Asthma Exacerbations Research Articles

How to implement the anti-inflammatory reliever treatment proposed by the Global Initiative for Asthma in low- and middle-income countries

There are no plausible arguments to consider that the best evidence-based asthma treatment should be different in low- and middle-income countries (LMICs). A few decades ago, the recognition of asthma as an inflammatory disease of the airways positioned the inhaled corticosteroids (ICS) as the cornerstone of the treatment of this disease, maintaining bronchodilators, especially the short-acting beta-agonists (SABA), as symptom-reliever medications for use as needed. However, adherence to regular use of ICS is very low, especially in LMICs, favoring the overuse of SABA, which has been related to an excess of exacerbations and mortality. Recently, the Global Initiative for Asthma (GINA) strategy has recommended the mandatory use of ICS every time a bronchodilator is used as needed (for symptoms relief), whether only as needed or with a background of regular dose of ICS, and has named it: anti-inflammatory reliever (AIR) therapy. This form of therapy, which has been related to a significant reduction of asthma exacerbations, is very attractive for LMICs where patients do not have guaranteed a proper medical follow-up and the access to on-the-counter medications is high. However, the implementation of AIR therapy in LMICs will face many of the already recognized barriers for the diagnosis and treatment of asthma in these countries, especially related to limited access to care in very different health systems, low education level of patients and communities, insufficient health personnel training in asthma in primary care, the unfordable cost of medications, and the lack of political commitment. This review analyzes some of these challenges and strategies for facing them in LMICs.

Clinic-Functional Assessment of Hemoglobin Desaturation by Oxygen in 6-Minute Walk Test Among Patients with Bronchial Asthma

The main purpose of the study is to assess the prevalence and clinical significance of hemoglobin desaturation by oxygen during the 6-minute walk exercise test in patients with bronchial asthma. Material and methods: 75 patients with exacerbation of mixed (48 %) and allergic (52 %) bronchial asthma were examined. Research explored following methods: collecting complaints and anamnesis, physical examination, spirometry, CO-metry of exhaled air to determine carboxyhemoglobin, transcutaneous 2-wave pulse oximetry (at rest and during 6-minute walk exercise test) with spectral analysis and correction for COHb. 6-minute walk exercise test was performed after relief of asthma exacerbation (before discharge from the hospital), assessing the desaturation-distance ratio (the ratio of the area of oxygen desaturation of hemoglobin to the 6-minute walk exercise test distance), O2-GAP index, the dynamics of fatigue and dyspnea before and after 6-minute walk exercise test. In smoking patients (n = 36, 48 %), the smoker index was calculated. Based on oximetry results during the 6-minute walk exercise test, patients were divided into “desaturators” (n = 28, 37 %) and “non-desaturators” (n = 47, 63 %). Results. The findings of the research illustrated that hemoglobin desaturation by oxygen, detected by reducing SpO2 to < 90 % during 6-minute walk exercise test, was associated with the severity of this disease exacerbation, more pronounced impairment of pulmonary ventilation and blood oxygenation, and the demand for longer hospitalization. The prevalence of tobacco smoking and the magnitude of the smoker index in both groups were identical but in “desaturators” we found a higher prevalence of the combination of asthma and COPD compared to “non-desaturators.” The “desaturators” had significantly higher level of desaturation-distance ratio and increased demand for additional oxygen flow to maintain SpO2 at ≥ 88 % during a 6-minute walk test, which indicates a higher “oxygen price” of physical activity in this group of patients. Conclusion. Thus, the high prevalence of the phenomenon of hemoglobin oxygen desaturation during 6-minute walk exercise test in patients with asthma and associated clinic-functional disorders supports the feasibility and clinical significance of conducting a stress test with a 6-minute walk not only in COPD patients, but also in bronchial asthma patients.

