Emphysema: Imaging for Endoscopic Lung Volume Reduction.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is characterized by two entities, the more airway-predominant type ("bronchitis") on the one hand, and emphysema-predominant type on the other. Imaging via high-resolution computed tomography plays an important role in phenotyping COPD. For patients with advanced lung emphysema, new endoscopic lung volume reduction therapies (ELVR) have been developed. Proper selection of suitable patients requires thin-section reconstruction of volumetric CT image data sets also in coronal and sagittal orientation are required. In the current manuscript we will describe emphysema subtypes (centrilobular, paraseptal, panlobular), options for quantifying emphysema and this importance of regional distribution (homogeneous or heterogeneous, target area) as this is crucial for patient selection. Analysis of the interlobular fissures is obligatory despite the lack of standardization, as incomplete fissures indicate collateral ventilation (CV) via parenchymal bridges, which is an important criterion in choosing endoscopic methods of LVR. Every radiologist should be familiar with modern LVR therapies such as valves and coils, and furthermore should know what a lung doctor expects from radiologic evaluation (before and after ELVR). Finally we present a checklist as a quick reference for all steps concerning imaging for ELVR. KEY POINTS: • High-resolution computed tomography with 3 D reconstructions becomes increasingly important in phenotyping COPD and diagnosing emphysema. • Patient selection is crucial for modern techniques of lung volume reduction, such as valves or coils. • Radiology plays a key role for fissural analysis and identifying a target area. • Success of this therapy depends on experience and multidisciplinary cooperation.

[pH-Testing - experience in clinical practice in a pulmonary division]. / pH-Metrie - Erfahrungen im klinischen Alltag einer pneumologischen Abteilung.

UNLABELLED: The association between lung disease and gastroesophageal reflux has been discussed for a long time. Aim of this retrospective study was to clarify evidence and acceptance of pH-testing in a pulmonary division. METHOD: pH-testing data at the Krankenhaus Grosshansdorf from January 2000 till March 2004 was evaluated and clinical and pulmonary functional data assessed. RESULTS: A total of 186 patients (113 female, 73 male) received a pH-monitoring. The most important indication was chronic cough (94.6 %). Of 165 evaluable subjects, 63 patients had asthma, 54 patients chronic cough, 18 COPD and 30 patients various diseases (fibrosis, pneumonia, tuberculosis, bronchiectasis a. s. o.). 51 % of patients showed a pathological gastroesophageal reflux (median DeMeester score 22.3). Neither BMI nor patient subgroups correlated significantly with DeMeester score. In 62 % of asthmatics, 57 % of patients with chronic cough and 33 % of COPD patients a pathological reflux was found. In the subgroup with various diseases there was pathological reflux detected in 30 %. CONCLUSIONS: pH-testing is a reliable and safe method to determine gastroesophageal reflux in pulmonary diseases. Pathological reflux is frequently found even without typical symptoms. It remains unclear whether there is a causal relationship.

The effect of 1 ppm nitrogen dioxide on bronchoalveolar lavage cells and inflammatory mediators in normal and asthmatic subjects.

Several studies have suggested that patients with bronchial asthma are more susceptible to the potential effects of nitrogen dioxide (NO2) than healthy subjects, with respect to airway responsiveness and lung function. We investigated whether these differences are paralleled by differences in the cellular and biochemical response within the airway lumen. Twelve subjects with mild extrinsic asthma and eight normal subjects breathed either filtered air or 1 ppm NO2 in a single-blind manner during intermittent exercise for 3 h. Bronchoscopy with bronchoalveolar lavage (BAL) was performed one hour after each exposure, and on a third day without exposure (baseline day). Prostanoids, leukotrienes and histamine were analysed in BAL fluid, and the cellular composition of BAL fluid was assessed. In the asthmatic subjects, NO2 induced a small mean drop in forced expiratory volume in one second (FEV1). Differential cell counts in BAL fluid did not reveal significant effects of NO2. Levels of 6-keto-prostaglandin1 alpha (6-keto-PGF1 alpha) were decreased, and levels of thromboxane B2 (TxB2) and prostaglandin D2 (PGD2) in BAL fluid were increased after NO2 compared to filtered air exposure; whereas, prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), histamine and leukotriene levels did not change significantly. The normal subjects showed no change in lung function parameters and a small increase in TxB2 after breathing NO2. We conclude that in subjects with mild asthma NO2 is capable of inducing an activation of cells, which is compatible with enhancement of airway inflammation, even if lung function parameters and cellular composition of BAL fluid are not markedly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein profile in bronchoalveolar lavage fluid from patients with sarcoidosis and idiopathic pulmonary fibrosis as revealed by SDS-PAGE electrophoresis and western blot analysis.

