Natural History Of Asthma Research Articles

Phenotype overlap in the natural history of asthma.

The heterogeneity of asthma makes it challenging to unravel the pathophysiologic mechanisms of the disease. Despite the wealth of research identifying diverse phenotypes, many gaps still remain in our knowledge of the disease's complexity. A crucial aspect is the impact of airborne factors over a lifetime, which often results in a complex overlap of phenotypes associated with type 2 (T2), non-T2 and mixed inflammation. Evidence now shows overlaps between the phenotypes associated with T2, non-T2 and mixed T2/non-T2 inflammation. These interconnections could be induced by different determinants such as recurrent infections, environmental factors, T-helper plasticity and comorbidities, collectively resulting in a complex network of distinct pathways generally considered as mutually exclusive. In this scenario, we need to abandon the concept of asthma as a disease characterised by distinct traits grouped into static segregated categories. It is now evident that there are multiple interplays between the various physiologic, cellular and molecular features of asthma, and the overlap of phenotypes cannot be ignored.

Aerosol inhalation of Mycobacterium vaccae ameliorates airway structural remodeling in chronic asthma mouse model

Background: Airway remodeling is accepted to be a determining component within the natural history of asthma. Nebulized inhalation of Mycobacterium vaccae (M. vaccae) has a protective effect on asthmatic mice. However, little is known regarding the effect of M. vaccae on airway structural remodeling in asthmatic mice. The purpose of this study was to explore the effect and the underlying mechanism of M. vaccae aerosol inhalation on airway structural remodeling in an asthma mouse model. Methods: Chronic asthma mouse models were established by ovalbumin induction. The number of inflammatory cells in bronchoalveolar lavage fluid (BALF), pathological alterations in lung tissue, and levels of associated cytokines (IL-5, IL-13, TNF-α, and ovalbumin-specific immunoglobulin E [OVA-sIgE]) were all assessed after M. vaccae therapy. The relative expression of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and Wnt1‐induced signaling protein 1 (WISP1) mRNA were detected. Western blotting and immunohistochemistry detected the expression of Wnt/β-catenin pathway-related proteins in lung tissue. Results: M. vaccae aerosol inhalation relieved airway inflammation, airway hyper-responsiveness, and airway remodeling. M. vaccae reduced the levels of IL-5, IL-13, TNF-α, and OVA-sIgE in and downregulated the expression of IL-1β, TNF-α, NF-κB, and WISP1 mRNA in the pulmonary. In addition, M. vaccae inhibited the expression of β-catenin, WISP1, and Wnt1 protein and upregulated the expression of glycogen synthase kinase-3beta (GSK-3β). Conclusion: Nebulized inhalation of M. vaccae can reduce airway remodeling during asthma.

No allergy left behind: The importance of food allergy in longitudinal cohorts

In recent years, the prevalence of immunoglobulin E (IgE)-mediated food allergy appears to be rising. Our ability to confirm this epidemiologic trend is limited. Over the past several decades, multiple cohorts have been established to investigate the etiologic risk factors and natural history of asthma and allergic diseases.1 The allergic (atopic) march includes the development of eczema, food allergy, allergic rhinitis, and asthma. One of the great tools of clinical epidemiology, the longitudinal cohort, has been successful in describing the allergic march, but this approach has been severely underutilized to study food allergy.

Advances in asthma: New understandings of asthma’s natural history, risk factors, underlying mechanisms, and clinical management

The last 2 years yielded a proliferation of high-quality asthma research. These include new understandings of the incidence and natural history of asthma, findings on the effects of exposure to air pollution, allergens, and intake of acetaminophen, soy isoflavones, and polyunsaturated fatty acids, and exposure to microbial products. The past 2 years have benefited from great strides in determining potential mechanisms of asthma development and asthma exacerbations. These novel understandings led to identification and development of exciting new avenues for potential therapeutic intervention. Finally, there has been significant progress made in the development of tools to facilitate the diagnosis of asthma and measurement of airway physiology and in precision diagnostic approaches. Asthma guidelines were updated and new insights into the pharmacologic management of patients, including biologics, were reported. We review the most notable advances in the natural history of asthma, risk factors for the development of asthma, underlying mechanisms, diagnostic approaches, and treatments. Although greater knowledge of the mechanisms underlying responses and nonresponses to novel therapeutics and across asthma phenotypes would be beneficial, the progress over just the past 2 years has been immense and impactful.

