Increased Asthma Exacerbations Research Articles

Multivariate time series approaches to extract predictive asthma biomarkers from prospectively patient-collected diary data: a systematic review

ObjectivesLongitudinal data are common in asthma studies, to assess asthma progression in patients and identify predictors of future outcomes, including asthma exacerbations and asthma control. Different methods can quantify temporal...

Impact of obesity on airway remodeling in asthma: pathophysiological insights and clinical implications.

The prevalence of obesity among asthma patients has surged in recent years, posing a significant risk factor for uncontrolled asthma. Beyond its impact on asthma severity and patients' quality of life, obesity is associated with reduced lung function, increased asthma exacerbations, hospitalizations, heightened airway hyperresponsiveness, and elevated asthma-related mortality. Obesity may lead to metabolic dysfunction and immune dysregulation, fostering chronic inflammation characterized by increased pro-inflammatory mediators and adipocytokines, elevated reactive oxygen species, and reduced antioxidant activity. This chronic inflammation holds the potential to induce airway remodeling in individuals with asthma and obesity. Airway remodeling encompasses structural and pathological changes, involving alterations in the airway's epithelial and subepithelial layers, hyperplasia and hypertrophy of airway smooth muscle, and changes in airway vascularity. In individuals with asthma and obesity, airway remodeling may underlie heightened airway hyperresponsiveness and increased asthma severity, ultimately contributing to the development of persistent airflow limitation, declining lung function, and a potential increase in asthma-related mortality. Despite efforts to address the impact of obesity on asthma outcomes, the intricate mechanisms linking obesity to asthma pathophysiology, particularly concerning airway remodeling, remain incompletely understood. This comprehensive review discusses current research investigating the influence of obesity on airway remodeling, to enhance our understanding of obesity's role in the context of asthma airway remodeling.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma

BackgroundHypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT).ObjectiveTo investigate whether genetic and type 2...

Preschool children from lower household incomes experience inequality in asthma treatment: findings from a Danish nationwide cohort study.

The obligation to pay for asthma medication in a country with universal healthcare might lead to increased asthma exacerbations and inequitable healthcare access for children from low-income households. Thus, the aim of this study was to examine the association between household income and childhood/preschool asthma regarding hospitalization and medication receipt. In this nationwide register-based cohort study, we encompassed all 3-year-old children residing in Denmark, born between 2000 and 2014, along with their linked parents and followed them until their sixth birthday. Household income was divided into quartiles. Asthma was categorized in two mutually exclusive groups as either the redemption of two prescriptions for asthma medication or receiving a hospital diagnosis. We utilized Poisson regression to estimate the risk ratio (RR). The analysis included 834 422 preschool children. The prevalence of asthma dependent on medication alone was 7.3%, while 1.8% of children necessitated asthma-related hospitalization. Income inequality was evident across all income quartiles. Notably, children from the lowest income quartile had a RR of 0.95 (95% CI: 0.92-0.98) of redeeming asthma medication and conversely a RR of 1.18 (95% CI: 1.14-1.23) of asthma-related hospitalization. Despite universal healthcare, income inequality has a dual impact on children from low-income households. They face a diminished risk of redeeming asthma medication and a higher susceptibility to asthma-related hospitalizations indicating an unequal access to healthcare. Prioritizing efforts to reduce childhood health inequalities is crucial. However, further research, particularly qualitative studies, is needed to better comprehend the underlying mechanisms to address the complexities of income inequality.

Gaps and Future Directions in Clinical Research on Obesity-Related Asthma.

Obesity is a major comorbidity for the development and worsening of asthma. It is associated with increased disease incidence, reduced response to inhaled and systemic steroids, increased asthma exacerbations, and poor disease control. Over the past twodecades, we have learned that there are clinical asthma phenotypes associated with obesity, which have unique immune, inflammatory, and metabolic disease mechanisms. The objectives of this review are to provide a brief overview of the associations and gaps between these chronic inflammatory diseases and the role that traditional therapies have on treating patients with obesity-related asthma, and to describe new clinical research of therapeutic developments targeting mechanisms that are more specific to this patient population.

