Retrospective, observational study of different medication regimens and outcome in children with cough variant asthma.

OBJECTIVE: This retrospective longitudinal cohort study aimed to explore the best therapeutic regimen and treatment duration of cough variant asthma (CVA) in children. METHODS: A total of 314 children with CVA were divided into receive inhaled corticosteroids (ICS) combined with long-acting beta2-agonist (LABA) group, ICS combined with leukotriene receptor antagonists (LTRA) group, ICS monotherapy group and LTRA monotherapy group. All clinical data were statistically analyzed. Logistic regression model was used to compare the advantages and disadvantages of different treatment schemes at each follow-up time point and the best treatment scheme. The Cox proportional hazard regression model based on inverse probability weighting was used to compare the effects of different medication regimens on adverse outcomes with asthma recurrence or progression as the end point. RESULTS: (1) After comprehensive analysis, ICS + LABA group was the preferred control regimen for CVA within 8 weeks. After 8 weeks of diagnosis, the efficacy of ICS group or LTRA group was comparable to that of ICS + LABA group and ICS + LTRA group. (2) The ICS + LABA group showed a significant improvement in cough at an early stage, particularly at 4 weeks; the symptoms of ICS + LTRA and ICS groups were significantly improved at 36 weeks. The LTRA group alone showed significant improvement at 20 weeks. CONCLUSION: ICS + LABA, ICS + LTRA, ICS alone and LTRA alone can effectively treat CVA. ICS + LABA could improve the symptoms most quickly within 8 weeks after CVA diagnosis, followed by ICS + LATR group. After 8 weeks, it can be reduced to ICS alone to control CVA for at least 36 weeks based on the remission of symptoms in children.

Impulse oscillometry in the diagnosis of cough variant asthma in children.

BACKGROUND: Cough variant asthma (CVA) is one of the most common causes of chronic cough in children worldwide. The diagnosis of CVA in children remains challenging. This study aimed to assess the diagnostic utility of impulse oscillometry (IOS) pulmonary function in children with CVA. METHODS: This study included children aged 4 to 12 years diagnosed with CVA who underwent IOS pulmonary function and bronchodilation (BD) tests. A control group of healthy children was matched. Pre- and post-BD IOS parameters were recorded and presented as mean ± standard deviation or median. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to evaluate the discriminatory potential of the IOS parameters for diagnosing CVA. RESULTS: A total of 180 patients with CVA and 65 control subjects were included. The baseline IOS parameters in the CVA group, except X5%pred, were significantly greater compared to the control group. After inhalation of salbutamol sulfate, all IOS parameters improved significantly in the CVA group. However, Z5%pred, R5%pred, and R20%pred remained greater in the CVA group compared to the control group. The improvement rates of IOS parameters in the CVA group significantly surpassed those in the control group. The ROC curve results for pre-BD IOS parameters and the improvement rate during the BD test showed that the combinations of pre-Z5%pred+△Z5% and pre-R5%pred+△R5% achieved the highest AUC value of 0.920 and 0.898, respectively. The AUC values of these combined parameters surpassed those of individual ones. CONCLUSIONS: This study highlights that children with CVA exhibit greater IOS parameters compared to healthy children. The changes in IOS parameters during the BD test provided valuable diagnostic information for CVA, and the combination of various parameters can help pediatricians accurately identify CVA in children.

[Effect and mechanism of Maxing Shigan Decoction on reducing inflammatory response in rats with cough variant asthma via TLR4/MyD88/NF-κB and p38 MAPK signaling pathways].