An update on the epigenetics of asthma.

Asthma is a common disease worldwide, however, its pathogenesis has not been fully elucidated. Emerging evidence suggests that epigenetic modifications may play a role in the development and natural history of asthma. The aim of this review is to highlight recent progress in research on epigenetic mechanisms in asthma. Over the past years, epigenetic studies, in particular DNA methylation studies, have added to the growing body of evidence supporting a link between epigenetic regulation of gene expression and asthma. Recent studies demonstrate that epigenetic mechanisms also play a role in asthma remission. Although most existing studies in this field have been conducted on blood cells, recent evidence suggests that epigenetic signatures are also crucial for the regulation of airway epithelial cells. Studies conducted on nasal epithelium revealed highly replicable epigenetic patterns that could be used for diagnostic purposes. Further research is needed to explore the diagnostic and therapeutic potential of epigenetic modifications in asthma. Multiomics studies on asthma will become increasingly important for a better understanding of etiology, heterogeneity, and severity of asthma, as well as establishing molecular biomarkers that could be combined with clinical information to improve the management of asthma patients.

Monoclonal Antibody Therapy in Childhood Asthma.

There has been an explosion of monoclonal antibodies in the treatment of severe uncontrolled adult asthma. Studies have now been published in severe pediatric asthma. There are numerous questions that need to be answered in determining whether these modalities are appropriate and safe in children. This is a narrative review examining the latest pediatric literature on monoclonal antibodies, both approved and in the pipeline, for uncontrolled asthma. Presently, all of the biologics are positioned to treat patients with underlying type 2 high disease. Two monoclonal antibodies are approved for children 6years of age and older, omalizumab and mepolizumab, with more likely approved in the near future. The effect of these agents in controlling severe pediatric asthma is promising. Data is limited to long-term efficacy and safety, and whether any agent has an effect on the natural history of asthma.

Disease Burden and Long-Term Risk of Persistent Very Poorly Controlled Asthma: TENOR II

Severe/difficult-to-treat disease occurs in 5% to 10% of patients with asthma, but accounts for more than 50% of related economic costs. Understanding factors associated with persistent very poorly controlled (VPC) asthma may improve outcomes. To characterize persistent VPC asthma after more than 10 years of standard of care. The Epidemiology and Natural history of asthma: Outcomes and treatment Regimens (TENOR) II (N= 341) was a multicenter, observational study of patients with severe/difficult-to-treat asthma with a single, cross-sectional visit more than 10 years after TENOR I. Persistent VPC asthma was defined as VPC asthma at TENOR I and TENOR II enrollment; without VPC asthma was defined as well- or not well-controlled asthma at either or both visits. Multivariable logistic regression assessed long-term predictors of persistent VPC asthma using TENOR I baseline variables. Of 327 patients, nearly half (48.0%, n= 157) had persistent VPC asthma. Comorbidities and asthma triggers were more frequent in patients with persistent VPC asthma than in patients without VPC asthma. Total geometric mean IgE was higher in patients with persistent VPC asthma (89.3 IU/mL vs 55.7 IU/mL); there was no difference in eosinophil levels. Lung function was lower in patients with persistent VPC asthma (mean % predicted pre- and postbronchodilator FEV1, 63.0% vs 82.8% and 69.6% vs 87.2%, respectively). Exacerbations in the previous year were more likely in patients with persistent VPC asthma (29.7% vs 9.0%, respectively). Predictors of persistent VPC asthma were black versus white race/ethnicity, allergic trigger count (4 vs 0), systemic corticosteroid use, and postbronchodilator FEV1 (per 10% decrease). The burden of persistent VPC asthma is high in severe/difficult-to-treat disease; management of modifiable risk factors, maximization of lung function, and trigger avoidance may improve outcomes.

Dust-mite inducing asthma: what advice can be given to patients?

