C Koch

University of Southern Denmark, Odense, South Denmark, Denmark

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Publications (133)616.56 Total impact

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    ABSTRACT: Deficiencies in many of the complement proteins and their regulatory molecules have been described and a variety of diseases, such as recurrent infections, systemic lupus erythematosus (SLE) and renal diseases, may be linked to deficiency in the complement system. Screening for complement defects is therefore of great importance. In this study, we present novel improved enzyme-linked immunosorbent assays for the functional assessment of the three individual pathways of the complement system. The method is applicable at high serum concentrations and we demonstrate that it minimizes both false negative as well as false positive results. In particular, for the functional mannose-binding lectin activity it represents an improvement on the existing assays. In this respect, the present assays represent novel improved diagnostic protocols for patients with suspected immunodeficiencies related to the complement system.
    Clinical & Experimental Immunology 03/2011; 164(3):388-95. DOI:10.1111/j.1365-2249.2011.04322.x · 3.28 Impact Factor
  • Christian Koch, Niels Høiby, Allan Wiik
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    ABSTRACT: The NBT-reduction induced in human peripheral neutrophils by stimulation with Pseudomonas aeruginosa antigens was found to depend upon the presence of serum factors. The response of the cells to stimulation was enhanced using immune serum, containing multiple precipitating antibodies against these antigens. The response was diminished by heat-inactivation of serum, prior to reaction with the antigens, and by elimination of precipitating immune complexes. Direct immunofluorescence studies demonstrated ingestion by the neutrophils of specific antigens with participation of immunoglobulins G, M, A, and complement C3. This was found, using immune serum, but also using normal serum, containing low-titred, cross-reactive antibodies to Ps. aeruginosa. Similar results were also obtained, using antigens from other bacterial species. It is suggested that bacterial antigens, upon interaction with immune as well as with normal serum, form large immune complexes, that are easily ingested by neutrophils, and that immune complex ingestion is closely linked to stimulated NBT-reduction. These studies suggest an important role of normally occurring, cross-reactive antibodies to bacterial antigens in promoting rapid clearing of toxic material, or material otherwise damaging to the host.
    Apmis 08/2009; 83C(2):144 - 156. DOI:10.1111/j.1699-0463.1975.tb01619.x · 1.92 Impact Factor
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    ABSTRACT: Høiby, N., Friis, B., Jensen, K., Koch, C, Møller, N.E., Støvring, S. and Szaff, M. (Statens Seruminstitut, Departments of Clinical Microbiology at Rigshospitalet and Hvidovre Hospital, and Paediatric Department TG, Rigshospitalet, Copenhagen, Denmark). Antimicrobial chemotherapy in cystic fibrosis patients. Acta Paediatr Scand 1982; suppl 301: 75-100. — Every effort should be undertaken to combat recurrent and chronic bacterial respiratory tract infections in patients with cystic fibrosis because infections are the main pathogenetic factors of lung damage in these patients. The principles and antibiotics used to treat bacterial infections in the Danish Cystic Fibrosis centre are outlined. The chemotherapy is based on microbiological diagnosis of secretions from the lower respiratory tract. S. aureus infections are efficiently treated with oral fusidic acid in combination with isoxazolyl penicillins or rifampicin in case of penicillin allergy or methicillin-resistant S. aureus. H. influenzae infections are treated efficiently with oral pivampicillin or amoxicillin or with erythromycin sometimes in combination with rifampicin in case of penicillin allergy or ampicillin-resistant H. influenzae. As a result of the efficient chemotherapy S. aureus and H. influenzae infections are now minor problems generally not related to prognosis of cystic fibrosis patients. Chronic P. aeruginosa infections are treated regularly four times per year with intravenous anti-pseudomonas β-lactam antibiotics in combination with tobramycin. P. aeruginosa is rarely permanently eradicated by this treatment, but significantly improved survival of the patients is obtained. The problems of resistant bacterial strains, allergy, and other side effects caused by the antibiotics are discussed.
