Inflammatory Process In Asthma Research Articles

Polyunsaturated Fatty Acids And Lipid Mediators Controlling Chronic Inflammation In Asthma

Asthma is a common chronic heterogeneous inflammatory respiratory disease with complex pathogenesis. Chronic lung inflammation can be the result of a defect in the resolution of the inflammatory process caused by an imbalance between the synthesis of proinflammatory and pro-resolving lipid mediators. The identification of immunomodulatory effects of eicosanoids, specialized pro-resolving mediators (SPMs), and endocannabinoids synthesized from polyunsaturated fatty acids (PUFAs) allows taking a fresh look at the ways of controlling inflammation rather than solely at its mechanisms. The use of ω-3 PUFA-containing food supplements in combination with standard therapy leads to improved asthma control due to the ability of ω-3 PUFAs to stimulate SPM synthesis and inhibit intracellular signaling pathways of inflammation. Lipid mediators are agonists of peroxisome proliferator-activated receptors (PPARs) and glucocorticoid receptors (GR) that have anti-inflammatory properties. The receptors that are widely expressed in the pulmonary epithelium, endothelium, dendritic cells, eosinophils, fibroblasts, and macrophages play an important role in the regulation of immunometabolic homeostasis in the bronchopulmonary system. Our review systematizes the published data on the properties and mechanism of action of biologically active ω-3 and ω-6 PUFAs involved in the inflammatory process in asthma. Also, this article presents the prospects of using ω-3 PUFAs for the resolution of inflammation in asthma.

The role of vitamin D in the severity and control of asthma in children and adolescents: A protocol for systematic review and meta-analysis

Vitamin D plays an important role in the immune system and consequently in the inflammatory process of asthma. It acts directly on the regulation of helper T lymphocytes 1 (Th1) and helper T lymphocytes 2 (Th2) cells, and regulatory T lymphocytes. Evidence shows that vitamin D acts on dendritic cells, raising inflammatory mediators and increasing the imbalance between Th1, Th2, and helper T lymphocytes 17 (Th17). Evidence shows a strong association between vitamin D levels and asthma incidence, especially in patients with severe and uncontrolled asthma. A systematic and comprehensive search will be performed using four main databases, PubMed, EMBASE, Cochrane Library, and Web of Science. Articles will be searched from the earliest available time to august 2022. The studied population will be composed of children and or adolescents with asthma. From the data obtained, all articles found will be transferred to the Rayyan platform. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Checklist (PRISMA P-2020). In addition, if sufficient data are available, a meta-analysis will be conducted. Two independent reviewers will conduct the studies selection, data extraction, and risk of bias assessment. The outcome measures will be to analyze the serum levels of vitamin D in patients with asthma and to relate this hormone to the control and severity of the disease and its anti- inflammatory effect. A systematic review will provide better knowledge regarding vitamin D and its role in the severity and control of asthma. The findings of this study will be published in a peer-reviewed journal.

A Case Study Showing Benralizumab’s Effectiveness in Treating Uncontrolled Severe Eosinophilic Asthma that is Resistant to Omalizumab

Asthma is a diverse illness that can range in severity. Because it has a significant impact on patients' quality of life and because people with severe asthma have symptoms, exacerbations, and drug side effects. Although first disregarded, eosinophils have since been directly linked to characteristics of the continuous inflammatory process in asthma, especially in the severe form. We present of the case of a 50year old female patient who presented with complaints of cough, breathing difficult on exertion and history of fever, chest pain and tiredness. The chest x ray showed left lower zone haziness. Patient was successfully treated with IV antibiotics, IV Proton pump inhibitor, Nebulised bronchodilators, IV Steroids, Anti-Hypertensive therapy and all other supportive medications along with pulmonary rehabilitations. In view of uncontrolled Eosinophilic asthma patient was treated with monoclonal antibody. Patient improved symptomatically better. This case study describes how benralizumab treatment for a patient with uncontrolled severe eosinophilic asthma resulted in significant improvements in lung function, asthma control, steroid use, and quality of life. Keywords: Benralizumab, Severe eosinophilic asthma, Omalizumab, Monoclonal antibodies

Psychological stress in asthma: repercussions on epigenetics-genetics, immune responses, and pulmonary function in the pediatric population.