Direct comparative study of anti-IgE and anti-IL4Rα therapy effectiveness in patients with severe allergic and mixed bronchial asthma

Introduction. There is insufficiency of direct comparative studies of genetically engineered biological drugs (GEBD) for severe bronchial asthma (SA) treatment in scientific databases.Aim. To compare omalizumab and dupilumab effectiveness in patients with allergic and mixed SA in real clinical practice.Materials and methods. The direct comparative study included SA patients with an allergic component from regional registry of Sverdlovsk region. The data of patients with allergic (n = 68) and mixed (n = 27) SA treated with omalizumab (n = 62) and dupilumab (n = 33) were analyzed. Therapy effectiveness was determined for 12 months in general group No. 1, allergic asthma group No. 2 and mixed asthma group No. 3 according to the following indicators: asthma control level (ACT), proportion of patients with uncontrolled asthma, need for systemic glucocorticosteroids (SGCS) and short‐acting beta agonists (SABA), basic therapy volume, asthma exacerbations number, emergency calls and hospitalizations, forced expiratory volume in the first second (FEV ), assessment of life quality (AQLQ and SNOT-22). Control evaluation visits were conducted before therapy start, after 4 and 12 months of biologics taking.Results. In general, during the 12 months of targeted therapy in patients receiving omalizumab statistically significant positive dynamics was observed in 12 of the 13 evaluated indicators; in patients receiving dupilumab – in 9 indicators. When analyzing such indicators as, ACT, taking SGCS, exacerbations of SA, FEV , statistically significant positive dynamics was revealed for all 4 indicators in patients receiving omalizumab in group No. 2 and in patients receiving dupilumab in group No. 3.Conclusions. Patients with allergic component of SA respond equally well to therapy with omalizumab and dupilumab. At the same time, a tendency towards the advantage of omalizumab in patients with allergic asthma, and dupilumab in patients with a mixed phenotype of the disease was revealed.

Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation.

Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.

The role of anti-IgE therapy in achieving remission of bronchial asthma

Bronchial asthma is one of the most common respiratory diseases, and follows a severe clinical course in 10% of patients. 70–80% of patients with severe asthma have signs of type 2 (T2) inflammation, which is clinically defined as an increase in blood and airways eosinophil counts. The emergence of genetically engineered biological drugs has made it possible to review the purpose of asthma therapy, that is, achieving remission instead of disease control, which includes managing the symptoms, absence of exacerbations, stabilization of functional parameters and normalization of biomarkers in the absence of therapy with systemic glucocorticoids. Clinical studies have shown that therapy with genetically engineered biological drugs can reduce the frequency of asthma exacerbations, decrease the need for maintenance therapy with systemic glucocorticoids, relieve symptoms, improve quality of life, which results in achieving a disease remission in 19.6–31.6% of patients. Predictors of suboptimal response to biological therapy were a high body mass index, admission to the intensive care unit and a history of severe asthma exacerbations, as well as initially more severe clinical manifestations of the disease. The most pronounced effect of omalizumab therapy was observed in patients with atopic severe asthma showing symptoms and exacerbations that are clinically associated with allergic sensitization confirmed by positive results of skin prick testing and (or) identification of serological allergen-specific IgE, elevated levels of T2 biomarkers. This publication presents the latest data on asthma remission: the concept, basic criteria, as well as the role of genetically engineered biological drugs in achieving a remission.

Caregiver burden among parents of school-age children with asthma: a cross-sectional study.

To investigate the caregiver burden of parents of school-age children with asthma and analyze the factors influencing their caregiver burden. A convenience sampling method was used to select 366 parents of school-age children with asthma who visited the outpatient departments of three tertiary hospitals in Sichuan Province, China, from January 2021 to July 2021. A general information questionnaire and the Caregiver Burden Inventory (CBI) were used to assess the current caregiver burden and analyze the influencing factors. The caregiver burden score of parents of school-age children with asthma was 27 (17, 39), with 40.43% of parents experiencing moderate to high levels of burden. Detailed results of univariate analysis showed that there were significant differences in caregiver burden scores based on parents' gender, highest education level, number of children, occupation, family history of asthma, monthly family income, annual medical expenses for the child, child's gender, whether the child had undergone lung function tests, number of emergency visits due to asthma exacerbation in the past 3 months, and whether the child had missed school due to asthma exacerbation in the past 3 months (p < 0.1). Detailed results of multivariate analysis showed that parents' gender, occupation, family history of asthma, monthly family income, annual medical expenses for the child, number of emergency visits due to asthma exacerbation in the past 3 months, and whether the child had missed school due to asthma exacerbation in the past 3 months were independent risk factors for caregiver burden in parents of school-age children with asthma (p < 0.05). Parents of school-age children with asthma experience a certain level of caregiver burden, with over one-third of parents experiencing moderate to high levels of burden. Being a mother, being a worker, having no family history of asthma, having low monthly family income, having high annual medical expenses for the child, having frequent emergency visits due to asthma exacerbation in the past 3 months, and having missed school due to asthma exacerbation in the past 3 months are independent risk factors for caregiver burden in parents of school-age children with asthma, healthcare providers should develop feasible coping strategies, such as paying attention to caregivers' psychological condition to reduce the burden of caring for parents of school-age children with asthma. The entire society should also make efforts in improving social support and strengthening healthcare coverage in order to achieve the aforementioned goals.

