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Airspace Dimensions Assessment with nanoparticles (AiDA) is a new method for non-invasive measurement of pulmonary distal airspaces. The aim of this study was to compare AiDA measurements with other pulmonary function variables to better understand the potential of AiDA in a clinical context.AiDA measurements and pulmonary function tests were performed in 695 subjects as part of the Swedish CArdioPulmonary bioImage Study. The measurement protocol included spirometry, measurement of diffusing capacity of carbon monoxide, oscillometry and pulmonary computed tomography. AiDA indices were compared to all other pulmonary examination measurements using multivariate statistical analysis.Our results show that AiDA measurements were significantly correlated with other pulmonary function examination indices, although covariance was low. We found that AiDA variables explained variance in the data that other lung function variables only influenced to a minor extent.We conclude that the AiDA method provides information about the lung that is inaccessible with more conventional lung function techniques.

Exposure to dog allergens is almost impossible to avoid, as dogs are part of our society and frequently encountered both outdoors and indoors. This poses problems to individuals allergic to dogs, a common condition with reported sensitization rates around 20% 1 . It is therefore crucial to increase our understanding on how dog allergens spread in the environment and on exposure by inhalation.

Introduction: Methods to measure changes in the peripheral lungs are highly needed to monitor lung diseases, including chronic obstructive pulmonary disease (COPD). We have developed a novel technique, Airspace Dimension Assessment (AiDA), which has been shown to reflect distal lung geometry. The aim of this study was to explore how AiDA measurements correlate with other pulmonary function tests (Aaltonen et al. 2020). Methods: AiDA measures the deposition of 50 nm aerosol particles during a series of breath-holds. From this, the effective airspace radii, rAiDA, at different volumetric depths can be calculated (Jakobsson et al. 2016, Londahl et al. 2017). An additional variable, zero second recovery R0, is conceptually understood to reflect particle losses during the dynamic process of breathing and model calculations of nanoparticle deposition indicate it reflects generation 10-15 of the lungs. In this work, AiDA measurements were performed on 618 subjects (270 men and 348 women aged 50-64) in a Swedish population cohort (SCAPIS). Subjects underwent complete lung function tests, including CT, according to the ERS guidelines. Results: The airspace radii, rAiDA, for the group was 0.29±0.04 µm and R0 0.49±0.19. The strongest correlations for rAiDA were found with age, diffusion capacity of carbon monoxide and CT measures of emphysema (p Conclusions: This study indicate that AiDA measurements can provide information about the peripheral lung and may be especially useful to detect emphysema.

Background Respiratory tract deposition of airborne particles is a key link to understand their health impact. Experimental data are limited for vulnerable groups such as individuals with respiratory diseases. The aim of this study is to investigate the differences in lung deposition of nanoparticles in the distal lung for healthy subjects and subjects with respiratory disease. Methods Lung deposition of nanoparticles (50 and 100 nm) was measured after a 10 s breath-hold for three groups: healthy never-smoking subjects (n = 17), asymptomatic (active and former) smokers (n = 15) and subjects with chronic obstructive pulmonary disease (n = 16). Measurements were made at 1300 mL and 1800 mL volumetric lung depth. Each subject also underwent conventional lung function tests, including post bronchodilator FEV1, VC, and diffusing capacity for carbon monoxide, DL,CO. Patients with previously diagnosed respiratory disease underwent a CT-scan of the lungs. Particle lung deposition fraction, was compared between the groups and with conventional lung function tests. Results We found that the deposition fraction was significantly lower for subjects with emphysema compared to the other subjects (p = 0.001–0.01), but no significant differences were found between healthy never-smokers and smokers. Furthermore, the particle deposition correlated with pulmonary function tests, FEV1%Pred (p

