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.

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.

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study

Jing Li,Jian Kang,Changzheng Wang,Jing Yang,Linda Wang,Ioannis Kottakis,Michael Humphries,Nanshan Zhong,China Omalizumab Study Group 대한천식알레르기학회 2016 Allergy, Asthma & Immunology Research Vol.8 No.4

Purpose: Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. Methods: This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). Results: A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. Conclusions: Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile.

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.