Asthma and stroke: a narrative review

To quantitatively analyze the effects of direct and indirect stimuli on the contraction of gastrocnemius in vivo and in vitro specimen by self-programming. All specimens were divided into four groups: indirect stimuli on specimen in vivo group (n=12), direct stimuli on specimen in vivo group (n=8), indirect stimuli on specimen in vitro group (n=12), direct stimuli on specimen in vitro group (n=8). Indirect stimuli (via sciatic nerve) and direct stimuli (acupuncture needle piercing into gastrocnemius) (stimuli starting from 0 V, cycle 3 s, increment 0.02 V, 150 times) were acted on in vivo and in vitro sciatic nerve gastrocnemius muscle specimen respectively. The effects of electric intensity on the contraction of gastrocnemius were recorded by the experimental system of BL-420F. The data were processed and analyzed by the help of self-programming, to quantitatively obtain key parameters for a single contraction. ① For in vivo specimen, compared with direct stimuli, effects of indirect stimuli were as follows: the threshold intensity, half-intensity and maximal intensity of the specimen were smaller (P＜0.05); the amplitude was larger, the contraction period was longer, and the rising slope was smaller (P＜0.05). ②For in vitro specimen, compared with direct stimuli, effects of indirect stimuli were as follows: the threshold intensity, half-intensity and maximal intensity of indirect stimuli were smaller (P＜0.05); the amplitude was larger, the contraction period was longer, and the rising slope was smaller (P＜0.05). ③Compared with in vitro specimen, there was no significant difference among all the above parameters of in vivo specimen, with either direct or indirect stimuli (P＞0.05). There is no significant difference in the features of single contraction between in vivo and in vitro specimen with either direct or indirect stimuli. However, indirect stimuli can trigger gastrocnemius to produce single contraction more easily than direct stimuli, and the amplitude is larger than that of direct stimuli.

Previous studies have shown that asthma is a risk factor for lung cancer, while the mechanisms involved remain unclear. We attempted to further explore the association between asthma and non-small cell lung cancer (NSCLC) via bioinformatics analysis. We obtained GSE143303 and GSE18842 from the GEO database. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) groups were downloaded from the TCGA database. Based on the results of differentially expressed genes (DEGs) between asthma and NSCLC, we determined common DEGs by constructing a Venn diagram. Enrichment analysis was used to explore the common pathways of asthma and NSCLC. A protein-protein interaction (PPI) network was constructed to screen hub genes. KM survival analysis was performed to screen prognostic genes in the LUAD and LUSC groups. A Cox model was constructed based on hub genes and validated internally and externally. Tumor Immune Estimation Resource (TIMER) was used to evaluate the association of prognostic gene models with the tumor microenvironment (TME) and immune cell infiltration. Nomogram model was constructed by combining prognostic genes and clinical features. 114 common DEGs were obtained based on asthma and NSCLC data, and enrichment analysis showed that significant enrichment pathways mainly focused on inflammatory pathways. Screening of 5 hub genes as a key prognostic gene model for asthma progression to LUAD, and internal and external validation led to consistent conclusions. In addition, the risk score of the 5 hub genes could be used as a tool to assess the TME and immune cell infiltration. The nomogram model constructed by combining the 5 hub genes with clinical features was accurate for LUAD. Five-hub genes enrich our understanding of the potential mechanisms by which asthma contributes to the increased risk of lung cancer.

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. This study was carried out to evaluate the level of vitamin D and immunoglobulin E (IgE) in asthmatic patients during exacerbation and after remission. This study was carried out on 30 patients with bronchial asthma diagnosed and classified according to Global Initiative for Asthma 2015 and 20 healthy individuals. Serum vitamin D and IgE were measured using enzyme-linked immunosorbent assay for all participants. Vitamin D level was highly significantly lower in the asthmatic group during exacerbation compared with the asthmatic group after remission and the control group, and the total IgE level was highly significantly higher in the asthmatic groups compared with the control group. Asthmatic patients might have an increased risk of having vitamin D deficiency during exacerbation and after remission, whereas the levels of serum total IgE level was high in asthmatic patients compared with normal individuals.

