Development Of Persistent Asthma Research Articles

The influence of disparities on intensive care outcomes in children with respiratory diseases: A systematic review.

The negative effects of socioeconomic, environmental and ethnic inequalities on childhood respiratory diseases are known in the development of persistent asthma and can result in adverse outcomes. However, little is known about the effects of these disparities on pediatric intensive care unit (PICU) outcomes in respiratory diseases. The purpose of this systematic review is to evaluate the literature on disparities in socioeconomic, environmental and ethnic determinants and PICU outcomes. We hypothesize that these disparities negatively influence the outcomes of children's respiratory diseases at the PICU. A literature search (in PubMed, Embase.com and Web of Science Core Collection) was performed up to September 30, 2022. Two authors extracted the data and independently evaluated the risk of bias with appropriate assessment methods. Articles were included if the patients were below 18 years of age (excluding neonatal intensive care unit admissions), they concerned respiratory diseases and incorporated socioeconomic, ethnic or environmental disparities. Eight thousand seven hundred fourty-six references were reviewed, and 15 articles were included; seven articles on the effect of socioeconomic status, five articles on ethnicity, one on the effect of sex and lastly two on environmental factors. All articles but one showed an unfavorable outcome at the PICU. Disparities in socioeconomic (such as a low-income household, public health insurance), ethnic and environmental factors (such as exposure to tobacco smoke and diet) have been assessed as risk factors for the severity of children's respiratory diseases and can negatively influence the outcomes of these children admitted and treated at the PICU.

Rothia from the Human Nose Inhibit Moraxella catarrhalis Colonization with a Secreted Peptidoglycan Endopeptidase.

Moraxella catarrhalis is found almost exclusively within the human respiratory tract. This pathobiont is associated with ear infections and the development of respiratory illnesses, including allergies and asthma. Given the limited ecological distribution of M. catarrhalis, we hypothesized that we could leverage the nasal microbiomes of healthy children without M. catarrhalis to identify bacteria that may represent potential sources of therapeutics. Rothia was more abundant in the noses of healthy children compared to children with cold symptoms and M. catarrhalis. We cultured Rothia from nasal samples and determined that most isolates of Rothia dentocariosa and "Rothia similmucilaginosa" were able to fully inhibit the growth of M. catarrhalis in vitro, whereas isolates of Rothia aeria varied in their ability to inhibit M. catarrhalis. Using comparative genomics and proteomics, we identified a putative peptidoglycan hydrolase called secreted antigen A (SagA). This protein was present at higher relative abundance in the secreted proteomes of R. dentocariosa and R. similmucilaginosa than in those from non-inhibitory R. aeria, suggesting that it may be involved in M. catarrhalis inhibition. We produced SagA from R. similmucilaginosa in Escherichia coli and confirmed its ability to degrade M. catarrhalis peptidoglycan and inhibit its growth. We then demonstrated that R. aeria and R. similmucilaginosa reduced M. catarrhalis levels in an air-liquid interface culture model of the respiratory epithelium. Together, our results suggest that Rothia restricts M. catarrhalis colonization of the human respiratory tract in vivo. IMPORTANCE Moraxella catarrhalis is a pathobiont of the respiratory tract, responsible for ear infections in children and wheezing illnesses in children and adults with chronic respiratory diseases. Detection of M. catarrhalis during wheezing episodes in early life is associated with the development of persistent asthma. There are currently no effective vaccines for M. catarrhalis, and most clinical isolates are resistant to the commonly prescribed antibiotics amoxicillin and penicillin. Given the limited niche of M. catarrhalis, we hypothesized that other nasal bacteria have evolved mechanisms to compete against M. catarrhalis. We found that Rothia are associated with the nasal microbiomes of healthy children without Moraxella. Next, we demonstrated that Rothia inhibit M. catarrhalis in vitro and on airway cells. We identified an enzyme produced by Rothia called SagA that degrades M. catarrhalis peptidoglycan and inhibits its growth. We suggest that Rothia or SagA could be developed as highly specific therapeutics against M. catarrhalis.

