Nils Milman

Serum ferritin, hemoglobin, and Helicobacter pylori infection: A seroepidemiologic survey comprising 2794 Danish adults

BACKGROUND & AIMSnHelicobacter pylori infection was recently associated with iron-deficiency anemia. The aim of this study was to examine the relationship between H. pylori infection, hemoglobin, and iron status using serum ferritin as a marker for total body iron.nnnMETHODSnSerum ferritin, hemoglobin, and immunoglobulin G (IgG) antibodies against H. pylori were assessed in 2794 Danish adults who attended a population survey. IgG antibodies were measured with an in-house enzyme-linked immunosorbent assay, serum ferritin with an immunoradiometric assay, and hemoglobin with Coulter-S.nnnRESULTSnThe seroprevalence of H. pylori infection did not relate to hemoglobin. Serum ferritin levels were significantly lower in men (114 vs. 120 microg/L; P = 0.01) and in postmenopausal women (63 vs. 77 microg/L; P = 0.02) who were IgG positive than in seronegative individuals. IgG-positive people more often had reduced serum ferritin levels (</=30 microg/L) than seronegative people. This association persisted in multivariate analysis after adjusting for possible confounding factors (odds ratio, 1.4; 95% confidence interval 1.1-1. 8).nnnCONCLUSIONSnSerum ferritin levels are reduced in people with increased IgG antibodies to H. pylori. H. pylori infection affects iron metabolism in humans.

Aspergillus infection in lung transplant patients : incidence and prognosis

Lung transplant recipients experience a particularly high incidence of Aspergillus infection in comparison with other solid-organ transplantations. This study was conducted to determine the incidence of Aspergillus colonisation and invasive aspergillosis, and the impact on long-term survival associated with Aspergillus infection. A retrospective study of 362 consecutive lung transplant patients from a single national centre who were transplanted 1992–2003 were studied. Twenty-seven patients were excluded due to incomplete or missing files. A total of 105/335 (31%) patients had evidence of Aspergillus infection (colonisation or invasion), including 83 (25%) patients with colonisation and 22 (6%) patients with radiographic or histological evidence of invasive disease. Most of the infections occurred within the first 3xa0months after transplantation. Cystic fibrosis (CF) patients had higher incidences of colonisation and invasive disease [15 (42%) and 4 (11%) of 36 patients] than non-CF patients [68 (23%) and 18 (6%) of 299 patients] (Pu2009=u20090.01). Invasive aspergillosis was associated with 58% mortality after 2xa0years, whereas colonisation was not associated with early increased mortality but was associated with increased mortality after 5xa0years compared to non-infected patients (Pu2009<u20090.05). An analysis of demographic factors showed that donor age [OR 1.40 per decade (95% CI 1.10-1.80)], ischaemia time [OR 1.17 per hour increase (95% CI 1.01–1.39)], and use of daclizumab versus polyclonal induction [OR 2.05 (95% CI 1.14–3.75)] were independent risk factors for Aspergillus infection. Invasive aspergillosis was associated with early and high mortality in lung transplant patients. Colonisation with Aspergillus was also associated with a significant increase in mortality after 5xa0years. CF patients have a higher incidence of Aspergillus infection than non-CF patients.

Exercise testing in the preoperative evaluation of patients with bronchogenic carcinoma

The aim of this study was to evaluate which parameters of preoperative spirometry and cardiopulmonary exercise test are the best predictors of postoperative morbidity and mortality in patients with bronchogenic carcinoma. Ninety seven patients were prospectively and consecutively examined. All patients had preoperative maximal exercise test and dynamic spirometry. Postoperative complications and causes of death were registered. Logistic regression was used and models explaining the relationship between preoperative variables and postoperative complications and deaths were constructed. We found significant differences in preoperative maximal workload and carbon dioxide output between groups, with and without cardiopulmonary-related complications, but not in spirometry variables. Logistic regression showed maximal workload to be the only predictor of cardiopulmonary complications. Maximal oxygen uptake was predictive of cardiopulmonary deaths. Maximal oxygen uptake and forced expiratory volume were predictive of postoperative complications. A maximal oxygen uptake <50% predicted was associated with high risk of death from cardiopulmonary causes. Kaplan-Meier survival curves showed that maximal oxygen uptake was correlated to long-term survival, while spirometric variables were not. Exercise testing can be used in the preoperative evaluation of patients with nonmetastatic bronchogenic carcinoma. A combination of the results of variables from spirometry and exercise testing is proposed to be used as a preoperative criterion for operability.

