Cost effectiveness of fluticasone propionate and flunisolide in the treatment of corticosteroid-naive patients with moderate asthma.

OBJECTIVE: The aim of this study was to determine the cost effectiveness of 2 inhaled corticosteroids, fluticasone propionate and flunisolide, in the management of asthma from a third-party payer perspective in Germany (German Sickness Fund). DESIGN AND SETTING: Direct treatment costs were retrospectively applied to 2 prospective randomised parallel group clinical trials conducted in Germany comparing fluticasone propionate and flunisolide: one 6-week open-label study (n = 332) and one 8-week double-blind study (n = 308) in corticosteroid-naive patients with asthma of moderate severity aged between 18 and 70 years. All costs were adjusted to 1997 Deutschmarks. Efficacy parameters included changes in morning and evening peak expiratory flow rate (PEFR) measurements, the number of successfully treated patients (defined as those with a PEFR improvement of > or = 10%) and proportion of symptom-free days. MAIN OUTCOME MEASURES AND RESULTS: The fluticasone propionate groups had higher respective proportions of successfully treated patients and symptom-free days than the flunisolide groups in both the open-label (56.8 vs 39.6% and 36.4 vs 28.5%) and double-blind (55.3 vs 44.5% and 35.1 vs 31.1%) studies. Improvements in both morning and evening PEFR measurements were also significantly (p < 0.01) greater with fluticasone propionate than with flunisolide. Although average daily treatment costs were slightly higher in the fluticasone propionate groups than in the flunisolide groups, all cost-effectiveness ratios (daily cost per successfully treated patient and daily cost per symptom-free day) favoured fluticasone propionate. Sensitivity analysis showed that these results were robust over a wide range of assumptions. CONCLUSION: In these patients, management with fluticasone propionate was more cost effective than with flunisolide in the German healthcare setting.

Different BALF protein composition in normal children and adults.

UNLABELLED: Quantification of proteins in bronchoalveolar lavage fluid (BALF) is being performed increasingly, because of their potency in elucidating pathophysiological processes and their possible clinical relevance. STUDY POPULATION: 37 normal children (12 female, 25 male, mean age +/- SD 7.9 +/- 3.5 years, range 3-16 years) undergoing elective surgery for nonpulmonary illnesses and 16 healthy adults (all male, mean age +/- SD 24.7 +/- 2.6 years, range 20-28 years, 8 smokers, 8 nonsmokers) have been studied after approval by the ethics committees of both institutions. METHODS: BAL was performed with normal saline in the right middle lobe or one of its segments. Lavage volume was 15 x 20 ml in adults and 3 x 1 ml/kg in children. In adults the first aliquot was processed separately, 2 aliquots of the following were pooled (resulting in 8 different fractions) so that different lavage protocols could be calculated. The concentrations of the plasma-proteins alpha 1-proteinase inhibitor (alpha-1PI), alpha 2-macroglobulin (alpha 2PI), albumin (Alb) and of the locally released proteins myeloperoxidase (MPO), lactoferrin (Lf), elastase (Ela) and fibronectin (Fib) were determined in BALF using chemiluminescence immunoassays. RESULTS: The BALF concentrations of the plasma proteins were higher in children compared to adults. In contrast, concentrations of the locally released proteins were similar in both groups. Protein concentrations in the first recovered aliquot were different from the following in healthy adults with higher values of MPO, Lf and Ela and lower concentrations of alpha 1PI, alpha 2PI and Alb. Subsequent aliquots did not show a progressive dilution of these proteins with increasing lavage volumes. In smokers, BALF concentrations of albumin, alpha 1PI and MPO were higher compared to nonsmokers. CONCLUSION: BALF protein concentrations are different in normal children and adults. These results underscore the necessity to establish independent reference values for children, as could be demonstrated earlier with regard to BAL cell composition.

Endobronchial actinomycosis.

Endobronchial actinomycosis was found to be the cause of right-sided atelectasis and haemoptysis in a 57 year old man without predisposing conditions. Fibreoptic bronchoscopy revealed occlusion of the intermediate bronchus by yellow-white masses. The diagnosis was confirmed histologically and by positive Actinomyces culture from bioptic material. Prolonged antibiotic treatment resulted in complete recovery, without need for surgical resection.

Oxidative metabolism of pulmonary phagocytes in acute pneumonia.

