hazard of emergency visits and/or admissions for asthma (hazard ratio 1.8, 95% confidence interval 1.1-2.9, P = .02). CONCLUSION: In this study of life-threatening asthma, we found that a spot blood eosinophil count correlates with severity of respiratory failure and predicts risk of subsequent exacerbations.

Identification of patterns of factors preceding severe or life-threatening asthma exacerbations in a nationwide study.

BACKGROUND: Reducing near-fatal asthma exacerbations is a critical problem in asthma management. OBJECTIVES: To determine patterns of factors preceding asthma exacerbations in a real-world setting. METHODS: In a nationwide prospective study of 190 patients who had experienced near-fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2-week period before admission. RESULTS: Three distinct clusters of symptoms were defined employing the self-reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle-aged patients with low Body mass index and tendency to depression who had stopped anti-asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle-aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long-acting beta-agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild-moderate symptoms. There were no differences in overuse of short-acting beta-agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters. CONCLUSION: To reduce severe or life-threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti-type 2 response-targeted therapies should be considered for cluster C.

Extracorporeal membrane oxygenation for life-threatening asthma refractory to mechanical ventilation: analysis of the Extracorporeal Life Support Organization registry.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in cases of near-fatal asthma (NFA) has increased, but the benefits and potential complications of this therapy have yet to be fully investigated. METHODS: Cases were extracted from the Extracorporeal Life Support Organization Registry between March 1992 and March 2016. All patients with a diagnosis of asthma (according to the International Classification of Diseases 9th edition), who also received ECMO, were extracted. Exclusion criteria included patients who underwent multiple courses of ECMO; those who received ECMO for cardiopulmonary resuscitation or cardiac dysfunction; and those with another primary diagnosis, such as sepsis. We analyzed survival to hospital discharge, complications, and clinical factors associated with in-hospital mortality, in patients with severe life-threatening NFA requiring ECMO support. RESULTS: In total 272 patients were included. The mean time spent on ECMO was 176.4 hours. Ventilator settings, including rate, fraction of inspired oxygen (FiO2), peak inspiratory pressure (PIP), and mean airway pressure, significantly improved after ECMO initiation (rate (breaths/min), 19.0 vs. 11.3, p < 0.001; FiO2 (%), 81.2 vs. 48.8, p < 0.001; PIP (cmH2O), 38.2 vs. 25.0, p < 0.001; mean airway pressure (cmH2O): 21.4 vs. 14.2, p < 0.001). In particular, driving pressure was significantly decreased after ECMO support (29.5 vs. 16.8 cmH2O, p < 0.001). The weaning success rate was 86.7%, and the rate of survival to hospital discharge was 83.5%. The total complication rate was 65.1%, with hemorrhagic complications being the most common (28.3%). Other complications included renal (26.8%), cardiovascular (26.1%), mechanical (24.6%), metabolic (22.4%), infection (16.5%), neurologic (4.8%), and limb ischemia (2.6%). Of the hemorrhagic complications, cannulation site hemorrhage was the most common (13.6%). Using multivariate logistic regression analysis, it was found that hemorrhage was associated with increased in-hospital mortality (odds ratio, 2.97; 95% confidence interval, 1.07-8.24; p = 0.036). Hemorrhage-induced death occurred in four patients (1.5%). The most common reason for death was organ failure (37.8%). CONCLUSIONS: ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation, and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA. However, careful management is required to avoid complications.

Severe or life-threatening asthma exacerbation: patient heterogeneity identified by cluster analysis.