Assessing the Response of a Sample of Iraqi Asthmatic Patients to Different Medication Regimens

Asthma is a chronic inflammatory disease of respiratory airways characterized by distinctive history of respiratory symptoms due to variable airflow obstruction which reverses either spontaneously or in response to certain medications. Acetylcholine is a parasympathetic neurotransmitter which plays fundamental roles in the development of persistent asthma. Treatment guidelines recommend using medium doses of inhaled corticosteroids in addition to another controller bronchodilator instead of using high doses inhaled steroid alone for treatment of moderate to severe persistent asthma. The inhaled long acting muscarinic antagonist, tiotropium, was approved recently to control unresponsive asthma to inhaled corticosteroid with or without a long acting ?-2 agonist. The aim of this study was to assess and compare the responses of a sample of Iraqi asthmatic patients to three different medication regimens.

Association of diabetes-related autoantibodies with the incidence of asthma, eczema and allergic rhinitis in the TRIGR randomised clinical trial.

This paper presents the relationship between islet autoantibodies, precursors of type 1 diabetes, and the development of persistent asthma, allergic rhinitis and atopic eczema. A total of 2159 newborns who had a first-degree relative with type 1 diabetes and selected HLA genotypes were followed until the youngest participant reached 10years of age. Islet cell antibodies (ICA) were detected using indirect immunofluorescence. Autoantibodies to insulin (IAA), GAD (GADA), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2A) and zinc transporter 8 (ZnT8A) were quantified with the use of specific radiobinding assays. As an ancillary study, the incidence of asthma, allergic rhinitis and eczema was assessed in 1106 of these children using the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire when the children were 9-11years old. HRs with 95% CIs were calculated to depict the incidence of these diseases following seroconversion to autoantibody positivity. The cumulative incidence of atopic eczema, allergic rhinitis and persistent asthma were 22%, 9% and 7.5%, respectively, by 9-11years of age. The occurrence of diabetes-related autoantibodies showed a protective association with subsequently reported incidence of asthma and eczema. The incidence of rhinitis was not significantly related to the occurrence of IAA or GADA (statistical power was limited), but demonstrated the same inverse relationship as did the other diseases with ICA or when multiple autoantibodies first appeared together. The findings add evidence to the relationships between these atopic diseases and diabetes-related autoimmunity and also suggest that, for eczema, the interaction depends upon which autoantibody appeared first. ClinicalTrials.gov NCT00179777 Graphical abstract.

Aeroallergen-induced IL-33 predisposes to respiratory virus-induced asthma by dampening anti-viral immunity

Abstract Frequent viral lower respiratory infections in early-life are an independent risk factor for asthma onset. This risk, and the development of persistent asthma, is significantly greater in children who later become sensitized. Here, we sought to elucidate the pathogenic processes that underlie the synergistic interplay between allergen exposures and viral infections. Mice were inoculated with a Pneumovirus (Pneumonia virus of mice; PVM) and exposed to low-dose cockroach extract (CRE) in early- and later-life, and airway inflammation, remodeling and hyperreactivity assessed. Mice were treated with anti-IL-33 or apyrase to neutralize or block the release of IL-33. PVM infection or CRE exposure alone failed to induce disease whereas PVM/CRE co-exposure acted synergistically to induce the features of asthma. CRE exposure during virus infection in early-life induced a biphasic IL-33 response and impaired IFN-a/l production, which in turn increased epithelial viral burden, airway smooth muscle growth, and type-2 inflammation. These features were ameliorated when CRE-induced IL-33 release was blocked or neutralized, while substitution of CRE with exogenous IL-33 recapitulated the phenotype observed in PVM/CRE co-exposed mice. Mechanistically, IL-33 down-regulated viperin and IFN regulatory factor 7 gene expression, and rapidly degraded IRAK1 expression in pDC, leading to TLR7 hypo-responsiveness and impaired IFN-a production. We identify a hitherto unrecognized function of IL-33 as a potent suppressor of innate antiviral immunity, and demonstrate that IL-33 contributes significantly to the synergistic interplay between respiratory virus and allergen exposures in the onset and progression of asthma.

