Long-Term Sequelae of Smoking and Cessation in Spontaneously Hypertensive Rats.

Smoking is a major risk factor for heart attack, stroke, and lung cancer. Tobacco smoke (TS) causes bronchitis, emphysema, persistent cough, and dyspnea. Smoking cessation minimizes risks of TS-related disease. To determine whether smoking cessation could reverse TS-induced pulmonary changes, 10-week-old male spontaneously hypertensive rats were exposed to TS or filtered air (FA) for 39 weeks and allowed to live out their normal lifespan. Significantly (P ≤ .05) decreased survival was noted by 21 months in TS versus FA rats. In TS rats, persistent peribronchiolar, perivascular, alveolar, and subpleural inflammation were observed with pervasive infiltration of pigmented foamy macrophages and plausible intra-alveolar fibrosis and osseous metaplasia. Alveolar airspace was significantly (P ≤ .05) increased in TS versus FA rats as was the volume of stored epithelial mucosubstances in the left central axial airway. Increased mucin contributes to airflow obstruction and increased lung infection risks. Findings suggest TS-induced changes do not attenuate with smoking cessation but result in irreversible damage similar to chronic obstructive pulmonary disease. The observed persistent pulmonary changes mirror common TS effects such as chest congestion, sputum production, and shortness of breath long after smoking cessation and represent important targets for treatment of former smokers.

Pulmonary health effects of wintertime particulate matter from California and China following repeated exposure and cessation.

Epidemiological studies show strong associations between fine particulate matter (PM2.5) air pollution and adverse pulmonary effects. In the present study, wintertime PM2.5 samples were collected from three geographically similar regions-Sacramento, California, USA; Jinan, Shandong, China; and Taiyuan, Shanxi, China-and extracted to form PMCA, PMSD, and PMSX, respectively, for comparison in a BALB/c mouse model. Each of four groups was oropharyngeally administered Milli-Q water vehicle control (50 µL) or one type of PM extract (20 µg/50 µL) five times over two weeks. Mice were necropsied on post-exposure days 1, 2, and 4 and examined using bronchoalveolar lavage (BAL), histopathology, and assessments of cytokine/chemokine mRNA and protein expression. Chemical analysis demonstrated all three extracts contained black carbon, but PMSX contained more sulfates and polycyclic aromatic hydrocarbons (PAHs) associated with significantly greater neutrophil numbers and greater alveolar/bronchiolar inflammation on post-exposure days 1 and 4. On day 4, PMSX-exposed mice also exhibited significant increases in interleukin-1 beta, tumor necrosis factor-alpha, and chemokine C-X-C motif ligands-3 and -5 mRNA, and monocyte chemoattractant protein-1 protein. These combined findings suggest greater sulfate and PAH content contributed to a more intense and progressive inflammatory response with repeated PMSX compared to PMCA or PMSD exposure.

In vivo and in vitro inflammatory responses to fine particulate matter (PM2.5) from China and California.

Ambient PM2.5 was collected during the winter season from Taiyuan, Shanxi, China; Jinan, Shandong, China; and Sacramento, California, USA, and used to create PMSX, PMSD, and PMCA extracts, respectively. Time-lag experiments were performed to explore the in vivo and in vitro toxicity of the PM extracts. In vivo inflammatory lung responses were assessed in BALB/c mice using a single oropharyngeal aspiration (OPA) of PM extract or vehicle (CTRL) on Day 0. Necropsies were performed on Days 1, 2, and 4 post-OPA, and pulmonary effects were determined using bronchoalveolar lavage (BAL) and histopathology. On Day 1, BAL neutrophils were significantly elevated in all PM- versus CTRL-exposed mice, with PMCA producing the strongest response. However, histopathological scoring showed greater alveolar and perivascular effects in PMSX-exposed mice compared to all three other groups. By Day 4, BAL neutrophilia and tissue inflammation were resolved, similar across all groups. In vitro effects were examined in human HepG2 hepatocytes, and U937 cells following 6, 24, or 48 h of exposure to PM extract or DMSO (control). Luciferase reporter and quantitative polymerase chain reaction assays were used to determine in vitro effects on aryl hydrocarbon receptor (AhR) activation and gene transcription, respectively. Though all three PM extracts activated AhR, PMSX produced the greatest increases in AhR activation, and mRNA levels of cyclooxygenase-2, cytochrome P450, interleukin (IL)-8, and interleukin (IL)-1ß. These effects were assumed to result from a greater abundance of polycyclic aromatic hydrocarbons (PAHs) in PMSX compared to PMSD and PMCA.

