Different Forms Of Asthma Research Articles

БРОНХІАЛЬНА АСТМА ЯК МАСКА АЛЕРГІЧНОГО БРОНХОЛЕГЕНЕВОГО АСПЕРГІЛЬОЗУ: ОСОБЛИВОСТІ ДІАГНОСТИКИ ТА ЛІКУВАННЯ

ASTHMA AS A MASK OF ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS: DIAGNOSIS AND TREATMENT O. M. Rekalova Abstract Asthma is a heterogeneous diseases with multiple phenotypes, 5–10 % of which are associated with severe course of disease, resistant to standard therapy. Allergic bronchopulmonary aspergillosis (ABPA), being a separate disease (ICD-10: B44.9 — aspergillosis unspecified), may mimic asthma. A literature review of major statements regarding ABPA, focusing on definition, pathogenesis, diagnostic criteria, association of different forms of asthma with fungal sensitization and Th2-response, stage, radiological picture, diagnostic algorithm in asthma and cystic fibrosis, characteristics of major applicable lab tests, principles and algorithm of treatment of ABPA patients, and treatment prospects. Lung radiological data using computer modeling from patient with ABPA (clinical case) has been presented as an illustration. Key words: allergic bronchopulmonary aspergillosis (ABPA), asthma, diagnosis, treatment. Ukr. P

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma

BackgroundIt is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features.Methods30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry.ResultsThere were no significant differences in atopy and FEV1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls.ConclusionsPatients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes.Trial registrationhttp://www.chictr.org.cn (ChiCTR-OOC-15006221)

Early origins of asthma (and allergy).

SummaryAsthma is the most common chronic disease starting in childhood and persisting into adulthood in many cases. During childhood, different forms of asthma and wheezing disorders exist that can be discriminated by the mechanisms they are caused by. Specific genetic constellations and exposure against environmental factors during early childhood and in utero play a decisive role in the early development of the disease. Epigenetic mechanisms which are master regulators of gene transcription and thus govern the accessibility and use of genome information, have recently been identified as a “third power” determining many features in the early development of asthma and allergy.

S-25: A role for ILC2s, ILC3s and the NLRP3 inflammasome in different forms of asthma

The lung is a gas exchange organ that contends with a large array of environmental factors, including allergens, infectious microbes and reactive oxygen species. A number of innate immune mechanisms have evolved to rapidly respond to these elements, and can mediate lung inflammation and asthma, a very heterogeneous disease with several distinct phenotypes. Indeed, several of different forms of asthma can develop independently of adaptive immunity, and appear to involve Type 2 as well as Type 3 innate lymphoid cells (ILCs), producing IL-5, IL-9, IL-13 or IL-17 and IL-22. Type 2 ILCs respond to allergen and to influenza infection, and can lead to airway hyperreactivity (AHR), a cardinal feature of asthma. In contrast, in obesity, which is associated with a steroid resistant form of severe asthma, CCR6+ Type 3 ILC3s expand in the lungs in response to IL-1β produced via the NLRP3 pathway in lung macrophages. Administration of IL-1β directly into the lungs of mice resulted in the expansion of lung ILC3s, and directly induced AHR. Furthermore, blockade of IL-1β with an IL-1 receptor antagonist reduced the number of lung ILC3 cells and abolished obesity-induced AHR in mice. Obesity-associated AHR was independent of adaptive immunity, as it occurred in obese Rag1−/− mice, and was dependent on interleukin-17A (IL-17A) and the NLRP3 inflammasome, as it did not develop in obese Il17a−/− or Nlrp3−/− mice, respectively. These studies suggest an important role for Type 2 and Type 3 ILCs in different forms of allergic and non-allergic asthma.

Infections in Children with Asthma

Asthma is one of the most common chronic disorders in childhood. Asthma symptoms normally find in first three years of a life when the growth and remodeling of lungs is at maximum pace. There is always a common concern regarding different forms of asthma and how to cure them. Studies showed us in US about 20 million people are suffering from asthma and out of which 9 millions are children. Globally around 70% of asthmatic children are suffering from Wheeze which is mostly a symptom of viral infection. This is also one of the global burdens due to respiratory viral infections imposed by asthma. The various types of infections include rhinovirus infections which plays a crucial role in asthma development; respiratory syncytial virus which cause lower respiratory tract infection such as bronchiolitis; influenza and par- influenza viruses; pertussis, one of the major reason of death for children below 3 months of age; epiglottitis; bronchiolitis which effects mainly children below age of 2; and pneumonia caused by bacteria, fungi, parasites or due to virus. In this article we will shed some light on the relationship of chest infections with asthma and how they impact the course of asthma disease in children. The most important factor is how several vitamins like Vitamin D plays a crucial role for asthma patients. General studies show prevention and long term control is major key in stopping asthma attacks. There are various medications available to avoid asthma attacks but it generally depends upon the patient’s symptoms, age and the various triggering factors. Further we will see how a balanced diet helps like pro-biotic supplements, bacterial derived product, OM-85 etc helps in controlling asthma infections.