Parallel detection of multiple biomarkers in a point-of-care-competent device for the prediction of exacerbations in chronic inflammatory lung disease

Sudden aggravations of chronic inflammatory airway diseases are difficult-to-foresee life-threatening episodes for which advanced prognosis-systems are highly desirable. Here we present an experimental chip-based fluidic system designed for the rapid and sensitive measurement of biomarkers prognostic for potentially imminent asthma or COPD exacerbations. As model biomarkers we chose three cytokines (interleukin-6, interleukin-8, tumor necrosis factor alpha), the bacterial infection marker C-reactive protein and the bacterial pathogen Streptococcus pneumoniae—all relevant factors in exacerbation episodes. Assay protocols established in laboratory environments were adapted to 3D-printed fluidic devices with emphasis on short processing times, low reagent consumption and a low limit of detection in order to enable the fluidic system to be used in point-of-care settings. The final device demonstrator was validated with patient sample material for its capability to detect endogenous as well as exogenous biomarkers in parallel.

Eosinophilic Granulomatosis with Polyangiitis with ophthalmic involvement: A Case report and Literature Review

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic necrotizing vasculitis primarily affecting small blood vessels. It is characterized by extravascular eosinophilic granulomas, peripheral eosinophilia, and often coexists with asthma. This rare condition can affect individuals of any gender and age, presenting with a variety of multisystemic symptoms. Prognosis is largely influenced by cardiac involvement, evaluated using the Five-Factor Score (FFS) to guide treatment decisions. Respiratory manifestations, particularly severe and corticosteroid-dependent asthma, are common in EGPA and may aid in its early diagnosis. In this case report, we describe a patient with an uncontrolled asthma admitted for moderate asthma exacerbation. Clinical examination revealed ocular redness and skin lesions, along with hypereosinophilia on assessment and reticulo-micronodular infiltrates on chest CT scan. EGPA diagnosis was confirmed based on the ACR 1990 criteria, wich have been updated and substituted with more objective criteria in 2022. According to the FFS score, the patient underwent systemic corticosteroid therapy in conjunction with azathioprine, leading to an overall favorable outcome over a 3-year follow-up period.

Levels of Galectin-7 in serum and sputum in children with asthma

Objective: To observe the expression of Galectin-7 in the serum and sputum of asthmatic children and to explore its significance in asthmatic children. Methods: The study prospectively case-control selected 183 children diagnosed with bronchial asthma at Department Ⅱ of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital of Capital Medical University. The control group consisted of 41 children with other bronchial diseases and 43 healthy children. Children in the asthma group were divided into acute and non-acute exacerbation groups. Acute exacerbation group was divided as mild acute, moderate acute and severe acute groups; non-acute exacerbation group was divided as mild persistent, moderate persistent and severe persistent groups. Children without acute exacerbation asthma in the asthma group were divided into high and low Galectin-7 groups based on median serum Galectin-7 levels. Serum and sputum were collected, Galectin-7 levels were measured using enzyme-linked immunosorbent assay. The study compared and analyzed the differences in Galectin-7 levels between children with asthma and the control groups using Mann-Whitney U test or the Kruskal-Wallis or the Chi-square test for inter-group comparisons. Results: Among 183 children, 61 cases had acute asthma exacerbation, and 122 cases had persistent asthma without acute exacerbation. The asthma group comprised 110 males and 73 females. The control group consisted of 41 children with other bronchial diseases, including 24 cases of bronchiectasis and 17 cases of obliterans bronchitis. The control group comprised 26 males and 15 females. Forty-three healthy children who underwent physical examination, including 22 males and 21 females. The levels of Galectin-7 in serum were significantly higher in children with an acute asthma exacerbation than that of healthy children (0.1 (0, 0.7) vs. 0 (0, 0.2) μg/L, Z=2.09, P=0.001). Galectin-7 levels in sputum were higher in children with an acute asthma exacerbation than that in children with other bronchial diseases (1.2 (0.1,3.7) vs. 0.4 (0.1, 1.5) μg/L, Z=2.20, P<0.001). Serum Galectin-7 levels were significantly higher in children with persistent asthma compared to children with other bronchial diseases and healthy children (0.6 (0.3, 1.2) vs. 0.1 (0, 0.5) and 0 (0, 0.2) μg/L, Z=-6.12,-7.63, both P<0.001), and the levels were significantly and positively correlated with asthma severity (r=0.77, P<0.001), disease duration (r=0.34, P=0.001), and number of previous attacks (r=0.51, P<0.001). There were 61 children in the high-Galectin-7 group and 61 children in the low-Galectin-7 group. Children with high Galectin-7 had more asthma triggers, a greater proportion with a positive family history, more previous asthma attacks, longer duration of asthma, and higher serum total IgE levels compared to those with low Galectin-7 (χ2=9.30, 22.46, Z=5.06, 3.57, 2.31, all P<0.05). Conclusion: The expression of Galectin-7 is found to be elevated in the serum and sputum of asthmatic children and correlated with asthma conditions.

