Obesity is a risk factor for exercise-induced bronchospasm in asthmatic adolescents.

INTRODUCTION: Exercise-induced bronchospasm (EIB) is common in young asthmatics and obesity is becoming an epidemic in this population. Both conditions can give rise to or worsen respiratory symptoms upon exercise and may interfere with recreational and sports activities. OBJECTIVE: To investigate the association between obesity and the risk and severity of EIB in asthmatic children and adolescents. METHODS: This study included data from asthmatic patients aged between 7 and 19 years undergoing treadmill running tests to evaluate EIB, defined as a reduction greater than or equal to 10% in forced expiratory volume in the first second (FEV1 ) compared to baseline. Eutrophic, obese, and overweight individuals were categorized according to body mass index z-score (eutrophic, -0.5 < z ≤ 1; overweight, 1 < z < 2; and obese, z ≥ 2). RESULTS: Of the 156 individuals studied (42% female), 58% were eutrophic, 22% overweight, and 19% obese. Seventy-three individuals (47%) presented with EIB, with higher risk among obese (OR, 2.86; 95% CI, 1.00-8.14; P = .05). Asthma severity was another independent risk factor for EIB (OR, 2.95; 95% CI, 1.36-6.42; P = .006). The number of patients in whom FEV1 returned to baseline values (difference less than 10% from baseline) at the 13th minute after challenge was lower in obese individuals compared to eutrophic and overweight ones (P = .04). Baseline FEV1 , gender, or age were not found to be risk factors for EIB in any of the groups. CONCLUSION: Obese youngsters with asthma present a greater risk for EIB with slower recovery than their nonobese peers. Clinicians should be aware of this association, especially in those with more severe disease, for adequate recognition and treatment.

The ß2-adrenergic receptor-ROS signaling axis: An overlooked component of ß2AR function?

ß2-Adrenergic receptor (ß2AR) agonists are clinically used to elicit rapid bronchodilation for the treatment of bronchospasms in pulmonary diseases such as asthma and COPD, both of which exhibit characteristically high levels of reactive oxygen species (ROS); likely secondary to over-expression of ROS generating enzymes and chronically heightened inflammation. Interestingly, ß2AR has long-been linked to ROS, yet the involvement of ROS in ß2AR function has not been as vigorously studied as other aspects of ß2AR signaling. Herein, we discuss the existing body of evidence linking ß2AR activation to intracellular ROS generation and importantly, the role of ROS in regulating ß2AR function. The reciprocal interplay of the ß2AR and ROS appear to endow this receptor with the ability to self-regulate signaling efficacy and ligand binding, hereby unveiling a redox-axis that may be unfavorably altered in pathological states contributing to both disease progression and therapeutic drug responses.

FUNCTION OF EXTERNAL RESPIRATION AND MARKERS OF OXIDATIVE STRESS IN CHILDREN-RESIDENTS OF RADIOACTIVELY CONTAMINATED TERRITORIES. / FUNKTsIIa ZOVNIShN'OGO DYKhANNIa I MARKERY OKSYDATYVNOGO STRESU U DITEY̆ ­ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆.

OBJECTIVE: to evaluate the influence of processes of lipid peroxidation, and antioxidant protection on the function of external respiration in children-residents of radioactive contaminated territories. MATERIALS AND METHODS: There were examined children of school age, inhabitants of radioactive contaminated ter- ritories (RCT) without respiratory and pulmonary pathology, and patients with bronchial asthma (BA). Examination of the ventilation lung function was performed by the method of pneumotachography according to the analysis of the «flow-volume¼ loop. End products of lipid peroxidation (LPO), reacting with thiobarbituric acid (malondialde- hyde), enzymes-antioxidants - catalase, superoxide dismutase, glutathione peroxidase, glutathione transferase were studied to determine the signs of oxidative stress. RESULTS: Examinations of ventilation lung function in children-residents of RCT without respiratory and pulmonary pathology showed no significant deviations of its parameters beyond the limits of physiological fluctuations; a decrease in bronchial patency at different levels of the bronchial tree was established in children with BA. An increased incidence of bronchial hyperreactivity was noted in both the patients with BA and those who did not have bronchopulmonary pathology. The absence of an increase in the content of LPO products (malondialdehyde) in blood serum of children-residents of RCT with increased activity of catalase and group of glutathione enzymes indi- cates the sufficiency of compensatory possibilities of antioxidant protection. CONCLUSIONS: Studies of correlation between the function of external respiration and markers of oxidative stress determined that the indices of bronchial patency directly correlate with the activity of enzymes-antioxidants of the glutathione group and inversely - with the content of the LPO products in children-residents of RCT. The frequency of bronchospasm inversely correlated with the activity of glutathione group antioxidants. There are inverse correla- tion of 137Cs content in the body with the activity of glutathione transferase and glutathione peroxidase.