Oculomotor Response to Cumulative Subconcussive Head Impacts in US High School Football Players: A Pilot Longitudinal Study.

Importance: Repetitive subconcussive head impacts in sports have emerged as a complex public health issue. Most of these head impacts remain asymptomatic yet have the potential to cause insidious neurological deficit if sustained repetitively. Near point of convergence (NPC) values have shown to reflect subclinical neuronal damage; however, the longitudinal pattern of NPC changes in association with subconcussive head impacts remains unclear. Objectives: To examine the NPC response to recurring subconcussive head impacts in a single high school football season through a series of repeated measurements. Design, Setting, and Participants: This prospective case-series study of US varsity high school football players included baseline measurements of NPC, measurements at pregame and postgame points from 6 in-season games, and postseason follow-up measurements (a total of 14 points). An accelerometer-embedded mouthguard measured head impact frequency and magnitude from all practices and games. During the 6 games, players wore chest-strap heart rate monitors to record heart rate and estimate their excess postexercise oxygen consumption, accounting for possible physical exertion effects on NPC values. Exposures: Players participated in practices and games with no restriction. Main Outcomes and Measures: Near point of convergence. Results: The 12 included players were all boys, with a mean (SD) age of 16.4 (0.5) years. A total of 8009 head impacts, 177 907 g of peak linear acceleration, and 16 123 371 rad/s2 of peak rotational acceleration were recorded from the players in a single football season. There was a significant increase in NPC over time until the middle of the season (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 3, 6.42 [1.93] cm; P = .01), which was significantly associated with subconcussive head impact frequency and magnitude (0.02 cm per 100 g of peak linear acceleration [SE, 0.0108; 95% CI, 0.0436-0.004]; P = .01; 0.023 cm per 10 000 rad/s2 of peak rotational acceleration [SE, 0.009; 95% CI, 0.041-0.0105]; P = .02). However, NPC values began to normalize toward baseline level from midseason (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 6, 5.75 [2.23] cm; P = .32), as supported by a significant quadratic trend (ß [SE], -0.002 [0.001] cm/d; P = .003), while participants continued to incur subconcussive head impacts. Conclusions and Relevance: This longitudinal case series study suggests that NPC can be perturbed over the long term by subconcussive head impacts but may normalize over time. The oculomotor system may have an adaptational capacity to subclinical head impacts, yet the mechanism for such remains an open question and warrants further investigation.

TH17-Induced Neutrophils Enhance the Pulmonary Allergic Response Following BALB/c Exposure to House Dust Mite Allergen and Fine Particulate Matter From California and China.

Asthma is a global and increasingly prevalent disease. According to the World Health Organization, approximately 235 million people suffer from asthma. Studies suggest that fine particulate matter (PM2.5) can induce innate immune responses, promote allergic sensitization, and exacerbate asthmatic symptoms and airway hyper-responsiveness. Recently, severe asthma and allergic sensitization have been associated with T-helper cell type 17 (TH17) activation. Few studies have investigated the links between PM2.5 exposure, allergic sensitization, asthma, and TH17 activation. This study aimed to determine whether (1) low-dose extracts of PM2.5 from California (PMCA) or China (PMCH) enhance allergic sensitization in mice following exposure to house dust mite (HDM) allergen; (2) eosinophilic or neutrophilic inflammatory responses result from PM and HDM exposure; and (3) TH17-associated cytokines are increased in the lung following exposure to PM and/or HDM. Ten-week-old male BALB/c mice (n = 6-10/group) were intranasally instilled with phosphate-buffered saline (PBS), PM+PBS, HDM, or PM+HDM, on days 1, 3, and 5 (sensitization experiments), and PBS or HDM on days 12-14 (challenge experiments). Pulmonary function, bronchoalveolar lavage cell differentials, plasma immunoglobulin (Ig) protein levels, and lung tissue pathology, cyto-/chemo-kine proteins, and gene expression were assessed on day 15. Results indicated low-dose PM2.5 extracts can enhance allergic sensitization and TH17-associated responses. Although PMCA+HDM significantly decreased pulmonary function, and significantly increased neutrophils, Igs, and TH17-related protein and gene levels compared with HDM, there were no significant differences between HDM and PMCH+HDM treatments. This may result from greater copper and oxidized organic content in PMCA versus PMCH.