Age-related effects of Mycoplasma pneumoniae infection and subsequent asthma exacerbation in children.

Mycoplasma pneumoniae causes community-acquired pneumonia in children and increases asthma risk, but large studies are lacking. To assess the link between M. pneumoniae infection and to asthma exacerbation, in children with allergies, and age of infection impact. This retrospective cohort study analyzed medical records of South Korean children between January 2002 and December 2017. The study's exposure was hospitalization with an M. pneumoniae-related diagnosis, and the outcome was defined as asthma exacerbation, confirmed by hospitalization at least 6 months after M. pneumoniae infection, with alternative validation using asthma diagnosis and systemic steroid prescription records. Hazard ratios (HRs) for asthma exacerbation risk were estimated for the matched cohort using a Cox proportional hazards model stratified by allergic comorbidities. Time-dependent covariates and age-stratified exposure groups were used to calculate odds ratios. The study included 84,074 children with M. pneumoniae infection and 336,296 unexposed children. Follow-up for 12.2 ± 2.3 years found the exposed group had a significant risk of asthma exacerbation (HR 2.86, 95% confidence interval [CI] 2.67-3.06) regardless of allergic comorbidities. The risk was highest (over threefold) in children infected between 24 and 71 months. Sensitivity analysis using an alternative definition of the outcome showed an HR of 1.38 (95% CI 1.35-1.42), further supporting the association between M. pneumoniae infection and asthma exacerbation. M. pneumoniae infection was significantly associated with an increased risk of subsequent asthma exacerbation regardless of allergic comorbidities. Further research needed for understanding and confirmation.

Homeostatic Measure of Insulin Resistance Is Associated With Future Asthma Exacerbations: A 1-Year Prospective Cohort Study

Recent evidence suggests that insulin resistance affects asthma outcomes. However, the effect of the homeostatic measure of insulin resistance (HOMA-IR) on airway inflammation and asthma exacerbations (AEs) is poorly understood. To analyze the relationship between HOMA-IR and clinical and inflammatory characteristics in patients with asthma, and the association between HOMA-IR and AEs in the following year. A prospective cohort study recruited participants with asthma, who were classified into the HOMA-IRhigh group and HOMA-IRlow group based on the cutoff value of 3.80 for HOMA-IR and were observed within 12 months. We evaluated the clinical and inflammatory features and conducted a 1-year follow-up to study the exacerbations. We used negative binomial regression models to analyze the association between HOMA-IR and AEs. Compared with patients in the HOMA-IRlow group (n= 564), those in the HOMA-IRhigh group (n= 61) had higher levels of body mass index, a higher waist circumference and waist-hip ratio, higher triglycerides, lower cholesterol high-density lipoproteins, more neutrophils in the peripheral blood, and elevated IL-5 levels in the induced sputum. Furthermore, patients in the HOMA-IRhigh group had a significantly increased risk for moderate to severe AEs (adjusted incidence rate ratio [aIRR]= 2.26; 95% CI, 1.38-3.70), severe AEs (aIRR= 2.42; 95% CI, 1.26-4.67), hospitalization (aIRR= 2.54; 95% CI, 1.20-5.38), and emergency visits (aIRR= 3.04; 95% CI, 1.80-8.53). The homeostatic measure of insulin resistance was associated with asthma-related clinical features and airway inflammation, and was an independent risk factor for future AEs. Therefore, insulin resistance may have important implications for managing asthma as a potential treatable trait.

