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Lung volume reduction surgery (LVRS) improves exercise capacity and relieves dyspnoea in patients with smoker's emphysema (SE). It is unclear, however, whether LVRS similarly improves lung function in alpha1-antitrypsin-deficiency emphysema (alpha1 E). To address this question, this study prospectively compared the intermediate-term functional outcome in 12 consecutive patients with advanced alpha1E and 18 patients with SE who underwent bilateral LVRS. Before surgery there were no statistically significant differences between the two groups in the six-minute walking distance, dyspnoea score, respiratory mechanics or lung function data, except for the forced expiratory volume in one second, which was lower in the deficient group (24 versus 31% of the predicted value; p

A 44 yr-old female with severe pulmonary emphysema and reduced α- 1-protease inhibitor (α1-PI) serum levels developed an acute anaphylactic reaction following the third intravenous infusion of human α1-PI which was administered to prevent the progression of pulmonary emphysema. Specific immunoglobulin E-anti- bodies against human α1-PI could be demonstrated in the patient's serum using an enzyme allergosorbent test. Because of the risk of further severe anaphylactic reac- tion, the replacement therapy with α1-PI was discontinued. Physicians should be aware of this rare complication. Eur Respir J 1998; 12: 996-997.

We have previously shown that AutoSet satisfactorily improves sleep-disordered breathing and sleep architecture in subjects with obstructive sleep apnoea (OSA) syndrome. The aim of this study was to determine, in subjects treated with long-term conventional fixed pressure continuous positive airway pressure (CPAP) at the AutoSet recommended pressure, whether: the long-term compliance is satisfactory; the improvement persists once initial rebound is over; the titration pressure is stable with time; and the titration pressure is comparable with manual titration pressure using a similar end-point. Twenty males with OSA, previously studied with full polysomnography on their diagnostic night, at manual and AutoSet titration, and at the AutoSet recommended fixed pressure, were re-studied after a mean of 3 and 8 months of treatment at the recommended fixed pressure. Re-study included home respiratory monitoring (Nellcor EdenTrace), and repeated manual and AutoSet titration with polysomnography. Compliance was assessed with hour-meter readings. Mean (+/-SEM) usage was 5.7 +/- 0.1 h.night-1 at 3 and 8 months. The arousal index remained normalized. Diagnostic respiratory disturbance index (RDI) was 60.3 +/- 5.7 events.h-1. On AutoSet at fixed CPAP, RDI was initially 2.6 +/- 0.7 events.h-1, then rose slightly (p < 0.001) to 4.3 +/- 0.6 events.h-1 at 3 months, and was 3.6 +/- 0.5 events.h-1 at 8 months. AutoSet titration pressure was: 9.9 +/- 0.4 cmH2O initially, 10.6 +/- 0.4 cmH2O at 3 months, and 9.7 +/- 0.5 cmH2O at 8 months (NS). Manual titration pressure at 8 months was 10.4 +/- 0.4 cmH2O. The standard deviation of the discrepancy with AutoSet was 0.84 cmH2O. In conclusion, the AutoSet recommended pressure varies little with time, and closely predicts the final manual titration pressure; the improvement in respiratory disturbance index was largely maintained, and compliance was good, although probably enhanced by close supervision.

This study tested the effectiveness of the AutoSet self-titrating nasal continuous positive airway pressure (nCPAP) system in treating obstructive sleep apnea (OSA), and choosing a suitable pressure for subsequent conventional fixed-pressure nCPAP therapy. Twenty-one adult men with untreated OSA were studied with full polysomnography on each of four nights: diagnostic, manual and AutoSet nCPAP titration (in random order), and conventional fixed-pressure nCPAP at the pressure recommended by the AutoSet titration. Titration was satisfactorily performed in 20 of 21 subjects. Severe mask leak prevented automated titration in one subject and caused transient unnecessary increases in pressure in three subjects. In the 20 subjects, respiratory disturbance index (RDI) was 60.3 +/- 5.7 events/h (mean +/- SEM) on the diagnostic night. RDI was lower with manual titration (10.1 +/- 3.0, p < 0.001), and lower still with Autoset (2.8 +/- 0.9, p < 0.01) and fixed pressure (2.5 +/- 0.7, p = ns versus AutoSet) nCPAP. There were similar changes in the arousal index, which was 52.7 +/- 4.6 events/h on the diagnostic night, 14.2 +/- 2.4 with manual titration and 8.9 +/- 0.9 with AutoSet titration, and 9.5 +/- 1.0 on the night of conventional fixed-pressure CPAP (p < 0.001 versus diagnostic). We conclude that the AutoSet system is suitable for automated nCPAP pressure titration.

