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The case of a 66-year-old, asymptomatic patient with a papillary adenoma of type-II pneumocytes is reported. Following the coincidental radiologic finding of a solitary pulmonary nodule, the diagnosis could be established in a bronchoscopically obtained endobronchial biopsy. A resection of the involved segments S8-10 on the left side was performed. Papillary adenoma of type-II pneumocytes is a rare tumor, whose origin is suspected in progenitor cells of the bronchioloalveolar epithelium with the potential to differentiate towards type-II pneumocytes and clara cells. The tumor is regarded as benign, however, a malignant potential is not excluded by some authors.

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Lung resection offers the best prospect of long-term survival in patients with nonmetastatic pulmonary neoplasia. In view of the dismal prognosis of unresected bronchial cancer, surgical resection should be encouraged even in patients with reduced cardiopulmonary function. Accurate estimation of the postoperative cardiopulmonary function is therefore desirable to avoid (a) refusal of potentially curative treatment and (b) severe postoperative disability. The origins of post-resection morbidity and mortality are multifactorial. Thus, no single pulmonary function test or hemodynamic measurement can accurately and reliably predict postoperative cardiorespiratory complications. Criteria of functional operability should be based on percent of predicted value, so that patient's age, sex, and height will be taken into consideration. Exercise testing offers the advantage that both pulmonary and cardiac risk can be evaluated simultaneously. The high predictive value of maximal oxygen uptake (VO2max) in assessing postoperative morbidity and mortality is established. The calculation of predicted postoperative lung function (ppo) is of importance. The postoperative values for the forced expiratory volume in one second (FEV1-ppo), the transfer factor (TL,CO-ppo), and VO2max-ppo can be predicted by using the same formula. Patients with nearly normal lung function (FEV1, TL,CO > 75% predicted) and no concomitant cardiac disease can undergo lung resection right up to pneumonectomy without further diagnostic procedures. In the others, FEV1-ppo and TL,CO-ppo should be estimated first by taking into account the number of segments to be resected. Patients with values < 30% predicted are usually regarded as being inoperable, whereas values > 40% predicted qualify for resection without the need for further diagnostics. VO2max < 10 ml/kg/min or < 40% predicted are prohibitive for surgery. If VO2max is > 20 ml/kg/min or > 75% predicted, functional operability without limitation is given. For those cases where diagnostic uncertainty still remains, FEV1-ppo, TL,CO-ppo, and VO2max-ppo can be calculated by means of quantitative lung scans. Patients with either FEV1-ppo and TL,CO-ppo < 30% predicted or VO2max-ppo < 8 ml/kg/min or < 35% predicted are deemed inoperable.

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Silicone and metal stents are available for the treatment of malignant bronchial stenoses. This project sought to compare the self-expanding nitinol Accuflex stent (Boston Scientific Corp; Watertown, Mass) with the passively expandable tantalum Strecker stent (Boston Scientific Corp; Watertown, Mass), both implanted by flexible bronchoscopy under local anesthesia and sedation. In 51 patients with malignant bronchial stenosis, 14 nitinol and 51 tantalum stents were used and stenoses of 75 to 100% were treated. The intervention was successful in all but one patient, a mean patency of 93% was achieved. In the follow-up period, the probability of survival was significantly lower in patients with total bronchus occlusion than in patients with stenotic alteration (44 vs 109 days; p < 0.05). In 10 patients, lung function analysis after stent implantation revealed a significant increase in PaO2 (65 vs 71 mm Hg; p < 0.01), inspiratory vital capacity (2.5 vs 2.7 L; p < 0.05), and FEV1 (1.8 vs 2.0 L; p < 0.05). Mucus retention was the main (39%) adverse factor in the early phase after stent implantation, whereas tumor penetration became the most frequent problem (67%) in the later phase. Recanalizing interventions were necessary in 18% of the cases in which tumor penetration occurred. Stent distortion occurred in 12 patients with Strecker and in none with Accuflex stents. In comparison to the Strecker stent, the self-expanding Accuflex stent is preferable owing to its excellent flexibility and faster delivery system. Both types of stents could be sufficiently deployed within the lesions and allowed for highly precise positioning. Furthermore, no general anesthesia was required. The fiber-bronchoscopy mode of implantation under sedation is very efficient even for tumor patients with severe impairment of their physical and respiratory condition.

