Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea‐pigs

Zheng, Fang; Huang, Chuqin; Zhang, Junfeng Jim; Xie, Jiaxing; Dai, Shikun; Ge, Erjia; Xiang, Jun; Yao, Hongmei; Huang, Rongquan; Bi, Xinhui; Wang, Boguang; Zhong, Nanshan; Lai, Kefang

doi:10.1111/cea.13308

Cited by 34 publications

(20 citation statements)

References 47 publications

(56 reference statements)

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“…We also observed a mild increase in the percentage of eosinophils in BALF after citric acid inhalation, but not after cold exposure. The airway eosinophilia was comparable to that observed in our previous study (Xu et al, 2018) and was possibly related to epithelial injury in the airway induced by the cough itself and bronchoconstriction during the repeated inhalation of citric acid (Fang et al, 2019). Such phenomena can be more representative of, or applicable to, the disease process of chronic cough in humans.…”

Section: Discussionsupporting

confidence: 85%

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

et al. 2020

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Cough exacerbation in cold environments is a characteristic feature of patients with chronic cough. There is consensus that inhalation of cold air stimulates cough receptors but this idea is not consistent with the fact that cold air is usually unable to directly enter the lower airway. To elucidate the effects of cold environments and transient receptor potential ankyrin 1 (TRPA1) on cough, we compared cough reactivity, airway inflammation, and TRPA1 expression in guinea pigs with chronic cough induced by the repeated inhalation of citric acid for 15 days. The guinea pigs were exposed to cold environments for three consecutive days from day 13 to 15. Repeated inhalation of citric acid increased cough reactivity to inhaled cinnamaldehyde. We found that exposure to cold environments further aggravated cough hyperreactivity in guinea pigs with chronic cough, but not in normal guinea pigs. Cough hyperreactivity was promoted when the whole body and trunk-limbs, but not the heads, of the guinea pigs were exposed to cold environments, and abolished by pretreating the skin through immersion in the TRPA1 antagonist, HC-030031. Substance P levels in bronchoalveolar lavage fluid, and TRPA1 expression in the trachea and skin, were increased in guinea pigs when the whole body and trunk-limbs, rather than the head, were exposed to cold environments. However, this trend was also abolished by pretreatment of the skin via immersion in HC-030031. Similar changes in TRPA1 expression were also detected in the sensory fibers of the trachea and skin, as identified by immunofluorescence and laser-scanning confocal microscopy analysis. These results suggest that exaggerated cough hyperreactivity induced by cold environments may be related to activation of the cold-sensing TRPA1 signaling pathway in the skin, rather than the inhalation of cold air.

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Section: Discussionsupporting

confidence: 85%

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

et al. 2020

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“…Previous evidence indicated that PM2.5 exacerbated accumulation of eosinophils and neutrophils into the airway submucosa [26,27]. Another study reached the same conclusion that PM2.5 caused signi cant increase of eosinophils and neutrophils in BALF over time [28]. Therefore, we believed the PM2.5-induced in ammatory injury was the combined action of type 1 and type 2 in ammation.…”

Section: Discussionsupporting

confidence: 54%

The effect and mechanism of Modified Guo-Min Decoction and Yu-Ping-Feng Powder on fine particulate matter-induced lung inflammatory injury and airway mucus hypersecretion in rats

Feng

Meng

et al. 2020

Preprint

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Background Exposure to fine particulate matter (PM2.5) severely impairs public health. The mechanism of PM2.5-induced lung injury is complex and diverse. Modified Guo-Min Decoction (MGMD) and Yu-Ping-Feng Powder (YPFP) have been found to improve clinical symptoms in respiratory patients during smog weather, but the mechanism remains unclear. This study aimed to investigate the effect and mechanism of YPFP and MGMD against PM2.5-induced lung injury. Methods We established the PM2.5 animal model by intratracheal instilling of PM2.5 suspensions. Rats were administrated MGMD/YPFP/distilled water via gavage every day, and all rats were sacrificed after 28 days. At the end of experiment, BALF and lung tissues were collected. Condition of lung injury, inflammatory cells infiltration, inflammatory cytokines, MUC5AC synthesis and release, and phosphorylation of TLR2-MyD88-NFκB and EGFR-PI3K-AKT signalling pathway were evaluated. Results The results demonstrated that both MGMD and YPFP protected rats from PM2.5-induced damaged structure of lung tissues. The infiltration of neutrophil, monocyte, lymphocyte, and eosinophil was reduced after the treatment of two therapies. The production of pro-inflammatory mediators, MCP-1 and NE, as well as the type2 inflammation-related cytokines, IgE and IL-4, were decreased by MGMD and YPFP. However, the MGMD showed more potent effect on inhibiting IL-4, while YPFP benefited in preventing ICMA-1, IL-1β, and IL-17A. Rare significance was detected in the TLR2-MyD88-NFκB of each group. Treatment with MGMD and YPFP decreased goblet cell hyperplasia and the expressions of MUC5AC. The further investigation demonstrated that YPFP had the effect of simultaneously inhibiting the phosphorylation of PI3K and AKT, whereas MGMD only showed a significant difference in AKT. Conclusions Therefore, both MGMD and YPFP could significantly attenuate PM2.5-induced inflammation of lung and airway mucus hypersecretion. Nevertheless, YPFP had more advantage in preventing type1 inflammation and mucus hypersecretion, while MGMD was more beneficial in reducing type2 inflammation.

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“…Rising levels of air pollution from industrial and traffic emissions have become a major threat to public health in China 28. It has been reported that pollutants can not only enhance cough reflex sensitivity, but also induce non-allergic eosinophilic airway inflammation 2930. In China, males account for over 80% of industrial workers31 and traffic police,32 as well as 95% of professional taxi33 and bus drivers,34 whose mean age was 37.6-38.5 years.…”

Section: Discussionmentioning

confidence: 99%

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

Lai

et al. 2019

Allergy Asthma Immunol Res

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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.

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Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea‐pigs

Cited by 34 publications

References 47 publications

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

The effect and mechanism of Modified Guo-Min Decoction and Yu-Ping-Feng Powder on fine particulate matter-induced lung inflammatory injury and airway mucus hypersecretion in rats

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

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