Life-threatening Asthma Exacerbation Research Articles

Compassionate Use of Reslizumab in a Life-threatening Asthma Exacerbation.

Compassionate Use of Reslizumab in a Life-threatening Asthma Exacerbation.

Management of Acute Life-Threatening Asthma Exacerbations in the Intensive Care Unit

Managing acute asthma exacerbations in critical care can be challenging and may lead to adverse outcomes. While standard management of an acute asthma exacerbation is well established in outpatient and emergency department settings, the management pathway for patients with life-threatening and near-fatal asthma still needs to be fully defined. The use of specific interventions such as intravenous ketamine, intravenous salbutamol, and intravenous methylxanthines, which are often used in combination to improve bronchodilation, remains a contentious issue. Additionally, although it is common in the intensive care unit setting, the use of non-invasive ventilation to avoid invasive mechanical ventilation needs further exploration. In this review, we aim to provide a comprehensive overview of the available treatments and the evidence for their use in intensive care. We highlight the ongoing need for multicentre trials to address clinical knowledge gaps and the development of intensive-care-based guidelines to provide an evidence-based approach to patient management.

Evidence Synthesis of Outcomes of Extracorporeal Membrane Oxygenation for Life-Threatening Asthma Exacerbations

Evidence Synthesis of Outcomes of Extracorporeal Membrane Oxygenation for Life-Threatening Asthma Exacerbations

Pneumomediastinum complicating acute asthma.

A 19 year old female with a history of asthma presented with an acute life-threatening asthma exacerbation. Atypical features, particularly a persistent oxygen requirement promted further investigation with a subsequent CT Thorax confirming pneumomediastinum. Her case was managed conservatively as per our treatment proctocol for asthma. Pneumomediastinum can present during an acute asthma exacerbation. Although it is benign and spontaneous recovery is to be expected, due to the risk of respiratory comprimise and profound hypoxia a high level of clinical suspicion and close monitoring is advised.

Cluster analysis of plasma cytokines identifies two unique endotypes of children with asthma in the pediatric intensive care unit

Children with life-threatening asthma exacerbations who are admitted to a pediatric intensive care unit (PICU) are a heterogeneous group with poorly studied inflammatory features. We hypothesized that distinct clusters of children with asthma in a PICU would be identified based on differences in plasma cytokine levels and that these clusters would have differing underlying inflammation and asthma outcomes within 1 year. Plasma cytokines and differential gene expression were measured in neutrophils isolated from children admitted to a PICU for asthma. Participants were clustered by differential plasma cytokine abundance. Gene expression differences were compared by cluster and pathway over-representation analysis was performed. We identified two clusters in 69 children with no clinical differences. Cluster 1 (n = 41) had higher cytokines compared to Cluster 2 (n = 28). Cluster 2 had a hazard ratio of 2.71 (95% CI 1.11–6.64) compared to Cluster 1 for time to subsequent exacerbation. Gene expression pathways that differed by cluster included interleukin-10 signaling; nucleotide-binding domain, leucine rich repeat containing receptor (NLR signaling); and toll-like receptor (TLR) signaling. These observations suggest that a subset of children may have a unique pattern of inflammation during PICU hospitalization that might require alternative treatment approaches.

Acute severe asthma in emergency department: clinical characteristics, risk factors, and predictors for poor outcome

BackgroundSevere asthma exacerbation can be a frightening experience to the patient and physician. Despite continuous efforts to frame management guidelines and advances in treatment, severe exacerbations still occur. In order to prevent and judicious management of asthma exacerbations, we should predict them first. This study aims to evaluate distinct clinical trajectories and management outcome of patients with severe asthma exacerbations and also evaluate predictors for poor outcome.MethodsPatients suffering from acute asthma exacerbation and presented to emergency room (forty patients) were grouped into 2 groups (groups A and B) according to severity of exacerbation. Assessment included full clinical history, laboratory investigations (including eosinophil cell count and serum IgE level), Beck’s anxiety and depression inventory scales, assessment of asthma medication adherence and control level, and peak expiratory flow measurement (at presentation, 1 and 6 h after).ResultsFifty-five percent of patients suffered from severe and life-threatening asthma exacerbations, 63.6% of them were females. The most important predictors for severe exacerbations were SO2 < 90% at baseline (OR = 4.56; 95% CI = 3.45–7.56; P < 0.001), PEFR after 1 h (OR= 3.34; 95%CI = 1.90–4.90; P < 0.001), and uncontrolled asthma (OR= 3.33; 95%CI = 2.50–5.05; P < 0.001). Predictors for hospitalization were old age (OR = 1.11; 95%CI = 1.09–2.11; P < 0.001), uncontrolled asthma (OR = 2.34; 95%CI = 2.01–4.40; P < 0.001), PEFR after 1 h (OR= 4.44; 95%CI= 3.24–7.68; P < 0.001), and SO2 <90% at baseline (OR= 5.67; 95%CI= 3.98–8.50; P < 0.001).ConclusionsSevere asthma exacerbations can be predicted by old age, previous history of mechanical ventilation, obstructive sleep apnea, overuse of SABA, uncontrolled asthma, moderate to severe depression, eosinophilia, SO2 <90%, and low peak expiratory flow rates.