Aeroallergen-induced IL-33 predisposes to respiratory virus–induced asthma by dampening antiviral immunity

Frequent viral lower respiratory infections in early life are an independent risk factor for asthma onset. This risk and the development of persistent asthma are significantly greater in children who later become sensitized. We sought to elucidate the pathogenic processes that underlie the synergistic interplay between allergen exposures and viral infections. Mice were inoculated with a murine-specific Pneumovirus species (pneumonia virus of mice [PVM]) and exposed to low-dose cockroach extract (CRE) in early and later life, and airway inflammation, remodeling, and hyperreactivity assessed. Mice were treated with anti-IL-33 or apyrase to neutralize or block IL-33 release. PVM infection or CRE exposure alone did not induce disease, whereas PVM/CRE coexposure acted synergistically to induce the hallmark features of asthma. CRE exposure during viral infection in early life induced a biphasic IL-33 response and impaired IFN-α and IFN-λ production, which in turn increased epithelial viral burden, airway smooth muscle growth, and type 2 inflammation. These features were ameliorated when CRE-induced IL-33 release was blocked or neutralized, whereas substitution of CRE with exogenous IL-33 recapitulated the phenotype observed in PVM/CRE-coexposed mice. Mechanistically, IL-33 downregulated viperin and interferon regulatory factor 7 gene expression and rapidly degraded IL-1 receptor-associated kinase 1 expression in plasmacytoid dendritic cells both invivo and invitro, leading to Toll-like receptor 7 hyporesponsiveness and impaired IFN-α production. We identified a hitherto unrecognized function of IL-33 as a potent suppressor of innate antiviral immunity and demonstrate that IL-33 contributes significantly to the synergistic interplay between respiratory virus and allergen exposures in the onset and progression of asthma.

Ethnic Variability in Persistent Asthma After In Utero Tobacco Exposure

The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent. To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children. There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview. The effect of in utero tobacco smoke exposure on the development of persistent asthma and related clinical outcomes was evaluated by logistic regression. Children with persistent asthma had a higher odds of exposure to in utero tobacco smoke, but not current tobacco smoke, than did children with intermittent asthma (odds ratio [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years of life did not alter this association. Furthermore, there were higher odds of in utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR: 2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency department visits (OR: 3.85; P = .015) within the year. Exposure to tobacco smoke in utero was significantly associated with persistent asthma among Mexican, Puerto Rican, and black children compared with those with intermittent asthma. These results suggest that smoking cessation during pregnancy may lead to a decrease in the incidence of persistent asthma in these populations.

Association between socioeconomic status and the development of asthma: analyses of income trajectories.

Using data on 2868 children born in the Western Australian Pregnancy Cohort (Raine) Study, we examined the association between changes in family socioeconomic status and childhood asthma. We determined the likelihood (odds ratio) of a child having asthma at ages 6 and 14 years for 4 family-income trajectories (chronic low, increasing, decreasing, and never low) over the child's lifetime. The trajectories were created from longitudinal latent-class models. We found a 2-fold increased risk of asthma at age 14 years among children who had lived in a low-income family since birth, especially for girls. Asthma was less likely to occur in children born to single parents; income rose over time in many of these families. Compared with children in chronic low-income families, children in households with increasing incomes had a 60% lower risk of asthma. Single-point measures of low income were not found to be associated with asthma. Chronic exposure to a low-income environment from birth was associated with the development of persistent asthma. There was also a protective effect against asthma among those children whose families had moved out of poverty.

Early introduction of oats associated with decreased risk of persistent asthma and early introduction of fish with decreased risk of allergic rhinitis

