Respiratory muscles's thermographic analysis in asthmatic youth with and without bronchospasm induced by eucapnic voluntary hyperpnea.

OBJECTIVE: To compare the thermographic pattern of regions of interest (ROI) of respiratory muscles in young asthmatics with and without bronchospasm induced by eucapnic voluntary hyperpnea (EVH). MATERIALS AND METHODS: Cross-sectional study carried out with 55 young (55% male and 45% females) aged 12.5 ± 3.3 years, divided in nine nonasthmatics, 22 asthmatics without exercise-induced bronchospasm compatible response (EIB-cr) and 24 asthmatics with EIB-cr. The diagnosis of EIB was given to subjects with a fall in forced expiratory volume in the first second (FEV1) ≥ 10% compared to baseline. Thermographic recordings of respiratory muscles were delimited in ROI of the sternocleidomastoid (SCM), pectoral, and rectus abdominis intention area. Thermal captures and FEV1 were taken before and 5, 10, 15 and 30 min after EVH. RESULTS: Twenty-four (52.1%) of asthmatics had EIB-cr. There was a decrease in temperature at 10 min after EVH test in the SCM, pectoral and rectus abdominis ROIs in all groups (both with p < 0.05). There was a decrease in temperature (% basal) in asthmatic with EIB-cr compared to nonasthmatics in the rectus abdominis area (p < 0.05). CONCLUSION: There was a decrease in temperature in the ROIs of different muscle groups, especially in asthmatics. The greater drop in FEV1 observed in individuals with EIB-cr was initially associated with a decrease in skin temperature, with a difference between the nonasthmatics in the abdominal muscle area. It is likely that this decrease in temperature occurred due to a temporary displacement of blood flow to the most used muscle groups, with a decrease in the region of the skin evaluated in the thermography.

Análisis bibliométrico de la producción científica cubana sobre asma en Scopus

Introducción: El asma es una entidad con alta prevalencia a nivel mundial y en Cuba, que ha suscitado nuevas investigaciones. Objetivo: Caracterizar la producción científica cubana sobre asma en la base de datos Scopus. Materiales y métodos: Se realizó un estudio observacional, descriptivo y bibliométrico de los artículos publicados sobre asma en Scopus con autores cubanos, desde 1973 hasta 2021. Para la recuperación de los registros se empleó una fórmula de búsqueda. Para el análisis de los datos se usaron los software Bibexcel y VOSviewer. Resultados: Se publicaron 154 investigaciones sobre asma, con predominio de artículos originales (136) y de revisión (12). Las áreas más productivas fueron Medicina (144) e Inmunología y Microbiología (34). Los artículos fueron publicados en 48 revistas; de ellas, 11 fueron cubanas, con la Revista Cubana de Medicina como la más productiva. México aportó el mayor número de colaboraciones (10). El Hospital Clínico Quirúrgico Docente General Calixto García (15) fue el más productivo. Se identificaron tres clústeres de palabras clave, con "human", "asthma" y "Cuban" como términos centrales y de mayor ocurrencia. Conclusiones: Existió una baja producción científica sobre asma, centrada principalmente en artículos originales, en el área de Medicina y en revistas nacionales. Se evidenció colaboración internacional. Los ejes principales de investigación fueron el diagnóstico, tratamiento, investigación básica en modelos animales, nuevas terapéuticas, factores de riesgo y prevención.