Iron status in Danish women aged 35–65 years: Relation to menstruation and method of contraception

Iron status was assessed by serum (S‐) ferritin and hemoglobin (Hb) in a population survey comprising 883 non‐gravid Danish women in age cohorts of 35, 45. 55, and 65 years. Premenopausal women (n = 676) had lower S‐ferritin, median 42 μg/1, than postmenopausal women (n = 207), median 80 μg/1 (p<0.0001). Of premenopausal women, 12.1% had S‐ferritin ≤ 20 μg/1 (i.e. depleted iron stores), and 35.6% S‐ferritin of 21–40 μg/1 (i.e. small iron stores). Corresponding figures in postmenopausal women were 0.5%, and 13.2%. Premenopausal blood donors (n = 88) had lower S‐ferritin than non‐donors (p<0.001). In premenopausal women, S‐ferritin levels were strongly dependent on the duration of menstrual bleeding (p < 0.0001). which in turn was related to the method of contraception. Women (n = 64) using hormonal contraceptives (the pill) had menstrual bleeding of shorter duration than those (n = 511) not using pills or intrauterine devices (IUD), who in turn had bleeding of shorter duration than those (n= 101) using IUD. Median S‐ferritin in pill users was 62 μg/L in those not using pills or IUD 42 μg/L and in IUD users 36 μg/l. S‐ferritin values < 40 μg/l (i.e. small and depleted iron stores) were seen in 25%) of pill users. in 48% of those not using pills nr IUD, and in 61% of IUD users. Hb values in premenopausal women were mean 134 ± 10 (SD) g/1 (8.3±0.6 mmol/l), median 132 g/l (8.2 mmol/l). being slightly lower than in postmenopausal women, mean 137 ± 10 g/l (8.5±0.6 mmol/1), median 135 g/l (8.4 mmol/ 1) (p<0.001). Iron deficiency anemia (i.e. S‐ferritin ≤20 μg/l and Hb < 121 g/l) was found in 3.0%) of premenopausal and in none of postmenopausal women.

Effect of the TNF‐α inhibitor adalimumab in patients with recalcitrant sarcoidosis: a prospective observational study using FDG‐PET

Background:u2002 Tumour necrosis factor‐alpha (TNF‐α) plays a crucial role in sarcoidosis. In severe disease, treatment with TNF‐α inhibitors may be effective.

Is serum ferritin within the reference range a risk predictor of cardiovascular disease? A population-based, long-term study comprising 2874 subjects.

The iron hypothesis claims that Fe depletion protects against IHD. The objective of the present study was to investigate the associations between serum ferritin levels and the risk of CVD and IHD in a population-based sample. A total of 2874 subjects with serum ferritin levels between 15 and 300 microg/l from the Danish part of the Monitoring of Trends and Determinants in Cardiovascular Disease (DAN-MONICA) I study and the 1914 Cohort survey were followed for 10 years. Information on behavioural and socio-demographic characteristics were collected and serum ferritin levels measured. Non-fatal and fatal CVD and IHD were identified by the International Classification of Diseases diagnoses numbers. Multivariable Cox proportional hazard regression models with restricted cubic splines were performed. During the follow-up period, 310 subjects (201 men; 109 women) and 161 subjects (117 men; forty-four women) experienced CVD and IHD, respectively. Our analyses revealed no statistically significant associations between serum ferritin levels and the risk of CVD or IHD in both sexes. However, in women, the results argue for a U-shaped relationship between serum ferritin levels and CVD as well as IHD. In concordance with former prospective studies, the present results do not support the hypothesis that normal body Fe stores should play a significant role in the development of CVD.

