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Background: Exposure to wood smoke is associated with negative respiratory health outcomes such as airway infections and development of chronic obstructive pulmonary disease (COPD). Previous controlled exposure studies in humans with bronchoscopy sampling have shown wood smoke-induced bronchial cytotoxicity and impaired macrophage phagocytosis. The present study investigated whether an early and transient acute inflammatory response, as reflected in bronchial mucosal biopsies and lavage fluids, could be detected 6 h after wood smoke exposure.

Methods: On two separate occasions, fourteen healthy participants were exposed, in a double-blind, randomised crossover design, for 2 h to filtered air and diluted wood smoke generated from incomplete wood log combustion with a mean particulate matter concentration of 409 ± 43 µg/m3. Bronchoscopy with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 6 h post-exposure. Biopsies were immunohistochemically stained, and lavage fluids analysed for soluble mediators.

Results: In bronchial mucosal biopsies, nuclear translocation of the transcription factors aryl hydrocarbon receptor (AhR) and phosphorylated c-jun (p-c-jun) was significantly reduced within the bronchial epithelium after wood smoke exposure compared to filtered air. There was no endothelial adhesion molecule-mediated recruitment of neutrophils or other inflammatory cells into the bronchial mucosa.

Conclusions: Exposure to wood smoke from incomplete wood log combustion suppressed nuclear translocation of transcription factors and the expected inflammatory response in endobronchial mucosal biopsies at 6 h post-exposure. This contrasts to the strong proinflammatory effects of other air pollutants such as ozone and diesel exhaust. Together with previous findings of increased cytotoxicity and impaired airway macrophage phagocytosis in humans, this response may be in line with compromised immune defence and increased susceptibility to airway infections, chronic bronchitis and COPD observed in populations exposed to high levels of indoor air pollution from wood smoke.

Background: Soft tissue subglottic stenosis (SGS) progressively reduces the airway dimension below the vocal folds. The cause is unknown. As no cure is available patients face a recurrent need for surgical treatment. Previous research has not established whether the need for repeated interventions diminishes or intensifies as the disease evolves. Our hypothesis is that the number of surgical interventions decrease with disease duration. If true, these findings may have an impact on the surgical setting. Aims/Objectives: To investigate if the number of surgical interventions decreases with disease duration.

Material and Methods: Participants were retrospectively included between 1999–2024 using medical records. The primary outcome measure was number of surgical interventions. A piecewise exponential additive mixed model (PAMM) was applied to assess changes in reoperation risk over time.

Results: 217 cases were identified, 60 (93% females) met the criteria for SGS. These 60 cases underwent 147 surgical procedures. There was a significant decrease in the hazard of re-operation along the timeline from the index surgery, corresponding to 7.7% annual reduction in the risk of requiring a new surgical intervention.

Conclusions and Significance: The risk of reoperation decreased by 7.7%/yr. (p = 0.008), reflected in increased treatment-free intervals and interpreted as decreasing disease activity.

摘要背景: 软组织声门下狭窄（SGS）会逐渐缩小声带下方的气道。其病因不明。由于目前尚无治愈方法，患者需要反复接受手术治疗。既往研究尚未确定随着病情发展，患者需要重复手术治疗的次数是减少还是增加。我们假设手术次数会随着病程的延长而减少。如果假设成立，这些发现可能会对外科治疗产生影响。目的: 探讨手术次数是否会随着病程的延而减少。材料与方法: 回顾性纳入1999年至2024年间的病例，数据来源于医疗记录。主要结果指标为手术次数。采用分段指数加性混合模型（PAMM）评估再次手术风险随时间的变化。结果: 共纳入217例患者，其中60例（93%为女性）符合SGS的诊断标准。这60例患者共接受了147次手术。沿着从首次手术开始的时间线，再次手术的风险显著降低，相当于每年降低7.7%需要再次手术干预的风险。结论和意义: 再次手术的风险每年降低7.7% (p=0.008)，通过TFI的增加反映出来，并被看作代表了疾病活动度的降低。

Background: Reliable access to the olfactory epithelium is important for clinical and translational research; however, data on bilateral biopsy performed in an outpatient setting are limited.

Objectives: To evaluate the feasibility and procedural outcomes of endoscopy-guided bilateral olfactory epithelium biopsy performed under local anaesthesia in an outpatient setting following controlled exposure sessions.

Methods: Healthy adults participated in a randomized, double-blind, crossover exposure study. Endoscopy-guided biopsies were obtained in an outpatient setting. Primary outcomes included bilateral biopsy success, tolerability, adverse events, and nucleic acid yield.

Results: Twenty-nine subjects were enrolled; 26 completed the study. Bilateral biopsies were obtained more frequently after implementation of pre-endoscopic screening than without screening (75.0% vs 30.0%; odds ratio 7.0, 95% CI 1.20–40.83). No serious procedural complications were observed. One self-limiting episode of delayed epistaxis. No participant reported postoperative olfactory dysfunction. All samples yielded RNA and DNA of sufficient quantity and purity for downstream analyses.

