Cough Variant Asthma Patients Research Articles

The Effects of Budesonide Inhalation Treatment on the Expression Levels of Serum IL-6, TGF-β1, and IgE and Pulmonary Function in Patients with Cough Variant Asthma and an Evaluation of Treatment Efficacy.

To retrospectively study the effects of budesonide inhalation combined with conventional symptomatic treatment on serum inflammatory factor expression levels and pulmonary function in patients with cough variant asthma (CVA) and to evaluate treatment efficacy. This retrospective cohort study included 200 patients diagnosed with CVA at the Second Hospital of Jiaxing between January 2022 and June 2023 and given conventional symptomatic treatment plus budesonide inhalation were included in this study. Patients were divided into a no remission group, a partial remission group and a complete remission group based on treatment effect. The expression levels of serum inflammatory factors, cough symptom scores, and small airway function indicators in the three groups of patients at different time points were compared. In the three groups of CVA patients, after receiving budesonide inhalation combined with conventional symptomatic treatment, the expression levels of serum IL-5, IL-6, IL-8, TNF-α, TGF-β1, and IgE and number of eosinophils significantly decreased (P <0.05). There were statistically significant differences in the IL-6 and TGF-β1 levels among the three groups of CVA patients at T1, T2 and T3. There were statistically significant differences in IgE levels, number of eosinophils, cough symptom scores, and small airway function indicators between T2 and T3 (P<0.05). The receiveroperatingcharacteristic (ROC) curve prediction analysis revealed significant differences in the expression of IL-6 and TGF-β1 at T1, T2, and T3. Budesonide inhalation combined with conventional symptomatic treatment can significantly reduce the levels of serum inflammatory factors in patients with CVA to reduce inflammation and the allergic response, thereby reducing the cough symptom score, improving pulmonary function, and improving therapeutic efficacy. In addition, IL-6 and TGF-β1 can be used as early predictors of budesonide inhalation efficacy.

Efficacy and Safety of Yukmijihwang-Tang in the Treatment of Cough-Variant Asthma: Study Protocol for a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Background: Cough-variant asthma (CVA), a precursor of typical asthma, is the main cause of chronic cough. We hypothesize that yukmijihwang-tang (YJT), which has been used for chronic cough in traditional medicine and has been reported to have an anti-inflammatory effect, could be an adjuvant to asthma treatment. Methods: We plan a randomized, double-blind, placebo-controlled, multicenter, phase 2 trial to investigate the efficacy and safety of YJT in CVA patients. A total of 60 patients with CVA will be recruited and randomly assigned to either a high-dose YJT group, standard-dose YJT group, or control group (placebo) in a 1:1:1 allocation ratio after a 2-week run-in period. For the run-in period, only inhaled corticosteroids (ICSs) will be used, and the investigational drug will be administered once a day with concomitant ICS for 6 weeks. Data will be collected at baseline, week 3, and week 6, and the primary outcome measure will be the mean cough symptom score (CSS) change before and after medication. The secondary outcome measures will include the Leicester cough questionnaire-Korean version (LCQ-K) score, eosinophil count and eosinophil cationic protein level, pulmonary function test, and the number of uses of rescue medication, and so on. Conclusion: This study aimed to evaluate the efficacy and safety of YJT in concomitant treatment with ICS in patients with CVA and to determine the optimal dosage of YJT. The results are expected to provide evidence for the use of YJT as an adjuvant treatment for CVA.

A comparative study on the value of lower airway exhaled nitric oxide combined with small airway parameters for diagnosing cough-variant asthma.

