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Persson, Hans Lennart
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Publications (10 of 38) Show all publications
Lyth, J., Lind, L., Karlsson, D., Persson, L. H. & Wiréhn, A.-B. (2018). Can a telemonitoring system lead to decreased hospital admissions in elderly patients?. In: : . Paper presented at ERS International Congress 2018, Paris, France, 15-19 September, 2018.
Open this publication in new window or tab >>Can a telemonitoring system lead to decreased hospital admissions in elderly patients?
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2018 (English)Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

Background: Populations of elderly patients with chronic obstructive pulmonary disease (COPD) or heart failure (HF) are growing. To prevent exacerbations leading to inpatient care, a 4 year (2013-2017) telehealth intervention non-randomized single-centre clinical study was performed. We hypothesized that the patients, grouped by advanced COPD or HF, would exhibit decreased need of hospital admissions.

Objective: To study hospital admissions in patients with COPD or HF using a telemonitoring system, the Health Diary.

Methods: A telemonitoring system, the Health Diary, based on digital pen technology, was employed. Patients with COPD or HF treated at the University Hospital in Linköping were included if they had at least 2 hospital admissions the previous year. Data on hospital admissions was obtained from the administrative healthcare database. Expected number of hospital admissions for the study year was calculated using 5-year data for a group of patients with matching diagnosis and history of hospital admissions and was compared to the actual value in the intervention group using Poisson regression.

Results: Together with the included patients, 159 HF and 136 COPD non-intervention patients was used to calculate the expected values for hospital admissions. For the 58 included HF patients, the average number of hospital admissions of 0.81 was 32.8 percent (p=0.04) lower than expected. For the 36 included COPD patients, the average number of hospital admissions of 1.44 was 37.0 percent (p=0.02) lower than expected.

Conclusions: Use of the telemonitoring system, the Health Diary, decreases hospital admissions in elderly with COPD and HF.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-153784 (URN)10.1183/13993003.congress-2018.PA1998 (DOI)
Conference
ERS International Congress 2018, Paris, France, 15-19 September, 2018
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-17Bibliographically approved
Lind, L., Lyth, J., Karlsson, D. M. G., Wiréhn, A.-B. & Persson, L. (2018). COPD patients require more health care than heart failure patients. In: ERS International Congress 2018: . Paper presented at ERS International Congress 2018, Paris, France, 15-19 September, 2018.
Open this publication in new window or tab >>COPD patients require more health care than heart failure patients
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2018 (English)In: ERS International Congress 2018, 2018Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

Background: Populations of elderly patients with advanced stages of chronic obstructive pulmonary disease (COPD) or heart failure (HF) are growing, urging the need for specialized health care in the patients’ home. A 4 year (2013-2017) telehealth intervention single-centre clinical study has been completed. We hypothesized that the two groups of patients, advanced COPD or HF, would exhibit differences regarding exacerbations and the need of health care.

Objective: To study exacerbations of COPD or HF, and patients’ need of health care.

Methods: A telemonitoring system, the Health Diary, which is based on digital pen technology, was employed. Patients with at least 2 hospital admissions the previous year were included. Responsible nurses and physicians at a specialized home care unit at a university hospital checked all daily patient reports. Physicians identified exacerbations using information provided through the telemonitoring system and patient contacts. Consumed health care was assessed as the number of patient contacts (home visits or telephone consultations).

Results: Totally, 94 patients with advanced disease were enrolled (36 COPD and 58 HF patients) of which 53 patients (19 COPD and 34 HF patients) completed the 1-yr study period. The major reason for not completing the study was death (13 COPD, 15 HF patients). Average numbers of exacerbations were 3.1 and 0.8 and patient contacts were 94 and 67 per COPD and HF patient, respectively.

