Prenatal Particulate Matter/Tobacco Smoke Increases Infants' Respiratory Infections: COCOA Study

Purpose

To investigate whether prenatal exposure to indoor fine particulate matter (PM_2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects.

Methods

The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician''s diagnosis. Indoor PM_2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase-mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis.

Results

Prenatal exposure to indoor PM_2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM_2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM_2.5 and ETS exposure were not found for upper RTIs.

Conclusions

Prenatal exposure to both indoor PM_2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species-related genes.     

阿奇霉素在吸烟支气管哮喘患者治疗中的作用

目的 探讨阿奇霉素在吸烟支气管哮喘患者中的治疗作用. 方法 选取80例吸烟的支气管哮喘未控制患者随机分为阿奇霉素组与对照组,阿奇霉素组以阿奇霉素联合布地奈德福莫特罗治疗,对照组以布地奈德福莫特罗治疗.观察两组治疗4周及12周后的肺功能变化情况、症状改善情况及呼出气一氧化氮水平. 结果 对照组治疗4周及12周后,患者的哮喘测试评分、肺功能指标与呼出气一氧化氮水平较治疗前均无统计学差异;阿奇霉素组的各项指标在治疗12周后均较治疗前明显好转,且两组间比较差异有统计学意义. 两组均未出现严重不良事件. 结论 阿奇霉素联合吸入布地奈德福莫特罗治疗吸烟的支气管哮喘患者安全有效.     

Health impacts of bushfire smoke exposure in Australia

Smoke exposure from bushfires, such as those experienced in Australia during 2019–2020, can reach levels up to 10 times those deemed hazardous. Short‐term and extended exposure to high levels of air pollution can be associated with adverse health effects, although the most recent fires have brought into sharp focus that several important knowledge gaps remain. In this article, we briefly identify and discuss the existing Australian evidence base and make suggestions for future research.     

Evaluation method for the cytotoxicity of cigarette smoke by in vitro whole smoke exposure

An in vitro whole smoke (WS) exposure method was established to evaluate the toxicological effects of fresh cigarette smoke using the VITROCELL^® system associated with the neutral red uptake (NRU) cytotoxicity assay. The VITROCELL^® system is a newly representative culture and exposure system for in vitro studies of gases or complex mixtures. The impacts of two factors on cytotoxicity measurements of cigarette smoke were investigated using this WS exposure system. The factors include synthetic air exposure and optimal time to perform the NRU assay after smoke exposure. Results showed that synthetic air exposure used in the system did not significantly alter cell survival; 24 h after smoke exposure appeared to be an optimal time-point to assess the cytotoxicity of cigarette smoke. A clear dose–response relationship between smoke exposure and cell viability was demonstrated using this system, and the evaluation method was sensitive to distinguish the differences in smoke-induced cytotoxic effects from different cigarettes. In addition, we tried converting the values of EC₅₀ from WS exposure testing into the values in unit used in total particulate matter (TPM) testing for a purpose of comparison, and the data indicate that the cytotoxicity of smoke measured by WS exposure is greater than that measured by TPM exposure.     

Pivotal role of MUC1 glycosylation by cigarette smoke in modulating disruption of airway adherens junctions in vitro

Cigarette smoke increases the risk of lung cancer by 20‐fold and accounts for 87% of lung cancer deaths. In the normal airway, heavily O‐glycosylated mucin‐1 (MUC1) and adherens junctions (AJs) establish a structural barrier that protects the airway from infectious, inflammatory and noxious stimuli. Smoke disrupts cell–cell adhesion via its damaging effects on the AJ protein epithelial cadherin (E‐cad). Loss of E‐cad is a major hallmark of epithelial–mesenchymal transition (EMT) and has been reported in lung cancer, where it is associated with invasion, metastasis and poor prognosis. Using organotypic cultures of primary human bronchial epithelial (HBE) cells treated with smoke‐concentrated medium (Smk), we have demonstrated that E‐cad loss is regulated through the aberrant interaction of its AJ binding partner, p120‐catenin (p120ctn), and the C‐terminus of MUC1 (MUC1‐C). Here, we reported that even before MUC1‐C became bound to p120ctn, smoke promoted the generation of a novel 400 kDa glycoform of MUC1's N‐terminus (MUC1‐N) differing from the 230 kDa and 150 kDa glycoforms in untreated control cells. The subsequent smoke‐induced, time‐dependent shedding of glycosylated MUC1‐N exposed MUC1‐C as a putative receptor for interactions with EGFR, Src and p120ctn. Smoke‐induced MUC1‐C glycosylation modulated MUC1‐C tyrosine phosphorylation (TyrP) that was essential for MUC1‐C/p120ctn interaction through dose‐dependent bridging of Src/MUC1‐C/galectin‐3/EGFR signalosomes. Chemical deglycosylation of MUC1 using a mixture of N‐glycosylation inhibitor tunicamycin and O‐glycosylation inhibitor benzyl‐α‐GalNAc disrupted the Src/MUC1‐C/galectin‐3/EGFR complexes and thereby abolished smoke‐induced MUC1‐C‐TyrP and MUC1‐C/p120ctn interaction. Similarly, inhibition of smoke‐induced MUC1‐N glycosylation using adenoviral shRNA directed against N‐acetyl‐galactosaminyl transferase‐6 (GALNT6, an enzyme that controls the initiating step of O‐glycosylation) successfully suppressed MUC1‐C/p120ctn interaction, prevented E‐cad degradation and maintained cellular polarity in response to smoke. Thus, GALNT6 shRNA represents a potential therapeutic modality to prevent the initiation of events associated with EMT in the smoker's airway. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