Современное представление о витамине D и генетической регуляции воспаления на примере бронхиальной астмы

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease characterized by a variety of symptoms in the form of wheezing, breathlessness, chest tightness and/or cough, as well as variable exhaled airflow limitation, with both the combination of symptoms and airflow limitation changing with time and intensity. Asthma is associated with both airway hyperresponsiveness to direct or indirect stimuli and chronic airway inflammation. Therapy for BA in accordance with national guidelines and clinical recommendations successfully controls asthma symptoms in most patients. However, there are several problems. Firstly, up to 5% of patients with asthma have a refractory course, respond inadequately to traditional therapeutic approaches and, therefore, are at greater risk of life-threatening asthma exacerbations. Secondly, a significant number of patients, even with mild to moderate asthma, have poor symptom control and may experience severe exacerbations. Low vitamin D levels are associated with decreased lung function, increased asthma exacerbations, and drug use, although it is not clear whether there is a causal relationship between these observations, and whether asthma patients may benefit from vitamin D supplementation. The authors present in this literature review the mechanisms by which vitamin D can reduce the severity of inflammation in BA. The research is focused on studying the mechanisms of chronic respiratory inflammation and their exogenous and genetic regulation involving genetic variants of the VDR gene and vitamin D metabolites. Keywords: children, vitamin D, 25(OH)D deficiency, asthma, inflammation, VDR

Management of Asthma Exacerbations in Southeast Asian Tertiary Care.

BackgroundThere have been limited reports looking into the care of patients with asthma exacerbations admitted to tertiary hospitals in Southeast Asia. This study aims to determine the extent in which the 2019 Global Initiative for Asthma (GINA) guidelines were being met.MethodsA retrospective study of patients with asthma exacerbations admitted to the University of Malaya Medical Centre (UMMC) and Pantai Hospital Kuala Lumpur (PHKL), Malaysia from 1 July 2019 to 31 December 2019.ResultsThere were significant numbers of patients with previous admissions for asthma in both centres, with almost 50% experiencing an exacerbation in the previous year. Approximately 75% of the patients considered their asthma to be controlled when asked, despite many of them having had a history of acute exacerbations in the previous year. When cross-checked, the level of GINA-defined asthma control remained low, with only 6.4% of the patients deemed to have good control, while asthma was partially controlled in 25.6% of the patients and uncontrolled in 68% of the patients. About 72.1% of the patients reported daytime symptoms, 65.1% of the patients reported night-time symptoms, 70.9% of the patients required frequent usage of rescue inhalers and 72.1% of the patients reported some limitation in their activity prior to the current asthma exacerbation. Almost a quarter of the patients who were admitted had severe or life-threatening exacerbations as defined by GINA. These patients had more hospitalizations in a year and were more likely to have previous admissions requiring non-invasive and invasive ventilation. They were also more likely to be on GINA Step 5 treatment, had a lower mean percent predicted FEV1 and a higher baseline blood eosinophil count. Multivariate analysis revealed that baseline eosinophil count were independently associated with severe or life-threatening asthma exacerbations (odds ratio: 1.01, 95% confidence interval: 1.00–1.01, p=0.001). Failure to adhere to daily controller medications was high in this study (37.2%).ConclusionAlthough the management of asthma exacerbations in tertiary hospitals in Southeast Asia is largely congruous with international guidelines, there is room for improvement. As there is a marked discrepancy between patient-perceived and guideline-defined asthma control, efforts to increase awareness on the dangers of uncontrolled asthma are warranted.

Medical crisis checklists in the emergency department: a simulation-based multi-institutional randomised controlled trial

BackgroundStudies carried out in simulated environments suggest that checklists improve the management of surgical and intensive care crises. Whether checklists improve the management of medical crises simulated in actual emergency...

Role of ketamine in life-threatening asthma exacerbation

Ketamine in life-threatening asthma exacerbation might be a novel approach to avoid the need for intubation and or invasive mechanical ventilation or asthma-related lethal outcomes. We present a case of a young man who presented with life-threatening asthma exacerbation who along with standard medications, improved with the addition of intravenous ketamine to his treatment regime. A 36 years old male farmer who was known to have asthma was referred from a Primary Health Centre Clinic with suspected life-threatening asthma. He was treated previously before arrival to our ED with nebulizers and IV Corticosteroids. In the ED, the patient received IV magnesium and IM Epinephrine. Intubation was anticipated, and the induction agent of Ketamine was considered. However, given there were anecdotal cases of patients responding to Ketamine Infusion, a bolus dose of 0.5mg/kg was given, and an infusion at a similar dose per hour was started. The patient began to respond gradually and was later admitted to ICU. Ketamine may have a role in life-threatening asthma. In our case, we used a low dose of ketamine infusion to try and avoid the need for intubation and mechanical ventilation and were successful.

[A retrospective study of the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China in 2013-2014].

Objective: To study the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China. Methods: Patients hospitalized for asthma exacerbation at 29 hospitals in China were retrospectively recruited during 2013-2014. Results: Clinical data of 3 240 asthmatic patients were collected and analyzed including 1 369(42.3%) males and 1 871(57.7%) females. The patients hospitalized for asthma exacerbation counted for 2.95% (6 375/215 955) of all patients hospitalized during the same period. The leading six inducing factors, in sequence, were acute upper respiratory tract infection [42.3%(1 370/3 240)], changes of weather [22.8%(738/3 240)], noxious gas [(4.3%(140/3 240), allergy challenges [3.5%(115/3 240)], strenuous exercise [1.8%(57/3 240)], and air pollution [1.5%(49/3 240)]. In older patients, more exacerbations were induced by weather changes, yet less sensitive to allergy challenges. As to middle-aged patients, they were less sensitive to upper respiratory tract infections, however the difference was not statistically significant (P>0.05). In winter more asthma patients were induced by upper respiratory tract infections, while in autumn more patients were induced by weather changes, strenuous exercise and air pollution. In spring and summer more patients were induced by allergy challenges, but the differences failed to achieve statistical significance (P>0.05). In northern cities more patients were induced by upper respiratory infections, whereas in southern cities more by noxious gases. Allergy challenges and air pollution tended to affect more patients in northern cities, but the difference was of no significance (P>0.05). The differences of inducing factors among patients of different gender, with or without a smoking history, and with different exacerbation severity didn't show any statistical significance. The patients with severe and life-threatening exacerbations counted for 20.1% (652/3 240). The percentage of patients older than 60 years was higher in patients with severe or life-threatening exacerbations than in whose with mild or moderate exacerbations, so did the percentage of male patients, of patients with disease duration longer than 10 years, with smoking history, and with a history of hospitalization or emergency department visits due to asthma exacerbation during the last year. Conclusion: The acute upper respiratory tract infection ranks top among all the inducing factors. Senility, male gender, long duration of disease, smoking history, and a history of frequent hospital visits might be the risk factors for severe or life-threatening asthma exacerbations.

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

BackgroundReducing near‐fatal asthma exacerbations is a critical problem in asthma management.ObjectivesTo determine patterns of factors preceding asthma exacerbations in a real‐world setting.MethodsIn 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.ResultsThree 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.ConclusionTo 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.

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

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. To examine the clinical characteristics and heterogeneity of patients with severe or life-threatening asthma exacerbation. 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. 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. 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.

Management of Status Asthmaticus

Status asthmaticus (SA) is a severe and life-threatening asthma exacerbation that requires aggressive treatment. First-line treatment entails continuous treatment of nebulized short-acting β-receptor agonists and intravenous (IV) steroid administration. This review article focuses on the current literature supporting the use of these medications as well as other treatment modalities such as inhaled anticholinergics, parenteral β-agonists, IV magnesium, and IV ketamine. We also explore the utility methylxanthines, volatile anesthetics, nitric oxide, antibiotics, IV fluids, and mucolytics in treating SA. Finally, we explore the data pertaining to the use of Heliox, non-invasive positive pressure ventilation, and bronchoscopy, and discuss ventilator management for patients with SA requiring intubation.