    Acta Paediatrica 01/2008; 71(s301):75 - 100. DOI:10.1111/j.1651-2227.1982.tb09643.x · 1.97 Impact Factor
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    ABSTRACT: Ficolin-2 (L-ficolin), derived from the FCN2 gene, is an innate immunity pattern recognition molecule found in human serum in which inter-individual variation in serum appears to be under genetic control. To validate and extend this finding, we developed a sandwich ELISA for detection of human Ficolin-2 in serum samples and identified FCN2 genotypes with a Taq Man-based minor groove binder assay and by sequencing. Serum samples were applied to gel-permeation chromatography and fractions were analysed by an ELISA, SDS-PAGE and subsequently Western blotting. In 214 Danish blood donors, the median Ficolin-2 serum concentration was determined to 5.4 microg/ml (range: 1.0-12.2 microg/ml). An ELISA, SDS-PAGE and Western blot analysis of gel-permeation chromatography fractions showed that Ficolin-2 comprises a mixture of covalently and non-covalently linked Ficolin-2 oligomers independent of the individual genotypes. The variation in serum concentration was associated with three polymorphisms in the promoter and one polymorphism in the structural part of the FCN2 gene. Further analysis indicated that two particular alleles on the same haplotype determined a low Ficolin-2 concentration. Our results show that inter-individual variation of Ficolin-2 concentration is associated with polymorphisms in the promoter and the structural part of the FCN2 gene.
    Scandinavian Journal of Immunology 05/2007; 65(4):383-92. DOI:10.1111/j.1365-3083.2007.01915.x · 1.88 Impact Factor
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    ABSTRACT: Aerosolized recombinant human deoxyribonuclease (rhDNase I (Pulmozyme)) has previously been shown to increase pulmonary function and reduce exacerbations of respiratory symptoms in cystic fibrosis (CF) patients with moderate to severe reduction in pulmonary function. To analyse whether aerosolized Pulmozyme could reduce the number of bacterial infections in the lower respiratory airways of CF patients without chronic pulmonary infection. Patients were randomized either to aerosolized Pulmozyme 2(1/2) mg once daily or to no rhDNase treatment. The study period was 1 y, and the study was blinded for the Department of Clinical Microbiology. Overall, the number of positive cultures was significantly higher in the untreated group (82%) compared with the treated group (72%) (p<0.05). The most striking difference was found for Staphylococcus aureus, with a prevalence of 30% in the untreated group compared with 16% in the treated group (chi2 test, p<0.0001). Pulmonary function (FEV1) in the treated group showed a significant increase of 7.3% compared to 0.9% in the untreated group (p<0.05). Long-term DNase treatment was beneficial to CF patients without chronic lower respiratory tract infection, leading to reduced demand for antibiotics and to improved lung function.
    Acta Paediatrica 09/2006; 95(9):1070-4. DOI:10.1080/08035250600752466 · 1.84 Impact Factor
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    ABSTRACT: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary accumulation of PMNs is reflected as a migration of PMNs through the blood in chronically infected CF patients. Blood and sputum samples from 37 stable, chronically (CF+P) and 6 non-infected (CF-P) CF patients without exacerbations were compared using FACS, leukocyte counting, and ELISA. Within the CF+P patients, the blood parameters were compared to the lung function (FEV1 and FVC) and to the sputum. Similar measurements were performed on 15 chronically infected CF patients before and after elective antibiotic treatment. In the CF+P patients the concentration of G-CSF in the sera and PMNs in the blood was increased and correlated to poor lung function. However, only the concentration of G-CSF in the sera was correlated to the concentration of TNF-alpha in the sputum. After the antibiotic treatment, the lung function was improved and the concentration of PMNs in the blood and G-CSF in the sera was reduced. G-CSF in the sera may contribute to the pulmonary inflammation in CF patients with chronic P. aeruginosa lung infection by regulating the number of PMNs available for migration and may be considered as an indicator of clinical status.
