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Helleday, Ragnberth
Publications (10 of 20) Show all publications
Pourazar, J., Behndig, A. F., Helleday, R., Muala, A., Rankin, G., Sehlstedt, M., . . . Bosson, J. A. (2015). Airway Inflammatory Response In Healthy Subjects Following Chamber Exposure To 100% Rme Biodiesel. Paper presented at International Conference of the American-Thoracic-Society (ATS), MAY 15-20, 2015, Denver, CO. American Journal of Respiratory and Critical Care Medicine, 191, Article ID A5252.
Open this publication in new window or tab >>Airway Inflammatory Response In Healthy Subjects Following Chamber Exposure To 100% Rme Biodiesel
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2015 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, article id A5252Article in journal, Meeting abstract (Other academic) Published
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-123483 (URN)000377582807072 ()
Conference
International Conference of the American-Thoracic-Society (ATS), MAY 15-20, 2015, Denver, CO
Available from: 2016-07-06 Created: 2016-07-04 Last updated: 2018-06-07Bibliographically approved
Bosson, J. A., Blomberg, A., Stenfors, N., Helleday, R., Kelly, F. J., Behndig, A. F. & Mudway, I. S. (2013). Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation. PLoS ONE, 8(12), Article ID e81816.
Open this publication in new window or tab >>Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e81816Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-85596 (URN)10.1371/journal.pone.0081816 (DOI)000329325200005 ()24391708 (PubMedID)
Available from: 2014-02-06 Created: 2014-02-06 Last updated: 2018-06-08Bibliographically approved
Behndig, A. F., Larsson, N., Brown, J. L., Stenfors, N., Helleday, R., Duggan, S. T., . . . Blomberg, A. (2011). Proinflammatory doses of diesel exhaust in healthy subjects fail to elicit equivalent or augmented airway inflammation in subjects with asthma. Thorax, 66(1), 12-19
Open this publication in new window or tab >>Proinflammatory doses of diesel exhaust in healthy subjects fail to elicit equivalent or augmented airway inflammation in subjects with asthma
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2011 (English)In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 66, no 1, p. 12-19Article in journal (Refereed) Published
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.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-39566 (URN)10.1136/thx.2010.140053 (DOI)20837873 (PubMedID)
Available from: 2011-02-01 Created: 2011-02-01 Last updated: 2018-06-08Bibliographically approved
Stenfors, N., Bosson, J., Helleday, R., Behndig, A. F., Pourazar, J., Törnqvist, H., . . . Blomberg, A. (2010). Ozone exposure enhances mast-cell inflammation in asthmatic airways despite inhaled corticosteroid therapy.. Inhalation Toxicology, 22(2), 133-139
Open this publication in new window or tab >>Ozone exposure enhances mast-cell inflammation in asthmatic airways despite inhaled corticosteroid therapy.
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2010 (English)In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 22, no 2, p. 133-139Article in journal (Refereed) Published
Abstract [en]

Asthmatics are recognised to be more susceptible than healthy individuals to adverse health effects caused by exposure to the common air pollutant ozone. Ozone has been reported to induce airway neutrophilia in mild asthmatics, but little is known about how it affects the airways of asthmatic subjects on inhaled corticosteroids. We hypothesised that ozone exposure would exacerbate the pre-existent asthmatic airway inflammation despite regular inhaled corticosteroid treatment. Therefore, we exposed subjects with persistent asthma on inhaled corticosteroid therapy to 0.2 ppm ozone or filtered air for 2 h, on 2 separate occasions. Lung function was evaluated before and immediately after exposure, while bronchoscopy was performed 18 h post exposure. Compared to filtered air, ozone exposure increased airway resistance. Ozone significantly enhanced neutrophil numbers and myeloperoxidase levels in airway lavages, and induced a fourfold increase in bronchial mucosal mast cell numbers. The present findings indicate that ozone worsened asthmatic airway inflammation and offer a possible biological explanation for the epidemiological findings of increased need for rescue medication and hospitalisation in asthmatic people following exposure to ambient ozone.

