Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease.

Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.

Assessing the impact of air pollutants on clinical visits for childhood allergic respiratory disease induced by house dust mite in Shanghai, China.

BACKGROUND: The prevalence of allergic respiratory disease (ARD) is increasing worldwide during the last few decades, causing a great disease burden especially for children. Air pollution has been increasingly considered as a potential contributor to this trend, but its role in ARD induced by house dust mite (HDM-ARD) remains unclear, especially in time-series study. METHODS: A positive reporting of respiratory allergy to named allergens was included by serum specific IgE testing. A time series Quasi-Poisson regression with distributed lag non-linear model, combined with generalized linear model was used to examine the effects of air pollutants on ARD, HDM-ARD and ARD induced by non-house dust mite (NHDM-ARD). RESULTS: A total of 16,249 cases of ARD, including 8,719 HDM-ARD and 8,070 NHDM-ARD from 1 Jan 2013 to 31 Dec 2017 were involved in this study. Air pollutants were significantly associated with clinical visits for childhood ARD and HDM-ARD. Exposure to higher O3 and interquartile range (IQR) increment in O3 (40.6 µg/m3) increased the risks of clinical visits for childhood HDM-ARD (RRlag0-5 for the 95th percentile of O3: 1.26, 95% confidence interval (CI): 1.03, 1.55; RRlag0-5 for IQR increment (40.6 µg/m3): 1.09, 95% CI: 1.01, 1.17) and ARD (RRlag0-5 for the 95th percentile of O3: 1.19, 95% CI: 1.03, 1.38; RRlag0-5 for IQR increment (40.6 µg/m3): 1.06, 95% CI: 1.01, 1.12). In addition, higher O3 was associated with increased RR of boys with ARD (RRlag0-5 for the 95th percentile: 1.26, 95% CI: 1.05, 1.51; RRlag0-5 for IQR increment (40.6 µg/m3): 1.09, 95% CI: 1.02, 1.16) and HDM-ARD (RRlag0-5 for the 95th percentile: 1.36, 95% CI: 1.06, 1.75; RRlag0-5 for IQR increment (40.6 µg/m3): 1.11, 95% CI: 1.02, 1.22), but not in girls. CONCLUSIONS: Exposure to O3 appeared to be a trigger of clinical visits for childhood ARD, especially for HDM-ARD and boys. These findings provide novel evidence on the impact of air pollution on HDM-ARD, which may have significant implications for designing effective intervention programs to control and prevent childhood ARD, especially HDM-ARD, in China and other similar developing countries.

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD. OBJECTIVE: Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD. METHODS: Single-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence. RESULTS: The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO+ epithelium in NPs from patients with AERD. CONCLUSIONS: Epithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.

Functional Fine-Tuning of Metabolic Pathways by the Endocannabinoid System-Implications for Health and Disease.

The endocannabinoid system (ECS) employs a huge network of molecules (receptors, ligands, and enzymatic machinery molecules) whose interactions with other cellular networks have still not been fully elucidated. Endogenous cannabinoids are molecules with the primary function of control of multiple metabolic pathways. Maintenance of tissue and cellular homeostasis by functional fine-tuning of essential metabolic pathways is one of the key characteristics of the ECS. It is implicated in a variety of physiological and pathological states and an attractive pharmacological target yet to reach its full potential. This review will focus on the involvement of ECS in glucose and lipid metabolism, food intake regulation, immune homeostasis, respiratory health, inflammation, cancer and other physiological and pathological states will be substantiated using freely available data from open-access databases, experimental data and literature review. Future directions should envision capturing its diversity and exploiting pharmacological options beyond the classical ECS suspects (exogenous cannabinoids and cannabinoid receptor monomers) as signaling through cannabinoid receptor heteromers offers new possibilities for different biochemical outcomes in the cell.

Monoclonal Antibodies and Airway Diseases.

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome-environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.

The emerging role of immunothrombosis in paediatric conditions.

