Feature Of Cough Variant Asthma Research Articles

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.

Role of prostaglandin E2 in bronchoconstriction-triggered cough response in guinea pigs

A feature of cough variant asthma is a heightened cough response to bronchoconstriction. The mediators of this response are unknown. This study was designed to elucidate the role of lipid mediators in bronchoconstriction-triggered cough response in an experimental animal model.We examined the influence of bronchoconstriction on cell components and mediators including prostaglandin E2 (PGE2) in bronchoalveolar lavage fluid (BALF). We studied the cough response to bronchoconstriction (CRB) by measuring the correlation between the increase in enhanced pause (Penh), an index of bronchoconstriction, and cough counts induced by methacholine (Mch) inhalation in conscious guinea pigs. We then examined the effects of intraperitoneal pretreatment with 16, 16-dimethyl-prostaglandin E2 (dm-PGE2) on CRB and cough counts.The total number of cells and cell components in the BALF were not influenced by bronchoconstriction. While levels of PGE2, prostaglandin I2, and cysteinyl leukotrienes were significantly increased, levels of prostaglandin D2, thromboxane B2, and substance P in the BALF were not. Dm-PGE2 significantly decreased the Mch-induced increase in Penh. Following bronchoconstriction by additional Mch inhalation, dm-PGE2 produced an increase in CRB and cough counts in a dose-dependent manner. Additionally, the heightened CRB following dm-PGE2 treatment was suppressed by pretreatment with PGE2 receptor (E-prostanoid EP) -1 and EP-3 antagonists in a dose-dependent manner, but not by EP-2 and EP-4 antagonists. The EP-1 antagonist also decreased cough counts.These results suggest that PGE2 acts as an exacerbating factor for bronchoconstriction-triggered cough. EP1 and EP3 may provide new therapeutic targets for cough variant asthma.

The measurement of cough response to bronchoconstriction induced by methacholine inhalation in healthy subjects: An examination using the Astograph method

ABSTRACTBackground: We demonstrated that heightened cough response to bronchoconstriction is a fundamental feature of cough variant asthma (CVA). To evaluate this physiological feature of CVA in daily clinical practice, it is necessary to clarify the cough response to bronchoconstriction in healthy subjects. We evaluated cough response to methacholine (MCh)-induced bronchoconstriction in healthy subjects. A forced oscillometry technique was used to measure airway resistance changes with Mch. Methods: Healthy never-smokers (21 men, 20 women; mean 22.3 ± 3.7 years) participated. None had a >3-week cough history, clinically significant respiratory or cardiovascular disorders, or disorders that might put subjects at risk or influence the study results or the subjects’ ability to participate. Twofold increasing concentrations of Mch chloride diluted in phosphate-buffered saline (0.039 to 160 mg/mL) were inhaled from nebulizers at 1-minute intervals during subjects’ tidal breathing after the baseline respiratory resistance (Rrs) was recorded. Mch inhalation continued until Rrs reached twice the baseline value and forced expiratory volume in 1 second (FEV1) decreased to <90% of baseline value. Spirometry was measured before Mch inhalation and immediately after Rrs had increased twofold. Coughs were counted during and for 30 minutes after Mch inhalation. The cough reflex sensitivity to capsaicin was also examined. Results: The number of coughs was 11.1 ± 14.3 (median, 7.0; range, 0 to 71; reference range, 0 to 39.7). There was no significant difference in the cough response between the sexes. The reproducibility of the cough response to bronchoconstriction was sufficient. No correlation existed between the bronchoconstriction-induced cough response and capsaicin cough-reflex sensitivity. Conclusions: Using the Astograph method, cough response to bronchoconstriction could be measured easily, safely and highly reproducibly in healthy subjects.

Bronchoconstriction-triggered cough in atopic cough: A retrospective study

ABSTRACTBackground: Atopic cough (AC) and cough variant asthma (CVA) were identified as major causes of chronic non-productive cough in a Japanese study. A characteristic feature of CVA is the presence of a heightened cough response to bronchoconstriction. On the other hand, the cough response to bronchoconstriction in AC remains unclear. Methods: Methacholine (Mch)-induced cough in AC was measured and compared with that in CVA. Diagnoses of AC and CVA were made based on patient history, physical examination, response to bronchodilator therapy, cough reflex sensitivity to capsaicin, spirometry, and airway responsiveness to methacholine. Results: Thirteen AC patients and 12 CVA patients in whom the criteria were met were recruited to the study. After inhalation of Mch at PC35-PEF40 that means milder bronchoconstriction than PC20-FEV1, cough was triggered a few times in AC. [cough number: 1/ 32 min (0–40)]. Conversely, significantly greater number of coughs was provoked in CVA, compared with AC [cough number: 35.5/ 32 min (25-125), p < 0.05]. Conclusions: The cough response to bronchoconstriction is reduced in AC compared to CVA. This feature may be useful in the diagnosis of chronic cough.

