Small Airway Dysfunction in Cough Variant Asthma: Prevalence, Clinical, and Pathophysiological Features

Introduction: Small airway dysfunction (SAD) commonly presents in patients with classic asthma, which is associated with airway inflammation, disease severity, and asthma control. However, the prevalence of SAD, its relationship with cough severity and airway inflammation, and its development after antiasthmatic treatment in patients with cough variant asthma (CVA) need to be clarified. This study aimed to investigate the prevalence of SAD and its relationship with clinical and pathophysiological characteristics in patients with CVA and the change in small airway function after antiasthmatic treatment.Methods: We retrospectively analyzed 120 corticosteroid-naïve patients with CVA who had finished a standard questionnaire and relevant tests in a specialist cough clinic, such as cough visual analog scale (VAS), differential cells in induced sputum, fractional exhaled nitric oxide (FeNO) measurement, spirometry, and airway hyper-responsiveness. Information of 1-year follow-up was recorded in a part of patients who received complete cough relief after 2 months of treatment. SAD was defined as any two parameters of maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow at 50% of forced vital capacity (FEF50%) pred, and forced expiratory flow at 75% of forced vital capacity (FEF75%) pred measuring <65%.Results: SAD occurred in 73 (60.8%) patients with CVA before treatment. The patients with SAD showed a significantly longer cough duration (24.0 vs. 6.0, p = 0.031), a higher proportion of women (78.1 vs. 59.6%, p = 0.029), older mean age (41.9 vs. 35.4, p = 0.005), and significantly lower forced expiratory volume in 1 s (FEV1%) pred, FEV1/FVC, MMEF% pred, FEF50% pred, FEF75% pred, PEF% pred, and PD20 (all p < 0.01) as compared with patients without SAD. There were no significant differences in cough VAS, sputum eosinophils count, FeNO, and TIgE level between patients with SAD and those without SAD. Among 105 patients who completed 2 months of antiasthmatic treatment and repeatedly experienced spirometry measurement, 57 (54.3%) patients still had SAD, despite a significant improvement in cough VAS, sputum eosinophils, FeNO, FEF50% pred, and PEF% pred (all p < 0.01). As compared with patients without SAD, patients with SAD showed no significant differences in the relapse rate (50.0 vs. 41.9%, p = 0.483) and wheeze development rate (10.4 vs. 0%, p = 0.063) during the follow-up.Conclusions: Small airway dysfunction occurred in over half of patients with CVA and persisted after short-term antiasthmatic treatment, which showed distinctive clinical and pathophysiological features.

Perspectives and Management of Atypical Asthma in Chinese Specialists and Primary Care Practitioners—A Nationwide Questionnaire Survey

Background and objective: To evaluate the awareness/knowledge and clinical practice for the treatment of atypical asthma among respiratory specialists and primary care practitioners (PCPs) in China.Methods: A total number of 1,997 physicians participated in the survey via WeChat. The questionnaire included six main items: physician demographic characteristics, awareness, diagnosis, medical prescription, assessment/education, and proposal.Results: Cough variant asthma (CVA) was recognized by 97.51% of physicians (1,166 respiratory specialists and 799 PCPs), followed by chest tightness variant asthma (CTVA, 83.72%) and occult asthma (73.54%). Specialists were more likely to follow diagnostic recommendations than PCPs (P < 0.01); however, 34.15% of physicians reported the utility of bronchodilation tests, airway provocation tests, and peak expiratory flow monitoring. A total of 91.70% and 92.01% of physicians prescribed inhaled corticosteroids (ICS) or ICS plus long-acting beta-agonists (LABA) for CVA and CTVA, respectively. Physicians prescribed an ICS or ICS/LABA for 4 (2–8) or 8 (4–12) weeks for CVA and 4 (2–8) or 5 (4–12) weeks for CTVA, and the prescription durations were significantly shorter for PCPs than for specialists (P < 0.01). Further, 52.42% and 35.78% reported good control of CVA and CTVA, respectively, with significantly lower control rates for PCPs than for specialists (P < 0.01). Additionally, specialists exhibited better assessment and educational habits than PCPs.Conclusion: While atypical asthma was identified by most specialists and PCPs, there remains a gap between management in real clinical practice and guideline recommendations, especially for PCPs. Further training of PCPs and clinical studies of atypical asthma are required to improve practice.