Lung volume reduction surgery (LVRS) in patients with severe lung emphysema restores the thoracic configuration to a more normal functional capacity. The aim of this study was to investigate whether reduction in intrathoracic volume by LVRS improves the inspiratory muscle force generation of the respiratory pump. Pulmonary function tests, maximal inspiratory mouth pressure (MIP), sniff nasal inspiratory pressure (SNIP), sniff transdiaphragmatic pressure (Pdi), and inspiratory mouth occlusion pressure (P0.1) were measured in 17 emphysematous patients (mean (+/- SEM) age 53 +/- 2 yrs) before and 1 month after LVRS. The mean value of forced expiratory volume in one second (FEV1) increased (0.82 +/- 0.07 vs 1.12 +/- 0.08 L; p < 0.0001), whilst there was a decrease (p < 0.0001) in residual volume (RV) (337 +/- 31 vs 250 +/- 21 % of predicted), functional residual capacity (FRC) (210 +/- 9 vs 159 +/- 9% pred), and total lung capacity (TLC) (138 +/- 6 vs 110 +/- 5% pred). The mean value of MIP increased by 52% from 4.8 +/- 0.4 to 7.3 +/- 0.6 kPa (p < 0.001), the mean value of SNIP increased by 66% from 3.9 +/- 0.4 to 6.5 +/- 0.5 kPa (p < 0.001), and the mean value of Pdi increased by 28% from 6.0 +/- 0.6 to 7.7 +/- 0.8 kPa (p < 0.05) after LVRS. P0.1 decreased on average by 24% from 0.46 +/- 0.03 to 0.35 +/- 0.02 kPa after LVRS. No significant correlations were found between inspiratory muscle (MIP, SNIP, Pdi) and respiratory drive (P0.1) indices, lung function data, 6 min walk distance, or dyspnoea score. In conclusion, the observed clinical improvement of patients with severe emphysema after lung volume reduction surgery results, in part, from an increased ability of the inspiratory muscles to generate force, which is paralleled by a significant decrease in central respiratory drive.

The method of preparation of bronchoalveolar lavage fluid (BALF) for cytological examination can significantly affect the results of cellular quantitation. Investigations have shown that cytocentrifugation leads to an underestimation of the number of lymphocytes and membrane filter preparation to an underestimation of the number of neutrophils. As a simple alternative to these two techniques, BALF cells could be prepared by the microscope slide smear technique, which is familiar as the means for preparing peripheral blood for differential counts. In order to compare cell differentials determined by microscope slide technique with differentials resulting from cytocentrifugation, cells were isolated from 35 BALF samples using standard methods, and counted using a haematocytometer. Forty thousand cells in 200 microL were prepared by cytocentrifugation (3 min, 57 x g; Cytospin 2) and 5 x 10(5) cells in 5 microL by microscope slide smear. Both samples were air-dried, stained using May-Grunwald Giemsa stain, and 600 cells were counted to obtain differentials. To test the adequacy of sampling by the microscope slide smear technique, known quantities of lymphocytes or neutrophils were added to fixed numbers of BALF cells, microscope slide smears prepared, and differentials determined on 600 cells. The resulting differentials were compared to the calculated differentials. Preparation of BALF cells with the microscope slide smear technique yielded well-preserved cell morphology. Compared to cytocentrifugation, microscope slide smear preparations had significantly higher percentages of lymphocytes. The microscope slide smears for the samples with predetermined numbers of cells yielded lymphocyte and neutrophil percentages which did not differ from the calculated differentials (59.6 +/- 1.5 vs 59.6 +/- 5.2% and 54.6 +/- 6.0 vs 53.1 +/- 6.0%, respectively). Varying the number of cells counted from 100 to 800 confirmed the reproducibility of the counts for counting 600 cells. Using 5 x 10(5), 2.5 x 10(5), or 1 x 10(5) cells per preparation demonstrated that adequate specimens could be obtained from as few as 1 x 10(5) cells. Thus, microscope slide smear preparation is a simple and accurate method for the quantitation of bronchoalveolar lavage fluid cytology.