Conclusions: Compared to HF patients, COPD patients exhibit exacerbations more frequently and demand much more home health care. This difference of health care consumption is mainly due to disease characteristics.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-153785 (URN)10.1183/13993003.congress-2018.PA743 (DOI)
Conference
ERS International Congress 2018, Paris, France, 15-19 September, 2018
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-17
Kentson, M., Leanderson, P., Jacobson, P. & Persson, H. L. (2018). Oxidant status, iron homeostasis, and carotenoid levels of COPD patients with advanced disease and LTOT. European Clinical Respiratory Journal, 5(1)
Open this publication in new window or tab >>Oxidant status, iron homeostasis, and carotenoid levels of COPD patients with advanced disease and LTOT
2018 (English)In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 5, no 1Article in journal (Refereed) Published
Abstract [en]

Background: The pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with oxidative stress. Both iron (Fe) and oxygen are involved in the chemical reactions that lead to increased formation of reactive oxygen species. Oxidative reactions are prevented by antioxidants such as carotenoids. Objective: To study the differences in Fe status, carotenoid levels, healthy eating habits, and markers of inflammation and oxidative damage on proteins in subjects with severe COPD ± long-term oxygen therapy (LTOT) and lung-healthy control subjects. Methods: Sixty-six Caucasians with advanced COPD (28 with LTOT) and 47 control subjects were included. Questionnaires about general health, lifestyle, and dietary habits were answered. Lung function tests and blood sampling were performed. Results: COPD subjects (±LTOT) did not demonstrate increased oxidative damage, assessed by protein carbonylation (PC), while levels of soluble transferrin receptors (sTfRs) were slightly elevated. Soluble TfRs, which is inversely related to Fe status, was negatively associated with PC. Levels of carotenoids, total and ß-cryptoxanthin, a- and ß-carotenes, were significantly lower in COPD subjects, and their diet contained significantly less fruits and vegetables. Lutein correlated inversely with IL-6, lycopene correlated inversely with SAT, while ß-carotene was positively associated with a Mediterranean-like diet. Conclusions: Fe could favor oxidative stress in COPD patients, suggesting a cautious use of Fe prescription to these patients. COPD subjects ate a less healthy diet than control subjects did and would, therefore, benefit by dietary counseling. COPD patients with hypoxemia are probably in particular need of a lycopene-enriched diet.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Antioxidants; free radicals; hypoxemia; inflammation; long-term oxygen therapy
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-152520 (URN)10.1080/20018525.2018.1447221 (DOI)29696082 (PubMedID)
Available from: 2019-03-08 Created: 2019-03-08 Last updated: 2019-04-30
Sioutas, A., Vainikka, L., Kentson, M., Dam-Larsen, S., Wennerström, U., Jacobson, P. & Persson, H. L. (2017). Oxidant-induced autophagy and ferritin degradation contribute to epithelial-mesenchymal transition through lysosomal iron. Journal of Inflammation Research, 10, 29-39
Open this publication in new window or tab >>Oxidant-induced autophagy and ferritin degradation contribute to epithelial-mesenchymal transition through lysosomal iron
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2017 (English)In: Journal of Inflammation Research, ISSN 1178-7031, E-ISSN 1178-7031, Vol. 10, p. 29-39Article in journal (Refereed) Published
Abstract [en]

Transforming growth factor (TGF)-ß1 triggers epithelial-mesenchymal transition (EMT) through autophagy, which is partly driven by reactive oxygen species (ROS). The aim of this study was to determine whether leaking lysosomes and enhanced degradation of H-ferritin could be involved in EMT and whether it could be possible to prevent EMT by iron chelation targeting of the lysosome.

Place, publisher, year, edition, pages
Dove Medical Press, 2017
Keywords
A549 cells; COPD; pulmonary disease; pulmonary fibrosis; transforming growth factor; tumor necrosis factor
National Category
Immunology
Identifiers
urn:nbn:se:liu:diva-145062 (URN)10.2147/JIR.S128292 (DOI)28405169 (PubMedID)
Available from: 2018-02-08 Created: 2018-02-08 Last updated: 2018-03-09
Sköld, C. M., Janson, C., Klackenberg Elf, Å., Fiaschi, M., Wiklund, K. & Persson, H. L. (2016). A retrospective chart review of pirfenidone-treated patients in Sweden: the REPRIS study. European Clinical Respiratory Journal, 3(1), Article ID 32035.
Open this publication in new window or tab >>A retrospective chart review of pirfenidone-treated patients in Sweden: the REPRIS study
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2016 (English)In: European Clinical Respiratory Journal, E-ISSN 2001-8525, Vol. 3, no 1, article id 32035Article in journal (Refereed) Published
Abstract [en]