Heightened cough response to bronchoconstriction in cough variant asthma

The pathophysiology of cough variant asthma (CVA) is poorly understood. We compared bronchoconstriction-triggered cough between CVA patients and normal control (NC) subjects. There were two protocols in the study. We measured bronchial responsiveness to methacholine (MCh) and counted the number of coughs in nine CVA patients and seven NC subjects (study A). Using partial and full flow-volume curves, expiratory flow of the partial flow-volume curve at 40% above residual volume level (PEF40) and FEV(1) were used to measure bronchoconstriction. Mild bronchoconstriction was defined as a 35% fall in PEF40 (PC(35) -PEF40), and more severe bronchoconstriction as a 20% fall in FEV1 (PC20) -FEV(1) ). In study B, the same measurements were obtained in six CVA patients before and after therapy. In study A, more coughs were provoked at PC35 -PEF40 in CVA patients (median, 60 coughs/32 min post challenge; range, 12-135) than in NC subjects (median, 0/32 min; range, 0-13; P < 0.05). At PC20 -FEV1 , more coughs were provoked in CVA patients (median, 60/32 min; range, 12-150) than in NC subjects (median, 20/32 min; range, 0-54; P < 0.05). In study B, the six CVA patients who underwent re-examination after treatment had less coughs at PC35 -PEF40 (median, 3/32 min; range, 0-14) and PC(20) -FEV1 (median, 13/32 min; range, 3-26) after therapy than before therapy (median, 54/32 min; range, 33-125 and 52/32 min, 45-96, respectively; P < 0.05). We identified heightened cough response to bronchoconstriction as a feature of CVA.

Cinical analysis on 36 patients with cough variant asthma

Objective To explore the clinical features of cough variant asthma (CVA), reduce misdiagnosis,improve the level of the diagnosis and treatment. Methods The clinical data of 36 patients with CVA was analyzed retrospectively. Results The patients with CVA performance showed no obvious causal chronic cough without asthma and with airway hyperresponsiveness, express positive of the bronchial provocation test and was misdiagnosed easily.13 cases with CVA were misdiagnosed, the misdiagnosis rate was 36.1%. The effect of treatment was obvious through bronchodilator and hormone to this patients. Conclusions The key to reduce misdiagnosis and improve the level of the diagnosis and treatment include increasing awareness of CVA , paying more attention to CVA in the patients with chronic cough specially, completing related check quickly, making early diagnosis and effective treatment. Key words: Cough variant asthma; Diagnosis; Treatment

Cough in asthma

Asthma is one of the most common causes of chronic cough, and cough may be the sole or predominant symptom of asthma. The mechanisms of cough in asthma are complex and presumbably multi-factorial. In particular, the pathophysiologic basis of cough variant versus classic asthma is poorly understood. Recent research utilizing various inhalation challenge tests suggests that preservation of the bronchodilating and bronchoprotective effects of deep inspirations is a distinguishing feature of cough variant asthma. This review outlines the tussive agents used in cough research (including tussive and direct, indirect and combined bronchoconstrictive stimuli), their mechanisms of action, the receptors involved in eliciting cough, and characteristic responses in classic asthma and cough variant asthma.

Features of cough variant asthma and classic asthma during methacholine-induced brochoconstriction: a cross-sectional study

BackgroundLittle is known regarding mechanistic and phenotypic differences between cough variant asthma (CVA), presenting with a chronic cough as the sole symptom that responds to bronchodilators, and classic asthma with wheezing during methacholine inhalation. Here we reported airway sensitivity, airway reactivity, and as the main concern, the appearance of cough and wheezes during methacholine inhalation in patients with CVA or classic asthma.MethodsWe cross-sectionally examined the degrees of airway sensitivity, the point where resistance started to increase, and reactivity, the slope of the methacholine-resistance curve, and the appearance of cough and wheezes in steroid-naïve adult patients with classic asthma (n = 58) or CVA (n = 55) while they were continuously inhaling methacholine during simultaneous measurement of respiratory resistance.ResultsPatients with CVA were less sensitive and less reactive to inhaled methacholine and wheezed less frequently but coughed more frequently during methacholine-induced bronchoconstriction than did patients with classic asthma. Multivariate analysis revealed that airway hypersensitivity and lower baseline FEV1/FVC were associated with the appearance of wheezes, whereas a diagnosis of CVA was associated with coughing.ConclusionThere are mechanistic and phenotypic differences between CVA and classic asthma during methacholine inhalation. Frequent coughing during bronchoconstriction may be a distinctive feature of CVA.