Introduction: Asthma is an entity with high prevalence worldwide and in Cuba, which has prompted new research. Objective: To characterize Cuban scientific production on asthma in the Scopus database. Materials and methods: An observational, descriptive and bibliometric study was carried out on articles on asthma published in Scopus by Cuban authors, from 1973 to 2021. A search formula was used to retrieve the records. Bibexcel and VOSviewer were used for data analysis. Results: 154 research papers on asthma were published; with a predominance of original (136) and review articles (12). The most productive areas were Medicine (144) and Immunology and Microbiology (34). Articles were published in 48 journals, of which 11 were Cuban, with the Revista Cubana de Medicina (Cuban Journal of Medicine) being the most productive. Mexico contributed the highest number of collaborations (10). The Teaching Hospital General Calixto García (15) was the most productive. 3 key word clusters were identified, with "human", "asthma" and "Cuban" as central and most occurring terms. Conclusions: There was a low scientific production on asthma, mainly focused on original articles, in the area of Medicine and in national journals. International collaboration was evident. The main areas of research were diagnosis, treatment, basic research in animal models, new therapeutics, risk factors and prevention.

Beyond forced exhalation: impulse oscillometry as a promising tool for bronchial hyperresponsiveness evaluation.

Introduction: The multiple forced expiratory maneuvers that must be performed during methacholine test require a high degree of collaboration and can lead to fatigue. However, impulse oscillometry (IOS) is a noninvasive test, quick and easy to perform, that does not require effort-dependent maneuvers.Objectives: The primary endpoint was to evaluate the relationship between IOS and spirometry during the methacholine test. The secondary endpoint was to study the predictive value of baseline IOS in the development of bronchial hyperreactivity.Methods: Observational, prospective, cross-sectional study, with recruitment of consecutive patients from the pulmonology department with clinical suspicion of bronchial asthma with negative bronchodilator test and normal FeNO.Results: Twenty-five patients were included, with a mean age of 49 ± 18 years. Thirteen patients (52%) had a positive methacholine test. The correlation between IOS indices and FEV1 was significant (p < 0.05) in all cases. The indices with the highest predictive power were R5-20 and AX. The optimal cutoff points were an increase of greater than 32.96% in R5, greater than 120.83% for X5, an increase of 30.30 [kPa l-1s-1] in R5-20, and an increase of 1.01 [kPa l-1] for AX. Baseline oscillometry demonstrated a strong predictive value in the development of bronchial hyperreactivity, with a sensitivity of 61.5% and a specificity of 91.7%, using the cut-off point of 160.0% for R5.Conclusions: IOS may be a valuable alternative to forced spirometry in detecting bronchial hyperreactivity during the methacholine test, showing a good correlation between both tests.

Association between the Consumption of Ultra-Processed Foods and Asthma in Adults from Ribeirão Preto, São Paulo, Brazil.

BACKGROUND: Ultra-processed Food (UPF) consumption can play a role in the pathogenesis and progression of asthma. The aim of this study was to evaluate the association between the consumption of UPF and asthma. METHODS: This cross-sectional study included 1857 adults aged 23-25 years from the Ribeirão Preto-SP birth cohort (1978/1979). The exposure variable was the consumption of UPF (expressed as their percentage contribution to energy intake-% total caloric value [%TCV] and their percentage contribution to the amount of food ingested-%grams), which was assessed with a food frequency questionnaire. Asthma was the outcome and was defined based on a positive methacholine challenge test and the presence of wheezing, chest tightness, or shortness of breath over the last 12 months. Poisson regression with robust variance was used to estimate the association between these variables. Unadjusted analyses and analyses adjusted for sex, age, household income, smoking, and physical activity level were performed. RESULTS: The prevalence of asthma in the sample was 13.2%. The mean total consumption of UPF was 37.9 ± 11.2% TCV (corresponding to 35.1 ± 15.1% grams). There was no association between the consumption of UPF and asthma in adults. CONCLUSION: This study provides no evidence for an association between the consumption of UPF and asthma in young adults.

Can development of asthma and bronchial hyperreactivity be reduced by subcutaneous immunotherapy in adult patients with allergic rhinitis?