This study aims to investigate the effect and mechanism of Maxingshigan Decoction on inflammation in the rat model of cough variant asthma(CVA). The SPF-grade SD rats of 6-8 weeks were randomized into normal, model, Montelukast sodium, and low-, medium-, and high-dose Maxing Shigan Decoction groups, with 8 rats in each group. The CVA rat model was induced by ovalbumin(OVA) and aluminum hydroxide sensitization and ovalbumin stimulation. The normal group and model group were administrated with equal volume of normal saline by gavage, and other groups with corresponding drugs by gavage. After the experiment, the number of white blood cells in blood and the levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α) in the serum were measured. The lung tissue was stained with hematoxylin-eosin(HE). Western blot was employed to determine the protein levels of nuclear factor-κB(NF-κB), Toll-like receptor 4(TLR4), myeloid differentiation protein(MyD88), and mitogen-activated protein kinase(MAPK) in the lung tissue. Real-time PCR was carried out to measure the mRNA levels of TLR4 and MyD88 in the lung tissue. Compared with the normal group, the model group showed increased white blood cells, elevated IL-6 and TNF-α levels(P<0.01), lowered IL-10 level(P<0.01), up-regulated protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK(P<0.01) and mRNA levels of TLR4 and MyD88(P<0.01) in the lung tissue. HE staining showed obvious infiltration of inflammatory cells around the airway and cell disarrangement in the model group. Compared with the model group, Montelukast sodium and high-dose Maxing Shigan Decoction reduced the white blood cells, lowered the IL-6 and TNF-α levels(P<0.01), and elevated the IL-10 level(P<0.01). Moreover, they down-regulated the protein levels of TLR4, MyD88, p-p65/NF-κB p65, p-p38 MAPK/p38 MAPK in the lung tissue(P<0.01) and the mRNA levels of TLR4 and MyD88 in the lung tissue(P<0.01). HE staining showed that Montelukast sodium and high-dose Maxing Shigan Decoction reduced inflammatory cell infiltration and cell disarrangement. The number of white blood cells, the levels of IL-10 and TNF-α in the serum, the protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK, and the mRNA levels of TLR4 and MyD88 in the lung tissue showed no significant differences between the Montelukast sodium group and high-dose Maxing Shigan Decoction group. Maxing Shigan Decoction can inhibit airway inflammation in CVA rats by inhibiting the activation of TLR4/MyD88/NF-κB and p38 MAPK signaling pathways.

Effect of the modified painless blistering moxibustion with wheat-grain sized moxa cone on cough variant asthma of pathogenic wind attacking the lung: a randomized controlled trial. / æ”¹è‰¯æ— ç—›éº¦ç²’åŒ–è„“ç¸æ²»ç–—é£Žé‚ªçŠ¯è‚ºåž‹å’³å—½å˜å¼‚æ€§å“®å–˜ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical effect of the modified painless blistering moxibustion with wheat-grain sized moxa cone on cough variant asthma (CVA) differentiated as pathogenic wind attacking the lung and explore the influences on eosinophil count (EOS) in the peripheral blood and the content of interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) in the serum of patients. METHODS: Ninety-two patients with CVA of pathogenic wind attacking the lung were randomly divided into an observation group and a control group, 46 cases in each group. In the observation group, the modified painless blistering moxibustion with wheat-grain sized moxa cone was applied to the unilateral Feishu (BL 13), Gaohuang (BL 43) and Zusanli (ST 36) in each session of treatment, once every 3 days. In the control group, budesonide and formoterol powder inhaler was delivered, 4.5 µg per inhalation, once every half an hour after breakfast and dinner; one more time of inhalation needed if the symptoms were not well controlled, but less than 6 times of inhalation per day. The duration of treatment was 8 weeks in both groups. Separately, before and after treatment, and during the 1-month follow-up after treatment completion, the score of the symptoms of traditional Chinese medicine (TCM) was observed in the two groups; using the lung function detector, the indexes of pulmonary function (forced expiratory volume in one second [FEV1], FEV1/forced vital capacity [FVC] and peak expiratory flow [PEF]) were determined, and the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum were determined before and after treatment; and the clinical effect was compared between the two groups. RESULTS: After treatment and in follow-up, the TCM symptom scores were decreased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that of the control group in follow-up (P<0.05). After treatment, FEV1, FEV1/FVC and PEF were increased when compared with those before treatment in the two groups (P<0.05), and the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum were reduced (P<0.05); there was no statistical difference in these indexes between the two groups (P>0.05). After treatment, the total effective rate of the observation group was 95.7% (44/46), which was not different statistically in comparison with the control group (93.5% [43/46], P>0.05). In the follow-up, the total effective rate of the observation group was 95.7% (44/46), which was higher than that of the control group (78.3% [36/46], P<0.05). CONCLUSIONS: The modified painless blistering moxibustion with wheat-grain sized moxa cone may ameliorate the symptoms of CVA of pathogenic wind attacking the lung and improve the pulmonary functions, which is probably related to the regulation of the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum, thereby, reducing the inflammatory response.