Bronchiolitis obliterans with organising pneumonia (BOOP) is a distinct clinical pathologic syndrome. Most patients experience a good response to therapy, and death from progressive BOOP is uncommon. This report describes the clinical features, etiologic factors, pathologic findings, and outcome of 10 patients with rapidly progressive BOOP that was characterised by severe respiratory failure. The major clinical manifestations were dyspnea, cough, fever, crackles on chest examination, and hypoxemia at rest. Underlying conditions or exposures included connective-tissue disease, exposure to birds, and chronic nitrofurantoin therapy. All patients had the characteristic histopathologic findings of BOOP. However, at autopsy in six patients, the predominant histologic pattern was that of alveolar septal inflammation and fibrotic honeycombing. Seven patients died and three patients survived but had persistent pulmonary dysfunction despite aggressive care. In two patients BOOP has progressed, with severe chronic respiratory decompensation. Thus, there is a subset of patients with BOOP who present with a fulminant course leading to death or chronic severe fibrosis and marked impairment of lung function. In addition, the histologic picture of BOOP may be a manifestation of early lung injury that can resolve or progress rapidly to alveolar septal inflammation, end-stage fibrosis, and honeycombing. (Am J Respir Crit Care Med 1994 ;149 :1670-5)

ST Schmid,1 J Koepke,1 M Dresel,1 A Hattesohl,1 E Frenzel,2 J Perez,3 DA Lomas,4 E Miranda,5 T Greulich,1 S Noeske,1 M Wencker,6 H Teschler,6 C Vogelmeier,1 S Janciauskiene,2,* AR Koczulla1,*1Department of Internal Medicine, Division for Pulmonary Diseases, University Hospital Marburg, Marburg, Germany; 2Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 3Department of Cellular Biology, University of Malaga, Malaga, Spain; 4Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; 5Department of Biology and Biotechnology, Istituto Pasteur – Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy; 6Department of Pneumology, West German Lung Clinic, Essen University Hospital, Essen, Germany*These authors contributed equally to this workBackground: The major concept behind augmentation therapy with human α1-antitrypsin (AAT) is to raise the levels of AAT in patients with protease inhibitor phenotype ZZ (Glu342Lys)-inherited AAT deficiency and to protect lung tissues from proteolysis and progression of emphysema.Objective: To evaluate the short-term effects of augmentation therapy (Prolastin®) on plasma levels of AAT, C-reactive protein, and chemokines/cytokines.Materials and methods: Serum and exhaled breath condensate were collected from individuals with protease inhibitor phenotype ZZ AAT deficiency-related emphysema (n = 12) on the first, third, and seventh day after the infusion of intravenous Prolastin. Concentrations of total and polymeric AAT, interleukin-8 (IL-8), monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein were determined. Blood neutrophils and primary epithelial cells were also exposed to Prolastin (1 mg/mL).Results: There were significant fluctuations in serum (but not in exhaled breath condensate) levels of AAT polymers, IL-8, monocyte chemotactic protein-1, IL-6, tumor necrosis factor- α, and vascular endothelial growth factor within a week of augmentation therapy. In general, augmented individuals had higher AAT and lower serum levels of IL-8 than nonaugmented subjects. Prolastin added for 3 hours to neutrophils from protease inhibitor phenotype ZZ individuals in vitro reduced IL-8 release but showed no effect on cytokine/chemokine release from human bronchial epithelial cells.Conclusion: Within a week, augmentation with Prolastin induced fluctuations in serum levels of AAT polymers and cytokine/chemokines but specifically lowered IL-8 levels. It remains to be determined whether these effects are related to the Prolastin preparation per se or to the therapeutic efficacy of augmentation with AAT.Keywords: Prolastin, augmentation therapy, cytokines, IL-8, exhaled breath condensate, neutrophils

WS5.1 Inhaled glutathione in cystic fibrosis M. Griese1, A. Hector2, M. Kappler2, M. Ballmann3, S. Junge3, E. Rietschel4, D. Staab5, S. van Koningsbruggen4, C. Rolinck-Werninghaus5, U. Mellis6, T. Kohnlein3, T. Wagner7, C. Corner-Rettberg8, H. Teschler6, E. Heuer9, M. Kopp10, S. Heyder11, J. Hammermann12, P. Kuster13, A. Reimann14, M. Honer14, U. Mansmann2, C. Eismann2, German IGOR-Study Group. 1University of Munich, Children’s Hospital, Munich, Germany; 2University of Munich, Munich, Germany; 3Medical School Hannover, Hannover, Germany; 4University of Cologne, Cologne, Germany; 5Charite, Berlin, Germany; 6University of Essen, Essen, Germany; 7University of Frankfurt, Frankfurt, Germany; 8University of Bochum, Bochum, Germany; 9Praxis, Hamburg, Germany; 10University of Freiburg, Freiburg, Germany; 11University of Leipzig, Leipzig, Germany; 12University of Dresden, Dresden, Germany; 13Clemenshospital, Munster, Germany; 14Mukoviszidose-Institut, Bonn, Germany