BACKGROUND: Severe or life-threatening asthma exacerbation is one of the worst outcomes of asthma because of the risk of death. To date, few studies have explored the potential heterogeneity of this condition. OBJECTIVES: To examine the clinical characteristics and heterogeneity of patients with severe or life-threatening asthma exacerbation. METHODS: This was a multicentre, prospective study of patients with severe or life-threatening asthma exacerbation and pulse oxygen saturation < 90% who were admitted to 17 institutions across Japan. Cluster analysis was performed using variables from patient- and physician-orientated structured questionnaires. RESULTS: Analysis of data from 175 patients with severe or life-threatening asthma exacerbation revealed five distinct clusters. Cluster 1 (n = 27) was younger-onset asthma with severe symptoms at baseline, including limitation of activities, a higher frequency of treatment with oral corticosteroids and short-acting beta-agonists, and a higher frequency of asthma hospitalizations in the past year. Cluster 2 (n = 35) was predominantly composed of elderly females, with the highest frequency of comorbid, chronic hyperplastic rhinosinusitis/nasal polyposis, and a long disease duration. Cluster 3 (n = 40) was allergic asthma without inhaled corticosteroid use at baseline. Patients in this cluster had a higher frequency of atopy, including allergic rhinitis and furred pet hypersensitivity, and a better prognosis during hospitalization compared with the other clusters. Cluster 4 (n = 34) was characterized by elderly males with concomitant chronic obstructive pulmonary disease (COPD). Although cluster 5 (n = 39) had very mild symptoms at baseline according to the patient questionnaires, 41% had previously been hospitalized for asthma. CONCLUSIONS & CLINICAL RELEVANCE: This study demonstrated that significant heterogeneity exists among patients with severe or life-threatening asthma exacerbation. Differences were observed in the severity of asthma symptoms and use of inhaled corticosteroids at baseline, and the presence of comorbid COPD. These findings may contribute to a deeper understanding and better management of this patient population.

Near fatal asthma: treatment and prevention.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.

Identification and characterization of near-fatal asthma phenotypes by cluster analysis.

BACKGROUND: Near-fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological features. However, there are no previous studies that identify in a unbiased way--using statistical methods such as clusters analysis--different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis. METHODS: Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two-steps algorithm was performed from data of 84 of these cases. RESULTS: The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired consciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti-inflammatory treatment and frequent sensitization to Alternaria alternata and soybean. CONCLUSIONS: These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations.

Use of venovenous (VV) extracorporeal membrane oxygenation (ECMO) in near-fatal asthma: a case series.

Introduction: Status asthmaticus (SA) and near-fatal asthma (NFA) are life-threatening conditions that continue to present a management challenge for physicians. Extracorporeal Membrane Oxygenation (ECMO) has been employed as a last resort in treating these patients. Case presentation: We described six patients who were admitted to the ICU for NFA and received ECMO treatment at a high-complexity institution in Cali, Colombia, between 2015 and 2019. All patients are registered in the ELSO registry. Baseline patient characteristics, arterial blood gases (ABG), ventilatory parameters, and complications were collected as specified in the ELSO registry form. Efficacy was analyzed in terms of the improvement in respiratory acidosis, the number of ventilator-free days (VFD), and a reduction in mechanical power (MP). MP, which refers to the energy associated with the mechanical forces involved in breathing and the functioning of the respiratory system, was calculated using a mathematical formula. Safety was evaluated based on the incidence of complications. After 12 hours of ECMO, we achieved a correction of respiratory acidosis, a significant decrease in all ventilatory parameters, and a reduction in MP ranging from 52.8% to 89%. There was one mortality. Among the five surviving patients, all except one, who required a tracheostomy, had a high VFD score, with a mode of 26 days, demonstrating a reduction in ventilation time. Conclusion: Further randomized controlled trials are needed to fully understand the efficacy and safety profiles of ECMO in SA/NFA. MP is being widely used to achieve safer ventilation, and although more data is required, it appears to be a promising option for evaluating the risk of developing VILI and the success of the therapy.

Rapid weaning from mechanical ventilation and bronchial thermoplasty for near-fatal asthma: A case report.

Background: The action mechanism of bronchial thermoplasty (BT) is poorly understood. Generally, patients with severe asthma who are in desperate need of treatment have relatively low baseline values. In this paper, we describe the case of an asthmatic patient who was saved by a combination of therapy and bronchial thermoplasty. Case information: A patient with near-fatal asthma was initially treated in our hospital with conventional medication, but his condition did not improve. The patient was next subjected to invasive mechanical ventilation, which did not provide significant relief. Additionally, he was treated with BT in conjunction with mechanical ventilation, which promptly reversed his status asthmaticus and stabilized his condition. Conclusion: Patients with near-fatal asthma who do not react effectively to aggressive therapy may benefit from BT.

Brittle Asthma: Still on Board?