BACKGROUND: Allergic rhinitis can be associated with bronchial hyperreactivity (BHR) and create an increased risk for allergic asthma development. We aimed to investigate the effects of subcutaneous immunotherapy (SCIT) on BHR and asthma development in adult patients with allergic rhinitis. METHODS: The retrospective case-control study was carried out between November 2018 and May 2019 in Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital. In this study, data was recorded for patients with a mite and/or grasses/cereals pollen allergy who were tested for BHR before planned SCIT, and who had allergic rhinitis, with or without asthma. The SCIT group was selected as those who received SCIT for at least one year. The control group was selected from those who were scheduled to receive SCIT but were waived and still receiving medication. Symptom scores, prick test results, PC20 levels (methacholine challenge that is a provocative concentration causing a 20% fall in FEV1), and the presence of asthma were recorded and compared with data from at least one year after treatment. RESULTS: A total of sixty-eight subjects (22 males, 46 females; mean age 40.54 ± 12.27 years; SCIT: 40, Control: 28) were enrolled.Although the changes in log PC20 levels were not statistically significant in both SCIT and control groups after an average of 30-35 months of treatment, it was found to be significant in favor of the SCIT group when two groups were compared in terms of the change in log PC20 (p = 0.026). The development and improvement of asthma were not significantly different between the SCIT and control group but tended to increase in the control group. The percentage of patients with progressed/BHR was significantly higher in the controls (70.6% vs. 38.1%, p = 0.046). DISCUSSION: In our real life study we have demonstrated the preventative effect of SCIT on BHR, but not on asthma developmen.

The effect of mitochondria-targeted slow hydrogen sulfide releasing donor AP39-treatment on airway inflammation.

Mitochondrial dysfunction has been shown to contribute to the pathophysiology of airway diseases. Therefore, mitochondria are targeted in the development of new therapeutic approaches. Hydrogen sulfide (H2S) has been shown to be involved in the pathophysiological processes of airway inflammation. We aimed to evaluate the effect of mitochondria-targeted slow H2S releasing donor AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol5yl)phenoxy)decyl)triphenylphosphoniumbromide)] on lipopolysaccharide (LPS)-induced airway inflammation in mice. LPS was applied to female Balb/c mice by intranasal (i.n.) route to induce airway inflammation and the subgroups of mice were treated with i.n. AP39 (250-1000 nmol/kg). 48 h after LPS administration airway reactivity was evaluated in vivo, then bronchoalveolar lavage (BAL) fluid and lungs were collected. LPS application led to bronchial hyperreactivity and neutrophil infiltration into the lung tissues along with increased TNF-α, IL-1ß and IL-6 levels in BAL fluid. LPS also induced an increase in the rate of glycolysis, glycogenolysis and Krebs-cycle. AP39 treatment prevented the LPS-induced bronchial hyperreactivity and reversed the increase in TNF-α and IL-6 levels in BAL fluid. The increase in neutrophil numbers in BAL fluid was also prevented by AP39 treatment at the highest dose. Our results indicate that AP39 can prevent bronchial hyperreactivity and decrease airway inflammation. Targeting H2S to the mitochondria may be a new therapeutic approach in airway inflammation.

Delayed Microbial Maturation Durably Exacerbates Th17-driven Asthma in Mice.

Microbial maturation disrupted by early-life dysbiosis has been linked with increased asthma risk and severity; however, the immunological mechanisms underpinning this connection are poorly understood. We sought to understand how delaying microbial maturation drives worsened asthma outcomes later in life and its long-term durability. Drinking water was supplemented with antibiotics on Postnatal Days 10-20. To assess the immediate and long-term effects of delaying microbial maturation on experimental asthma, we initiated house dust mite exposure when bacterial diversity was either at a minimum or had recovered. Airway hyperresponsiveness, histology, pulmonary leukocyte recruitment, flow cytometric analysis of cytokine-producing lymphocytes, and assessment of serum IgG1 (Immunoglobulin G1) and IgE (Immunoglobulin E) concentrations were performed. RT-PCR was used to measure IL-13 (Interleukin 13)-induced gene expression in sequentially sorted mesenchymal, epithelial, endothelial, and leukocyte cell populations from the lung. Delayed microbial maturation increased allergen-driven airway hyperresponsiveness and Th17 frequency compared with allergen-exposed control mice, even when allergen exposure began after bacterial diversity recovered. Blockade of IL-17A (Interleukin 17A) reversed the airway hyperresponsiveness phenotype. In addition, allergen exposure in animals that experienced delayed microbial maturation showed signs of synergistic signaling between IL-13 and IL-17A in the pulmonary mesenchymal compartment. Delaying microbial maturation in neonates promotes the development of more severe asthma by increasing Th17 frequency, even if allergen exposure is initiated weeks after microbial diversity is normalized. In addition, IL-17A-aggravated asthma is associated with increased expression of IL-13-induced genes in mesenchymal, but not epithelial cells.