Immunoglobulin Ige Levels And Clinical Dynamics Of Asthma In Children And Adolescents.

The involvement of IgE in type 1 hypersensitivity reactions, including asthma and allergic rhinitis, is widely recognized, and established. However, within this region, there exists a dearth of research exploring the relationship between serum IgE levels and the severity of asthma within the pediatric population. Consequently, the primary objective of this study was to compare the IgE status among children and adolescents diagnosed with asthma, and to examine its association with asthma exacerbations and hospitalizations. By investigating these parameters, we aimed to shed light on the potential role of IgE in influencing disease outcomes in this specific population. A retrospective study was conducted at The Aga Khan University Hospital from January 2015 to December 2020. Children and adolescents aged 6-18 years who were diagnosed and admitted with asthma, and who had measurement of IgE levels during asthma exacerbation were included in the study. The participants were stratified into two groups based on their IgE levels: normal IgE levels and high IgE levels. Various parameters, including the number of asthma exacerbations, emergency room (ER) visits, hospitalizations, average length of stay, as well as other clinical characteristics such as the presence of allergic rhinitis in the past and a family history of asthma were assessed. A total of 122 patients were included in the study. Of them 57 patients (46.72%) were found to have high IgE levels, and 65 patients (53.28%) had normal IgE levels based on their age group. The average number of exacerbations per year was significantly greater the in high IgE group (3.6±1.09), in comparison to the normal IgE group (2.49±1.22). Higher serum IgE levels correlated with increased asthma exacerbations, emergency room visits, hospitalizations, and a positive family history of asthma, suggesting a potential link between IgE and asthma severity in the pediatric population of Pakistan.

Impacts of Wildfire Smoke and Air Pollution on a Pediatric Population with Asthma: A Population-Based Study.

Wildfires are increasing yearly in number and severity as a part of the evolving climate crisis. These fires are a significant source of air pollution, a common driver of flares in cardiorespiratory disease, including asthma, which is the most common chronic disease of childhood. Poorly controlled asthma leads to significant societal costs through morbidity, mortality, lost school and work time and healthcare utilization. This retrospective cohort study set in Calgary, Canada evaluates the relationship between asthma exacerbations during wildfire smoke events and equivalent low-pollution periods in a pediatric asthma population. Air pollution was based on daily average levels of PM2.5. Wildfire smoke events were determined by combining information from provincial databases and local monitors. Exposures were assumed using postal codes in the health record at the time of emergency department visits. Provincial claims data identified 27,501 asthma exacerbations in 57,375 children with asthma between 2010 to 2021. Wildfire smoke days demonstrated an increase in asthma exacerbations over the baseline (incidence rate ratio: 1.13; 95% CI: 1.02-1.24); this was not seen with air pollution in general. Increased rates of asthma exacerbations were also noted yearly in September. Asthma exacerbations were significantly decreased during periods of COVID-19 healthcare precautions.

Interactions between microbiome and underlying mechanisms in asthma

Microbiome primes host innate immunity in utero and play fundamental roles in the development, training, and function of the immune system throughout the life. Interplay between the microbiome and immune system maintains mucosal homeostasis, while alterations of microbial community dysregulate immune responses, leading to distinct phenotypic features of immune-mediated diseases including asthma. Microbial imbalance within the mucosal environments, including upper and lower airways, skin, and gut, has consistently been observed in asthma patients and linked to increased asthma exacerbations and severity. Microbiome research has increased to uncover hidden microbial members, function, and immunoregulatory effects of bacterial metabolites within the mucosa. This review provides an overview of environmental and genetic factors that modulate the composition and function of the microbiome, and the impacts of microbiome metabolites and skin microbiota on immune regulation in asthma.