So far bronchoalveolar lavage (BAL)-protein in interstitial lung disease (ILD) is evaluated by measuring concentrations of single proteins. Due to the high dilution of most proteins in BAL, analysis of protein profile has been disappointing. This study describes a new method to overcome this problem and to reveal a highly differentiated picture of BAL proteins. Eighteen patients with pulmonary sarcoidosis, 18 patients with idiopathic pulmonary fibrosis (IPF) and 22 patients with no clinical, roentgenologic or functional evidence of ILD underwent BAL. Total and differential cell count was performed. Normal values for the control group, a lymphocytic alveolitis in sarcoidosis and a granulocytic alveolitis in IPF-patients were found. Median total protein concentration in sarcoidosis showed an increase five times higher than that of the controls (150 mg 1(-1) and 27 mg 1(-1), respectively) with p < 0.001, IPF protein concentration (58 mg 1(-1)) exceeded twice the control values (0.01 > p > 0.001). Analysis of electrophoretic protein profile in controls with Western blot analysis and the biotin/streptavidin staining system revealed a highly differentiated range of bands. Staining with immunoglobulin antibody identified six bands. Four proteins with molecular weight < 21.000 dalton were present only in sarcoidosis patients. These proteins may be identical with fragmented serum proteins or different cell mediators detected in alveolar cell supernatants. Furthermore, in sarcoidosis the intensity and number of bands with molecular weight more than 67.000 dalton was increased. This gives strong evidence for an injury of the alveolar membrane integrity in the alveolitis during the course of sarcoidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute passive smoking on exercise-induced bronchoconstriction in asthmatic children.

This study was designed to investigate the acute effects of environmental tobacco smoke (ETS) in children with mild asthma during rest and exercise. We studied 13 children [8 males, 5 females; mean age 10 (range 8-13) yr; mean forced expired volume in 1 s (FEV1) 93% (range 82-108%) of predicted] with exercise-induced bronchoconstriction [46 +/- 4% (SE) fall in FEV1 after exercise during cold air breathing]. Children were exposed to ETS (20 ppm carbon monoxide) or ambient air (AA) for 1 h. During the first 54 min of exposure, children were at rest, and during the last 6 min they exercised on a bicycle ergometer (2 W/kg body wt). Spirometry was performed before and during exposure and after exercise. Respiratory symptoms were recorded before and after exposures. In seven children the experiments with AA and ETS were done in duplicate. FEV1 between 5 and 54 min of exposure at rest decreased by 3.2 +/- 0.8% (SE) during AA and by 7.2 +/- 2.3% during ETS exposure compared with preexposure values; the difference between AA and ETS was statistically significant (P = 0.04). The drop in FEV1 was achieved within 5 min and did not change with ongoing exposure. Analysis of individual data revealed that the mean changes during ETS were mainly effected by three children with a significant fall and one child with a significant improvement in FEV1 (P < 0.05). Maximum postexercise fall of FEV1 was 25 +/- 4% after AA and 24 +/- 3% after ETS, which did not differ significantly. Upper and lower respiratory tract symptoms were not significantly different between exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased secretion of tumor necrosis factor-alpha, interleukin-1-beta, and interleukin-6 by alveolar macrophages from patients with sarcoidosis.

