The effect of lower airway inflammation on inflammatory cytokine gene expression in bronchoalveolar lavage fluid and whole blood in racing Thoroughbreds.

BACKGROUND: Immunological mechanisms involved in the pathogenesis of mild to moderate equine asthma (MEA) are not completely understood. There are limited data on bronchoalveolar lavage fluid (BALF) and blood inflammatory cytokine profiles in racehorses with MEA, and the effect of racing on inflammatory cytokines is unknown. HYPOTHESIS/OBJECTIVES: We hypothesized that inflammatory cytokine gene expression in BALF and resting blood would be higher in racehorses with lower airway inflammation compared to healthy controls, and that gene expression in blood collected immediately post-race would be increased compared to resting blood in racehorses with lower airway inflammation. ANIMALS: 38 racing Thoroughbreds (samples: 30 resting blood, 22 post-race BALF, 41 post-race blood). METHODS: Prospective observational study. Inflammatory cytokine gene expression was determined in resting blood, post-race BALF and post-race blood from racehorses with lower airway inflammation and controls. RESULTS: Lower airway inflammation was diagnosed in 79 % of racehorses (23 % neutrophilic, 67 % mastocytic, and 10 % mixed). There was no difference in gene expression in BALF or resting blood between racehorses with lower airway inflammation and controls. IL-8 gene expression was higher in post-race blood compared to resting peripheral blood, regardless of disease (p = 0052). BALF neutrophil proportions increased with increasing IL-1ß gene expression in all sample types (p = 0.0025). BALF mast cell proportions increased with increasing TNF-α gene expression in post-race blood (p = 0.015). CONCLUSIONS AND CLINICAL IMPORTANCE: Lower airway inflammation was common in a population of racehorses without respiratory signs or exercise intolerance. Exercise alone increased peripheral blood IL-8 gene expression. Inflammatory cytokine gene expression was not increased in BALF or resting blood in horses with subclinical lower airway inflammation, precluding its diagnostic utility in clinical practice.

Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes.

Asthma is a common disease in paediatrics and adults with a significant morbidity, mortality, and financial burden worldwide. Asthma is now recognized as a heterogeneous disease and emerging clinical and laboratory research has elucidated understanding of asthma's underlying immunology. The future of asthma is classifying asthma by endotype through connecting discernible characteristics with immunological mechanisms. This comprehensive review of the immunology of asthma details the currently known pathophysiology and clinical practice biomarkers in addition to forefront biologic and targeted therapies for all of the asthma endotypes. By understanding the immunology of asthma, practitioners will be able to diagnose patients by asthma endotype and provide personalized, biomarker-driven treatments to effectively control patients' asthma.

Development of a tool predicting severity of allergic reaction during peanut challenge.

BACKGROUND: Reliable prognostic markers for predicting severity of allergic reactions during oral food challenges (OFCs) have not been established. OBJECTIVE: To develop a predictive algorithm of a food challenge severity score (CSS) to identify those at higher risk for severe reactions to a standardized peanut OFC. METHODS: Medical history and allergy test results were obtained for 120 peanut allergic participants who underwent double-blind, placebo-controlled food challenges. Reactions were assigned a CSS between 1 and 6 based on cumulative tolerated dose and a severity clinical indicator. Demographic characteristics, clinical features, peanut component IgE values, and a basophil activation marker were considered in a multistep analysis to derive a flexible decision rule to understand risk during peanut of OFC. RESULTS: A total of 18.3% participants had a severe reaction (CSS >4). The decision rule identified the following 3 variables (in order of importance) as predictors of reaction severity: ratio of percentage of CD63hi stimulation with peanut to percentage of CD63hi anti-IgE (CD63 ratio), history of exercise-induced asthma, and ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio. The CD63 ratio alone was a strong predictor of CSS (P < .001). CONCLUSION: The CSS is a novel tool that combines dose thresholds and allergic reactions to understand risks associated with peanut OFCs. Laboratory values (CD63 ratio), along with clinical variables (exercise-induced asthma and FEV1/FVC ratio) contribute to the predictive ability of the severity of reaction to peanut OFCs. Further testing of this decision rule is needed in a larger external data source before it can be considered outside research settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02103270.