Sensitization to fungal allergens: Resolved and unresolved issues

Exposure and sensitization to fungal allergens can promote the development and worsening of allergic diseases. Although numerous species of fungi have been associated with allergic diseases in the literature, the significance of fungi from the genera Alternaria, Cladosporium, Penicillium, Aspergillus, and Malassezia has been well documented. However, it should be emphasized that the contribution of different fungal allergens to allergic diseases is not identical, but species-specific.Alternaria and Cladosporium species are considered to be important outdoor allergens, and sensitization and exposure to species of these genera is related to the development of asthma and rhinitis, as well as epidemics of asthma exacerbation, including life-threatening asthma exacerbation. In contrast, xerophilic species of Penicillium and Aspergillus, excluding Aspergillus fumigatus, are implicated in allergic diseases as indoor allergens. A. fumigatus has a high capacity to colonize the bronchial tract of asthmatic patients, causing severe persistent asthma and low lung function, and sometimes leading to allergic bronchopulmonary aspergillosis. Malassezia are common commensals of healthy skin, although they are also associated with atopic dermatitis, especially on the head and neck, but not with respiratory allergies.Despite its importance in the management of allergic diseases, precise recognition of species-specific IgE sensitization to fungal allergens is often challenging because the majority of fungal extracts exhibit broad cross-reactivity with taxonomically unrelated fungi. Recent progress in gene technology has contributed to the identification of specific and cross-reactive allergen components from different fungal sources. However, data demonstrating the clinical relevance of IgE reactivity to these allergen components are still insufficient.

Critical Asthma Syndrome in the ICU

Critical asthma syndrome represents the most severe subset of asthma exacerbations, and the critical asthma syndrome is an umbrella term for life-threatening asthma, status asthmaticus, and near-fatal asthma. According to the 2007 National Asthma Education and Prevention Program guidelines, a life-threatening asthma exacerbation is marked by an inability to speak, a reduced peak expiratory flow rate of <25 % of a patient's personal best, and a failed response to frequent bronchodilator administration and intravenous steroids. Almost all critical asthma syndrome cases require emergency care, and most cases require hospitalization, often in an intensive care unit. Among asthmatics, those with the critical asthma syndrome are difficult to manage and there is little room for error. Patients with the critical asthma syndrome are prone to complications, they utilize immense resources, and they incite anxiety in many care providers. Managing this syndrome is anything but routine, and it requires attention, alacrity, and accuracy. The specific management strategies of adults with the critical asthma syndrome in the hospital with a focus on intensive care are discussed. Topics include the initial assessment for critical illness, initial ventilation management, hemodynamic issues, novel diagnostic tools and interventions, and common pitfalls. We highlight the use of critical care ultrasound, and we provide practical guidelines on how to manage deteriorating patients such as those with pneumothoraces. When standard asthma management fails, we provide experience-driven recommendations coupled with available evidence to guide the care team through advanced treatment. Though we do not discuss medications in detail, we highlight recent advances.

Considerations for Care: Management of Asthma in the Child with Sickle Cell Disease.

Asthma is difficult to diagnose in the child with sickle cell disease because symptoms and pulmonary function abnormalities are similar to the spectrum of pulmonary manifestations in sickle cell disease. There are no published reports of controlled trials of asthma medications in children with sickle cell disease. Thus, treatment decisions should be guided by the Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf). However, issues specific to children with sickle cell disease should be considered. Initial strategies should focus on control of environmental triggers, as effectiveness on asthma outcomes is proven and the cost for implementation can be low. Use of short- and long-acting β2-agonists may prolong QTc, particularly in this population of children who already have a higher prevalence of prolonged QTc than the general population. Long-acting β2-agonist use has been associated with life-threatening asthma exacerbations with potentially higher risks in African Americans. Montelukast has been reported to increase suicidal thinking and behavior, and persons with asthma and sickle cell disease are already at risk for these events. Oral corticosteroids in the treatment of acute chest syndrome may increase risk of readmission even in children with asthma. The lack of prospective controlled trials of asthma drug treatment in children with asthma and sickle cell disease compels us to move this issue forward.

