Cross-Sectional Study of Cholinergic Urticaria Subtypes And Bronchial Hyperresponsiveness

Background: Cholinergic urticaria (CholU) is classified into several subtypes: 1) conventional sweat allergy-type CholU (conventional SAT-CholU), 2) CholU with palpebral angioedema (CholU-PA), 3) CholU with acquired anhidrosis and/or hypohidrosis (CholU-Anhd); 1) and 2) include SAT based on pathogenesis. There have been no studies on differences in the prevalence of bronchial asthma among the subtypes. We evaluated the bronchial responsiveness of each subtype. Methods: We analyzed bronchial responsiveness using the methacholine dose indicator Dmin, respiratory symptoms, and exhaled nitric oxide (FeNO). Results: Median log10 Dmin (interquartile range) of patients with conventional SAT-CholU (n=11), CholU-PA (n=11), and CholU-Anhd (n=11) was 0.381 (−0.829, 1.079), 0.717 (0.249, 0.787), and 1.318 (0.121, 1.699), respectively (p=0.516). Respiratory symptoms evaluated using the International Primary Care Airways Group questionnaire were less frequently observed in CholU-Anhd (0 [0, 1]) than in conventional SAT-CholU (1 [0–2]) or CholU-PA (1 [1–3]) (p=0.049). FeNO of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 23 (18.5, 65.0), 39 (32.0, 59.5), and 25 (19.0, 33.0) ppb, respectively (p=0.237). Conclusions: Log Dmin tended to be lower in patients with SAT-CholU than in those with CholU-Anhd. Distinguishing between CholU subtypes may reveal different degrees of bronchial responsiveness based on a distinct pathogenesis.

Changes in lung inflation in asthma in patients with osmotic airway hyperresponsiveness

The scientific literature does not provide enough information on whether bronchial hyperresponsiveness to hypoosmotic stimulus in patients with asthma can lead to more pronounced disturbances of regional lung ventilation.Aim. to characterize lung inflation in asthma patients with osmotic airway hyperresponsiveness.Methods. The lung inflation was studied by body plethysmography, as well as by three-dimensional volumetry, planimetry, and multispiral CT densitometry in 24 patients (group 1) with persistent mild asthma and osmotic airway hyperresponsiveness, identified by the bronchoprovocation test with inhalation of distilled water (IDW) (the average ДРБУ1 was —21.1 ± 3.2%). The comparison group (group 2) consisted of 49 patients with no response to IDW (the average ДББУ1 was —3.7 ± 0.5%; p = 0.00001).Results. Group 1 had lower lung function (FEVj was 83.6 ± 4.5%; FEF50 was 58.1 ± 5.8%) at baseline in comparison with the group 2 (96.7 ± 2.2%, p = 0.0042 and 75.5 ± 2.2%, p = 0.016, respectively) and higher indices of lung inflation at body plethysmography (RV was 153.2 ± 12.5 and 127.5 ± 4.0%, respectively; p = 0,027; RV/TLC was 128.8 ± 5.5 and 109.9 ± 2.8%, respectively; p = 0.015). According to three-dimensional volumetry, the indicators of expiratory lung inflation (526.0 ± 117.8 vox) and average residual inflation of both lungs (13.1 ± 2.6 vox) in group 1 were significantly higher than in group 2 (301.5 ± 55.8 vox, р < 0.05 and 9.1 ± 1.6 vox,р < 0,05, respectively). The patients with osmotic airway hyperresponsiveness also showed higher values of the expiratory area in the middle zone (235.3 ± 29.4 and 149.2 ± 14.9 pix, respectively; p = 0.00 47) and the lower zone (292.3 ± 37.9 and 178.6 ± 18.6 pix, respectively; p = 0.0034) of the lungs.Conclusion. Asthma patients with osmotic airway hyperresponsiveness have lung hyperinflation with impaired lung ventilation predominantly in the middle and lower zones.

Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway

Allergic asthma is a heterogeneous inflammatory disorder triggered by inhaled allergens, leading to airflow obstruction, bronchial inflammation, and airway hyperresponsiveness (AHR). T helper (Th) 2 cell-mediated immune response and airway inflammation are the key features of allergic asthma. Bruceine D (BD) is a bioactive compound extracted from the seeds of Brucea javanica. The present study aimed to investigate the effects of increased doses of BD on AHR, secretion of Th1-/Th2-associated cytokines, and inflammatory cell infiltration in ovalbumin (OVA)-induced allergic asthma mice. The results showed that BD reduced OVA-induced inflam-matory cell infiltration and bronchial hyperresponsiveness into the peribronchial tissues and perivascular areas. Mice treated with BD also showed significantly decreased expressions of Th2-associated cytokines (i.e., interleukin (IL)-4, IL-5, and IL-13) and elevated production of Th1-associated cytokines (i.e., interferon gamma and IL-2) following OVA stimulation. BD treatment dose-dependently inhibited OVA-induced accumulation of inflammatory cells in asth-matic mice. Further analysis revealed that OVA exposure upregulated pulmonary expressions of NOTCH signaling receptors, a group of transmembrane proteins that communicate signals upon binding to transmembrane ligands expressed on adjacent cells, while BD treatment sig-nificantly abolished OVA-induced activation of the NOTCH pathway. In conclusion, BD protected mice against OVA-induced allergic asthma by reducing AHR and restoring the Th1/Th2 balance through the NOTCH signaling pathway. Our findings highlighted the potential of BD as a therapeutic agent for allergic asthma.

Salidroside Mitigates Airway Inflammation in Asthmatic Mice via the AMPK/Akt/GSK3β Signaling Pathway

<b><i>Introduction:</i></b> This study aimed to explore the effects and mechanisms of salidroside (SAL) in airway inflammation in asthmatic mice. <b><i>Methods:</i></b> Mice were sensitized with ovalbumin (OVA) to establish an asthma model. They were divided into the control group, OVA group, SAL low-dose group (SAL-L), SAL high-dose group (SAL-H), and dexamethasone (DXM) group. The airway reactivity of the mice was measured, and the total cells, neutrophils, eosinophils, and lymphocytes were counted, respectively. The levels of IL-4, IL-5, IL-13, and IFN-γ in bronchoalveolar lavage fluid (BALF) were detected by ELISA. Immunohistochemistry was used to detect the expression levels of p-AMPK, p-Akt, and p-GSK3β. Western blot was used to detect cytokine levels in lung tissue and p-AMPK, p-Akt, and p-GSK3β levels in LPS-induced 16HBE cells. <b><i>Results:</i></b> The airway hyperresponsiveness of asthmatic mice in the SAL-H group decreased (<i>p</i> &#x3c; 0.05), and the total number of cells, neutrophils, eosinophils, and lymphocytes decreased significantly (<i>p</i> &#x3c; 0.05). In addition, the airways of mice showed airway inflammatory infiltration and goblet cell proliferation, and the corresponding cellular inflammatory factors IL-4, IL-5, and IL-13 were significantly decreased. However, the expression of IFN-γ in BALF and lung tissues was increased (<i>p</i> &#x3c; 0.05). Moreover, after the mice were treated with SAL, the phosphorylation level of AMPK was significantly increased, which further reduced the phosphorylation levels of Akt and GSK3β (<i>p</i> &#x3c; 0.05). Both SAL and AMPK inhibitors exerted effects on LPS-induced 16HBE cells, consistent with in vivo results. <b><i>Conclusion:</i></b> SAL can inhibit bronchial hyperresponsiveness and reduce tracheal inflammation by increasing AMPK phosphorylation and inhibiting Akt and GSK3β signaling pathways.

Cross-sectional Study of Cholinergic Urticaria Subtypes and Bronchial Hyperresponsiveness

BackgroundCholinergic urticaria (CholU) is classified into several subtypes: 1) conventional sweat allergy-type CholU (conventional SAT-CholU), 2) CholU with palpebral angioedema (CholU-PA), 3) CholU with acquired anhidrosis and/or hypohidrosis (CholU-Anhd), and other rare type; 1) and 2) include SAT based on pathogenesis. There have been no studies on differences in the prevalence of bronchial asthma among the CholU subtypes. This is investigated in the present study by evaluating the bronchial responsiveness of each subtype.MethodsPatients 16–80 years of age with CholU were enrolled. We analyzed bronchial responsiveness, respiratory symptoms, and exhaled nitric oxide (FeNO). Bronchial responsiveness was assessed using the methacholine dose indicator Dmin.ResultsA total of 11 patients with conventional SAT-CholU, 11 with CholU-PA, and 11 with CholU-Anhd were enrolled. Median log10 Dmin (interquartile range) of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 0.381 (−0.829, 1.079), 0.717 (0.249, 0.787), and 1.318 (0.121, 1.699), respectively (p=0.516). Dmin was lower in patients with SAT (conventional SAT-CholU and CholU-PA) than in those with CholU-Anhd, although the differences among the 3 types were not significant. Respiratory symptoms evaluated using the International Primary Care Airways Group questionnaire were less frequently observed in CholU-Anhd (0 [0, 1]) than in conventional SAT-CholU (1 [0–2]) or CholU-PA (1 [1–3]) (p=0.049). FeNO of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 23 (18.5, 65.0), 39 (32.0, 59.5), and 25 (19.0, 33.0) ppb, respectively (p=0.237). One of 11 conventional SAT-CholU patients (9.1%) and 6 of 11 CholU-PA patients (54.5%) required treatment for bronchial asthma.ConclusionsLog Dmin tended to be lower in patients with SAT-CholU than in those with CholU-Anhd. Distinguishing between CholU subtypes may reveal different degrees of bronchial responsiveness based on a distinct pathogenesis.Trial registration numberUMIN 000025669; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000027550

Does bronchial hyperresponsiveness predict a diagnosis of cough variant asthma in adults with chronic cough: a cohort study

Bronchial hyperresponsiveness is a typical, but non-specific feature of cough variant asthma (CVA). This study aimed to determine whether bronchial hyperresponsiveness may be considered as a predictor of CVA in non-smoking adults with chronic cough (CC). The study included 55 patients with CC and bronchial hyperresponsiveness confirmed in the methacholine provocation test, in whom an anti-asthmatic, gradually intensified treatment was introduced. The diagnosis of CVA was established if the improvement in cough severity and cough-related quality of life in LCQ were noted.The study showed a high positive predictive value of bronchial hyperresponsiveness in this population. Cough severity and cough related quality of life were not related to the severity of bronchial hyperresponsiveness in CVA patients. A poor treatment outcome was related to a low baseline capsaicin threshold and the occurrence of gastroesophageal reflux-related symptoms. In conclusion, bronchial hyperresponsiveness could be considered as a predictor of cough variant asthma in non-smoking adults with CC.

Immunobiology of Steroid-Unresponsive Severe Asthma

Asthma is a heterogeneous respiratory disease characterized by airflow obstruction, bronchial hyperresponsiveness and airway inflammation. Approximately 10% of asthma patients suffer from uncontrolled severe asthma (SA). A major difference between patients with SA from those with mild-to-moderate asthma is the resistance to common glucocorticoid treatments. Thus, steroid-unresponsive uncontrolled asthma is a hallmark of SA. An impediment in the development of new therapies for SA is a limited understanding of the range of immune responses and molecular networks that can contribute to the disease process. Typically SA is thought to be characterized by a Th2-low and Th17-high immunophenotype, accompanied by neutrophilic airway inflammation. However, Th2-mediated eosinophilic inflammation, as well as mixed Th1/Th17-mediated inflammation, is also described in SA. Thus, existing studies indicate that the immunophenotype of SA is diverse. This review attempts to summarize the interplay of different immune mediators and related mechanisms that are associated with airway inflammation and the immunobiology of SA.

The role of occupational factors and individual susceptibility in the development and course of bronchopulmonary diseases

Over the past decades, the world has seen an increase in occupational lung diseases, the leaders being asthma and chronic obstructive pulmonary disease (COPD). The article presents the results of 5-year observation of food industry workers. Clinical functional and molecular genetic studies have been carried out to identify the frequency and severity of asthma and COPD along with the individual predisposition to pulmonary conditions.Methods. 76 people of both sexes with the average age of 43.5 ± 3.6 years were examined on an outpatient basis. All subjects had daily contact with toxic and allergenic aerosols and organo-mineral dust. The respiratory function and the presence of bronchial hyperresponsiveness to occupational factors was assessed by spirography and peak flowmetry in response to exposure and elimination of industrial aerosols. Immunological and molecular genetic tests were performed: identification of hyposecretory alleles of the α1 -АТ gene, determination of polymorphisms of the GSTM1 and GSTT1 genes, immunoglobulin levels (IgE, IgM, IgG) and cytokine status (IL-4, -6, -8; TNF-α).Results. During the 5-year follow-up period, there was a significant increase in the number of employees with severe respiratory symptoms – 36.8% (95% CI – 21.2–36.8; p < 0.05) and a statistically significant decrease in the respiratory function (p < 0.001). Progressive decrease in the respiratory function in healthy individuals and the appearance of new and more severe cases of asthma and COPD were registered primarily among workers with hyposecretory alleles of the α1 -АТ gene and/or zero alleles of the glutathioneS-transferase genes (GSTM1 and GSTT1) in combination with abnormal cytokine status.Conclusion. Individual risk factors for the development of asthma and COPD in individuals working in contact with toxic and allergenic aerosols and organo-mineral dust are hyposecretory PiMZ variant of the α1 -АТ gene and deletions in the glutathione-S-transferase genes (GSTM1 0/0 and GSTT1 0/0) in combination with abnormal cytokine status. Long-term research results suggest the prognostic value of assessing individual sensitivity to industrial aerosols and the development of bronchopulmonary pathology.