Mechanisms and Biomarkers of Exercise-Induced Bronchoconstriction.

Exercise is a common trigger of bronchoconstriction. In recent years, there has been increased understanding of the pathophysiology of exercise-induced bronchoconstriction. Although evaporative water loss and thermal changes have been recognized stimuli for exercise-induced bronchoconstriction, accumulating evidence points toward a pivotal role for the airway epithelium in orchestrating the inflammatory response linked to exercise-induced bronchoconstriction. Overproduction of inflammatory mediators, underproduction of protective lipid mediators, and infiltration of the airways with eosinophils and mast cells are all established contributors to exercise-induced bronchoconstriction. Sensory nerve activation and release of neuropeptides maybe important in exercise-induced bronchoconstriction, but further research is warranted.

Exercise-Induced Bronchoconstriction and the Air We Breathe.

An association between airway dysfunction and airborne pollutant inhalation exists. Volatilized airborne fluorocarbons in ski wax rooms, particulate matter, and trichloromines in indoor environments are suspect to high prevalence of exercise-induced bronchoconstriction and new-onset asthma in athletes competing in cross-country skiing, ice rink sports, and swimming. Ozone is implicated in acute decreases in lung function and the development of new-onset asthma from exposure during exercise. Mechanisms and genetic links are proposed for pollution-related new-onset asthma. Oxidative stress from airborne pollutant inhalation is a common thread to progression of airway damage. Key pollutants and mechanisms for each are discussed.

Exercise-Induced Bronchoconstriction: Background, Prevalence, and Sport Considerations.

The transient airway narrowing that occurs as a result of exercise is defined as exercise-induced bronchoconstriction (EIB). The prevalence of EIB has been reported to be up to 90% in asthmatic patients, reflecting the level of disease control. However, EIB may develop even in subjects without clinical asthma, particularly in children, athletes, patients with atopy or rhinitis, and following respiratory infections. The intensity, duration, and type of training have been associated with the occurrence of EIB. In athletes, EIB seems to be only partly reversible, and exercise seems to be a causative factor of airway inflammation and symptoms.

Testing for Exercise-Induced Bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) is a form of airway hyperresponsiveness that occurs with or without current symptoms of asthma. EIB is an indicator of active and treatable pathophysiology in persons with asthma. The objective documentation of EIB permits the identification of an individual who may be at risk during a recreational sporting activity or when exercising as an occupational duty. EIB can be identified with laboratory exercise testing or surrogate tests for EIB. These include eucapnic voluntary hyperpnea and osmotic stimuli (eg, inhaled mannitol) and offer improved diagnostic sensitivity to identify EIB and improved standardization when compared with laboratory exercise.

Pharmacologic Strategies for Exercise-Induced Bronchospasm with a Focus on Athletes.

Exercise-induced bronchoconstriction (EIB) is the transient narrowing of the airways during and after exercise that occurs in response to increased ventilation in susceptible individuals. It occurs across the age spectrum in patients with underlying asthma and can occur in athletes without baseline asthma. The inflammatory mechanisms underlying EIB in patients without asthma may be distinct from those underlying EIB in patients with asthma. This review summarizes mechanistic and clinical data that can guide the choice of chronic and acute pharmacologic therapies targeting control of EIB. Relevant regulations from the World Anti-Doping Agency are also discussed.

Nonpharmacologic Strategies to Manage Exercise-Induced Bronchoconstriction.

Pharmacologic management of exercise-induced bronchoconstriction (EIB) is the mainstay of preventative therapy. There are some nonpharmacologic interventions, however, that may assist the management of EIB. This review discusses these nonpharmacologic interventions and how they may be applied to patients and athletes with EIB.

An unusual case of wheat dependent exercise induced anaphylaxis (WDEIA) triggered by Tri a 14 in a pediatric patient: a case report.

