Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

Acute asthma

Asthma is a common chronic condition, characterised by episodic acute exacerbations, which may require emergency treatment. According to Asthma UK, nationally 5 400 000 people are being treated for asthma; with life-threatening asthma attacks occurring every 10 seconds and three lives lost daily. In acute asthma, symptoms, including breathlessness, chest tightness, wheeze and cough, deteriorate progressively. Individuals with asthma symptoms often present to primary care and it is important that GPs can recognise and appropriately manage acute asthma. This article reviews the background, recognition and management of acute asthma in adults and children over the age of five, drawing on current guidelines.

Management of Children with Acute Asthma Attack: A RAND/UCLA Appropriateness Approach

Bronchial asthma is the most frequent chronic disease in children and affects up to 20% of the pediatric population, depending on the geographical area. Asthma symptoms vary over time and in intensity, and acute asthma attack can resolve spontaneously or in response to therapy. The aim of this project was to define the care pathway for pediatric patients who come to the primary care pediatrician or Emergency Room with acute asthmatic access. The project was developed in the awareness that for the management of these patients, broad coordination of interventions in the pre-hospital phase and the promotion of timely and appropriate assistance modalities with the involvement of all health professionals involved are important. Through the application of the RAND method, which obliges to discuss the statements derived from the guidelines, there was a clear increase in the concordance in the behavior on the management of acute asthma between primary care pediatricians and hospital pediatricians. The RAND method was found to be useful for the selection of good practices forming the basis of an evidence-based approach, and the results obtained form the basis for further interventions that allow optimizing the care of the child with acute asthma attack at the family and pediatric level. An important point of union between the primary care pediatrician and the specialist hospital pediatrician was the need to share spirometric data, also including the use of new technologies such as teleconsultation. Monitoring the progress of asthma through spirometry could allow the pediatrician in the area to intervene early by modifying the maintenance therapy and help the patient to achieve good control of the disease.

Evaluating the transitions in care for children presenting with acute asthma to emergency departments: a retrospective cohort study

Background Acute asthma is a common presentation to emergency departments (EDs) worldwide and, due to overcrowding, delays in treatment often occur. This study deconstructs the total ED length of stay into stages and estimates covariate effects on transition times for children presenting with asthma. Methods We extracted ED presentations in 2019 made by children in Alberta, Canada for acute asthma. We used multivariable Cox regressions in a multistate model to model transition times among the stages of start, physician initial assessment (PIA), disposition decision, and ED departure. Results Data from 6598 patients on 8270 ED presentations were extracted. The individual PIA time was longer (i.e., HR < 1) when time to the crowding metric (hourly PIA) was above 1 h (HR = 0.32; 95% CI:0.30,0.34), for tertiary (HR = 0.65; 95% CI:0.61,0.70) and urban EDs (HR = 0.77; 95% CI:0.70,0.84), for younger patients (HR = 0.99 per year; 95% CI:0.99,1.00), and for patients triaged less urgent/non-urgent (HR = 0.89; 95% CI:0.84,0.95). It was shorter for patients arriving by ambulance (HR = 1.22; 95% CI:1.04,1.42). Times from PIA to disposition decision were longer for tertiary (HR = 0.47; 95% CI:0.44,0.51) and urban (HR = 0.69; 95% CI:0.63,0.75) EDs, for patients triaged as resuscitation/emergent (HR = 0.51; 95% CI:0.48,0.54), and for patients arriving by ambulance (HR = 0.78; 95% CI:0.70,0.87). Times from disposition decision to ED departure were longer for patients who were admitted (HR = 0.16; 95% CI:0.13,0.20) or transferred (HR = 0.42; 95% CI:0.35,0.50), and for tertiary EDs (HR = 0.93; 95% CI:0.92,0.94). Conclusions All transition times were impacted by ED presentation characteristics. The sole key patient characteristic was age and it only impacted time to PIA. ED crowding demonstrated strong effects of time to PIA but not for the transition times involving disposition decision and ED departure stages.

An Emergency Department Management on Acute Asthma Exacerbations in Children Younger than 12 Years

Objectives: The main objective of the study is to clinically audit and analyse the acute asthma exacerbations in children younger than 12 years regarding management of emergency department. Methods: This clinical audit was done in Bahawal Victoria Hospital, Bahawalpur during January 2020 till June 2020. We retrospectively revised all the files of children aged 0–12 years who were visited for acute asthma in the Paediatric ED of Hospital. All the patients with a diagnosis of “acute asthma,” “wheezing bronchitis,” and “bronchospasm” were included. Results: A total of 864 patients were seen in the Emergency Department during the study. Of these, a total of 293 patients were seen for a presentation of acute asthma. As some patients had multiple visits, the 293 records represented 278 unique patients. For assessing age and gender distribution of the patients, only data from the first visit were used. Otherwise, each record was treated independently for the purpose of analyses. Conclusion: It is concluded that acute asthma management still remains an area of medical practice that continues to have long-standing difficulties.

Potential Application of Lung Ultrasound in Children with Severe Uncontrolled Asthma: Preliminary Hypothesis Based on a Case Series

In recent years, lung ultrasound (LUS) has been increasingly used for the diagnosis of respiratory diseases in both adult and pediatric patients. However, asthma is a field in which the use of LUS is not yet well defined or is in development. In the following case series, we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of 6 children with asthma: some of them with acute asthma attack and with inadequately controlled allergic asthma or childhood asthma; others with acute asthma and allergic or infantile asthma adequately controlled by preventive therapy. Finally we describe the clinical, laboratory and imaging parameters of a child with severe allergic asthma in the absence of exacerbation. In these cases, albeit at different times, LUS played an important role in both the initial diagnostic process and follow-up. It also showed different ultrasound features depending on the severity of the individual asthma based on the type of asthmatic phenotype and control of it.

New onset asthma during pregnancy: two case reports

Introduction: Asthma is the most common chronic respiratory disease during pregnancy. However, reports of new onset asthma during pregnancy are lacking. We report two cases of new onset asthma during pregnancy following respiratory tract infection, subsequently one case with M. pneumoniae infection and the other case with a combined infection with respiratory syncytial virus and rhinovirus. Case presentation: Both patients presented with the clinical features of an acute asthma exacerbation during pregnancy without a medical history of asthma. During follow up the diagnosis of asthma was supported by spirometry showing significant reversibility and elevated fractional exhaled nitric oxide (FeNO). Patients were hospitalized and received supplemental oxygen, treatment for an acute asthma exacerbation with systemic corticosteroids, high dose inhalation therapy. These therapeutic interventions subsequently led to a good outcome for the mother and newborn in both cases. Conclusions: New onset asthma should be part of the differential diagnosis in pregnant patients with respiratory symptoms, particularly in case of mycoplasma infection. Diagnosing asthma during pregnancy can be challenging. In these circumstances, additional diagnostic tests like inflammatory biomarkers FeNO and blood eosinophils) can be helpful to support the diagnosis.