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BACKGROUND/AIMS: Pulmonary side effects of interferon-alpha therapy of chronic hepatitis C seem to be rare. So far, only two cases of sarcoidosis in association with interferon-alpha treatment of chronic hepatitis C have been described. METHODS/CASES: We report on three patients who were treated with recombinant interferon-alpha2a for chronic hepatitis C, two of them in combination with ribavirin. These patients developed pulmonary sarcoidosis 12, 20 and 21 weeks, respectively, after beginning interferon therapy, one patient with Löfgren's syndrome. In one patient sarcoidosis emerged only after discontinuation of interferon therapy because of treatment failure. Clinical symptoms of sarcoidosis in the three patients were suggestive of side effects of interferon-alpha. Interferon therapy was discontinued and spontaneous remission was observed in all three cases 5, 6, and 8 months, respectively, after the onset of symptoms. CONCLUSION: The occurrence of sarcoidosis in association with interferon-alpha therapy for chronic hepatitis C may have been underestimated so far. This could be due to the fact that symptoms of sarcoidosis and common side effects of interferon are similar, and sarcoidosis may occur after the end of interferon therapy. We hypothesize that interferon-alpha as a potent stimulator for T-helper 1 (Th1) immune responses may trigger the compartmentalized Th1 reaction that has been shown to take place in sarcoidosis.

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Silicone and metal stents are available for the treatment of malignant bronchial stenoses. This project sought to compare the self-expanding nitinol Accuflex stent (Boston Scientific Corp; Watertown, Mass) with the passively expandable tantalum Strecker stent (Boston Scientific Corp; Watertown, Mass), both implanted by flexible bronchoscopy under local anesthesia and sedation. In 51 patients with malignant bronchial stenosis, 14 nitinol and 51 tantalum stents were used and stenoses of 75 to 100% were treated. The intervention was successful in all but one patient; a mean patency of 93% was achieved. In the follow-up period, the probability of survival was significantly lower in patients with total bronchus occlusion than in patients with stenotic alterations (44 vs 109 days; p<0.05). In 10 patients, lung function analysis after stent implantation revealed a significant increase in PaO2 (65 vs 71 mm Hg; p<0.01), inspiratory vital capacity (2.5 vs 2.7 L; p<0.05), and FEV1 (1.8 vs 2.0 L; p<0.05). Mucus retention was the main (39%) adverse factor in the early phase after stent implantation, whereas tumor penetration became the most frequent problem (67%) in the later phase. Recanalizing interventions were necessary in 18% of the cases in which tumor penetration occurred. Stent distortion occurred in 12 patients with Strecker and in none with Accuflex stents. In comparison to the Strecker stent, the self-expanding Accuflex stent is preferable owing to its excellent flexibility and faster delivery system. Both types of stents could be sufficiently deployed within the lesion and allowed for highly precise positioning. Furthermore, no general anesthesia was required. The fiberbronchoscopic mode of implantation under sedation is very efficient even for tumor patients with severe impairment of their physical and respiratory condition.

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We present a case report of a patient suffering from Behet's syndrome with pulmonary involvement. The development of endobronchial granulomatosis in the bronchus intermedius and right upper lobe bronchus led to severe bronchial stenosis and dyspnoea. Also aphthous ulcerations in the bronchial mucosa occurred. Treatment of the granulomatous stenosis consisted of Neodym-YAG laser resection and immunosuppression. On follow-up there was a recurrence of the stenosis, characterised by fibrotic strictures. Therefore a balloon dilation was performed and immunosuppression instituted, which led to an increase in airway diameter and a reduction in dyspnoea. These clinical results suggest that recanalisation therapy with Neodym-YAG laser and/or balloon dilation with additional immunosuppression is suitable in benign stenosis (granulomatous or fibrotic), caused by Behet's disease.

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Plasma atrial natriuretic peptide (ANP) is an endogenous vasodilator, which might counteract pulmonary hypertension due to hypoxaemia. The aim of this study was to investigate the influence of acute and chronic hypoxia on plasma (ANP) concentrations in humans. Venous plasma ANP concentrations in six healthy subjects were measured before and after inhalation of hypoxic air (11% O2) at rest for 30 min, and following 5 min of mild hypoxic exercise (25 W). Pulmonary arterial plasma ANP levels were determined in 31 right heart catheterized patients with lung disease. In healthy subjects, mean arterial oxygen tension (Pao2) was 6.8 +/- 1.9 kPa after 30 min hypoxia at rest, and 4.7 +/- 0.9 kPa after hypoxic exercise testing. Hypoxia at rest did not induce significant changes in ANP concentrations, whereas hypoxic exercise led to significantly increased ANP levels. Among hypoxaemic patients, significantly elevated plasma ANP levels were found only in the subgroup with increased mean pulmonary artery pressure, but not in the subgroup with normal pulmonary artery pressure. In summary, severe acute hypoxia induced by hypoxic exercise, but not moderate acute hypoxia at rest, leads to increased ANP levels in healthy subjects. Chronic hypoxia alone does not lead to elevated plasma ANP levels; whereas, hypoxia combined with pulmonary hypertension causes increased plasma ANP concentrations in diseased subjects.