Latent Myofascial Trigger Points Release Therapy for Adult Cough Variant Asthma

Background:Cough variant asthma (CVA) is a chronic inflammatory airway disease characterized by airway hyper-responsiveness (AHR). However, it’s precise mechanism is not clear yet. The date show that latent myofascial trigger points (MTrPs) can induce autonomic phenomena, such as over secretion, airway hyper-responsiveness, and so on. Therefore, we assumed that latent MTrPs might disrupt the balance between sympathetic and parasympathetic, which might play an essential role in the etiology of CVA.Results:Recurrence rate was lower in the intervention group than the control group (36w, 5.0% vs. 34.5%, P=0.001). There were significant between-group differences in change from baseline to 36 weeks in VAS (5.80±1.20 to 1.70±1.49 and 5.53±1.21 to 3.18±2.04, respectively; 95%CI, -2.00 to -1.00; P=0.001); ACT-scores (12.78±1.86 to 21.38±2.65 and 13.09±1.97 to 18.53±3.00, respectively; 95%CI, 2.00 to 4.00; P<0.001); ACQ5-scores (2.35±0.86 to 0.85±0.55 and 2.38±0.50 to 1.52±0.62, respectively; 95%CI, -1.00 to -0.40; P<0.001); AQLQ-scores (119.65±17.55 to 174.40±18.22 and 126.22±15.58 to 151.69±24.04, respectively; 95%CI, 14.00 to 34.00; P<0.001); Rate of rescue medication used (36w, 5.0% vs. 29.1%, P=0.003). Fewer adverse events were founded between the two groups (7.5% vs. 14.5%, P=0.462). Conclusions:Compared with budesonide-formoterol plus montelukast therapy, latent MTrPs injection therapy provided a long-acting, practical, short treatment course and safety methods for CVA. The findings indicated that latent MTrPs might play a vital role in the pathogenesis of CVA.Clinical Trials Registration: Chinese Clinical Trial Registry, ChiCTR2100044079. Registered 9 March 2021, http://www.chictr.org.cn/index.aspx

Clinical Analysis of Dispelling Wind, Eliminating Lung and Relieving Cough Combined with Western Medicine in the Treatment of Cough Variant Asthma in Children

Objective: This study mainly explores the clinical effect of dispelling wind, eliminating lung and relieving cough combined with western medicine in the treatment of cough variant asthma. Methods: 80 children with cough variant asthma accepted by our hospital from January 2018 to December 2020 were randomly selected for the study and divided into two groups. One group was the reference group (40 cases) treated with procaterol hydrochloride tablets and montelukast sodium, and the other group was the research group (40 cases). The method of eliminating wind, eliminating lung and relieving cough was combined with procaterol hydrochloride tablets and montelukast sodium to observe and compare the curative effects of the two groups. Results: There was no significant difference in TCM symptom score and eosinophil (EOS) count between the two groups before treatment (P > 0.05); After treatment, the TCM symptom scores of coughs, pharyngeal itching, expectoration, nasal congestion and nasal itching in the research group were lower than those in the reference group, and the EOS count was lower than that in the reference group (P < 0.05); The effective rate of research group was higher than that of reference group (P < 0.05). Conclusions: For children with cough variant asthma, Qufeng Sufei cough relieving method combined with procaterol hydrochloride and montelukast sodium can improve children’s symptoms and reduce eosinophil count.

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.

Elevated Serum Levels of Herpes Virus Entry Mediator and IL-5 in Cough Variant Asthma Versus Classic Asthma Patients

Background Cough variant asthma (CVA) is a special phenotype of asthma. We aimed to elucidate the differential inflammatory features in patients with CVA in contrast to patients with classic asthma (CA). Methods A total of 68 patients with persistent uncontrolled asthma (34 with CVA, 34 with CA) were enrolled. We collected the demographic data, pulmonary function test (PFT) parameters, hematological variables, and several serum biomarkers. The independent-samples t test was used for analyzing measurement data, and Chi-square test was for count data. Multivariate logistic regression analysis was used to determine the possibility of different phenotypes. Receiver operating characteristic (ROC) curves were generated to evaluate the values of biomarkers for distinguishing between CVA and CA. Linear correlation analysis was performed to assess the linear relationship between two variables. Results Compared with CA group, CVA group had a higher percentage of females, lower proportion of asthma family history, shorter disease course, and better pulmonary function (P all < 0.05). Increased levels of blood eosinophil count (P = 0.045), eosinophil percentage (P = 0.046), serum IL-5 (P = 0.011), and serum herpesvirus entry mediator (HVEM) (P = 0.002) were also found in CVA patients compared to those in CA patients compared to those in CA patients. The logistic analysis revealed that serum HVEM had a strong predictive power for CVA group (OR = 1.105, P = 0.015). The sensitivities and specificity of serum HVEM and IL-5 to distinguish between CVA and CA at optimal cut-offs were 85.0% and 61.1%; 85.0% and 61.1%, respectively. Area under the curves (AUCs) of serum HVEM and IL-5 were 0.789 and 0.739, respectively. Furthermore, serum HVEM and IL-5 had no correlation with PFT parameters in CVA group (P all > 0.05). Conclusions Elevated serum levels of HVEM and IL-5 are exhibited in CVA patients, which may indicate their important roles in the pathogenesis and progression of CVA.