BACKGROUND: Immunothrombosis is a physiological process based on the release of neutrophil extracellular traps (NETs) to immobilise, contain and kill bacteria. This is an innate immune response in which the local activation of blood coagulation exerts the critical protective function during microbial infection. In recent years, there has been much interest in the adult literature about the key role of immunothrombosis in pathologic states including thrombosis, cancer, sepsis and trauma. Currently, little research has been done into its role in paediatric conditions. METHODS: We conducted a literature search of the National Library of Medicine (MEDLINE/PubMed) from the years 2000 to May 2018 and qualitatively identified 24 relevant papers. References of articles included for full-text review were checked for relevant publications. RESULTS: Our aim is to summarise the most relevant evidences regarding an excessive production or defective removal of NETs in paediatric conditions. In particular, we have divided the role of immunothrombosis into acute (sepsis, necrotising enterocolitis, otitis media, neonatal arterial ischaemic stroke, haemolytic anaemic diseases) and chronic (systemic lupus erythematous, type 1 diabetes mellitus, respiratory diseases, graft-versus-host disease) conditions to find important similarities in their pathophysiology. CONCLUSION: The field of immunothrombosis in paediatric conditions is still in its infancy. We have presented multiple pathways of NET-induced disease together with possible areas of future research and treatments.

Mucosal-associated invariant T cells: new players in CF lung disease?

The past decade has witnessed a surge in research centered around exploring the role of the enigmatic innate immune-like lymphocyte MAIT cell in human disease. Recent evidence has led to the elucidation of its role as a potent defender at mucosal surfaces including lungs due to its capacity to mount a formidable immediate response to bacterial pathogens. MAIT cells have a unique attribute of recognizing microbial ligands in conjunction with non-classical MHC-related protein MR1. Recent studies have demonstrated their contribution in the pathogenesis of chronic pulmonary disorders including asthma and chronic obstructive pulmonary disease. Several cellular players including innate immune cells are active contributors in the immune imbalance present in cystic fibrosis(CF) lung. This immune dysregulation serves as a central pivot in disease pathogenesis, responsible for causing immense structural damage in the CF lung. The present review focuses on understanding the role of MAIT cells in CF lung disease. Future studies directed at understanding the possible relationship between MAIT cells and regulatory T cells (Tregs) in CF lung disease could unravel a holistic picture where a combination of antimicrobial effects of MAIT cells and anti-inflammatory effects of Tregs could be exploited in synergy to alleviate the rapid deterioration of lung function in CF lung disease due to the underlying complex interplay between persistent infection and inflammation.

From "Immunity Debt" to "Immunity Theft"-How COVID-19 Might Be Tied to Recent Respiratory Disease Surges.

This Medical News story discusses the relationship between the COVID-19 pandemic and recent increases in other respiratory diseases.

Emerging Regulatory Roles of Dual-Specificity Phosphatases in Inflammatory Airway Disease.

Inflammatory airway disease, such as asthma and chronic obstructive pulmonary disease (COPD), is a major health burden worldwide. These diseases cause large numbers of deaths each year due to airway obstruction, which is exacerbated by respiratory viral infection. The inflammatory response in the airway is mediated in part through the MAPK pathways: p38, JNK and ERK. These pathways also have roles in interferon production, viral replication, mucus production, and T cell responses, all of which are important processes in inflammatory airway disease. Dual-specificity phosphatases (DUSPs) are known to regulate the MAPKs, and roles for this family of proteins in the pathogenesis of airway disease are emerging. This review summarizes the function of DUSPs in regulation of cytokine expression, mucin production, and viral replication in the airway. The central role of DUSPs in T cell responses, including T cell activation, differentiation, and proliferation, will also be highlighted. In addition, the importance of this protein family in the lung, and the necessity of further investigation into their roles in airway disease, will be discussed.

Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice.

BACKGROUND: Cigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associated with smoking and lipid homeostasis disruption. Several immunization strategies against oxidized lipid species to help with their clearance have been shown to reduce the formation of atherosclerotic lesions. Since oxidized lipids are generated during cigarette smoke exposure, we investigated the impact of a prophylactic immunization protocol against OxLDL on the pulmonary effects of cigarette smoke exposure in mice. METHODS: Mice were immunized systemically with a mixture of human OxLDL (antigen source) and AddaVax (adjuvant) or PBS alone prior to the initiation of acute (2 week) or sub-chronic (8 weeks) cigarette smoke exposure protocols. Anti-OxLDL antibodies were measured in the bronchoalveolar lavage (BAL) fluid and serum by direct ELISA. Pulmonary impacts of cigarette smoke exposure and OxLDL immunization were assessed by measuring BAL inflammatory cells, lung functions, and changes in lung structure and gene levels of matrix/matrix-related genes. RESULTS: Immunization to OxLDL led to a marked increase in circulating and pulmonary antibodies against OxLDL that persisted during cigarette smoke exposure. OxLDL immunization did not exacerbate or reduce the inflammatory response following acute or sub-chronic exposure to cigarette smoke. OxLDL immunization alone had effects similar to cigarette smoke exposure on lung functions but OxLDL immunization and cigarette smoke exposure had no additive effects on these parameters. No obvious changes in lung histology, airspace or levels of matrix and matrix-related genes were caused by OxLDL immunization compared to vehicle treatment. CONCLUSIONS: Overall, this study shows for the first time that a prophylactic immunization protocol against OxLDL can potentially have detrimental effects lung functions, without having additive effects over cigarette smoke exposure. This work sheds light on a complex dynamic between anti-OxLDL antibodies and the pulmonary response to cigarette smoke exposure.