Place, publisher, year, edition, pages
Informa Healthcare, 2010
Keywords
Airway inflammation, air pollution, BAL, bronchial mucosa, myeloperoxidase, neutrophil
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
urn:nbn:se:umu:diva-35692 (URN)10.3109/08958370903005736 (DOI)000273643300009 ()20044881 (PubMedID)
Available from: 2010-08-31 Created: 2010-08-31 Last updated: 2018-06-08Bibliographically approved
Behndig, A. F., Blomberg, A., Helleday, R., Duggan, S. T., Kelly, F. J. & Mudway, I. S. (2009). Antioxidant responses to acute ozone challenge in the healthy human airway. Inhalation Toxicology, 21(11), 933-942
Open this publication in new window or tab >>Antioxidant responses to acute ozone challenge in the healthy human airway
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2009 (English)In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, no 11, p. 933-942Article in journal (Refereed) Published
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.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-23216 (URN)10.1080/08958370802603789 (DOI)19459773 (PubMedID)
Available from: 2009-06-04 Created: 2009-06-04 Last updated: 2018-06-08Bibliographically approved
Behndig, A. F., Blomberg, A., Helleday, R., Kelly, F. J. & Mudway, I. S. (2009). Augmentation of respiratory tract lining fluid ascorbate concentrations through supplementation with vitamin C.. Inhalation toxicology, 21(3), 250-8
Open this publication in new window or tab >>Augmentation of respiratory tract lining fluid ascorbate concentrations through supplementation with vitamin C.
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2009 (English)In: Inhalation toxicology, ISSN 1091-7691, Vol. 21, no 3, p. 250-8Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-22870 (URN)10.1080/08958370802474736 (DOI)19009458 (PubMedID)
Available from: 2009-05-19 Created: 2009-05-19 Last updated: 2018-06-08
Behndig, A., Mudway, I., Brown, J., Stenfors, N., Helleday, R., Duggan, S., . . . Blomberg, A. (2006). Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.. European Respiratory Journal, 27(2), 359-365
Open this publication in new window or tab >>Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.
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2006 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 2, p. 359-365Article in journal (Refereed) Published
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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-144204 (URN)
Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2018-06-09
Behndig, A., Mudway, I., Brown, J., Stenfors, N., Helleday, R., Duggan, S., . . . Blomberg, A. (2006). Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.. European Respiratory Journal, 27(2), 359-365
Open this publication in new window or tab >>Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.
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2006 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 2, p. 359-365Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-16114 (URN)10.1183/09031936.06.00136904 (DOI)16452593 (PubMedID)
Available from: 2007-08-17 Created: 2007-08-17 Last updated: 2018-06-09Bibliographically approved
Ädelroth, E., Hedlund, U., Blomberg, A., Helleday, R., Ledin, M.-C., Levin, J.-O., . . . Järvholm, B. (2006). Airway inflammation in iron ore miners exposed to dust and diesel exhaust.. Eur Respir J, 27(4), 714-719
Open this publication in new window or tab >>Airway inflammation in iron ore miners exposed to dust and diesel exhaust.
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2006 (English)In: Eur Respir J, ISSN 0903-1936, Vol. 27, no 4, p. 714-719Article in journal (Refereed) Published
Keywords
Adult, Carbon/analysis, Dust/analysis, Fibronectins/analysis, Humans, Interleukin-10/analysis, Iron, Macrophages; Alveolar/immunology, Male, Matrix Metalloproteinase 9/analysis, Middle Aged, Mining, Neutrophils/immunology, Nitrogen Dioxide/analysis, Occupational Exposure/*adverse effects/analysis, Pneumoconiosis/*etiology, Reference Values, Risk Factors, Sputum/cytology/immunology, Vehicle Emissions/analysis/*toxicity
Identifiers
urn:nbn:se:umu:diva-15398 (URN)10.1183/09031936.06.00034705 (DOI)16455836 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2018-06-09Bibliographically approved
Helleday, R., Segerstedt, B., Forsberg, B., Mudway, I., Nordberg, G., Bernard, A. & Blomberg, A. (2006). Exploring the time dependence of serum clara cell protein as a biomarker of pulmonary injury in humans.. Chest, 130(3), 672-675
Open this publication in new window or tab >>Exploring the time dependence of serum clara cell protein as a biomarker of pulmonary injury in humans.
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2006 (English)In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 130, no 3, p. 672-675Article in journal (Refereed) Published
Keywords
Adult, Air Pollution/*adverse effects, Biological Markers/blood, Cell Membrane Permeability/drug effects/physiology, Circadian Rhythm, Environmental Exposure, Female, Humans, Lung Diseases/blood/chemically induced/diagnosis/pathology, Male, Middle Aged, Models; Theoretical, Ozone/*adverse effects/pharmacology, Respiratory Mucosa/drug effects/pathology/physiopathology, Respiratory System/*injuries/pathology/physiopathology, Uteroglobin/*blood
Identifiers
urn:nbn:se:umu:diva-15342 (URN)doi:10.1378/chest.130.3.672 (DOI)16963661 (PubMedID)
Available from: 2007-12-12 Created: 2007-12-12 Last updated: 2018-06-09Bibliographically approved
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