Conclusion: Endoscopy-guided bilateral olfactory epithelium biopsy appears feasible in a carefully screened outpatient cohort. Pre-endoscopic anatomical assessment was associated with improved procedural success. Although objective olfactory testing was not performed, and subtle functional changes cannot be excluded, this technique provides a reproducible methodological framework for future studies involving the olfactory cleft.

Background: The use of alternative and renewable fuels in the transport sector is growing rapidly due to increasing demand for sustainable energy solutions, however implying an increased risk for human exposure to emissions from these new fuels.

Methods: In this study, we examined the effects on BEAS-2B cells of particulate matter (PM) emissions, derived from the use of petroleum diesel (SD10) and rapeseed methyl ester (RME100) in a truck engine. We assessed several endpoints, including the induction of apoptotic and necrotic cell death, reactive oxygen species generation inside cells, inflammatory response, and cell cycle alterations.

Results: The characteristics of the exhaust PM varied between the two fuels, where the RME100-derived PM contained lower levels of polycyclic aromatic hydrocarbons and elemental carbon compared to SD10. Toxicological analyses revealed that PM from RME100 induced weaker oxidative stress and cell death responses than SD10. However, unlike SD10, RME100 PM caused a notable arrest in the S-G2/M phase of the cell cycle.

Conclusions: In summary, fuel type clearly influenced the characteristics of PM emissions from a heavy-duty diesel engine, which in turn affected the particles’ biological activity. Overall, RME100 exhaust PM exhibited lower toxicity compared to petroleum diesel PM in the BEAS-2B cell model.

Background: Exposure to standard petrodiesel exhaust is linked to adverse health effects. Moreover, there is a mounting request to replace fossil-based fuels with renewable and sustainable alternatives and, therefore, rapeseed methyl ester (RME) and other biofuels have been introduced. However, recent toxicological research has indicated that biodiesel exhaust may also induce adverse health-related events.

Aim: To determine whether exposure to 100% RME biodiesel (BD100) exhaust would cause an acute airway neutrophilic recruitment in humans.

Methods: Fourteen healthy subjects underwent exposure to diluted BD100 exhaust and filtered air for 1-h, in a blinded, random fashion. Bronchoscopy with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed six hours after exposure. Differential cell counts and inflammatory markers were determined in the supernatant and biopsies were stained immunohistochemically.

Results: Compared with filtered air, BD100 exhaust exposure increased bronchial mucosal endothelial P-selectin adhesion molecule expression, as well as neutrophil, mast cell and CD68 + macrophage numbers. An increased influx of neutrophils and machrophages was also seen in BW.

Conclusion: Exposure to biodiesel exhaust was associated with an acute airway inflammation that appeared similar to preceding petrodiesel exposure studies. The present findings, together with the recently reported adverse cardiovascular effects after similar biodiesel exposure, indicate that biodiesel is not free of toxicity and may affect human health.

The aim of this study was to investigate the relationship between source-specific ambient particulate air pollution concentrations and the incidence of dementia. The study encompassed 70,057 participants from the Västerbotten intervention program cohort in Northern Sweden with a median age of 40 years at baseline. High-resolution dispersion models were employed to estimate source-specific particulate matter (PM) concentrations, such as PM10 and PM2.5 from traffic, exhaust, and biomass (mainly wood) burning, at the residential addresses of each participant. Cox regression models, adjusted for potential confounding factors, were used for the assessment. Over 884,847 person-years of follow-up, 409 incident dementia cases, identified through national registers, were observed. The study population’s average exposure to annual mean total PM10 and PM2.5 lag 1–5 years was 9.50 µg/m3 and 5.61 µg/m3, respectively. Increased risks were identified for PM10-Traffic (35% [95% CI 0–82%]) and PM2.5-Exhaust (33% [95% CI − 2 to 79%]) in the second exposure tertile for lag 1–5 years, although no such risks were observed in the third tertile. Interestingly, a negative association was observed between PM2.5-Wood burning and the risk of dementia. In summary, this register-based study did not conclusively establish a strong association between air pollution exposure and the incidence of dementia. While some evidence indicated elevated risks for PM10-Traffic and PM2.5-Exhaust, and conversely, a negative association for PM2.5-Wood burning, no clear exposure–response relationships were evident.