Ozone impairs endogenous compensatory responses in allergic asthma

Asthma is a chronic inflammatory airway disease characterized by acute exacerbations triggered by inhaled allergens, respiratory infections, or air pollution. Ozone (O3), a major component of air pollution, can damage the lung epithelium in healthy individuals. Despite this association, little is known about the effects of O3 and its impact on chronic lung disease. Epidemiological data have demonstrated that elevations in ambient O3 are associated with increased asthma exacerbations. To identify mechanisms by which O3 exposure leads to asthma exacerbations, we developed a two-hit mouse model where mice were sensitized and challenged with three common allergens (dust mite, ragweed and Aspergillus fumigates, DRA) to induce allergic inflammation prior to exposure to O3 (DRAO3). Changes in lung physiology, inflammatory cells, and inflammation were measured. Exposure to O3 following DRA significantly increased airway hyperreactivity (AHR), which was independent of TLR4. DRA exposure resulted in increased BAL eosinophilia while O3 exposure resulted in neutrophilia. Additionally, O3 exposure following DRA blunted anti-inflammatory and antioxidant responses. Finally, there were significantly less monocytes and innate lymphoid type 2 cells (ILC2s) in the dual challenged DRA-O3 group suggesting that the lack of these immune cells may influence O3-induced AHR in the setting of allergic inflammation. In summary, we developed a mouse model that mirrors some aspects of the clinical course of asthma exacerbations due to air pollution and identified that O3 exposure in the asthmatic lung leads to impaired endogenous anti-inflammatory and antioxidant responses and alterations inflammatory cell populations.

Short-acting β2 -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.

In adults and adolescents with asthma, use of ≥3 short-acting β2 -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population. This population-based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18 years) treated in secondary care between 2006-2015. Exacerbation risk, by baseline SABA collection (0-2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1-year follow-up using negative binomial regression. Of 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0-5, 6-11, and 12-17 years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0-2) was associated with increased exacerbation risk during follow-up (incidence rate ratios [95% confidence interval]: 1.35 [1.29-1.42], 1.22 [1.15-1.29], and 1.26 [1.19-1.34] for 0-5-, 6-11-, and 12-17-year-olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%-44% increased risk versus. 14%-21% for those with atopic disease across groups). High SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use.

Levels of indoor particulate matter and association with asthma in children in Benin City, Nigeria.

The relationship between indoor particulate matter and asthma in children was assessed in this study. Forty-five (45) locations were randomly selected across the five local government areas in Benin City, Edo State, for air quality assessment. Indoor and outdoor particulates (PM1.0, PM2.5, and PM10) were monitored monthly using a handheld BLATN particulate sampler (Br-Smart-126S series). Reported clinical cases of asthma in children from 2008 to 2017 were collected from two major hospitals in the metropolis. The data obtained were analysed with SPSS for Windows version 21.0. The average concentrations of indoor and ambient PM ranged between 10.7-26.2 and 19.0-49.4µg/m3 (PM1.0), 27.4-59.6 and 45.6-93.0µg/m3 (PM2.5), and 33.5-67.9 and 60.9-106.1µg/m3 (PM10) in the wet and dry seasons. PM2.5 and PM10 concentrations were observed above the WHO standards. Indoor particulate concentration was significantly (p = 0.001-0.012) higher in the dry season across the locations. Outdoor PM correlated positively (R = 0.568-0.855, p < 0.05; R2 = 0.322-0.724, p < 0.001) with their corresponding indoor PM concentration. The hazard ratio (HR) values of PM2.5 and PM10 exceeded 1 in all the sampling locations during the dry season, while the mean total hazard ratio (THR) of both PM metrics was considerably higher during the dry season than in the wet season. Indoor PM concentrations showed a significant positive correlation with reported cases of asthma (R = 0.498-0.542, p < 0.001) and accounted for 40.6% of the asthma cases during the dry season. The study showed that children in the selected households are at risk of increased asthma exacerbation due to exposure to particulate matter pollution.