    Journal of Cystic Fibrosis 09/2006; 5(3):145-51. DOI:10.1016/j.jcf.2005.12.004 · 3.82 Impact Factor
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    ABSTRACT: P. aeruginosa is the most significant pathogen in CF lung disease. Chronic infection is preceded by a period of intermittent colonization. Early aggressive antimicrobial treatment at initial detection of P. aeruginosa in lower respiratory tract (LRT) secretions can prevent transition to chronic infection in approximately 80% of the patients, while the rest progress to chronic infection in spite of treatment. To analyze risk factors for development of chronic infection, a cohort of 89 CF patients free of chronic infection at the study period start was followed for 10 years. 28 of the patients (study group) developed chronic infection in spite of early treatment and 28 age-matched patients who did not (controls) were included in the analysis. During the 3 years period prior to onset of chronic infection, P. aeruginosa-positive cultures were more frequent in the study group than in the controls (2.2 vs. 0.5 per year, p<0.0001). Growth of mucoid strains of P. aeruginosa was more frequent in study group than in controls (11.5% vs. 0%, p<0.0001). Most important, specific anti-pseudomonal IgG serum antibodies were significantly higher in the study group than in controls (0.98 Elisa Units vs. 0.53, p=0.04) already 3 years prior to onset of chronic infection and increased 0.44 EU pr year in the study group but remained at the initial level in the control group (p<0.005). Occurrence of Aspergillus-positive cultures were significantly more frequent in the study group than in controls (p=0.01). The strongest risk factor for development of chronic P. aeruginosa infection was increasing levels of specific anti-pseudomonal antibodies, specifically of IgG1 and IgG4 subclass and total anti-Pseudomonas IgG, 3 years prior to onset of chronic infection, with odds ratio (OR) 8.9, 7.7 and 7.4, respectively (p<0.005), and growth of mucoid P. aeruginosa strains with OR of 7.4, p=0.006). Occurrence of Aspergillus was also a risk factor for developing chronic P. aeruginosa infection with the OR of 4.7 (p=0.008).
    Journal of Cystic Fibrosis 02/2006; 5(1):9-15. DOI:10.1016/j.jcf.2005.11.002 · 3.82 Impact Factor
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    ABSTRACT: Lower airway colonisation with Aspergillus fumigatus and the complicating hypersensitivity reaction allergic bronchopulmonary aspergillosis (ABPA) is well recognised in patients with cystic fibrosis (CF). There is a wide range in reported prevalence of ABPA in CF. Differences in predisposing factors such as atopy and climatic humidity, but also differences in reporting may in part explain this observation. In the Australian population there is a high frequency of atopy and the climate is relatively humid. Children and adolescents with CF (n = 277) from the CF Clinic, Children's Hospital at Westmead, Sydney, Australia were included in a retrospectively conducted study of Aspergillus colonisation and ABPA (1998-2003). The prevalence of Aspergillus colonised patients increased significantly from 7.4% in 1998 to 18.8% in 2002. No seasonal variation in initial positive Aspergillus culture or in humidity was observed. A total of 13 patients (4.7%) were diagnosed with ABPA over the study period, with a significant increase in prevalence from 0.3% in 1998 to 4.0% in 2002. In addition, the criteria used for reporting ABPA in the study population were in agreement with the recently published diagnostic criteria for ABPA in CF. In spite of a high frequency of atopy and a relatively humid climate in the Sydney area, Aspergillus colonisation and ABPA in CF patients was not disproportionate. Moreover, criteria for reporting of ABPA in this setting was not different from that in the Northern Hemisphere.
    Respiratory Medicine 08/2005; 99(7):887-93. DOI:10.1016/j.rmed.2004.11.018 · 2.92 Impact Factor
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    ABSTRACT: The inflammation in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection is dominated by polymorphonuclear neutrophils (PMNs). There seems to be a relationship between the PMN-dominated inflammation, pronounced antibody production and a Th2-dominated response. Apart from mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses. Therefore, the present study examines the correlation between the mobilizing cytokines in serum and the Th responses. The IFN-gamma and IL-4 production by peripheral blood mononuclear cells, and the concentrations of GM-CSF and G-CSF in serum as well as lung function, were determined in 37 CF patients with and 6 CF patients without chronic P. aeruginosa lung infection. The GM-CSF/G-CSF ratio correlated both with the IFN-gamma production and good lung function. In addition, an inverse correlation between IL-3 and IFN-gamma was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment.