BACKGROUND: Alveolar macrophages from patients with sarcoidosis were analyzed for their ability to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta), and interleukin-6 (IL-6). RESULTS: Constitutive release of all three monokines in these patients was concomitantly increased in the active state of disease in comparison with inactive sarcoidosis or healthy control subjects. Alveolar macrophages from patients with inactive sarcoidosis compared with cells from healthy subjects showed increased spontaneous secretion of TNF-alpha and IL-6 only, whereas the constitutive release of IL-1-beta was similar as in healthy volunteers. In vitro stimulation of alveolar macrophages from healthy control subjects with lipopolysaccharide or pokeweed mitogen led to a time- and dose-dependent enhanced secretion of TNF-alpha, IL-1-beta, and IL-6. In a similar manner, with corresponding cells from patients with sarcoidosis the secretion of all three cytokines could be further increased by stimulation with lipopolysaccharide or pokeweed mitogen. CONCLUSIONS: The data presented indicate that an increased release of TNF-alpha, IL-1-beta, and IL-6 correlates to disease activity and may play a critical part in the pathogenesis of sarcoidosis.

Increased LTB4 metabolites and PGD2 in BAL fluid after methacholine challenge in asthmatic subjects.

The bronchoconstrictor potency of inhaled methacholine is widely used to assess airway responsiveness. However, evidence has accumulated that methacholine inhalation challenge may lead to an inflammatory response in the lower respiratory tract. We therefore compared cellular, leukotriene and prostanoid profiles in bronchoalveolar lavages (BAL) obtained five hours after methacholine challenge to control lavages without prior challenge. Eight subjects with asymptomatic to mild bronchial asthma and nine nonatopic healthy controls were enrolled in the study. Without prior challenge, the percentage of BAL eosinophils was higher in the asthmatic subjects ((mean +/- SD), 1.1 +/- 0.9%) than in the control subjects (0.1 +/- 0.1%. Leukotriene B4 (LTB4), and its omega-oxidation products (20-OH-LTB4 and 20-COOH-LTB4) were the only leukotrienes detectable in the baseline BAL fluids in five of the eight asthmatic patients. After methacholine challenge, no change in BAL cell profile occurred, but in the asthmatic patients, the total amounts of LTB4 and its omega-oxidation products rose from 0.52 +/- 0.50 ng.ml-1 (pre-challenge) to 1.55 +/- 1.32 ng.ml-1 (post-challenge), and prostaglandin D2 (PGD2) rose from 49.1 +/- 15.7 (pre-challenge) to 94.4 +/- 25.4 pg.ml-1 (post-challenge), with no change in 6-keto-PGF1 alpha, thromboxane B2 (TXB2), and prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2). In the healthy controls, no consistent change in BAL cell profile and mediators occurred after methacholine provocation. We conclude that inhaled methacholine stimulates LTB4 and PGD2 release in asthmatics, but not in healthy controls, without affecting the number of inflammatory cells in BAL fluid.

Effect of one hour of passive cigarette smoking on lung function and airway responsiveness in adults and children with asthma.