Prevalence and causes of chronic cough in Japan.

BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.

Clinical efficacy of montelukast sodium combination therapy for cough variant asthma in children: A meta-analysis.

This meta-analysis aims to assess the clinical effectiveness of combination therapy with montelukast sodium for the treatment of cough variant asthma (CVA) in children, intending to provide clinical evidence and data to guide the selection of clinical therapy. A literature review was conducted using numerous databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, Embase, PubMed, and Web of Science, from inception to December 2023. Trials meeting the criteria for the combined treatment of montelukast sodium for CVA in children were included. Stata 16.0 software was utilized for meta-analysis. The combined treatment group received montelukast sodium in addition to the control group, while the control group received budesonide, fluticasone propionate, salmeterol-fluticasone, or ketotifen alone. This investigation included 18 papers. All subjects were from the Chinese population. Compared to the control group, the combined treatment group demonstrated a higher effective rate (relative ratio [RR] = 1.23, 95% confidence interval [CI]: 1.18-1.29, p < .001), but no difference in the incidence of adverse reactions (RR = 0.65, 95% CI: 0.42-1.02, p = .060) after treatment. Moreover, the peak expiratory flow (PEF) (SMD = 1.69, 95% CI: 1.09-2.30, p < .001), forced vital capacity (FVC) (SMD = 1.67, 95% CI: 0.94-2.39, p < .001), forced expiratory volume in 1 s (FEV1) (SMD = 1.74, 95% CI: 1.09-2.40, p < .001), and FEV1/FVC (SMD = 1.84, 95% CI: 0.41-3.28, p = .012) were significantly higher in the combined treatment group than in the control group after treatment. Compared with the control group, the levels of tumor necrosis factor-α (SMD = -2.38, 95% CI: -3.22 to -1.55, p < .001), IL-4 (SMD = -2.65, 95% CI: -3.26 to -2.04, p < .001), and IgE (SMD = -2.98, 95% CI: -3.24 to -2.72, p < .001) were significantly lower in the combined treatment group after treatment. The combined use of montelukast sodium in the treatment of pediatric CVA in China is associated with a significant clinical effect, making it a reasonable therapeutic approach.

Microbiota Alterations in Lung, Ileum, and Colon of Guinea Pigs with Cough Variant Asthma.

Alterations in the microbiota composition, or ecological dysbiosis, have been implicated in the development of various diseases, including allergic diseases and asthma. Examining the relationship between microbiota alterations in the host and cough variant asthma (CVA) may facilitate the discovery of novel therapeutic strategies. To elucidate the diversity and difference of microbiota across three ecological niches, we performed 16S rDNA amplicon sequencing on lung, ileum, and colon samples. We assessed the levels of interleukin-12 (IL-12) and interleukin-13 (IL-13) in guinea pig bronchoalveolar lavage fluid using the enzyme-linked immunosorbent assay (ELISA). We applied Spearman's analytical method to evaluate the correlation between microbiota and cytokines. The results demonstrated that the relative abundance, α-diversity, and ß-diversity of the microbial composition of the lung, ileum, and colon varied considerably. The ELISA results indicated a substantial increase in the level of IL-13 and a decreasing trend in the level of IL-12 in the CVA guinea pigs. The Spearman analysis identified a correlation between Mycoplasma, Faecalibaculum, and Ruminococcus and the inflammatory factors in the CVA guinea pigs. Our guinea pig model showed that core microorganisms, such as Mycoplasma in the lung, Faecalibaculum in the ileum, and Ruminococcus in the colon, may play a crucial role in the pathogenesis of CVA. The most conspicuous changes in the ecological niche were observed in the guinea pig ileum, followed by the lung, while relatively minor changes were observed in the colon. Notably, the microbial structure of the ileum niche approximated that of the colon niche. Therefore, the results of this study suggest that CVA development is closely related to the dysregulation of ileal, lung, and colon microbiota and the ensuing inflammatory changes in the lung.