Demographics, Clinical Course, and Outcomes of Children with Status Asthmaticus Treated in a Pediatric Intensive Care Unit: 8-Year Review

Objective. This study was done to understand the demographics, clinical course, and outcomes of children with status asthmaticus treated in a tertiary care pediatric intensive care unit (PICU). Methods. The medical charts of all patients above 5 years of age admitted to the PICU at Nationwide Children’s Hospital, Columbus, OH, USA, with status asthmaticus from 2000 to 2007 were reviewed retrospectively. Data from 222 encounters by 183 children were analyzed. Results. The mean age at admission in years was 11 ± 3.8. The median PICU stay was 1 day (range, 1–12 days) and median hospital stay was 3 days. The ventilated group (n = 17) stayed a median of 2 days longer in the PICU and hospital. Nearly half of the children (n = 91; 50%) did not receive daily controller asthma medications. Adherence to asthma medications was reported in 125 patient charts of whom 43 (34%) were compliant. Exposure to smoking was reported in 167 of whom 70 (42%) were exposed. Among patients receiving metered dose inhaler (MDI), only 39 (18%) were using it with a spacer. Among 105 patient charts asthma severity data were available, of them 21 (20%) were labeled as mild intermittent, 29 (28%) were mild persistent, 26 (25%) were moderate persistent, and 29 (28%) were severe persistent. Compared to children with only one PICU admission during the study period (n = 161), children who had multiple PICU admissions (n = 22) experienced more prior emergency department visits and hospitalizations for asthma symptoms. There were no fatalities. Conclusion. Asthmatics with any disease severity are at risk for life-threatening asthma exacerbations requiring PICU stay, especially those who are not adherent with their daily medications.

Magnesium sulfate for acute asthma in adults: a systematic literature review.

Magnesium sulfate (MgSO4) has been considered as an adjunct therapy for severe and life-threatening asthma exacerbation. The literature search was performed using MEDLINE, EMBASE, Cochrane Library and Google Scholar to summarize the current state of knowledge regarding magnesium therapy in acute exacerbation of adult asthma. A total of 16 trials and 4 meta-analyses were identified. As results, intravenous MgSO4 was beneficial in severe exacerbation, but evidence for nebulized magnesium was insufficient. However, larger trials are required to draw confirmative conclusions on the efficacy. Regarding the safety concern, the risk of major toxicity appears to be very low at usual doses described in the literature. Additionally, results from 4 surveys were examined on the gaps between knowledge and practice, and on the barrier to the use of MgSO4 at emergency departments. This literature review summarized the up-to-date evidence on the issues regarding the use of MgSO4 for acute asthma. We expect more studies to be conducted for evidence making in the Asian-Pacific regions.

Cleavage of IPS-1 in Cells Infected with Human Rhinovirus

Rhinoviruses are prevalent human pathogens that are associated with life-threatening acute asthma exacerbations. The innate immune response to rhinovirus infection, which may play an important role in virus-induced asthma induction, has not been comprehensively investigated. We examined the innate immune response in cells infected with human rhinovirus 1a (HRV1a). Beta interferon (IFN-beta) mRNA was induced in HRV1a-infected cells at levels significantly lower than in cells infected with Sendai virus. To understand the basis for this observation, we determined whether components of the pathway leading to IFN-beta induction were altered during infection. Dimerization of the transcription factor IRF-3, which is required for synthesis of IFN-beta mRNA, is not observed in cells infected with HRV1a. Beginning at 7 h postinfection, IPS-1, a protein that is essential for cytosolic sensing of viral RNA, is degraded in HRV1a-infected cells. Induction of apoptosis by puromycin led to the cleavage of IPS-1, but treatment of HRV1a-infected cells with the pan-caspase inhibitor, zVAD, did not block cleavage of IPS-1. IPS-1 is cleaved in vitro by caspase-3 and by the picornaviral proteinases 2A(pro) and 3C(pro). Expression of HRV1a and polioviral 2A(pro) and 3C(pro) led to degradation of IPS-1 in cells. These results suggest that IPS-1 is cleaved during HRV1a infection by three different proteases. Cleavage of IPS-1 may be a mechanism for evasion of the type I IFN response, leading to a more robust infection.