Summary: Anakinra, one of the novel biological agents, is a recombinant human IL-1 receptor antagonist. It is preferred as an alternative drug for familial Mediterranean fever cases where colchicine is not sufficient or cannot be used due to its side effects. Like all other biologics, hypersensitivity reactions to anakinra are quite rare. This is the first case which was successfully desensitized with anakinra after a severe immediate-type hypersensitivity reaction. We report a case of WDEIA in an asthmatic boy admitted to our Unit with suspected mushroom acute toxicity. The symptoms occurred during a gym session, approximately 2 hours after the ingestion of a meal based on pasta and cooked mushroom found in the family's garden. Acute toxicity due to mushroom ingestion was then excluded. Triptase serum levels resulted elevated in acute phase and normal after 24 hours. Food specific IgE showed a sensitization to lipid transfer protein Pru p 3 and to Tri a 14. This case highlights that WDEIA is underdiagnosed, especially when patients are firstly visited in Emergency Unit. Moreover, Tri a 14 is seldom described as responsible for WDEIA, compared to omega 5 gliadin.

Respiratory inflammation and infections in high-performance athletes.

Upper respiratory illness is the most common reason for non-injury-related presentation to a sports medicine clinic, accounting for 35-65% of illness presentations. Recurrent or persistent respiratory illness can have a negative impact on health and performance of athletes undertaking high levels of strenuous exercise. The cause of upper respiratory symptoms (URS) in athletes can be uncertain but the majority of cases are related to common respiratory viruses, viral reactivation, allergic responses to aeroallergens and exercise-related trauma to the integrity of respiratory epithelial membranes. Bacterial respiratory infections are uncommon in athletes. Undiagnosed or inappropriately treated asthma and/or allergy are common findings in clinical assessments of elite athletes experiencing recurrent URS. High-performance athletes with recurrent episodes of URS should undergo a thorough clinical assessment to exclude underlying treatable conditions of respiratory inflammation. Identifying athletes at risk of recurrent URS is important in order to prescribe preventative clinical, training and lifestyle strategies. Monitoring secretion rates and falling concentrations of salivary IgA can identify athletes at risk of URS. Therapeutic interventions are limited by the uncertainty of the underlying cause of inflammation. Topical anti-inflammatory sprays can be beneficial for some athletes. Dietary supplementation with bovine colostrum, probiotics and selected antioxidants can reduce the incidence or severity of URS in some athletes. Preliminary studies on athletes prone to URS indicate a genetic predisposition to a pro-inflammatory response and a dysregulated anti-inflammatory cytokine response to intense exercise as a possible mechanism of respiratory inflammation. This review focuses on respiratory infections and inflammation in elite/professional athletes.

Increased postexercise lipoxin A4 levels in exhaled breath condensate in asthmatic children with exercise-induced bronchoconstriction

Background: Lipoxins could be potential modulators of inflammation in the lungs. To our knowledge, the role of exhaled breath condensate (EBC) lipoxin A4 (LXA4) in asthmatic children with exercise-induced bronchoconstriction (EIB) has not been investigated. Objective: The aim of our study was to determine the involvement of EBC LXA4 in EIB. Methods: Forty-five patients aged between 5 and 17 years were included in the study. Patients were divided into 2 groups: asthmatic children with a positive response to exercise (n=17) and asthmatic children with a negative response to exercise (n=28). Levels of LXA4 were determined in EBC before and immediately after the exercise challenge using ELISA. Results: EBC LXA4 levels were significantly increased immediately after exercise in asthmatic children with a positive response to the exercise challenge (P=.05). No significant differences were observed in children with a negative response to exercise (P>.05). There was an inverse correlation between LXA4 levels and the percent degree of reduction in forced expiratory volume in the first second (FEV1%) postexercise in children with a positive exercise challenge (P=.05, r=-0.50). No significant differences were observed in LXA4 levels between atopic and nonatopic asthmatics (P>.05, Mann-Whitney U test). Conclusions: Levels of EBC LXA4 increased immediately after exercise in asthmatic children with a positive exercise challenge response. We hypothesize that airway LXA4 levels increase to compensate bronchoconstriction and suppress acute inflammation, and that spontaneous bronchodilatation after EIB may be due to LXA4 (AU)