Cocaine-Induced Bronchospasm Mimicking Acute Asthma Exacerbation.

Cocaine can cause a myriad of changes in the lung, which can range from bronchoconstriction to destruction of the alveolar-capillary membrane and acute lung injury. Cocaine-induced bronchospasm is a diagnosis of exclusion that should be considered when the clinical presentation of acute hypoxic and hypercapneic respiratory failure cannot be explained by chronic obstructive pulmonary disease or asthma exacerbation, anaphylaxis to food or medications, exercise, or infection. Here, we present two patients with acute hypoxic and hypercapneic respiratory failure that was ultimately attributed to cocaine use shortly prior to symptom onset.

Acute Management, Diagnosis, and Follow-Up of Suspected Perioperative Hypersensitivity Reactions in Flanders 2001-2018.

BACKGROUND: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists. OBJECTIVE: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium. METHODS: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia. RESULTS: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine. CONCLUSIONS: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA.

FEATURES OF NITRIC OXIDE METABOLISM AND RISK OF DEVELOPING ENDOTHELIAL DYSFUNCTION IN CHILDREN WITH e-NOS GENE 4a/4b POLYMORPHISM UNDER LONG-TERM ENTERING 137Cs TO BODY. / OSOBLYVOSTI METABOLIZMU OKSYDU AZOTU TA RYZYK ROZVYTKU ENDOTELIAL'NOÏ DYSFUNKTsIÏ U DITEI Z 4a/4b POLIMORFIZMOM GENA eNOS PRY TRYVALOMU NADKhODZhENNI 137Cs DO ORGANIZMU.

OBJECTIVE: To determine the features of the nitrogen oxide metabolism and risk of developing endothelial dysfunc-tion in children with e-NOS 4a/4b gene polymorphism, who live under prolonged enter 137Cs to the body. MATERIALS AND METHODS: There were examined 117 children-residents of radioactively contaminated territories and50 children of control group. The level of stable metabolites was defined in blood serum (NO2- and NO3-). The ther-mographic method was used to register the endothelium dependent reaction of the vascular bed to changes in theblood supply. The ventilation capacity of the lungs was evaluated using this method of pneumotachography.Polymorphism in intron 4 of the gene e-NOS was studied by the method of polymerase chain reaction. The contentof 137Cs in the body of children was determined using a human radiation counter Skrynner M-3. RESULTS AND CONCLUSIONS: In children-residents of radioactively contaminated territories with genotype 4a/4b com-paring to children who had genotype 4b/4b, the decrease in the nitric content of in the blood serum, the increase inthe thermographic index of the recovery period of blood circulation to the baseline level after occlusion test werenoted, that is indicative of the decreased NO-synthase active of vascular endothelium in the carriers of the minorallele a in the 4th intron of gene eNOS (genotype 4a/4b), and is a risk factor for development of endothelial dysfunc-tion. It was proved a decrease in the index of lung tissue elasticity and stretchability - FVC / NFVC of the lungs com-paring to children with genotype 4b/4b, there was a reduction of integral index of respiratory tract permeability -FEV1/NFEV1. The inverse correlation dependence between the presence of allele a in the genotype and the values ofFVC/NFVC of the lungs (r = -0.259; p <0.05) and FEV1/NFEV1 (r = -0.2267; p <0.05) was found. Signs of bron-chospasm were found in the carriers of the allele a in 1.5 times more often than in children-carriers of homozy-gotes from allele b.

