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Biomedical subjects

Matthias Griese

Publications and source records attributed to Matthias Griese.

At least 37 records · Page 2Linked to original sources
PubMed2005

Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough.

BACKGROUND: Cough is a frequent symptom in children, but the differentiation of asthmatic cough from cough of other origins can be difficult. Chemokines recruit T lymphocytes to inflamed tissues, and the corresponding chemokine receptors are differentially expressed on T H 1 and T H 2 cells. OBJECTIVE: We sought to determine whether levels of T H 1/T H 2-related chemokines and their receptors differ in bronchoalveolar lavage fluid (BALF) from 12 children with allergic asthma, 15 nonatopic children with chronic cough, and 10 children without airway disease. METHODS: The T H 1-related (IFN-gamma-inducible protein of 10 kd [IP-10], IFN-gamma-inducible T cell alpha chemoattractant [ITAC], monokine induced by IFN-gamma [Mig], and IFN-gamma) and T H 2-related (thymus- and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC], IL-5, and IL-4) chemokines and cytokines were quantified in BALF by ELISA and a particle-based multiplex array. Percentages of pulmonary lymphocytes expressing CXCR3 + and CCR5 + (T H 1) and CCR4 + and CCR3 + (T H 2) chemokine receptors were determined in BALF by flow cytometry. RESULTS: Pulmonary CCR4 + CD4 + cells and levels of TARC and MDC were significantly increased in asthmatic children versus children with chronic cough or without airway disease. In asthmatic children CCR4 + CD4 + cells correlated positively with levels of TARC, MDC, and serum IgE levels and negatively with FEV 1 . In contrast, CXCR3 + CD8 + cells and levels of ITAC were significantly increased in children with non-atopic chronic cough compared with the other groups. In children with chronic cough, CXCR3 + CD8 + cells correlated with levels of ITAC and IFN-gamma. CONCLUSION: Pulmonary CCR4 + CD4 + and CXCR3 + CD8 + cells and their ligands TARC, MDC, and ITAC clearly differentiate asthmatic children from nonatopic children with chronic cough. The analysis of these markers could facilitate the diagnostic discrimination of asthma versus other reasons for chronic cough in children.

Adolescent↗
PubMed2005

Skin prick test reactivity to supplemental enzymes in cystic fibrosis and pancreatic insufficiency.

BACKGROUND: Patients with cystic fibrosis and pancreatic insufficiency take supplemental pancreatic enzymes of porcine or plant origin on a daily basis. OBJECTIVE: The frequency of immediate skin prick hypersensitivity reactions to such enzymes and the correlations to gastrointestinal symptoms and nutritional status were assessed in a single center prospective descriptive study. METHODS: Skin prick tests using five different freshly prepared porcine pancreatic enzyme preparations, one enzyme preparation of fungal origin, porcine meat and cat epithelia were performed in patients with cystic fibrosis and pancreatic insufficiency and in healthy control subjects. RESULTS: Positive skin tests in the 48 patients with cystic fibrosis were no more frequent than in 21 control subjects. No correlations with the frequency of gastrointestinal symptoms, nutritional status and lung function were found. CONCLUSION: Although immediate hypersensitivity reactions to pancreatic enzyme preparations in subjects with cystic fibrosis are not common, individuals with possible allergic reactions to supplemental enzymes should be identified by skin prick tests and in unclear cases by double-blind placebo-controlled provocation tests.

Adolescent↗
PubMed2004

Exhaled carbon monoxide is not flow dependent in children with cystic fibrosis and asthma.

STUDY OBJECTIVES: Exhaled nitric oxide (eNO) and carbon monoxide (eCO) concentrations are elevated in inflammatory airway diseases like asthma and have been investigated as potential diagnostic markers. For eNO concentrations knowledge about the inverse flow dependency is essential for reproducibility and comparability of measurements. The aim of this investigation was to evaluate a possible expiratory flow dependency of eCO in children with different inflammatory airway diseases. DESIGN: ENO and eCO concentrations were measured electrochemically and via chemiluminescence in the exhaled air of 20 healthy children, 17 stable cystic fibrosis (CF)-patients and 15 steroid-naive asthmatics in a combined analyzer at five different expiratory flows (10, 20, 45, 86, 184 ml/sec). RESULTS: ECO was not flow dependent in any of the three groups. At 45 ml/sec the mean eCO-concentration of healthy children was 3.72 +/- 0.23 ppm, of CF-patients 3.67 +/- 0.37 ppm and of asthmatics 4.99 +/- 0.45 ppm. Elevated eCO (p<0.0122) was found in asthmatics but not in CF-children. There was no age dependency and no correlation between eNO and eCO. CONCLUSIONS: In contrast to CF-patients in the exhaled air of steroid-naive asthmatics elevated eCO concentrations are found that may serve as non-invasive inflammatory marker. In contrast to eNO, eCO did not show any expiratory flow dependency.

