Abstract Background Despite the high prevalence and clinical significance of emphysema, few genetic risk loci have been consistently replicated. We conducted a genome-wide association study (GWAS) of CT-based emphysema, with a particular focus on non-smoking-related genetic determinants. Methods We analyzed 25,639 individuals of European ancestry from the SCAPIS national cohort, aged 50–65 years, of which 51% were never-smokers. Emphysema was assessed through semi-quantitative visual scoring of CT scans. GWAS was performed in the whole sample and stratified on smoking status. We also examined the association of previously reported emphysema- and lung function-related variants with emphysema in our dataset. Results Emphysema criteria were fulfilled for 1,479 participants (5.6%), with higher prevalence among current ( N = 576, 18.2%) and former smokers ( N = 612, 6.5%) compared to never-smokers ( N = 263, 2.0%). We identified three independent genetic loci for emphysema in smokers and no signals in never-smokers. The strongest signal was observed in the well-established nicotinic acetylcholine receptor cluster (CHRNA5-A3-B4) locus on chromosome 15. Additionally, we discovered novel associations near the dysferlin (DYSF) gene on chromosome 2 and in an intergenic region on chromosome 3. By assessing previously lung phenotype-associated variants we also found evidence supporting association with emphysema in smokers for variants in the EFEMP1/MIR217HG/PNPT1 locus on chromosome 2, previously linked to reduced FEV 1 /FVC ratio. Conclusion This study, based on the largest unselected population sample to date, provides novel insights into the genetic architecture of emphysema. However, no signals were detected in never-smokers despite the large sample-size, likely due to the low prevalence of emphysema in that group. The proposed genetic risk loci require external replication.

The Particle in Exhaled Air (PExA) method provides a non-invasive way to evaluate how electronic (e)-cigarette aerosols affect the small airways by providing a sample of their lining fluid. This study explored for the first time the changes in the lipid profiles of airway lining fluid and their links to systemic inflammatory marker IL-13-producing T cells in blood, local airway type Ⅱ inflammatory marker FeNO, and local innate immune marker TLR2 in sputum among e-cigarette users, cigarette smokers, and non-smokers. PEx samples were collected on a single occasion from 24 non-smokers, 21 cigarette smokers, and 17 e-cigarette users aged 20 to 65 years. Participants completed a questionnaire including information on cigarette and e-cigarette use. All participants had normal lung function (FEV1/VC ≥ 0.7) and no history of allergy or lung diseases. Statistical significances were tested by the Kruskal-Wallis test followed by the Mann-Whitney test as post-hoc, linear regression, and OPLS-DA analysis. A total of 86 lipid species across 9 lipid classes were identified in the analysis. Significant differences in both phospholipid classes and individual lipid species were found among e-cigarette users, cigarette smokers, and non-smokers, with the most pronounced differences between e-cigarette users and non-smokers. Notably, the percentages of lysophosphatidylcholine (LPC), sphingomyelin (SM), and phosphatidylethanolamine (PE) lipid classes were higher in e-cigarette users compared to non-smokers. Additionally, a strong association was identified between IL-13-producing T cells and lipid profiles in e-cigarette users compared to non-smokers. The observed changes in lipid profiles among e-cigarette users may indicate disruptions in lipid homeostasis linked to chronic inflammatory lung diseases. This underscores the need for further research on the long-term effects of e-cigarette use, as the precise implications remain unclear.