Noninvasive ventilation and respiratory physical therapy reduce exercise-induced bronchospasm and pulmonary inflammation in children with asthma: randomized clinical trial.

BACKGROUND: Asthma is characterized by hyperresponsiveness of the airways, and exercise-induced bronchospasm (EIB) is a symptom that limits a large proportion of asthmatic patients, especially children. Continuous positive airway pressure (CPAP) leads to a reduction in the reactivity of the airways. The aim of this study was to evaluate the effect of outpatient treatment with CPAP and bilevel pressure combined with respiratory physical therapy for children and adolescents with asthma following bronchial hyperresponsiveness caused by an exercise bronchoprovocation test. METHODS: A randomized, controlled, blind, clinical trial was conducted involving 68 asthmatic children and adolescents aged 4 to 16 years divided into three groups: G1, treated with bilevel pressure (inspiratory positive airway pressure: 12 cm H2O; expiratory positive airway pressure: 8 cm H2O), G2, treated with CPAP (8 cm H2O) and G3, treated with respiratory muscle training (RMT), considered as the control group. All groups were treated at an outpatient clinic and submitted to 10 1-hour sessions, each of which also included respiratory exercises. Evaluations were performed before and after treatment and involved spirometry, an exercise bronchoprovocation test, respiratory pressures, fraction of nitric oxide (FeNO), the Asthma Control Questionnaire (ACQ6) and anthropometric variables. This study received approval from the local ethics committee (certificate number: 1487225/2016) and is registered with ClinicalTrials [ ClinicalTrials.gov identifier: NCT02939625]. RESULTS: A total of 64 patients concluded the protocol; the mean age of the patients was 10 years. All were in the ideal weight range and had adequate height ( z score: -2 to +2). The three groups demonstrated improved asthma control after the treatments, going from partial to complete control. A significant increase in maximal inspiratory pressure occurred in the three groups, with the greatest increase in the RMT group. A reduction in FeNO in the order of 17.4 parts per billion (effect size: 2.43) and a reduction in bronchial responsiveness on the exercise bronchoprovocation test occurred in the bilevel group. An improvement in FeNO on the order of 15.7 parts per billion (effect size: 2.46) and a reduction in bronchial responsiveness occurred in the CPAP group. No changes in lung function or responsiveness occurred in the RMT group. CONCLUSION: Positive pressure and respiratory exercises were effective in reducing pulmonary inflammation, exercise-innduced bronchoespasm (EIB), and increased the clinical control of asthma, as well as RMT, which also resulted in improved clinical control.

Evaluating the Athlete with Suspected Exercise-Induced Asthma or Bronchospasm.

Exercise-induced asthma (EIA) and exercise-induced bronchospasm (EIB)/bronchoconstriction (EIC) describes two clinical entities by which exercise triggers bronchial hyperresponsiveness. Exercise is a common trigger of bronchospasm in the asthmatic (EIA), as well as athletes without the underlying inflammation associated with asthma (EIC/EIB). Approximately 10% to 20% of the general population have EIA or EIB (). The approach to the diagnosis and subsequent management relies on the clinician's ability to recognize clinical signs and symptoms, then selecting the correct diagnostic test. A baseline spirometry/pulmonary function test is recommended for all athletes to evaluate for underlying asthma. Subsequent direct or indirect bronchial provocation testing is recommended to correctly diagnose EIA or EIB (). Athletes should not be treated empirically with bronchodilators based on symptoms alone without confirmatory spirometry and provocative testing.

Mechanistic link between diesel exhaust particles and respiratory reflexes.

BACKGROUND: Diesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms and asthma exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms, such as cough and bronchospasm. OBJECTIVE: We sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs. METHODS: In this study we use in vitro and in vivo electrophysiologic techniques, including a unique model that assesses depolarization (a marker of sensory nerve activation) of human vagus. RESULTS: We demonstrate a direct interaction between DEP and airway C-fiber afferents. In anesthetized guinea pigs intratracheal administration of DEPs activated airway C-fibers. The organic extract (DEP-OE) and not the cleaned particles evoked depolarization of guinea pig and human vagus, and this was inhibited by a transient receptor potential ankyrin-1 antagonist and the antioxidant N-acetyl cysteine. Polycyclic aromatic hydrocarbons, major constituents of DEPs, were implicated in this process through activation of the aryl hydrocarbon receptor and subsequent mitochondrial reactive oxygen species production, which is known to activate transient receptor potential ankyrin-1 on nociceptive C-fibers. CONCLUSIONS: This study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea pig and human sensory nerves, which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible subjects who are most at risk.

