Ingunn Skogstad Riddervold

Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function.

BackgroundExposure to wood smoke is associated with respiratory symptoms, whereas knowledge on systemic effects is limited. We investigated effects on systemic inflammation, oxidative stress and microvascular function (MVF) after controlled wood smoke exposure.MethodsIn a randomised, double-blinded, cross-over study 20 non-smoking atopic subjects were exposed at rest to 14, 220, or 354 μg/m3 of particles from a well-burning modern wood stove for 3 h in a climate controlled chamber with 2 week intervals. We investigated the level of oxidatively damaged DNA, inflammatory markers and adhesion molecules before and 0, 6 and 20 h after exposure. Six h after exposure we measured MVF non-invasively by digital peripheral artery tonometry following arm ischemia.ResultsThe MVF score was unaltered after inhalation of clean air (1.58 ± 0.07; mean ± SEM), low (1.51 ± 0.07) or high (1.61 ± 0.09) concentrations of wood smoke particles in atopic subjects, whereas unexposed non-atopic subjects had higher score (1.91 ± 0.09). The level of oxidatively damaged DNA, mRNA of ITGAL, CCL2, TNF, IL6, IL8, HMOX1, and OGG1 and surface marker molecules ICAM1, ITGAL and L-selectin in peripheral blood mononuclear cells were not affected by inhalation of wood smoke particles.ConclusionsExposure to wood smoke had no effect on markers of oxidative stress, DNA damage, cell adhesion, cytokines or MVF in atopic subjects.

Expression of adhesion molecules, monocyte interactions and oxidative stress in human endothelial cells exposed to wood smoke and diesel exhaust particulate matter

Toxicological effects of wood smoke particles are less investigated than traffic-related combustion particles. We investigated the effect of wood smoke particles, generated by smouldering combustion conditions, on human umbilical endothelial cells (HUVECs) co-cultured with or without monocytic THP-1 cells. Standard reference material (SRM) 2975 diesel exhaust particles were used as benchmark particles. Wood smoke particles at 50 μg/ml or 100 μg/ml caused adhesion of THP-1 monocytes onto HUVECs in co-cultures, whereas SRM2975 had no such effect. Both types of particles from 1 μg/ml increased VCAM-1 expression on HUVECs in mono-cultures. However, only the exposure to wood smoke particles was associated with increased expression of TNF and IL8 mRNA in THP-1 cells. We found no effect on the intracellular production of reactive oxygen species by the fluorescent probe DCFH-DA, whereas especially the wood smoke particles caused increased level of DNA strand breaks and oxidised guanines at concentrations with low cytotoxicity. In conclusion, our results indicate that the adherence of monocytes on endothelial cells in wood smoke particle exposed cultures depend on activation of both cell types.

Effects of wood smoke particles from wood-burning stoves on the respiratory health of atopic humans.

BackgroundThere is growing evidence that particulate air pollution derived from wood stoves causes acute inflammation in the respiratory system, increases the incidence of asthma and other allergic diseases, and increases respiratory morbidity and mortality. The objective of this study was to evaluate acute respiratory effects from short-term wood smoke exposure in humans. Twenty non-smoking atopic volunteers with normal lung function and without bronchial responsiveness were monitored during three different experimental exposure sessions, aiming at particle concentrations of about 200 μg/m3, 400 μg/m3, and clean air as control exposure. A balanced cross-over design was used and participants were randomly allocated to exposure orders. Particles were generated in a wood-burning facility and added to a full-scale climate chamber where the participants were exposed for 3 hours under controlled environmental conditions. Health effects were evaluated in relation to: peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC). Furthermore, the effects were assessed in relation to changes in nasal patency and from markers of airway inflammation: fractional exhaled nitric oxide (FENO), exhaled breath condensate (EBC) and nasal lavage (NAL) samples were collected before, and at various intervals after exposure.ResultsNo statistically significant effect of wood smoke exposure was found for lung function, for FENO, for NAL or for the nasal patency. Limited signs of airway inflammation were found in EBC.ConclusionIn conclusion, short term exposure with wood smoke at a concentration normally found in a residential area with a high density of burning wood stoves causes only mild inflammatory response.