ABSTRACTIntroduction: Amongst allergic asthmatics, high allergen exposure increases asthma severity. However, there is no consensus on the role of mite allergen avoidance in the management of asthma, and various guidelines differ in their recommendations.Areas covered: Several systematic reviews/meta-analyses on mite avoidance in the management of asthma have been published, and their findings have been used for a call to provide a recommendation in British guidelines that dust-mite control measures should not be recommended. However, there are several problems with such analysis (such as combining studies in adults and children), and we question whether these are appropriate tools to evaluate available evidence about mite allergen avoidance, and whether it is correct to rely disproportionately on the results of meta-analyses/systematic reviews to inform clinical practice in this area. Recent evidence in children suggests that mite–impermeable bed encasings reduce emergency hospital attendance with severe asthma exacerbations.Expert opinion: The practical questions include how to achieve a sufficient real-life reduction allergen exposure, and how to identify patients who will benefit from effective intervention. The intervention should start early in the natural history of asthma, and consideration for choosing patients should include using the titre of allergen-specific IgE antibodies or the size of skin test wheal as an indicator.

New perspectives of childhood asthma treatment with biologics.

Asthma is no longer considered as a single disease but rather as a syndrome corresponding to different entities and pathophysiologic pathways. A targeted strategy is part of personalized medicine which aims to better define each patient's phenotype and endotype so as to prescribe the most suitable treatment at an individual level. Omalizumab and, more recently, mepolizumab are the first biologics approved for children (6-18years). Omalizumab is now widely used to treat severe allergic asthma in children and is highly effective for asthma exacerbations and asthma control with a good safety profile. Moreover, several other drugs-lebrikizumab, dupilumab, tezepelumab, mepolizumab, reslizumab, benralizumab-are used or are being studied in both teenagers and adults and could benefit younger children in the near future. We hypothesize that defining the asthma phenotype/endotype regarding the type and intensity of inflammation, association with allergic or non-allergic comorbidities, and airway remodeling should contribute to the choice of a specific biologic. Pediatric specificities have to be addressed and validated by studies in children. Long-term effectiveness and particularly the impact on the natural history of asthma should also be investigated. Severe asthma in children is a complex disease, and patients have to be referred to a specialized pediatric asthma center to confirm diagnosis and initiate the best treatment strategy which could include biologics while taking into account their high cost.

Asthma knowledge in a sample of students at college of Health and Medical Technologies in Baghdad

Background: Bronchial Asthma (BA) is a chronic inflammatory, disease of the airway characterized. by therecurrent attacks, of the shortness, of breath that associated with wheezing, recurrent cough as well as chest tightness ,may be get worse, during exposure to smoke, dust, change in weather. The prevalence, of a,sthmawas .increasing globally, so the natural history of asthma is still,not well defined it thought to be of genetic and environmental factors represented by exposure to allergens. Aim: To determine the level of knowledge about asthma among students in College of health and medical technologies. Methodology: one hundred forty college students were selected using a designed questionnaire for collect information of students about,the,epidemiology of asthma, symptoms, trigger factors and source of their information. The knowledge, score was estimated the,measure level of the ,students’ knowledge.Results,: More than half of the sample had moderate knowledge level.

Effect of indoor air quality on the natural history of asthma in an urban population in Poland.

Background: Indoor air pollution may have an impact on asthma. Objective: To evaluate the influence of indoor air pollution on the natural history of asthma. Methods: Data collection by using the European Community Respiratory Health Survey and International Study of Asthma and Allergies in Childhood standardized questionnaire (N = 18,617) and medical examinations (N = 4783) in selected Polish regions was used. Statistical analysis was performed by using the χ² test. A value of p < 0.05 was considered statistically significant. Results: Questionnaire results demonstrated that people who used the central heating system were less likely to declare the occurrence of asthma (odds ratio [OR] 0.84) and were corroborated with clinical findings of moderate asthma (OR 0.35). Symptomatic asthma occurred more frequently in people who used a solid-fuel heating device (OR 1.36) and electric heaters (OR 1.54). The use of cooking appliances with municipal natural gas (OR 1.77) and gas storage tanks (OR 2.03) was correlated with more frequent declarations of asthma. Symptomatic asthma was more common among people who smoked for at least 1 year (OR 2.26) and those who smoked over the course of the preceding month (OR 1.60). Passive exposure to tobacco smoke provided for a 1.5-fold increase in the incidence of symptomatic asthma (OR 1.53), regardless of the time of exposure. Conclusion: Both active and passive tobacco smoke exposure as well as the use of certain types of heating and cooking appliances have a significant impact on the incidence of asthma and the intensification of its symptoms in rooms with limited air exchange. Highlights of the study included the following: (1) central heating had an amelioratory effect on asthma, (2) heating technologies used at home had a significant impact on the incidence of asthma, and (3) devices used for cooking (municipal and cylinder gas stoves) played an important role in the intensification of asthma symptoms.