Experience of correcting endothelial dysfunction in children-residents of radioactively contaminated areas by nitric oxide potential donator citrulline. / DOSVID KOREKTsIÏ ENDOTELIAL'NOÏ DYSFUNKTsIÏ U DITEY̆, MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆, ZA DOPOMOGOIu POTENTsIY̆NOGO DONATORA OKSYDU AZOTU ­ TsYTRULINU.

OBJECTIVE: to determine the effectiveness of citrulline use for correcting endothelial dysfunction in children resi dents of radioactively contaminated areas. MATERIALS AND METHODS: A group of children residents of radioactively contaminated areas with the presence of clinical and paraclinical signs of endothelial dysfunction was selected to assess the effectiveness of correcting endothelial dysfunction by the usage of NO potential donator - citrulline according to the data of selective screen ing. There were determined the biochemical parameters of the content of NO stable metabolites, L arginine, lipid peroxidation, antioxidant enzymes in the blood serum; the indices of cellular and humoral immunity; the instrumen tal indices of vascular endothelium dependent reaction on occlusion test, the lung ventilation capacity, the bioelec tric activity of the myocardium, the autonomic regulation of the cardiovascular system.Examined children were received a course of citrulline malate. RESULTS AND CONCLUSIONS: An increased content of serum L arginine, nitrite, and amounts of NO metabolites was established in children with endothelial dysfunction who were received a course of citrulline malate. Bronchospasm elimination was noted in the significant part of examined patients after the drug use. Decreased recovery period and increased period of hypercompensation for thermographic circulation index in the test with post occlusion reac tive hyperemia were detected by an evaluation of indicators for vascular endothelium dependent vasodilatation using thermographic method indicating an increased endothelial vasomotor capacity. There was tendency to improve the processes of autonomic regulation of the heart rhythm and repolarization of the heart muscle. The antioxidant effect of used citrulline malate course was determined as: decreased content of serum LPO end products that react with thiobarbituric acid under elevated activity of antioxidant - catalase. An increase in the percentage of T lymphocyte, normalization of their subpopulation composition was noted in dynamics of citrulline malate application.

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Exercise-induced bronchospasm in a hot and dry region: study of asthmatic, rhinitistic and asymptomatic adolescents.

BACKGROUND: Exercise-induced bronchospasm (EIB) is the bronchial narrowing that occurs after intense exercise in a significant number of asthmatics and in some non-asthmatics. This study aims to evaluate the occurrence of EIB in adolescents with asthma, rhinitis and respiratory asymptomatics in a hot and dry climate. RESEARCH DESIGN AND METHODS: This is a cross-sectional study based on an epidemiological study that evaluated the prevalence of asthma in schoolchildren in a semi-arid zone of Brazil. The EIB was defined as a reduction in forced expiratory volume in first second (FEV1) greater than 10%. RESULTS: A total of 114 individuals participated in the study (36.8% male), of whom 54 were asymptomatic, 30 asthmatic and 30 with rhinitis. Asthmatics presented a higher proportion of EIB in comparison to rhinitis and asymptomatics (46.7% vs. 13.3% and 7.4%, p = 0.001) and none of the individuals had severe EIB (ΔFEV1 ≥ 50%). CONCLUSIONS: A large proportion of the asthmatics selected from the community for the clinical study had EIB. Among participants with rhinitis, EIB was found in slightly more than 10%, while in the asymptomatics the frequency was slightly more than 5%. This study presents an important aspect in individuals living in hot and dry climates.

[Mediators of inflammatory response in asthma and its association with obesity]. / Mediadores de la respuesta inflamatoria en asma y su relación con obesidad.