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that usually results in respiratory failure and death. Pirfenidone was approved as the first licensed therapy for IPF in Europe based on phase III trials where patients with a forced vital capacity (FVC) greater than50% of predicted were included. The aim of this study was to characterise patients treated with pirfenidone in Swedish clinical practice and to describe the adherence to the reimbursement restriction since reimbursement was only applied for patients with FVC below 80% of predicted.less thanbr /greater thanMethods: This was a retrospective, observational chart review of IPF patients treated with pirfenidone from three Swedish university clinics. Patients initiated on treatment during the period 28 June 2012 to 20 November 2014 were included. Data on patient characteristics, basis of diagnosis, treatment duration, quality of life, and adverse drug reactions (ADRs) were collected from medical charts.less thanbr /greater thanResults: Forty-four patients were screened and 33 were included in the study. The mean treatment duration from start of pirfenidone until discontinuation or end of study was 38 weeks. At the initiation of pirfenidone treatment, FVC was 62.7% (12.1) [mean (SD)], diffusion capacity (DLco) was 45.1% (13.8) of predicted, and the ratio of forced expiratory volume on 1 sec (FEV1) to FVC was 0.78 (0.1). The percentage of patients with an FVC between 50 and 80% was 87%. Ten of the patients had ADRs including gastrointestinal and skin-related events, cough and signs of impaired hepatic function, but this led to treatment discontinuation in only two patients.less thanbr /greater thanConclusion: Data from this chart review showed that adherence to the Swedish reimbursement restriction was followed in the majority of patients during the study period. At the start of pirfenidone treatment, lung function, measured as FVC, was lower in the present cohort of Swedish IPF patients compared with other registry and real-life data. About a third of the patients had ADRs, but discontinuation of the treatment because of ADRs was relatively uncommon.

Place, publisher, year, edition, pages
Järfälla: Co-Action Publishing, 2016
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-135050 (URN)10.3402/ecrj.v3.32035 (DOI)27435431 (PubMedID)
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-05-14
Toren, K., Olin, A.-C., Lindberg, A., Vikgren, J., Schioler, L., Brandberg, J., . . . Bergstrom, G. (2016). Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS). The International Journal of Chronic Obstructive Pulmonary Disease, 11, 927-933
Open this publication in new window or tab >>Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS)
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2016 (English)In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 11, p. 927-933Article in journal (Refereed) Published
Abstract [en]

Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPD(VC) as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. Results: Prevalence of GOLDCOPD(FVC) was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPD(VC) and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. Conclusion: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.

Place, publisher, year, edition, pages
DOVE MEDICAL PRESS LTD, 2016
Keywords
obstructive; epidemiology; general population; air trapping; spirometry; slow vital capacity; asthma
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128772 (URN)10.2147/COPD.S104644 (DOI)000375178100001 ()27194908 (PubMedID)
Note

Funding Agencies|Swedish Heart Lung Foundation; Knut and Alice Wallenberg Foundation; Swedish Research Council (VR); VINNOVA; Swedish Council for Working Life, Health, and Welfare (FORTE); Sahlgrenska Academy at the University of Gothenburg, Krefting Research Centre; ALF/LUA in western Sweden

Available from: 2016-05-30 Created: 2016-05-30 Last updated: 2017-11-30
Lind, L., Carlgren, G., Mudra, J., Synnergren, H., Hilding, N., Karlsson, d., . . . Persson, H. L. (2015). Preliminary results of a telemonitoring study: COPD and heart failure patients exhibit great difference in their need of health care. In: Marc Humbert (Ed.), European Respiratory Journal: Official Scientific Journal of ERS. Paper presented at ERS International Congress, ERS2015, Amsterdam, Netherlands, 26-30 September 2015 (pp. PA2790-PA2790). European Respiratory Society, 46/suppl 59
Open this publication in new window or tab >>Preliminary results of a telemonitoring study: COPD and heart failure patients exhibit great difference in their need of health care
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2015 (English)In: European Respiratory Journal: Official Scientific Journal of ERS / [ed] Marc Humbert, European Respiratory Society , 2015, Vol. 46/suppl 59, p. PA2790-PA2790Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Background: Growing populations of elderly patients with advanced stages of COPD or heart failure (HF) urge the need for specialized health care in the patients' home. A telemonitoring study has been initiated including patients using digital pens. Health care was provided by the specialized home care unit at a university hospital. Through an IT system the staff checked all daily patient reports. We hypothesized that the two groups of patients, advanced COPD or HF, would exhibit differences regarding exacerbations and the need of health care.

Objective: To study exacerbations of COPD or HF, and patient health care consumption.