Modulation of Distinct Asthmatic Phenotypes in Mice by Dose-Dependent Inhalation of Microbial Products

Background: Humans with asthma display considerable heterogeneity with regard to T helper (Th) 2–associated eosinophilic and Th17-associated neutrophilic inflammation, but the impact of the environment on these different forms of asthma is poorly understood.Objective: We studied the nature and longevity of asthma-like responses triggered by inhalation of allergen together with environmentally relevant doses of inhaled lipopolysaccharide (LPS).Methods: Ovalbumin (OVA) was instilled into the airways of mice together with a wide range of LPS doses. Following a single OVA challenge, or multiple challenges, animals were assessed for pulmonary cytokine production, airway inflammation, and airway hyperresponsiveness (AHR).Results: Mice instilled with OVA together with very low doses (≤ 10–3 μg) of LPS displayed modest amounts of Th2 cytokines, with associated airway eosinophilia and AHR after a single challenge, and these responses were sustained after multiple OVA challenges. When the higher but still environmentally relevant dose of 10–1 μg LPS was used, mice initially displayed similar Th2 responses, as well as Th17-associated neutrophilia. After multiple OVA challenges, however, the 10–1 μg LPS animals also accumulated large numbers of allergen-specific T regulatory (Treg) cells with high levels of inducible co-stimulatory molecule (ICOS). As a result, asthma-like features in these mice were shorter-lived than in mice sensitized using lower doses of LPS.Conclusions: The nature and longevity of Th2, Th17, and Treg immune responses to inhaled allergen are dependent on the quantity of LPS inhaled at the time of allergic sensitization. These findings might account in part for the heterogeneity of inflammatory infiltrates seen in lungs of asthmatics.Citation: Whitehead GS, Thomas SY, Cook DN. 2014. Modulation of distinct asthmatic phenotypes in mice by dose-dependent inhalation of microbial products. Environ Health Perspect 122:34–42; http://dx.doi.org/10.1289/ehp.1307280

Natural killer T cells are important in the pathogenesis of asthma: The many pathways to asthma

The pathogenesis of bronchial asthma, a complex trait associated with a number of environmental factors (eg, allergens, infection, air pollution, exercise, and obesity), involves multiple cell types and several distinct cellular and molecular pathways. These pathways include adaptive and innate immunity and involve T(H)2 cells, mast cells, basophils, eosinophils, neutrophils, airway epithelial cells, and subsets of a newly described cell type called natural killer T (NKT) cells. A role for subsets of NKT cells in asthma has been suggested by extensive studies in animal models of asthma induced with allergen, viral infection, ozone exposure, or bacterial components, suggesting that NKT cells function in concert with T(H)2 cells or independently of adaptive immunity in causing airway hyperreactivity. The clinical relevance of NKT cells in human asthma is supported by the observation that NKT cells are present in the lungs of some patients with asthma, particularly patients with severe, poorly controlled asthma, although additional research is required to more precisely define the specific role of NKT cells in human asthma. These studies of NKT cells greatly expand our understanding of possible mechanisms that drive the development of asthma, particularly in the case of asthma associated with neutrophils, viral infection, and air pollution.

Natural killer T cells regulate the development of asthma

Studies in mice, monkeys and humans suggest that invariant natural killer (iNK) T cells play a very important role in the pathogenesis of asthma, a heterogeneous disease associated with airway inflammation and airway hyper-reactivity. The requirement for iNK T cells in multiple mouse models of asthma is novel and surprising, challenging the prevailing dogma that CD4+ T cells responding to environmental allergens are the key cell type in asthma. In this article, we examine the recent studies of iNK T cells and asthma, and discuss how different subsets of NK T cells function in different forms of asthma, including forms that are independent of adaptive immunity and Th2 cells. Together, these studies suggest that iNK T cells, which can interact with many other cell types including Th2 cells, eosinophils and neutrophils, provide a unifying pathogenic mechanism for many distinct forms of asthma.

T Cells and NKT Cells in the Pathogenesis of Asthma

Asthma is an immunological disease with multiple inflammatory and clinical phenotypes, characterized by symptoms of wheezing, shortness of breath, and coughing due to airway hyperreactivity (AHR) and reversible airway obstruction. In allergic asthma, the most common form of asthma, airway inflammation is mediated by adaptive immune recognition of protein allergens by Th2 cells, resulting in airway eosinophilia. However, in other forms of asthma, inflammation is associated with immune responses to respiratory infections and airway neutrophilia. A central feature common to all forms of asthma is AHR, the heightened responsiveness of the airways to nonspecific stimuli. AHR has been shown recently in animal models of asthma to require the presence of CD1d-restricted, invariant T cell receptor-positive, natural killer T (iNKT) cells. Although allergen-specific Th2 cells and iNKT cells have many phenotypic similarities (e.g., expression of CD4 and production of Th2 cytokines), they have complementary activities, such as production of Th2 cytokines under different conditions, differential sensitivity to corticosteroids, and responsiveness to different classes of antigen (proteins versus glycolipids). We hypothesize that Th2 cells and iNKT cells interact synergistically to induce asthma but that different forms of asthma result from distinct roles of CD4(+) iNKT cells versus Th2 cells.