There is an increase in the prevalence of asthma and obesity, constituting a public health problem at national and global levels. The association between the two pathologies has not been clearly determined; however, a certain synergy has been proposed, which leads to more severe bronchospasms, longer recovery time, and more prolonged use of medications in obese asthmatic patients. The discovery of leptin, an adipokine that is directly related to the amount of total body fat and the production of proinflammatory cytokines, has generated greater interest in white adipose tissue. Our objective was to describe the possible mechanisms involved and the association between obesity and asthma. A bibliographic search was conducted in the scientific literature using the National Biotechnology Information Center (NCBI) database of the USA as a search tool; keywords used were: asthma, leptin, obesity and inflammation. There are numerous clinical and experimental studies that explore the role of obesity as an inflammatory entity in asthma, some of which have evaluated the role of "shared" genetic polymorphisms in both pathologies. Apparently, the interaction between asthma and obesity is complex, there are mechanisms that link both pathologies, these can influence the improvement or exacerbation of symptoms.

El incremento en la prevalencia de asma y obesidad constituye un problema de salud pública en los ámbitos nacional y mundial. Se ha propuesto una sinergia entre estas patologías que genera broncoespasmos más severos, mayor tiempo de recuperación y uso de medicamentos por un lapso más prolongado en los pacientes asmáticos con obesidad. El descubrimiento de la leptina, relacionada directamente con la cantidad de grasa corporal total y la producción de citocinas proinflamatorias ha generado mayor interés en el tejido adiposo blanco. El objetivo de esta investigación fue describir la asociación entre obesidad, asma y los mecanismos fisiopatológicos involucrados. Se realizó una búsqueda bibliográfica en la literatura científica empleando el Centro Nacional de Información sobre Biotecnología (NCBI) de Estados Unidos como herramienta de búsqueda; las palabras claves utilizadas fueron asma, leptina, obesidad e inflamación. Numerosos estudios clínicos y experimentales exploran la participación de la obesidad como una entidad inflamatoria en el asma; algunos han evaluado el papel de polimorfismos genéticos "compartidos" por ambas patologías. Al parecer, existen mecanismos comunes a ambas patologías que pueden influir en la exacerbación de los síntomas del asma en pacientes con obesidad.

Exhaled Breath Condensate Acidification Occurs During Surgery for Abdominal Cancer.

BACKGROUND/AIM: Acidification of exhaled breath condensate (EBC), reflecting airway inflammation and oxidative stress, has been reported in lung cancer patients undergoing lobectomy. We undertook this study to examine EBC pH changes during surgery for abdominal cancer. PATIENTS AND METHODS: EBC pH was measured from 20 patients undergoing abdominal cancer resection before and during surgery. Repeated-measures of ANOVA and random-effects linear models were applied to compare mean EBC pH values in samples collected at different times. Cox and linear regression models were used to determine the association of EBC pH with occurrence of acute bronchospasm intra-operatively and the duration of hospitalization. RESULTS: Significant acidification of EBC was observed during surgery (p=0.007) associated with 0.77% (95% confidence interval=-0.14-1.68, p-value=0.097) increase in the risk for developing acute bronchospasm, after adjustment for potential confounders. CONCLUSION: EBC acidification occurs in patients undergoing abdominal cancer resection and is associated with the occurrence of acute bronchospasm intraoperatively.

Bedside Breath-Wise Visualization of Bronchospasm by Electrical Impedance Tomography Could Improve Perioperative Patient Safety: A Case Report.

Bronchospasm appears in up to 4% of patients with obstructive lung disease or respiratory infection undergoing general anesthesia. Clinical examination alone may miss bronchospasm. As a consequence, subsequent (mis)treatment and ventilator settings could lead to pulmonary hyperinflation, hypoxia, hypercapnia, hypotension, patient-ventilator asynchrony, volutrauma, or barotrauma. Electrical impedance tomography (EIT), a new noninvasive technique, can potentially identify bronchospasms by determining regional expiratory time constants (τ) for each one of the pixels of a functional EIT image. We present the first clinical case that highlights the potential of breath-wise EIT-based τ images of the lung to quickly identify bronchospasm at the bedside, which could improve perioperative patient management and safety.