Bronchial Hyperresponsiveness in the Assessment of Asthma Control: Airway Hyperresponsiveness in Asthma: Its Measurement and Clinical Significance

Exhaled NO is increased in patients with asthma and may reflect disease severity. We examined whether the level of exhaled NO is related to the degree of airway obstruction induced by direct and indirect stimuli in asthma. Therefore, we measured exhaled NO levels before and during recovery from histamine and hypertonic saline (HS) challenge (Protocol 1) or histamine, adenosine 5'-monophosphate (AMP), and isotonic saline (IS) challenge (Protocol 2) in 11 and in nine patients with mild to moderate asthma, respectively. The challenges were randomized with a 2-d interval. Exhaled NO and FEV1 were measured before and at 4, 10, 20, and 30 min after each challenge. NO was measured during a slow VC maneuver with a constant expiratory flow of (0.05 x FVC)/s against a resistance of 1 to 2 cm H2O. Baseline exhaled NO levels were not significantly different between study days in Protocol 1 (mean +/- SD: 4.8 +/- 1.8 ppb [histamine] versus 5.4 +/- 2.1 ppb [HS], p = 0.4) or in Protocol 2 (7.9 +/- 4.7 ppb [histamine], 8.3 +/- 5.2 ppb [AMP], and 7.2 +/- 3.7 ppb [IS], p = 0.7). A significant reduction in exhaled NO was observed directly after HS (mean +/- SEM: 39.2 +/- 3.9 %fall) and AMP challenge (32.3 +/- 7.3 %fall) (MANOVA, p < 0.001), respectively, whereas exhaled NO levels tended to decrease after histamine challenge. Isotonic saline challenge did not induce changes in exhaled NO (p = 0.7). There was a positive correlation between %fall in FEV1 and the %fall in exhaled NO after histamine, HS, and AMP challenge as indicated by the mean slope of the within-subject regression lines (p <= 0.04). We conclude that acute bronchoconstriction, as induced by direct and indirect stimuli, is associated with a reduction in exhaled NO levels in asthmatic subjects. This suggests that airway caliber should be taken into account when monitoring exhaled NO in asthma.

Background: Bronchial asthma (BA) is characterized by chronic airway inflammation. Although a majority of BA patients are controlled by standard treatment containing inhaled corticosteroids, some patients suffer acute exacerbation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells which are involved in the pathogenesis of BA. However, the role of ROS levels as a biomarker in BA patients is not yet clear. Aims and objectives: We tried to determine the role of ROS levels as a biomarker in the clinical settings of BA. Methods: We enrolled patients with BA from 2013 through 2015 at the Department of Respiratory Medicine, Kyorin University Hospital. Pulmonary function tests, FeNO, serum reactive oxygen metabolite (ROM) levels and serum IL-6 and IL-8 were measured. Serum ROM levels were measured by d-ROMs test. Results: A total of 110 patients with BA were recruited. Serum ROM levels correlated with WBC (rs = 0.273, P = 0.004), neutrophil (rs = 0.235, P = 0.014), CRP (rs = 0.403, P P 1 (rs = -0.306, P = 0.001, rs = - 0.240, P = 0.012, respectively). Serum ROM levels were significantly higher in patients with severe exacerbation group than in patients without exacerbation group ( P = 0.025). Receiver-operating characteristics analysis showed that ROM levels associated with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597 to 0.801, P = 0.025). Conclusions: ROM levels might reflect neutrophilic inflammation, and correlated with airway obstruction. This biomarker may be useful for predicting severe exacerbations of BA.

The beta2-adrenoceptor exhibits genetic polymorphism which may be clinically relevant in terms of treatment response or bronchial hyper-responsiveness (BHR). The combined effect of these genotypes, or the haplotype, has not been fully characterized in terms of BHR. We performed a retrospective analysis of the effects of haplotypes of amino acid substitution at position 16 (Gly/Arg) and position 27 (Gln/Glu) on spirometry and BHR to methacholine and adenosine monophosphate (AMP) in 594 asthmatic patients. There was a significant (P < 0.05) overall effect for forced expiratory volume (FEV(1)) but not after correction for steroid dose and atopic status. There were no significant differences for BHR to methacholine or AMP between the different haplotypes and no difference between the numbers of patients with or without clinically relevant BHR. Methacholine PD20 geometric mean-fold difference was 1.63 (95% CI: 0.95-2.80) between Arg-Arg/Gln-Gln and Gly-Gly/Gln-Gln and 1.26 (95% CI: 0.75-2.11) between Gly-Gly/Gln-Gln and Gly-Gly/Glu-Glu. The degree of BHR to indirect and direct stimuli does not differ between beta2-adrenoceptor haplotypes, and haplotypes cannot be used to predict BHR in patients presenting with asthma. Although beta2-adrenoceptor haplotypes do not predict BHR they may be important in predicting response to bronchodilator therapy.