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid

BackgroundThe 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear. MethodsThe “Limma” package or “DESeq2” package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets. Results192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects. ConclusionsThis study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.

Effects of coronavirus disease 2019 pandemic on children, adolescents, and young adults with asthma in Rhode Island: Patterns in emergency department utilization with geospatial mapping

Despite early concerns for increased asthma exacerbations owing to the respiratory involvement of coronavirus disease 2019 (COVID-19), trends indicate decreases in the frequency of emergency department (ED) visits and asthma-related hospitalizations for children, adolescents, and young adults with asthma during spring 2020 when the first COVID-19 cases emerged and were rising in the United States.1,2 Less is known as to whether these patterns were maintained throughout summer and fall months of 2020 as the COVID-19 rates continued to increase.

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

Intimate Partner Violence and Adult Asthma Morbidity: A Population-Based Study

The etiologies for difficult-to-control asthma are complex and incompletely understood. Intimate partner violence (IPV) is a pervasive problem and may play a role in difficult-to-control asthma. IPV is associated with increased prevalence of asthma. There are no prior studies evaluating IPV's association with adult asthma exacerbations. This study hypothesized that IPV exposure would be associated with increased asthma exacerbations, higher symptom burden, and poorer asthma control among adults. Analyses are based on 2634 adults who participated in the 2005 Behavioral Risk Factor Surveillance System survey, reported active asthma, and completed the asthma and IPV questions. We used multivariate logistic regression to examine the association of IPV with asthma morbidity outcomes while controlling for the following potential confounders: sex, race, education, health care coverage, smoking status, age, and body mass index. The prevalence of IPV was 32.4%. IPV was associated with increased odds of an asthma exacerbation (adjusted odds ratio [AOR]= 1.75, 95% confidence interval [CI]= 1.26-2.43), higher symptom burden (AOR= 2.33, 95% CI= 1.53-3.55), and lack of asthma control (AOR= 2.23, 95% CI= 1.22-4.09) when using composite measures for these outcomes. When using single-item measures for outcomes, IPV was also associated with increased asthma-related emergency department or urgent care visits (AOR= 2.35, 95% CI= 1.56-3.54), other urgent provider visits(AOR= 1.84, 95% CI= 1.28-2.64), perceived asthma attacks (AOR= 1.53, 95% CI= 1.12-2.09), limitations (AOR= 2.07, 95% CI= 1.49-2.89), daytime symptoms (AOR= 1.92, 95% CI= 1.35-2.72), and nocturnal awakenings (AOR= 1.88, 95% CI= 1.32-2.69). IPV is prevalent in adult asthmatics and consistently and significantly associated with worsened adult asthma morbidity, even after adjusting for key confounders. Further research is needed to more fully understand the mechanisms underlying these relationships.

Invited Perspective: Oil and Gas Development and Adverse Birth Outcomes: What More Do We Need to Know?

Invited Perspective: Oil and Gas Development and Adverse Birth Outcomes: What More Do We Need to Know?

Asthma Patients Who Stop Asthma Biologics Have a Similar Risk of Asthma Exacerbations as Those Who Continue Asthma Biologics

There is limited information about outcomes associated with stopping asthma biologics. To compare outcomes in people who stopped or continued asthma biologics. We identified a cohort of people with asthma who stopped or continued asthma biologics in the Optum Labs Database Warehouse, using a propensity matching method for case and control groups with the variables of age, sex, race, region, insurance, income, specialist access, Charlson comorbidity, specific medical conditions, pre-index exacerbation count, pre-index rescue inhaler pharmacy fills, and pre-index inhaled corticosteroid with or without long-acting β-agonist pharmacy fills. Primary outcome used to assess failure of stopping was an increase of 50% or more in the asthma exacerbation rate in the 6 months after discontinuing the biologic compared with the 6-month period before biologic initiation. Among a cohort of 4960 asthma biologic users, 1249 were observed to stop use after 6 to 12 months of use. We identified a matched cohort of 1247 stoppers and 1247 people who continued biologic use for at least 18 months. In the first 6 months after stopping or sham stopping, 10.2% of stoppers and 9.5% of continuers had an increase of 50% or more in asthma exacerbations. We found a similar adjusted odds of failing among stoppers and continuers (odds ratio= 1.085; 95% confidence interval, 0.833-1.413). An increase in asthma exacerbations is infrequently observed in people who stopped asthma biologics and was observed at similar rates as in matched controls who continued asthma biologics.