Spirometry in the diagnosis of cough variant asthma in children.

OBJECTIVE: This study aimed to assess the diagnostic utility of spirometry, particularly focusing on small airway parameters, in children with cough variant asthma (CVA). METHODS: This study included children aged 5-12 years with a diagnosis of CVA. Pre- and postbronchodilation spirometry parameters, including FEV1 %pred, FVC%pred, FEV1 /FVC%pred, PEF%pred, FEF25 %pred, FEF50 %pred, FEF75 %pred, MMEF%pred, were recorded. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) was calculated to assess the discriminatory potential of these spirometry parameters for CVA. A prediction model based on logistic regression (LR) was performed. RESULTS: A total of 200 patients with CVA and 73 control subjects were included. Baseline spirometry parameters in the CVA group, except for FVC%pred, were significantly lower compared to the control group. After inhalation of salbutamol sulfate, all parameters showed significant improvement in the CVA group. However, these parameters, except for FEV1 %pred and FVC%pred, remained lower in the CVA group compared to the control group. The improvement rate of each parameter in the CVA group, except for ∆ FVC%, was significantly higher than that in the control group. △ MMEF% achieved the highest AUC of 0.797 with a threshold value of 16.09%, followed by △ FEF75 % (0.792), △ FEV1 % (0.756), and △ FEF50 % (0.747) with threshold values of 19.01%, 4.48%, and 19.4%, respectively. The clinical prediction model included four variables (age, △ FEF25 %, △ FEF75 %, and △ MMEF%) and demonstrated excellent performance distinguishing patients with and without CVA (AUC = 0.850). In the CVA group, the △ FEV1 % showed a positive correlation with small airway parameters. CONCLUSIONS: This study highlights that children with CVA exhibit lower pulmonary function parameters compared to healthy children. Changes in small airway parameters during bronchodilator tests can be valuable in diagnosing CVA, and the LR prediction model incorporating age and several pulmonary parameters can assist physicians in accurately identifying CVA in clinical practice.

Alveolar nitric oxide concentration plays an important role in identifying cough variant asthma and assessing asthma control in children.

OBJECTIVE: To study the value of alveolar nitric oxide concentration (CaNO) in the identification and disease control of cough variant asthma. METHODS: A retrospective study was conducted on cough variant asthma (CVA-Group), nonasthmatic cough (NAC-Group) and healthy control children (C-Group) aged 5-12 years. The exhaled nitric oxide and spirometry test results of the three groups were collected and compared. RESULTS: A total of 410 children were included in this study, including 190 in the CVA-Group, 183 in the NAC-Group, and 37 in the C-Group. The CaNO values of the CVA-Group [11.40 ppb (8.48-14.25)] were significantly higher than those of the NAC-Group and C-Group (all p values <.05). The MMEF %pred values of the CVA-Group [63.65 (56.28-73.58)] were significantly lower than those of the NAC-Group and C-Group (all p values <.05). FeNO50, JawNO and other spirometry indices (FVC %pred, FEV1%pred, FEV1/FVC %pred) showed no significant difference among the three groups. ROC curve analysis showed that the optimal cutoff point value of CaNO was 9.45 ppb, corresponding to 0.816 sensitivity and 0.736 specificity. Spearman correlation analysis showed a significant negative correlation between the CaNO measurement and CVA control score. CONCLUSIONS: CaNO can not only help identify CVA early in children aged 5-12 years with chronic cough but is also significantly negatively correlated with the CVA control score.