CATALASE CRS-262T GENE POLYMORPHISM AND CHANGES IN VENTILATION LUNG CAPACITY IN CHILDREN-RESIDENTS OF RADIOACTIVELY CONTAMINATED TERRITORIES. / POLIMORFIZM SRS-262T GENA KATALAZY I ZMINY VENTYLIaTsIINOÏ SPROMOZhNOSTI LEGENIV U DITEI - MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII.

OBJECTIVE: to determine the association of catalase С-262Т gene polymorphism with the presence of bronchial hyper-reactivity in children living in radioactively contaminated territories. MATERIALS AND METHODS: There were examined school-age children-residents of radioactively contaminated territories (RCT), who did not have clinical signs of respiratory pathology. Catalase (CAT) С-262Т gene deletion polymorphism was studied in the molecular genetic laboratory of the State Institution «Reference Center for Molecular Diagnostic of Public Health Ministry of Ukraine¼. Determination of the polymorphic variant by the catalase С-262Т gene was performed by Polymerase Chain Reaction (PCR) using specific oligonucleotide primers, followed by Restriction Fragment Length Polymorphism (RFLP) analysis. The CAT С-262Т gene polymorphism in children living in RCT was compared with that in the reference group of practically healthy individuals. Ventilation lung capacity was performed by computer spirometry according to the analysis of the loop «the flow-volume¼. A pharmacological inhalation test with a bronchodilator that acts on ß2-adrenergic receptors of the lungs was used to detect early changes in the ventilatory capacity of the lungs - bronchial hyperreactivity. RESULTS: Comparative analysis showed that in the presence of bronchial hyperreactivity in children living in RCT, the CT genotype was more common than in children without bronchial hyperreactivity, and the frequency of the CC genotype was correspondingly reduced. There was a trend towards a decrease in the frequency of the TT genotype. An analysis of the frequency distribution of allelic variants of the CAT С-262Т gene polymorphism in children living in the RCT revealed a tendency to increase in the frequency of the T-allele and according to the decrease in the frequency of C-allele in the presence of bronchial hyperreactivity.Сonclusions. Thus, among children living in RCT, CT-homozygotes of CAT С-262Т gene polymorphism had bronchial hyperreactivity probably more often than CC-heterozygotes. In the presence of bronchial hyperreactivity, there was a trend towards an increase in the frequency of the T-allele and, accordingly, a decrease in the frequency of the C-allele.

Distinct Endotypes of Pediatric Rhinitis Based on Cluster Analysis.