Factors Associated With Increased Asthma Exacerbations After Stopping Biologic Treatment

Factors Associated With Increased Asthma Exacerbations After Stopping Biologic Treatment

The safety of cardioselective β1-blockers in asthma: literature review and search of global pharmacovigilance safety reports.

IntroductionBeta-blockers are key in the management of cardiovascular diseases but blocking airway β2-receptors can cause severe and sometimes fatal bronchoconstriction in people with asthma. Although cardioselective β1-blockers may be safer than non-selective β-blockers, they remain relatively contraindicated and under-prescribed. We review the evidence of the risk associated with cardioselective β1-blocker use in asthma.MethodsWe searched “asthma” AND “beta-blocker” in PubMed and EmbaseOvid from start to May 2020. The World Health Organization (WHO) global database of individual case safety reports (VigiBase) was searched for reports of fatal asthma or bronchospasm and listed cardioselective β1-blocker use (accessed February 2020). Reports were examined for evidence of pre-existing asthma.ResultsPubMed and EmbaseOvid searches identified 304 and 327 publications, respectively. No published reports of severe or fatal asthma associated with cardioselective β1-blockers were found. Three large observational studies reported no increase in asthma exacerbations with cardioselective β1-blocker treatment. The VigiBase search identified five reports of fatalities in patients with pre-existing asthma and reporting asthma or bronchospasm during cardioselective β1-blocker use. Four of these deaths were unrelated to cardioselective β1-blocker use. The circumstances of the fifth death were unclear.ConclusionsThere were no published reports of cardioselective β1-blockers causing asthma death. Observational data suggest that cardioselective β1-blocker use is not associated with increased asthma exacerbations. We found only one report of an asthma death potentially caused by cardioselective β1-blockers in a patient with asthma in a search of VigiBase. The reluctance to use cardioselective β1-blockers in people with asthma is not supported by this evidence.

Seasonality of asthma exacerbation in children caused by respiratory virus infection and allergen sensitization

Purpose: Acute asthma exacerbations in children have seasonal variations and occur frequently in fall. Respiratory viral infections and environmental allergens are associated with asthma exacerbation. This study aimed to identify seasonal trends of asthma exac-erbation and the effects of respiratory viral infection and allergen sensitization on the seasonality of asthma exacerbation in children. Methods: Children under the age of 18 years who visited to the Emergency Department or hospitalized for acute asthma exacerba-tions from 2011 to 2019 were included. We reviewed medical records, including demographics, date of asthma exacerbation, results of respiratory virus and allergen sensitization, and they were analyzed to identify the seasonal trends of asthma exacerbation. Results: A total of 320 asthma exacerbations were included, with the highest frequency in fall. Human rhinovirus was positive in 64.7% and 60.0% in fall and spring exacerbations, respectively. House dust mite sensitization was highest in fall at 78.5%, while food sensitization was highest in spring at 76.9%. In patients who were sensitized to house dust mites or food allergens, respiratory viral infections further increased asthma exacerbation in fall and spring, respectively. Conclusion: Respiratory virus may be associated with asthma exacerbation in fall and spring. House dust mite and food sensitiza-tions may be associated with fall and spring asthma exacerbations by worsening the severity of asthma symptoms caused by respi-ratory viral infections. In childhood asthmatic patients with allergen sensitization, avoidance of sensitized allergens, prevention of viral infection, and more active treatment of viral infection may help prevent acute asthma exacerbations. (Allergy Asthma Respir Dis 2021;9:238-244)