Adolescent↗
PubMed2004

Pulmonary surfactant, lung function, and endobronchial inflammation in cystic fibrosis.

Cystic fibrosis (CF) lung disease is primarily a disease of the small airways. We hypothesized that even in patients with normal lung function, a reduced surfactant function would be present and favor small airway obstruction. Bronchoalveolar lavages from 76 patients with CF (5-31 years, median 11) with well-conserved lung function (FEV1 94% predicted, range 78-121) and from 10 healthy control subjects were investigated. The deviation of the biophysical surfactant performance from normal, assessed in a bubble surfactometer, was small; however, the ability of the surfactant to maintain the patency of a narrow airway (% open) was significantly reduced. Surfactant protein (SP)-C level was increased, SP-B and SP-D were unchanged, whereas SP-A was decreased. Among the patients with CF, neutrophilic inflammation was modestly related to a poorer surfactant activity, but not to lung function. SP-D was reduced in proportion to the degree of inflammation and in the presence of bacteria. These findings in a large cohort of patients with CF with normal lung function show that the endobronchial airway inflammation is linked to early perturbations of the biophysical properties and immunologic components of pulmonary surfactant and opens fields for novel therapeutic interventions.

Adolescent↗
PubMed2004

Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease.

Pulmonary surfactant protein C (SP-C) is a highly hydrophobic peptide produced by type-II alveolar cells through the processing of a high-molecular weight precursor (pro-SP-C), that enhances surface tension and facilitates the recycling of pulmonary surfactant in vitro. Recently, two seemingly dominant-negative mutations of the pro-SP-C-encoding gene (SFTPC, MIM 178620), were reported in families with vertically-inherited interstitial lung disease (Nogee et al. [2001: N Engl J Med 344:573-579]; Thomas et al. [2002: Am J Respir Crit Care Med 165:1322-1328]). We have examined the SP-C protein and its precursor as well as the encoding gene, in a cohort of 34 sporadic or familial cases with unexplained respiratory distress (URD) in which surfactant protein B (SP-B) deficiency related to SFTPB mutation had been ruled out. One patient with complete SP-C deficiency had no detectable mutation of SFTPC. Of the 10 patients with abnormal pro-SP-C processing, as suggested from analysis of broncho-alveolar lavage (BAL) fluid, two distinct heterozygous SFTPC missense mutations were identified. The first, g.1286T > C (p.I73T), was de novo and resulted in progressive respiratory failure with intra-alveolar storage of a granular, protein- and lipid-rich, periodic acid Schiff (PAS)-positive material (pulmonary alveolar proteinosis (PAP)), and interstitial lung disease. The second, g.2125G > A (p.R167Q), was found in two PAP patients from the endogamous white settler population of Réunion Island in which URD has an unexpectedly high prevalence. Since this mutation was diagnosed in subjects from this subpopulation who did not have evidence for lung disease, we propose environmental exposures or modifier genes to play a role in the phenotype, as suggested from murine models lacking the SP-C protein, although we cannot rule out a rare polymorphism, hitherto restricted to that subpopulation. Most remarkably, these observations extend the phenotypic spectrum related to SFTPC mutation from interstitial lung disease to PAP. Notably, the reported mutations do not appear to be dominant negatives. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Improvement of alveolar glutathione and lung function but not oxidative state in cystic fibrosis.

Chronic neutrophilic inflammation leads to oxidative damage, which may play an important role in the pathogenesis of cystic fibrosis lung disease. Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in patients with cystic fibrosis. Here we evaluated the effects of glutathione aerosol on lower airway glutathione levels, lung function, and oxidative status. Pulmonary deposition of a radiolabeled monodisperse aerosol generated with a Pari LC Star nebulizer (Allergy Asthma Technology, Morton Grove, IL) connected to an AKITA inhalation device (Inamed, Gauting, Germany) was determined in six patients. In 17 additional patients bronchoalveolar lavage fluid was assessed before and after 14 days of inhalation with thrice-daily doses of 300 or 450 mg of glutathione. Intrathoracic deposition was 86.3 +/- 1.4% of the emitted dose. Glutathione concentration in lavage 1 hour postinhalation was increased three- to fourfold and was still almost doubled 12 hours postinhalation. FEV(1) transiently dropped after inhalation but increased compared with pretreatment values after 14 days (p < 0.001). This improvement was not related to the lavage content of oxidized proteins and lipids, which did not change with treatment. These results show that, using a new inhalation device with high efficacy, glutathione treatment of the lower airways is feasible. Reversion of markers of oxidative injury may need longer treatment, higher doses, or different types of antioxidants.

