Abstract Background The objective of this study was to explore the potential of Airspace Dimension Assessment (AiDA) to rapidly determine the type and severity of airway obstruction, detect emphysema in individuals with chronic airflow limitation (CAL), and distinguish it from non-emphysematous obstruction, asthma, and absence of respiratory disease with normal spirometry. Methods Among the 744 participants measured with AiDA within the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort, 40 had asthma, and 34 had a CAL (defined by a post-bronchodilator FEV1/FVC < 0.7), whereof 12 had CT-detected emphysema. AiDA measurements were compared across these groups and to 111 healthy controls (never-smokers with normal spirometry and no history of respiratory disease). Results Subjects with CAL had significantly larger distal airspaces radii (median r AiDA=298 μm) than controls (r AiDA=278 μm, p < 0.001), but no significant difference was observed in asthmatics (r AiDA=273 μm, p = 0.79). Subjects with CT-detected emphysema in the CAL group displayed further differentiation from the control (r AiDA=349 μm, p < 0.001), while those without emphysema displayed no significant increase. Unlike r AiDA, neither low attenuation volume nor 15th percentile density could clearly distinguish between obstruction and radiologist-assessed emphysema. In addition, the zero-second particle recovery (R 0), which is theorized to reflect conducting airway dysfunction, was decreased in both asthmatics (R 0 = 0.41, p = 0.011), and in the CAL group (R 0 = 0.45, p = 0.020) when compared to controls (R 0 = 0.56). Conclusions These findings display AiDA’s potential in identifying emphysema as well as obstructive airway disease. The absence of an increased distal airspace radius in asthmatics confirm that r AiDA is a measure of the distal airspaces, unaffected by abnormalities in the conducting airways. However, the decreased R 0 in both asthma and CAL suggests that R 0 does reflect conducting airway abnormality.

BACKGROUND:Aerosol therapy is commonly performed during invasive mechanical ventilation. Although heated humidification is standard practice, studies suggest that humidity can reduce the delivered dose. In this study, we aimed to investigate whether the delivered dose can be increased by decoupling humidity control from heating during aerosol drug delivery. METHODS:In a bench study setup, albuterol sulfate solution was nebulized into an adult invasive mechanical ventilation circuit with a vibrating-mesh nebulizer. An absolute humidifier with decoupled heating and humidification was tested at 0 and 25 mg H2O/L of added humidity during nebulization and compared with 2 conventional pass-over humidifiers with no independent humidity control. The delivered dose, experimentally determined by the drug deposition on a filter between the endotracheal tube and the test lung, was quantified with a UV-Vis spectrometer. The particle size distribution of the aerosol entering the test lung was measured and used to model the lung deposited dose for healthy and diseased lungs. RESULTS:The absolute humidifier at 0 mg/L added humidity led to a significantly higher delivered dose (37.2%) than the pass-over humidifiers (21.2% and 24.1%, P = .01 for both), whereas the absolute humidifier at 25 mg H2O/L added humidity led to a comparable dose (24.9%) as one of the pass-over humidifiers. All these test scenarios achieved sufficient humidity (>33 mg H2O/L) in the gas flow during nebulization. Regional lung deposition simulations suggest that <10% of the nebulized dose deposits in healthy lungs for the pass-over humidifiers and around 16% for the absolute humidifier at 0 mg/L added humidity. Simulations also suggest that bronchial obstruction increases the deposited dose, whereas alveolar enlargement decreases the deposited dose. CONCLUSIONS:The delivered dose and hence the simulated lung deposited dose was improved by allowing independent humidity control during nebulization for adult invasive mechanical ventilation.

BACKGROUND:Low-cost particulate matter sensors have enabled new opportunities for exposure monitoring but require evaluation before application in epidemiological studies. This study assessed the performance of the SPS30 sensor integrated into the ARMIE portable monitoring sensor-node under controlled laboratory conditions. METHODS:Sensors were co-located with two comparison instruments-the optical DustTrak photometer and the combined Scanning Mobility Particle Sizer (SMPS) and Aerodynamic Particle Sizer (APS)-across multiple aerosol sources, including candle burning, cooking, cigarette smoke, and clean air, under both regular and high-humidity conditions. Calibration performance was evaluated using leave-one-sensor-out and leave-one-source-out approaches. RESULTS:The ARMIE node demonstrated strong agreement with the DustTrak (r = 0.93-0.98) and maintained linear response characteristics across emission types. Calibration reduced mean errors and narrowed the limits of agreement. Agreement with the SMPS + APS was moderate (r = 0.74-0.94) and characterized by systematic underestimation at higher concentrations. CONCLUSIONS:Overall, the ARMIE node achieved high correlation with the DustTrak, demonstrating that low-cost optical sensors can reliably capture temporal variability in particle concentrations relative to mid-cost photometers.

It is generally established that respiratory droplets and aerosols are formed from the fluid lining the respiratory tract. However, unlike modeling of the fate of inhaled aerosols, modeling the formation of respiratory droplets and aerosols is a much less studied area. In the fall of 2024, aerosol science experts in both experimental and clinical aspects of respiratory aerosols, along with experts in mathematical and computational modelling of viscoelastic fluids, participated in a weeklong workshop to address the challenges of characterizing respiratory aerosol composition and of modeling their formation. Topics that were discussed include the mechanisms of formation, the measurement of viscoelastic and rheological properties of the lung lining fluids, the intersubject production variability, and how in-vivo/in-vitro data can be used to inform and validate modeling. This publication summarizes the current consensus on the topic as it was discussed at the workshop. It also highlights the current experimental and numerical challenges, and key gaps in the available data. The most critical needs for a more predictive understanding of respiratory aerosol generation were identified as 1) robust, high-resolution rheological and compositional measurements of lung lining fluids, 2) experimental systems that replicate dynamic airway processes under controlled conditions, 3) multiscale simulations that incorporate nonlinear constitutive behavior, complex geometries, and surface-driven instabilities with appropriate validation, and 4) integration of pathogen viability and chemical microenvironments into aerosol fate models.

Studying how single nucleotide polymorphisms (SNPs) crosstalk with non-autologous factors to cause complex autoimmune diseases is challenging. An amino acid replacement in the neutrophil cytosolic factor 1 (NCF1-339/NCF1R90H) leading to lower reactive oxygen species induction has been reported as the major SNP for systemic lupus erythematosus (SLE). Here we show that infection with the murine norovirus (MNV) contributes to the induction of lupus in Ncf190H mice. Mutant NCF190H upregulates the IFN-α/JAK1/STAT1 pathway in macrophages and anti-MNV-antibody production. In parallel, the MNV infection of NCF190H mice upregulates Toll-like receptor 7 in macrophages, plasmacytoid dendritic cells and B220+ splenocytes, thereby promoting germinal center formation and lupus-associated autoantibodies production. These compounded effects lead to protection against MNV infection but also glomeruloneph ritis with proteinuria and lupus arthritis in the absence of chemical inducers such as pristane. Our data thus suggest that this SLE-associated SNP, NCF190H, synergizes with MNV infection to induce the development of mouse lupus.

Although Chronic Obstructive Pulmonary Disease (COPD) is generally considered a progressive condition with limited reversibility, recent data suggests potential for lung function improvement with exercise. Mechanistic insights into exercise-induced benefits remain limited, but in vitro models offer promise for understanding cellular and molecular changes. This study aims to elucidate the mechanisms behind lung tissue regeneration in COPD through adapted exercise training as well as validating advanced lung function tests, such as Impulse Oscillometry (IOS) and Airspace Dimension Assessment (AiDA) for improved detection of early physiological /structural changes and predicting clinical outcomes. This is the protocol of a multicenter, hypothesis-generating, single-arm study exploring the mechanisms for lung regeneration in subjects with COPD induced by exercise. The exercise protocol includes supervised and individually tailored moderate-intensity aerobic- and muscle strengthening exercise, performed three times per week for 12 weeks. Eighty sedentary adults with a clinically stable COPD will be recruited at two study sites. Included participants will be assessed at baseline and at 12 weeks by comprehensive pulmonary function testing (including spirometry, IOS, body plethysmography, diffusing capacity of the lung, single breath nitrogen wash-out, AiDA, questionnaires, physical capacity performance (including 6-minutes walking test (6MWT), one-minute sit-to-stand test, and cardiopulmonary exercise testing (CPET)), and collection of blood and urine samples and bronchoscopy. A mid-intervention assessment at week 6 will include medication use, health status, questionnaires, spirometry, and blood sampling. Understanding the molecular and cellular activities related to lung function induced by exercise provides insights into repair pathways, challenges the notion of irreversible lung damage in COPD, and paves the way for improved management strategies with potential identification of biomarkers and pharmacological interventions. ClinicalTrials.gov ID NCT06335992 (Registration date 2024-03-28).

Biogenic ice-nucleating particles (INPs) can significantly impact mixed-phase clouds by enhancing precipitation and reducing albedo. As Arctic sea ice diminishes, the exposure of open ocean may increase aerosolization rates of marine bioaerosols and INPs. We investigated INP concentrations and microbial communities in ambient marine air, sea bulk water (SBW), and sea surface microlayer (SML) along a transect from the Davis Strait to Baffin Bay. INP concentrations in SBW increased with latitude, regardless of the extent of terrestrial freshwater input. We further identified correlations between INP levels and abundances of specific microbial taxa, including Formosa, Lewinella, Micromonas, and Dino-Group-I-Clade-5, suggesting potential ice nucleation activity of these taxa. Air samples exhibited distinct microbiomes compared to seawater, indicating terrestrial contributions, but at the highest observed wind speeds (7-8 m/s), substantial contributions of the seawater microbiome were detected in the air. Elevated atmospheric INP concentrations at higher latitudes correlated with seawater INP levels, which was supported by laboratory sea spray experiments showing that INPs in SBW influenced aerosol INP levels. Our findings highlight the Arctic Ocean as a significant source of biogenic atmospheric INPs and enhance our understanding of marine microbes as contributors to biogenic INPs. By identification of potential ice nucleation active microbial taxa and examination of aerosolization processes, this study provides a framework for future research on Arctic marine-derived INPs and their atmospheric impact.

An integrated framework is introduced and applied to assess the health impact of airborne pollution with greater physiological relevance, moving beyond conventional exposure metrics. Measured particle number size distribution data was integrated with a regional respiratory tract deposition fractions to estimate total and alveolar deposited particle surface area concentrations. Land use regression modeling, combined with randomized commuting patterns, enabled the evaluation of city-specific alveolar surface area deposition doses, providing new insight into localized average exposure and its implications for public health. The results showed that although the mean street-level air pollution in Lithuania is higher than in other European cities, the urban background levels are on the same level. We found that the total respiratory deposited surface area concentration is up to 18-fold higher due to coarse particles, which also determines alveolar deposited particle surface area dose. Our findings advocate for using integrated pollution assessments and region-specific policies rather than broad diesel vehicle-targeted bans. The proposed methodology is expected to enhance traditional exposure assessments by switching to lung deposited surface area, which can be further refined by incorporating daytime activity patterns, socio-economic status, and personal health conditions.

Transmissibility has increased during the evolution of SARS-CoV-2, possibly by improved airborne transmission. An increased transmission was noted also in many hospitals. We analyzed SARS-CoV-2 in room air of hospitalized Omicron infected patients and compared results with previous findings with pre-Delta variants to study if SARS-CoV-2 was more prevalent in patient rooms after the introduction of Omicron. Only 4 of 75 (5%) air samples, from 3 of 43 included patients, were positive during the early Omicron wave, compared to 14/120 (12%), from 10 of 60 included patients during the initial wave. No certain statistical difference between virus variants could be established, but the tendency was a lower occurrence at Omicron infected patients, also when adjusting for relevant confounders. These finding do not support the initial hypothesis that increased SARS-CoV-2 aerosol emission from diagnosed patients with Omicron could explain any increased risk of hospital transmission.

Aerosolised Polystyrene Latex (PSL) nanoparticles are, due to their well-defined size, spherical shape, and inert surface, useful in many experimental applications, including studies of particle deposition in the human lung. Aerosolising nanoparticles entails added challenges, and nano-particles can potentially be more hazardous than otherwise equivalent microparticles. The objective of this work was to evaluate methods for aerosolising PSL nanoparticles and assess their toxicity. We investigated a Collison-type generator, a TSI Electrospray, and the recent Kanomax NanoAerosol Generator (NAG). We also examined the cyto-and genotoxicity of nano-PSL to human bronchial epithelial cells (BEAS-2B) in serum-free conditions and to monocyte-derived macrophages (THP-1) in both serum-free and serum-enriched conditions. When comparing the generators, we found that the NAG produced an aerosol with greater separation between the PSL and residual particles than the Collison and was the most stable generator tested. The electrospray generated an aerosol without any overlap between the residual and the PSL modes but was also the most unpredictable, making it less suited for areas where ease of use and high repeatability are needed. We found that the Collison is generally unsuitable to generate nano-sized aerosol. The lowest observed effect level for cytotoxicity in BEAS-2B was 25, 50 and 50 mu g/mL for 30, 50 and 100 nm PSL, respectively. For serum-free THP-1 macrophages, it was 50 mu g/mL for 30 nm PSL and 150 mu g/mL for 50 and 100 nm PSL. THP-1 macrophages displayed no cytotoxicity in serum-enriched culture. None of the tested particles were genotoxicin the alkaline comet assay. Overall, the NAG exceeded the Collison and electrospray in stability but produced a more polydisperse aerosol than the electrospray. PSL particles induced dose-and size-dependent cytotoxicity in BEAS-2B and in THP-1 cells with the smallest particles (30 nm) being the most toxic. However, the concentration is several orders of magnitude higher than typical concentrations for experimental applications.

Exposure to airborne particulate matter is associated with a number of negative health effects ranging from respiratory diseases to systemic effects and cancer. One important factor for understanding the health effects is the individual variation in the respiratory tract deposition of inhaled particles. In this study, we describe an experimental set-up for size-resolved measurements of the lung deposited fraction of airborne particles, covering the diameter range from 15 to 5000 nm. The set-up includes a system for generating a stable aerosol with a sufficiently broad size distribution. We used a scanning mobility particle sizer and an aerodynamic particle sizer to determine particle number and size. The set-up was used to investigate individual differences in the deposition fraction (DF) of particles in the respiratory tract for a group of 67 subjects of both sexes aged 7–70 years. The measured DF was applied to two model aerosols, one representing an urban environment and one a rural environment, and the particle deposition rates were derived (i.e., the deposited amount of particles per unit time). Furthermore, the deposition rates were normalized to lung surface area and body mass — two dose measures that are considered relevant for the health effects of airborne particles. In addition to validation of the set-up, we show that there is a large individual variation in DF, with some subjects having a DF that is more than twice as high as that of others. Although we observe differences in the DF between different subgroups, most individual variation was explained neither by age nor by gender. When normalizing the deposition rates to lung surface area or body mass, the deposition rates of children become significantly higher than those of adults. Furthermore, the individual variability is larger for the lung surface area or body mass normalized deposition rates than for DF.

Background: Healthcare workers in obstetric clinics may be exposed to airborne SARSCoV-2 when treating patients with COVID-19. Method: In this study, performed during the midst of the pandemic, air samples were collected in delivery rooms during childbirth and analysed for SARS-CoV-2 RNA content. Result: Six of 28 samples collected inside delivery rooms were positive for SARS-CoV-2, but none in anterooms or corridors. Five of the six positive samples were from the same occasion. Discussion: This indicates that some patients could be major sources of exhaled virus, although the individual variation is large, and it is thus difficult to predict the risk of infection. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The respiratory tract deposited fraction (DF) is the link between exposure and health effects of airborne particles. Here, we investigate how breathing pattern alterations at increasing physical activity affect DF in different regions of the respiratory tract and compare DF between adults and children (5 and 10 years old). We performed a literature review on the alteration of tidal volume with minute ventilation at increasing physical activity and used the results to model the size resolved (0.001–10 µm) DF, primarily using the deposition models from NCRP and Yeh and Schum (1980), but also MPPD. We found a shift in the deposited size distribution with increasing physical activity—DF of ultrafine particles increased in the alveolar region and decreased in the other regions, while DF of coarser particles decreased in the alveolar region and increased in the extra-thoracic region. Children had a 10–20% higher DF of ultrafine particles in the alveolar region compared to adults. We also present parametrizations of the daily average size resolved (0.005–5 µm) DF, accounting for varying physical activity throughout the day and oral/nasal breathing. These can be applied to any size distribution to estimate deposited doses. We found that deposited mass and number doses were more than twice as high for 5-year-olds compared to adults when normalized for body weight, primarily caused by their higher weight normalized minute ventilation. This demonstrates the importance of studying children’s exposure to air pollution and not only rely on data from adults.

Rationale Preterm infants diagnosed with bronchopulmonary dysplasia (BPD) are thought to have fewer and larger alveoli than their term peers, but it is unclear to what degree this persists later in life.Objectives To investigate to what degree the distal airspaces are enlarged in adolescents born preterm and to evaluate the new Airspace Dimension Assessment (AiDA) method in investigating this group.Methods We investigated 41 adolescents between 15 and 17 years of age, of whom 25 were born very preterm (a gestational age <31 weeks, with a mean of 26 weeks) and 16 were term-born controls. Of the preterms, 17 were diagnosed with BPD. The AiDA method was used to measure the average distal airspace radius (rAiDA) in the lungs. In addition, lung function was evaluated by spirometry, impulse oscillometry and diffusing capacity of carbon monoxide (DLCO).Measurements and main results We observed a mean rAiDA of 295±53 µm for the preterm group compared with 231±12 µm for the control group (p<0.0001). The adolescents diagnosed with BPD had a mean rAiDA of 313±54 µm. There was a strong negative correlation between gestational age and distal airspace radius (p<0.0001). The BPD group had a decreased FEV1 (forced expiratory volume in 1 s, z-score: −1.28±1.37, p=0.012) and DLCO (z-score: −0.92±1.01, p=0.013) compared with the controls, but all other lung function variables showed normal values.Conclusions Our results suggest that the enlarged airspaces seen in preterm infants likely remain in adolescence. Distal airspace radius as measured by AiDA was the lung function variable that showed the most significant difference between preterm and term-born adolescents.