The diagnosis of cough-variant asthma (CVA) is based on bronchial provocation test, which is challenging to be conducted. Most CVA patients have type 2 airway inflammation and small airway dysfunction. FeNO200, reflecting small airway inflammation, may be used to diagnose CVA. This study aimed to explore and compare the value of lower airway exhaled nitric oxide (FeNO50, FeNO200, and CaNO) combined with small airway parameters for diagnosing CVA. Chronic cough patients who attended the clinic from September 2021 to August 2022 were enrolled and divided into CVA group (n = 71) and non-CVA (NCVA) group (n = 212). The diagnostic values of FeNO50, FeNO200, concentration of alveolar nitric oxide (CaNO), maximal mid-expiratory flow (MMEF), forced expiratory flow at 75% of forced vital capacity (FEF75%) and forced expiratory flow at 50% of forced vital capacity (FEF50%) for CVA were evaluated. FeNO50 [39(39) ppb versus 17(12) parts per billion (ppb), p < 0.01], FeNO200 [17(14) ppb versus 8(5) ppb, p < 0.01] and CaNO [5.0(6.1) ppb versus 3.5(3.6) ppb, p < 0.01] in CVA group were significantly higher than those in NCVA group. The optimal cut-off values of FeNO50, FeNO200, and CaNO for diagnosis of CVA were 27.00 ppb [area under the curve (AUC) 0.88, sensitivity 78.87%, specificity 79.25%], 11.00 ppb (AUC 0.92, sensitivity 88.73%, specificity 81.60%) and 3.60 ppb (AUC 0.66, sensitivity 73.24%, specificity 52.36%), respectively. For diagnosing CVA, the value of FeNO200 was better than FeNO50 (p = 0.04). The optimal cut-off values of MMEF, FEF75%, and FEF50% for the diagnosis of CVA were 63.80% (AUC 0.75, sensitivity 53.52%, specificity 86.32%), 77.9% (AUC 0.74, sensitivity 57.75%, specificity 83.49%) and 73.50% (AUC 0.75, sensitivity 60.56%, specificity 80.19%), respectively. The AUCs of FeNO50 combined with MMEF, FEF75%, and FEF50% for the diagnosis of CVA were all 0.89. The AUCs of FeNO200 combined with MMEF, FEF75%, and FEF50% for the diagnosis of CVA were all 0.93. FeNO200 > 11 ppb contributed strongly for differentiating CVA from chronic cough, especially in patients with small airway dysfunction.

Study on the Relationship Between Bronchoalveolar Lavage Fluid Cell Count, Th1/Th2 Cytokines and Pulmonary Function in Patients with Cough Variant Asthma

This study aimed to compare lung function and airway inflammation among cough variant asthma (CVA), chronic cough and classical asthma (CA) and investigate the relationship between these indicators and their possible mechanisms of action in the progression of CVA to CA. 36 patients with chronic cough, 39 patients with CA, and 57 patients with CVA were included in this study. Pulmonary function tests, bronchial provocation tests and FeNO tests were performed. The patients' bronchoalveolar lavage fluid (BALF) was collected, the cells in BALF were counted, and the levels of Th1 and Th2 cytokines were detected. The neutrophils, lymphocytes, and eosinophils in BALF in the CA and CVA groups were significantly higher than those in the chronic cough group. Also, they were negatively correlated with FEV1, FVC, and FEV1/FVC and positively correlated with IgE and FeNO. The expression of Th2-related cytokines was increased in CVA and CA patients, and it was positively correlated with FEV1, FVC and FEV1/FVC and negatively correlated with IgE and FeNO, while the results of Th1-related cytokines were the opposite of those for Th2-related cytokines. CVA differs from asthma and chronic cough in terms of Th1/Th2 cytokines and lung function and provides a reference for understanding the disease mechanism of early clinical progression of CVA to CA.

The Effectiveness and Safety of Huangqi Xixin Decoction for Cough Variant Asthma: A Systematic Review and Meta-Analysis.

Objective A comprehensive and systematic review is needed to evaluate the safety and effectiveness of Huangqi Xixin decoction (HQXXD) for cough variant asthma (CVA). In this systematic review, we comprehensively interrogate the safety and effectiveness of HQXXD for CVA. Methods An overall search for studies in main English and Chinese electronic databases from their inception to June 30, 2022, was performed. Randomized controlled trials (RCTs) involving HQXXD for CVA were included. According to Cochrane Reviewer's Handbook, the risk of bias related to the included studies was evaluated. A meta-analysis using RevMan 5.4 software from the Cochrane Collaboration was used to integrate the outcomes of the included RCTs. Results A systematic review and meta-analysis were conducted using the seven eligible RCTs that had been retrieved. The included RCT-related risk of bias was evaluated. According to the findings of the meta-analysis, the HQXXD group had significantly higher total effective rates of clinical efficacy and airway responsiveness, and a significantly lower recurrence rate in comparison with the conventional Western medicine treatment group. Conclusion In the treatment of CVA patients, HQXXD is safe and effective, which benefits clinical efficacy and airway responsiveness, reduces the recurrence rate, and has no adverse effects.