Adolescent↗
PubMed2004

Celiac disease and pulmonary hemosiderosis in a patient with chronic granulomatous disease.

We report on a patient with the hitherto undescribed combination of chronic granulomatous disease, pulmonary hemosiderosis, and celiac disease. The hemosiderosis resolved with a gluten-free diet and glucocorticosteroid pulse therapy, but the restrictive lung function pattern remained unchanged. Lung function improved markedly by immunosuppression with daily glucocorticosteroid and azathioprine treatment.

Aconitine↗
PubMed2003

Effect of treatment with dornase alpha on airway inflammation in patients with cystic fibrosis.

Recombinant human deoxyribonuclease (rhDNase) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis (CF), but its long-term effect on airway inflammation remains unknown. In this study, we used bronchoalveolar lavage (BAL) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease. A total of 105 patients with CF (> or =5 years of age) having normal lung function were randomized to receive rhDNase (2.5 mg/day) or no rhDNase. Patients with a normal percentage of neutrophils in BAL fluid at baseline were not randomized and served as the control group. The percentage of neutrophils in the pooled BAL sample was similar in both randomized groups at baseline. A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects, whereas neutrophils remained unchanged in patients treated with rhDNase. Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase. We conclude that in patients with CF, an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment.

Adolescent↗
PubMed2003

Prospective study on nontuberculous mycobacteria in patients with and without cystic fibrosis.

Recent reports indicated an increase of nontuberculous mycobacteria (NTM) in cystic fibrosis (CF) patients. However, it is still a matter of discussion whether criteria for diagnosis of NTM pulmonary infection established by the American Thoracic Society (ATS) are applicable for CF patients. We determined incidence and prevalence of NTM in CF patients and non-CF patients without HIV infection, and validity of ATS criteria for CF patients. Over a period of 2 years, 1,251 respiratory samples were investigated for mycobacteria from 91 CF and 162 non-CF patients. For all patients with NTM recovery, we reviewed clinical charts and determined outcome for up to 2 years. Incidence and prevalence for repeated recovery of NTM were higher in CF patients, but not significantly. CF patients with repeated recovery of NTM met clinical and bacteriological ATS criteria, but radiographic criteria were not met. Treated CF patients showed favorable clinical outcomes, as opposed to untreated patients. We propose a modified definition for diagnosis and hence treatment of NTM pulmonary infection in CF patients.

Adolescent↗
PubMed2003

Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB.

We have analyzed surfactant protein B (SP-B) and its encoding gene (SFTPB, MIM 178640) in 40 unrelated pediatric patients with unexplained respiratory distress (URD). There was high consanguinity (eight kindreds) and an underlying autosomal recessive trait could be inferred in most cases, with overall high sex ratio (32/17) suggesting proband's gender to impact on penetrance. The clinical/biological presentations fitted into three major nosologic frameworks. I: SP-B deficiency (nine probands), complete or incomplete, with homozygous/compoundly heterozygous mutations identified (six probands), including one from the population isolate of Réunion Island (496delG). In addition, there was a consanguineous kindred in which incomplete deficiency was unambiguously unlinked to SFTPB. II: pulmonary alveolar proteinosis (PAP, 19 probands), with typical storage of PAS-positive material within the alveoli with foamy macrophages and variable interstitial reaction, which was diagnosed in most patients from Réunion Island. In contrast to previously published findings, mutation and/or segregation analyses excluded SFTPB as a disease locus, although slight metabolic derangement related to SP-B and/or mild SFTPB changes could somehow contribute to disease. III: URD without evidence for SP-B deficiency or PAP (12 probands), equally unlinked to SFTPB, although a single patient had a possibly causal, maternally-derived, heterozygous genetic change (G4521A). The population frequency of five known and four novel SNPs was studied, providing as many potential markers for pulmonary disease related to SFTPB. Overall, URD was found to be heterogeneous, both phenotypically and genetically, even in population isolates where a founder effect might have been expected. When disease loci are identified, patient genotyping will be crucial as a diagnostic aid, for devising proper treatment, and as a basis for genetic counseling.

