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  • 1.
    Andersen, Grethe Neumann
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Nilsson, Kenneth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Hackett, Tillie-Louise
    Kazzam, Elsadig
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Warner, Jane
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Sandström, Thomas
    Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 10, p. 2199-2206Article in journal (Refereed)
    Abstract [en]

    Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.

  • 2. Baharom, Faezzah
    et al.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sorensen, Anna
    Human Lung Mononuclear Phagocytes in Health and Disease2017In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 499Article, review/survey (Refereed)
    Abstract [en]

    The lungs are vulnerable to attack by respiratory insults such as toxins, allergens, and pathogens, given their continuous exposure to the air we breathe. Our immune system has evolved to provide protection against an array of potential threats without causing collateral damage to the lung tissue. In order to swiftly detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)-together termed mononuclear phagocytes (MNPs)-line the respiratory tract with the key task of surveying the lung microenvironment in order to discriminate between harmless and harmful antigens and initiate immune responses when necessary. Each cell type excels at specific tasks: monocytes produce large amounts of cytokines, macrophages are highly phagocytic, whereas DCs excel at activating naive T cells. Extensive studies in murine models have established a division of labor between the different populations of MNPs at steady state and during infection or inflammation. However, a translation of important findings in mice is only beginning to be explored in humans, given the challenge of working with rare cells in inaccessible human tissues. Important progress has been made in recent years on the phenotype and function of human lung MNPs. In addition to a substantial population of alveolar macrophages, three subsets of DCs have been identified in the human airways at steady state. More recently, monocyte-derived cells have also been described in healthy human lungs. Depending on the source of samples, such as lung tissue resections or bronchoalveolar lavage, the specific subsets of MNPs recovered may differ. This review provides an update on existing studies investigating human respiratory MNP populations during health and disease. Often, inflammatory MNPs are found to accumulate in the lungs of patients with pulmonary conditions. In respiratory infections or inflammatory diseases, this may contribute to disease severity, but in cancer patients this may improve clinical outcomes. By expanding on this knowledge, specific lung MNPs may be targeted or modulated in order to attain favorable responses that can improve preventive or treatment strategies against respiratory infections, lung cancer, or lung inflammatory diseases.

  • 3. Baharom, Faezzah
    et al.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Scholz, Saskia
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sörensen, Anna
    Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry2017In: Jove-journal pf visualized experiments, ISSN 1940-087X, no 119, article id e55222Article in journal (Refereed)
    Abstract [en]

    The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.

  • 4. Baharom, Faezzah
    et al.
    Thomas, Saskia
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lepzien, Rico
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sorensen, Anna
    Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans2016In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, no 11, p. 4498-4509Article in journal (Refereed)
    Abstract [en]

    Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.

  • 5.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Langrish, Jeremy P.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Goudie, Colin
    Newby, David E.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Short-Term Exposure to Ozone Does Not Impair Vascular Function or Affect Heart Rate Variability in Healthy Young Men2013In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 135, no 2, p. 292-299Article in journal (Refereed)
    Abstract [en]

    Air pollution exposure is associated with cardiovascular morbidity and mortality, yet the role of individual pollutants remains unclear. In particular, there is uncertainty regarding the acute effect of ozone exposure on cardiovascular disease. In these studies, we aimed to determine the effect of ozone exposure on vascular function, fibrinolysis, and the autonomic regulation of the heart. Thirty-six healthy men were exposed to ozone (300 ppb) and filtered air for 75min on two occasions in randomized double-blind crossover studies. Bilateral forearm blood flow (FBF) was measured using forearm venous occlusion plethysmography before and during intra-arterial infusions of vasodilators 2–4 and 6–8h after each exposure. Heart rhythm and heart rate variability (HRV) were monitored during and 24h after exposure. Compared with filtered air, ozone exposure did not alter heart rate, blood pressure, or resting FBF at either 2 or 6h. There was a dose-dependent increase in FBF with all vasodilators that was similar after both exposures at 2–4h. Ozone exposure did not impair vasomotor or fibrinolytic function at 6–8h but rather increased vasodilatation to acetylcholine (p = .015) and sodium nitroprusside (p = .005). Ozone did not affect measures of HRV during or after the exposure. Our findings do not support a direct rapid effect of ozone on vascular function or cardiac autonomic control although we cannot exclude an effect of chronic exposure or an interaction between ozone and alternative air pollutants that may be responsible for the adverse cardiovascular health effects attributed to ozone.

  • 6.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lucking, Andrew J
    Langrish, Jeremy P
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Westerholm, Roger
    Löndahl, Jakob
    Donaldson, Ken
    Mudway, Ian S
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions2010In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 7, no 1, p. 19-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.

    OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.

    METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.

    MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).

    CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.