PURPOSE: Despite the wide spectrum of pediatric rhinitis, endotyping of rhinitis based on type 2 inflammation and bronchial hyper-responsiveness (BHR) is lacking. This study aimed to investigate endotypes of pediatric rhinitis using cluster analysis. METHODS: Cluster analysis was performed on data from 241 children with rhinitis by using 12 variables reflecting clinical characteristics of skin prick, laboratory, and pulmonary function tests. After extracting clusters, between-cluster differences in clinical features, such as nasal symptom scores and asthma comorbidity, were assessed to investigate the association between the endotypes and clinical features. RESULTS: Four clusters were extracted by hierarchical cluster analysis. Cluster 1 (n = 32 [13.3%]) was the non-allergic rhinitis dominant cluster with low type 2 inflammation and the lowest rate of BHR. Patients in cluster 1 had the mildest nasal symptoms and no asthma comorbidity. Cluster 2 (n = 114 [47.3%]) was the largest cluster and exhibited intermediate type 2 inflammation and low BHR. Cluster 3 (n = 65 [27.0%]) showed high type 2 inflammation and intermediate BHR. However, the severity of nasal symptoms and asthma comorbidity in this cluster were comparable with those in cluster 2. Cluster 4 (n = 30 [12.4%]) revealed high type 2 inflammation and BHR with potential functional airway impairment. Additionally, cluster 4 displayed the most severe nasal symptoms and frequent asthma comorbidity. CONCLUSIONS: Four distinct endotypes of pediatric rhinitis based on allergen sensitization, type 2 inflammation, and BHR correlate to symptoms and asthma comorbidity. These endotypes may aid clinicians in understanding the wide spectrum of pediatric rhinitis.

Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review.

RSV is one of the major infectious agents in paediatrics, and its relationship with air pollution is frequently observed. However, the molecular basis of this interaction is sparsely reported. We sought to systematically review the existing body of literature and identify the knowledge gaps to answer the question: which molecular mechanisms are implied in the air pollutants-RSV interaction? Online databases were searched for original studies published before August 2022 focusing on molecular mechanisms of the interaction. The studies were charted and a narrative synthesis was based upon three expected directions of influence: a facilitated viral entry, an altered viral replication, and an inappropriate host reaction. We identified 25 studies published between 1993 and 2020 (without a noticeable increase in the number of studies) that were performed in human (n = 12), animal (n = 10) or mixed (n = 3) models, and analysed mainly cigarette smoke (n = 11), particulate matter (n = 4), nanoparticles (n = 3), and carbon black (n = 2). The data on a damage to the epithelial barrier supports the hypothesis of facilitated viral entry; one study also reported accelerated viral entry upon an RSV conjugation to particulate matter. Air pollution may result in the predominance of necrosis over apoptosis, and, as an effect, an increased viral load was reported. Similarly, air pollution mitigates epithelium function with decreased IFN-γ and Clara cell secretory protein levels and decreased immune response. Immune response might also be diminished due to a decreased viral uptake by alveolar macrophages and a suppressed function of dendritic cells. On the other hand, an exuberant inflammatory response might be triggered by air pollution and provoke airway hyperresponsiveness (AHR), prolonged lung infiltration, and tissue remodeling, including a formation of emphysema. AHR is mediated mostly by increased IFN-γ and RANTES concentrations, while the risk of emphysema was related to the activation of the IL-17 → MCP-1 → MMP-9 → MMP-12 axis. There is a significant lack of evidence on the molecular basics of the RSV-air pollution interaction, which may present a serious problem with regards to future actions against air pollution effects. The major knowledge gaps concern air pollutants (mostly the influence of cigarette smoke was investigated), the mechanisms facilitating an acute infection or a worse disease course (since it might help plan short-term, especially non-pharmacological, interventions), and the mechanisms of an inadequate response to the infection (which may lead to a prolonged course of an acute infection and long-term sequelae). Thus far, the evidence is insufficient regarding the broadness and complexity of the interaction, and future studies should focus on common mechanisms stimulated by various air pollutants and a comparison of influence of the different contaminants at various concentrations.

A vitamin E long-chain metabolite and the inspired drug candidate α-amplexichromanol relieve asthma features in an experimental model of allergen sensitization.