Assessment of Acupoint Therapy of Traditional Chinese Medicine on Cough Variant Asthma: A Meta-analysis.

Acupoint application has been used in China to treat various illnesses for ages. In cough variant asthma (CVA), the main clinical sign is episodic night cough. Acupoint application therapy of traditional Chinese medicine is an effective procedure to treat cough variant asthma. The current study is designed to systematically assess the effectiveness of acupoint application therapy in traditional medicine for patients with cough variant asthma. The comprehensive computer retrieval related to comparison between acupoint application and nonacupoint application therapy for cough variant asthma was carried out in various databases (n = 8) from database establishment until July 4, 2021. Both English and Chinese articles about original investigations in humans were searched. Two independent authors extracted the data, and disagreements were resolved by discussion. ReviewManager 5.3 software provided by Cochrane did a meta-analysis of selected randomized controlled trials (RCTs). Quality of experimentation and risk bias were analyzed by the Cochrane Handbook tool. A total of thirteen randomized controlled clinical articles along with 1237 patients were included in the study. Findings of meta-analysis showed that compared with nonacupoint application treatment, the total effective rate of acupoint application treatment is more effective (RD = 0.13, 95% CI (0.09, 0.17), Z = 6.70, P < 0.00001). Besides, acupoint application can improve patients' lung function, the lung function index FVC (mean difference = 0.55, 95% confidence interval (0.42, 0.68), Z = 8.40, P < 0.00001), FEV1 (MD = 0.35, 95% CI (0.23, 0.47), Z = 5.86, P < 0.00001), FEV1/FVC (%) (MD = 12.68, 95% CI (4.32, 21.03), Z = 2.97, P = 0.003), FEV1 (%) (MD = 8.63, 95% CI (8.01, 9.25), Z = 27.44, P < 0.00001), and PEF (day) (MD = 0.62, 95% CI (0.52, 0.71), Z = 12.40, P < 0.00001) of patients treated by acupoint application therapy were increased. Moreover, acupoint application might lower the level of immunoglobulin E (MD = −54.58, 95% CI (−63.54, −45.61), Z = 11.93, P < 0.00001) and EOS (MD = −0.21, 95% CI (−0.35, −0.06), Z = 2.77, P = 0.006). The LCQ (Leicester cough questionnaire) total score of CVA patients was also increased (MD = 2.30, 95% CI (1.55, 3.06), Z = 5.98, P < 0.00001). Acupoint application therapy is effective in controlling symptoms of CVA. It also has a positive effect in improving lung function and life quality of patients. It can reduce the eosinophil levels and peripheral blood IgE levels of patients as well.

The clinical differences between cough variant asthma cells and humoral immunology indicators.

The Purpose of this study was to study and analyze the clinical differences between cough variant asthma (CVA) cells and humoral immunology indicators. For this aim, 73 sick children with CVA were enrolled in this study and were admitted to the Pediatric Inpatient Department of Weifang Maternal and Child Health Hospital for treatment from April 2019 to May 2021. They were divided into the attack stage group (n=45) and the remission stage group (n=28). Meanwhile, 30 children with normal physical examination results were selected as normal controls. Differences in serum levels of TNF-, hs-CRP, IL-4, IL-5, IL-6 and IL-13 were compared among the three groups, as well as the differences in humoral immunology indicators such as T lymphocyte subsets CD3+, CD4+, CD8+, CD4+/ CD8+ and IgA, IgG, IgG, IgM, IgE, IgE and IgG subtypes. Results showed that serum levels of TNF-α and hs-CRP were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). The serum levels of TNF-α and hs-CRP were higher in the remission stage group than those in the normal control group, and the difference was not statistically significant (P>0.05). Serum levels of IL-4, IL-5, IL-6 and IL-13 were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). CD4+ and CD4+/CD8+ were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). The difference in serum levels of IgG1, IgG2 and IgG3 was not statistically significant (P>0.05) among the three groups. While the level of IgG4 subsets in the attack stage group was significantly higher than that in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). Then the cytokines, cells and humoral immunology indicators of CVA patients are not in their normal range. They are involved in the pathogenesis of CVA. The combined detection is of great clinical significance in the diagnosis of early CVA to avoid misdiagnosis and missed diagnosis.

Suhuang Antitussive Capsule Ameliorates Corticosteroid Insensitivity in Cough Variant Asthma Guinea Pigs by Inhibiting p38 MAPK Signal Pathway.