  • 7.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Olin, Anna-Carin
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Diesel exhaust but not ozone increases fraction of exhaled nitric oxide in a randomized controlled experimental exposure study of healthy human subjects2013In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 12, p. 36-Article in journal (Refereed)
    Abstract [en]

    Background: Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airway inflammation that may be used to assess respiratory effects of air pollution. We evaluated FENO as a measure of airway inflammation after controlled exposure to diesel exhaust or ozone. Methods: Healthy volunteers were exposed to either diesel exhaust (particle concentration 300 mu g/m(3)) and filtered air for one hour, or ozone (300 ppb) and filtered air for 75 minutes. FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after each exposure. Results: Exposure to diesel exhaust increased FENO at 6 hours compared with air at expiratory flow rates of 10 mL/s (p = 0.01) and at 50 mL/s (p = 0.011), but FENO did not differ significantly at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours. Ozone did not affect FENO at any flow rate or time point. Conclusions: Exposure to diesel exhaust, but not ozone, increased FENO concentrations in healthy subjects. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone, with implications for the use of FENO as an index of exposure to air pollution.

  • 8.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas, L
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Olin, Anna-Carin
    Dept. of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Fraction of exhaled nitric oxide after experimental exposure to diesel exhaust and ozone in manManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airways inflammation that may be used to assess the respiratory effects of air pollution, and when sampled at multiple expiratory flow rates can measure inflammation at different levels of the airway tract. We evaluate FENO as a measure of airways inflammation after controlled exposure to dilute diesel exhaust and ozone.

    Methods: Using a double blind randomised cross-over design, healthy volunteers (26±5 years) were exposed to either diesel exhaust (particle concentration 300 µg/m3) and filtered air for one hour (n=10), or ozone(300 ppb) and filtered air for 75 minutes (n=36). FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after the end of each exposure.

    Results: Exposure to diesel exhaust increased FENO at 6 hours compared to filtered air at expiratory flow rates of 10 mL/s [mean±SEM 60.8 ± 6.0 ppb versus 50.2 ± 5.9 ppb; P=0.01] and at 50 mL/s [18.6 ± 1.6 ppb versus 15.9 ± 1.5 ppb; P=0.011], but concentrations did not differ at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours and exposure to ozone did not affect FENO at any flow rate or time point.

    Conclusion: Exposure to diesel exhaust, but not ozone, increases the concentration of FENO in healthy subjects consistent with an inflammatory effect in the central airways. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone with implications for the use of FENO as an index of exposure to air pollution.

  • 9.
    Behndig, A. F.
    et al.
    Umeå University.
    Linder, Robert
    Umeå University.
    Pourazar, Jamshid
    Umeå University.
    Lindberg, A.
    Umeå University.
    Blomberg, Anders
    Umeå University.
    Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies2016In: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, ISSN 1073-449X, Vol. 193Article in journal (Refereed)
  • 10.
    Behndig, Annelie F
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Duggan, Sean T
    Kelly, Frank J
    Mudway, Ian S
    Adaptive antioxidant responses at the air lung interface in healthy humans following ozone exposureManuscript (preprint) (Other (popular science, discussion, etc.))
  • 11.
    Behndig, Annelie F
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Duggan, Sean T
    Kelly, Frank J
    Mudway, Ian S
    Antioxidant responses to acute ozone challenge in the healthy human airway2009In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, no 11, p. 933-942Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to characterize ozone-induced antioxidant responses in the human airway, including the resident leukocyte population, bronchial mucosa, and respiratory-tract lining fluids. Fifteen healthy subjects were exposed to 0.2 ppm ozone for 2 h, with bronchial wash, bronchoalveolar lavage, and biopsy sampling performed 6 h postexposure. Nasal lavage was also performed at multiple time points pre- and postexposure to evaluate responses during the actual exposure period. During the ozone challenge significant losses of nasal lining fluid urate and vitamin C were observed, which resolved 6 h postexposure. At this time point, increased numbers of neutrophils and enhanced concentrations of total glutathione, vitamin C, and urate were seen in bronchial airway lavages. In bronchoalveolar lavage, increased concentrations of total glutathione, vitamin C, urate, alpha-tocopherol, and extracellular superoxide dismutase occurred 6 h post ozone. In alveolar leukocytes significant losses of glutathione were observed, whereas ascorbate concentrations in endobronchial mucosal biopsies were elevated after ozone at this time. These data demonstrate that ozone elicits a broad spectrum of airway antioxidant responses, with initial losses of vitamin C and urate followed by a phase of augmentation of low-molecular-weight antioxidant concentrations at the air-lung interface. The temporal association between the increased RTLF glutathione following ozone and the loss of this thiol from macrophages implies a mobilization to the lung surface, despite the absence of a quantitative association. We propose this constitutes an acute protective adaptation to ozone.