Benefits for vitamin E intake in diseases with inflammatory components have been described and related in part, to endogenously formed metabolites (long-chain metabolites, LCM). Here, we have evaluated the role of LCM in relieving asthma features. To this aim, the endogenous vitamin E metabolite α-13'-carboxychromanol (α-T-13'-COOH) that acts as potent 5-lipoxygenase inhibitor has been administered either intraperitoneally or by oral gavage to BALB/c mice sensitized by subcutaneous injection of ovalbumin (OVA). We also have taken advantage of the metabolically stable α-T-13'-COOH derivative α-amplexichromanol (α-AC). Intraperitoneal treatment with α-T-13'-COOH reduced OVA-induced airway hyperreactivity (AHR) as well as peri-bronchial inflammatory cell infiltration. α-AC was more efficacious than α-T-13'-COOH, as demonstrated by better control of AHR and in reducing subepithelial. Both compounds exerted their protective function by reducing pulmonary leukotriene C4 levels. Beneficial effects of α-AC were coupled to inhibition of the sensitization process, as indicated by a reduction of IgE plasma levels, lung mast cell infiltration and Th2 immune response. Metabololipidomics analysis revealed that α-AC raises the pulmonary levels of prostanoids, their degradation products, and 12/15-lipoxygenase metabolites. Following oral administration, the pharmacodynamically different profile in α-T-13'-COOH and α-AC was abrogated as demonstrated by a similar and improved efficacy in controlling asthma features as well as by metabololipidomics analysis. In conclusion, this study highlights a role for LCM and of vitamin E derivatives as pharmacologically active compounds that ameliorate asthmatic features and defines an important role for endogenous vitamin E metabolites in regulating immune response underlying the sensitization process.

Anesthetic considerations in children with asthma.

Due to the high prevalence of asthma and general airway reactivity, anesthesiologists frequently encounter children with asthma or asthma-like symptoms. This review focuses on the epidemiology, the underlying pathophysiology, and perioperative management of children with airway reactivity, including controlled and uncontrolled asthma. It spans from preoperative optimization to optimized intraoperative management, airway management, and ventilation strategies. There are three leading causes for bronchospasm (1) mechanical (eg, airway manipulation), (2) non-immunological anaphylaxis (anaphylactoid reaction), and (3) immunological anaphylaxis. Children with increased airway reactivity may benefit from a premedication with beta-2 agonists, non-invasive airway management, and deep removal of airway devices. While desflurane should be avoided in pediatric anesthesia due to an increased risk of bronchospasm, other volatile agents are potent bronchodilators. Propofol is superior in blunting airway reflexes and, therefore, well suited for anesthesia induction in children with increased airway reactivity.

The Changes in Expression of NaV1.7 and NaV1.8 and the Effects of the Inhalation of Their Blockers in Healthy and Ovalbumin-Sensitized Guinea Pig Airways.

BACKGROUND: The presented study evaluated the suppositional changes in the airway expression of Nav1.8 and Nav1.7 and their role in the airway defense mechanisms in healthy animals and in an experimental asthma model. METHODS: The effects of the blockers inhalation on the reactivity of guinea pig airways, number of citric-acid-induced coughs and ciliary beating frequency (CBF) were tested in vivo. Chronic inflammation simulating asthma was induced by repetitive exposure to ovalbumin. The expression of Nav1.7 and Nav1.8 was examined by ELISA. RESULTS: The Nav 1.8 blocker showed complex antitussive and bronchodilatory effects and significantly regulated the CBF in healthy and sensitized animals. The Nav1.7 blockers significantly inhibited coughing and participated in CBF control in the ovalbumin-sensitized animals. The increased expression of the respective ion channels in the sensitized animals corresponded to changes in CBF regulation. The therapeutic potency of the Nav1.8 blocker was evidenced in combinations with classic bronchodilators. CONCLUSION: The allergic-inflammation-upregulated expression of Nav1.7 and Nav1.8 and corresponding effects of blocker inhalation on airway defense mechanisms, along with the Nav1.8 blocker's compatibility with classic antiasthmatic drugs, bring novel possibilities for the treatment of various respiratory diseases. However, the influence of the Nav1.8 blocker on CBF requires further investigation.

Exposure to Polyhexamethylene Guanidine Exacerbates Bronchial Hyperresponsiveness and Lung Inflammation in a Mouse Model of Ovalbumin-Induced Asthma.

