Variation in Systemic Corticosteroid Prescribing for Asthma Exacerbations at Children's Hospitals.

How Viral Infections Cause Exacerbation of Airway Diseases

Background: Little information is available on eosinophil activation and the cytokine profile in virus-induced acute exacerbation of bronchial asthma; therefore, we examined the effects of treatments that included systemic corticosteroids on serum eosinophil cationic protein (ECP) and 17 cytokines/chemokines in rhinovirus- and respiratory syncytial (RS) virus-induced acute exacerbation of childhood asthma. Methods: We measured the peripheral eosinophil count, as well as the serum levels of ECP and 17 types of cytokines/chemokines (IL-1β, 2, 4, 5, 6, 7, 8, 10, 12, 13, and 17 and IFN-γ, TNF-α, GM-CSF, G-CSF, MCP-1, and MIP-1β), using a multiplex bead-based assay in 21 cases of rhinovirus- and 12 cases of RS virus-induced acute exacerbation of childhood asthma and 13 controls. We also compared the clinical data and the effects of systemic corticosteroids on these responses between rhinovirus and RS virus groups. Results: The serum levels of ECP, IL-5, and IL-6 were significantly elevated in patients with rhinovirus-induced acute exacerbation of asthma compared with controls, while serum IL-1β and IFN-γ were significantly lower in patients with rhinovirus-induced acute exacerbation of asthma than in controls. On the other hand, in RS virus-induced acute exacerbation of asthma, only the peripheral eosinophil count was significantly decreased compared with that in rhinovirus-induced acute exacerbation of asthma and controls. Furthermore, the serum levels of ECP, IL-5, and IL-6 in rhinovirus-induced acute exacerbation of asthma and levels of G-CSF in RS virus-induced acute exacerbation of asthma were significantly reduced after treatments that included systemic corticosteroids, respectively. Conclusion: These results suggest that the effects of systemic corticosteroids on serum ECP and the cytokine profile are different between rhinovirus- and RS virus-induced acute exacerbation of childhood asthma.

Introduction: Although current guidelines recommend against routine antibiotic prescription for acute exacerbation of bronchial asthma, children with acute exacerbation of asthma receive antibiotic treatment more frequently. In addition, those antibiotics are often prescribed only for exacerbation of asthma without concurrent bacterial infection. Objective: To clarify the association between antibiotic treatment and bacterial colonization in acute exacerbation of asthma, we investigated whether or not antibiotics affect the clinical condition, laboratory findings, and pharyngeal bacterial colonization in those patients. Methods: Potential bacterial pathogens were investigated in pharyngeal samples of 111 children with acute exacerbation of asthma (mean/median age: 2.8/2.6 years old, respectively). We collected clinical data, such as the duration of wheezing and antibiotic use, and measured the peripheral white blood cell counts, C-reactive protein, and serum levels of total and allergen-specific IgE. Results: Antibiotics were used in 50.5% patients with acute asthma exacerbation and included cephalosporin, penicillin, macrolide, and others. Episodes of wheezing were significantly longer in patients with antibiotic treatment than in those without it (6.7 ± 3.6 days vs. 6.0 ± 3.1, p = 0.044). Similarly, episodes of wheezing were significantly longer in moderate exacerbation patients with antibiotics than in those without them. Furthermore, in patients with Streptococcus pneumoniae, antibiotic treatment was associated with an extended duration of wheezing in cases of acute moderate exacerbation (7.0 ± 2.4 days vs. 4.8 ± 4.1, p = 0.043). Conclusions: These results suggest that antibiotic treatment in acute exacerbation of asthma might lead to longer asthmatic symptoms, specifically in patients with pharyngeal S. pneumoniae colonization.

Underestimation of Influenza Viral Infection in Childhood Asthma Exacerbations

Fractional exhaled nitric oxide change in pediatric patients after emergency department care of asthma exacerbations

The impact of education program on nurses' knowledge and performance about acute exacerbations of chronic bronchial asthma in PICUs.