  • 12.
    Behndig, Annelie F
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J
    Mudway, Ian S
    Augmentation of respiratory tract lining fluid ascorbate concentrations through supplementation with vitamin C.2009In: Inhalation toxicology, ISSN 1091-7691, Vol. 21, no 3, p. 250-8Article in journal (Refereed)
    Abstract [en]

    Low molecular weight antioxidants within human respiratory tract lining fluids (RTLFs) have been proposed to confer protection against the damaging action of inhaled oxidant gases. There is therefore considerable interest in augmenting the concentrations of these moieties at the air-lung interface to protect against injury to the airway epithelium, the induction of inflammation, and declines in lung function. To determine whether RTLF ascorbate concentrations could be augmented through vitamin C supplementation, 24 healthy subjects with low plasma ascorbate (< 50 microM) were recruited into a double-blinded study. Subjects were divided into two groups, one receiving 60 mg/day of vitamin C for 14 days, the other placebo. On days 8 and 15 of this protocol, plasma, urine, and nasal lavage were obtained for ascorbate determination. After a 7-14-day non-intervention period, subjects previously on placebo received supplements containing 125 mg ascorbate, whilst the group previously on supplements received the placebo compound. This "switching" protocol was repeated three more times utilizing 250, 500, and 1000 mg/day ascorbate dosage regimens. Plasma ascorbate increased incrementally with vitamin C dose, as did its urinary excretion. Despite this, nasal lavage concentrations remained unaltered 24 h after the final supplement at all doses. Closer examination of this issue demonstrated that nasal lavage ascorbate concentrations increased acutely after ingestion of a high dose (1000 mg) supplement, peaking at 2-4 h (p < 0.05) before returning to baseline concentrations 24 h post-supplement. In the absence of a quantitative association between plasma and lavage ascorbate concentrations we contend that this response does not simply reflect ascorbate transudation from the plasma and interstitial space into the lavage medium. We therefore conclude that RTLF ascorbate can be augmented, albeit transiently, by oral vitamin C supplementation, with the transient nature of this response likely reflecting oxidative losses within the RTLF or its sequestration into airway cells.

  • 13.
    Behndig, Annelie F
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Larsson, Nirina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brown, Joanna L
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Duggan, Sean T
    Dove, Rosamund E
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J
    Mudway, Ian S
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Proinflammatory doses of diesel exhaust in healthy subjects fail to elicit equivalent or augmented airway inflammation in subjects with asthma2011In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 66, no 1, p. 12-19Article in journal (Refereed)
    Abstract [en]

    Exposure to diesel exhaust at concentrations consistent with roadside levels elicited an acute and active neutrophilic inflammation in the airways of healthy subjects. This response was absent in subjects with asthma, as was evidence supporting a worsening of allergic airway inflammation.

  • 14.
    Behndig, Annelie F.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Linder, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Inflammatory Markers In Different COPD Subgroups Compared To Smokers And Healthy Controls2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, article id A2884Article in journal (Other academic)
  • 15.
    Behndig, Annelie F
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian S
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J
    Ascorbate and dehydroascorbate in nasal lining fluid following vitamin C supplementationManuscript (preprint) (Other (popular science, discussion, etc.))
  • 16.
    Behndig, Annelie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, IS
    Brown, JL
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Duggan, ST
    Wilson, SJ
    Boman, C
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Cassee, FR
    Frew, AJ
    Kelly, FJ
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.2006In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 2, p. 359-365Article in journal (Refereed)
    Abstract [sv]

    Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.

  • 17.
    Behndig, Annelie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, IS
    Brown, JL
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Duggan, ST
    Wilson, SJ
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Cassee, FR
    Frew, AJ
    Kelly, FJ
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.2006In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 2, p. 359-365Article in journal (Refereed)
    Abstract [sv]

    Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.

  • 18. Bergström, G
    et al.
    Berglund, G
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brandberg, J
    Engström, G
    Engvall, J
    Eriksson, M
    de Faire, U
    Flinck, A
    Hansson, M G
    Hedblad, B
    Hjelmgren, O
    Janson, C
    Jernberg, T
    Johnsson, Å
    Johansson, L
    Lind, L
    Löfdahl, C-G
    Melander, O
    Östgren, C J
    Persson, A
    Persson, M
    Sandström, Anette
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmidt, C
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sundström, J
    Toren, K
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Thoracic Center, Umeå University Hospital.
    Wedel, H
    Vikgren, J
    Fagerberg, B
    Rosengren, A
    The Swedish CArdioPulmonary BioImage Study: objectives and design.2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 6, p. 645-659Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

  • 19.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Update in environmental and occupational medicine 20112012In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 185, no 11, p. 1166-1170Article in journal (Refereed)
  • 20.
    Blomberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sköld, M
    Linden, A
    Patofysiologi vid KOL2009In: Lungmedicin / [ed] Thomas Sandström, Anders Eklund, Lund, Sweden: Studentlitteratur , 2009, p. 371-385Chapter in book (Other academic)
  • 21.
    Blomberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Desmyter, L
    Deneys, V
    Hermans, C
    Exposure to diesel exhaust nanoparticles does not induce blood hypercoagulability in an at-risk population.2005In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 3, no 9, p. 2103-2105Article in journal (Refereed)
  • 22.
    Bosson, Jenny A.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Update in Environmental and Occupational Medicine 20122013In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 188, no 1, p. 18-22Article in journal (Refereed)
  • 23.
    Bosson, Jenny A
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian S.
    Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e81816Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ozone concentrations are predicted to increase over the next 50 years due to global warming and the increased release of precursor chemicals. It is therefore urgent that good, reliable biomarkers are available to quantify the toxicity of this pollutant gas at the population level. Such a biomarker would need to be easily performed, reproducible, economically viable, and reflective of ongoing pathological processes occurring within the lung.