In urban areas, inhalation of fine particles from combustion sources such as diesel engines causes adverse health effects. For toxicity testing, a substantial amount of particulate matter (PM) is needed. Conventional sampling involves collection of PM onto substrates by filtration or inertial impaction. A major drawback to those methodologies is that the extraction process can modify the collected particles and alter their chemical composition. Moreover, prior to toxicity testing, PM samples need to be resuspended, which can alter the PM sample even further. Lastly, the choice of the resuspension medium may also impact the detected toxicological responses. In this study, we compared the toxicity profile of PM obtained from two alternative sampling systems, using in vitro toxicity assays. One system makes use of condensational growth before collection in water in an impinger – BioSampler (CG-BioSampler), and the other, a Dekati® Gravimetric Impactor (DGI), is based on inertial impaction. In addition, various methods for resuspension of DGI collected PM were compared. Tested endpoints included cytotoxicity, formation of cellular reactive oxygen species, and genotoxicity. The alternative collection and suspension methods affected different toxicological endpoints. The water/dimethyl sulfoxide mixture and cell culture medium resuspended particles, along with the CG-BioSampler sample, produced the strongest responses. The water resuspended sample from the DGI appeared least toxic. CG-BioSampler collected PM caused a clear increased response in apoptotic cell death. We conclude that the CG-BioSampler PM sampler is a promising alternative to inertial impaction sampling.

The use of alternative diesel fuels has increased due to the demand for renewable energy sources. There is limited knowledge regarding the potential health effects caused by exhaust emissions from biodiesel- and renewable diesel-fueled engines. This study investigates the toxic effects of particulate matter (PM) emissions from a diesel engine powered by conventional petroleum diesel fuel (SD10) and two biodiesel and renewable diesel fuels in vitro. The fuels used were rapeseed methyl ester (RME), soy methyl ester (SME), and Hydrogenated Vegetable Oil (HVO), either pure or as 50% blends with SD10. Additionally, a 5% RME blend was also used. The highest concentration of polycyclic aromatic hydrocarbon emissions and elemental carbon (EC) was found in conventional diesel and the 5% RME blend. HVO PM samples also exhibited a high amount of EC. A dose-dependent genotoxic response was detected with PM from SD10, pure SME, and RME as well as their blends. Reactive oxygen species levels were several times higher in cells exposed to PM from SD10, pure HVO, and especially the 5% RME blend. Apoptotic cell death was observed in cells exposed to PM from SD10, 5% RME blend, the 50% SME blend, and HVO samples. In conclusion, all diesel PM samples, including biodiesel and renewable diesel fuels, exhibited toxicity.

Biodiesel is considered to be a sustainable alternative for fossil fuels such as petroleum-based diesel. However, we still lack knowledge about the impact of biodiesel emissions on humans, as airways and lungs are the primary target organs of inhaled toxicants. This study investigated the effect of exhaust particles from well-characterized rapeseed methyl ester (RME) biodiesel exhaust particles (BDEP) and petro-diesel exhaust particles (DEP) on primary bronchial epithelial cells (PBEC) and macrophages (MQ). The advanced multicellular physiologically relevant bronchial mucosa models were developed using human primary bronchial epithelial cells (PBEC) cultured at air–liquid interface (ALI) in the presence or absence of THP-1 cell-derived macrophages (MQ). The experimental set-up used for BDEP and DEP exposures (18 µg/cm2 and 36 µg/cm2) as well as the corresponding control exposures were PBEC-ALI, MQ-ALI, and PBEC co-cultured with MQ (PBEC-ALI/MQ). Following exposure to both BDEP and DEP, reactive oxygen species as well as the stress protein heat shock protein 60 were upregulated in PBEC-ALI and MQ-ALI. Expression of both pro-inflammatory (M1: CD86) and repair (M2: CD206) macrophage polarization markers was increased in MQ-ALI after both BDEP and DEP exposures. Phagocytosis activity of MQ and the phagocytosis receptors CD35 and CD64 were downregulated, whereas CD36 was upregulated in MQ-ALI. Increased transcript and secreted protein levels of CXCL8, as well as IL-6 and TNF-α, were detected following both BDEP and DEP exposure at both doses in PBEC-ALI. Furthermore, the cyclooxygenase-2 (COX-2) pathway, COX-2-mediated histone phosphorylation and DNA damage were all increased in PBEC-ALI following exposure to both doses of BDEP and DEP. Valdecoxib, a COX-2 inhibitor, reduced the level of prostaglandin E2, histone phosphorylation, and DNA damage in PBEC-ALI following exposure to both concentrations of BDEP and DEP. Using physiologically relevant multicellular human lung mucosa models with human primary bronchial epithelial cells and macrophages, we found BDEP and DEP to induce comparable levels of oxidative stress, inflammatory response, and impairment of phagocytosis. The use of a renewable carbon-neutral biodiesel fuel does not appear to be more favorable than conventional petroleum-based alternative, as regards of its potential for adverse health effects.

Background: Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE.

Methods: Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM₁₀, 300 µg/m³) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo–keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed.

Results: DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = −0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo–keto reductases, or epoxide hydrolase protein expression.

Conclusion: These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways.