Search PubMed⌕ Search

Biomedical subjects

K Häussinger

Publications and source records attributed to K Häussinger.

At least 19 recordsLinked to original sources
PubMed2002

Inhalation of aerosolized vitamin a: reversibility of metaplasia and dysplasia of human respiratory epithelia -- a prospective pilot study.

The objective of this preliminary uncontrolled study was twofold: First, to assess the feasibility of retinyl palmitate inhalation and second, to analyze the changes of metaplastic lesions of the respiratory epithelium (metaplasia or dysplasia) following retinyl palmitate inhalation. The response to a daily dose of 18.000 I.U. retinyl palmitate by inhalation over a period of 3 month was assessed in 11 subjects (9 smokers, 2 ex-smokers). Using white-light bronchoscopy combined with autofluorescence bronchoscopy, bronchial biopsies were taken before and after a 3 month-period. The biopsy samples were evaluated blind by a referee lung pathologist. The overall response rate (remission or partial remission) was 56% (95% CI 0.30 0.79; p<0.05). These data suggest that inhalation of retinyl esters could be a promising therapeutical approach for chemoprevention of lung cancer. Vitamin A; chemoprevention; lung cancer; squamous metaplasia; dysplasia; retinoids

Administration, Inhalation↗
PubMed2002

[Tuberculosis].

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed2002

[Pneumological diagnostics by means of models aerosols. IV. Clearance of aerosol particles from the pulmonary alveoli. Foundations and first clinical results].

The elimination of deposited particles (inorganic and organic particles, bacteria, viruses) from the periphery of the human lung (alveolar clearance) implies phagocytosis by alveolar macrophages, intracellular digestion, migration and translocation. Alveolar clearance of poorly soluble particles happens very slowly and primarily depends on the function of alveolar macrophages. In humans, the transport of particles to the bronchial tree is of secondary relevance, suggesting that the elimination of particles primarily depends on digestion (dissolution) processes within macrophages. The dissolved material is excreted via urine, if there is no further metabolization within the body. The pathophysiology of the alveolar clearance mechanisms in the human lung can be studied by a magnetic tracer technique (magnetopneumography). Ferromagnetic magnetite test-particles are deposited in the periphery of the lung by controlled inhalation. After magnetization and particle alignment in a strong external magnetic field pulse, the amount of retained particles can be detected by a sensitive magnetic field sensor (SQUID, superconducting quantum interference device). Long lasting cigarette smoking and chronic lung inflammations (sarcoidosis, interstitial lung fibrosis) induce a significant impairment of alveolar clearance capacity, while patients with chronic bronchitis show only a moderate impairment of alveolar clearance.

Aerosols↗
PubMed2001

Increased sputum IL-8 and IL-5 in asymptomatic nonspecific airway hyperresponsiveness.

Since asymptomatic, nonspecific airway hyperresponsiveness (BHR) may be due to an enhanced local inflammatory response, we studied molecular markers of inflammation in induced sputum from subjects with asymptomatic BHR (n = 14) compared with control subjects (n = 13) and patients with chronic obstructive pulmonary disease (COPD) (n = 10). Pulmonary lung function parameters were measured by spirometry and body plethysmography. Hyperresponsiveness was defined based on histamine challenge. Induced sputum samples were collected and the solid phase was isolated and analyzed for leukocyte numbers and differential and for cytokines (ELISA). IL-8 was 2.4-fold increased (p = 0.036) in the sputum of subjects with asymptomatic BHR (24.8 +/- 22.0 ng/mL; +/- SD) and 11.2-fold enhanced in patients with COPD (117.8 +/- 106.3 ng/mL) as compared with control subjects (10.5 +/- 7.7 ng/mL). In control subjects, no IL-5 was measured, however, sputum of those with asymptomatic BHR contained IL-5 at 0.044 +/- 0.090 ng/mL fluid and COPD patients at 1.00 +/- 2.01 ng/mL. GM-CSF could not be detected in sputum samples of any subjects investigated. Number of total leukocytes was higher in those with asymptomatic BHR and COPD (with BHR: 9.4 +/- 10.8 x 10(5); COPD: 83.5 +/- 182.5 x 10(5)) compared with persons without BHR (2.9 +/- 3.4 x 10(5)). PMN were increased in patients with asymptomatic BHR (4.1 +/- 5.3 x 10(5)) (38.8 +/- 24.7%) and COPD (32.9 +/- 71.0 x 10(5)) (75.4 +/- 18.6%) compared with controls (0.7 +/- 0.9 x 10(5)) (25.8 +/- 25.7%). In contrast to PMN counts in those with asymptomatic BHR (0.06 +/- 0.11 x 10(5)) (1.5 +/- 3.7%), eosinophil counts were only slightly increased compared with control subjects (0.01 +/- 0.02 x 10(5)) (0.6 +/- 0.9%). This study supports the hypothesis that BHR in asymptomatic people is associated with airway inflammation that may predispose to development of chronic diseases such as COPD.

Adult↗
PubMed2001

[Measurement of the Fowler dead space in patients with pulmonary emphysema using C18O2].

In patients with lung emphysema, changes in lung volumes as well as changes in airway resistance are well known. The change in airway resistance is caused by obstruction of central airways, which is supposed to reduce the respiratory dead space. Until now, it was not possible to measure the respiratory dead space in patients with lung emphysema using the method of Fowler [2], because in this method distinction of the three phases of an inert gas expirogram is essential. While this distinction is easy in healthy subjects (fig. 1; expirogram 3), the separation of the three phases in patients with lung emphysema is not possible due to gradual transition of phase II into phase III in these patients (fig. 1; expirogram 2). The use of C18O2 as tracer gas allows to separate phase II and phase III even if the patients have severe emphysema (fig. 1; expirogram 1). CO2 labeled with the stable oxygen isotope 18O (C18O2) is completely taken up in the gas exchanging region of the lung, but not from the conducting airways. Therefore C18O2 is only expired from the dead space of the lung, but not from the alveolar region. Hence, C18O2 allows exact measurement of the respiratory dead space in patients with lung emphysema. 21 healthy nonsmoking subjects and 29 patients with clinical signs of lung emphysema participated in this study. There was a good correlation between respiratory dead space, measured by the use of Ar-gas and C18O2-gas in healthy subjects (fig. 2). This indicates, that the use of C18O2 is a valid method to measure the functional dead space. As expected, there was also a correlation between the airway resistance and respiratory dead space in patients with lung emphysema (fig. 3), but not in healty subjects. There was no significant difference of the mean values of the respiratory dead space between these two groups (223 +/- 43 ml in healthy subjects vs. 227 +/- 52 ml in patients), even though there were large differences in airway resistance (0.20 +/- 0.10 kPa/l/s vs. 0.49 +/- 0.27 kPa/l/s). This may be due to a loss of alveolar function in the area of the terminal bronchioli, which is typical for emphysematous patients. This entails a shift of functional dead space towards lung periphery and therefore causes an increase of the volume of functional dead space. But this enlargement may be compensated by the volume reduction, caused by the airway obstruction. Hence, these two oppositional mechanisms may result in only minimal change of dead space volume.

Adult↗
PubMed2001

Impulse oscillometry in healthy nonsmokers and asymptomatic smokers: effects of bronchial challenge with methacholine.

The clinical application of respiratory impedance measurements by oscillation techniques for monitoring bronchial challenge testing is hampered by the fact that data in healthy nonsmokers and asymptomatic smokers are very limited. The objective of this study was to analyze the changes in impedance to a methacholine provocation test in healthy nonsmokers and asymptomatic smokers, and to investigate whether smokers show a different response compared to nonsmokers. The response to methacholine challenge was assessed by impulse oscillometry (IOS) (resistance R and reactance X at 5, 10, 15, 20, 25, and 35 Hz) and spirometry (FEV1, MEF50) in 105 healthy subjects (55 nonsmokers: "NS"; 50 asymptomatic smokers: "S") in whom the provocation dose of 2.44 mg methacholine did not result in a fall of FEV1 below 20% predicted of the baseline value. The baseline reactance X values of S were significantly lower compared to NS from 10 to 35 Hz (p < or = 0.01), whereas S and NS did not differ in resistance R over the whole frequency spectrum from 5 to 35 Hz. S showed a significantly higher mean baseline resonant frequency X(f0); i.e., the frequency at which inertial forces are equal and opposite to elastic forces, compared to NS (NS: X(fo) = 10.8+/-2.9 Hz; S = 12.6+/-4.0 Hz, p = 0.01). In both groups methacholine challenge resulted in an increase in R (f) especially at 5 and 10 Hz, and a marked decrease in X(f) over the whole frequency spectrum. In S a significantly higher decrease of postchallenge X5Hz and X10Hz was measured compared to NS (NS: deltaX(5Hz) = -0.044+/-0.003; S: deltaX(5HZ) = -0.083+/-0.013; p = 0.0017. NS: deltaX(10Hz) = -0.050+/-0.001; S: deltaX(10Hz) = -0.082+/-0.017; p = 0.008). R and X at low frequencies showed a three to four times higher postchallenge reaction compared to FEV1. Pre- and postchallenge FEV1 did not correlate with resistance R (f) and reactance X(f) over the whole frequency spectrum. In S perchallenge X(f) values from 10 to 35 HZ were significantly lower, and postchallenge decrease of X5Hz and X10Hz values were significantly higher compared to that of NS, whereas pre- and postchallenge R(f) values were similar in both groups. These results can be explained by changes in the elastic properties of the lung induced by a diffuse subclinical respiratory bronchiolitis.

Adult↗
PubMed2001

All trans-retinoic acid selectively down-regulates matrix metalloproteinase-9 (MMP-9) and up-regulates tissue inhibitor of metalloproteinase-1 (TIMP-1) in human bronchoalveolar lavage cells.

BACKGROUND: The balance between proteinases and antiproteinases plays an important role in tissue destruction and remodelling. In chronic obstructive pulmonary disease (COPD) and emphysema, an imbalance between matrix metalloproteinases (MMPs) and inhibitors of tissue metalloproteinase (TIMPs) has been reported. Alveolar macrophages are considered to be the main source of MMPs. We therefore have analyzed the effects of free and liposomal all trans-retinoic acid (ATRA) on the expression of MMP-9 and TIMP-1 in bronchoalveolar lavage (BAL) cells from patients with COPD and patients with other lung diseases. MATERIAL AND METHODS: BAL cells were incubated 1-3 day with either liposomal or free ATRA. Supernatants were tested for MMP-9 and TIMP-1 protein in specific ELISA systems; mRNA analysis was performed by semi-quantitative RT-PCR and by quantitative LightCycler PCR. RESULTS: We demonstrate that either liposomal or free ATRA selectively down-regulates MMP-9 and up-regulates TIMP-1. At the protein level, MMP-9 is decreased 3-fold and TIMP-1 is increased 3.5-fold compared to the base line with empty liposomes or untreated cells. The ratio of MMP-9 and its inhibitor TIMP-1, which may be crucial to the overall proteolytic potential decreased by factor 8. That this countercurrent effect of ATRA is not due to an altered protein stability but to transcriptional regulation could be demonstrated by RT-PCR. Quantitative LightCycler analysis revealed a 2.5-fold decrease of MMP-9 mRNA and a 4.5 fold increase of TIMP- 1 mRNA. CONCLUSIONS: These data suggest that ATRA treatment via its impact on the proteinase/antiproteinase ratio may become a new therapeutic strategy for patients with inflammatory destructive lung diseases.

Antineoplastic Agents↗
PubMed2000

[Bronchoscopy in Germany. Cross-sectional inquiry with 681 institutions].

Bronchoscopy represents an integral part of the diagnostic tools in pulmonary medicine. Recently, it has also gained considerable attention for its therapeutic properties. To elucidate equipment, indications and procedural techniques of bronchoscopy units, a retrospective survey of 1232 hospitals and practices is conducted. 687 questionnaires are received back (response rate 56%). 681 of which are statistically evaluated. Two thirds of the physicians in charge are internists, one third are pulmonary care specialists. A total of 200,596 endoscopic procedures is included. The majority of procedures is done with an average of 3 bronchoscopists and in over 57% (388) of cases with an average number of 100 or less procedures per year. The five main indications are tumor, hemoptysis, infection or pneumonia, drainage of secretions and suspected interstitial disease. Overall complication rate amounts to 2.7% with an incidence of 4.6% minor and 0.7% major complications and a bronchoscopy-related mortality of 0.02%. The patterns seen in premedication, intra- and post-procedural monitoring, disinfection practices as well as documentation are quite heterogeneous. It is suggested to establish revised and updated standards for bronchoscopy, which should take the data collected into particular account. Those standards should provide the basis for a high level bronchological care throughout Germany.

Bronchoscopy↗
PubMed2000

Aerosol morphometry and aerosol bolus dispersion in patients with CT-determined combined pulmonary emphysema and lung fibrosis.

The simultaneous occurrence of pulmonary fibrosis and emphysema may present considerable problems in clinical assessment. Recent studies have shown that Aerosol Derived Airway Morphometry (ADAM) and Aerosol Bolus Dispersion (ABD) are changed in patients with pulmonary emphysema. This study was performed to assess the effect of simultaneous lung fibrosis in patients with emphysema on ADAM and ABD. ADAM and ABD measurements were performed in 20 patients with lone high resolution CT scan (HRCT) confirmed emphysema (E), and compared to those in 15 emphysematics with HRCT-confirmed superimposed pulmonary fibrosis (FE). In both groups the peripheral effective airspace dimension (EAD) (E: 0.63 +/- 0.20 mm; FE: 0.60 +/- 0.27 mm, N.S.) was increased by more than a factor of two compared to that of healthy subjects (0.28 +/- 0.05 mm) (p < 0.001). Patients with E showed a significantly higher bolus dispersion than patients with FE (724 +/- 122 cm3 vs. 546 +/- 80 cm3; p < 0.001). However, in patients with FE, bolus dispersion was still significantly higher than in previously published control groups of healthy subjects (546 +/- 80 cm3 vs. 455 +/- 68 cm3; p < 0.001). The results of this study confirm that ADAM and ABD are powerful tools for identifying emphysema even in patients with superimposed pulmonary fibrosis.

Aerosols↗
PubMed1999

Intrapulmonary distribution of deposited particles.

Inhalation drug delivery for both topical and systemic treatments has many advantages over oral, intravenous, or subcutaneous drug delivery. Because some drugs should be deposited within the bronchial tree and others should deposit within the respiratory zone of the lung, it should be possible to determine and influence the preferential site of drug deposition to develop efficient inhalation therapy strategies. In this article, a method that allows estimation of the longitudinal distribution of deposited particles in the lungs of individual subjects is introduced. From the photometrically measured deposition of monodisperse di-2-ethylhexyl sebacate (DEHS) droplets, the longitudinal distribution of deposited particles (i.e., the number of particles that are deposited in a certain lung volume element) can be assessed. In this study in four healthy volunteers the distribution of deposited particles was assessed for different airflow rates, tidal volumes (VTS), and particle sizes. The results showed that there are considerable differences in the longitudinal distribution of deposited particles between subjects and that the distribution is strongly dependent on particle size: if particle size is increased, the site of particle deposition is shifted proximally. Particles with diameters greater than approximately 5 microns cannot penetrate to a volumetric lung depth (VP) greater than approximately 600 cm3 even if the VT is increased. Airflow rate has a minor effect on the distribution of deposited particles, but if airflow rate increases, the site of particle deposition is slightly shifted peripherally. This method can be used to investigate individual patterns of drug deposition in human lungs noninvasively and to develop and optimize inhalation strategies for inhalation drug delivery.

Administration, Inhalation↗
PubMed1999

Increased fine particle deposition in women with asymptomatic nonspecific airway hyperresponsiveness.

Previous studies suggest that lung function tests using monodisperse aerosols can help to identify early stages of lung diseases. We investigated intrapulmonary particle loss and aerosol bolus dispersion-a marker of convective gas transport-in 32 women with asymptomatic nonspecific bronchial hyperresponsiveness (BHR) compared with 60 women without BHR. Deposition of inhaled particles (0.9 micrometer mass median aerodynamic diameter [MMAD]) was calculated from particle losses of inhaled aerosol boluses consisting of di-2-ethylhexyl sebacate droplets. Convective gas mixing was assessed by the aerosol bolus dispersion method. Women with BHR, nonsmokers as well as smokers, showed significantly increased deposition of aerosol particles (nonsmokers: 45.6 +/- 8.8%; smokers: 49.2 +/- 5.4%; mean +/- SD) compared with the control group of female nonsmokers without BHR (38.2 +/- 9.1%; mean +/- SD) (p < 0.01). Aerosol bolus dispersion values showed a trend for higher values in subjects with BHR (nonsmokers: 572 +/- 122 cm3; smokers: 587 +/- 85 cm3) compared with the control group (542 +/- 88 cm3) (p = 0.2). Also, the maximal expiratory flow at 25% vital capacity (MEF25) showed a trend for decreased values in nonsmokers with BHR compared with nonsmokers without BHR (64 +/- 16% of predicted versus 78 +/- 24% of predicted; p = 0.03). These results suggest that deposition of inhaled particles (0.9 micrometer MMAD) administered by the aerosol bolus technique is a sensitive index of peripheral lung injury that is usually not assessable by conventional methods.

Adult↗
PubMed1999

Noninvasive diagnosis of emphysema. Aerosol morphometry and aerosol bolus dispersion in comparison to HRCT.

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (ABD) test are altered in patients with emphysema. We examined the diagnostic power of these aerosol methods in comparison with the noninvasive "gold-standard" HRCT in 50 consecutive patients with various lung diseases. The severity of airflow limitation was mild to moderate in the group of patients without emphysema and moderate to severe in the group of patients with HRCT-confirmed emphysema (FEV(1), 78 +/- 23% pred versus 53 +/- 33% pred; p < 0. 001). Among all lung function parameters under consideration ADAM showed the highest sensitivity and specificity for separating patients with emphysema from those without emphysema (area under the operating characteristics curve: p(ROC), 0.92), followed by ABD (p(ROC), 0.90), a marker for ventilation inhomogeneities. In patients with HRCT-confirmed macroscopic emphysema, peripheral air-space dimensions (EAD) at a relative volumetric lung depth V(pr) of 0.20 measured by ADAM were 155% larger, and bolus dispersion (ABD) at a lung depth of V(p) 600 ml was 53% larger than those observed in patients with other lung diseases (EAD = 0.84 +/- 0.53 mm versus 0.33 +/- 0.10 mm, p < 0.0001; ABD = 706 +/- 154 cm(3) versus 462 +/- 109 cm(3); p < 0.0001). EAD showed a significant correlation with the HRCT visual score (r = 0.78, p = 0.01). ABD showed weak significant correlations with all HRCT parameters under consideration (visual score, pixel density, mean lung density) (r = 0.45 to 0.66; p < 0.05). ADAM and ABD are powerful tools for the noninvasive diagnosis of macroscopic emphysema.

Aerosols↗