In the assessment of childhood asthma, identifying the risk factors associated with exacerbations and broadening this view to understand psychological stress and its repercussions on the inflammatory process of asthma allow a different perspective on this biopsychosocial disease. Psychological stress, as a risk factor for the onset and noncontrol of asthma, has been increasingly evaluated from the perspective of the repercussions on the body of the stimulus generated in the hypothalamic-pituitary axis and adrenal glands, with cortisol release and immune system action. These processes trigger changes in T helper 2 cells, which polarize allergic processes, and dysfunctions in immune tolerance mechanisms, with a decrease in regulatory T cells. Genetic and epigenetic changes in β2-adrenergic and glucocorticoid receptors, with decreased response to these drugs, were also identified in studies, in addition to changes in respiratory function patterns, with worsening of obstruction and inflammation identified via decreased forced expiratory volume in one second and increased exhaled inflammatory gases in allergic asthma. Therefore, the present review sought to identify studies on the effect of personal and parental acute or chronic psychological stress, emphasizing the repercussions on genetics, epigenetics, and immune and pulmonary functional and inflammatory responses in the pediatric population.

Tezepelumab normalizes serum interleukin-5 and -13 levels in patients with severe, uncontrolled asthma

Asthma is a chronic, heterogeneous disease of the airways that involves a multitude of inflammatory processes triggered by various airborne stimuli. Thymic stromal lymphopoietin (TSLP)—an epithelial cell–derived cytokine produced in response to triggers such as allergens, viruses, or pollutants—has a central role in activating and maintaining downstream inflammatory processes in asthma.1 Tezepelumab is an anti-TSLP human monoclonal antibody. In the PATHWAY phase 2b (NCT02054130) and NAVIGATOR phase 3 (NCT03347279) studies, tezepelumab significantly reduced exacerbation rates vs placebo in patients with severe, uncontrolled asthma.

Lack of association between interleukin 13, interleukin 4 receptor alpha, andMS4A2 gene polymorphisms and asthma in adult Saudis

Objectives: Several genes, including interleukin-13 (IL13), MS4A2, and IL 4 receptor alpha (IL4Rα), have been shown to associate with the inflammatory process in asthma. We investigated the possible association between asthma and five single-nucleotide polymorphisms (SNPs) in the IL13, IL4Rα, and MS4A2 gene in comparison with the level of the IL-13 protein in the Saudi asthmatics and controls. Subjects and Methods: The study group included 50 adult asthmatic patients and 50 normal healthy controls. Blood was extracted, and DNA was prepared. Genotyping was performed on DNA using direct sequencing for four SNPs (rs20541, rs1800925, rs1801275, and rs569108), and real-time polymerase chain reaction allelic discrimination to study rs1805010 polymorphism. Levels of IL-13 were measured in plasma using (enzyme-linked immunosorbent. Genotype and allele frequencies were calculated for each SNP. Results: The results showed that GG genotype of rs1801275 in the IL4Rα gene was more common in the asthmatic patients compared to the control group, though the results did not show any statistical significance (P G transition nonsynonymous mutation, resulting in the substitution of glutamine by arginine showed an association, but it was statistically not significant. Interestingly, presence of the mutant allele of both SNPs of IL-13 gene significantly elevated IL-13 level. Comparison of the Saudi results with those of other populations, showed several significant differences. We conclude that further more detailed studies are necessary in Saudis to identify the contribution of SNPs in cytokine genes in asthma development.