Raising the Bar for Asthma Care in the Emergency Department

Infections, Immunity & their Effects on Asthma

Beyond Our Pages

Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are important events and are associated with critical illness. Eosinophilic inflammation is a treatable trait commonly found during acute exacerbations of asthma and COPD. We hypothesised that for patients with eosinophilic exacerbations, a single injection of benralizumab, a humanised monoclonal antibody against interleukin-5 receptor-α, alone or in combination with prednisolone, will improve clinical outcomes compared with prednisolone, the standard of care. The Acute exacerbations treated with BenRAlizumab trial (ABRA) was a multicentre, phase 2, double-blind, double-dummy, active placebo-controlled randomised trial completed in the UK at Oxford University Hospitals NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust. Patients were recruited from urgent care clinics and emergency departments of these two hospitals. At the time of an acute exacerbation of asthma or COPD, adults with blood eosinophil counts of equal to or more than 300 cells per μL were randomly assigned in a 1:1:1 ratio to receive acute treatment with: prednisolone 30 mg once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA plus PRED group); placebo tablets once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA group); or prednisolone 30 mg once daily for 5 days and placebo subcutaneous injection once (PRED group). Randomisation was performed with a centralised interactive computer randomisation service. All patients and study research staff involved in data collection were masked to study blood results and treatment allocation. The co-primary outcomes were proportion of treatment failures over 90 days and total visual analogue scale (VAS) symptoms at day 28 in the pooled benralizumab groups compared with the prednisolone alone group and analysed in the intention-to-treat population. The trial was registered on Clinicaltrials.govNCT04098718. Between May 13, 2021, and Feb 5, 2024, 287 patients were screened for study inclusion. 129 were excluded due to not having an exacerbation captured or not meeting the eosinophil exclusion criteria. 158 patients were randomly assigned at acute eosinophilic exacerbation of asthma or COPD where 86 (54%) patients were female and 72 (46%) were male with a mean age of 57 years (range, 18-84). 53 patients were randomly assigned to the PRED group, 53 were randomly assigned to the BENRA group, and 52 were assigned to the BENRA plus PRED treatment group. At 90 days, treatment failures occurred in 39 (74%) of 53 in the PRED group, and 47 (45%) of 105 in the pooled-BENRA group (OR 0·26 [95% CI 0·13-0·56]; p=0·0005). The 28-day total VAS mean difference was 49 mm (95% CI 14-84; p=0·0065), favouring the pooled-BENRA group. There were no fatal adverse events and benralizumab was well tolerated. Notably, hyperglycaemia and sinusitis or sinus infection adverse events were related to the prednisolone study drug only. Benralizumab can be used as a treatment of acute eosinophilic exacerbations and achieves better outcomes than the current standard of care with prednisolone alone. These results offer a new way of treating eosinophilic endotypes of asthma and COPD exacerbations. AstraZeneca.

Glutathione and arginine levels: Predictors for acetaminophen-associated asthma exacerbation?