Coronary and Cerebrovascular Events and Exacerbation of Existing Conditions After Laboratory‐Confirmed Influenza Infection Among US Veterans: A Self‐Controlled Case Series Study

ABSTRACTBackgroundInfluenza may contribute to coronary/cerebrovascular events and exacerbate underlying conditions.MethodsWe used self‐controlled case series (SCCS) design to analyze data from US Veterans ≥18 years with coronary/cerebrovascular or exacerbation event +/−1 year of lab‐confirmed influenza (LCI) during 2010–2018. We estimated the incidence ratio (IR) (95% CI) of the event for risk interval (Days 1–7 post‐LCI) versus control interval (all other times +/−1 year of LCI) with fixed‐effects conditional Poisson regression. We included biomarker data for mediation analysis.ResultsWe identified 3439 episodes with coronary/cerebrovascular‐related hospitalizations. IRs (95% CI) for LCI risk versus control interval were STEMI 0.6 (0.1, 4.4), NSTEMI 7.3 (5.8, 9.2), ischemic stroke 4.0 (3.0, 5.4), hemorrhagic stroke 6.2 (3.4, 11.5), and coronary spasm 1.3 (0.5, 3.0). IR significantly increased for NSTEMI and ischemic stroke among those ≥ 65 years. IR for NSTEMI and ischemic stroke dropped 26% and 10%, respectively, when white blood cell (WBC) and platelet count were considered. LCI was significantly associated with exacerbation of preexisting asthma, chronic obstructive pulmonary disease, and congestive heart failure.ConclusionsWe found significant association between LCI and hospitalization for NSTEMI, ischemic stroke, and hemorrhagic stroke, the latter possibly due to unaccounted time‐varying confounding in SCCS design.

Innate immune responses are increased in children with acute asthma exacerbation.

Little is known about the immune responses during acute asthma exacerbation. In this study, we examined immune responses in children following an acute asthma exacerbation. We evaluated pro-inflammatory cytokine levels and gene expression profiles in blood samples from pediatric patients admitted for acute asthma exacerbation. Viral PCR was performed to differentiate between viral or non-viral-associated exacerbations. Following informed consent, clinical data were obtained from 20 children with asthma (median [interquartile range, IQR]: age 11.5 [8.0, 14.2]) years and 14 healthy age-matched controls (10.5 [7.0, 13.0]). Twelve had positive nasopharyngeal Polymerase chain reaction (PCR) for viral infection (11 rhinoviruses and 1 respiratory syncytial virus (RSV)). Nine were in the pediatric intensive care unit (PICU) and among them five required continuous positive airway pressure (CPAP). Mean (±SD) days on systemic steroids before drawing blood sample were 2.5 ± 1.6. Twelve had history of environmental allergies with 917 (274, 1396) IU/mL total IgE (median (IQR)). Compared with controls, IL-1RA and IL-10 levels were significantly increased and TNF-α significantly decreased in asthma subjects (p < .05 for all). RNA-seq analysis revealed 852 differentially expressed genes in subjects with asthma. Pathway analysis found upregulated genes and pathways involved in innate immune responses in subjects with asthma. Significantly reduced genes included pathways associated with T helper cell differentiation and activation. In acute asthma exacerbation, innate immune pathways remained increased while adaptive immune responses related to T helper cells are blunted and are independent of trigger or asthma severity. Our novel findings highlight the need to identify new therapies to target persistent innate immune responses to improve outcomes in acute asthma.