    METHODOLOGY: We examined whether blood neutrophilia occurred following a controlled ozone challenge and addressed whether this could serve as a biomarker for ozone-induced airway inflammation. Three separate groups of healthy subjects were exposed to ozone (0.2 ppm, 2h) and filtered air (FA) on two separate occasions. Peripheral blood samples were collected and bronchoscopy with biopsy sampling and lavages was performed at 1.5h post exposures in group 1 (n=13), at 6h in group 2 (n=15) and at 18h in group 3 (n=15). Total and differential cell counts were assessed in blood, bronchial tissue and airway lavages.

    RESULTS: In peripheral blood, we observed fewer neutrophils 1.5h after ozone compared with the parallel air exposure (-1.1±1.0x10(9) cells/L, p<0.01), at 6h neutrophil numbers were increased compared to FA (+1.2±1.3x10(9) cells/L, p<0.01), and at 18h this response had fully attenuated. Ozone induced a peak in neutrophil numbers at 6h post exposure in all compartments examined, with a positive correlation between the response in blood and bronchial biopsies.

    CONCLUSIONS: These data demonstrate a systemic neutrophilia in healthy subjects following an acute ozone exposure, which mirrors the inflammatory response in the lung mucosa and lumen. This relationship suggests that blood neutrophilia could be used as a relatively simple functional biomarker for the effect of ozone on the lung.

  • 24.
    Bosson, Jenny. A.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Connolly-Andersen, Anne-Marie
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Langrish, J. P.
    Increased Soluble Thrombomodulin In Plasma Following Diesel Exhaust Exposure2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, article id A3210Article in journal (Other academic)
  • 25.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans2008In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 31, no 6, p. 1234-1240Article in journal (Refereed)
    Abstract [en]

    Exposure to particulate matter and ozone cause adverse airway reactions. Individual pollutant effects are often addressed separately, despite coexisting in ambient air. The present investigation was performed to study the effects of sequential exposures to diesel exhaust (DE) and ozone on airway inflammation in human subjects. Healthy subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial wash (BW) sampling on two occasions. Once following a DE exposure (with 300 mug.m(-3) particles with a 50% cut-off aerodynamic diameter of 10 mum) with subsequent exposure to O(3) (0.2 ppm) 5 h later. The other bronchoscopy was performed after a filtered air exposure followed by an ozone exposure, using an identical protocol. Bronchoscopy was performed 24 h after the start of the initial exposure. Significant increases in neutrophil and macrophage numbers were found in BW after DE followed by ozone exposure versus air followed by ozone exposure. DE pre-exposure also raised eosinophil protein X levels in BAL compared with air. The present study indicates additive effects of diesel exhaust on the ozone-induced airway inflammation. Together with similar results from a recent study with sequential diesel exhaust and ozone exposures, the present data stress a need to consider the interaction and cumulative effects of different air pollutants.

  • 26.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian
    Frew, Anthony
    Kelly, Frank
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Early suppression of NFκB and IL-8 bronchial epithelium after ozone exposure in healthy human subjects2009In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, no 11, p. 913-919Article in journal (Refereed)
    Abstract [en]

    Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor κB (NFκB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-α, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFκB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

  • 27.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian S
    Frew, Anthony J
    Kelly, Frank J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects2009In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, no 11, p. 913-919Article in journal (Refereed)
    Abstract [en]

    Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor kappaB (NFkappaB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-alpha, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFkappaB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

  • 28.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ozone enhances the airway inflammation initiated by diesel exhaust.2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 6, p. 1140-1146Article in journal (Refereed)
    Abstract [en]

    Exposure to air pollution is associated with adverse health effects, with particulate matter (PM) and ozone (O(3)) both indicated to be of considerable importance. Diesel engine exhaust (DE) and O(3) generate substantial inflammatory effects in the airways. However, as yet it has not been determined whether a subsequent O(3) exposure would add to the diesel-induced airway inflammatory effects. Healthy subjects underwent two separate exposure series: A 1-h DE exposure at a PM-concentration of 300 microg/m(3), followed after 5h by a 2-h exposure to filtered air and 0.2 ppm O(3), respectively. Induced sputum was collected 18 h after the second exposure. A significant increase in the percentage of neutrophils (PMN) and concentration of myeloperoxidase (MPO) was seen in sputum post DE+O(3) vs. DE+air (p<0.05 and <0.05, respectively). Significant associations were observed between the responses in MPO concentration and total PMN cells (p=0.001), and also between MPO and matrix metalloproteinase-9 (MMP-9) (p<0.001). The significant increase of PMN and MPO after the DE+O(3) exposures, compared to DE+air, denotes an O(3)-induced magnification of the DE-induced inflammation. Furthermore, the correlation between responses in MPO and number of PMNs and MMP-9 illustrate that the PMNs are activated, resulting in a more potent inflammatory response. The present study indicates that O(3) exposure adds significantly to the inflammatory response that is established by diesel exhaust. This interaction between exposure to particulate pollution and O(3) in sequence should be taken into consideration when health effects of air pollution are considered.