The evidence of the effect of the age at introduction of new foods during infancy on the development of asthma and allergic rhinitis is inconsistent and scarce. We set out to study these associations. A prospective birth cohort of infants with increased HLA-DQB1-conferred risk for type 1 diabetes was recruited in 1996-2000. The families completed at home a record on the age at introduction of new foods. Persistent asthma and allergic rhinitis were assessed at the age of 5 years with an International Study of Asthma and Allergies in Childhood-type questionnaire. The Cox proportional hazards regression analyses were adjusted for parental asthma and allergic diseases, and several perinatal and sociodemographical factors. Out of the 1293 children, 77 (6.0 %) developed persistent asthma; and out of the 1288 children, 185 (14.4 %) developed allergic rhinitis by the age of 5 years. Early age at introduction of oats was associated with a reduced risk of persistent asthma (hazard ratio (HR; 95 % CI) for the first and mid-tertiles compared with the latest tertile was 0.36 (0.15, 0.85) and 0.37 (0.22, 0.62), respectively, P < 0.001). Early age at introduction of fish was dose dependently associated with a decreased risk of allergic rhinitis (HR (95 % CI) for the first and mid-tertiles compared with the latest tertile was 0.34 (0.22, 0.54) and 0.45 (0.28, 0.70), respectively, P < 0.001). The present finding that age at introduction of oats is inversely and independently associated with development of persistent asthma is novel. We confirmed the earlier observation that the age at introduction of fish is inversely related to the risk of allergic rhinitis. Clinical implications remain to be determined.

Natural history of asthma: Persistence versus progression—does the beginning predict the end?

Environmental exposures during the early years and airway obstruction that develops during this time, in conjunction with genetic susceptibility, are important factors in the development of persistent asthma in childhood. Established risk factors for childhood asthma include frequent wheezing during the first 3 years, a parental history of asthma, a history of eczema, allergic rhinitis, wheezing apart from colds, and peripheral blood eosinophilia, as well as allergic sensitization to aeroallergens and certain foods. Risk factors for the development of asthma in adulthood remain ill defined. Moreover, reasons for variability in the clinical course of asthma--persistence in some individuals and progression in others--remain an enigma. The distinction between disease persistence and disease progression suggests that these are different entities or phenotypes. There is currently no consensus on whether disease progression requires either airway inflammation or airway remodeling or the combination of the two. For patients with irreversible airway obstruction, inflammation might, in part, be necessary but perhaps not entirely sufficient to induce the irreversible component, some of which could be attributed to alterations in the structure of the bronchial wall. Intervening with intermittent or daily inhaled corticosteroids in high-risk infants and children does not prevent disease progression or impaired lung growth. These findings, however, might not apply to adults, and further study in adults is needed to determine the effect of inhaled corticosteroid therapy on disease progression.

Systematic Review of the Relationship Between Early Introduction of Solid Foods to Infants and the Development of Allergic Disease

To assess the evidence that early solid feeding (before age 4 months) increases the risk of allergic disease. MEDLINE, the Cochrane Library, and the Drugs and Pharmacology section of EMBASE with key words "infant," "food," and "allergy." We found 2719 article citations and reviewed references of relevant articles. We critically evaluated the methods and results of articles that met inclusion criteria. We identified 13 studies that met inclusion criteria. There was only 1 controlled trial. Allergic disease. Five studies found a positive association between early solid feeding and eczema, with a persistence of the association for 10 years in 1 study. Four studies found no association. One study found an association between early solid feeding and pollen allergy. We found no strong evidence to support the association between early solid feeding and the development of persistent asthma, persistent food allergy, allergic rhinitis, or animal dander allergy. Systematic review of available evidence suggests that early solid feeding may increase the risk of eczema. However, there are little data supporting an association between early solid feeding and other allergic conditions. Since many studies had problematic methods, additional controlled trials are needed to help guide physicians as they advise parents about the allergic risks of early introduction of solids.

Risk Factors for Developing Wheezing and Asthma in Childhood

Wheezing lower respiratory tract illness in infancy and asthma share the clinical findings of wheezing and respiratory distress. Although the link between wheezing lower respiratory tract illness in infancy and the subsequent development of asthma is a limited one, both conditions do share some common risk factors, including exposure to environmental tobacco smoke, difficult living conditions (low socioeconomic class, crowding, allergen exposure), and increased risk in males. The impact of baseline lung function on wheezing lower respiratory tract illness risk is substantial and may be independent of airway reactivity. In contrast, the development of chronic airway inflammation mediated by allergic sensitization plays a central role in the development of persistent asthma. Although the endogenous risks for these two outcomes may be fixed, it is clear that caregivers may help to reduce or eliminate the exogenous risks listed earlier by parental education and improvement of the living conditions of young children.