Humidifier disinfectants (HDs) exposure has now been associated with acute lung injury and pulmonary fibrosis; polyhexamethylene guanidine (PHMG) has been confirmed to cause severe lung inflammation and fibrosis in mice. Recent evidence also indicates that HDs exposure increases the asthma risk in children, but the underlying mechanisms remain unclear. We aimed to investigate the effects of PHMG exposure on asthma in mice and the potential underlying mechanisms. BALB/c mice were intranasally administered PHMG (0.1 mg/kg/day; 5 days per week) during 2 episodes of ovalbumin (OVA) sensitization and were then challenged with 1% OVA by inhalation. Bronchial hyperresponsiveness (BHR), inflammatory cell influx into bronchoalveolar lavage (BAL) fluid, serum total and OVA-specific immunoglobulin (Ig) E levels, and histopathological changes in the lung were analyzed. The levels of asthma-related cytokines and chemokines were assayed in the lung tissues to evaluate possible mechanisms. Exposure to PHMG following OVA sensitization and challenge significantly enhanced BHR, inflammatory cell counts in BAL fluid, airway inflammation, and total serum IgE levels in the asthma mouse model. In addition, the levels of chemokine ligand (CCL) 11 and serpine F1/pigment epithelium-derived factor (SERPINF1) were significantly elevated in the lungs of these mice compared to those in the control and OVA-treated only groups. Our findings suggest that PHMG can enhance the development of allergic responses and lung inflammation via CCL11- and SERPINF1-induced signaling in a mouse model of asthma.

Reactive airways dysfunction syndrome following inhalation of hydrogen chloride vapor.

Hydrogen chloride is available commercially as an anhydrous gas or an aqueous solution, hydrochloric acid. Exposure to this gas has been associated with the development of reactive airways dysfunction syndrome. However, there are few published reports. A 37-year-old woman developed progressive bronchospasm and acute respiratory failure after cleaning an enclosed space with an unknown concentration of hydrochloric acid gas from a cleaning substance. She had no prior history of asthma or atopy. Severe bronchospasm developed, leading to hypoxemia and diffuse interstitial infiltrates, necessitating orotracheal intubation and admission to the intensive care unit. Asthma-like symptoms such as cough, wheezing, and dyspnea; requiring bronchodilators, and repeated hospitalizations are persistent a year after the accident. Pulmonary function testing showed mild airflow obstruction.

Predictive Markers of Bronchial Hyperreactivity in a Large Cohort of Young Adults With Cough Variant Asthma.

Cough variant asthma (CVA), a common asthma phenotype characterized by nonproductive cough and bronchial hyperreactivity (BHR), is usually detected by bronchial provocation tests (BPTs) which are time-consuming, expensive, and unsafe. The primary study objective was to provide proof of concept for the use of fractional exhaled nitric oxide (FENO), eosinophil count percentage in induced sputum (sEOS%), forced expiratory flow between 25 and 75% of forced vital capacity (FEF25-75%) % predicted value, and FEF25-75% z-scores as surrogate markers predicting BHR in young adults with suspected CVA; the secondary objective was to compare the diagnostic performance of the various techniques. Three hundred and ten subjects (median age 24 years) were included in a cross-sectional study. Subjects were characterized as BHR positive (POS) (n = 147) or BHR negative (NEG) (n = 163) according to methacholine BPT. Classification accuracies were expressed as areas under the receiver operator characteristic curves (AUC). Compared with BHR NEG, FEF25-75% % predicted value and FEF25-75% z-scores were lower in the BHR POS group (p < 0.001), whereas FENO (p < 0.001) and sEOS% were higher (p < 0.001). AUC values for detecting BHR were as follows: FENO, 0.98 (SD = 0.02); sEOS%, 0.98 (SD = 0.02); FEF25-75% % pred, 0.93 (SD = 0.05); FEF25-75% z scores, 0.92 (SD = 0.05). Optimal cutoff values (OCV) for BHR prediction were as follows: FENO, 32.7 ppb (sensitivity = 0.93, specificity = 0.96), sEOS%, 3.80% (sensitivity = 0.94, specificity = 0.94), FEF25-75% % predicted value, 80.0% (sensitivity = 0.90, specificity = 0.87), and FEF25-75% z-score, -0.87 (sensitivity = 0.89, specificity = 0.87). Non-invasive/semi-invasive airway inflammatory or small airway functional measures might be used as surrogate markers predicting BHR in young adults with suspected CVA.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