We exposed 18 adults with bronchial asthma, 16 healthy controls and 11 children with asthma for 1 h either to ambient air (AA) or to environmental tobacco smoke (ETS). Exposure was performed at rest in an exposure chamber. Before and after exposure symptom scores and lung function were determined. After exposure bronchoprovocation tests with methacholine (adults) or histamine (children) were performed to determine the concentrations causing a 100% increase in SRaw (PC100SRaw), and a 20% fall in FEV1 (PC20FEV1). In adult asthmatics mean (SD) SRaw before and after Sham was 8.8 (3.6) and 8.4 (3.6) cmH2O.s, and mean FEV1 (SD) was 3.18 (0.97) and 3.14 (0.9) 1, respectively. Before and after passive smoking mean SRaw (SD) was 7.5 (3.0) and 7.2 (2.7) cmH2O.s, and mean FEV1 (SD) was 3.31 (1.0) and 3.21 (0.88) 1, respectively. Geometric mean (SD) PC100SRaw and PC20FEV1 after Sham were 0.38 (4.5) and 0.29 (4.1) mg/ml, after passive smoking 0.39 (5.1) and 0.36 (4.7) mg/ml, respectively. In healthy controls there was no consistent effect on the respective parameters during exposure. In children mean (SD) SRaw before and after Sham was 8.7 (3.6) and 9.0 (3.2) cmH2O.s, and mean FEV1 (SD) was 1.97 (0.32) and 1.98 (0.40) 1, respectively. Before and after passive smoking mean SRaw (SD) was 10.4 (5.3) and 9.4 (3.3) cmH2O.s, and mean FEV1 (SD) was 1.95 (0.37) and 1.94 (0.35) 1, respectively. Geometric mean (SD) PC100SRaw and PC20FEV1 after Sham were 1.39 (3.0) and 0.70 (2.7) mg/ml, and after passive smoking 1.65 (2.5) and 0.96 (2.3) mg/ml, respectively. There were no significant differences in lung function and airway responsiveness between exposure to ambient air or ETS.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on cultured fibroblasts from patients with cutaneous malignant melanoma.

Cultured fibroblasts from patients with cutaneous malignant melanoma (CMM) were tested for chromosomal instability by determination of micronuclei (MN) and sister chromatide exchange (SCE). The constitutive as well as the UV-induced level of MN was increased in CMM patients, being most pronounced in the familial cases. There was an increased UV sensitivity in CMM by using SCE, but no spontaneously enhanced SCE value. The enhanced UV sensitivity in CMM patients was in a comparable range as those of XP heterozygotes. We thus conclude that chromosomal instability is a concurrent feature of a genetic predisposition for CMM.

Acute effect of passive smoking on lung function and airway responsiveness in asthmatic children.

The effect of a 1-hour exposure at rest during passive cigarette smoking (20 ppm CO) or Sham was investigated in 11 children with bronchial asthma (age range, 8-13 yr; ten boys, one girl). Nine of the subjects were on regular therapy with inhaled beta 2-agonists and disodium cromoglycate. Both drugs were withheld at least 6 hours prior to each study session. Exposure was performed in an environmental chamber. Before and immediately after exposure, lung function and symptom scores were determined. After exposure, a histamine inhalation challenge was performed to determine the concentrations that caused a 100% increase in SRaw (PC100SRaw) and a 20% fall in FEV1, (PC20FEV1). Mean (SD) SRaw before and after Sham was 8.7 (3.6) and 9.0 (3.2) cmH2O.s, and mean FEV1 (SD) was 1.97 (0.32) and 1.98 (0.40) L, respectively. Before and after cigarette smoking, mean SRaw (SD) was 10.4 (5.3) and 9.4 (3.3) cmH2O.s, and mean FEV1 (SD) was 1.95 (0.37) and 1.94 (0.35 L, respectively. Geometric mean (SD) PC100 SRaw and PC20FEV1 after Sham was 1.39 (3.0) and 0.70 (2.7) mg/mL, and after passive smoking 1.65 (2.5) and 0.96 (2.3) mg/mL, respectively. There were no statistical differences in lung function and PC values between Sham and passive cigarette smoking. The main symptoms during passive smoking were irritation of the eye and the nasopharynx. Our observations suggest that in children with mild bronchial asthma 1 hour of passive cigarette smoking does not cause consistent changes of lung function and bronchial responsiveness.

Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma.

Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light.

[Oculocutaneous albinism and brain atrophy]. / Oculocutaner Albinismus und Hirnatrophie.

We present a 4 months old female infant with oculocutaneous albinism and the clinical picture of motor retardation. Otherwise development appears to be normal. The finding of cerebral atrophy by CT scan is discussed as cerebral residual damage after perinatal hypoxia. A possible relation between albinism and CNS-disorder is described.