    Apmis 07/2005; 113(6):400-9. DOI:10.1111/j.1600-0463.2005.apm_142.x · 1.92 Impact Factor
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    ABSTRACT: In cystic fibrosis (CF), chronic endobronchial infection with Pseudomonas aeruginosa is a serious complication. Macrolides can increase lung function and weight in patients, and reduce exacerbations. In 2001, we introduced long-term, low-dose azithromycin (AZ) treatment as an integral part of our routine treatment of these patients. Our study is an observational cohort study of all CF patients with chronic P. aeruginosa infection in our CF center comparing clinical parameters of the patients 12 months prior to treatment with the same values during 12 months of treatment. 45 patients (27 men, median age 29 years) completed 1-year treatment. Median weight increased from 63.1 kg in the pre-treatment period to 63.9 kg during treatment (p=0.01). Median slope of decline in lung function increased from pre-treatment FEV1 -4.1% and FVC -3.0% to +0.8% (p<0.001) and +1.6% (p=0.01), respectively. 90% of sputum samples contained mucoid P. aeruginosa before treatment, decreasing to 81% during treatment (p=0.003). Median CRP decreased from 6.2 mmol/l to 5.8 mmol/l (ns). Long-term, low-dose AZ treatment in adult CF patients with chronic P. aeruginosa infection is safe and reduces the decline in lung function, increases weight, and reduces the percentage of mucoid strains of P. aeruginosa in sputum samples.
    Journal of Cystic Fibrosis 03/2005; 4(1):35-40. DOI:10.1016/j.jcf.2004.09.001 · 3.82 Impact Factor
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    ABSTRACT: A majority of patients with cystic fibrosis (CF) become colonised with Aspergillus fumigatus (Af.), but only a minority develops allergic bronchopulmonary aspergillosis (ABPA). ABPA is associated with increased levels of specific immunoglobulin G (IgG) anti-Af. antibodies with a characteristic IgG subclass distribution. We examined whether this characteristic immune response was under the influence of GM and KM allotypes, which are genetic markers (antigenic determinants) on gamma- and kappa-light chains, respectively. Sera from 233 CF patients were typed for seven GM determinants and two KM determinants. The types were correlated to IgG subclass anti-Af. antibody levels and to the presence or absence of Af. colonisation as well as ABPA. The IgG2 antibody level was significantly higher in heterozygous GM (1,2,17 23 5,21 and 1,3,17 23 5,21) compared to homozygous GM allotypes (p = 0.02). Patients with the same allotypes tended to have higher IgG1 (p = 0.051). In patients with ABPA, being heterozygous for G1M and G3M was linked to higher IgG4 and lower IgG3 as compared to the other genotypes. The KM markers did not influence the antibody levels. The allotype GM(3 23 5), associated with atopic bronchial asthma, tended to make a relatively larger group in ABPA patients compared to non-ABPA and patients not colonised with Af. (p = 0.09). An influence of the GM allotypes on the immune response to Af. and on the development of ABPA in patients with CF is suggested.
    Journal of Cystic Fibrosis 09/2004; 3(3):173-8. DOI:10.1016/j.jcf.2004.05.048 · 3.82 Impact Factor
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    ABSTRACT: In a 4-year prospective study, we evaluated specific airway resistance (sRaw) by whole-body plethysmography, respiratory resistance by the interrupter technique, and respiratory resistance and reactance at 5 Hz by the impulse oscillation technique combined with measurement of responsiveness to bronchodilators and cold air in 30 children (mean [range] age 5.7 [2 to 8] years) with cystic fibrosis (CF). Spirometry was done at school age. Mean sRaw was consistently abnormal: the mean z score (SD) was 2.52 (2.02) (p < 0.001) at the start and was unchanged 36 months later at 2.74 (2.02). Mean z score (SD) for FEV(1) at first satisfactory measurement, at a mean age (range) of 6.1 (4.9-7.5) years was -1.2 (1.2) and was further reduced to -1.85 (1.2) 4 years from inclusion at a mean age (range) of 9.9 (6.8-12) years. Neither respiratory resistance by the interrupter technique nor the impulse oscillation technique demonstrated consistent abnormal levels. Patients with CF as a group did not differ from healthy subjects in responsiveness to bronchodilators and cold air. sRaw may be a useful tool in CF during early childhood. Reduced lung function was documented from consistently abnormal levels of sRaw and FEV1 during the study. Bronchodilator responsiveness and response to cold air challenge were normal.