Immunoglobulin constant heavy G subclass chain genes in asthma and allergy

The IGHG (ImmunoGlobulin constant Heavy G chain) genes are situated close to the IGHE gene on chromosome 14q32, 5'mu, delta, gamma3, gamma1, alpha1, gamma2, gamma4, epsilon, alpha2, 3', in linkage disequilibrium. The polymorphism of gamma3, gamma1 and gamma2 genes, is investigated as alternative allotypes. They are inherited in a Mendelian fashion and are expressed randomly in allelic exclusion. The alternative and functionally different gamma3, gamma1 and gamma2 gene variants, are found in four IGHG haplotypes, coding 4 B-cell variants: IGHG*bfn (=B1-cells), IGHG*bf-n (=B2-cells), IGHG*gan (=B3-cells) and IGHG*ga-n (=B4-cells). The dominance of the IGHG2*n allele from the IGHG*bfn haplotype (=B1-cells) has been shown in repeated investigations, namely in patients with asthma and allergy with increased serum levels of IgE > 600 ku/l and more often so in those with IgE > 1,000 ku/l or IgG4>1 g/l, in childhood asthma patients with mean level of IgE = 1,762 ku/l and in allergen exposed individuals developing laboratory animal allergy. In children with non-atopy and mean IgE level = 9.5 ku/l there is instead a dominance of the alternative allotypes from the IGHG*ga-n (=B4-cells) with IGHG2*-n alleles. In a case-control study allergic children with a family history of allergy, clinically manifest allergy and/or positive SPT, the IGHG*bfn haplotype (=B1-cells) with the IGHG2*n allele dominates, with increased risk of atopy and the IGHG*bf-n haplotype (=B2-cells) with the IGHG2*-n allele is infrequent with low risk, probably protective against atopy. The phenotypic expressions of the IGHG*bfn haplotype (=B1 cells) and IGHG*bfn/*bfn diplotypes (B1/B1-cells) are increased IgG2*n allotype together with increased IgE serum levels and IgE sensitisation in agreement with atopy. The alternative IGHG*ga-n/*ga-n diplotype (B4/B4-cells) express low IgG1*a- and IgG2*-n allotypes, together with low IgE and non-IgE sensitisation, in agreement with non-atopy. Together these studies have given us a greater understanding of the involvement of IGHG genes, IGHG coded B-cells and immunochemical and functional variants of IgG molecules describing different forms of asthma and allergy, which will improve diagnoses and treatment.

Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma

Allergic asthma is characterized by airway inflammation initiated by adaptive immune responses to aeroallergens. Recent data suggest that severe asthma may be a different form of asthma rather than an increase in asthma symptoms and that innate immune responses to LPS can modulate adaptive immune responses to allergens. In this study, we evaluated the hypothesis that airway exposure to different doses of LPS induces different form of asthma. Our study showed that neutrophilic inflammation and IFN-gamma expression were higher in induced sputum from severe asthma patients than from mild to moderate asthmatics. Animal experiments indicated that allergen sensitization with low-dose LPS (0.1 microg) induced type 2 asthma phenotypes, i.e., airway hyperresponsiveness, eosinophilic inflammation, and allergen-specific IgE up-regulation. In contrast, allergen sensitization with high-dose LPS (10 microg) induced asthma phenotypes, i.e., airway hyperresponsiveness and noneosinophilic inflammation that were not developed in IFN-gamma-deficient mice, but unaffected in the absence of IL-4. During the allergen sensitization period, TNF-alpha expression was found to be enhanced by both low- and high-dose LPS, whereas IL-12 expression was only enhanced by high-dose LPS. Interestingly, the asthma phenotypes induced by low-dose LPS, but not by high-dose LPS, were completely inhibited in TNF-alpha receptor-deficient mice, whereas the asthma phenotypes induced by high-dose LPS were abolished in the homozygous null mutation of the STAT4 gene. These findings suggest that airway exposure levels of LPS induces different forms of asthma that are type 1 and type 2 asthma phenotypes by high and low LPS levels, respectively.

What can we learn from late-onset and occupational asthma?

Late-onset asthma and occupational asthma may provide interesting models of human asthma to compare with the most frequent type of atopic early-onset asthma. The discovery of similarities and discrepancies in the aetiology and pathogenesis of these different diseases might provide new insights on different mechanisms producing the same phenotype and, thus, by recognizing the different underlying mechanisms of the different forms of asthma, may allow better targeting of prevention and treatment. Occupational asthma, in addition to being a late-onset asthma, provides the unique opportunity to study the development of asthma under measurable exposure conditions, and consequently to examine the effect of cessation of exposure which, at variance with allergen avoidance, is possible in most of the cases.