(1) Background: "Brittle Asthma" was considered an asthma clinical phenotype and deemed to be life-threatening in the early 2000s; then, this definition disappeared. The purpose of this review is to examine what has historically been referred to as this term and see whether it may be applied to modern clinical practice, thus acquiring fresh relevance and meaning. (2) Methods: A non-systematic search of the literature was conducted using both MeSH and free-text phrases. No limitations on the research design or type of publication were applied. (3) Results: Reliable data regarding "Brittle Asthma" are lacking due to the paucity of current data and the few studies available. After a few years of reworking, it was divided into two sub-classes: one characterized by a wide PEF variability despite high-dose therapy and the other by sudden acute attacks in otherwise apparently normal airway functions or well-controlled asthma. Their characteristics were hardly defined because of their low prevalence. Data regarding risk factors, atopy, mechanisms, and treatments were analyzed. (4) Conclusions: Over time, different terminology has been introduced to define asthma severity and control. It would be worth investigating whether the term "Brittle Asthma" previously used may be helpful to find new hints to stratify patients and improve disease management.

Extracorporeal membrane oxygenation (ECMO) and beyond in near fatal asthma: A comprehensive review.

The treatment of choice in severe asthma exacerbations with respiratory failure includes ventilatory support, both invasive and/or non-invasive, along with different kinds of asthma medication. Of note, the rate of mortality of patients with asthma has decreased substantially in recent years mainly due to significant advances in pharmacological treatment and other management strategies. However, the risk of death in patients with severe asthma who require invasive mechanical ventilation has been estimated between 6.5% and 10.3%. When conventional measures fail, rescue strategies, such as extracorporeal membrane oxygenation (ECMO) or extracorporeal CO2 removal (ECCO2R) may need to be implemented. While ECMO does not constitute a definitive treatment per se, it can minimize further ventilator associated lung injury (VALI) and can enable diagnostic-therapeutic maneuvers that cannot be performed without ECMO such as bronchoscopy and transfer for diagnostic imaging. Asthma is one of the diseases that is associated with excellent outcomes for patients with refractory respiratory failure requiring ECMO support, as shown by the Extracorporeal Life Support Organization (ELSO) registry. Moreover, in such situations, the use of ECCO2R for rescue has been described and utilized in both children and adults and is more widely spread in different hospitals than ECMO. In this article, we aim to review the evidence for the usefulness of extracorporeal respiratory support measures in the management of severe asthma exacerbations that lead to respiratory failure.

Extracorporeal Membrane Oxygenation (ECMO): A Life Saver in Near-Fatal Asthma.

Near-fatal asthma (NFA) is a life-threatening condition that represents the most severe clinical phenotype of asthma and can progress to fatal asthma. Patients with NFA do not respond adequately to conventional medical therapy and urgent intervention is needed to provide adequate oxygenation by invasive mechanical ventilation. While mechanical ventilation is a potentially life-saving intervention, it could cause lung injury, barotrauma, and dynamic hyperinflation due to high ventilator settings resulting in hemodynamic instability. Extracorporeal membrane oxygenation (ECMO) provides full respiratory support with adequate gas exchange in patients with NFA and improves survival rate. We present a case of a young female patient who presented with NFA, and her clinical condition was worsening despite invasive positive pressure mechanical ventilation.

Thunderstorm allergy and asthma: state of the art.

Thunderstorm-triggered asthma (TA) can be defined as the occurrence of acute asthma attacks immediately following a thunderstorm during pollen seasons. Outbreaks have occurred across the world during pollen season with the capacity to rapidly inundate a health care service, resulting in potentially catastrophic outcomes for allergic patients. TA occurs when specific meteorological and aerobiological factors combine to affect predisposed atopic patients with IgE-mediated sentitization to pollen allergens. Thunderstorm outflows can concentrate aeroallergens, most commonly grass pollen but also other pollens such as Parietaria and moulds in TA, at ground level to release respirable allergenic particles after rupture by osmotic shock related to humidity and rainfall. Inhalation of high concentrations of these aeroallergens by sensitized individuals can induce early asthmatic responses which can be followed by a late inflammatory phase. There is evidence that, during pollen season, thunderstorms can induce allergic asthma outbreaks, sometimes also severe asthma crisis and sometimes deaths in patients suffering from pollen allergy. It has been observed that changes in the weather such as rain or humidity may induce hydratation of pollen grains during pollen seasons and sometimes also their fragmentation which generates atmospheric biological aerosols carrying allergens. Asthma attacks are induced for the high concentration at ground level of pollen grains which may release allergenic particles of respirable size after rupture by osmotic shock. In other words, it is a global health problem observed in several cities and areas of the world that can strike without sufficient warning, inducing sometimes severe clinical consequences also with deaths of asthma patients. Due to constant climate change, future TA events are likely to become more common, more disastrous and more unpredictable, as a consequence it is important to have deep knowledge on this topic to prevent asthma attacks. Other environmental factors, such as rapid changes in temperature and agricultural practices, also contribute to causing TA.