Introduction: Variceal hemorrhage (VH) is a dreaded condition that requires urgent hospitalization. Multiple studies have shown that socioeconomic disparities are linked to poor healthcare outcomes. In this study, we aim to characterize the differences in the hospitalization outcomes of VH based on the household income area. Methods: Patients with a 1ry discharge diagnosis of VH were identified from the national inpatient sample (NIS) 2016-2018 data and classified based on household income for patients’ living areas as: low [LIA] (≤ 50% ) or high [HIA] ( >50%). The living area household income was provided by Claritas as a quartile classification per ZIP code and incorporated into the NIS data. Inverse probability weighting based on propensity score was used to adjust for differences between the two groups. Our outcomes include time to first esophagogastroduodenoscopy (EGD) (early: ≤ 24 hours vs late: > 24 hours), length of hospital stay (LOS), hospital charges, mortality, and discharge disposition. Results: Out of 62,775 included patients, 37,420 were identified as LIA group. These patients were more likely to be Black or Hispanic, covered by Medicare or Medicaid, admitted to larger bed-size hospitals, use tobacco, had lower Elixhauser’s comorbidity score, and diagnoses of shock compared to the HIA group (Table). In the outcome analyses, the LIA group had lower odds ratio (OR) of having early EGD (0.86, 95% CI 0.78 – 0.95, P 0.002) and higher OR of death (1.3, 95% CI 1.028 – 1.644, P 0.03). There were no differences in LOS (MD 0.12, 95% CI -0.09 – 0.34, P 0.26), hospital charges (MD $1699.61, 95% CI -1707.76 – 5106.98, P 0.33), discharge to nursing facilities (OR 1.01, 95% CI 0.82 – 1.25, P 0.9), discharge with visiting nurse (OR 1.08, 95% CI 0.9 – 1.29, P 0.42), and discharge to other hospitals (OR 0.81, 95% CI 0.619 – 1.053, P 0.11). In an interaction term analyses, the differences in the EGD timing between LIA and HIA groups did not explain the differences in death or other hospitalization outcomes (Figure) Conclusion: This notional study showed that patients who lived in LIA and were admitted with VH had less likelihood of receiving EGD within 24 hours and a higher likelihood of death despite having fewer comorbidities compared to patients who lived in HIA. However, the differences in EGD timing did not explain the differences in death. More studies are needed to confirm these findings and to help understand and minimize the disparity in the healthcare system in the United States.Figure 1.: Hospitalization outcomes for patients with VH based on the interaction term analyses of household income and EGD timing. Abbreviations: EGD = Esophagogastroduodenoscopy, LOS= Length of hospital stay, OSH= outside hospital, VNA= home visiting nurse. Table 1. - Baseline characteristics Characteristics LIA HIA P-value Total number (Weighted) 37,420 25,355 Age (mean(SD)) 56.10 (11.97) 57.02 (12.47) <0.001 Female (%) 12,060 (32.2) 8,200 (32.4) 0.9 Race (%) <0.001 White 21,125 (57.8) 16,800 (68.2) Black 2,975 (8.1) 1,015 (4.1) Hispanic 9,730 (26.6) 4,725 (19.2) Others 2,715 (7.4) 2,105 (8.5) Patient Location: NCHS Urban-Rural Code (%) <0.001 "Central" counties of ≥1 million population 11,925 (31.9) 8,900 (35.1) "Fringe" counties of ≥1 million population 4,380 (11.7) 8,760 (34.5) Counties of 250,000-999,999 population 9,840 (26.3) 5,060 (20.0) Counties of 50,000-249,999 population 4,810 (12.9) 1,765 (7.0) Not metropolitan or micropolitan counties 6,460 (17.3) 870 (3.4) Expected primary payer (%) <0.001 Medicare 12,075 (32.4) 7,995 (31.6) Medicaid 11,065 (29.7) 6,035 (23.8) Private insurance 8,150 (21.8) 8,445 (33.3) Self-pay/ Others/No charge 6,020 (16.1) 2,855 (11.3) Shock (%) 4,295 (11.5) 3,290 (13) 0.01 Acute kidney injury (%) 6,870 (18.4) 4,775 (18.8) 0.51 Acute respiratory failure (%) 4,180 (11.2) 2,690 (10.6) 0.33 Blood transfusion (%)* 0.35 (0.51) 0.38 (0.53) 0.001 FFP or clotting factors transfusion (%)* 0.13 (0.38) 0.14 (0.40) 0.03 Advanced vascular access (%)* 2,550 (6.8) 1,775 (7) 0.69 Intubation and mechanical ventilation (%)* 4,125 (11) 2,920 (11.5) 0.4 Weighted Elixhauser’s score (mean(SD)) 14.18 (11.17) 15.30 (11.15) <0.001 Alcohol use disorder 22,835 (61) 15,205 (60) 0.26 Tobacco use 10,585 (28.3) 6,215 (24.5) <0.001 Long-term (current) anticoagulant use (%) 790 (2.1) 475 (1.9) 0.35 Long-term (current) aspirin use (%) 2,140 (5.7) 1,395 (5.5) 0.6 Long-term (current) NSAID and other antiplatelets/antithrombotic use (%) 870 (2.3) 515 (2) 0.27 Bed size of the hospital <0.001 Small 5,835 (15.6) 5,305 (20.9) Medium 11,395 (30.5) 8,285 (32.7) Large 20,190 (54) 11,765 (46.4) Abbreviations: EGD = Esophagogastroduodenoscopy, FFP = Fresh frozen plasma, HIA = High income area, LIA = Low income area, NSAID = Nonsteroidal anti-inflammatory drugs, NCHS = National Center for Health Statistics, SD = Standard deviation.*Procedures were done prior on the same day of EGD.