Potential Biomarkers for NSAID-Exacerbated Respiratory Disease.

Asthma is a common chronic disease with several variant phenotypes and endotypes. NSAID-exacerbated respiratory disease (NERD) is one such endotype characterized by asthma, chronic rhinosinusitis (CRS) with nasal polyps, and hypersensitivity to aspirin/cyclooxygenase-1 inhibitors. NERD is more associated with severe asthma than other asthma phenotypes. Regarding diagnosis, aspirin challenge tests via the oral or bronchial route are a standard diagnostic method; reliable in vitro diagnostic tests are not available. Recent studies have reported various biomarkers of phenotype, diagnosis, and prognosis. In this review, we summarized the known potential biomarkers of NERD that are distinct from those of aspirin-tolerant asthma. We also provided an overview of the different NERD subgroups.

Indoor Fungal Exposure and Allergic Respiratory Disease.

A gathering body of evidence has repeatedly revealed associations between indoor fungi and initiation, promotion, and exacerbation of allergic respiratory disease. The relationship between the exposure and outcome are complicated by the difficulties in measuring both exposure and outcome, the multifactorial nature of the disease, and the wide range of potential confounders. New technologies are becoming available that may enable better measurement of exposure and tighter case definitions so as to build more confidence in the associations discovered. The growing strength of the evidence base will aid the design of future public health interventions and generate new hypotheses on the cause of the rapid increase in allergic respiratory disease prevalence.

Peri-operative adverse respiratory events in children.

Three quarters of all critical incidents and a third of all peri-operative cardiac arrests in paediatric anaesthesia are caused by adverse respiratory events. We screened for risk factors from children's and their families' histories, and assessed the usefulness of common markers of allergic sensitisation of the airway as surrogates for airway inflammation and increased risk for adverse respiratory events. One hundred children aged up to 16 years with two or more risk factors undergoing elective surgery were included in the study. Eosinophil counts, IgE level, specific IgE for D. pteronyssinus, cat epithelia and Gx2 (grass pollen) were measured for each child and adverse respiratory events (bronchospasm, laryngospasm, oxygen desaturation < 95%, severe persistent coughing, airway obstruction and postoperative stridor) were recorded. Twenty-one patients had an adverse respiratory event but allergic markers were poor predictors. Binary logistic regression showed a lack of predictive value of the eosinophil range and adverse respiratory events (p = 0.249). Receiver operating characteristic (ROC) curves for the presence of adverse respiratory events vs level of specific IgE antibody (to Gx2 (AUC 0.614), cat epithelia (0.564) and D. pteronyssinus (0.520)) demonstrated poor predictive values. However, the presence of risk factors was strongly associated with adverse respiratory events (p < 0.001) and a ROC-curve analysis indicated a fair capacity to predict adverse respiratory events (AUC 0.788). There was a significant difference (p = 0.001) between the presence of adverse respiratory events in patients with more than four (p = 0.006), compared with less than four (p = 0.001), risk factors. We conclude that while risk factors taken from the child's (or family) history proved good predictors of adverse respiratory events, immunological markers of allergic sensitisation demonstrated low predictive values. Pre-operative identification of children at high risk for an adverse respiratory event should rely on clinical, rather than immunological, assessment.

Role of specific IgE in predicting the clinical course of lentil allergy in children.