Atopic features of cough variant asthma and classic asthma with wheezing

Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear. To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group. Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment. Patients with classic asthma had higher total IgE (P<0.0001), larger numbers of sensitized allergens (P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P<0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens (P=0.02) and had higher rates of sensitization to HDM (P=0.01) and dog dander (P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease (n=60) and the subgroup with moderate-to-severe disease (n=55), as reported previously. Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential.

Effect of montelukast in a guinea pig model of cough variant asthma

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged non-productive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity and slightly increased bronchial responsiveness. Recently, we reported the animal model of cough variant asthma. The aim of this study was to clarify the involvement of cysteinyl leukotrienes (cysLTs) in this model by using a specific leukotriene receptor antagonist, montelukast. Cough number and specific airway resistance (sRaw) were measured during the antigen inhalation (1.5 min) and following 18.5 min, which was carried out 72 h after the first antigen inhalation in actively sensitized guinea pigs, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALF) were measured. Montelukast significantly reduced the antigen re-inhalation-induced cough, increase in sRaw, and increase in total cell number in BALF. In conclusion, cysLTs may play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.

Prevalence and clinical features of cough variant asthma in a general internal medicine outpatient clinic in Japan

The aims of the present study were to examine the prevalence and clinical features of cough variant asthma (CVA) among patients with chronic and persistent cough at an outpatient clinic in Japan, and the efficacy of treatment with an inhaled corticosteroid. This prospective study was conducted at a general internal medicine outpatient clinic in Japan over a 12-month period. CVA was diagnosed as chronic cough without wheezing or any apparent cause, that had persisted for more than 8 weeks, with a normal CXR and spirometry but with bronchial hyperresponsiveness to methacholine, and relief of cough after bronchodilator treatment. We also examined the effects of inhaled beclomethasone propionate on symptoms and differences in PEF between early morning and evening. Of 55 patients suffering from chronic cough, 23 satisfied the criteria for CVA. Their cough occurred more frequently at night and early in the morning. Early morning PEF was significantly lower than evening PEF with a mean variability of 11.5 +/- 4.1%. Treatment with beclomethasone propionate improved coughing and significantly increased early morning PEF, reducing variability to less than 10%. These findings suggest that CVA is most common among patients with chronic cough not due to any apparent cause. The efficacy of inhaled corticosteroid suggests that early intervention is effective in the treatment of CVA.

A GUINEA PIG MODEL FOR COUGH VARIANT ASTHMA AND ROLE OF TACHYKININS

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged nonproductive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity, and slightly increased bronchial responsiveness. Animal model of cough variant asthma has not been reported. The aim of this study was to establish an animal model for studying detailed pathophysiology of cough variant asthma. Bronchial responsiveness to methacholine and cough reflex sensitivity to capsaicin were measured 72 hours after antigen (ovalbumin, OA) inhalation in actively sensitized guinea pigs. Next, cough number and specific airway resistance (sRaw) were measured during 20 minutes following reinhalation of OA solution, which was carried out 72 hours after the first OA inhalation, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALF) were measured. Bronchial responsiveness to methacholine, but not cough reflex sensitivity to capsaicin, was significantly increased 72 hours after the first inhalation of OA solution. Number of coughs, sRaw and total cell number in BALF increased significantly by the OA reinhalation, and the cough number and the increase in sRaw were significantly suppressed by β2 agonist, procaterol. FK224, a specific neurokinin (NK) receptor antagonist, did not significantly influence the OA reinhalation–induced cough and increase in sRaw and total cell number in BALF in this model. In conclusion, pathophysiologic feature of this animal model is similar to that of clinical cough variant asthma. Tachykinins may not play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.

A Study of Clinical Features of Cough Variant Asthma

Patients with cough variant asthma (CVA) and classic asthma are frequently among subjects who present at clinics complaining of a chronic persistent cough. To reveal the features of CVA, we examined the differences in the clinical appearance between CVA and classic asthma. Ten CVA subjects and 11 classic asthmatics were enrolled in the study; they were recruited among patients who presented at the National Minamiokayama Hospital complaining of a chronic cough. The number of eosinophils in peripheral blood was 256 ± 45.8/µl in CVA and 400 ± 123/µl in classic asthma. Eosinophils represented 67% of the cells of sputum in CVA and 82% in classic asthma. Bronchial responsiveness to methacholine was Dmin 1.37 ± 0.56 U in CVA and 0.71 ± 0.46 U in classic asthma. There was no significant difference in these three parameters. There was only a significant difference in v̇25 between CVA and classic asthma, 80.0 ± 6.9 and 52.2 ± 10.0%, respectively. Eosinophil inflammation was almost the same in both CVA and classic asthma.