The oxidative response of activated phagocytes is a primary host defense mechanism in pneumonia, but is in addition capable of causing tissue damage. We evaluated amount and significance of the local oxidant production in immunocompetent and immunocompromised pneumonia patients; the relative contribution of neutrophils and alveolar macrophages to the total oxidant load was differentiated using chemiluminescence (CL) with different amplifiers. Luminol-enhanced CL correlated to neutrophil percentage and myeloperoxidase levels in the bronchoalveolar lavage and was markedly increased in both pneumonia groups. Lucigenin-enhanced CL was produced by both phagocyte types and not significantly increased. In both pneumonia groups elevated levels of serum proteins indicated severe alveolocapillary leakage. In conclusion the oxidative response in acute pneumonia was mainly due to neutrophil recruitment and activation; this defense mechanism was preserved even in severely immunocompromised patients.

Characterization of protein-antiproteinase imbalance in bronchoalveolar lavage from patients with pneumonia.

In order to clarify the mode of inactivation of alpha1-proteinase inhibitor (alpha 1-PI) in pneumonia, 21 immunocompetent patients and 19 immunocompromised patients with acute pneumonia (Groups I and II) were studied. Nine patients successfully treated for pneumonia and 10 healthy volunteers served as controls (Groups III and IV, respectively). The concentrations of alpha 1-PI, elastase and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) were determined using a luminometric assay. Elastase inhibition capacity was determined using a colorimetric assay. Thus, the functional activity of alpha 1-PI was calculated. Both elastase and MPO were significantly higher in group I, when compared with the other groups. The mean concentration of alpha 1-PI was significantly higher in patients with acute pneumonia (Group I 13 mg.l-1, Group II 4.22 mg.l-1) than in Groups III and IV (2.65 and 0.33 mg.l-1, respectively), whereas, the proportion of active alpha 1-PI was significantly lower in Group I than in the other groups. Only a small proportion was present as a complex with elastase (ca. 5.9%) or in oxidised form (ca. 4.8%), 85% of alpha 1-PI was irreversibly proteolyzed. This resulted in free elastase activity in 7 of the 40 patients (18%) with acute pneumonia. We conclude that functional activity of alpha 1-PI is markedly impaired due to irreversible proteolysis in acute pneumonia, despite high immunological concentrations.

Intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of mononuclear cell alveolitis in pulmonary sarcoidosis.

BACKGROUND: Alveolitis in pulmonary sarcoidosis is characterised by an accumulation of highly activated macrophages and CD4+ lymphocytes in the alveolar compartment. The role of intercellular adhesion molecule 1 (ICAM-1) expression on alveolar cells has been studied in this context. METHODS: Using a sandwich ELISA technique, ICAM-1 expression on alveolar macrophages from 17 consecutive untreated patients with pulmonary sarcoidosis and six healthy normal volunteers was quantified. In addition, parameters of macrophage activation (tumour necrosis factor alpha (TNF alpha) and superoxide anion release) were evaluated. RESULTS: Significantly elevated expression could be demonstrated on alveolar macrophages from patients with pulmonary sarcoidosis compared with healthy controls (mean (SD) 0.74 (0.24) ELISA units (EU) v 0.46 (0.12) EU). On subdividing the patients into those with active and those with inactive disease, only the former showed increased ICAM-1 levels on alveolar macrophages (0.82 (0.27) EU) compared with control alveolar macrophages. No differences were detected in serum levels of soluble ICAM-1 between patients and controls. ICAM-1 expression on alveolar macrophages from patients with sarcoidosis correlated with the spontaneous release of TNF alpha but not with the release of the superoxide anion by the activated macrophages. There was no correlation with the percentage of lymphocytes or the absolute number of CD4+ cells in bronchoalveolar lavage fluid. CONCLUSIONS: Increased ICAM-1 surface expression on alveolar macrophages reflects disease activity in the pulmonary compartment. Considering the significance of adhesion molecules during antigen presentation and lymphocyte activation, ICAM-1 expression on alveolar macrophages may have an important role in the immune process of pulmonary sarcoidosis.

Diagnostic value of bronchoalveolar lavage in patients with opportunistic and nonopportunistic bacterial pneumonia.

In 29 patients with community-acquired pneumonia, 24 patients with hospital-acquired pneumonia and 35 patients with pneumonia in the immunocompromised host the diagnostic value of bronchoalveolar lavage (BAL) with quantitative bacterial and fungal cultures was studied; 32 patients with noninfectious pulmonary diseases and 14 healthy volunteers served as controls. An infectious etiology could be established in 81% of the pneumonia patients without differences between the three groups; significant infection was associated with colony counts of > or = 10(4) cfu/ml. Prior antibiotic therapy lowered the yield of BAL culture only in community-acquired pneumonia (94% vs 55% positive cultures in untreated vs pretreated patients, p < 0.02). Furthermore the culture results were related to the radiographic extension of pulmonary infiltrates (92% positive cultures in multilobar vs 54% in lobar or segmental infiltrates, p < 0.001). Therapeutic consequences of BAL were shown by resistance of the isolated organisms to predefined empiric treatment regimens in 41% community-acquired pneumonia, 43% pneumonia in the immunocompromised host and 67% hospital-acquired pneumonia patients.