  • 29.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Holgate, Stephen
    Kelly, Frank
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan
    Frew, Anthony
    Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects2003In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, no 6, p. 777-782Article in journal (Refereed)
    Abstract [en]

    Background Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group.

    Objective This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility.

    Methods Healthy and mild allergic asthmatic subjects (using only inhaled β2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, GRO-α, granulocyte–macrophage colony-stimulating factor (GM–CSF), fractalkine and ENA-78.

    Results When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM–CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects.

    Conclusion The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.

  • 30. Brown, J L
    et al.
    Behndig, A F
    Sekerel, B E
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, F J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Frew, A J
    Wilson, S J
    Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls.2007In: Clin Exp Allergy, ISSN 0954-7894, Vol. 37, no 5, p. 688-95Article in journal (Refereed)
  • 31. Carlsten, Chris
    et al.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pui, Mandy
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wong, Sze Wing
    Alexis, Neil
    Hirota, Jeremy
    Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study2016In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 71, no 1, p. 35-44Article in journal (Refereed)
    Abstract [en]

    Rationale Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. Objective To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. Methods 18 blinded atopic volunteers were exposed to filtered air or 300 mg PM2.5/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. Results Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. Conclusion Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.

  • 32. Crüts, Björn
    et al.
    Driessen, Anique
    van Etten, Ludo
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Borm, Paul Ja
    Reply to comment on Cruts et al. (2008), "Exposure to diesel exhaust induces changes in EEG in human volunteers" by Valberg et al.2008In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 5, p. 11-Article in journal (Other academic)
  • 33. Cullinan, Paul
    et al.
    Muñoz, Xavier
    Suojalehto, Hille
    Agius, Raymond
    Jindal, Surinder
    Sigsgaard, Torben
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Charpin, Denis
    Annesi-Maesano, Isabella
    Gulati, Mridu
    Kim, Yangho
    Frank, Arthur L
    Akgün, Metin
    Fishwick, David
    de la Hoz, Rafael E
    Moitra, Subhabrata
    Occupational lung diseases: from old and novel exposures to effective preventive strategies2017In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 5, no 5, p. 445-455Article in journal (Refereed)
    Abstract [en]

    Occupational exposure is an important, global cause of respiratory disease. Unlike many other non-communicable lung diseases, the proximal causes of many occupational lung diseases are well understood and they should be amenable to control with use of established and effective approaches. Therefore, the risks arising from exposure to silica and asbestos are well known, as are the means of their prevention. Although the incidence of occupational lung disease has decreased in many countries, in parts of the world undergoing rapid economic transition and population growth-often with large informal and unregulated workforces-occupational exposures continue to impose a heavy burden of disease. The incidence of interstitial and malignant lung diseases remains unacceptably high because control measures are not implemented or exposures arise in novel ways. With the advent of innovative technologies, new threats are continually introduced to the workplace (eg, indium compounds and vicinal diketones). In developed countries, work-related asthma is the commonest occupational lung disease of short latency. Although generic control measures to reduce the risk of developing or exacerbating asthma are well recognised, there is still uncertainty, for example, with regards to the management of workers who develop asthma but remain in the same job. In this Review, we provide recommendations for research, surveillance, and other action for reducing the burden of occupational lung diseases.

  • 34.
    Dove, Rosamund E.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.
    Leong-Smith, Pheneatia
    Roos-Engstrand, Ester
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Shah, Mittal
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian S.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD2015In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 2, article id 27837Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke.

    METHODS: Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13).

    RESULTS: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.

    CONCLUSIONS: We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.

  • 35.
    Eriksson Ström, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Linder, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bucht, Anders
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking2018In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, article id 244Article in journal (Refereed)
    Abstract [en]

    Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.

    Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

    Results: In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells – but not iNKT or NKT-like cells – were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.

    Conclusions: In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.

    Trial registration: Clinicaltrials.gov identifier NCT02729220.