BACKGROUND: Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. METHODS: In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16 years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12 years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. RESULTS: 55% of the study cohort (N = 122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P < .0001) FVC (P < .0001) and FEV1 /FVC (P < .0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16 years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28 mg/mL at 7 years to 0.53 mg/mL at 12 years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P = .0003). CONCLUSIONS: Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.

Aqueous Pyrostegia venusta (Ker Gawl.) Miers extract attenuates allergen-induced asthma in a mouse model via an antioxidant mechanism.

Objective:Pyrostegia venusta (Ker-Gawl.) Miers (Bignoniaceae) is a perennial invasive vine, distributed worldwide. In folk medicine, its parts are used for the treatment of inflammatory respiratory diseases. Extracts of P. venusta have antioxidant, antimicrobial, and antinociceptive properties. The aim of this study was to evaluate the effects of two extracts (aqueous and hydroethanolic) of P. venusta in the treatment of asthma in an animal model.Methods: Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally (ip), one week apart, and after one week, challenged with OVA intranasally on four alternate days. Mice were treated ip with 300 mg/kg of aqueous or hydroethanolic extracts for seven consecutive days. Control groups received saline on the same days. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, lung and airway inflammation, and antioxidant activity in lung tissue were assessed.Results: Treatment with aqueous extract significantly decreased bronchial hyperresponsiveness, measured by total and tissue resistance and elastance. The administration of hydroethanolic extract did not reduce bronchial hyperresponsiveness. In addition, both extracts significantly reduced total cell and eosinophil counts in bronchoalveolar lavage. Both extracts did not change significantly IL-4, IL-5, IL-9, IL-13, IFN-gamma, and TGF-beta levels. Of note, only the aqueous extract significantly increased the total antioxidant activity and reduced lung inflammation.Conclusion: Aqueous extract of P. venusta reduced bronchial hyperresponsiveness, lung and airway inflammation, probably via an antioxidant mechanism. These results demonstrate that P. venusta may have potential for asthma treatment.

Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis.

OBJECTIVE: Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the optimal roles of the two agents for assessing BHR remain unclear. We compared the diagnostic performance of methacholine and mannitol in bronchial challenge tests. METHODS: A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary of the receiver-operating characteristic curve (HSROC) of the two agents for detecting BHR in asthma were pooled using meta-analysis. A meta-regression analysis was used to identify potential sources of heterogeneity within the selected studies. RESULTS: We identified six studies comprising 565 patients. The pooled sensitivity, specificity, and DOR of methacholine were 0.61 (95%CI, 0.44-0.76), 0.93 (95%CI, 0.70-0.99), and 23.47 (95% CI, 2.51-219.89), respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of mannitol were 0.50 (95%CI, 0.28-0.73), 0.97 (95% CI, 0.94-0.99), and 35.22 (95% CI, 8.82-140.62), respectively. The area under the HSROC for mannitol was higher than that for methacholine (0.97 vs. 0.81, p < 0.01). Considerable between-study heterogeneity was present for sensitivity and specificity in studies of both index tests. Univariate meta-regression analysis revealed that age and sex of the study participants were probable sources of heterogeneity for specificity in studies of methacholine. CONCLUSION: Although mannitol showed better diagnostic performance than methacholine for identifying BHR in asthma, substantial between-study heterogeneity necessitates caution when interpreting the data.