Methods: A tele-monitoring system, the Health diary, which is based on digital pen technology, was employed. Exacerbations were identified using information provided through the telemonitoring system. Consumed health care was assessed as the number of patient contacts (home visits or telephone consultations).

Results: Presently, 33 patients with advanced disease are enrolled (13 COPD and 20 HF patients) of which 11 patients (6 COPD and 5 HF patients) have completed the 1-yr study period or have died during the study period (2 COPD and 4 HF patients). Exacerbations were 2.8 and 0.8 and patient contacts were 96 and 42 per COPD and HF patient, respectively. While HF patients were significantly older than COPD patients, the two groups demonstrated no difference regarding gender distribution and comorbidity.

Conclusions: COPD patients exhibit exacerbations more frequently and demand much more home health care than patients with HF do. It seems that this difference of health care consumption is mainly due to disease characteristics.

Place, publisher, year, edition, pages
European Respiratory Society, 2015
Series
The European Respiratory Journal, ISSN 0903-1936
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-128905 (URN)10.1183/13993003.congress-2015.PA2790 (DOI)
Conference
ERS International Congress, ERS2015, Amsterdam, Netherlands, 26-30 September 2015
Projects
eHälsodagboken
Available from: 2016-06-07 Created: 2016-06-07 Last updated: 2018-03-26Bibliographically approved
Norberg, P., Persson, H. L., Schmekel, B., Alm Carlsson, G., Wahlin, K., Sandborg, M. & Gustafsson, A. (2014). Does quantitative lung SPECT detect lung abnormalities earlier than lung function tests?: Results of a pilot study. EJNMMI Research, 4(39), 1-12
Open this publication in new window or tab >>Does quantitative lung SPECT detect lung abnormalities earlier than lung function tests?: Results of a pilot study
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2014 (English)In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, no 39, p. 1-12Article in journal (Refereed) Published
Abstract [en]

Background: Heterogeneous ventilation in lungs of allergic individuals, cigarette smokers, asthmatics and chronic obstructive pulmonary disease (COPD) patients has been demonstrated using imaging modalities such as PET, MR and SPECT. These individuals suffer from narrow and/or closed airways to various extents. By calculating regional heterogeneity in lung ventilation SPECT images as the coefficient of variation (CV) in small elements of the lung, heterogeneity maps and CV-frequency curves can be generated and used to quantitatively measure heterogeneity. This work explores the potential to use such measurements to detect mild ventilation heterogeneities in lung healthy subjects.

Method: Fourteen healthy subjects without documented lung disease or respiratory symptoms, and two patients with documented airway disease, inhaled on average approximately 90 MBq 99mTc-Technegas immediately prior to the 20 min SPECT acquisition. Variation in activity uptake between subjects was compensated for in resulting CV values. The area under the compensated CV frequency curve (AUC), for CV values greater than a threshold value CVT, AUC(CV> CVT), was used as the measure of ventilation heterogeneity.

Results: Patients with lung function abnormalities, according to lung function tests, generated higher AUC(CV>20%) values compared to healthy subjects (p=0.006). Strong linear correlations with the AUC(CV>20%) values were found for age (p=0.006) and height (p=0.001). These demonstrated that ventilation heterogeneities increased with age and that they depend on lung size. Strong linear correlations were found for the lung function value related to indices of airway closure/air trapping, RV/TLC (p=0.009), and DLCOc (p=0.009), a value partly related to supposed ventilation/perfusion mismatch. These findings support the association between conventional lung function tests and the AUC(CV>20%) value.

Conclusions: Among the healthy subjects there is a group with increased AUC(CV>20%) values, but with normal lung function tests, which implies that it might be possible to differentiate ventilation heterogeneities earlier in a disease process than by lung function tests.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2014
Keywords
Quantitative lung SPECT, ventilation heterogeneities, lung function tests
National Category
Clinical Medicine Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-106666 (URN)10.1186/s13550-014-0039-1 (DOI)000358049300001 ()26055938 (PubMedID)2-s2.0-84905881037 (Scopus ID)
Note

On the date of the defence date of the Ph.D. Thesis the status of this article was Manuscript.

