Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity

Kefang Lai,Li Long,Fang Yi,Jiaman Tang,Zhe Chen,Fagui Chen,Jianmeng Zhou,Wen Peng,Liting Zhang,Hu Li,Wenzhi Zhan,Ruchong Chen,Wei Luo,Qiaoli Chen,Kian Fan Chung,Nanshan Zhong 대한천식알레르기학회 2019 Allergy, Asthma & Immunology Research Vol.11 No.6

Purpose: An older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients. Methods: We analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers. Results: The mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with coughvariant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 μmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years. Conclusions: In China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients.

Limited Clinical Utility of Lipid-Laden Macrophage Index of Induced Sputum in Predicting Gastroesophageal Reflux-Related Cough

Dong Junguo,Huang Junfeng,Liu Jiaxing,Tang Yufang,Sivapalan Dhinesan,Lai Kefang,Zhong Nanshan,Luo Wei,Chen Ruchong 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.5

Gastroesophageal reflux disease (GERD) is a common cause of chronic cough (CC). However, the diagnosis of GERD associated with CC based on 24-hour esophageal pH-monitoring or favorable response to empirical anti-reflux trials is invasive and time-consuming. Lipid-laden macrophages (LLMs) are supposed to be a biomarker for micro-aspiration of gastric content in the respiratory tract. This study was conducted to collect LLMs by the sputum induction technique and observe the relationship among the amount of LLMs, cough severity, parameters of 24-hour esophageal pH-monitoring and therapeutic response. The 24-hour esophageal pH-monitoring and sputum induction were performed on 57 patients with suspected GERD associated with CC. Thirty-four patients were followed up after empirical anti-reflux trials of 8 weeks to record the therapeutic response. Lipid-laden macrophage index (LLMI), a semiquantitative counting of LLMs, showed no significant correlation with the values of 24-hour esophageal pH monitoring at the proximal or remote electrode. No difference in LLMI or DeMeester score, as well as cough symptom association probability, were found between the responders and the non-responders. Reflux symptoms were more common in the responders (50%) compared to the non-responders (6%) (P < 0.05). Our study suggests that LLMI shows limited utility in clinically diagnosing GERD associated with CC as an underlying etiology or in predicting response to anti-reflux therapy. Anti-reflux therapy is more effective for CC patients with reflux symptoms than for those without.

Pulmonary IFN-γ Causes Lymphocytic Inflammation and Cough Hypersensitivity by Increasing the Number of IFN-γ-Secreting T Lymphocytes

Deng Zheng,Ding Wenbin,Li Fengying,Shen Shuirong,Huang Chuqin,Lai Kefang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.6

Purpose: Respiratory viral infection increases the number of lung-resident T lymphocytes, which enhance cough sensitivity by producing interferon-γ (IFN-γ). It is poorly understood why IFN-γ-secreting T lymphocytes persist for a long time when the respiratory viruses have been removed. Methods: Repeated pulmonary administration of IFN-γ and intraperitoneal injection with different inhibitors were used to study the effects of pulmonary IFN-γ in mice and guinea pigs. Results: IFN-γ administration caused the increasing of IFN-γ-secreting T lymphocytes in both lung and blood, followed by the elevated physiological level of IFN-γ in the lung, the airway inflammation and the airway epithelial damage. IFN-γ administration also enhanced the cough sensitivity of guinea pigs. IFN-γ activated the STAT1 and extracellular signal-regulated kinase (ERK) pathways in lung tissues, released IFN-γ-inducible protein 10 (IP-10), and resulted in F-actin accumulation in lung-resident lymphocytes. The CXC chemokine receptor 3 (CXCR3) inhibitor potently suppressed all the IFN-γ-induced inflammatory changes. The STAT1 inhibitor mitigated IFN-γ-secreting T lymphocytes infiltration by inhibiting T lymphocytes proliferation. F-actin accumulation and the ERK1/2 pathway contributed to pulmonary IFN-γ-induced augmentation of the airway inflammation and increasing of IFN-γ-secreting T lymphocytes in blood. Conclusions: High physiological levels of IFN-γ in the lung may cause pulmonary lymphocytic inflammation and cough hypersensitivity by increasing the number of IFN-γ-secreting T lymphocytes through the IP-10 and CXCR3 pathways.

alAn Intratracheal Challenge Murine Model of Asthma: Can Bronchial Inflammation Affect the Nose?

Jiaxing Xie,Yin Xi,Qingling Zhang,Guoqin Chen,Luo Wei,Kefang Lai,Nanshan Zhong 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.1

Purpose: Extensive data support the influence of the upper airway on lower airway inflammation and pathophysiology in allergic disease. However, few studies have focused on allergic inflammation in the nose after an isolated lower airway allergen challenge, a situation that can exist clinically when human subjects breathe primarily through the mouth, as occurs when nasally congested. This study used a mouse model to investigate whether upper airway inflammation and hyperresponsiveness were induced by an isolated lower airway allergen challenge. Methods: BALB/c mice were sensitized by systemic intraperitoneal injection of ovalbumin/saline and challenged with intratracheal ovalbumin/saline. Inflammation in the nose and lungs was assessed by cytology and histology of nasal tissues and bronchoalveolar lavage fluid (BALF), while nasal airway resistance and response were measured over 3 days post-challenge. Results: Intratracheal application of an allergen in anaesthetized mice resulted in exclusive deposition in the lower airway. Compared to control animals, ovalbumin -sensitized mice after challenge showed bronchial hyperreactivity and increased IL-5 in the serum BALF, as well as eosinophil infiltration in the lungs. However, nasal histology of the ovalbumin-sensitized mice showed no increase in eosinophil infiltration. The nasal lavage fluid revealed no increase in eosinophils or IL-5, and the nasal airway resistance did not increase after challenge either. Conclusions: In a mouse allergy model, exclusive allergen challenge of the lower airway can elicit a pulmonary and systemic allergic response, but does not induce upper airway inflammatory or physiological responses.

Fructus mume Protects Against Cigarette Smoke Induced Chronic Cough Guinea Pig

Juan Xiang,Xiaodong Liu,Shan Zhong,Zhangfu Fang,Shuirong Shen,Jiaman Tang,Siqi Lai,Kefang Lai 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.2

Fructus mume was recorded in the Chinese Pharmacopoeia and traditional Chinese medical books for chronic cough, but the effect and related constituents are still unknown. Thus, we investigated the protect effects and the relevant constituents of F. mume in a guinea pig model with chronic cough induced by cigarette smoke (CS). The organic acids and polysaccharides in F. mume were detected by high performance liquid chromatography, gel permeation chromatography, and gas chromatography–mass spectrometry. The guinea pigs were orally administered with vehicle or the water extract of Fructus mume (FW) during the 14 days of CS exposure. Citric acid induced coughs were automatically measured by Buxco system. The differential cells in bronchoalveolar lavage fluid (BALF) and histopathological changes in lung tissue were assessed by hematoxylin and eosin staining. The tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) levels in lung tissue were detected via enzyme-linked immunosorbent assay. The mucus productions in tracheas were determined with Alcian blue-periodic acid Schiff staining. The results suggested relatively high concentration of citric acid, chlorogenic acid, and neochlorogenic acid in F. mume, and high proportion of galactose and glucose and lower molecular weight of polysaccharides. Administration of FW significantly reduced the cough frequency, decreased inflammatory cells in BALF and lung tissue, and attenuated the thickening of airway epithelium and submucosa compared with CS-exposure group. Moreover, the overproduction of TNF-α and IL-8 in lung tissues, and mucus in central airways of CS-induced guinea pigs was markedly inhibited by FW. The extract could also protect against CS exposure-induced chronic cough in guinea pigs by reducing coughs, airway inflammation, and mucus overproduction.

Sputum Transcriptomics Reveals FCN1+ Macrophage Activation in Mild Eosinophilic Asthma Compared to Non-Asthmatic Eosinophilic Bronchitis

Zhan Wenzhi,Luo Wei,Zhang Yulong,Xiang Keheng,Chen Xiaomei,Shen Shuirong,Huang Chuqing,Xu Tingting,Ding Wenbin,Chen Yuehan,Lin Mingtong,Pan Xinghua,Lai Kefang 대한천식알레르기학회 2024 Allergy, Asthma & Immunology Research Vol.16 No.1

Purpose: Eosinophilic asthma (EA) and non-asthmatic eosinophilic bronchitis (EB) share similar eosinophilic airway inflammation. Unlike EA, EB did not present airway hyperresponsiveness or airflow obstruction. We aimed to compare the mechanism underlying the different manifestations between EA and EB via sputum transcriptomics analysis. Methods: Induced-sputum cells from newly physician-diagnosed EA, EB patients, and healthy controls (HCs) were collected for RNA sequencing. Results: Bulk RNA sequencing was performed using sputum cells from patients with EA (n = 18), EB (n = 15) and HCs (n = 28). Principal component analysis revealed similar gene expression patterns in EA and EB. The most differentially expressed genes in EB compared with HC were also shared by EA, including IL4, IL5 IL13, CLC, CPA3, and DNASE1L3. However, gene set enrichment analysis showed that the signatures regulating macrophage activation were enriched in EA compared to EB. Sputum cells were profiled using single-cell RNA sequencing. FABP4+ macrophages, SPP1+ macrophages, FCN1+ macrophages, dendritic cells, T cells, B cells, mast cells, and epithelial cells were identified based on gene expression profiling. Analysis of cell-cell communication revealed that interactions between FCN1+ macrophages and other cells were higher in EA than in EB. A wealth of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) interactions between FCN1+ macrophages and other cells have been shown in EA. The gene expression levels of EREG, TGFBI, and VEGFA in FCN1+ macrophages of EA were significantly higher than those of EB. Furthermore, signatures associated with the response to TGF-β, cellular response to VEGF stimulus and developmental cell growth were enriched in FCN1+ macrophages of EA compared to those of EB. Conclusions: FCN1+ macrophage activation associated with airway remodeling processes was upregulated in EA compared to that in EB, which may contribute to airway hyperresponsiveness and airflow obstruction.