Methods The CVA guinea pig model was successfully established by use of ovalbumin (OVA) sensitization and cigarette smoke (CS) exposure. The guinea pigs were divided into 6 groups: a control group, an OVA model group, an OVA + CS model group, a Suhuang treatment group, a BUD treatment group, and a combination (Suhuang and BUD) treatment group. The effects of the treatment were determined by measuring lung function (RI/Cydn) and cough symptoms (coughs number/cough latency) as outcome criteria. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA. Lung tissues were stained by hematoxylin and eosin (H&E). The expressions of GR/total p38 MAPK/p-p38 MAPK were detected by Western blot. The MKP-1 mRNA levels were detected by RT-PCR. Results Combination treatment significantly decreased RI/coughs numbers and increased Cydn/cough latency. Significantly, the results indicated that combination treatment decreased injury to pulmonary tissues. Results also revealed that levels of inflammatory cytokines were reduced in all treatment groups but most markedly in the combination treatment group. Moreover, Suhuang treatment significantly ameliorated corticosteroid insensitivity by improving the expression of glucocorticoid receptors (GR). The expressions of total p38 MAPK and p-p38 MAPK in lung tissue were significantly inhibited in the Suhuang and combination treatment groups. The MKP-1 mRNA levels in Suhuang and combination treatment groups were also increased significantly. Conclusion Suhuang was effective for reversing corticosteroid insensitivity by regulating the p38 MAPK signal pathway, and combining BUD and Suhuang treatment showed synergistic interactions in CVA guinea pigs. Our findings showed that this combination therapy might be a promising therapeutic agent for CVA and also clarified its underlying mechanism of action, providing a theoretical basis for clinical combination treatment with Suhuang and BUD in CVA patients.

Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma

BackgroundWhether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.MethodsNinety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.ResultsThe median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05).ConclusionsMontelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar.Trial registration ClinicalTrials.gov, number NCT01404013.

Fractional Exhaled Nitric Oxide (FeNO) Integrating Airway Hyperresponsiveness (AHR) Examination Promotes Etiologic Diagnosis and Treatment for Children with Chronic Cough.

BackgroundChronic cough is the main reason why parents seek medical treatment for their children. This study aimed to evaluate changes in airway function and inflammation levels and associated values in diagnosing and treating chronic cough.Material/MethodsThis study involved 118 children with chronic cough, including 45 cough-variant asthma (CVA) patients, 53 upper-airway cough syndrome (UACS) patients, and 20 post-infection cough (PIC) patients. Chronic cough was diagnosed as described by guidelines of the American College of Chest Physicians for evaluating chronic cough. Pulmonary ventilation function and airway hyperresponsiveness (AHR) were evaluated. Fractional exhaled nitric oxide (FeNO) levels and eosinophilic airway inflammation were measured. Eosinophil (EOS) count in sputum was also examined. CVA patients were treated with inhaled glucocorticoids, which have anti-inflammatory effects.ResultsFeNO and sputum EOS levels were higher in CVA patients compared with UACS and PIC patients (P<0.05). CVA patients demonstrated significantly higher small airway indexes, including 25% forced expiratory flow (FEF), 50% FEF, and 75% FEF, compared with UACS and PIC patients (P<0.05). FeNO level was positively correlated with EOS in sputum (r=0.468, P=0.0001) and cough symptom scores (r=0.402, P<0.05). FeNO, EOS, and cough symptoms were significantly improved in CVA patients after glucocorticoid treatment. AHR was improved in all chronic cough patients after treatment. Cough-relief CVA patients demonstrated significantly higher FeNO levels compared with those without cough relief (P<0.05).ConclusionsFeNO integrating pulmonary function and AHR examination can improve etiologic diagnosis and treatment for chronic cough in children.

A multicenter, prospective, observational study on montelukast monotherapy or montelukast-based combinations treating cough variant asthma.