Available from: 2014-05-19 Created: 2014-05-19 Last updated: 2017-12-05Bibliographically approved
Wajda, A., Engström, H. & Persson, L. (2014). Medical talc pleurodesis: which patient with cancer benefits least?. Journal of Palliative Medicine, 17(7), 822-828
Open this publication in new window or tab >>Medical talc pleurodesis: which patient with cancer benefits least?
2014 (English)In: Journal of Palliative Medicine, ISSN 1096-6218, E-ISSN 1557-7740, Vol. 17, no 7, p. 822-828Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND OBJECTIVE:

Successful talc pleurodesis (TP) for malignant pleural effusion (MPE) gives symptom relief, but may be too exhaustive in cases with poor performance status. The selection of eligible patients is therefore a challenging task. The study was undertaken to evaluate frequency of successful TPs, side effects, complications, performance status, hospitalization time, remaining time alive, and the responsible physician's prediction of a successful TP judged by radiologic findings prior to TP.

METHODS:

Side effects of TPs performed during a 1-year period were consecutively recorded and the TP outcomes were retrospectively evaluated 6 years later.

RESULTS:

TP success rate was 56% and 79% among best support of care subjects (BSC; n=10) and subjects eligible for cancer therapy (non-BSC; n=19), respectively, while side effects did not differ. Performance status was poorer and survival shorter among BSC subjects. Time spent in hospital of the remaining time alive for BSC and non-BSC subjects was 42%±27% and 4%±4%, respectively. Poor performance status of subjects with lung cancer correlated with short survival time, which in turn correlated with many days at hospital for TP. The physician's prediction of a successful TP was correct in 50% of all cases.

CONCLUSIONS:

Performance status of BSC subjects are probably too poor for TP and these subjects have to spend too much time at hospital during the procedure. The responsible physician is able to correctly predict a successful TP outcome in only every second case, supporting the need of additional predictive analysis.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-109389 (URN)10.1089/jpm.2013.0591 (DOI)000338946400014 ()24885834 (PubMedID)
Available from: 2014-08-15 Created: 2014-08-15 Last updated: 2017-12-05Bibliographically approved
Persson, H. L., Eklund, D., Welin, A., Paues, J., Idh, J., Fransson, S.-G., . . . Schön, T. (2013). Alveolar macrophages from patients with tuberculosis exhibit reduced capacity of restricting growth of Mycobacterium tuberculosis: a pilot study of vitamin D stimulation in vitro. HOAJ Biology
Open this publication in new window or tab >>Alveolar macrophages from patients with tuberculosis exhibit reduced capacity of restricting growth of Mycobacterium tuberculosis: a pilot study of vitamin D stimulation in vitro
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2013 (English)In: HOAJ Biology, ISSN 2050-0874Article in journal (Refereed) Published
Abstract [en]

Background: The role of vitamin D supplementation as adjuvant treatment of tuberculosis (TB) has lately attracted increasing interest. Our aim was to investigate the capacity of alveolar macrophages (AMs) from patients with or without exposure to TB to control intracellular growth of virulent Mycobacterium tuberculosis (Mtb).

Methods: AMs were freshly harvested from the bronchoalveolar lavage fluid of 7 patients with a history of TB (4 patients with previous TB and 3 patients with current TB) and 4 non-TB subjects. The H37Rv strain, genetically modified to express Vibrio harveyi luciferase, was used to determine the growth of Mtb by luminometry in the AMs from study subjects. Cytokine levels in culture supernatants were determined using a flow cytometry-based bead array technique.

Results: AMs from patients with a TB history were less efficient in restricting Mtb growth. Stimulation with 100 nM1, 25-dihydroxyvitamin D (1,25D3) did not significantly influence the capacity of AMs from any study subjects to control the infection. Out of the cytokines evaluated (TNF-α, IL-1β, IL-10 and IL-12p40) only TNF-α demonstrated detectable levels in culture supernatants, but did not respond to stimulation with 1,25D3.

Conclusions: We conclude that AMs of TB-patients show reduced ability to control mycobacterial growth in vitro, and, that AMs in this pilot study do no respond to 1, 25D3-stimulation. The former observation supports the concept that innate immunity is crucial for the control of TB infection.

Place, publisher, year, edition, pages
United Kingdom: Herbert Publications Ltd, 2013
Keywords
Alveolar macrophages, bronchoalveolar lavage, cytokines, H37Rv, tuberculosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91314 (URN)10.7243/2052-6180-1-6 (DOI)
Available from: 2013-04-22 Created: 2013-04-22 Last updated: 2018-03-26
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