Amino Acid Sequence↗
PubMed2003

Elemental and ion composition of exhaled air condensate in cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF) the exact ion composition of the airway surface fluid is still debated and it is not clear if it differs from healthy subjects. The air that we exhale contains small droplets, which are generated by shear forces from the airway surface fluid and very likely mirror its ion composition. We hypothesized that differences between CF-patients and healthy controls would be reflected by differences in their exhaled air. METHODS: In nasally collected exhaled breath condensate from 20 children and young adults with cystic fibrosis and 20 healthy subjects, the elements and anions were determined by optical emission spectroscopy and ion-exchange chromatography. RESULTS: The concentrations of the major components Na and Cl- did not differ, Zn was higher and NO3- was lower in CF-patients. During a given time period, CF-patients produced a slightly larger volume of breath condensate and they exhaled more Na, K and Zn. Fluoride was detected in half of all samples, whereas copper, iron, magnesium, phosphorus and sulfur were present only sporadically, with no differences. CONCLUSIONS: These data detail the composition of exhaled breath condensate and suggest a similar Na and Cl- concentration in CF-airway surface fluid as in healthy subjects.

Adolescent↗
PubMed2003

Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide.

We investigated the role of the surfactant proteins (SPs) A and D in the pulmonary immune defense of nonmucoid strains of Pseudomonas aeruginosa, the most etiologic agents of nosocomial Pseudomonas pneumonia. We first examined the interactions of recombinant human SP-D dodecamers and purified natural or recombinant human SP-A with two smooth, and two rough, clinical isolates of nonmucoid P. aeruginosa. SP-D bound to all four isolates, but agglutinated only one rough and one smooth strain. SP-D functioned as an opsonin to enhance the uptake of all four strains by the human monocytic cell line Mono Mac 6 (MM6). SP-D also enhanced tumor necrosis factor-alpha secretion by MM6 cells in response to purified lipopolysaccharide (LPS) isolated from the rough, but not the smooth, strains. Although SP-A bound to all four strains, it did not cause bacterial aggregation or enhance uptake. It showed small but statistically significant inhibitory effects on the cytokine response of MM6 cells to one strain of smooth organisms, but did not significantly alter the response to purified LPS. This study in combination with previously published data strongly suggests that SP-D may play important roles in the local innate pulmonary defense against nonmucoid P. aeruginosa of diverse LPS phenotypes, and preferentially augments the cellular response to rough P. aeruginosa endotoxin.

Animals↗
PubMed2002

Surfactant proteins A and D in children with pulmonary disease due to gastroesophageal reflux.

Children with gastroesophageal reflux often suffer from chronic, severe lung damage and recurrent infections. The mechanisms may involve reflux induced lung injury with alterations of the surfactant proteins (SP) SP-A and SP-D, which bind specifically to various microbes and increase their elimination by granular leukocytes and macrophages. In 20 children with gastroesophageal reflux disease (GERD) the bronchoalveolar lavage content and macromolecular organization of SP-A and SP-D was determined by enzyme linked immunosorbent assay and gel chromatography. For comparison, lavages from 17 children without respiratory diseases were investigated. Both, SP-A and SP-D were significantly reduced in children with GERD-median (25, 75 percentiles) SP-A: 362 (169, 494) ng/ml versus 867 (656, 1,761) in control subjects and SP-D: 174 (73, 456) ng/ml versus 518 (295, 748) ng/ml in control subjects. The more active, higher molecular weight oligomers of SP-A and especially those of SP-D were diminished, whereas the smaller sized forms of SP-D were markedly increased. In children with GERD, significantly reduced amounts of SP-A and SP-D and an altered structural organization of the surfactant protein oligomers were demonstrated. Such impairments of central components of the innate host defense system may contribute to the pathogenesis of the chronic lung disease commonly observed in these children.

Adolescent↗
PubMed2002

Eradication of initial Pseudomonas aeruginosa colonization in patients with cystic fibrosis.