Objective Occupational exposures to dust have been associated with pulmonary alveolar proteinosis (PAP) in case series, but population-based epidemiological data are needed. Methods We identified 286 cases of PAP from the Swedish National Patient Register and the Cause-of-Death Register between 1991 and 2022. For the present analysis, we included 212 cases aged 20-65 years with available occupational information before the index date or within two years thereafter. Controls matched on age and sex were drawn from the population register and assigned the same index date as their corresponding case; of these, 1438 controls had available occupational information and were included in the analyses. We linked cases and controls to Swedish registries to obtain socioeconomic status and occupational data. We applied an established job-exposure matrix to characterize occupational exposure to inorganic dust, with the subset silica dust, fumes, vapors and gases and organic dust. We used adjusted conditional logistic analyses to estimate the odds ratios (OR) with 95% confidence intervals (CI) for the occupational exposures in the year before index date and PAP. Results None of the occupational exposures analyzed showed a statistically significant association to PAP. The OR for inorganic dust was 1.08 (95% CI 0.75-1.55); silica dust alone was 1.55 (95% CI 0.75-3.23) and organic dust was 1.48 (95% CI 0.92-2.38). Among men, however, exposure to organic dust was associated with PAP [OR 1.92 (95% CI 1.18-3.23)]. Among women, the results were inconclusive. Conclusions There were no associations between occupational exposure to fumes, vapors and gases and inorganic dust and risk of PAP. Among men, exposure to organic dust was associated with increased risk for PAP. Some occupational inhalants may increase the risk of PAP.

Exercise-induced bronchoconstriction (EIB) commonly develops after exercise in cold, dry environments, but the effects of acute exercise in the cold on airway physiology remain incompletely understood. Exhaled particle (PEx) analysis offers a novel, non-invasive approach to assess respiratory tract lining fluid (RTLF) composition and may provide mechanistic insights into airway responses before clinically detectable changes occur. This study investigated the PEx response to moderate-intensity exercise in sub-zero conditions among healthy atopic and non-atopic individuals. Eighteen participants (14 male, 29 ± 6 years) performed two moderate-intensity exercise trials (30 and 90 min duration) in a climate chamber at -15 °C. PEx samples were collected using the PExA® method, before and 30 min after exercise to assess particle mass and count across eight size bins (0.4-5µm) and for subsequent lipidomic analysis. Exercise induced a significant increase in smaller PEx (0.4-0.7μm;p< 0.01). Three lipid species were altered after 30 min exercise, and 11 after 90 min exercise. Phosphatidylethanolamine PE(16:1_18:0) was the only lipid that consistently increased across both exercise durations (30 min:p= 0.023; 90 min:p= 0.044;g= 0.97). Three specific lipid species showed differential exercise responses between atopic and non-atopic participants, including an oxidised phosphatidylcholine species PC(16:0_9:0;O) (p= 0.006,q= 0.59,g= 0.86). These results provide preliminary insight into airway surfactant responses to exercise in a cold climate and contribute to the growing understanding of how the PExA® method can be applied as a non-invasive tool for respiratory health assessment in an acute setting.

OBJECTIVES:To study if the adverse effects of welding fume exposure are more pronounced in individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS:In this cross-sectional study, spirometry, oscillometry, multiple breath washout (MBW), and diffusing capacity were tested in 44 exposed workers and 62 unexposed individuals. A history of coronavirus disease 2019 (COVID-19) was present in 34% of exposed and 68% of unexposed individuals. Statistical analyses included Mann-Whitney test, Kruskal-Wallis test, and multiple regression analyses. RESULTS:Welding fume exposure was significantly associated with increased small airway resistance (R 5-20 ), assessed by oscillometry, while exposure combined with past COVID-19 was associated with increased ventilation heterogeneity in the small conducting airways, as assessed by MBW, and reduced diffusing capacity. CONCLUSIONS:Welding-fume-exposed individuals with prior COVID-19 had more pronounced small airway impairment, as assessed by MBW, than exposed workers with no COVID-19 history.

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.

Extracellular vesicles (EVs) are heterogeneous and play important roles in intercellular communication, contributing to physiological and pathological processes. Since few markers currently exist to differentiate subtypes of EVs, this study aimed to determine proteomic and lipidomic differences among four EV subpopulations. Large and small EVs (L-EVs and S-EVs) were isolated from human mast cells (HMC-1) and monocytes (THP-1) by differential ultracentrifugation and then further separated by density cushions into two different densities [low-density (LD) and high-density (HD)]. L-EVs were pelleted at 16,500 × g, and S-EVs were pelleted at 118,000 × g. LD EVs were collected at 1.079-1.146 g/mL, while HD EVs were collected at 1.146-1.185 g/mL. The morphology, size and yield of EVs were determined by TEM and western blot. The proteome and lipidome of the EV subpopulations were determined with mass spectrometry. A total of 5364 proteins were quantified, and L-EVs LD were enriched in mitochondrial proteins such as TIMM/TOMM and MICOS proteins, while L-EVs HD were enriched in cytoskeleton- and cytokinesis-associated proteins, such as KIF proteins. S-EVs LD were enriched in tetraspanins, ADAM10 and ESCRT machinery proteins, while S-EVs HD were enriched in proteins commonly viewed as contaminants, such as histones, complement factors and collagen. Proteins involved in membrane trafficking between the plasma membrane and organelles, such as adaptor protein complexes, the conserved oligomeric Golgi complex, the trafficking protein particle complex, sortin-nexins, TBC1 domain proteins and coatomer subunits, were expressed at similar levels across all EV subtypes. Furthermore, 107 lipids were quantified, and phosphatidylethanolamine (PE) was less abundant in L-EVs LD as compared to the other EV subtypes, while ceramides were enriched in L-EVs as compared to S-EVs.This study demonstrates that there is a core proteome and lipidome that is similar across all four EV subtypes, but importantly, it also shows that a portion of the proteome and lipidome differs in EV subpopulations separated based on size and density. We suggest that these could be important markers in future EV studies and that they may reflect a different biogenesis and EV function.

OBJECTIVE:To investigate alterations in the respiratory tract lining fluid phospholipids and their association with pulmonary function in welding fume-exposed workers. METHOD:Particles in exhaled air were collected from 134 subjects. Pulmonary function was assessed via spirometry and diffusing capacity for carbon monoxide. Small airway function was measured with impulse oscillometry and multiple breath washout. Data were analyzed using univariate (Wilcoxon rank sum, Kendall tau, linear regression) and multivariate (OPLS, machine learning) statistics. RESULTS:Increased proportions of polyunsaturated fatty acids in the respiratory tract lining fluid among welding fume exposed. Some lipids correlated with diffusing capacity for carbon monoxide and small airway dysfunction outcomes. CONCLUSION:Welding fume exposure may alter respiratory tract lining fluid phospholipid composition, potentially contributing to chronic pulmonary diseases. Further research into these mechanisms is needed.

Background Preserved ratio impaired spirometry (PRISm) is a spirometry pattern of interest regarding incident airflow obstruction and higher mortality risk. We applied a proteomic approach to gain more insight into the biological mechanisms associated with PRISm. Methods From the population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS), participants in the Main (n=4835) and Pilot (n=1054) studies, were included as discovery and replication cohorts. The lower limit of normal (LLN) of post-bronchodilator forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC was defined as the fifth percentile in healthy, never-smoking SCAPIS participants. Participants were subdivided into five groups: reference: FEV 1 /FVC≥LLN and FEV 1 ≥LLN and FVC≥LLN (n=4084)); mild chronic airflow limitation (CAL): FEV 1 /FVC

OBJECTIVES:There is a lack of knowledge about whether occupational exposures increase the risk of emphysema, especially in never-smokers. Our objective was to determine if occupational exposures are associated with emphysema and impaired diffusing capacity. METHODS:In the Swedish CArdioPulmonary bioImage Study (SCAPIS), persons from the general population aged 50-64 answered a questionnaire and underwent CT of the lung as well as assessment of the diffusing capacity of their lungs for carbon monoxide (DLCO), presented as DLCO<lower limit of normal (LLN). Emphysema was defined as emphysema in any part of the lungs. Occupational exposures were assessed by a job exposure matrix based on longest held job. ORs with 95% CIs were calculated using logistic multivariable models. RESULTS:In this cross-sectional study (27 370 persons including 13 981 never-smokers), occupational exposure to inorganic dust was associated with emphysema (OR 1.25, 95% CI 1.07 to 1.47), also among never-smokers, (OR 1.46, 95% CI 1.00 to 2.11). There were associations with DLCO<LLN for occupational exposure to inorganic dust and vapour and gases. With all exposures in the same model, inorganic dust was associated with emphysema (OR 1.30, 95% CI 1.08 to 1.57), and vapour and gases were associated with DLCO<LLN (OR 1.17, 95% CI 1.00 to 1.38). In those with emphysema and impaired DLCO, there was an association with inorganic dust (OR 1.65, 95% CI 1.20 to 2.28), also among never-smokers (OR 3.79, 95% CI 1.35 to 10.63). CONCLUSIONS:Occupational exposures to inorganic dust are associated with emphysema. The association is stronger in those with the combination of emphysema and impaired DLCO indicating serious exposure effects in the alveoli.

RATIONALE Changes in the composition of phospholipids in small airway lining fluid have been observed in various lung diseases such as asthma. Also, exposure to air pollution and aeroallergens can cause severe respiratory effects, especially in asthma. However, knowledge of how exposure may impact small airway lining fluid, the first line barrier to inhaled material, is unclear. This study explores the influence of exposure on the phospholipid composition of small airway lining fluid and possible differences in response in allergic asthma and healthy individuals. METHODS Subjects with allergic asthma and birch allergy (n=23) and healthy controls (n=13) were examined during two consecutive pollen seasons and once outside the season. Personal exposure measurements of ozone (O₃), nitric oxides (NOₓ), and particulate matter (PM₁₀) were conducted before clinical examinations which included sampling of small airway lining fluid using the particles in exhaled air (PExA) method, nitrogen single breath washout test (N₂ SBW), and asthma control questionnaire (ACQ-7). Associations between lipid composition, asthma, pollutants, and seasons were analyzed using mixed effects regression. RESULTS A total of 78 lipids were quantified. Eighteen lipid species significantly differed between subjects with asthma and controls in at least one season. Six species differed exclusively during both pollen seasons and three in the non-pollen season. Interaction effects between season and exposure were identified for seven lipids. Phospholipids containing arachidonic acid were negatively associated with ACQ, whereas there were positive associations with lipids containing linoleic acid. Also, 23 lipids were associated with ventilation inhomogeneity, as determined by the N₂ SBW test. In healthy, 59 lipid species showed significant associations with NOx, O3, and/or PM10, whereas only four lipid species in asthma. Significant interaction effects between exposure and group (asthma/healthy) were identified for three lipids. In response to NOx, estimates of PE(O-2:0/20:4) and PC(16:0_18:3) were significantly lower in individuals with asthma compared to healthy, while PC(14:1_16:0) was higher in asthma in response to PM10 exposure.CONCLUSIONS Our findings suggest that allergic asthma is associated with alterations in the lipid composition in small airway lining fluid. The associations between asthma control and lipids containing linoleic acid and arachidonic acid further indicate a possible association with inflammatory pathways. Exposure to air pollutants was associated with numerous phospholipids in healthy individuals, whereas only a few associations in asthma. The underlying reason is unclear but may suggest that the protective function of surfactant phospholipids is absent in asthma.

OBJECTIVE:To explore if the phospholipid composition in the small airway lining fluid differed between a group of tunnel construction workers exposed to respirable crystalline silica (RCS) and a reference group. METHODS:In total, 19 healthy, non-smoking workers under exposure to RCS and 21 unexposed referents from the same construction site were included. The participants underwent a health examination including lung function measurements and collection of exhaled particles (PEx) using the Particles in exhaled air (PExA) method. Analysis of PEx included determination of lipids. In total, 95 lipid species, primarily phospholipids, were determined. Non-parametric analyses (Wilcoxon rank-sum test and quantile regression), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for data analysis. RESULTS:A difference in mol% of phospholipids between the RCS exposed tunnel construction workers and unexposed referents was observed. On lipid class level there was a higher mol% of sphingomyelin (SM) species among exposed workers compared to referents. Regarding single phospholipid species, higher mol % of phosphatidylcholine (PC) and phosphatidylglycerol (PG) species containing diacyl chains with 18:2 (linoleic acid) and 20:4 (arachidonic acid) fatty acid components were observed in the exposed group. Additionally, lower mol% of saturated PC species were observed among the exposed. CONCLUSIONS:Differences in phospholipid composition in the small airway lining fluid between workers exposed to RCS and a reference group were observed. This indicates a possible impact of RCS exposure on phospholipids in the small airways. However, whether these are linked to health effects is currently not known.

The use of electronic (e)-cigarettes in the long term has been associated with an increased risk of respiratory diseases. Dual use of e-cigarettes and traditional cigarettes may increase these risks even more due to the combined exposure effects of these products. The aim of this study was to investigate the local and systemic effects of e-cigarette use for more than one year and compare them with healthy non-smokers, cigarette smokers, and dual users. The clinical study was conducted among 22 healthy non-smokers, 20 e-cigarette users, 20 cigarette smokers, and 20 dual users. Participants were matched with age and BMI, had normal baseline lung function, and had no allergies. Exhaled FeNO and bronchial responsiveness were assessed along with reactive oxygen species (ROS), toll-like receptor (TLR) expression, and inflammatory cytokines in blood and sputum. Exhaled FeNO was higher in e-cigarette users (14 ppb, p = 0.04) and lower in cigarette smokers (9 ppb, p = 0.04) compared to healthy non-smokers (11 ppb). Bronchial responsiveness was increased in e-cigarette users (1.9 mg, p = 0.01) and cigarette smokers (1.9 mg, p = 0.01) compared to healthy non-smokers (2.9 mg). ROS in blood and sputum in e-cigarette users (p = 0.005 and p = 0.04) and dual users (p = 0.003 and p = 0.04) were increased. Also, TLR2 expression in blood granulocytes in all exposed groups (p = 0.001), TLR2 and TLR4 expression in sputum in e-cigarette users (p = 0.04 and p = 0.03) and dual users (p < 0.0001 and p = 0.004) were increased. Moreover, the percentage of IL13 and IFNγ cytokine-producing T cells in blood were increased in e-cigarette users (p = 0.0001 and p < 0.0001) and dual users (p = 0.001 and p < 0.0001). Our research indicates that both local and systemic inflammatory responses, along with innate immune receptor activity, were significantly altered in e-cigarette users and dual users. Notably, these alterations were detected in e-cigarette users within a short timeframe of just 1 to 3 years of use. Not applicable.

BACKGROUND:Low lung function has been consistently associated with increased cardiovascular disease (CVD) risk, with emerging evidence suggesting a potential causal relationship. However, underlying biological mechanisms remain unclear. AIM:To investigate relationships between CVD-associated plasma proteins and lung function. METHODS:We analysed plasma protein profiles in two Swedish population-based cohorts: the Swedish CArdioPulmonary bioImage Study (SCAPIS) (n = 4,982, mean age 57.6 years) as the discovery cohort and the SCAPIS pilot study (n = 1,054, mean age 57.7 years) for replication. Multiple linear regression models were used to assess associations between 92 CVD-associated proteins and z-scores of FEV1, FVC, and FEV1/FVC, adjusting for known confounders. P-values were corrected using the Benjamini-Hochberg method (5% FDR). Significantly associated proteins were validated in the replication cohort. RESULTS:A total of 69 proteins were associated with FEV1, 57 with FVC, and 9 with FEV1/FVC. Several inflammatory proteins and adipokines, including leptin, interleukin-6, fatty acid-binding protein (adipocyte), were consistently linked to lower lung function. Leptin had the strongest negative association (FEV1: β = -0.50, 95 % CI: [-0.69, -0.31], p < 0.001; FVC: β = -0.52, 95 % CI: [-0.68, -0.35], p < 0.001 per-SD increase). CONCLUSIONS:Multiple CVD-associated proteins, mainly reflecting inflammatory and metabolic processes, were associated with reduced FEV1 and FVC, supporting a link between systemic inflammation, adipokine metabolism and impaired lung function. Leptin had the strongest association, suggesting that its effects on lung function may extend beyond adiposity. Further research is needed to clarify the mechanisms driving these associations and to assess whether these proteins could serve as early biomarkers or intervention targets.

Introduction Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed vesicles released by cells. They play important roles in intercellular communication and contribute to several physiological and pathological processes. Cells release subpopulations of EVs with distinct biogenesis and functions, however, we currently have few markers to differentiate them. This study, therefore, aimed to determine proteomic and lipidomic differences among four EV subpopulations of varying sizes and densities. Methods Large and small EVs (L-EVs and S-EVs) were isolated from two immune cell lines by differential ultracentrifugation at 16,500 × g and 118,000 × g, respectively. The crude EVs were then further separated by density cushion centrifugation. EVs were isolated from the interphase between 1.079-1.146 and 1.146-1.185 g/ml, hereafter referred to as low density (LD) and high density (HD), respectively. This resulted in four subpopulations of EVs: L-EVs LD, L-EVs HD, S-EVs LD, and S-EVs HD. The morphology, size, and yield of EVs were determined by nanoparticle tracking analysis, electron microscopy, and western blot. The proteome and lipidome of the four subpopulations of EVs were determined with mass spectrometry. Results A total of 5364 proteins were quantified in the dataset. L-EV and S-EVs as well as LD and HD were well separated. Briefly, L-EVs LD were enriched in mitochondrial proteins such as the TIMM/TOMM complex, MICOS, and ATP5 proteins. In contrast, L-EVs HD were enriched in proteins associated with the cytoskeleton, such as KIF proteins. Furthermore, S-EVs LD were enriched in tetraspanins and ESCRT machinery proteins, while S-EVs HD were enriched in histones, CCT proteins, and proteins from the complement pathway. Proteins such as flotillins, RABs, annexins, and integrins were enriched in two or several subpopulations. Furthermore, 107 lipids were quantified, and the most abundant lipids in EVs were phosphatidylcholine (PC), sphingomyelin, and phosphatidylethanolamine (PE). The most profound difference was that PE was less abundant in L-EVs LD as compared to the other EV subtypes, and ceramides were enriched in L-EVs as compared to S-EVs. Conclusion This study demonstrates that the proteome and lipidome differ in EV subpopulations separated based on size and density. Furthermore, it validates several protein groups that have previously been suggested to be enriched in either S-EVs or L-EVs. ### Competing Interest Statement C.L. and R. C. have developed EV-associated patents for putative clinical utilisation. C. L. and R.C. have equity in Exocure Sweden AB, a startup developing EVs for therapeutic purposes. The remaining authors have no competing interests.

Introduction: Welding is associated with increased risk of respiratory disease and lung cancer. The lining fluid of small airways, mainly composed of surfactant lipids, constitute the first line of defense against inhaled welding fumes. The hypothesis for the study is that exposure induce alterations in phospholipid composition of the lining fluid that are associated with inflammatory changes and pulmonary function in welding fume-exposed workers. Method: 55 welders and 79 unexposed controls were examined with small airway functioning and the PExA-method (Particles in Exhaled Air (PExA), a method to sample small airway lining fluid non-invasively. PExA samples were analyzed with tandem mass spectrometry. Pulmonary function tests included: spirometry, diffusing capacity of carbon monoxide (DLCO), impulse oscillometry (IOS) and multiple breath washout (MBW). Statistical analyses were perfomed with multivariate analyses using SIMCA, and multiple regression using R. Results: 90 lipid species belonging to the eight major lipid classes hexosylceramide (HexCer), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylinositol (PI) and sphingomyelin (SM) were identified in the PExA samples. The proportions of polyunsaturated fatty acids (PUFAs) were significantly higher among welders, as exemplified by higher proportions of PC(16:0_18:3), PG(18:1_18:2), PG(16:0_18:2), PC(18:1_18:2), PE(16:0_18:2). On the other hand, the levels of plasmalogens were reduced among exposed, for example lnPE(O-2:1a/18:1): – 42% (95% CI: – 61- -23%) and lnPE(O-2:1a/18:2): – 32% (95% CI: – 52-14%). The lipid PC(15:0_16:0) correlated with MBW-derived Sacin (τ -0.16, p <0.01) and the lipid (16:0_18:3) correlated with DLCO (τ -0.18, p <0.01) see Figure 1. Both lipids correlated with resistance in small airways (R5-R20) measured by IOS (τ -0.18, p <0.05 and τ 0.22, p <0.01 respectively). Conclusion: The phospholipid composition of the respiratory tract lining fluid is altered among the welders indicating oxidative stress, as indicated by lower levels of plasmalogens that are suggested to serve as scavengers for reactive oxygen species. The altered composition may both serve protective functions but reflect also inflammatory processes leading to chronic pulmonary diseases associated with welding fume exposure.