Bronchoalveolar lavage (BAL) provides a simple method of sampling inhaled particles deposited in the lower respiratory tract. We hypothesized that BAL could be used to measure the quantity and quality of lung asbestos burden. This would be true if BAL fluid asbestos fiber content reflected the total content as well as the size distribution of both uncoated and coated asbestos fibers in lung parenchyma. Therefore, we analyzed the asbestos fiber counts of 23 individual sample pairs in both BAL fluid and lung tissue samples obtained from 20 patients with occupational asbestos exposure using transmission electron microscopy (TEM). In addition, fiber type, fiber size, and aspect ratio were compared. Coated asbestos fibers were found in 10 of 23 BAL samples and 16 of 23 biopsies. The mean concentrations of coated asbestos fibers (i.e., asbestos bodies) in BAL and lung parenchyma showed a positive correlation (r = 0.75, p < 0.001). Likewise, the mean amphibole fiber concentrations correlated positively (r = 0.55, p < 0.01). However, there was no relationship between the mean chrysotile fiber counts in BAL and lung parenchyma (r = 0.18, p = 0.40). Asbestos fibers in lung tissue were significantly longer (8.2 +/- 0.5 versus 4.8 +/- 0.6 microns; p < 0.001) but had the same width (0.12 +/- 0.27 versus 0.11 +/- 0.15 microns; p = 0.24) when compared with those retrieved by BAL from the airspace compartment. The aspect ratio (dividing fiber length by width) was much higher in lung tissue than in BAL fluid (66.4 +/- 0.4 versus 42.9 +/- 0.5; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Asbestos-related lung diseases tend to have distinct local distributions, for example, asbestosis first appears and tends to be more severe in the peripheral parts of the lower lung zones. The risk for asbestosis is related to the total asbestos burden of the lung. This suggests that the lower lobes in asbestos-exposed individuals may contain more asbestos than the other lobes. To test whether such topographic differences exist, we compared the number of retrieved asbestos bodies (AB) per ml BAL fluid in three groups of occupationally asbestos-exposed subjects who underwent BAL at different sampling sites. In Group 1 (n = 24) we performed BAL at three sites, namely in a segment of the right upper, right middle, and right lower lobe, to evaluate differences in asbestos body burden from lung apex to basis. There was a distinct increase in BAL asbestos body concentrations from the upper (21.2 +/- 9.1 AB/ml BAL fluid) to the middle (30.4 +/- 12.8 AB/ml BAL fluid) and to the lower lobe (56.0 +/- 20.2 AB/ml BAL fluid), all differences being significant (p0.01). In Group 2 (n = 40), we found good interlobar correlations for asbestos body counts between the right middle lobe (21.0 +/- 5.8 AB/ml BAL fluid) and the lingula (22.4 +/- 5.9 AB/ml BAL fluid) (r = 0.941, p0.001) and, in Group 3 (n = 15), between the ventral basal segment of the right (41.2 +/- 13.6 AB/ml BAL fluid) and left lung (39.0 +/- 13.6 AB/ml BAL fluid) (r = 0.966, p0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The expression of maturation-associated antigens on alveolar macrophages (AMs) was studied in bronchoalveolar fluid of 30 patients with sarcoidosis and 11 control subjects. The percent of AMs expressing CD14 or CD11b (common for blood monocytes) was significantly increased in patients with active sarcoidosis compared to those with inactive disease, and control subjects. On the other hand, the mean expression of antigens characteristic for mature macrophages showed no significant difference (25F9), or was even increased in patients with sarcoidosis (CD71, KiM8). Since CD14 and CD11b molecules were also frequently expressed on large phagocytes morphologically similar to mature macrophages, and recent studies showed modulation of these glycoproteins by the activation of myeloid cells, our data indicate that the majority of AMs recovered by bronchoalveolar lavage in sarcoidosis are mature, activated cells.

Background: Tacrolimus (TAC) dosing in lung transplantation is traditionally based on blood trough levels (C0). Best sampling strategy for estimation of total drug exposure (area-under-the-curve, AUC) has not been determined. Methods: Thirty-one 12 hour pharmacokinetic profiles were studied in 15 patients (8 men and 7 women, 42.0 13 years) post bilateral lung transplantation (7.3 3.7 months, range 3–18 months). 12 hour AUC (AUC0-12) was calculated by trapezoidal rule. Relationships between individual concentration points or abbreviated kinetics (2–4 concentration points) and AUC0-12 was determined by linear regression analysis (R; absolute prediction error, APE). Results: Pharmacokinetic profiles showed high variability, particularly in the absorption phase. AUC was 221 47.2 ng/ml (range 156 –329.3 ng/ml at C0 10 –15 ng/ml and was independent of TAC dose (R 0.002). C0 was poorly predictive of AUC0-12 (R 0.64, APE 16.1 10.9%, range 1.4 –37.8%). Predictive performance for AUC0-12 was highest with abbreviated kinetics using four (C0/C2/ C3/C4: R 0.99, APE.2.6 2.0%, range 0.1–7%) or three concentration points (C0/C2/C4: R 0.98, APE. 2.6 2.1, range 0.1– 9.1%). Of the 2-point kinetics C2/C6 (R 0.96, 5.3 3.7%, range 0.1–12.7%) and C0/C4 (R2 0.94, APE 4.1 2.9%, range 0.5– 11.4%) performed best. Single point strategies (best was C4: R2 0.94, APE 7.1 5.5%, range 0.2–24.1%, all had unacceptably high APE (range 15%). Conclusion: True TAC exposure shows high variability in stable lung transplant patients and is poorly predicted by C0. Abbreviated kinetics covering at least two concentration points between 0 and 4 hours post drug intake are required for accurate estimation of AUC.

Eine segmentale Strukturierung des Korpers ist beim Menschen zu grosen Teilen verloren gegangen, da im Verlauf der phylogenetischen Entwicklung gravitationsbedingte Umstrukturierungen angestosen wurden. Trotz dieser Tatsache sind jedoch segmentale Gliederungen und Zusammenhange erkennbar, die wichtige therapeutische und diagnostische Bedeutung haben. Die Zusammenhange der sog. Segmentalreflektorik lassen sich zum grosen Teil aus der Embryogenese erklaren: In der Embryonalentwicklung entstehen unterschiedliche Zelltypen, die spezifische Funktionen innerhalb eines Segments haben. Wahrend der Segmentierung des Embryos entstehen im dorsolateralen Korperbereich aus dem mesodermalen Gewebe, beidseits ventrolateral von Neuralrohr und Chorda dorsalis, die Ursprungsgewebe der Segmente, die sog. Somiten. Funktion der Somiten ist die Entwicklung der Grundform des embryonalen Korpers und die segmentale Gliederung des mesodermalen Stammgewebes. Im weiteren Entwicklungsverlauf des Embryos bilden sich aus jedem Somiten wichtige Bestandteile des Achsenskeletts und des Bindegewebes aus: ein Dermatom (Dermis), ein Myotom (Rumpf- und Extremitatenmuskulatur) und ein Sklerotom.

In diesem Kapitel wird Husten als ein wichtiges Symptom bei Atemwegs- und Lungenerkrankungen charakterisiert.Grundsatzlich ist Husten ein lebenswichtiger Reflex des menschlichen Korpers zur Reinigung der Trachea und der Atemwege von Fremdkorpern oder Krankheitserregern. Viele Patienten mit einer Erkaltung leiden in den ersten Tagen an akutem Husten, weswegen die Differenzialdiagnose zwischen einer unkomplizierten Erkaltung, akuter Bronchitis oder Exazerbation einer COPD schwierig sein kann. Ein milder Infekt der oberen Atemwege kann mit Halsschmerzen, Schnupfen und gelegentlich auch mit Fieber, Myalgien und Abgeschlagenheit assoziiert sein.

BACKGROUND: Although many different types of physical therapy are commonly applied in the treatment of respiratory disease, there is no good evidence for all of them. Pursed-lips-breathing (PLB) is an easy and commonly used method to help patients with obstructive ventilatory disease to breathe under physical stress. Not each patient with chronic obstructive pulmonary disease (COPD) performs PLB spontaneously. OBJECTIVE: Verification of the null hypothesis that PLB has no benefit for patients with severe COPD. METHODS: A prospective randomised cross-over trial was carried out to test whether PLB can improve functional performance in patients with severe COPD. Patients performed a 6-minute-walk-test (6-MWT) with and without PLB (prevented by a mouthpiece). Heart-rate, O 2 -saturation (pulse oximeter), dyspnoea (modified Borg scale) before and after 6-MWT as well as the walking distance and breaks were measured. RESULTS: The evaluation of 14 patients showed that PLB improved saturation decrease and heart rate acceleration under physical stress. The patients had less subjective dyspnoea and achieved a longer distance in the 6-MWT. CONCLUSIONS: Functional performance of patients with severe COPD can be improved by PLB. Breathlessness and stress on the respiratory system are beneficially modified. Because of the progressive nature of the disease, all COPD patients should be taught PLB.