Introduction: Little is known about the association between bacterial infections and exacerbations of bronchial asthma. Objective: To elucidate the effect of bacterial infections on bronchial asthma, we examined pharyngeal bacterial colonization, duration of wheezing, and serum levels of cytokines and chemokines during acute exacerbations of asthma in children. Methods: Potential bacterial pathogens were investigated in pharyngeal samples and viruses obtained from nasal secretions of 111 children who were outpatients and/or in patients with acute exacerbations of asthma (mean/median age: 2.8/2.6, respectively). We also measured serum levels of 27 different cytokines/chemokines. Results: Pharyngeal bacterial cultures were positive in 110 of 111 children. The 3 major bacterial pathogens were Streptococcus pneumoniae (29.7%), Moraxella catarrhalis (11.7%), and Haemophilus influenzae (10.8%). M. catarrhalis was detected more frequently in patients with pneumonia. Furthermore, patients with S. pneumoniae colonization had significantly shorter wheezing episodes than those without it. In contrast, the duration of wheezing did not differ significantly among cases with other bacteria such as M. catarrhalis and H. influenzae. Furthermore, the length of wheezing episode in patients with S. pneumoniae colonization showed significant inverse correlation with peripheral white blood cell count, neutrophil count, and C-reactive protein, while there was no significant correlation between duration of wheezing and these 3 parameters among patients with M. catarrhalis or H. influenza. Among the 27 cytokines/chemokines, only serum tumor necrosis factor (TNF)-α was significantly lower in patients with S. pneumoniae colonization than in those without it. Conclusions: These results suggested that pharyngeal S. pneumoniae colonization plays a suppressive role on the pathophysiology during acute exacerbations of asthma.

BackgroundEvidence regarding high-dose inhaled corticosteroids (HDICS) in asthma exacerbations in adults is insufficient. This study compares the treatment outcomes of HDICS as add-on therapy to the outcomes of standard treatment...

Children in the emergency department (ED) with acute asthma were enrolled to assess the impact of asthma on their activities of daily living and evaluate their access to care and preventive strategies, determine the proportion who adhered to the National Heart, Lung, and Blood Institute (NHLBI) guidelines for proper steps to take at home during an acute asthma exacerbation, and compare adherence rates for those with persistent and mild intermittent asthma. Children 2 to 18 years old who presented to the Children's Hospital of Philadelphia's ED with acute asthma exacerbations were enrolled prospectively. Parents and patients completed the 108-item Asthma Exacerbation Response Questionnaire with a focus on determining the home management steps they took both at the onset of the asthma exacerbation and just before coming to the ED. Among the 433 children studied, 76% had at least 1 doctor visit, 75% had at least 1 ED visit, and 43% had at least 1 hospitalization for asthma in the preceding 12 months. Overall, 64% had persistent asthma by NHLBI criteria, yet just 4% were cared for by an allergist or pulmonologist, 38% took daily anti-inflammatory therapy, and 18% received a daily inhaled corticosteroid. Also, 48% did not use a holding chamber with their metered-dose inhalers, and 66% did not use their peak flow meters. Regarding exacerbation response, 71% did not have a written action plan, and 89% did not maintain a symptom diary. Both at the onset of wheezing and just before coming to the ED, administration of a beta2-agonist was the only step that the majority of children performed. One-third or fewer followed the other steps recommended by the NHLBI, including using a peak flow meter, beginning oral corticosteroids, calling or going to see the doctor, or going to the ED. Children with persistent asthma were not more adherent to the guidelines than those with mild intermittent disease. Asthma has a significant adverse effect on the lives of these children. The NHLBI guidelines, first published a decade ago, were designed to reduce asthma's increasing morbidity and mortality, but this study uncovered a high rate of nonadherence with many aspects of the guidelines, including preventive strategies and home management of an exacerbation.