Introducción: Las lipoxinas pueden actuar potencialmente como inmunomoduladores de la actividad inflamatoria en el pulmón. A nuestro entender, el papel de la lipoxina A4 (LXA4), determinada en condensado de aire exhalado (EBC) en niños asmáticos con broncoconstricción inducida por el ejercicio (BEI) no ha sido previamente investigado. Objetivo: El objetivo de nuestro estudio fue determinar la implicación de la LXA4 determinada en EBC, en el broncoespasmo inducido por ejercicio. Métodos: Se incluyeron en el estudio un total de cuarenta y cinco pacientes de edades comprendidas entre 5 y 17 años. Los pacientes se dividieron en dos grupos: niños asmáticos con respuestas positivas (n = 17) y negativas (n = 28) a la provocación bronquial con ejercicio. Los niveles de LXA4 en EBC se determinaron inmediatamente antes y después de la provocación bronquial mediante un método ELISA. Resultados: Los niveles de LXA4 en EBC aumentaron significativamente tras la provocación con ejercicio en aquellos niños asmáticos con respuestas positivas en la provocación (p = 0,05). Sin embargo, no pudimos encontrar ninguna diferencia estadísticamente significativa en pacientes con respuesta negativa al ejercicio (p > 0,05). Hubo una correlación inversa entre el incremento de los niveles de LXA4 y el grado de reducción porcentual del volumen espiratorio forzado en un segundo (FEV1%) en los pacientes con respuesta positiva a la provocación (p = 0,05, r = -0,50). No se observaron diferencias significativas en los niveles de LXA4 entre asmáticos alérgicos y no alérgicos (p> 0,05, prueba de Mann-Whitney). Conclusiones: Los niveles de EBC LXA4 se incrementan inmediatamente después de la broncoconstricción inducida por el ejercicio en niños asmáticos. Se postula que los niveles de las vías respiratorias aumentan LXA4 para suprimir la inflamación aguda en la vía respiratoria, y podrían ser responsables de la inducción de broncodilatación espontánea que aparece tras el EIB (AU)

Measurement of lung function and bronchial inflammation in children is underused by spanish allergists

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Damage-associated molecular pattern and innate cytokine release in the airways of competitive swimmers.

BACKGROUND: Daily intensive exercise by elite athletes can result in exercise-induced asthma especially in elite swimmers and this may be linked to epithelial damage. OBJECTIVE: To study airway epithelial damage and release of damage-associated molecular patterns (DAMPs) after intensive exercise in elite athletes and controls. METHODS: We recruited competitive swimmers (n = 26), competitive indoor athletes (n = 13) and controls (n = 15) without any history of asthma. Lung function was measured before, immediately after and 24 h after a 90-min intensive exercise protocol. Sputum induction was performed at baseline and 24 h after exercise. Exercise-induced bronchoconstriction (EIB) was assessed by the eucapnic voluntary hyperventilation test. RESULTS: Baseline sputum uric acid, high mobility group box-1, CXCL8 mRNA, sputum neutrophils and serum Clara cell protein-16 (CC-16) were significantly higher in competitive swimmers compared with controls. Intensive swimming for 90 min resulted in an increase of sputum IL-1ß, IL-6 and TNF mRNA in competitive swimmers, and of sputum IL-6 mRNA and sputum neutrophils in controls. Although all participants were asymptomatic, seven competitive swimmers, one indoor athlete and one control met the criteria for EIB. CONCLUSION: Our findings show that the intensive training combined with exposure to by-products of chlorination induces airway epithelial damage in competitive swimmers. This is associated with increased damage-associated molecular patterns, innate cytokine release and neutrophilic airway inflammation.

Developing and emerging clinical asthma phenotypes.

For more than a century, clinicians have attempted to subdivide asthma into different phenotypes based on triggers that cause asthma attacks, the course of the disease, or the prognosis. The first phenotypes that were described included allergic asthma, intrinsic or nonallergic asthma, infectious asthma, and aspirin-exacerbated asthma. These phenotypes are being reviewed elsewhere in this issue of the journal. The present article focuses on developing and emerging clinical asthma phenotypes. First, asthma phenotypes that are associated with environmental exposures (occupational agents, cigarette smoke, air pollution, cold dry air); second, asthma phenotypes that are associated with specific symptoms or clinical characteristics (cough, obesity, adult onset of disease); and third, asthma phenotypes that are based on biomarkers. This latter approach is the most promising because it attempts to identify asthma phenotypes with different underlying mechanisms so that therapies can be better targeted toward disease-specific features and disease outcomes can be improved.