BACKGROUND: Legumes, and particularly lentils, are frequently consumed in Mediterranean, Middle Eastern, and some Asian countries. The aim of this study was to document the demographic features of children with lentil allergy and to determine the role of specific IgE (sIgE) in predicting the risk of clinical reactivity and disease persistence. METHODS: Thirty children were enrolled. The diagnosis of lentil allergy was based on convincing history of symptoms or anaphylaxis after the ingestion of lentils, with positive skin tests and/or sIgE to lentils. To determine the diagnosis and prognosis of lentil allergy, 24 children were evaluated with food challenges. RESULTS: The median age at the onset of symptoms was 1.5 yr (0.9-2.3) (inter-quartile range). The most frequent symptoms were immediate cutaneous (97%) and respiratory (30%) reactions, whereas eight patients (27%) reported anaphylactic reactions. The median level of lentil sIgE at the time of diagnosis was 3 kU/l (1.2-9.6). Of the 24 challenges, 12 were positive. Fifteen patients (50%) outgrew the lentil allergy by the age of 3.5 (2.5-11) years. Children with an initial lentil sIgE < 4.9 kU/l had a significantly higher likelihood (68.4% vs. 18.2%) of outgrowing the lentil allergy than children with an initial lentil sIgE ≥ 4.9 k/l (p = 0.008). CONCLUSIONS: Our results suggest that sIgE levels may be important for predicting clinical reactivity and persistence of lentil allergy.

Work-related allergic respiratory disease and asthma in spice mill workers is associated with inhalant chili pepper and garlic exposures.

OBJECTIVE: The aim of the study was to determine the prevalence and risk factors for allergic respiratory disease in spice mill workers. METHODS: A cross-sectional study of 150 workers used European Community Respiratory Health Survey questionnaires, Phadiatop, serum specific IgE (garlic, chili pepper), spirometry and fractional exhaled nitric oxide (FeNO). Personal air samples (n=62) collected from eight-hour shifts were analysed for inhalable particulate mass. Novel immunological assays quantified airborne garlic and chili pepper allergen concentrations. RESULTS: Mean dust particulate mass (geometric mean (GM)=2.06 mg/m(3)), chili pepper (GM=0.44 µg/m(3)) and garlic allergen (GM=0.24 µg/m(3)) were highest in blending and were highly correlated. Workers' mean age was 33 years, 71% were men, 46% current smokers and 45% atopic. Spice-dust-related asthma-like symptoms (17%) were common, as was garlic sensitisation (19%), with 13% being monosensitised and 6% cosensitised to chili pepper. Airflow reversibility and FeNO>50 ppb was present in 4% and 8% of workers respectively. Spice-dust-related ocular-nasal (OR 2.40, CI 1.09 to 5.27) and asthma-like (OR 4.15, CI 1.09 to 15.72) symptoms were strongly associated with airborne garlic in the highly exposed (>0.235 µg/m(3)) workers. Workers monosensitised to garlic were more likely to be exposed to higher airborne chili pepper (>0.92 µg/m(3)) (OR 11.52, CI 1.17 to 113.11) than garlic allergens (OR 5.08, CI 1.17 to 22.08) in this mill. Probable asthma was also more strongly associated with chili pepper than with garlic sensitisation. CONCLUSIONS: Exposure to inhalable spice dust (GM >2.06 mg/m(3)) containing garlic (GM>0.24 µg/m³) and chili pepper (GM >0.44 µg/m(3)) allergens increase the risk of allergic respiratory disease and asthma.

Children's urinary phthalate metabolites and fractional exhaled nitric oxide in an urban cohort.

RATIONALE: Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children's phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examined. OBJECTIVES: We hypothesized that urinary concentrations of four phthalate metabolites would be positively associated with Fe(NO) and that these associations would be stronger among children with seroatopy or wheeze. METHODS: In an urban ongoing birth cohort, 244 children had phthalate metabolites determined in urine collected on the same day as Fe(NO) measurement. Repeated sampling gathered 313 observations between ages 4.9 and 9.1 years. Seroatopy was assessed by specific IgE. Wheeze in the past year was assessed by validated questionnaire. Regression models used generalized estimating equations. MEASUREMENTS AND MAIN RESULTS: Log-unit increases in urinary concentrations of metabolites of diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) were associated with a 6.6% (95% confidence interval [CI] 0.5-13.1%) and 8.7% (95% CI, 1.9-16.0%) increase in Fe(NO), respectively, adjusting for other phthalate metabolites and potential covariates/confounders. There was no association between concentrations of metabolites of di(2-ethylhexyl) phthalate or di-n-butyl phthalate and Fe(NO). There was no significant interaction by seroatopy. The BBzP metabolite association was significantly stronger among children who wheeze (P = 0.016). CONCLUSIONS: Independent associations between exposures to DEP and BBzP and Fe(NO) in a cohort of inner-city children were observed. These results suggest that these two ubiquitous phthalates, previously shown to have substantial contributions from inhalation, are positively associated with airway inflammation in children.