Effect of Toll-like Receptor-3 Antagonist on Viral Asthma Exacerbations Via a TLR3/dsRNA Complex Pathway

Background: The Toll-like receptor-3 (TLR3) ligand Poly(I:C) has been shown to induce a viral aggravation of severe asthma by identifying double-stranded RNA (dsRNA). This study aimed to evaluate the therapeutic role of the TLR3/dsRNA complex inhibitor-calbiochem compound in the treatment of Poly(I:C)-induced viral asthma exacerbations through the ovalbu-min-induced asthma model in Swiss albino mice. Methods: Poly(I:C) and Ovalbumin drugs were injected in mice to sensitize (i.p. on 0, 7, and 14th day) and challenge (i.n. on the 21st and 22nd days). In contrast, the treatment drug TLR3/dsRNA complex inhibitor-calbiochem was given on the 21st and 22nd days intraperitoneally within the study period. In-vivo measurements were carried out in BALF and serum for pro-inflammatory cytokines, inflammatory leukocyte counts, lactate dehydrogenase (LDH) and nitrite levels, lungs/body weight index, and lung tissue histopathology using H and E staining in mice airways. Results: High levels of cytokines (NF-κB, IL-1β, IL-5, RANTES, MIP-2, and MCP-1) are seen in groups exposed to OVA and Poly (I:C). Further, inflammatory leukocyte cell counts, lung-body weight (LW/BW) index, airway hyperresponsiveness (AHR), and lung tissue damage sug-gest exacerbations in mice airways. On the other hand, TLR3/dsRNA complex inhibitor-calbio-chem and dexamethasone significantly reversed these changes toward normal levels. Conclusions: These results suggest that the novel compound TLR3/dsRNA complex inhibitor-calbiochem has a better therapeutic role than dexamethasone for managing inflammatory char-acteristics in asthmatic mice lungs and is a potent target for viral asthma exacerbations

Congenital Long QT Syndrome Unmasked by Albuterol in an Adolescent with Asthma

BackgroundPatients with congenital long QT syndrome (LQTS) are prone to ventricular dysrhythmia but may be initially asymptomatic with a normal QTc interval on resting electrocardiogram (ECG). Albuterol is listed as a medication that poses a “special risk” to patients with congenital LQTS, but its effects have been rarely described. We present a case of previously unknown, asymptomatic congenital LQTS unmasked by albuterol in an adolescent with asthma. Case ReportA 12-year-old girl with a history of asthma presented to the emergency department (ED) with shortness of breath, wheezing, and tachycardia for 24 h, consistent with acute asthma exacerbation. She received two doses of her home albuterol inhaler 2 h prior to presentation. Initial ECG demonstrated a QTc of 619 ms. Her remaining history, clinical examination, and laboratory workup, including electrolytes, were unremarkable. She was observed with cardiac monitoring before being discharged from the ED in stable condition for next-day outpatient pediatric cardiology follow-up. Resting office ECGs revealed QTcs from 440–470 ms. Exercise stress test revealed QTc prolongation of 520 ms and 500 ms at minute-2 and minute-4 of recovery, respectively. Genetic testing revealed heterozygous pathogenic variants in KCNQ1, consistent with type 1 LQTS. Why Should an Emergency Physician Be Aware of This?Albuterol may be a cause of marked QTc prolongation in ED patients with underlying congenital LQTS, which can be a diagnostic clue in previously unidentified patients. Extreme QTc prolongation also serves as an indication in the ED for Cardiology consultation, laboratory evaluation for electrolyte imbalances, and observation with cardiac monitoring.

Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.

Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker-signature to predict sputum eosinophilia in asthma. VOCs emitted into the space above sputum samples (headspace) from severe asthmatics (n=36) were collected onto sorbent tubes and analysed using thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia ≥3% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: (I) acute asthmatics according to blood eosinophilia ≥0.3x109cells/L or sputum eosinophilia of ≥ 3% in the UK EMBER consortium (n=65) and U-BIOPRED-IMI consortium (n=42). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analysed by gas-chromatography-mass spectrometry (GC×GC-MS -EMBER or GC-MS -U-BIOPRED). The in vitro headspace identified 19 VOCs associated with sputum eosinophilia and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia ≥ 3% in headspace (AUROC (95% CI) 0.90(0.80-0.99), p<0.0001), correlated inversely with sputum eosinophil % (rs= -0.71, p<0.0001) and outperformed FeNO (AUROC (95% CI) 0.61(0.35-0.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89(0.76-1.0) (EMBER cohort) with sputum eosinophilia and 0.90(0.75-1.0) in U-BIOPRED - again outperforming FeNO in U-BIOPRED 0.62 (0.33-0.90). We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point of care clinical sensors.