[Oxygen radical formation in pulmonary sarcoidosis. The signs of early macrophage activation]. / Sauerstoffradikalbildung bei pulmonaler Sarkoidose. Zeichen der frühzeitigen Makrophagenaktivierung.

Oxygen radical formation of alveolar macrophages (by luminogenic substrate-intensified chemiluminescence) and the concentrations of phagocyte products myeloperoxidase, elastase and lactoferrin, as well as alpha-proteinase inhibitor and albumin were measured in bronchoalveolar lavage fluid of 28 patients with pulmonary sarcoidosis. There were 15 men and 13 women (mean age 41 [18-62] years), 10 of them with sarcoidosis I, 10 with clinically active sarcoidosis II and 8 with inactive sarcoidosis II. Six healthy persons served as controls. The purpose of the study was to demonstrate the extent of correlation between macrophage activity and stage of sarcoidosis. Patients in stage I had significantly higher luminescence (346 +/- 253 relative light units [RLU] per second) than the controls (117 +/- 29 RLU/s; P less than 0.02). But the difference between controls and patients in clinically active stage II (294 +/- 75 RLU/s) was not significant and the luminescence in patients with clinically inactive stage II was within normal range (119 +/- 33 RLU/s). The concentrations of proteins measured in the lavage fluid was increased, independent of the site of formation. These data indicate that in pulmonary sarcoidosis there exists, early and independent of stage, a marked activation of alveolar macrophages with increased production of oxygen radicals and a resulting increase in permeability of the alveolo-capillary membrane.

[Myeloperoxidase, lactoferrin and elastase in bronchoalveolar lavage and plasma in pneumonia]. / Myeloperoxidase, Lactoferrin und Elastase in bronchoalveolärer Lavage und Plasma bei Pneumonie.

Neutrophilic granulocytes in the lower respiratory tract are of decisive importance for the elimination of pathogenic germs in bacterial pneumonia. On the other hand, the liberation of phagocyte products (e.g. elastase) can result in tissue damage in the parenchyma of the lungs. For this reason, we determined in patients suffering from acute pneumonia (n = 21), in patients with acute pneumonia associated with immunosuppression (n = 12), in patients who had overcome their pneumonia (n = 9) and in controls (n = 17) in bronchoalveolar lavage (BALF) and in plasma, the concentration of the locally produced granulocyte products myeloperoxidase (MPO), lactoferrin (LF) and elastase-alpha 1 proteinase complex (ELA) as well as of the alpha 1 proteinase inhibitor (alpha 1 Pi) and alpha 2 proteinase inhibitor (alpha 2 Pi) via chemoluminescence immunoassay, and compared the same with the differential cell count in the BALF. The protein concentrations were referred to the albumin concentration (Alb) for standardisation. This concentration did not differ significantly between the various patients and control groups. The BALF concentration of ELA in the group with pneumonia (median: 86.3 micrograms/l or 8.5 micrograms/mg Alb) was about eight times higher than in the group of patients suffering from pneumonia with immunosuppression (median: 16 micrograms/l or 1.0 micrograms/l Alb, p less than 0.001) or in whom the pneumonia was no longer present (17.6 micrograms/l or 0.5 micrograms/mg), and approximately 40 times higher than in the control group (3 micrograms/l or 0.2 micrograms/mg, respectively). Similar results were obtained for LF (61 micrograms/mg Alb vs. 11.3; 16.8 and 5.9 micrograms/mg; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Bronchoscopic diagnosis of pneumonia with quantitative microbial count determination]. / Bronchoskopische Pneumoniediagnostik mit quantitativer Keimzahlbestimmung.

Micro-organism counts of bronchoalveolar lavage (BAL) and microbrush swabs were obtained from 40 immunocompetent (group A) and 23 immunosuppressed (group B) patients with nosocomial pneumonia, and a control group consisting of 40 patients with noninfectious pulmonary infiltrates. The sensitivity of BAL was high: 77.5% for group A and 85% for group B, while microbrush swabs gave many false-negative results. Microorganism counts were at or above 10(5) cfu/ml in 32 of 44 examinations (bacterial or mycotic pneumonia), but in only one case of the control group. Lower counts were obtained with localized infection and microorganisms difficult to culture (Aspergilla and Legionella). Granulocytosis in the lavage fluid was demonstrated in 38 of 41 patients with bacterial pneumonia and thus proved useful in the differential diagnosis. In 16 of 40 immunocompetent and 13 of 23 immunosuppressed patients with pneumonia the results were therapeutically of importance. Thus, invasive diagnosis is indicated especially in complicated or treatment-resistant nosocomial infections.