    American Journal of Respiratory and Critical Care Medicine 06/2004; 169(11):1209-16. DOI:10.1164/rccm.200303-347OC · 11.99 Impact Factor
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    ABSTRACT: We studied the effects of increasingly intensive treatment regimens on anti-pseudomonal antibody response and survival in five successive cohorts of a total of 157 Danish cystic fibrosis patients after they had acquired chronic P. aeruginosa lung infection. The time periods were 1971-1975 (N = 21), 1976-1980 (N = 64), 1981-1986 (N = 27), 1987-1993 (N = 26), and 1994-2000 (N = 19). During this 30-year period, we introduced elective 2-week courses of chemotherapy every third month in all chronically infected patients, early aggressive treatment with inhalation of colistin and oral ciprofloxacin for 3 months whenever P. aeruginosa was cultured in sputum from noncolonized patients, and inhalation of recombinant human dornase alfa. There was a significant correlation between the calendar year when chronic P. aeruginosa infection was acquired and the subsequent increase in the level of precipitins (P < 0.00001). The median number of precipitins increased by 5 per year in the oldest calendar year cohort, and 1 per year in the youngest. The median age of onset of chronic P. aeruginosa increased from 9.3 years from 1981-1986 to 13.8 years from 1987-2000. Survival after acquisition of chronic P. aeruginosa lung infection improved with time (P = 0.008). Our study shows that CF patients who are treated intensively have lower antibody responses and longer survival after acquisition of chronic P. aeruginosa lung infection.
    Pediatric Pulmonology 05/2004; 37(5):427-32. DOI:10.1002/ppul.10457 · 2.30 Impact Factor
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    ABSTRACT: Patients with cystic fibrosis (CF) have an abnormal propensity for recurrent and chronic infections of the lower respiratory tract (LRT), and the most common cause of a shortened lifespan is chronic infection with Pseudomonas aeruginosa. A few other gram-negative organisms, primarily Burkholderia cepacia complex have, however, emerged as serious pathogens capable of establishing chronic LRT infection. Details of these and other CF pathogens can be found in the article by Dr. John LiPuma, Burkholderia and Emerging Pathogens in Cystic Fibrosis, in this issue. Chronically infected patients constitute a major microbial reservoir from which noninfected patients can be infected with both P. aeruginosa and B. cepacia complex by direct patient-to-patient transmission, and possibly also by exposure to contaminated environments. Other more rare pathogens such as Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM) appear less capable of causing patient-to-patient transmission. Both the physical proximity and the duration of exposure of noninfected patients to patients chronically infected with P. aeruginosa and B. cepacia complex are important determinants of the risk of cross-infection. Cohorting of patients according to presence or absence of specific pathogens coupled with conventional hygienic precautions can, however, lead to a decrease in incidence and prevalence of chronic infections with these two species, wherefore patient cohorting is now an integral component of infection control in patients with CF.
    Seminars in Respiratory and Critical Care Medicine 01/2004; 24(6):703-16. DOI:10.1055/s-2004-815666 · 3.02 Impact Factor
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    ABSTRACT: We show that Pandoraea apista must be added to the increasing list of pathogens capable of causing chronic lung infection in cystic fibrosis (CF) patients. It is most likely that this strain of P. apista was transmissible among patients with CF, leading to spread of infection from the index patient to 5 other patients exposed during participation in winter camps and/or hospitalization. All patients developed chronic infection with high levels of antibodies, and 4 patients had a downhill course of lung disease. P. apista must therefore be considered a new and sometimes important pathogen for CF patients. Cohort isolation prevented further spread of P. apista in our CF center.
    Pediatric Pulmonology 12/2003; 36(5):439-46. DOI:10.1002/ppul.10383 · 2.30 Impact Factor
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    ABSTRACT: Dornase alfa (Pulmozyme) treatment for patients with cystic fibrosis (CF) has been shown to improve pulmonary function and reduce exacerbations of infection in a number of placebo-controlled double-blind studies. Data in the Epidemiologic Registry of Cystic Fibrosis (ERCF) in November 1998 were used to assess the long-term effectiveness in routine clinical practice of dornase alfa in terms of pulmonary function and frequency of acute pulmonary exacerbations in CF. At that time, the ERCF contained data on 13,684 CF patients, with a mean observation period of 2.3 years. To be included in the analysis, patients had to have 2 years of data in the Registry in appropriate detail. Overall, untreated patients showed a decline in forced expiratory volume in 1 sec over a 2-year period of -2.3% predicted, but treated patients were stable, showing a change of 0.3% predicted, i.e., a treatment benefit of 2.5%. Compared to untreated patients, there were 25 fewer exacerbations per 100 treated patients per year. The analysis suggested that younger patients were likely to benefit more from treatment. The findings of randomized clinical trials were supported by the data collected in routine clinical practice.