The optimal treatment for the eradication of initial P. aeruginosa infection in CF is still unclear. Recently long-term inhaled tobramycin has been proposed. Here we report the results with brief inhaled and/or systemic anti-pseudomonal treatments. Initial P. aeruginosa colonization was successfully eradicated as demonstrated by negative repetitive throat cultures or sputa and serum antipseudomonal antibodies in 15 of 17 patients for at least two years. Randomized, controlled trials are urgently needed to define the optimal protocol for the eradication of P. aeruginosa. Pseudomonas aeruginosa, infection, treatment, antibodies; inhaled tobramycin

Administration, Inhalation↗
PubMed2002

Bronchoalveolar lavage protein patterns in children with malignancies, immunosuppression, fever and pulmonary infiltrates.

Severe respiratory infections are a major cause of morbidity and mortality in children receiving immunosuppressive therapy for malignancies. The goal of this study was to assess the major changes in the protein patterns in these children. Bronchoalveolar lavage (BAL) fluids of seven control children and of ten children with malignancies and fever not responding to broad spectrum antibiotic treatment was separated by horizontal two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the isoelectric point range 3-9. We observed a large increase of alpha(1)-antitrypsin (p = 0.0004) and decreases of the immunoglobulin (Ig) binding factor, transthyretin and cystatin S. Significant changes occurred also in the small acidic proteins. The relative abundance of the IgG heavy and light chains may hinder the separation and identification of many minor protein spots located in the basic area of the gel, suggesting that their removal during sample preparation may be warranted. This study demonstrated significant alterations in BAL fluid proteome in immunosuppressed children with persistent fever and pulmonary infiltrates. Future target regions of interest were identified. Sample prefractionation and the selection of suitable narrow isoelectric point ranges will be necessary for optimized detection and separating conditions.

Adolescent↗
PubMed2002

Protein pattern of exhaled breath condensate and saliva.

The proteins recovered in exhaled breath condensate (EBC) might be used to non-invasively monitor respiratory diseases. However, the range of proteins and their source are still unresolved and contamination by saliva or a similar protein pattern in the nasal and bronchial compartments may make interpretation of the data difficult. We studied nasal EBC (collected through a "free of touch" technique by negative pressure), oral tidal, and oral forced EBC (collected through a rebreathing valve as a saliva trap connected to tubing submerged into ice) and matched saliva samples from five healthy adult subjects. The protein samples were separated by two-dimensional electrophoresis and the silver stained gels were analyzed by Melanie 2 software. In both nasal and oral EBC, three spots (72 kDa/isoelectric point (pI) 6.6-7.0, 66 kDa/pI 5.9-6.7 and 45-48 kDa/pI 8.0-8.6) were consistently present in all subjects. Several other proteins were only sporadically detected. Despite improbable saliva contamination (no phosphorus contamination in the same oral and nasal EBC, no amylase activity in 10 pairs of nasal and oral EBC collected by the same technique), on average 63% and 71% of the spots identified in oral and nasal EBC were also found in the matched individual saliva samples. Compared to saliva, the range and amount of protein in all types of EBC was very small. Even when collected free of saliva contamination the majority of proteins present in EBC was also found in saliva, suggesting that these proteins are present in both compartments, e.g. saliva and secretions of the lower airspaces. The quantification and identification of specific proteins in the various compartments is warranted in future studies to determine the practical value of EBC.

Adult↗
PubMed2002

Exhaled nitric oxide in healthy children: variability and a lack of correlation with atopy.

Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme nitric oxide synthetase (NOS) and can be easily measured in exhaled air by chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines and endotoxin, NO is elevated in several chronic inflammatory airway diseases. Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway inflammation in daily routine, the role of possibly influencing factors such as age, time of the day, smoking exposure and intra-individual variability have to be clarified. NO concentrations were measured in 107 healthy children aged 4-18 years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were performed and a questionnaire on family history of atopy, personal symptoms of atopic disease and smoke exposure was completed. For intra-individual variability nitric oxide was measured in six children three times daily on 6 consecutive days. Median eNO concentration was 5.7 p.p.b., and increased significantly with age but did not vary with gender. No correlation was found between eNO and smoke exposure, positive skin-prick test, FEV1, MEF25 and time of the day. There was no circadian rhythm found in the six children measured on 6 consecutive days, but the eNO showed an intra-individual coefficient of variation of 25.9%. With the help of a two-compartment model of the lung the alveolar NO concentration was estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the airway part of NO steadily increased with age. When comparing eNO values with standardized measurement techniques, the age of the children and the large intra-subject coefficient of variation have to be taken into account, whereas in healthy children subject-specific factors such as atopic history, gender and skin test reactivity did not affect eNO measurement.

Breath Tests↗