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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: Asthma severity is influenced by complex immunologic and environmental factors. While allergic asthma is linked to increased susceptibility to respiratory infections, the combined role of allergy and antibiotic-treated infections in progression to severe asthma has not been fully evaluated.

Objective: To evaluate whether allergic asthma and recurrent respiratory infections (RRI) requiring antibiotics are associated with increased risk of developing severe asthma.

Methods: We conducted a registry-based cohort study using Swedish national registry data. Adults with mild-to-moderate asthma were identified in 2014 (baseline) based on prescription records and absence of severe disease indicators. During a two-year exposure window (2015–2016), RRI was defined as ≥ 2 antibiotic prescriptions for lower respiratory tract infections. The outcome was development of severe asthma during 2017–2019, based on ERS/ATS treatment criteria. Allergic asthma was defined by ≥ 2 prescriptions for anti-allergic medications at baseline.

Results: Among 113,393 patients, 24,692 (21.8%) had allergic asthma. RRI occurred more frequently in allergic versus non-allergic asthma (7.5% vs. 5.9%, p < 0.001). A total of 869 patients (0.77%) developed severe asthma. Incidence was higher in those with RRI and highest among patients with both allergic asthma and RRI (2.0%), corresponding to a relative risk of 3.47 (95% CI: 2.49–4.83) versus patients with neither exposure. Results were consistent after adjustment for age, sex and comorbidities.

Conclusion: Allergic asthma and antibiotic-treated respiratory infections were independent and additive predictors of severe asthma progression. These findings support a clinically actionable risk profile and may inform targeted preventive strategies in asthma management.

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: Extrapulmonary manifestations including cognitive impairment, reduced muscle and cardiovascular function is common in COPD. While high-intensity exercise offers extrapulmonary benefits, its implementation in COPD is challenging. This randomised cross-over trial examined the feasibility and physiological responses of a novel supramaximal high-intensity interval-training (SupraHIIT) protocol compared to moderate-intensity continuous training (MICT) in people with COPD and matched healthy controls (HCs).

Methods: Sixteen people with COPD and 16 HCs performed SupraHIIT and MICT. SupraHIIT consisted of 10x6 sec intervals at ≈150% and ≈200% of maximum aerobic power (MAP), while MICT was performed for 20 min at 60% of MAP. Outcomes were exercise intensity, change in exerkines, feasibility, and cardiorespiratory demand of the modalities.

Results: SupraHIIT was feasible and enabled up to a 3.5-fold increase in external exercise intensity compared to MICT (184±66 and 245±88 watt versus 71±22 watt in COPD, p<0.001). All participants could complete SupraHIIT which was the preferred modality in both groups (p<0.01) while 5/16 participants with COPD interrupted MICT due to intolerable dyspnea or exhaustion (p=0.005). Both modalities increased plasma brain-derived neurotrophic factor (pBDNF) by an average of 59% (range 30%-87%, p<0.05). When normalised for duration at target power, SupraHIIT produced a 5–10-fold greater increase than MICT. Both modalities lead to a variable response in other exerkines including clusterin, lactate, hepatocyte growth factor and interleukin-6.

Conclusion: In COPD, short duration SupraHIIT is more feasible and enables markedly higher external exercise intensities than MICT. By elevating pBDNF and other potentially beneficial exerkines, it shows potential for extrapulmonary benefits.

Background Cognitive impairment is increasingly recognized as an extrapulmonary manifestation of COPD, yet little is known across cognitive domains and associations with exercise capacities and inflammation remain underexplored.

Aims and objectives: To compare cognitive function in COPD and age-, sex- and physical activity matched healthy controls (HCs) and examine associations with exercise performance and systemic inflammation.

Methods: Multi-domain cognitive function was assessed at baseline in 44 individuals with COPD and 39 matched HCs. Correlations of exercise performance including CPET Wpeak and anaerobic capacity (Borg cycle strength test [BCST Wpeak]) and inflammation were analysed.

Results: COPD participants exhibited lower cognitive function across most domains compared to HCs (Table 1). In COPD, BCST Wpeak correlated with trail making tests ([TMT] TMT-A: r=-.43; TMT-B: r=-.32; p<0.05)) visual processing (VP1: r=.43; p<0.05) and memory (PAL: r=.35; p<0.05), while CPET Wpeak showed no associations. Higher fibrinogen levels correlated with poorer TMT-B and PAL1 performance (r=.38 & r=-.40; p<0.05).

Conclusion: Cognitive impairment spans across multiple domains in COPD, even in those with relatively preserved fitness and lung function. Cognitive deficits were associated to anaerobic, but not aerobic exercise capacity and were associated with systemic inflammation in some, but not all domains.

Introduction: Resistance training (RT) is crucial in pulmonary rehabilitation to counteract muscle dysfunction in COPD. However, knowledge about how progression of RT volume is associated with changes in muscle function and functional capacity in COPD is limited.

Method: This secondary analysis from a multicenter RCT included 57 COPD patients (70±7 yrs, FEV1% 49±21, 58% male) who performed 8 weeks of either RT to improve muscle strength or to non-linear periodized resistance training (NLPRT) focusing on muscle strength and muscle endurance. Assessment of muscle strength, muscle endurance and functional capacity (1–Minute Sit-To-Stand, Endurance Shuttle Walk Test, and Unsupported Upper Limb Exercise Test) were conducted at baseline and after 8 weeks. Progression of training volume (set x reps x load) was calculated as the percentage change from week one to week eight.

Results: Significant associations were found between training volume progression and muscle endurance for both RT (r=.48) and NLPRT (r=.64). Significant associations were also identified between progression of training volume and muscle strength for RT (r=.50) and NLPRT (r=.52) (all <0.05). Progression of training volume was not associated with changes in functional capacity.

Discussion: The result from this study indicates that the progression of resistance training volume over time is associated with greater effects on muscle endurance and muscle strength in people with COPD.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs, mostly affecting young and middle-aged women. Significant questions remain as to its pathogenesis, especially the triggers for the associated interstitial lung disease (SSc-ILD). We examined the extent to which SSc and SSc-ILD were related to oxidative stress and altered metal homeostasis at the air-lung interface.

Methods: In this case-control study, we recruited 20 SSc patients, of which 11 had SSc-ILD. Eighteen healthy individuals were recruited as age-matched healthy controls, for a total of 38 study participants. Low molecular weight antioxidants (ascorbate, urate and glutathione), metal transport and chelation proteins (transferrin and ferritin) and metals (Fe and Cu) concentrations, including a measure of the catalytically active metal pool, were determined in respiratory tract lining fluid (RTLF) collected by bronchoalveolar lavage from the SSc group and compared with healthy controls.

Results: In the SSc group, 14 individuals were of female sex (70%) and the median age was 57 years (range 35–75). We observed evidence of oxidative stress in the RTLFs of SSc patients, characterised by increased concentrations of glutathione disulphide (GSSG, P<0.01), dehydroascorbate (DHA, P<0.05) and urate (P<0.01). This was associated with elevated RTLF Fe (P=0.07) and Cu (P<0.001), and evidence of a catalytic metal pool, demonstrated by an enhanced rate of ascorbate oxidation in the recovered lavage fluid (p<0.01). Cu concentrations were significantly associated with the ascorbate depletion rate (r=0.76, P<0.001), and GSSG (r=0.38, P<0.05) and protein carbonyl (r=0.44, P<0.01) concentrations. Whilst these markers were all increased in SSc patients, we found no evidence for an association with SSc-ILD.

Conclusions: These data confirm the presence of oxidative stress in the airways of SSc patients and, for the first time, suggest that an underlying defect in metal homeostasis at the air-lung interface may play a role in disease progression.

Accurate prescription of supramaximal exercise requires exercise tests covering the intensity domain between maximal aerobic and peak power output. All-out tests are commonly used for this objective but are considered challenging for people with chronic obstructive pulmonary disease (COPD) due to the extreme physiological demand. The modified Borg cycle strength test (mBCST), previously used in older adults to achieve supramaximal intensities, might be a suitable alternative in people with COPD. We aimed to determine the feasibility of the mBCST in people with COPD and to compare the physiological response with that of healthy older adults. Eighteen people with COPD and 16 age-, sex- and physical activity-matched healthy adults performed a cardiopulmonary exercise test and a mBCST. The mBCST is an incremental test [30 s:30 s cycling:rest; with individualized starting load and step size (15-50 W)] with end-of-test criteria of a rating of perceived exertion of >= 17 or cadence of <75 RPM for >5 s. Feasibility was assessed using a framework covering the aim, interpretability, familiarity, duration, scoring/completion complexity, costs and safety. Measurements of external exercise intensity, rating of perceived exertion, symptoms and cardiorespiratory demand were obtained. The mBCST was deemed feasible according to the feasibility framework. Expressed relative to the cardiopulmonary exercise test, all participants reached supramaximal external exercise intensities during the mBCST [COPD, 145 (125-168)%; healthy, 154 (148-163)%], without differences in intensity or physiological response between groups (p > 0.05). The mBCST is feasible in people with COPD and enables supramaximal external exercise intensities, with similar physiological response to healthy older adults. The mBCST could be considered when selecting an exercise test to prescribe supramaximal exercise.

Objectives: The adipocyte-derived hormone leptin has been associated with the pathogenesis of cardiovascular disease. The mechanisms underlying this association are unclear but may relate to effects on the vascular endothelium. Our aim was to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary artery disease.

Design: The vascular effects of leptin were assessed infusing recombinant human leptin in healthy volunteers during measuring vasomotor response by venous occlusion plethysmography. Additionally, circulating levels of leptin were analysed in relation to endothelial dysfunction in patients with established coronary artery disease.

Results: In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n = 10) did not affect basal forearm blood flow, plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 concentrations (all p > 0.05). However, during concomitant co-infusion with leptin (800 ng/min; n = 10), drug-induced vasodilatation was reduced (p = 0.001), and tPA activity increased (p = 0.002). In patients with coronary artery disease, those with the high plasma leptin levels had reduced drug-induced vasodilatation (p < 0.001), and increased net release of tPA antigen and activity (p < 0.001 and p = 0.03, respectively) compared to those with low levels. The study has been registered retrospectively at Clinical Trials with number NCT04374500.

Conclusion: Intrabrachial leptin infusion did not affect the basal vascular tone, whereas acute and chronic hyperleptinemia was associated with blunted vasoreactivity in healthy volunteers, and in patients with coronary artery disease.

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.