Racial Disparities in Asthma-Related Health Outcomes in Children with Severe/Difficult-to-Treat Asthma

There are limited data that examine differences in asthma etiology between black and white children with severe or difficult-to-treat asthma. To describe demographic, clinical, and asthma-related outcomes in black and white children and examine whether differences in outcomes are explained by confounding factors in sequential multivariable models. Black (n= 86) and white (n= 262) children aged 6-11 years from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens 3-year observational study were analyzed. Baseline demographics and clinical characteristics were described for both cohorts, and outcomes at month 12 were analyzed using statistical models, sequentially adjusting for potential confounders. Black children were more likely to be male (79.1% vs 66.4%; P < .05), obese (12.8% vs 1.5%; P < .001), and from a lower income stratum (USD43,400 vs 55,770; P < .001) than white children. Black children had higher geometric mean IgE levels (434.8 vs 136.8 IU/mL; P < .001), were more likely to have very poorly controlled asthma (72.1% vs 53.4%), use long-term systemic corticosteroids (30.2% vs 9.2%; P < .001), have poorer quality of life (5.5 vs 6.1; P < .001), and have an emergency department visit (27.4% vs 7.7%, P < .001) in the 3 months before month 12. Differences in asthma control and the severity of exacerbations persisted even after accounting for all confounding factors. Among children with severe or difficult-to-treat asthma, asthma burden is greater in black than white children particularly related to several clinical and patient-reported outcome measures that are not explained by differences in background or clinical characteristics.

PRS34 - Economic Value of Precision Medicine: An Example of Asthma

Precision medicine is an emerging approach, under which treatments are optimised after accounting for individuals’ genotypic, phenotypic, and/or environmental characteristics. We assess the economic value of precision medicine, using an example of patients with asthma who are receiving GINA (Global Initiative for Asthma) step 2 treatment in the US. A Markov model was developed to estimate the costs and benefits across the natural history of asthma, represented by five GINA steps. In the model, patients could step up/down the treatment, experience an exacerbation, remit or die. A new treatment X (Tx) could expedite step-downs, delay step-ups, and reduce exacerbations among patients with a specific genotype (GT). Those who tested positive for GT will receive Tx, and the rest, standard of care (SoC). To assess the value of Tx when compared to using SoC alone, its efficacy, the sensitivity/specificity of GT testing, and GT prevalence in patients were varied to estimate the cost-effective price of Tx (at a willingness-to-pay threshold of $50,000 per a quality-adjusted life year [QALY]). Parameters were estimated from the literature. Costs and QALYs were discounted at 3.0% per year. The cost-effective price of Tx was higher when GT was more prevalent and the diagnostic test more precise. Following a cohort of asthma patients, at an efficacy level of 50%, the monthly cost-effective price of Tx increased from $170 to $405, if the prevalence of GT and the sensitivity/specificity of GT testing both increased from 25% to 75%. The cost-effective price was most sensitive at high prevalence/low precision, and low prevalence/high precision of the genotype/its diagnostic test respectively. The economic value of precision medicine depends not only on the treatment efficacy, but also the prevalence of the genotypes/phenotypes of interest, and in our example, even more so, on the accurate identification of eligible patients.

Asthma in the USA: the good, the bad, and the disparity

Asthma in the USA: the good, the bad, and the disparity

Association between Bronchial Asthma and Pubertal Delay in Pediatric Patients

Background: asthma is a chronic inflammatory disease with a considerable prevalence and unfavorable impacts on various body systems. The natural history of asthma has been extensively investigated in terms of the varied effects on age and gender. Aim of the study: this study aims to achieve a better understanding of the unclear relationship between bronchial asthma and pubertal delay in the pediatric age group. Methods: we reviewed the scientific literature concerned with studying the effect of asthma and its treatment on the growth of children and the onset of puberty using some international medical databases (Medline, Google scholar, EMBASE). Conclusion: Although there have been some community-based surveys and studies based on young children which failed to find an association between asthma and growth, others revealed that asthma can cause growth retardation through different mechanisms, including hypoxia, impaired lung functions, or endocrine malfunctions. Pubertal delay is also observed in untreated asthmatic boys and girls. In addition, inhaled corticosteroids, the best available treatment of asthma, were found also to have an effect on pubertal delay and this effect is dependent on the dose, duration and the outcome of therapy. When concentrating on pubertal delay, it seems that more longitudinal studies are required to comprehensively investigate the effects of asthma and its treatment on this vital stage of life.