Extracorporeal and advanced therapies for progressive refractory near-fatal acute severe asthma in children.

Asthma is the most common chronic illness and is one of the most common medical emergencies in children. Progressive refractory near-fatal asthma requiring intubation and mechanical ventilation can lead to death. Extracorporeal membrane oxygenation (ECMO) can provide adequate gas exchange during acute respiratory failure although data on outcomes in children requiring ECMO support for status asthmaticus is sparse with one study reporting survival rates of nearly 85% with asthma being one of the best outcome subsets for patients with refractory respiratory failure requiring ECMO support. We describe the current literature on the use of ECMO and other advanced extracorporeal therapies available for children with acute severe asthma. We also review other advanced invasive and noninvasive therapies in acute severe asthma both before and while on ECMO support.

Extracorporeal carbon dioxide removal in heart-beating donor with acute severe asthma: A case report.

Status asthmaticus is a life-threatening disorder that can manifest in dangerous levels of hypercapnia and acidosis. The use of extracorporeal carbon dioxide removal (ECCO2R) has been used successfully to control pH and PaCO2 in patients with acute severe asthma. The present report describes the use of this technology in near-fatal asthma with brain death, and awaiting organ harvest. The ProLUNG® system consists of a veno-venous hemoperfusion circuit with an artificial lung polymethylpentene membrane coated with phosphorylcholine with a surface of 1.81 m2. The system can reach a blood flow of 450 ml/min trough a double-lumen central venous catheter (13.0 Fr) placed in femoral, subclavian or jugular vein. The platform is provided with automated management of airflow and VCO2 monitoring during treatment. The patient was maintained on extracorporeal treatment ensuring stable arterial pH control and PaCO2 control. In acute status asthmaticus, complicated with cardiac arrest, mini-invasive ECCO2R was an effective method of controlling pH and PaCO2, for optimizing hemodynamic and aerobic metabolism and for performing protective ventilation for an optimal organ donor preservation until the organ harvest occurs.

A winter to remember! Extracorporeal membrane oxygenation for life-threatening asthma in children: A case series and review of literature.

Progressive refractory near-fatal asthma requiring intubation and mechanical ventilation can lead to death. Data on outcomes in children requiring extracorporeal membrane oxygenation (ECMO) support for status asthmaticus is sparse. We describe our experience of three patients in the winter of 2018 to 2019 successfully rescued with ECMO. We also report our novel use of extubation while still being on ECMO support. Awareness and use of ECMO in refractory asthma can help lower the mortality for this very common disease in children. We also review the current literature on the use of ECMO and other extracorporeal therapies in asthma.

Intravenous and intramuscular therapy in near fatal asthma. A response to Al-Shamrani.

The invited review by Al-Shamrani et al. (2020) [1] failed to address the management of a patient having an asthma attack who arrives in the Emergency Department with respiratory failure or in a moribund condition. The only route available for drug therapy in these patients is intravenously (IV) or intramuscularly in a final attempt to reduce bronchoconstriction. This could avoid tracheal intubation and lung ventilation, or make these procedures safer (Sellers, 2013; Williams et al., 1992) [2,3] for the patient if some bronchodilation occurs. Intubation and ventilation prevent coughing but tenacious mucus remains which blocks the bronchi. There are no randomised controlled trials or national asthma guidelines to inform practice at this stage of the disease, especially in under 18 year olds, so case report evidence, experience, common sense, and pharmacological principles must be engaged to save the patient's life.