Airway hyperresponsiveness to a wide variety of bronchoconstrictor agonists is a characteristic finding in patients with current, symptomatic asthma. The agonists include inhaled pharmacological agonists, such as histamine (1) acting on airway H 1 receptors, the cholinergic agonist methacholine (2) acting on airway M 3 receptors, the cysteinyl-leukotrienes (3) acting on airway Cys-LT 1 receptors, and the stimulatory prostaglandins (PG)D 2 (4) and PGF 2a (5) likely acting on airway TP receptors. These agonists are considered to be direct stimuli causing bronchoconstriction in individuals with asthma, because their action is directly on specific airway receptors. Airway hyperresponsiveness is also present to a number of physical stimuli such as exercise (6), isocapnic hyperventilation of cold, dry air (7), and hypo- and hypertonic aerosols (8). The bronchoconstriction that develops after exposure to the physical stimuli is indirect, because it occurs through the release of constrictor mediators from cells within the airways, which subsequently act on their specific receptors to mediate bronchoconstriction. Another important indirect stimulus for bronchoconstriction in many individuals with asthma is environmental allergens. The responses after inhaled allergens are often quite different from those after the other indirect stimuli, in that the acute bronchoconstrictor responses are often followed by the development of late-phase bronchoconstrictor responses (9), airway inflammation (10), and an increase in airway hyperresponsiveness (11). The focus of this article is to evaluate the evidence that the cysteinyl-leukotrienes (LT) C 4 , D 4 , and E 4 are released in asthmatic airways and are the main cause of bronchoconstriction after exposure to exercise and environmental allergens, and of the changes in airway hyperresponsiveness after the inhalation of allergen.

Asthma has become a global health issue, suffering more than 300 million people in the world, which is a heterogeneous disease, usually characterized by chronic airway inflammation and airway hyperreactivity. Combination of inhaled corticosteroids (ICS) and long acting β-agonists (LABA) can relieve asthma symptoms and reduce the frequency of exacerbations, especially for patients with refractory asthma, but there are limited treatment options for people who do not gain control on combination ICS/LABA. The increase in ICS dose generally provides little additional benefit, and there is an increased risk of side effects. Therefore, therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. Some findings suggest autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. The chinese herbal medicine (CHM) have been demonstrated clinically as potent therapeutic interventions for asthma. Moreover some reports have found that the bioactive components isolated from CHM could modulate autophagy, and exhibit potent Anti-inflammatory activity. These findings have implied the potential for CHMs in asthma or allergic inflammation therapy via the modulation of autophagy. In this review, we discuss the basic pathomechanisms underpinning asthma, and the potential role of CHMs in treating asthma with modulating autophagy.

Proteomic Analysis of Peripheral T-Lymphocytes in Patients With Asthma

IL-13 in asthma and allergic disease: Asthma phenotypes and targeted therapies

Chronic inflammation and airway remodelling are two key features of asthma. Whilst CD4+CD25+ Treg cells have been shown to prevent allergen induced airway inflammation, the role of Treg cells in asthma with established airway remodelling has not been investigated. To address this issue, we induced airway remodelling in OVA‐sensitized mice by chronic aerosol OVA exposure, followed by adoptive transfers of OVA peptide‐specific Treg cells. Without further allergen challenges, residual leukocyte infiltrates in the lungs can be found regardless of the cell types transferred. Airway hyper‐responsiveness (AHR) and pulmonary vasculature were significantly reduced after Treg transfers (P&lt;0.001), suggesting a relationship between pulmonary vasculature and AHR and an anti‐angiogenic effect of Treg cells in airway remodelling. A direct anti‐angiogenic function of Treg cells was validated by both in vitro and in vivo angiogenesis assays which showed a significant reduction of vessel formation at the presence of Treg cells (P&lt;0.001). Notch signaling pathway is known to regulate both peripheral T cell differentiation and angiogenesis. We found that the anti‐angiogenic effect of Treg cells was abrogated by pre‐incubation with recombinant Notch‐Fc proteins. This study demonstrates a novel function of Treg cells in chronic airway inflammation where Treg inhibits angiogenic remodelling via Notch signaling pathway.The project was supported by grants from the Taiwan National Science Council and National Taiwan University Hospital.

Association of the CAT-262C>T polymorphism with asthma in smokers and the nonemphysematous phenotype of chronic obstructive pulmonary disease

Bronchial hyperresponsiveness is a fundamental component of the asthmatic inflammatory process causing airway narrowing on exposure to a bronchoconstrictor stimulus. This in turn causes patients to experience symptoms of breathlessness, chest tightness, cough and wheeze. Bronchial challenge tests can be performed in the laboratory to establish the degree of bronchial hyperresponsiveness to both direct and indirect stimuli. The extent to which asthma pharmacotherapy attenuates bronchial hyperresponsiveness is therefore an important measure of efficacy. This review article discusses the effects of inhaled and oral asthma treatment upon bronchial hyperresponsiveness and highlights how, in conjunction with conventional measures of asthma control, it can be used as an aid to optimally manage patients.

Inhibition of angiogenesis by IL-32: Possible role in asthma