An explorative study on respiratory health among operators working in polymer additive manufacturing.

Additive manufacturing (AM), or 3D printing, is a growing industry involving a wide range of different techniques and materials. The potential toxicological effects of emissions produced in the process, involving both ultrafine particles and volatile organic compounds (VOCs), are unclear, and there are concerns regarding possible health implications among AM operators. The objective of this study was to screen the presence of respiratory health effects among people working with liquid, powdered, or filament plastic materials in AM. Methods: In total, 18 subjects working with different additive manufacturing techniques and production of filament with polymer feedstock and 20 controls participated in the study. Study subjects filled out a questionnaire and underwent blood and urine sampling, spirometry, impulse oscillometry (IOS), exhaled NO test (FeNO), and collection of particles in exhaled air (PEx), and the exposure was assessed. Analysis of exhaled particles included lung surfactant components such as surfactant protein A (SP-A) and phosphatidylcholines. SP-A and albumin were determined using ELISA. Using reversed-phase liquid chromatography and targeted mass spectrometry, the relative abundance of 15 species of phosphatidylcholine (PC) was determined in exhaled particles. The results were evaluated by univariate and multivariate statistical analyses (principal component analysis). Results: Exposure and emission measurements in AM settings revealed a large variation in particle and VOC concentrations as well as the composition of VOCs, depending on the AM technique and feedstock. Levels of FeNO, IOS, and spirometry parameters were within clinical reference values for all AM operators. There was a difference in the relative abundance of saturated, notably dipalmitoylphosphatidylcholine (PC16:0_16:0), and unsaturated lung surfactant lipids in exhaled particles between controls and AM operators. Conclusion: There were no statistically significant differences between AM operators and controls for the different health examinations, which may be due to the low number of participants. However, the observed difference in the PC lipid profile in exhaled particles indicates a possible impact of the exposure and could be used as possible early biomarkers of adverse effects in the airways.

Exploring Methods for Surveillance of Occupational Exposure from Additive Manufacturing in Four Different Industrial Facilities.

3D printing, a type of additive manufacturing (AM), is a rapidly expanding field. Some adverse health effects have been associated with exposure to printing emissions, which makes occupational exposure studies important. There is a lack of exposure studies, particularly from printing methods other than material extrusion (ME). The presented study aimed to evaluate measurement methods for exposure assessment in AM environments and to measure exposure and emissions from four different printing methods [powder bed fusion (PBF), material extrusion (ME), material jetting (MJ), and vat photopolymerization] in industry. Structured exposure diaries and volatile organic compound (VOC) sensors were used over a 5-day working week. Personal and stationary VOC samples and real-time particle measurements were taken for 1 day per facility. Personal inhalable and respirable dust samples were taken during PBF and MJ AM. The use of structured exposure diaries in combination with measurement data revealed that comparatively little time is spent on actual printing and the main exposure comes from post-processing tasks. VOC and particle instruments that log for a longer period are a useful tool as they facilitate the identification of work tasks with high emissions, highlight the importance of ventilation and give a more gathered view of variations in exposure. No alarming levels of VOCs or dust were detected during print nor post-processing in these facilities as adequate preventive measures were installed. As there are a few studies reporting negative health effects, it is still important to keep the exposure as low as reasonable.

Exhaled particles as markers of small airway inflammation in subjects with asthma.

Exhaled breath contains suspended particles of respiratory tract lining fluid from the small airways. The particles are formed when closed airways open during inhalation. We have developed a method called Particles in Exhaled air (PExA® ) to measure and sample these particles in the exhaled aerosol. Here, we use the PExA® method to study the effects of birch pollen exposure on the small airways of individuals with asthma and birch pollen allergy. We hypothesized that birch pollen-induced inflammation could change the concentrations of surfactant protein A and albumin in the respiratory tract lining fluid of the small airways and influence the amount of exhaled particles. The amount of exhaled particles was reduced after birch pollen exposure in subjects with asthma and birch pollen allergy, but no significant effect on the concentrations of surfactant protein A and albumin in exhaled particles was found. The reduction in the number of exhaled particles may be due to inflammation in the small airways, which would reduce their diameter and potentially reduce the number of small airways that open and close during inhalation and exhalation.

Comparison of exhaled endogenous particles from smokers and non-smokers using multivariate analysis.

BACKGROUND: Smoking, along with many respiratory diseases, has been shown to induce airway inflammation and alter the composition of the respiratory tract lining fluid (RTLF). We have previously shown that the phospholipid and protein composition of particles in exhaled air (PEx) reflects that of RTLF. In this study, we hypothesized that the composition of PEx differs between smokers and non-smokers, reflecting inflammation in the airways. OBJECTIVE: It was the aim of this study to identify differences in the phospholipid composition of PEx from smokers and non-smokers. METHODS: PEx from 12 smokers and 13 non-smokers was collected using a system developed in-house. PEx was analysed using time-of-flight secondary ion mass spectrometry, and the mass spectral data were evaluated using multivariate analysis. Orthogonal partial least squares (OPLS) was used to relate smoking status, lung function and pack years to the chemical composition of RTLF. The discriminating ions identified by OPLS were then used as explanatory variables in traditional regression analysis. RESULTS: There was a clear discrimination between smokers and non-smokers according to the chemical composition, where phospholipids from smokers were protonated and sodiated to a larger extent. Poor lung function showed a strong association with higher response from all molecular phosphatidylcholine species in the samples. Furthermore, the accumulated amount of tobacco consumed was associated with variations in mass spectra, indicating a dose-response relationship. CONCLUSION: The chemical composition of PEx differs between smokers and non-smokers, reflecting differences in the RTLF. The results from this study may suggest that the composition of RTLF is affected by smoking and may be of importance for lung function.

Surfactant protein A and albumin in particles in exhaled air.

In this study we test the hypothesis that endogenous particles in exhaled air (PEx), non-invasively sampled from lower airways, are well suited for the analysis of respiratory tract lining fluid (RTLF) proteins, i.e., surfactant protein A (SP-A) and albumin. Ten healthy volunteers were included in the study and participated in two sampling sessions. Blood, exhaled breath condensate (EBC) and PEx were collected at each session. 100 L of breath were collected for each exhaled sample. Serum and exhaled samples were analyzed for SP-A using an in-house ELISA. Albumin was analyzed in exhaled samples using a commercial ELISA kit. SP-A detection rates were 100%, 21%, and 89% for PEx, EBC and serum, respectively. Albumin was detected in PEx, but not in EBC. SP-A measurements in PEx showed good repeatability with an intra-individual coefficient of variation of 13%. Both SP-A and albumin showed significant correlation to mass of PEx (r(s) = 0.93, p < 0.001 and r(s) = 0.86, p = 0.003, respectively). Sampling and analysis of PEx is a valid non-invasive method to monitor RTLF proteins sampled from the lower respiratory tract, as demonstrated here by example of SP-A and albumin analysis.

Exhaled endogenous particles contain lung proteins.

BACKGROUND: We recently developed a novel, noninvasive method for sampling nonvolatile material from the distal airways. The method is based on the collection of endogenous particles in exhaled air (PEx). The aim of this study was to characterize the protein composition of PEx and to verify that the origin of PEx is respiratory tract lining fluid (RTLF). METHOD: Healthy individuals exhaled into the sampling device, which collected PEx onto a silicon plate inside a 3-stage impactor. After their extraction from the plates, PEx proteins were separated by SDS-PAGE and then analyzed by LC-MS. Proteins were identified by searching the International Protein Index human database with the Mascot search engine. RESULTS: Analysis of the pooled samples identified 124 proteins. A comparison of the identified PEx proteins with published bronchoalveolar lavage (BAL) proteomic data showed a high degree of overlap, with 103 (83%) of the PEx proteins having previously been detected in BAL. The relative abundances of the proteins were estimated according to the Mascot exponentially modified protein abundance index protocol and were in agreement with the expected protein composition of RTLF. No amylase was detected, indicating the absence of saliva protein contamination with our sampling technique. CONCLUSIONS: Our data strongly support that PEx originate from RTLF and reflect the composition of undiluted RTLF.

Effect of airway opening on production of exhaled particles.

The technique of sampling exhaled air is attractive because it is noninvasive and so allows repeated sampling with ease and no risk for the patient. Knowledge of the biomarkers' origin is important to correctly understand and interpret the data. Endogenous particles, formed in the airways, are exhaled and reflect chemical composition of the respiratory tract lining fluid. However, the formation mechanisms and formation sites of these particles are unknown. We hypothesize that airway opening following airway closure causes production of airborne particles that are exhaled. The objective of this study was to examine production of exhaled particles following varying degrees of airway closure. Ten healthy volunteers performed three different breathing maneuvers in which the initial lung volume preceding an inspiration to total lung capacity was varied between functional residual capacity (FRC) and residual volume (RV). Exhaled particle number concentrations in the size interval 0.30-2.0 microm were recorded. Number concentrations of exhaled particles showed a 2- to 18-fold increase after exhalations to RV compared with exhalations where no airway closure was shown [8,500 (810-28,000) vs. 1,300 (330-13,000) particles/expired liter, P = 0.012]. The difference was most noticeable for the smaller size range of particles (<1 microm). There were significant correlations between particle concentrations for the different maneuvers. Our results show that airway reopening following airway closure is an important mechanism for formation of endogenous exhaled particles and that these particles originate from the terminal bronchioles.