Sleep and allergic disease: a summary of the literature and future directions for research.

Atopic diseases, such as asthma and allergic rhinitis, are common conditions that can influence sleep and subsequent daytime functioning. Children and patients with allergic conditions from ethnic minority groups might be particularly vulnerable to poor sleep and compromised daytime functioning because of the prevalence of these illnesses in these groups and the high level of morbidity. Research over the past 10 years has shed light on the pathophysiologic mechanisms (eg, inflammatory mediators) involved in many atopic diseases that can underlie sleep disruptions as a consequence of the presence of nocturnal symptoms. Associations between nocturnal symptoms and sleep and poorer quality of life as a result of missed sleep have been demonstrated across studies. Patients with severe illness and poor control appear to bear the most burden in terms of sleep impairment. Sleep-disordered breathing is also more common in patients with allergic diseases. Upper and lower airway resistance can increase the risk for sleep-disordered breathing events. In patients with allergic rhinitis, nasal congestion is a risk factor for apnea and snoring. Finally, consistent and appropriate use of medications can minimize nocturnal asthma or allergic symptoms that might disrupt sleep. Despite these advances, there is much room for improvement in this area. A summary of the sleep and allergic disease literature is reviewed, with methodological, conceptual, and clinical suggestions presented for future research.

Swedish natalizumab (Tysabri) multiple sclerosis surveillance study.

A post-marketing surveillance program was implemented to monitor the safety and open label efficacy of natalizumab since its launch in Sweden August 2006. Patients are registered in the Swedish multiple sclerosis (MS)-registry that has a nationwide coverage using a standardized follow-up that includes EDSS, MSSS, SDMT, MSIS-29, and recording of adverse events (AEs). As of 31 January, 2010, 1,115 patients had been included, of which 363 were treated ≥ 24 months. Dropout rate was 10%, mainly due to planned pregnancy. Serious AEs were rare, but included three cases of progressive multifocal leukoencephalopathy (PML), none of which had received previous immunosuppressive therapy. All analyzed clinical outcome parameters showed significant improvements compared to baseline for patients exceeding 24 months of treatment. Our results demonstrate good general tolerability and sustained efficacy of natalizumab for patients with severe MS, though the risk of PML remains a concern.

Mutant Mice and Animal Models of Airway Allergic Disease.

Eosinophilia is a hallmark of allergic airway inflammation, and eosinophils represent an integral effector leukocyte through their release of various granule-stored cytokines and proteins. Numerous mouse models have been developed to mimic clinical disease and they have been instrumental in furthering our understanding of the role of eosinophils in disease. Most of these models consist of intranasal (i.n.) administration of antigenic proteases including papain and house dust mite (HDM) or the neo-antigen ovalbumin, with a resulting Th2-biased immune response and airway eosinophilia. These models have been particularly informative when combined with the numerous transgenic mice available that modulate eosinophil frequency or the mechanisms involved in their migration. Here, we describe the current models of allergic airway inflammation and outline some of the transgenic mice available to study eosinophil disease.

Eosinophils in Asthma Models to House Dust Mite for Drug Development.

Murine models of asthma are developed to better understand the mechanisms of asthma including eosinophil recruitment in the airways with the aim of evaluating new therapeutic strategies. They are intended to model the typical features of human disease, in particular airway inflammation, hyperresponsiveness (AHR), and remodeling. The phenotype of inflammatory cells recovered from the bronchoalveolar lavage fluid (BAL) is studied with innovative flow cytometry techniques while airway obstruction is measured using the forced oscillation technique, and airway responsiveness approached by barometric plethysmography in awake and unconstrained animals. We here describe models of asthma of house dust mite (HDM) as a clinically relevant allergen: a short study design (8 days) model of hypereosinophilic asthma and a chronic (31 days) asthma model, both suitable to evaluate the potential of new drug candidates to prevent allergic asthma.