Wood smoke in a controlled exposure experiment with human volunteers

Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung function and normal bronchial reactivity were randomly exposed for 3 h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m3 (low) and 400 µg/m3 (high) under controlled environmental conditions. The range for PM2.5 load observed for single experiments was 165–303 µg/m3 for the low exposure and 205–662 µg/m3 for the high exposure, whereas particle loads during clean air exposure most often were below the detection limit (<20 µg/m3). Health effects were evaluated in relation to rated changes in symptoms and environmental perception using a computerized questionnaire and a potentiometer. Subjective symptoms were generally weak, but when combining the effect of each of the symptoms into categorical symptom indices, significant effects were found for “environmental perception” (p = 0.0007), “irritative body perceptions” (p = 0.0127), “psychological/neurological effects” (p = 0.0075) and “weak inflammatory responses” (p = 0.0003). Furthermore, significant effects (p = 0.0192) on self-reported general mucosa irritation were found. In conclusion, exposure to wood smoke affected symptom rating and caused irritated mucosas in humans. The knowledge gained in this study on subjective-rated symptoms may be important for understanding human response to wood-smoke exposure.

Efficacy and safety of intravenous fentanyl administered by ambulance personnel

Management of pain in the pre‐hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered by ambulance personnel.

Systemic Effects of Wood Smoke in a Short-Term Experimental Exposure Study of Atopic Volunteers

Objective: To investigate whether short-term systemic effects of wood smoke occurred in atopic subjects after experimental wood smoke exposures. Methods: A double-blind climate chamber study was conducted on 20 healthy atopic subjects with exposures to filtered air and wood smoke. Pneumoproteins, coagulation and adhesion factors, and cytokines were measured. Heart rate was monitored with pulse monitors. Data were analyzed with mixed models. Results: Few differences in the outcomes were observed. Plasma tissue factor remained elevated during filtered air exposure (P = 0.002). P-selectin declined independent of exposure (P = 0.0006). Interleukin-6 increased after filtered air (P = 0.03). Conclusions: The study confirmed previous observations among nonatopics of limited changes after a 3-hour wood smoke exposure.

A novel protocol for dispatcher assisted CPR improves CPR quality and motivation among rescuers—A randomized controlled simulation study

BACKGROUND Emergency dispatchers use protocols to instruct bystanders in cardiopulmonary resuscitation (CPR). Studies changing one element in the dispatchers protocol report improved CPR quality. Whether several changes interact is unknown and the effect of combining multiple changes previously reported to improve CPR quality into one protocol remains to be investigated. We hypothesize that a novel dispatch protocol, combining multiple beneficial elements improves CPR quality compared with a standard protocol. METHODS A novel dispatch protocol was designed including wording on chest compressions, using a metronome, regular encouragements and a 10-s rest each minute. In a simulated cardiac arrest scenario, laypersons were randomized to perform single-rescuer CPR guided with the novel or the standard protocol. PRIMARY OUTCOME a composite endpoint of time to first compression, hand position, compression depth and rate and hands-off time (maximum score: 22 points). Afterwards participants answered a questionnaire evaluating the dispatcher assistance. RESULTS The novel protocol (n=61) improved CPR quality score compared with the standard protocol (n=64) (mean (SD): 18.6 (1.4)) points vs. 17.5 (1.7) points, p<0.001. The novel protocol resulted in deeper chest compressions (mean (SD): 58 (12)mm vs. 52 (13)mm, p=0.02) and improved rate of correct hand position (61% vs. 36%, p=0.01) compared with the standard protocol. In both protocols hands-off time was short. The novel protocol improved motivation among rescuers compared with the standard protocol (p=0.002). CONCLUSIONS Participants guided with a standard dispatch protocol performed high quality CPR. A novel bundle of care protocol improved CPR quality score and motivation among rescuers.

Acute versus subacute angiography in patients with non-ST-elevation myocardial infarction – the NONSTEMI trial phase I

Background: The 2015 European Society of Cardiology non-ST-elevation myocardial infarction (NSTEMI) guidelines recommend angiography within 24 h in high-risk patients with NSTEMI. An organized STEMI-like approach with pre-hospital or immediate in-hospital triage for acute coronary angiography (CAG) may be of therapeutic benefit but it remains unknown whether the patients can be properly diagnosed in the pre-hospital setting. We aim to evaluate whether it is feasible to diagnose patients with NSTEMI in the pre-hospital phase or immediately upon admission. Methods and results: We randomized 250 patients to either acute or subacute CAG (i.e. <72 h of admission). Pre-hospital electrocardiogram acquisition and point-of-care troponin-T measurement ensured that 148 (59%) patients were identified already in the ambulance, whereas the remaining 102 (41%) patients were identified immediately after hospital admission. An acute coronary syndrome was verified in 215 (86%) and NSTEMI in 159 (64%) patients. The CAG rate was significantly higher in the acute CAG group (98% vs. 87%, p<0.001). A culprit lesion was identified in 74% and 64% of the patients underwent coronary revascularization: acute CAG group: 53% percutaneous coronary intervention, 5% hybrid, 7% coronary artery bypass grafting; conventional treatment: 48% percutaneous coronary intervention, 2% hybrid, 14% coronary artery bypass grafting, p=0.32. In patients randomized to acute CAG, time from randomization to CAG was 1.1 h; in patients randomized to subacute CAG it was two days. Time from randomization to initial revascularization was 1.3 h versus 2.4 days, and the median hospital stay was 4.0 days versus 4.5 days. Among patients randomized to subacute CAG, 17% crossed over to acute CAG and 5% developed STEMI before catheterization. Conclusion: Diagnosing NSTEMI patients in the pre-hospital phase or immediately upon hospital admission is feasible. Acute CAG may impact the mode of revascularization and is associated with earlier revascularization and shorter hospital stay. The clinical benefit of acute CAG in NSTEMI patients remains to be clarified.

The change in nasal inflammatory markers after intranasal challenges with particulate chitin and lipopolysaccharide: a randomized, double-blind, placebo-controlled, crossover study with a positive control

We investigated the effect of chitin on the inflammation and immune modulation of the nasal mucosa. This compound was compared to placebo and as a positive control we used lipopolysaccharide (LPS).

Predictive value of routine point-of-care cardiac troponin T measurement for prehospital diagnosis and risk-stratification in patients with suspected acute myocardial infarction

Objective: The purpose of this study was to determine the predictive value of routine prehospital point-of-care cardiac troponin T measurement for diagnosis and risk stratification of patients with suspected acute myocardial infarction. Methods and results: All prehospital emergency medical service vehicles in the Central Denmark Region were equipped with a point-of-care cardiac troponin T device (Roche Cobas h232) for routine use in all patients with a suspected acute myocardial infarction. During the study period, 1 June 2012–30 November 2015, prehospital point-of-care cardiac troponin T measurements were performed in a total of 19,615 cases seen by the emergency medical service and 18,712 point-of-care cardiac troponin T measurements in 15,781 individuals were matched with an admission. A final diagnosis of acute myocardial infarction was confirmed in 2187 cases and a total of 2150 point-of-care cardiac troponin T measurements (11.0%) had a value ≥50 ng/l, including 966 with acute myocardial infarction (sensitivity: 44.2%, specificity: 92.8%). Patients presenting with a prehospital point-of-care cardiac troponin T value ≥50 ng/l had a one-year mortality of 24% compared with 4.8% in those with values <50 ng/l, log-rank: p<0.001. The following variables showed the strongest association with mortality in multivariable analysis: point-of-care cardiac troponin T≥50 ng/l (hazard ratio 2.10, 95% confidence interval: 1.90–2.33), congestive heart failure (hazard ratio 1.93, 95% confidence interval: 1.74–2.14), diabetes mellitus (hazard ratio 1.42, 95% confidence interval: 1.27–1.59) and age, one-year increase (hazard ratio 1.08, 95% confidence interval: 1.08–1.09). Conclusions: Patients with suspected acute myocardial infarction and a prehospital point-of-care cardiac troponin T ≥50 ng/l have a poor prognosis irrespective of the final diagnosis. Routine troponin measurement in the prehospital setting has a high predictive value and can be used to identify high-risk patients even before hospital arrival so that they may be re-routed directly for advanced care at an invasive centre.