Clinical efficacy of Unani herbal formulation in Zeeq-Un-Nafas Shoabi (Bronchial asthma)

Asthma and chronic obstructive pulmonary disease (COPD) are among the top ten most common diseases worldwide causing significant social and economic burden on the patient, family and health system. Despite the availability of safe and effective respiratory medication, problems such as under diagnosis, medication, adherence issue and poor understanding of asthma and COPD have led to the condition being poorly managed worldwide. The term Zeeq-Un-Nafas Shoabi (Bronchial Asthma) is clinically used for those conditions where longstanding irritation in mucous membrane of bronchioles results in cough and excessive production of sputum. Although Zeeq-Un-Nafas Shoabi (bronchial asthma) has not been described as such in Unani literature but the features mentioned under the headings of sual barid, sual ratab and sual nazli muzmin in various books correspond with the signs and symptoms of Zeeq-Un-Nafas Shoabi (Bronchial Asthma). Among all the treatment modalities, polyherbal combinations are said to be well-accepted, safe and effective in asthma. The reason for the therapeutic efficacy of herbal combinations in asthma is due to multiple blocking and homeostasis of very complex and interdependent cellular and mediator networks supporting and involved in the inflammatory process of asthma, whereas modern synthetic drug therapy aimed at blocking one mediator alone would be unlikely to have any significant effect on the disease process. None of the available treatments are found to be effective to provide a complete cure of this disease.

Severe Eosinophilic Asthma.

Asthma is a heterogeneous disease with varying severity. Severe asthma is a subject of constant research because it greatly affects patients’ quality of life, and patients with severe asthma experience symptoms, exacerbations, and medication side effects. Eosinophils, although at first considered insignificant, were later specifically associated with features of the ongoing inflammatory process in asthma, particularly in the severe case. In this review, we discuss new insights into the pathogenesis of severe asthma related to eosinophilic inflammation and the pivotal role of cytokines in a spectrum that is usually referred to as “T2-high inflammation” that accounts for almost half of patients with severe asthma. Recent literature is summarized as to the role of eosinophils in asthmatic inflammation, airway remodeling, and airway hypersensitivity. Major advances in the management of severe asthma occurred the past few years due to the new targeted biological therapies. Novel biologics that are already widely used in severe eosinophilic asthma are discussed, focusing on the choice of the right treatment for the right patient. These monoclonal antibodies primarily led to a significant reduction of asthma exacerbations, as well as improvement of lung function and patient quality of life.

A specific combined long-chain polyunsaturated fatty acid supplementation reverses fatty acid profile alterations in a mouse model of chronic asthma

BackgroundThe immune-modulating potential of long-chain polyunsaturated fatty acids (LCPUFAs) based on their conversion into lipid mediators in inflammatory situations has been proven by several studies. Respecting the immune-modulative role of lipid mediators in bronchoconstriction, airway inflammation and resolution of inflammatory processes, LCPUFAs play an important role in asthma. To design a disease-specific and most beneficial LCPUFA supplementation strategy, it is essential to understand how asthma alters LCPUFA profiles. Therefore, this study characterizes the alterations of LCPUFA profiles induced by allergic asthma. In addition, this study explores whether a simple eicosapentaenoic acid (EPA) alone or a specific combined LCPUFA supplementation could restore imbalanced LCPUFA profiles.MethodsMice were sensitized with a daily dose of 40 μg house dust mite (HDM)-extract in a recall model and fed with either normal diet, EPA or a specific combined (sc)-LCPUFA supplementation containing EPA, docosahexaenoic acid (DHA), γ -linolenic acid (GLA) and stearidonic acid (SDA) for 24 days. After recall with HDM, mice were sacrificed and blood and lung tissue were collected. Fatty acid profiles were determined in plasma, blood cells and lung cells of asthmatic mice by capillary gas-chromatography.ResultsIn lung cells of asthmatic mice, arachidonic acid (AA, p < 0.001) and DHA (p < 0.01) were increased while dihomo-γ-linolenic acid (DGLA, p < 0.05) was decreased. EPA supplementation increased only EPA (p < 0.001) and docosapentaenoic acid (DPA, p < 0.001), but neither DGLA nor DHA in lung cells of asthmatic mice. In contrast, a specific combined dietary supplementation containing n-3 and n-6 LCPUFAs could decrease AA (p < 0.001), increase EPA (p < 0.001), DPA (p < 0.001) and DHA (p < 0.01) and could reverse the lack of DGLA (p < 0.05).ConclusionsIn summary, allergic asthma alters LCPUFA profiles in blood and lung tissue. In contrast to the EPA supplementation, the distinct combination of n-3 and n-6 LCPUFAs restored the LCPUFA profiles in lung tissue of asthmatic mice completely. Subsequently, sc-LCPUFA supplementation is likely to be highly supportive in limiting and resolving the inflammatory process in asthma.

The impact of asthma on quality of life and anxiety: a pilot study

Introduction: Asthmatic patients are at risk for psychiatric symptoms. The objective of this study is to test the hypothesis that asthmatics have worse quality of life and anxiety scores in relation to a control group. Methods: This study is a cross-sectional study in which quality of life and anxiety scores were compared in a sample of 102 individuals, 51 asthmatics and 51 non-asthmatics. Quality of life and anxiety scores were quantified using validated questionnaires. The differences between the averages and the correlations between the total score for quality of life and anxiety were compared with t-tests and Pearson's correlation tests, respectively. The odds ratio compared the prevalence of moderate and severe anxiety between the groups. Results: The asthma group had higher average anxiety (p < 0.001) and lower averages in all areas of quality of life: physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning and mental health (p < 0.05 for all variables). There was a significant and inverse correlation between the total score for quality of life and anxiety scores but only in the asthma group (r = −0.71). Conclusions: Asthmatics have worse indicators of quality of life and anxiety, even though the symptoms of asthma are under clinical control. Moreover, the inverse correlation between the quality of life and the average anxiety scores in the asthma group suggests that the pulmonary inflammatory process of asthma may be related to the pathophysiology of emotional commitment in that group.

Hubungan Kadar Periostin Serum dan Nilai Asthma Control Test pada Pasien Asma di RSUD Dr. Soetomo Surabaya

Background: Asthma is a heterogenous disease composed of various phenotype. Chronic airway inflammation are fundamental features of asthma. The main treatment of asthma is corticosteroid. The administration of inhaled corticosteroids will reduce the inflammatory process in asthma. Even with adequate inhaled corticosteroid treatment, there are still patients who develop symptoms with lower asthma control test score. Periostin is an extracellular matrix protein as the best single systemic biomarker for assessing tissue eosinophilia, airway remodeling in uncontrolled asthma. The objective of this study was to examine whether serum periostin is correlated with ACT in asthmatic patients. Methods: This research was an observational analytical with cross sectional design conducted in outpatient clinic Dr. Soetomo General Hospital Surabaya for 3 months. In total, we found 40 asthmatic patients who were qualified to the inclusion and exclusion criteria as the research samples. The questionnaire was filled in to assess the Asthma Control Test and venous blood tests to measure serum periostin levels using Sandwich Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: The mean periostin level profile of the sample was 94.82 ± 19.21 ng/ml and the median was 94.7 ng/ml. The average ACT score was 16.55 ± 2.93 with 85% were uncontrolled asthma. The results of the independent t-test showed serum periostin levels and the level of asthma control based on ACT score in asthmatics patients had a significant correlation (p = 0.024). Conclusion: There is a significant correlation between serum periostin levels and ACT score in asthmatic patients.

Association between TSLP gene polymorphism and bronchial asthma in children in Beni Suef Governorate in Egypt

Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2 (TH2) cells. Thymic stromal lymphopoietin (TSLP) gene can exacerbate the lung inflammatory process in asthma by enhancing TH2 differentiation through dendritic cell activation. Many studies showed that TSLP polymorphisms are related to bronchial asthma susceptibility in different populations. The objectives of this study are to study the polymorphism of the two SNPs Rs2289276 and Rs2289278 in TSLP gene and to analyze any possible relation to pediatric bronchial asthma liability in Egypt using case-control study. DNA was extracted from blood samples withdrawn from 40 asthmatic patients and 20 age- and sex-matched normal controls, then the genotypes of SNPs Rs2289276 and Rs2289278 in TSLP gene were identified with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and genotypes and allele frequencies were calculated and statistically analyzed. Genotypes of Rs2289276 site in the asthmatic patients were dissimilar from those of the controls (P = 0.045). The genotypes of Rs2289278 in asthmatic patients were significantly different between those of intermittent and severe asthma (P = 0.044). Bronchial asthma susceptibility and severity are related to TSLP variants. Thus, TSLP might be a new target molecule for asthma treatment.

Effects of genetic factors to inhaled corticosteroid response in children with asthma: a literature review.

Numerous studies have examined the association between pharmacogenetic effects and the response to inhaled corticosteroids (ICS) in patients with asthma. In fact, several single nucleotide polymorphisms of a number of candidate genes have been identified that might influence the clinical response to ICS in children with asthma. Their direct or indirect effects depend on their role in the inflammatory process in asthma or the anti-inflammatory action of corticosteroids, respectively. Among the genes identified, variants in T-box 21 (TBX21) and Fc fragment of IgE receptor II (FCER2) contribute indirectly to the variability in the response to ICS by altering the inflammatory mechanisms in asthma, while other genes such as corticotropin releasing hormone receptor 1 (CRHR1), nuclear receptor subfamily 3 group C member 1 (NR3C1), stress induced phosphoprotein 1 (STIP1), dual specificity phosphatase 1 (DUSP1), glucocorticoid induced 1 (GLCCI1), histone deacetylase 1 (HDAC), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and vascular endothelial growth factors (VEGF) directly affect this variability through the anti-inflammatory mechanisms of ICS. The results to date indicate various potential genetic factors associated with the response to ICS, which could be utilized to predict the individual therapeutic response of children with asthma to ICS. Clinical trials are underway and their results are greatly anticipated. Further pharmacogenetic studies are needed to fully understand the effects of genetic variation on the response to ICS in children with asthma.

ChemInform Abstract: Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma

AbstractReview: 61 refs.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma.

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy.

HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2.

The proinflammatory factor high mobility group box protein 1 (HMGB1) has been implicated as an important mediator of many chronic inflammatory diseases, including asthma. Human bronchial epithelial cells (HBECs) play a central role in the pathogenesis of asthma. However, the effects of HMGB1 on HBECs and the underlying mechanisms remain unknown. Here, we investigated receptor expression and proinflammatory cytokine production by primary cultures of HBECs stimulated by HMGB1. We then examined the effects of specific receptor blockade and inhibition of p38 MAPK, ERK1/2, or PI3-K on HMGB1-induced expression of proinflammatory cytokines. HMGB1 increased the expression and secretion of TNF-α, TSLP, MMP-9, and VEGF in a dose- and time-dependent manner. HMGB1 also induced elevated expression of RAGE protein. Secretion of TNF-α, VEGF, MMP-9, and TSLP was significantly decreased by RAGE blockade and p38 MAPK pathway inhibition, while a less pronounced effect was mediated by ERK1/2 inhibition. These observations suggest that HMGB1 binds RAGE and promotes activities of p38 MAPK and ERK1/2 pathways in HBECs. This then enhances the expression of TNF-α, VEGF, MMP-9, and TSLP, which are the important inflammatory factors in asthma. These results demonstrate that HMGB1 enhances the inflammatory responses of HBECs, which are involved in the modulation of inflammatory processes in asthma.

8-Oxoguanine DNA glycosylase-1-driven DNA base excision repair: role in asthma pathogenesis.

To provide both an overview and evidence of the potential cause of oxidative DNA base damage and repair signaling in chronic inflammation and histological changes associated with asthma. Asthma is initiated/maintained by immunological, genetic/epigenetic, and environmental factors. It is a world-wide health problem, as current therapies suppress symptoms rather than prevent/reverse the disease, largely due to gaps in understanding its molecular mechanisms. Inflammation, oxidative stress, and DNA damage are inseparable phenomena, but their molecular roles in asthma pathogenesis are unclear. It was found that among oxidatively modified DNA bases, 8-oxoguanine (8-oxoG) is one of the most abundant, and its levels in DNA and body fluids are considered a biomarker of ongoing asthmatic processes. Free 8-oxoG forms a complex with 8-oxoG DNA glycosylase-1 and activates RAS-family GTPases that induce gene expression to mobilize innate and adaptive immune systems, along with genes regulating airway hyperplasia, hyper-responsiveness, and lung remodeling in atopic and nonatopic asthma. DNA's integrity must be maintained to prevent mutation, so its continuous repair and downstream signaling 'fuel' chronic inflammatory processes in asthma and form the basic mechanism whose elucidation will allow the development of new drug targets for the prevention/reversal of lung diseases.

Non-invasive optical imaging of eosinophilia during the course of an experimental allergic airways disease model and in response to therapy.

BackgroundMolecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils.Methodology/Principal FindingsAn ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h–72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs.Conclusion/SignificanceWe show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.

Adult Serum Cytokine Concentrations and the Persistence of Asthma

Background: Cytokines play a pivotal role in regulating the development and persistence of the inflammatory process in asthma. Our aim was to investigate whether asthma persistence or remission is associated with a specific cytokine profile. Methods: The Tasmanian Longitudinal Health Study followed participants from 7 to 44 years of age. Serum concentrations of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-α) were measured at age 44 years. Participants were categorized into five phenotypes (early-onset noncurrent asthma, early-onset current asthma, late-onset noncurrent asthma and late-onset current asthma). Those who had never had asthma formed the reference group. Multivariable linear regression was used to compare serum cytokine concentrations between each phenotype and the reference group. Results: IL-10 concentrations were significantly lower in serum from the early-onset current asthma group than in the reference group (ratio of geometric means 0.58; 95% confidence interval 0.33-0.99; p = 0.048). IL-6 concentrations for the late-onset remitted group were also significantly lower than in the reference group (p = 0.009). The TNF-α concentrations were significantly lower for both early-and late-onset remitted asthma phenotypes when compared with the reference group. No associations were detected between serum concentrations of IL-4, IL-5 or IL-8 and these specific longitudinal asthma phenotypes. Conclusion: Our findings suggest a possible role for deficient IL-10 responses in the persistence of early-onset asthma. Lower IL-6 and TNF-α concentrations in serum from those with remitted asthma suggest that these proinflammatory cytokines may be actively suppressed during asthma remission.

Relationship of Mannitol Challenge to Methacholine Challenge and Inflammatory Markers in Persistent Asthmatics Receiving Inhaled Corticosteroids

Mannitol is a novel osmotic indirect bronchial challenge agent used to aid asthma diagnosis and management and is thought to reflect underlying inflammatory processes in asthma. Our objective was to evaluate relationships between mannitol airway hyperresponsiveness (AHR) and other measures of airway inflammation as well as direct-acting methacholine challenge in persistent asthmatics receiving inhaled corticosteroids. We analysed screening data of mild to moderate persistent asthmatics, all receiving inhaled corticosteroids (ICS), who had mannitol and/or methacholine challenges, fractional exhaled nitric oxide (FeNO), and salivary eosinophilic cationic protein (ECP) performed as part of the same screen. Mannitol AHR was grouped by PD(10) (cumulative provocative dose required to produce a 10% fall in FEV(1)): mild (315-635mg), moderate (75-315mg), and severe (0-75mg). FeNO groups were low (<25ppb), medium (25-50ppb), and high (>50ppb) and methacholine PC(20) (provocative concentration of methacholine required to cause a 20% fall in FEV(1)) groups were mild (2-8mg/ml), moderate (0.5-2mg/ml), and severe (0-0.5mg/ml). Mannitol PD(10) groups were significantly different overall for FeNO (p=0.023): 43% higher in the severe vs. the mild group. There was a significant overall difference for methacholine PC(20) (p=0.006): a 2.1 doubling dilution difference between severe vs. mild mannitol groups. FeNO groups were significantly different overall for mannitol PD(10) (p=0.01) and methacholine PC(20) (p=0.029). Methacholine PC(20) groups were significantly different overall for mannitol PD(10) (p<0.001) and FeNO (p=0.005). No significant differences were found across any groups for salivary ECP, FEV(1) % predicted, or ICS dose. Mannitol PD(10), methacholine PC(20), and FeNO as continuous variables all correlated with each other. Mannitol challenge reflects underlying inflammation using FeNO and direct AHR using methacholine. Thus, mannitol may be a useful screening tool for the assessment of asthmatic patients receiving inhaled corticosteroids.