BackgroundEvidence of treatment against cough variant asthma (CVA) is insufficient for the clinical practice in China. We aimed at evaluating the real-world effectiveness of montelukast (MONT) alone or in combination with low-dose inhaled corticosteroids (ICS) and low-dose ICS plus long-acting beta-2-agonists (LABA) for Chinese CVA patients in a multicentre, prospective, cohort study.MethodsAdult patients diagnosed with CVA defined as chronic cough >8 weeks with a positive bronchial provocation test and normal chest X-ray findings were enrolled at respiratory clinics. Study treatment followed routine clinical practice. The investigators initiated MONT by 10 mg/day alone or in combination with a low-dose ICS +/− LABA and followed up treatment outcomes for 4 weeks. The primary outcome measure was the change in cough score (CS) from baseline.ResultsThe study enrolled 247 patients (MONT =146, MONT + ICS =38, MONT + ICS/LABA =63). In the primary analysis, the mean change (95% CI) in CS at the end of the study was −1.2 (−1.6, −0.9), −0.9 (−1.5, −0.4), and −1.3 (−1.7, −0.8) in the three groups, respectively. MONT monotherapy had a satisfactory rate of weekly asthma control at the end of the study (83.5%, 95% CI: 75.1%, 89.4%) in the per-protocol analysis. Rates of weekly asthma control were similar in two MONT-based combination regimens (83.9%, 81.4%). Short-acting beta-2-agonist (SABA) user (≥2 times per week) was 16.8% in the MONT group.ConclusionsThe real-world effectiveness of MONT alone or in combination with ICS or ICS and LABA was acceptable for CVA short-term control.

The secondary prevention effect and influence on serum sIgG4, IL-27 and IL-33 levels of subcutaneous immunotherapy in children with allergic rhinitis and cough variant asthma

Objective:To observe the secondary prevention efficacy of subcutaneous immunotherapy in children with allergic rhinitis（AR） and cough variant asthma（CVA） and to analyze its effect on the levels of serum sIgG4, IL-27 and IL-33. Method:The clinical data of 112 children aged 5-12 years with AR and CVA were retrospectively analyzed and divided into control group（52 cases） and SCIT group（60 cases）. The patients were followed up for 3 years. The control group was received symptomatic treatment only, and the SCIT group was received SCIT on the basis of the control group. The numbers of cases of the two groups of children who produced new allergens and developed CA were analyze during the 3-year treatment. Changes in serum sIgG4, IL-27, IL-33 levels, TNSS, DCSS, NCSS, TRMS, TCMS, VAS score, and FEV1% before and after treatment were analyzed. Result:During the treatment, 4 patients（6.67%） in the SCIT group produced the new allergen, and 20 patients（38.46%） in the control group（χ²=16.73, P<0.05）. There were only 3 cases（5.00%） in the SCIT group, which developed into CA, while 15 cases（28.85%） in the control group. The difference between the groups was statistically significant（χ²=11.74, P<0.05）. Compared with baseline, serum levels of sIgG4 and IL-27 in both groups were significantly increased after 3 years of treatment（P<0.05）, while serum levels of IL-33 were significantly decreased（P<0.05）. After 3 years of treatment, serum levels of sIgG4 and IL-27 in the SCIT group were significantly higher than those in the control group, and serum levels of IL-33 were significantly lower than those in the control group（P<0.05）. Compared with baseline, TNSS, DCSS, NCSS, TRMS, TCMS, VAS, and FEV1% in both groups were significantly improved at 1, 2, and 3 years of treatment（P<0.05）. There was no significant difference in TNSS, DCSS, NCSS, TRMS, TCMS, VAS and FEV1% between the two groups at baseline（P>0.05）, while after 1, 2 and 3 years of treatment the above indicators in the SCIT group were significantly better than those in the control group（P<0.05）. Conclusion:SCIT treatment can prevent AR with CVA patients from producing new allergens and developing into CA, and improve serum sIgG4 and IL-27 and IL-33 levels.

The Efficacy and Prevalence of Montelukast Therapy in Cough-Variant Asthma Patients in Al-Kindy Teaching Hospital

