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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

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

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

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.