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Pulmonary and laryngeal manifestations of localized and organ-limited amyloidosis are sometimes seen, although pulmonary and laryngeotracheal amyloidosis are not always associated. Diagnosis can only be established histologically by the characteristic green birefringence in polarized light after Congo red staining and by immunohistochemical techniques. We describe the case of a 77-year-old woman who presented with hoarseness and an unproductive cough due to extensive amyloid deposits in both the upper and lower respiratory tract, immunohistochemically proven as the A lambda-type.

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Plasma samples from 5 asthma patients were taken in 4-h intervals before and 1, 2, 4 and 6 h after the oral application of 100 mg methylprednisolone. Reversed-phase HPLC allowed simultaneous measurement of both endogenous hydrocortisone and exogeneous methylprednisolone. Suppression of endogeneous hydrocortisone secretion occurs immediately after administration of a single oral dose of an exogeneous glucocorticoid and cannot be avoided by morning application.

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1. The pharmacological actions of the beta-adrenoceptor antagonists, celiprolol, bisoprolol and propranolol were investigated in human lung tissue by radioligand binding experiments as well as in human isolated bronchi by functional experiments in organ baths. 2. Data from lung tissue were compared to those obtained from myocardial membranes. 3. Lung tissue was obtained from 10 patients having undergone lung resection for bronchial carcinoma and myocardial tissue from a patient who had received a heart transplantation. 4. In radioligand binding experiments, celiprolol exhibited a high affinity binding to beta 1-adrenoceptors in heart and a low affinity binding to beta 2-adrenoceptors in lung tissue. The selectivity obtained for the beta 1-adrenoceptor was calculated to a factor of eleven. 5. Compared to bisoprolol and propranolol, celiprolol elicited the lowest affinity for the beta-adrenoceptor, as judged from the K1-values. 6. In the absence and presence of the guanine nucleotide Gpp(NH)p celiprolol did not affect receptor binding. 7. In functional experiments on intact bronchi, celiprolol, bisoprolol and propranolol failed to produce relaxation (+/- forskolin) or a significant difference in efficacy in antagonizing the relaxant effects of isoprenaline. However, a rank order of potencies was revealed (propranolol:bisoprolol:celiprolol = 46:12:1). 8. Plasma concentrations for celiprolol and bisoprolol usually achieved in vivo were below the IC50 value obtained in vitro. In contrast, for propranolol, plasma concentrations were nearly identical with the IC50 value. 9. It is concluded that celiprolol is a selective beta 1-adrenoceptor antagonist on human heart and has no agonistic properties on intact human bronchi. Compounds such as celiprolol and bisoprolol may in comparison to propranolol, possess reasonable therapeutic advantages in the treatment of patients with obstructive lung disease due to their low affinity for beta 2-adrenoceptors.

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Lung cancer is a leading cancer site in men and women with a high incidence and mortality rate. Most patients are diagnosed when the disease has already spread. An early, detection and immediate and accurate histological or cytological diagnosis are essential for a hopeful outcome. In most patients, bronchoscopy is the method of choice in establishing a suspected lung neoplasm. With the rigid and flexible method, two complementary techniques are available. The methods bear a very low mortality rate if sufficient monitoring and resuscitative instrumentation is available. Rigid bronchoscopy offers the possibility of obtaining large biopsy specimens from the tumorous tissue and provides an effective tool in the control of major haemorrhage. However, it cannot be used for the inspection of further peripherally located parts of the bronchial system and needs general anaesthesia. In contrast, the flexible method can be quickly and readily performed at practically any location using portable equipment. Bronchi can be inspected up to the 8th order and with bronchial washing, forceps biopsy, brush biopsy and fluorescence bronchoscopy techniques with a high diagnostic yield are available. This holds true, especially if these sampling techniques are used as complementary methods.

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OBJECTIVES: The saccharide ultrasound contrast agent SHU 508 A was used to test the hypothesis that an intravenous, transpulmonary contrast method can enhance color Doppler flow signals in the left atrium in a clinically useful manner. BACKGROUND: Color Doppler display of mitral regurgitation may be unreliable because of variable signal to noise ratios that are at times poor. Traditional contrast agents enhance color Doppler flow signals in the right heart chambers. This study describes our observation of a recently developed contrast agent, SHU 508 A, capable of pulmonary transit after peripheral venous injection. METHODS: Control subjects (n = 10) and patients with suspected mitral regurgitation (n = 23) were studied by color Doppler flow imaging before and after 3-g intravenous doses of SHU 508 A. Reference grading of mitral regurgitation (0 to 3) was formulated from left ventricular angiography. In the four-chamber view of the left atrium, we selected for analysis the systolic frame with the maximal retrograde jet of mitral regurgitation (aliased/blue) and the diastolic frame with the maximal color coding from anterograde pulmonary venous flow (red) for planimetry and for grading the intensity of the color Doppler signal (0 to 5). RESULTS: The score of the color Doppler signal intensity increased by > or = 2.5 after 3 g of SHU 508 A (p < 0.001). Flow detection improved, as shown by the increased jet area of mitral regurgitation (> or = 170%), after 3 g of SHU 508 A (3 +/- 3 vs. 12 +/- 8 cm2, p < 0.001) and by a > or = 200% increase in normal anterograde flow area (p < 0.001) in both the mitral regurgitation group and the control group. After contrast enhancement, the correlation between angiographic grading and the relation of jet area to the left atrial area increased from r = 0.79 to r = 0.91. CONCLUSIONS: Contrast-mediated increased echogenicity of the left atrial blood pool improves the signal to noise ratio of Doppler images of mitral regurgitation and anterograde atrial flow. The technique is safe and simple and seems to minimize variability due to instrument design and anatomic signal attenuation.

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To clarify the mode of action of an oral bacterial extract (OM-85 BV) on local airway immunity pre- and posttherapeutic washings from bronchoalveolar lavage (BAL) fluid of 28 adult patients with nonobstructive chronic bronchitis were analysed. In comparison to healthy controls, an elevation of total cell count due to an increased number of PMN leukocytes, and an impaired activity of the alveolar macrophages measured by the chemiluminescence response to opsonized zymosan was observed in patients with chronic bronchitis. After treatment with OM-85 BV, the BAL CD4+/CD8+ lymphocyte ratio and BAL interferon-gamma levels were increased. The alveolar macrophage activity was normalized and the BAL IgA was regulated from a reduced or hyperelevated to a moderately increased level.

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To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. Plasma cortisol concentrations did not appear to be related to the principal cause of "nocturnal asthma;" they rather reflected an endogenous defense mechanism to the disease.

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In 28 adult patients with nonobstructive chronic bronchitis we investigated components of the immune system of the lower airways and the effects of treatment with Broncho-Vaxom (BV). An analysis of the washing from bronchoalveolar lavage (BAL) showed, in comparison with healthy controls, an elevation of total cell count (p = 0.003) as well as the IgA/albumin values (p = 0.02) and a reduction of the macrophage activity (p less than 0.001) in patients with chronic bronchitis. After BV a reduction in the total cell count (p = 0.05), an increase in the helper/suppressor T lymphocyte ratio (due mainly to the reduction in the suppressor cells; p = 0.04), a modulation of the IgA/albumin ratio, a stimulation of the impaired alveolar macrophage activity (p = 0.03) and increased concentrations of gamma-interferon (p = 0.03) were found in the BAL fluid of patients with chronic bronchitis. The salivary IgA/albumin ratio remained unchanged, the serum IgE concentration fell (p = 0.02) and the urinary IgA concentration rose (p = 0.002). Bronchial mucosa lesions, evaluated endoscopically in terms of structural damage, hyperemia and mucus production, were improved (p less than 0.01). These findings indicate that orally administered BV modulates disordered local and systemic immune functions in patients with chronic bronchitis.

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Our findings demonstrate that Broncho-Vaxom (BV) displays possibly via the gut-associated immune system different effects on the lymphatic system of the lung: a positive influence on the helper/suppressor T-lymphocyte balance, an increase of gamma interferon, a stimulation of the reduced alveolar macrophage activity, and a regulation of BAL IgA to a distinct level whereby the serum IgE is reduced. By these effects BV is able to modulate impaired local and systemic immune function. The observed relationship between the inflammation score and the BAL fluid composition supports the view that the improvement of the mucosa lesion found in nearly all of our patients with chronic bronchitis occurs as the result of the pleiotropic immunomodulating effects of Broncho-Vaxom.

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