[Long-term substitution in homozygous alpha 1-antitrypsin deficiency. Effect of the proteinase-antiproteinase equilibrium in plasma and sputum]. / Dauersubstitution bei homozygotem alpha 1-Antitrypsin-Mangel. Einfluss auf das Proteinasen-Antiproteinasen-Gleichgewicht in Plasma und Sputum.

Long-term replacement with human alpha 1-antitrypsin (60 mg/kg once a week intravenously) was carried out in seven patients with homozygous alpha 1-antitrypsin deficiency (7 males, mean age 50.8 [40-59] years) and progressive pulmonary emphysema for an average of 16 (13-20) weeks. After at least 12 weeks' therapy the concentrations of alpha 1-antitrypsin, elastase-alpha 1-antitrypsin complex, alpha 2-macroglobulin, lactoferrin and elastase inhibition capacity in plasma and sputum were assayed, these assays being performed before starting the alpha 1-antitrypsin infusion and at various times during the following week. After the infusion the plasma concentration of alpha 1-antitrypsin rose from a depressed initial level (median 1.22 g/l) to a level approximately five times higher (median after 1 hour: 5.96 g/l, P less than 0.001), and then declined exponentially, though it never fell below the threshold of 35% of normal which is regarded as the protective level. Elastase inhibition capacity displayed similar changes (r = 0.85). The sputum concentration of alpha 1-antitrypsin rose more slowly than the plasma concentration; from the initial level (median 8 mg/l) it reached a maximum about four times higher after 24 hours (median 36 mg/l; P less than 0.02). Elastase inhibition capacity rose from 151 mIU/ml (median) before the alpha 1-antitrypsin infusion to 450 mIU/ml at 24 hours. These findings suggest that alpha 1-antitrypsin replacement will have beneficial effects on proteinase-antiproteinase equilibrium. Determination of elastase inhibition capacity in the sputum is suitable for monitoring dosage during replacement therapy.

[The diagnostic value of bronchoalveolar lavage in opportunistic pneumonia following kidney transplantation]. / Diagnostischer Wert der bronchoalveolären Lavage (BAL) bei opportunistischer Pneumonie nach Nierentransplantation.

In 18 renal transplant patients with pneumonia under ciclosporin therapy the diagnostic value of BAL and of covered micro brush smears were compared. In 10 out of 18 cases partly atypical bacterial pathogens were cultivated and cytomegaly was diagnosed 4 times, mycosis twice, whereas 2 cases could not be clarified. A granulocytosis in the differential cell pattern correlated with a bacterial infection.

[IGA concentration in serum, sputum and bronchoalveolar lavage in chronic bronchitis]. / IgA-Konzentration in Serum, Sputum und bronchoalveolärer Lavage bei chronischer Bronchitis.

IgA concentrations in serum, sputum and bronchoalveolar lavage were determined in 11 patients with chronic obstructive lung disease exacerbated by infection and in 22 with similar disease during an infection-free period. Patients with infection had a higher serum-IgA concentration than those without. But there was no difference in sputum-IgA concentration between the two groups. Both for sputum and broncho-alveolar lavage there was a positive correlation between anti-elastolytic inhibition capacity and IgA concentration. In vitro it has been demonstrated that IgA concentration measured immunologically decreases with increasing elastase concentration, in line with increasing free elastolytic activity. Local IgA deficiency in patients with infection apparently results from proteolytic splitting of the immunoglobulin.

[Therapy of pneumologic diseases in the aged]. / Zur Therapie pneumologischer Erkrankungen im Alter.

Chronic obstructive lung disease (COLD), especially obstructive bronchitis and obstructive lung emphysema, are the most common pulmonary diseases of the elderly. In around 10% of over 65's they cause the death of the individual. The aetiology of these phenomena is still not clear. In pathophysiological terms, a loss in lung function occurs during the natural process of aging, pulmonary and extrapulmonary disease and other environmental factors. Any reduction in function of other organ systems must be taken into consideration when ordering therapeutical measures in treating COLD. The following stepwise-orientated scheme can be recommended in the treatment of COLD in elderly patients: Theophylline, beta 2-adrenergic agents, Anticholinergic drugs, Corticoid therapy, Mucolytica and secretolytica, Physiotherapy, Measures to increase arterial pO2 - either with oxygen therapy at home or with Almitrin, Antibiotica.