More than a decade follow-up in patients with severe or difficult-to-treat asthma: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) II

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR I) study demonstrated high morbidity in patients with severe or difficult-to-treat asthma despite standard-of-care treatment. We sought to determine the long-term natural history of disease and outcomes in patients in TENOR I after more than a decade. TENOR I was a multicenter observational study (2001-2004) of 4756 patients with severe or difficult-to-treat asthma. TENOR II was a follow-up study of TENOR I patients using a single cross-sectional visit in 2013/2014. Overall, the sites participating in TENOR II originally enrolled 1230 patients in TENOR I. Clinical and patient-reported outcomes were assessed, including very poorly controlled asthma based on National Heart, Lung, and Blood Institute guidelines. A total of 341 (27.7%) patients were enrolled in TENOR II and were representative of the TENOR I cohort. The most frequent comorbidities were rhinitis (84.0%), sinusitis (47.8%), and gastroesophageal reflux disease (46.3%). Mean percent predicted prebronchodilator and postbronchodilator FEV1 were 72.7% (SD, 21.4%) and 78.2% (SD, 20.7%), respectively. Atotal of 231 (72.9%) of 317 patients had positive test responses to 1 or more allergen-specific IgEs. The mean blood eosinophil count was 200/μL (SD, 144/μL). Eighty-eight (25.8%) patients experienced an asthma exacerbation in the prior 3months requiring hospital attention, oral corticosteroids, or both. More than half (197/339 [58.1%]) had very poorly controlled asthma. Medication use suggested undertreatment. TENOR II provides longitudinal data to characterize disease progression, heterogeneity, and severity in patients with severe or difficult-to-treat asthma. Findings show continued morbidity, including a high degree of comorbid conditions, allergic sensitization, exacerbations, and very poorly controlled asthma, including reduced lung function.

Pharmacogenetics and the treatment of asthma.

Heterogeneity defines both the natural history of asthma as well as patient's response to treatment. Pharmacogenomics contribute to understand the genetic basis of drug response and thus to define new therapeutic targets or molecular biomarkers to evaluate treatment effectiveness. This review is initially focused on different genes so far involved in the pharmacological response to asthma treatment. Specific considerations regarding allergic asthma, the pharmacogenetics aspects of polypharmacy and the application of pharmacogenomics in new drugs in asthma will also be addressed. Finally, future perspectives related to epigenetic regulatory elements and the potential impact of systems biology in pharmacogenetics of asthma will be considered.

Microbes, allergic sensitization, and the natural history of asthma.

Understanding factors that lead to asthma development in early life is essential to developing strategies aimed at primary or secondary prevention. This article will review current evidence addressing the development of early life allergic sensitization in relation to microbes and the gut and airway microbiome. Wheezing illnesses, particularly viral, remain a significant risk factor for asthma inception; however, bacterial pathogens have recently emerged as an additional important contributor to asthma risk, either alone or as cofactors with viral infections. The combined influence and interaction of early life viral wheezing and aeroallergen sensitization is important, with allergic sensitization preceding the onset of viral wheeze. Lastly, we review recent data from longitudinal studies regarding the development of irreversible airway obstruction and its impact on the natural history of asthma. The development of asthma remains complex and incompletely understood. There is interplay between genetic predisposition and environmental exposures, including allergens and microbes. Interventions aimed at these risk factors during the preschool years may prevent the longitudinal course of asthma progression to irreversible airway obstruction.

Biologics in practice: A unique opportunity for allergist/immunologist expertise

Biologics in practice: A unique opportunity for allergist/immunologist expertise

Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations

Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. We examined associations between prenatal and/or postnatal stress and children's asthma (n=765) and effect modification by sex in a prospective cohort study. Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend=.03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend=.001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend=.005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction=.07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction=.61). Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma.