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Chronic obstructive pulmonary disease (COPD) and asthma are characterised by increased oxidative stress in the lungs. The precise contribution of this stress to COPD aetiology remains unclear, partly due to the confounding influence of physiological ageing. Previous reports of increased oxidative stress in bronchoalveolar lavage (BAL) samples from individuals with COPD may at least in part be attributable to the subjects’ age. This study investigated whether increased metal concentrations at the air–lung interface would contribute to oxidative stress in the lungs. We analysed BAL samples from young and old never-smokers, young asthmatic never-smokers, older smokers without COPD and COPD patients (both current and ex-smokers). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify a range of transition metals, including iron, copper, zinc, arsenic and cadmium. BAL concentrations of copper and zinc were significantly lower in young groups compared to the older groups, irrespective of smoking status or disease (p < 0.001 for both). BAL copper was significantly associated with several markers of oxidative stress, all of which were elevated with age: glutathione disulphide (ρ = 0.50, p < 0.001), dehydroascorbate (ρ = 0.67, p < 0.001) and 4-Hydroxynonenal (ρ = 0.43, p < 0.001). These data indicate that age-related increases in respiratory tract copper concentrations contribute to elevated levels of oxidative stress at the air–lung interface independently of respiratory disease.

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. R

ESULTS: 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.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs, mostly affecting young and middle-aged women. Significant questions remain as to its pathogenesis, especially the triggers for the associated interstitial lung disease (SSc-ILD). We examined the extent to which SSc and SSc-ILD were related to oxidative stress and altered metal homeostasis at the air-lung interface.

Methods: In this case-control study, we recruited 20 SSc patients, of which 11 had SSc-ILD. Eighteen healthy individuals were recruited as age-matched healthy controls, for a total of 38 study participants. Low molecular weight antioxidants (ascorbate, urate and glutathione), metal transport and chelation proteins (transferrin and ferritin) and metals (Fe and Cu) concentrations, including a measure of the catalytically active metal pool, were determined in respiratory tract lining fluid (RTLF) collected by bronchoalveolar lavage from the SSc group and compared with healthy controls.

Results: In the SSc group, 14 individuals were of female sex (70%) and the median age was 57 years (range 35–75). We observed evidence of oxidative stress in the RTLFs of SSc patients, characterised by increased concentrations of glutathione disulphide (GSSG, P<0.01), dehydroascorbate (DHA, P<0.05) and urate (P<0.01). This was associated with elevated RTLF Fe (P=0.07) and Cu (P<0.001), and evidence of a catalytic metal pool, demonstrated by an enhanced rate of ascorbate oxidation in the recovered lavage fluid (p<0.01). Cu concentrations were significantly associated with the ascorbate depletion rate (r=0.76, P<0.001), and GSSG (r=0.38, P<0.05) and protein carbonyl (r=0.44, P<0.01) concentrations. Whilst these markers were all increased in SSc patients, we found no evidence for an association with SSc-ILD.

Conclusions: These data confirm the presence of oxidative stress in the airways of SSc patients and, for the first time, suggest that an underlying defect in metal homeostasis at the air-lung interface may play a role in disease progression.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms.

Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50–64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing.

Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA.

Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (DLCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D-LCO. We examined if the GLI LLN for D-LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden. Spirometry, D-LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women). Both the median and LLN for D-LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D-LCO <GLI LLN (and also <SCAPIS LLN) was 3.9%, while the prevalence of D-LCO >GLI LLN but <SCAPIS LLN was 5.7%. Subjects with D-LCO >GLI LLN but <SCAPIS LLN (n=860) had more emphysema (14.3% versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal D-LCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma. The GLI LLN for D-LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D-LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

Background: Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study.

Method: The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002–04 (n = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002–2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2–3 with rapid decline in FEV₁ and group B) COPD grade 2–3 without rapid decline in FEV₁ (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A–C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D.

Results: From the database groups A–D were identified; group A n = 37, group B n = 29, group C n = 41, and group D n = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A (n = 12) and B (n = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome.

Conclusion: The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.