The analysis of asthma control using Markov models: MOSAR study (Multicenter Observational Study of Asthma in Rabat-Morocco)

Background This study aimed to analyze the probabilities of transitioning between controlled, uncontrolled, and partially controlled states of asthma patients and investigate the influence of age, smoking, dust allergy, and obesity on these probabilities. Methods This study aimed to analyze the probabilities of transitioning between controlled, uncontrolled, and partially controlled states of asthma patients and investigate the influence of age, smoking, dust allergy, and obesity on these probabilities. Results Results showed that controlled patients were more likely to remain in that state, with approximately 79 out of 100 patients expected to stay in optimal control in the long term. A discrete nonhomogeneous time Markov Model with the stationarity criterion was used to examine the factors affecting patient states and transitions. Patients seen during the spring and summer seasons were more likely to move into a controlled state compared with those seen in the fall and winter seasons. Patients with dust allergies and obesity significantly impacted asthma exacerbation, with overweight patients more likely to transition into a controlled state. The study estimated the transition intensities matrix under certain conditions, assuming the regularity of patients. In the long term, the probability of an asthmatic patient being in a controlled state was approximately 0.8. Conclusion This study provided insights into the probabilities and factors influencing asthma progression in Morocco. Dust allergy and obesity were identified as significant contributors to asthma exacerbation, emphasizing the need for effective management strategies.

Predictors of exacerbation in Japanese patients with severe asthma: Analysis of the severe asthma research program (Okayama-SARP) cohort

BackgroundBecause exacerbation of severe asthma decreases patients’ quality of life, this study aimed to identify predictive factors for asthma exacerbation. MethodsJapanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program). ResultsA total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51–72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV1 (%FEV1) at enrollment were 204 (IQR, 49–436)/μL, 28 (IQR, 15–43) ppb, 172 (IQR, 56–473) IU/mL, and 80.0 (IQR, 61.1–96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period. ConclusionsExacerbation during the previous year, low ACT score, and low %FEV1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor.

Investigation of lactotransferrin messenger RNA expression levels as an anti–type 2 asthma biomarker

Lactotransferrin (LTF) has an immunomodulatory function, and its expression levels are associated with asthma susceptibility. We sought to investigate LTF messenger RNA (mRNA) expression levels in human bronchial epithelial cells (BECs) as an anti-type 2 (T2) asthma biomarker. Association analyses between LTF mRNA expression levels in BECs and asthma-related phenotypes were performed in the Severe Asthma Research Program (SARP) cross-sectional (n= 155) and longitudinal (n= 156) cohorts using a generalized linear model. Correlation analyses of mRNA expression levels between LTF and all other genes were performed by Spearman correlation. Low LTF mRNA expression levels were associated with asthma susceptibility and severity (P< .025), retrospective andprospective asthma exacerbations, and low lung function (P< 8.3×10-3). Low LTF mRNA expression levels were associated with high airway T2 inflammation biomarkers (sputum eosinophils and fractional exhaled nitric oxide; P<8.3×10-3) but were not associated with blood eosinophils or total serum IgE. LTF mRNA expression levels were negatively correlated with expression levels of TH2 or asthma-associated genes (POSTN, NOS2, and MUC5AC) and eosinophil-related genes (IL1RL1, CCL26, and IKZF2) and positively correlated with expression levels of TH1 and inflammation genes (IL12A, MUC5B, and CC16) and TH17-driven cytokines or chemokines for neutrophils (CXCL1,CXCL6, and CSF3) (P< 3.5×10-6). Low LTF mRNA expression levels in BECs are associated with asthma susceptibility, severity, and exacerbations through upregulation of airway T2 inflammation. LTF is a potential anti-T2 biomarker, and its expression levels may help determine the balance of eosinophilic and neutrophilic asthma.

Clinical characterisation of exacerbations of severe eosinophilic asthma occurring on mepolizumab and placebo.

Asthma exacerbations in people treated with mepolizumab result in less peak expiratory flow reduction than placebo but similar symptom scores. Symptoms recover slower, indicating these exacerbations may be less prednisolone responsive. https://bit.ly/3xQsFRB.