羟基红花黄色素A对香烟提取物诱导A549细胞炎症因子表达作用的研究

目的:探讨羟基红花黄色素A(HSYA)抑制香烟烟雾提取物(CSE)诱导的A549肺泡上皮细胞炎症介质表达升高的作用。方法:用CSE刺激A549肺泡上皮细胞建立损伤模型,细胞分七组:单纯HSYA组、Sham组、CSE组、CSE+HSYA低剂量组(1μmol/L)、CSE+HSYA中剂量组(4μmol/L)、CSE+HSYA高剂量组(16μmol/L)和CSE+阳性对照药红霉素(5μg/mL)组。以RT-qPCR技术检测白介素(IL)-6、白介素(IL)-1β、肿瘤坏死因子(TNF)-α、细胞间黏附分子(ICAM)-1和血管细胞黏附分子(VCAM)-1 mRNA的表达水平;ELISA法检测细胞培养液中IL-6、IL-1β及TNF-α的蛋白水平表达;蛋白质印迹法(western blot)检测细胞p38MAPK磷酸化的水平。结果:与Sham组相比,CSE组IL-6、IL-1β、TNF-α、ICAM-1和VCAM-1 mRNA水平均明显升高(P0.001),给予不同浓度的HSYA后炎症因子的高表达受到抑制,红霉素组也见较明显的抑制。与Sham组相比,CSE组细胞上清液中IL-6、IL-1β和TNF-α蛋白的表达水平明显升高(P0.001),给予不同浓度的HSYA后CSE所诱发的炎症因子的高表达受到抑制,红霉素组也见较明显的抑制。与Sham组比较,CSE组的p38 MAPK的磷酸化水平明显升高(P0.001),给予不同浓度的HSYA后细胞p38 MAPK的磷酸化水平升高受到抑制,红霉素组也可见明显的抑制。结论:HSYA可抑制CSE诱导A549细胞的炎症因子的表达升高。     

Pulmonary function assessment in the early phase of patients with smoke inhalation injury from fire

Objectives

Fire smoke contains toxic gases and numerous chemical compounds produced by incomplete combustion, and may cause injury to the airways. Increased airway reactivity, as well as a decrease in lung function, has been reported as a sequela of smoke inhalation injury. This study was undertaken to assess lung functions in the early phase of patients with smoke inhalation damage from fires.

Methods

A total of 15 patients with fire smoke inhalation (fire smoke group) and 15 subjects with chronic cough but no previous history of lung disease (chronic cough group) were enrolled. For diagnosis of inhalation injury, we performed bronchoscopy, high-resolution computed tomography (HRCT), as well as arterial carboxyhemoglobin (COHb) at admission. Clinical characteristics, pulmonary function tests (PFTs) and mannitol bronchial provocation tests (BPTs) were analyzed and compared between the two groups.

Results

In fire smoke group, initial COHb levels and the PaO₂/FiO₂ ratio were (14.8±18.49)% and 425.7±123.68, respectively. Of seven patients performing HRCT, 4 (57.1%) showed the CT findings compatible with lung involvement of inhalation injury. Post bronchodilator value of the percent of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁) were (76.0±24.27)% and (79.8±27.82)%, respectively. Pre-and post- bronchodilator forced expiratory flow between 25% and 75% of the FVC (FEF_25-75) and the percent predicted FEF_25-75 were 2.41±1.47 vs. 2.65±1.45 L (P=0.045), and (68.7±37.29)% vs. (76.4±36.70)% (P=0.031), respectively. Two patients (13.3%) had positive bronchodilator response (BDR). In fire smoke and chronic cough group, all the subjects showed mannitol BPTs within normal limits.

Conclusions

Fire smoke inhalation leads to mild obstructive small airway disease pattern of pulmonary function in the early phase of patients with fire smoke damage. Further studies, however, need to be followed to identify the relationship between airway narrowing to inhaled mannitol and smoke inhalation injury.     

抑制SCD1对被动吸烟小鼠肺部炎症的影响

目的 研究硬脂酰辅酶A去饱和酶1（stearoyl-CoA desaturase 1,SCD1）对被动吸烟小鼠肺部炎症水平的影响。方法 将C57BL/6小鼠随机分为对照（CON）组、SCD1抑制剂（CAY）组、吸烟（Smoke）组及吸烟加抑制剂（Smoke+CAY）组,每组11~14只,记录各组小鼠体重及肝脏系数。RT-qPCR及Western blot检测CON组与Smoke组内SCD1表达水平。肺组织HE病理染色、肺泡灌洗液（bronchoalveolar lavage fluid,BALF）蛋白浓度测定及细胞计数比较肺部炎症损伤水平。ELISA检测BALF中TNF-α、IL-6、IL-1β水平。电化学发光法检测血浆中IL-4、IL-10、IL-13水平。结果 被动吸烟小鼠肺内SCD1水平升高。给予SCD1抑制剂后,小鼠体重减轻、肝脏系数降低。Smoke+CAY组小鼠较其他组肺部炎症改变明显,BALF中蛋白浓度、细胞计数、TNF-α、IL-6、IL-1β水平均明显升高。各组血浆中IL-4、IL-10、IL-13水平变化不明显。结论 吸烟后小鼠肺内SCD1水平升高,且抑制SCD1会加重被动吸烟小鼠肺部炎症损伤。