  • 36.
    Fischer, Alexandra
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sundström, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Adherence to a Mediterranean-like Diet as a Protective Factor Against COPD: A Nested Case-Control Study2019In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, E-ISSN 1541-2563Article in journal (Refereed)
    Abstract [en]

    A diet rich in nutrients has been suggested to have protective effects against the development of chronic obstructive pulmonary disease (COPD). Since the traditional Mediterranean diet is high in nutrients, including antioxidants, vitamins, and minerals, it is of interest to study as a protective factor against COPD. Our aim was therefore to study its associations with development of COPD using population-based prospective data from the Vasterbotten Intervention Programme (VIP) cohort. Data on diet from 370 individuals, who later visited the Department of Medicine at the University Hospital, Umea, Sweden, with a diagnosis of COPD, were compared to 1432 controls. Adherence to a Mediterranean diet was assessed by a modified version of the Mediterranean diet score (MDS). Cases were diagnosed with COPD 11.1 years (mean) (standard deviation [SD] 4.5 years) after first stating their dietary habits in the VIP at a mean age of 55.5 years (SD 6.6 years). Higher MDS was associated with a higher level of education and not living alone. After adjustment for co-habiting and education level, individuals with an intermediate MDS and those with the highest MDS had a lower odds of developing COPD (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.56-0.95; OR 0.56, 95% CI 0.37-0.86, respectively). These results remained also after adjustment for smoking intensity, i.e., numbers of cigarettes smoked per day (OR 0.73, 95% CI 0.53-0.99; OR 0.59, 95% CI 0.35-0.97), respectively). To conclude, adherence to a Mediterranean-like diet seems to be inversely associated with the development of COPD.

  • 37.
    Ghorbani, Ramin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Extended breath CO analysis: baseline and diurnal variation of pulmonary gas exchange parametersManuscript (preprint) (Other academic)
  • 38.
    Ghorbani, Ramin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Modeling pulmonary gas exchange and single-exhalation profiles of carbon monoxide2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 927Article in journal (Refereed)
    Abstract [en]

    Exhaled breath carbon monoxide (eCO) is a candidate biomarker for non-invasive assessment of oxidative stress and respiratory diseases. Standard end-tidal CO analysis, however, cannot distinguish, whether eCO reflects endogenous CO production, lung diffusion properties or exogenous sources, and is unable to resolve a potential airway contribution. Coupling real-time breath gas analysis to pulmonary gas exchange modeling holds promise to improve the diagnostic value of eCO. A trumpet model with axial diffusion (TMAD) is used to simulate the dynamics of CO gas exchange in the respiratory system and corresponding eCO concentrations for the first time. The mass balance equation is numerically solved employing a computationally inexpensive routine implementing the method of lines, which provides the distribution of CO in the respiratory tract during inhalation, breath-holding and exhalation with 1 mm spatial and 0.01 s temporal resolution. Initial estimates of the main TMAD parameters, the maximum CO fluxes and diffusing capacities in alveoli and airways, are obtained using healthy population tissue, blood and anatomical data. To verify the model, mouth-exhaled expirograms from two healthy subjects, measured with a novel, home-built laser-based CO sensor, are compared to single-exhalation profiles simulated using actual breath sampling data, such as exhalation flow rate (EFR) and volume. A very good agreement is obtained in exhalation phases I and III for EFRs between 55 and 220 ml/s and after 10 s and 20 s of breath-holding, yielding a unique set of TMAD parameters. The results confirm the recently observed EFR dependence of CO expirograms and suggest that measured end-tidal eCO is always lower than alveolar and capillary CO. Breath-holding allows the observation of close-to-alveolar CO concentrations and increases the sensitivity to the airway TMAD parameters in exhalation phase I. A parametric simulation study shows that a small increase in airway flux can be distinguished from an increase in alveolar flux, and that slight changes in alveolar flux and diffusing capacity have a significantly different effect on phase III of the eCO profiles.

  • 39.
    Gonzalez, Manuel Cruz
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Robinson, Simon
    Mills, Nicholas L
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hyperleptinemia is associated with altered endothelial functionManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction The adipocyte-derived hormone leptin has been associated with increased risk of cardiovascular disease but the underlying mechanisms are unclear. Leptin effects on vascular endothelium may be a key mediator although contradictory results have been presented. We aimed to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary heart disease.

    Methods and Results The vascular effects of leptin were assessed using venous occlusion plethysmography in healthy volunteers (n=17) and in patients with stable coronary heart disease (CHD) (n=83). In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n=10) did not affect forearm blood flow or plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 (PAI-1) concentrations (all P>0.05).  However, during concomitant co-infusion with leptin (800 ng/min; n=10), induced vasodilatation was reduced (P=0.001), and tPA activity increased (P=0.002). In line with this, patients with coronary heart disease included in the highest tertile of plasma leptin concentrations had reduced substance P-induced vasodilatation (P<0.001), and increased tPA antigen and activity release (p<0.001 and p=0.03 respectively) compared to those in the lowest tertile.

    Conclusions Although leptin does not directly affect basal vascular function, acute local and chronic systemic hyperleptinemia are associated with altered endothelial function in healthy volunteers and patients with coronary heart disease respectively. These results support hyperleptinemia as a link between obesity and cardiovascular disease.