Fluorodeoxyglucose PET Scan in Pulmonary Sarcoidosis during Treatment with Inhaled and Oral Corticosteroids

The objective was to investigate longitudinal changes in fluorodeoxyglucose PET scan (FDG-PET) in a patient with pulmonary sarcoidosis prior to and during treatment with inhaled corticosteroids followed by systemic corticosteroids. The patient was a 41-year-old man presenting with stage I pulmonary sarcoidosis (hilar adenopathy), which had progressed to stage II (pulmonary infiltrates) 19 months later. FDG-PET was performed at 19, 29 and 33 months after presentation. No treatment was given prior to the 1st PET. Subsequently, before the 2nd PET, the patient was treated with inhaled beclomethasone (QVAR Autohaler®) 0.8 mg/day for 8 months. Finally, prior to the 3rd PET, the patient was treated with oral prednisolone 30 mg/day for 3 months. The 1st PET showed a high FDG uptake in the hilar and mediastinal lymph nodes and a high focal uptake in the peripheral parts of the lungs. The 2nd PET showed a slight uptake in a few mediastinal lymph nodes and an unchanged high focal uptake in the peripheral parts of the lungs and the pleura. The 3rd PET showed no abnormal uptake at all. In conclusion, as assessed by FDG-PET, inhaled beclomethasone had no recognizable influence on sarcoid inflammatory activity. Treatment with oral prednisolone depressed the inflammatory activity to such a degree that it was undetectable by PET. The results are in accordance with clinical studies on pulmonary sarcoidosis, showing a marginal effect of inhaled corticosteroids and a marked effect of systemic corticosteroids.

Recurrent sarcoid granulomas in a transplanted lung derive from recipient immune cells

From 1992–2004, single lung transplantation has been performed in seven patients with end-stage pulmonary sarcoidosis at the Danish National Centre for Lung Transplantation. The objective was to assess whether recurrent sarcoid granulomas in the lung graft are derived from recipient or donor immune cells. Three patients had sarcoid recurrence in the lung graft, but none had clinically overt extra-thoracic sarcoidosis. Graft sex-mismatch was present in one patient, a 52-yr-old female having a lung graft from a male donor. In order to discriminate between recipient and donor cells fluorescence in situ hybridisation (FISH), using probes for both X- and Y-chromosomes, was applied on transbronchial lung biopsies (TBB) from the lung graft containing sarcoid granulomas. The recipients explanted lung contained multiple active sarcoid granulomas. TBB from the implanted donor lung 5 months after transplantation showed sarcoid granulomas. FISH showed that the immune cells in the granulomas were X-chromosome positive and Y-chromosome negative and, therefore, were derived from the recipient. In conclusion, the results indicate that recurrent sarcoid granulomas in the transplanted lung are derived from recipients immune cells, having colonised the lung allograft.

The BTNL2 A allele variant is frequent in Danish patients with sarcoidosis

Background:u2002 The butyrophilin‐like 2 (BTNL2) gene is located on chromosome 6p21.3 close to the HLA‐class II genes. An association has been reported between sarcoidosis and a single nucleotide polymorphism in BTNL2, rs2076530, also termed the A allele.

A prospective study evaluating the presence of Rickettsia in Danish patients with sarcoidosis

Rickettsia helvetica has previously been proposed as an aetiological agent in sarcoidosis. The purpose of the present study was to detect possible signs of Rickettsia infection in a Danish population of patients with sarcoidosis. Twenty-six patients with newly diagnosed sarcoidosis were prospectively enrolled in the study. The diagnosis was confirmed by biopsy in 18 and by clinical characteristics in 8 patients; 11 patients with different non-sarcoid lung diseases were recruited as controls. We obtained information regarding tick exposure and sarcoid disease manifestations by a structured interview. Evidence of rickettsial infection was assessed by an immunofluorescence assay testing for antibodies towards Rickettsia as well as specific real-time polymerase chain reaction (PCR) on lung biopsy specimens. We performed fluorescent in situ hybridization (FISH) on the biopsies to detect rickettsial and eubacterial rRNA. One sarcoidosis patient had serum rickettsial IgG antibodies above the chosen cut-off level. We found no positive rickettsial PCR or FISH analyses in any of the biopsy specimens. One sarcoid patient sample and 1 control sample contained unidentified bacteria. There was no difference in the reported frequency of tick bite between patients and controls. In conclusion, we found no evidence of Rickettsia being involved in the pathogenesis of sarcoidosis in Denmark.