    Pediatric Pulmonology 11/2003; 36(5):427-32. DOI:10.1002/ppul.10348 · 2.30 Impact Factor
  • Ugeskrift for laeger 06/2003; 165(21):2198-201.
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    M Skov, N Høiby, C Koch
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    ABSTRACT: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is a potentially fatal inflammatory disease due to the dual-type immune response provoked by the fungal antigens. Despite serious side effects long-term treatment with corticosteroids is often required. Itraconazole has been reported to be a useful steroid-sparing agent. In a retrospective follow-up of 21 CF patients from a total of 250 treated once or twice within a five-year study period (1994-98), 9 patients were treated with systemic glucocorticosteroids in combination with itraconazole and 12 patients were treated with itraconazole (200-600 mg/day) as monotherapy. During treatment the percentage of Aspergillus fumigatus (AF)-positive sputum cultures significantly reduced (P < 0.05); precipitating antibodies to AF decreased significantly in all patients (P < 0.05); forced expiratory volume (FEV1) increased to pre-exacerbation level; total IgE levels decreased in 42% of patients on monotherapy and in 56% on combination therapy. Specific IgE (radioallergosorbant; RAST) level decreased in 6 of 21 patients. Eleven patients had transient increased levels of alanine transaminase (ALAT). One patient had isolated increase in alkaline phosphatase and another in aspartate transaminase (ASAT). High dose itraconazole as monotherapy or in combination with systemic glucocorticosteroids seems effective in CF patients with ABPA. No hepatotoxicity was observed during long-term therapy.
    Allergy 09/2002; 57(8):723-8. DOI:10.1034/j.1398-9995.2002.23583.x · 6.00 Impact Factor
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    ABSTRACT: A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide. An adrenocorticotrophic hormone (ACTH) test (250 microg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls. Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2-10 months after itraconazole treatment had been discontinued. Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.
    European Respiratory Journal 08/2002; 20(1):127-33. DOI:10.1183/09031936.02.00248002 · 7.13 Impact Factor
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    ABSTRACT: Deficiency of mannose-binding lectin has been shown to be a risk factor for cystic fibrosis (CF) patients. We, therefore, decided to treat a patient with CF, mannose-binding lectin deficiency, severe bronchopulmonary Pseudomonas aeruginosa infection, and rapid deterioration of lung function with purified mannose-binding lectin in an attempt to ameliorate the course of the lung disease. The mannose-binding lectin used originated from pooled human donor plasma and was given as an intravenous infusion twice a week for a period of 3 months. The patients's clinical condition was stabilized during the treatment period, but was not improved. No adverse events were observed. However, the lung function assessed as percent forced expiratory volume in 1 sec (FEV1%) and percent forced vital capacirt (FVC%) correlated significantly with the mannose-binding serum lectin levels (rho=+0.68, P=0.008, and rho=+0.73, P=0.004). Additionally, an inverse correlation with the acute phase-reactant C-reactive protein and the proinflammatory cytokine IL-6 was observed (rho=-0.49, P=0.007 and rho=-0.41, P=0.04, respectively). The results emphasize the importance of mannose-binding lectin as a secondary disease modifier in CF. Moreover, purified mannose-binding lectin can safely be administered to chronically ill patients, and may be a potential treatment in CF and other diseases in which mannose-binding lectin deficiency plays a pathophysiological role.
    Pediatric Pulmonology 03/2002; 33(3):201-7. DOI:10.1002/ppul.10064 · 2.30 Impact Factor

Publication Stats

6k Citations
616.56 Total Impact Points


  • 2007–2011
    • University of Southern Denmark
      • Institute of Molecular Medicine
      Odense, South Denmark, Denmark
  • 1994–2006
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Steno Diabetes Center
      Gjentofte, Capital Region, Denmark
  • 1993–2006
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1996–2005
    • National University (California)
      San Diego, California, United States
  • 2001
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
  • 2000
    • Cystic Fibrosis Canada
      Toronto, Ontario, Canada
  • 1987–1999
    • Rigshospitalet
      • • Department of Clinical Microbiology
      • • Department of Paediatrics
      Copenhagen, Capital Region, Denmark
  • 1988
    • Aarhus University
      • Department of Medical Microbiology and Immunology
      Aars, Region North Jutland, Denmark