  • 40.
    Gouveia-Figueira, Sandra C.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust2018In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, p. 62-69Article in journal (Refereed)
    Abstract [en]

    Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

  • 41.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure2017In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 11, p. 2967-2980Article in journal (Refereed)
    Abstract [en]

    The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 mu g/m(3)) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, Nacylethanolamines, and related lipid metabolites in the collected BWand BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

  • 42.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mass spectrometry profiling of oxylipins, endocannabinoids and N-acylethanolamines in human lung lavage fluids reveal responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposureManuscript (preprint) (Other academic)
  • 43.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Effect of controlled exposure to biodiesel exhaust on human plasma bioactive lipid profilesManuscript (preprint) (Other academic)
  • 44. Gruber, Jan
    et al.
    Tang, Soon Yew
    Jenner, Andrew M
    Mudway, Ian
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Kasiman, Katherine
    Lee, Chung-Yung J
    Seet, Raymond C S
    Zhang, Wenxia
    Chen, Christopher
    Kelly, Frank J
    Halliwell, Barry
    Allantoin in human plasma, serum, and nasal-lining fluids as a biomarker of oxidative stress: avoiding artifacts and establishing real in vivo concentrations.2009In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 11, no 8, p. 1767-1776Article in journal (Refereed)
    Abstract [en]

    Urate is the terminal product of purine metabolism in primates, including humans. Urate is also an efficient scavenger of oxidizing species and is thought to be an important antioxidant in human body fluids. Allantoin, the major oxidation product of urate, has been suggested as a candidate biomarker of oxidative stress because it is not produced metabolically. Although urate is converted to allantoin under strongly alkaline pH, such conditions have been used in the past to facilitate extraction of allantoin. We evolved a method for the determination of allantoin concentrations in human plasma and serum by gas chromatography-mass spectrometry without such artifact. With this method, we show that alkaline conditions do indeed cause breakdown of urate, leading to significant overestimation of allantoin concentration in human samples. By using our alternative method, serum samples from 98 volunteers were analyzed, and allantoin levels were found to be significantly lower than was previously reported. The in vivo utility and sensitivity of our method was further evaluated in human nasal-lining fluids. We were able to demonstrate an ozone-induced increase in allantoin, in the absence of increases in either ascorbate or glutathione oxidation products.

  • 45.
    Helleday, Ragnberth
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Segerstedt, Bo
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Mudway, Ian
    Nordberg, Gunnar
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Bernard, Alfred
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Exploring the time dependence of serum clara cell protein as a biomarker of pulmonary injury in humans.2006In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 130, no 3, p. 672-675Article in journal (Refereed)
  • 46.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sundqvist, Martin
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sahlin, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rohani, Morteza
    Al-Khalili, Faris
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rosenqvist, Mårten
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Atrial fibrillation in patients with sleep apneaManuscript (preprint) (Other academic)
  • 47.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sundqvist, Martin
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sahlin, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rohani, Morteza
    Al-Khalili, Faris
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rosenqvist, Mårten
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Atrial fibrillation among patients under investigation for suspected obstructive sleep apnea2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0171575Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: Obstructive sleep apnea is common among patients with atrial fibrillation, but the prevalence and risk factors for atrial fibrillation among patients who are being investigated on suspicion of sleep apnea are not well known. The aim of the study was to estimate the prevalence of atrial fibrillation among patients investigated for suspected obstructive sleep apnea and to identify risk factors for atrial fibrillation among them.

    METHODS: The prevalence of atrial fibrillation was investigated among 201 patients referred for suspected obstructive sleep apnea. Patients without known atrial fibrillation were investigated with a standard 12-lead ECG at hospital and short intermittent handheld ECG recordings at home, during 14 days.

    RESULTS: Atrial fibrillation occurred in 13 of 201 subjects (6.5%), and in 12 of 61 men aged 60 years and older (20%). The prevalence of atrial fibrillation increased with sleep apnea severity (p = 0.038). All patients with atrial fibrillation were men and all had sleep apnea. Age 60 or older, the occurrence of central sleep apnea and diabetes mellitus were independent risk factors for atrial fibrillation after adjustments for body mass index, gender, sleep apnea and cardiovascular disease.

    CONCLUSIONS: Atrial fibrillation is common among subjects referred for sleep apnea investigation and the prevalence of atrial fibrillation increases with sleep apnea severity. Independent risk factors for atrial fibrillation among patients investigated for suspected obstructive sleep apnea include the occurrence of coexisting central sleep apnea, age 60 years or older and diabetes mellitus.

  • 48. Holgate, Stephen T
    et al.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Frew, Anthony J
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nördenhall, Charlotta
    Salvi, Sundeep
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Söderberg, Margaretha
    Health effects of acute exposure to air pollution. Part I: Healthy and asthmatic subjects exposed to diesel exhaust2003In: Research report (Health Effects Institute), ISSN 1041-5505, no 112, p. 1-30; discussion 51Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to assess the impact of short-term exposure to diluted diesel exhaust on inflammatory parameters in human airways. We previously exposed control subjects for 1 hour to a high ambient concentration of diesel exhaust (particle concentration 300 pg/m3--a level comparable with that found in North Sea ferries, highway underpasses, etc). Although these exposures did not have any measurable effect on standard indices of lung function, there was a marked neutrophilic inflammatory response in the airways accompanied by increases in blood neutrophil and platelet counts. Endothelial adhesion molecules were upregulated, and the expression of interleukin 8 messenger RNA (IL-8 mRNA*) was increased in a pattern consistent with neutrophilia. Individuals with asthma have inflamed airways and are clinically more sensitive to air pollutants than are control subjects. The present study was designed to assess whether this clinical sensitivity can be explained by acute neutrophilic inflammation or an increase in allergic airway inflammation resulting from diesel exhaust exposure. For this study, we used a lower concentration of diesel exhaust (100 microg/m3 PM10) for a 2-hour exposure. At this concentration, both the control subjects and those with asthma demonstrated a modest but statistically significant increase in airway resistance following exposure to diesel exhaust. This increase in airway resistance was associated with an increased number of neutrophils in the bronchial wash (BW) fluid obtained from control subjects (median after diesel exhaust 22.0 vs median after air 17.2; P = 0.015), as well as an increase in lymphocytes obtained through bronchoalveolar lavage (BAL) (15.0% after diesel exhaust vs 12.3% after air; P = 0.017). Upregulation of the endothelial adhesion molecule P-selectin was noted in bronchial biopsy tissues from control subjects (65.4% of vessels after diesel exhaust vs 52.5% after air). There was also a significant increase in IL-8 protein concentrations in BAL fluid and IL-8 mRNA gene expression in the bronchial biopsy tissues obtained from control subjects after diesel exhaust exposure (median IL-8 expression 65.7% of adenine phosphoribosyl transferase [APRT] gene expression value after diesel exhaust vs 51.0% after air; P = 0.007). There were no significant changes in total protein, albumin, or other soluble inflammatory markers in the BW or BAL fluids. Red and white blood cell counts in peripheral blood were unaffected by diesel exhaust exposure. Airway mucosal biopsy tissues from subjects with mild asthma (defined as forced expiratory volume in 1 second [FEV1] greater than or equal to 70% of the predicted value) showed eosinophilic airway inflammation after air exposure compared with the airways of the corresponding control subjects. However, among the subjects with mild asthma, diesel exhaust did not induce any significant change in airway neutrophils, eosinophils, or other inflammatory cells; cytokines; or mediators of inflammation. The only clear effect of diesel exhaust on the airways of subjects with asthma was a significant increase in IL-10 staining in the biopsy tissues. This study demonstrated that modest concentrations of diesel exhaust have clear-cut inflammatory effects on the airways of nonasthmatic (or control) subjects. The data suggest a direct effect of diesel exhaust on IL-8 production leading to upregulation of endothelial adhesion molecules and neutrophil recruitment. Despite clinical reports of increased susceptibility of patients with asthma to diesel exhaust and other forms of air pollution, it does not appear that this susceptibility is caused either directly by induction of neutrophilic inflammation or indirectly by worsening of preexisting asthmatic airway inflammation. The increased level of IL-10 after diesel exhaust exposure in airways of subjects with asthma suggests that this pollutant may induce subtle changes in airway immunobiology. This is an important topic for further investigation. Other possible explanations for the apparent lack of response to diesel exhaust among subjects with asthma include (1) the time course of the response to diesel may differ from the response to allergens, which peaks 6 to 8 hours after exposure; (2) a different type of inflammation may occur that was not detectable by the standard methods used in this study; and (3) the increased sensitivity of patients with asthma to particulate air pollution may reflect the underlying bronchial hyperresponsiveness found in asthma rather than any specific increase in inflammatory responses.

  • 49.
    Hunter, Amanda
    et al.
    University of Edinburgh.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Langrish, Jeremy P
    University of Edinburgh.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Raftis, Jennifer B
    University of Edinburgh.
    Miller, Mark R
    University of Edinburgh.
    Lucking, Andrew J
    University of Edinburgh.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Nyström, Robin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Donaldson, Kenneth
    University of Edinburgh.
    Flapan, Andrew D
    University of Edinburgh.
    Pung, Louis
    University of Edinburgh.
    Sadiktsis, Ioannis
    Stockholm University.
    Masala, Silvia
    Stockholm University.
    Westerholm, Roger
    Stockholm University.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    University of Edinburgh.
    Mills, Nicholas L
    University of Edinburgh.
    Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters2014In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 11, article id 62Article in journal (Refereed)
    Abstract [en]

    Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.

  • 50. Kumar, Abhinav
    et al.
    Bicer, Elif Melis
    Morgan, Anna Babin
    Pfeffer, Paul E.
    Monopoli, Marco
    Dawson, Kenneth A.
    Eriksson, Jonny
    Edwards, Katarina
    Lynham, Steven
    Arno, Matthew
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Somers, Graham
    Hassall, Dave
    Dailey, Lea Ann
    Forbes, Ben
    Mudway, Ian S.
    Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid2016In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 12, no 4, p. 1033-1043Article in journal (Refereed)
    Abstract [en]

    When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semiquantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. From the Clinical Editor: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. (C) 2016 Published by Elsevier Inc.

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