H Laura Aaltonen,1,2,* Simon S Kindvall,3,* Jonas K Jakobsson,4 Jakob Löndahl,4 Lars E Olsson,3,5 Sandra Diaz,1,2 Sophia Zackrisson,1,2 Per Wollmer1,2 1Department of Medical Imaging and Physiology, Skåne University Hospital, Malmö, Sweden; 2Department of Translational Medicine, Lund University, Malmö, Sweden; 3Department of Medical Radiation Physics, Lund University, Malmö, Sweden; 4Department of Design Sciences, Lund University, Lund, Sweden; 5Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden *These authors contributed equally to this work Background: Airspace Dimension Assessment with inhaled nanoparticles is a novel method to determine distal airway morphology. This is the first empirical study using Airspace Dimension Assessment with nanoparticles (AiDA) to estimate distal airspace radius. The technology is relatively simple and potentially accessible in clinical outpatient settings. Method: Nineteen never-smoking volunteers performed nanoparticle inhalation tests at multiple breath-hold times, and the difference in nanoparticle concentration of inhaled and exhaled gas was measured. An exponential decay curve was fitted to the concentration of recovered nanoparticles, and airspace dimensions were assessed from the half-life of the decay. Pulmonary tissue density was measured using magnetic resonance imaging (MRI). Results: The distal airspace radius measured by AiDA correlated with lung tissue density as measured by MRI (ρ = -0.584; p = 0.0086). The linear intercept of the logarithm of the exponential decay curve correlated with forced expiratory volume in one second (FEV1) (ρ = 0.549; p = 0.0149). Conclusion: The AiDA method shows potential to be developed into a tool to assess conditions involving changes in distal airways, eg, emphysema. The intercept may reflect airway properties; this finding should be further investigated. Keywords: nanoparticles, respiratory diagnostics, distal airspaces, airspace dimension assessment with nanoparticles, magnetic resonance densitometry

Background: The diagnosis of chronic obstructive pulmonary disease (COPD) is often based on spirometry, which is not sensitive to early emphysema. We have recently described a method for assessing distal airspace dimensions by measuring recovery of nanoparticles in exhaled air after a single-breath inhalation followed by breath-hold. Recovery refers to the non-deposited particle fraction. The aim of this study was to explore differences in the recovery of exhaled nanoparticles in subjects with COPD and never-smoking controls. A secondary aim was to determine whether recovery correlates with the extent of emphysema. Method: A total of 19 patients with COPD and 19 controls underwent three repeats of single-breath nanoparticle inhalation followed by breath-hold. Particle concentrations in the inhaled aerosol, and in an alveolar sample exhaled after breath-hold, were measured to obtain recovery. Findings: The patients with COPD had a significantly higher mean recovery than controls, 0·128 ± 0·063 versus 0·074 ± 0·058; P = 0·010. Also, recovery correlated significantly with computed tomography (CT) densitometry variables (P

Approximately 16 % of adult onset asthma is caused by occupational exposure. The need for early detection of irritant caused asthma is key in treating and preventing the progression of the disease. The aim of the work was to investigate if exposure to irritants cause change in gas composition in exhaled breath, the “exhalome”. We studied 15 female hairdressers exposed to a controlled dose of aerosolized bleach powder in a sealed climate chamber. The subjects’ self-reported symptoms, spirometry and gas components were monitored. The exhalome was collected for breath holding times of 2 and 10 seconds from central (400 ml) and peripheral lung (1500 ml), once prior to and twice after exposure. Thus, subjects were their own controls. The composition of the gas was analyzed using a Proton Transfer Reaction – Time of Flight – Mass Spectrometer (PTR-ToF-MS) where volatile organic compounds of mass up to 253 atomic mass units are identified with high time resolution. Preliminary analysis of the data shows a variation of the concentrations of the different gases in exhalome over the course of the day and that levels of isoprene and acetone are higher for longer breath holding time. More analysis is needed to evaluate if the technique is able to detect differences in the exhalome caused by the exposure. Detailed information on the relationships between the exhalome and inflammation processes in the respiratory tract induced by irritants is also required. This may contribute to a deeper understanding of asthma. In the future a PTR-ToF-MS could potentially be used as a real-time non-invasive tool for early detection asthma in exposed workers.

There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4–1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide (DL,CO), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology., Video abstract

Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine-disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labeled airborne phthalates: particle-phase D4-DEHP (di(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone and combined inhalation + dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014 ± 0.00088 (μg kg–1 bw)/(μg m–3)/h. No dermal uptake of D4-DEHP was observed during the 3 h exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation + dermal was 0.0067 ± 0.0045 an...

Airspace Dimension Assessment (AiDA) is a technique to assess lung morphology by measuring lung deposition of inhaled nanoparticles. Nanoparticles deposit in the lungs predominately by diffusion, and average diffusion distances, corresponding to effective airspace radii ( rAiDA), can be inferred from measurements of particle recovery after varied breath holds. Also, particle recovery after a 0-s breath hold ( R0) may hold information about the small conducting airways. This study investigates rAiDA at different volumetric sample depths in the lungs of healthy subjects. Measurements were performed with 50-nm polystyrene nanospheres on 19 healthy subjects aged 17–67 yr. Volumetric sample depths ranged from 200 to 5,000 ml and breath-hold times from 5 to 20 s. At the examined volumetric sample depths, rAiDA values ranged from ~200–600 μm, which correspond to dimensions of the bronchiolar and the gas-exchanging regions of the lungs. R0 decreased with volumetric sample depth and showed more intersubject variation than rAiDA. Correlations were found between the AiDA parameters, anthropometry, and lung function tests, but not between rAiDA and R0. For repeated measurements on 3 subjects over an 18-mo period, rAiDA varied on average within ± 7 μm (± 2.4%). The results indicate that AiDA has potential as an efficient new in vivo technique to assess individual lung properties. The information obtained by such measurements may be of value for lung diagnostics, especially for the distal lungs, which are challenging to examine directly by other means. NEW & NOTEWORTHY This is the first study to measure effective airspace radii ( rAiDA) at volumetric sample depths 200–5,000 ml in healthy subjects by Airspace Dimension Assessment (AiDA). Observed rAiDA were 200–600 μm, which corresponds to airspaces for the bronchiolar and the gas-exchanging regions around airway generation 14–17. rAiDA correlated with lung function tests and anthropometry. Measurements of rAiDA on 3 subjects over 11–18 mo were within ± 7 μm.

Ice nucleation active bacteria have attracted particular attention due to their unique ability to produce specific ice nucleation proteins (INpros), which are the most efficient ice nuclei known as they induce nucleation at temperatures close to 0 degrees C. Our model bacterium Pseudomonas syringae strain R10.79 produced INpros containing 67 tandem repeats, forming the proposed ice-binding surface. To understand the role of the INpro repeats as well as the role of intermolecular interactions between INpros for their ice nucleation behavior, we produced a truncated version of the protein with only 16 tandem repeats (INpro(16R)). The purified INpro(16R) produced oligomers of varying sizes. Immersion freezing ice nucleation behavior of purified INpro(16R) was characterized by droplet-freezing assays and in the Leipzig Aerosol Cloud Interaction Simulator. Predominant INpro(16R) oligomers introduced into Leipzig Aerosol Cloud Interaction Simulator as single particles with diameters of 50nm or 70nm were ice nucleation active at temperatures of -26 degrees C and -24 degrees C, respectively. These are much lower temperatures compared to that of intact INpros (-12 degrees C). The data clearly indicated that the number of repeats determines the ice nucleation temperature. In addition, ice nucleation between -9 degrees C and -10 degrees C, comparable to the activity of intact INpro, was caused by higher-order INpro(16R) oligomers. This supported previous observations that INpro oligomerization increases the ice-binding surface, thereby affecting ice nucleation activity. In conclusion, both repeat number and oligomerization contribute in a seemingly independent manner to the nucleation mechanism of INpros.

AIM: To evaluate three types of ventilation systems for operating rooms with respect to air cleanliness (in colony forming units, CFU/m(3)), energy consumption, and working environment comfort (noise and draught) as reported by surgical team members.METHODS: Two commonly used ventilation systems, vertical laminar airflow (LAF) and turbulent mixed airflow (TMA), were compared with a newly developed ventilation technique: temperature controlled airflow (TcAF). CFU concentrations were measured at three locations in an operating room during 45 orthopaedic surgeries: close to the wound (FINDINGS: We showed that LAF and TcAF, but not TMA, resulted in less than 10 CFU/m(3) at all measurement locations in the room during ongoing surgery. Median values of CFU/m(3) close to the wound (250 samples) were 0 for LAF, 1 for TcAF and 10 for TMA. Peripherally in the room, the CFU concentrations were lowest for TcAF. The CFU concentrations did not scale proportionally with airflow rates. Compared to LAF, TcAF's power consumption was 28% lower and there was significantly less disturbance from noise and draught.CONCLUSION: TcAF and LAF remove bacteria more efficiently from the air than TMA, especially close to the wound and instrument table. Like LAF, the new TcAF ventilation system maintained very low levels of CFU in the air, but TcAF used substantially less energy and provided a more comfortable working environment than LAF. This enables energy savings with preserved air quality.

The recovery of nanoparticles in exhaled gas after inhalation of a nanoaerosol and a standardised breath-hold as, measured by Airspace Dimension Assessment technique (AiDA), is increased in subjects with emphysema. This may reflect increased diffusion distances in the distal air spaces. The purpose of this study was to measure recovery of nanoparticles in exhaled gas after different breath-hold times and to relate recovery to pulmonary function tests and indications of emphysema. An aerosol of nanoparticles was generated in a reservoir from which the subjects inhaled the aerosol by a vital capacity. The subjects exhaled after various pre-set times. Particle concentration was measured in inhaled and exhaled gas and the recovery fraction calculated. We found that recovery falls exponentially with increasing breath-hold time. We therefore fitted the equation , to the recovery data, where N(t) is particle recovery after a breath-hold of t s, N 0 recovery after a breath-hold of 0 s and k a constant reflecting rate of particle deposition during the breath-hold. We studied 178 subjects randomly selected from the population aged 50-65 years. There were 23 current smokers and 155 non-smokers. N 0 differed significantly (p k did not. N 0 correlated with FEV 1 (r=0.22, p k differed significantly between subjects with and without emphysema (p N 0 did not. k correlated with D L,CO (r=0.19, p The AiDA technique may reflect not only increased diffusion distances in the distal air spaces but also independently airflow obstruction.

Assessment of respiratory tract deposition of nanoparticles is a key link to understanding their health impacts. An instrument was developed to measure respiratory tract deposition of nanoparticles in a single breath. Monodisperse nanoparticles are generated, inhaled and sampled from a determined volumetric lung depth after a controlled residence time in the lung. The instrument was characterized for sensitivity to inter-subject variability, particle size (22, 50, 75 and 100 nm) and breath-holding time (3–20 s) in a group of seven healthy subjects. The measured particle recovery had an inter-subject variability 26–50 times larger than the measurement uncertainty and the results for various particle sizes and breath-holding times were in accordance with the theory for Brownian diffusion and values calculated from the Multiple-Path Particle Dosimetry model. The recovery was found to be determined by residence time and particle size, while respiratory flow-rate had minor importance in the studied range 1–10 L/s. The instrument will be used to investigate deposition of nanoparticles in patients with respiratory disease. The fast and precise measurement allows for both diagnostic applications, where the disease may be identified based on particle recovery, and for studies with controlled delivery of aerosol-based nanomedicine to specific regions of the lungs.

Introduction: Spirometry, the standard method to diagnose COPD, has poor sensitivity for early emphysema. This may delay diagnosis and lead to a poorer prognosis. Nanoparticles are deposited in the lungs by diffusion only, which makes their deposition depend on time and diffusion distance in distal airspaces. Aim: To determine whether emphysema can be identified and graded according to nanoparticle deposition after a single inhalation. Emphysema patients are expected to have reduced deposition relative to controls, due to a larger diffusion distance in enlarged distal airspaces. Further, we expect a correlation between disease severity and nanoparticle deposition. Methods: 22 patients with COPD and 15 normal subjects underwent Airspace Dimension Test (ADT) and spirometry after bronchodilation. ADT is performed as a single, maximal inhalation of nanoaerosol. Particle concentration is measured in the inhaled aerosol and an alveolar sample exhaled after a standardised breath-hold. The difference in particle concentration reflects deposition. CT was performed in the patient group. The images were reconstructed and processed with syngo.via Pulmo3D software to perform CT densitometric analysis. Low attenuation regions were quantified as the 15th percentile point (PD15). Results: All COPD patients fulfilled the GOLD criteria, while all healthy subjects had normal spirometry. There was highly significant difference in deposition of nanoparticles between the two groups (p Conclusion: The ADT can identify emphysema in patients with COPD. The results show a correlation to the extent of emphysema as measured by CT densitometry.

There is a need for cost-effective and simple methods for diagnosis of morphological changes in the small airways, for instance due to emphysema. We hypothesise that measurement of lung deposition of airborne nanoparticles may provide a new opportunity for assessment of peripheral airspace dimensions. Here we outline a basic theoretical background for the method. Nanoparticles deposit almost completely by diffusion. Based on this notion, the effective airway diameter could be calculated from experimental data with a simple deposition model derived from the Fokker-Planck equation. First, the particle deposition in the lung is determined for different breath-holding times. Thereafter, these data are used to compute the particle half-life time, t ½ . Finally, the airway radius, r , is calculated as r =2.89√( D·t ½ ) where D is the diffusion coefficient given by the Stokes-Einstein relation. The method was validated for 7 healthy subjects aged 20-34 yrs. The respiratory tract deposition was measured for three particle sizes (50, 75 and 100 nm) and four breath-holding times (5, 7, 10 and 15 s) at a volumetric lung depth of 1.5 L (Figure 1). Obtained radiuses were on average 296±36, 225±15 and 204±29 µm for the three particle sizes, respectively. Using nanoparticles can have several benefits as a tool in diagnosis of emphysema as low price, no x-ray and high sensitivity for morphology in the gas exchange region of the lung.