BACKGROUND: Cough-variant asthma (CVA) is a type of asthma in which the main symptom is a dry, non-productive cough.&#x0D; OBJECTIVE: The objective of the study was to evaluate the therapeutic effect of Montelukast in CVA and to investigate the prevalence of Montelukast in CVA.&#x0D; METHODS: A cross-sectional study was conducted on 30 patients with chronic cough at least 8 weeks using Montelukast at Al-Kindy Hospital over the period of January 2018‒March 2018. An interview using questionnaire was used to collect the data that were specifically prepared to meet the objective of study including age, sex, associated disease, exacerbation factors, and classical therapy.&#x0D; RESULTS: There was a reduction of the symptoms associated with CVA after treatment with Montelukast. The prevalence of exacerbation factors was as follows: Dust (73.3%) of patients, food (36.7%), exercise (60%), psychological (56.7%), smoking (30%), and others (perfume and cold weather) (26.7%). The usage of Montelukast in this study was 73.3% (22 patients). Patients using Montelukast have shown improvement of symptoms as follows: Chest pain was relieved from 57.1% of patients, exhaustion (58.3%), vomiting (76.5%), sleep disturbance (54.5%), affecting daily life in 57.1%, and syncope 66.7%.&#x0D; CONCLUSION: The prevalence of Montelukast administration to the patients with chronic cough in our study was found to be more than 70% of the 30 total patients. Montelukast usage leads to reduction in the frequency of chronic cough and the symptoms associated with it.

Determinants of response to bronchodilator in patients with cough variant asthma- A randomized, single-blinded, placebo-controlled study

BackgroundNot all patients with cough variant asthma (CVA) show responsiveness to bronchodilators (RB) in clinic. Whether there are specific clinical and pathophysiological features can indicate RB in patients with CVA needs further investigation. Thus, we aimed to investigate the RB in patients with CVA and associated factors. MethodsForty-two CVA patients were randomized in a 2:1 ratio to receive oral bambuterol hydrochloride (10 mg, once daily, for 3 days) or matched placebo, 36 patients (24 with bronchodilator and 12 with placebo) completed the study eventually. RB was considered when cough visual analogue scale (VAS) score decreased 30% or more after 3 days treatment. The baseline clinical and pathophysiological characteristics between patients with RB and patients without RB were compared. CRS was presented with the lowest concentration of capsaicin inducing at least 5 coughing (C5). ResultsThe responsive rate of patients with bronchodilator was significantly higher than that with placebo (62.5% vs 16.7%, p < 0.01). Patients with RB showed a significant greater mean decline of FEV1% predicted after bronchial provocation (26.7% vs 22.4%, p < 0.05) and higher geometric mean of sputum eosinophils (1.37 vs 0.69, p < 0.05) as compared with these without RB. No significant differences in sputum neutrophil, Log C5 were found between patients with RB and patients without RB. There was a moderate correlation between the decline of FEV1% pred and RB (rs = 0.443, p < 0.05). The regression analysis showed that nocturnal cough was a predictor of RB (OR, 7.33, 95% CI: 1.11–48.26, p = 0.038). No adverse events were reported by all of the patients after the study. ConclusionMore than one-third of patients with CVA do not respond to bronchodilator treatment, indicating that the response to bronchodilator should not be a diagnostic requirement of CVA. CVA patients with higher airway responsiveness will more likely respond to bronchodilator. Cough of CVA might be elicited by different mechanisms, which suggests that CVA could be divided into two phenotypes according to the response to bronchodilators.

Diagnostic value of volumetric capnography in patients with chronic cough variant asthma

OBJECTIVES:To evaluate the quantitative changes and diagnostic performance of volumetric capnography (VCap) parameters in patients with cough variant asthma.METHODS:This cross-sectional study enrolled 31 patients with cough variant asthma and 30 patients with chronic cough without asthma between November 2010 and March 2012. VCap measurements were recorded at baseline, during the five steps of the histamine challenge, and after bronchodilation with salbutamol. They were then compared between the baseline and histamine challenge, and between the two groups. Receiver operating characteristic curve analysis was performed for different VCap measurements.RESULTS:The slope of phase III (dc\\dv3) and the ratio of phase III slope to phase II slope (SR23%) decreased from baseline upon challenge with 1.1 mg histamine in cough variant asthma patients but increased in patients with chronic cough without asthma. Additionally, the change upon challenge with 1.1 mg histamine in dc\\dv3 from baseline (S6-S1dc\\dv3) in cough variant asthma patients had the largest area under the curve (AUC) (0.814, 95% CI: 0.697-0.931; p<0.001). The AUC for change upon challenge with 1.1 mg histamine in SR23% from baseline was 0.755 (95%CI: 0.632-0.878; p<0.001). At a cutoff of 19.8, S6-S1 dc\\dv3 had a sensitivity of 74.2% and specificity of 90.0% and at a cutoff of 40.7, S6-S1 SR23% had a sensitivity of 48.4% and specificity of 96.7%.CONCLUSION:Patients with cough variant asthma exhibit distinct VCap responses for dead space parameters upon challenge with histamine in comparison to patients with chronic cough. VCap parameters like phase III slope and phase III/phase II slope ratio could be used to aid the diagnosis of cough variant asthma.

Suhuang Zhike Capsules for the Treatment of Cough Variant Asthma: A Meta-analysis.

Cough variant asthma (CVA) is a unique type of asthma characterized by cough as the only or primary clinical presentation. Inhaled glucocorticoid is the main treatment in clinical practice currently, but its efficacy remains relatively unsatisfactory. Traditional Chinese medicine has certain advantages in the treatment of CVA, and at present, the most commonly used traditional Chinese medicine is Suhuang Zhike Capsule (SZC). The aim of this study was to systematically evaluate the efficacy and safety of SZC in the treatment of CVA using a meta-analysis. A comprehensive search of papers published in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM), Wanfang Database, and VIP Information (VIP) from January 2018 to June 2019 was conducted. Review Manager 5.3 was used to carry out a meta-analysis of 10 studies that fulfilled the inclusion criteria. In a total of 10 randomized controlled trials, 896 CVA patients were included. The results showed the following: (1) compared with conventional Western medicine, SZC can effectively increase the efficacy rate of CVA (RR 1.25, 95% CI, 1.16–1.35, P < 0.00001) and (2) compared with other traditional Chinese medicines, SZC can effectively increase the efficacy rate of CVA (RR 1.44, 95% CI, 1.01–2.05, P=0.05), In conclusion, our study builds on existing clinical evidence showing that SZC is safe and effective in treating CVA. However, larger randomized controlled trials are required for further validation.

Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma

Pulmonary dysfunction is tightly associated with cough variant asthma (CVA), a respiratory damage disease. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, plays a crucial role in the treatment and complication of CVA in the long clinical application. In this study, we aimed to investigate the protective effects and underlying antitussive mechanisms of Suhuang on pulmonary function in ovalbumin (OVA)-induced CVA rats. Administration (i.g.) of Suhuang significantly alleviated pulmonary damage and dysfunction. Suhuang improved ER stress and PKCε translocation via regulation of Ca2+ trafficking. Suhuang also inhibited NLRP3 inflammasome activation, as evidenced by disrupting the assembly of NLRP3 inflammasome and reducing the expression of cleaved caspase-1, and decreased IL-1β secretion. Besides, it’s identified that TXNIP induction and RIP1-RIP3-Drp1 pathway were required for the inhibitory routes of Suhuang from ER stress to NLRP3 inflammasome activation. Consistent with the in vivo findings, Suhuang also attenuated ER stress/NLRP3 inflammasome activation, and thereby restored pulmonary homeostasis in vitro. Meantime, these functions were diminished by blocking ER stress, indicating that ER stress is essential for the effects of Suhuang on pulmonary function. A further in vivo analysis showed that Suhuang-driven pharmacological inactivation of NLRP3 inflammasome and amelioration of pulmonary dysfunction were reversed by an ER stress inducer tunicamycin, well confirming the beneficial effects of Suhuang on pulmonary function by regulation of ER stress. Collectively, these results indicated that Suhuang contributed to impairing NLRP3 inflammasome activation via inhibition of ER stress, which was responsible for the protection of pulmonary homeostasis. These findings may provide a pharmacological groundwork and important new experimental data regarding the clinical treatment of Suhuang in CVA patients.

Clinical and pulmonary function changes in cough variant asthma with small airway disease

BackgroundIt is known that small airway disease is present across all asthma severities; however, its prevalence and clinical characteristics in cough variant asthma (CVA) have not been fully illuminated.MethodsA total of 77 CVA patients with preserved proximal airway function (FEV1/FVC > 70%) were enrolled in this study. The correlation between forced expiratory flow at 50% (FEF50%) and FEF25–75% in the CVA population was first evaluated. FEF50% was determined to be an easy and feasible parameter for identifying small airway disease. CVA with small airway disease is defined as FEF50% < 70%, whereas CVA with normal small airways is identified as FEF50% > 70%. Demographic features, clinical characteristics, lung function and induced sputum test results were determined at the initial visit and at the final visit 1 year later.ResultsFEF50% is a good marker for small airway disease. The cutoff value of 70% is more sensitive than the previously published 60% for identifying more patients with small airway problems early. Nearly half of the CVA population (45.4%) in our cohort had small airway disease. In both group, symptoms improved greatly after anti-asthmatic treatment. Interestingly, the changes in symptom scores [Asthma Control Test (ACT) and ACQ] were even greater in the CVA with small airway disease group than in the control group because of the higher medication usage in this subpopulation in real life. However anti-asthmatic therapy can not reverse small airway dysfunction. At last visit, FEF50% of CVA with small airway diseases was 57.2% ± 10.5%, still much lower than the control group (FEF50% = 92.6% ± 16.5%).ConclusionsIn our cohort, nearly half of the CVA population had small airway disease. Their demographic features, clinical characteristics, airway eosinophils and drug responsiveness were quite similar between two groups, which means these indices can not be used as markers to identify small airway obstruction. We found FEF50% is an easy and feasible marker for early identification. Regular anti-asthmatic medication helped to improve clinical scores in patients with small airway disease, but the obstruction could not be reversed over 1-year period.

A retrospective study of clinical features of cough variant asthma in Chinese adults

BackgroundClinical features of cough variant asthma (CVA) in Chinese adults are largely uncertain.MethodsA total of 303 patients newly diagnosed as uncontrolled asthma (symptom control and future risk of adverse outcomes), including 175 CVA and 128 classic asthma (CA), were enrolled in this retrospective survey. Clinical features including basic characteristics, pulmonary function, airway hyperresponsiveness (AHR) and cell counts of induced sputum, were compared retrospectively. All patients were classified into four inflammatory subtypes based on the counts of induced sputum eosinophils and neutrophils as eosinophilic (E), neutrophilic (N), mixed granulocytic (M), and paucigranulocytic (P) subtypes. Inflammatory subtype distribution was also compared.ResultsCompared with CA patients, CVA patients were younger (P = 0.009), had a higher prevalence of female patients (P = 0.001), higher parameter values of baseline pulmonary function (P ≤ 0.01 for all), shorter duration of disease (P = 0.002), lower AHR (P = 0.001) and lower sputum eosinophil% (P = 0.009). There was a difference in the AHR distribution as the percentage of moderate and severe AHR in CVA was significantly lower than in CA (41.72% VS 64.70%, P = 0.001). The inflammatory subtype distribution was different as the proportion of E and M subtypes in CVA was lower than in CA (56.0% vs 67.19%, P = 0.049). The proportion of subtype P was the lowest and subtype M was the highest in both CVA and CA patients. There was a similar negative correlation of sputum eosinophil% with AHR in CVA and CA (r = − 0.337, P < 0.0001 and r = − 0.27, P = 0.026, respectively), and a positive correlation between sputum eosinophil% and improvement rate of FEV1 after inhalation of bronchodilator (ΔFEV1%) (r = 0.33, P = 0.01).ConclusionsCVA patients showed a better pulmonary function and lower airway inflammation in contrast to CA patients, which may participate in the pathogenesis of chronic cough in CVA.

A meta-analysis of Yupingfeng powder in conjunction of western medicine on cough variant asthma

Objective To evaluate the efficacy and safety of Yupingfeng powder in conjunction treatment of western medicine on cough variant asthma (CVA). Methods We searched CNKI, Wanfang database, VIP database and PubMed through computer from the database building to October 31st 2017. The randomized controlled trails (RCT) with the comparison in the treatment of CVA with Yupingfeng powder and western medicinal were identified and included. The quality of RCTs was assessed by Jadad scores, and meta-analyses were performed by Review Manager 5.3 software. Results Totally 15 RCTs involving 1 318 patients were included into the study, which all belonged to the low methodological quality. The meta-analysis results showed that compared with the western medicine alone, the treatment in conjunction of Yupingfeng powder can significantly improve the clinical effective rate [OR=3.45, 95% CI (2.38-5.02), P<0.01], reduce the recurrence rate [OR=0.25, 95% CI (0.16-0.38), P<0.01]. There were no statistical significant differences with untoward effect between above two treatment groups [OR=0.70, 95% CI (0.34-1.46), P=0.35]. Conclusions The Yupingfeng powder combined with the routine therapy may improve the clinical effective rate, and reduce the recurrence rate for CVA patients. However, we need more high-quality RCTs to comfirm such results. Key words: Yu Ping Feng San; Cough variant asthma; Randomized controlled trial; Meta-analysis