Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer.

BACKGROUND: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL). METHODS: Patients were randomly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 (arm A) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms. RESULTS: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0-4.2), 4.1 (3.4-4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4-5.9), 5.1 (4.3-6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4-11.6), 9.8 (8.8-11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3-4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms. CONCLUSIONS: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.

Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study.

UNLABELLED: We evaluated asthma control and medication use 5 years after introduction of an inhaled corticosteroid (budesonide via Turbuhaler) in 462 patients with persistent asthma and symptoms of different duration. An early treatment group with symptoms for <2 years (group A) was compared with a delayed treatment group (group B) (median duration 5 years and 3 months). Most patients received budesonide 400 microg twice daily as initial dose. We report 5-year follow-up data on 404 patients (group A n = 253; group B n = 151) and on a few more patients after treatment for 6 months, 1 year and 3 years. At 5 years the mean maintenance doses of budesonide were 412 microg (A) and 825 microg (B), respectively (P<0.001). Nevertheless, treatment goals (normal lung function, normal exercise tolerance, minimal use of reliever medication, no asthma exacerbations) were all statistically significantly more frequently achieved in group A. At 5 years group B patients also used significantly more additional asthma medications, e.g. inhaled long-acting beta2-agonists by 64% compared with 6% in group A. In group A 43 patients (17%) had been able to stop budesonide treatment compared to five patients (3%) in group B. A subgroup of group B patients with higher mean baseline FEV1 values than group A showed nevertheless significantly poorer response. No treatment-related serious adverse events were reported. Budesonide was well tolerated in both groups. CONCLUSION: Duration of asthma symptoms when starting treatment with an inhaled corticosteroid is an important determinant for the response. Early treatment gives significantly better airway function and asthma control than delayed treatment and at lower maintenance doses.

Studies of cytokine levels in bronchoalveolar fluid lavage from patients with interstitial lung diseases.

Cytokine levels in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia (n = 7), allergic alveolitis (n = 11), (cryptogenic) fibrosing alveolitis (n = 8), sarcoidosis (n = 10) were determined, as well as levels in control samples from healthy non-smoking volunteers (n = 11). Fibronectin levels were increased in all the patient categories, the highest absolute levels of fibronectin (100-fold increase) being found in eosinophilic pneumonia and allergic alveolitis. TGF-beta (transforming growth factor-beta) was significantly elevated in allergic alveolitis only. There was a significant difference between allergic alveolitis on the one hand and both sarcoidosis and fibrosing alveolitis on the other. Tumour necrosis factor-alpha (TNF-alpha) was significantly increased in eosinophilic pneumonia and allergic alveolitis; allergic alveolitis and fibrosing alveolitis differed significantly in this respect. Platelet-derived growth factor-BB (PDGF-BB) levels were significantly elevated in allergic alveolitis and fibrosing alveolitis. It was found that the level of PDGF-BB was significantly decreased in the case of sarcoidosis, with no overlapping with allergic alveolitis or fibrosing alveolitis. Interferon-gamma (IFN-gamma) was decreased in all patient categories. A significant difference in extent of the decrease was found between allergic alveolitis and sarcoidosis. The interstitial lung diseases thus differed in the pattern of cytokines expressed, indicating that these cytokines could well be a part of the pathogenic process, and also that the measurement of cytokine levels could be diagnostically useful.

High pleural fluid hyaluronan concentrations in rheumatoid arthritis.

Previous studies have shown that high pleural fluid (Pf) hyaluronan (HYA) concentrations may be due not only to malignant mesothelioma but also to inflammatory diseases. The objective of this study was to evaluate Pf-HYA in various nonmalignant inflammatory pleural disorders. A radiometric assay was used to determine HYA in Pf and serum (S) of 126 patients, 12 of whom had rheumatoid arthritis (RA), 22 tuberculosis, 22 pneumonia, 41 lung cancer, 10 malignant mesothelioma and 19 congestive heart failure. Pf-HYA values were correlated with values for Pf-tumour necrosis factor (TNF)-alpha and Pf-interleukin (IL)-1beta, as determined by radioimmunoassay. The highest median Pf-HYA (125.6 mg x L(-1), range 0.04-386.5 mg x L(-1)) occurred in patients with malignant mesothelioma. Among patients with nonmalignant inflammatory diseases, significantly higher median Pf-HYA were observed in those with rheumatoid arthritis (64.2 mg x L(-1), range 25.8-106.9 mg x L(-1)) than in those with tuberculosis (25.5 mg x L(-1), range 14.9-57.1 mg x L(-1), p<0.0005) or pneumonia (20.9 mg x L(-1), range 9.5-129.4 mg x L(-1), p<0.005). There was no correlation between Pf-HYA and S-HYA. Pf-HYA correlated positively with Pf-TNF-alpha (r=0.62) and Pf-IL-1beta (r=0.52). High pleural fluid hyaluronan occurs not only in malignant mesothelioma, but also in certain nonmalignant inflammatory diseases, especially rheumatoid arthritis. One explanation for the increase in pleural fluid hyaluronan may be local production of proinflammatory cytokines, such as tumour necrosis factor-alpha and interleukin-1beta.

Concomitant chemotherapy and IFN-alpha for small cell lung cancer: a randomized multicenter phase III study.

Patients with any stage of small cell lung cancer were given low-dose interferon-alpha (IFN-alpha) from the first day of treatment as long as possible irrespective of changes in treatment dictated by disease progression. All patients received 6 cycles of the chemotherapy (CT): cisplatin 70 mg/m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1, 2, 3 every 28 days. Seventy-eight patients were assigned to arm 1: CT alone, 75 patients to arm 2: CT + natural IFN-alpha (3 MU three times a week i.m.), and 66 patients to arm 3: CT + recombinant IFN alpha-2a (3 MU three times a week i.m.). There was no difference in median survival between the arms (10.2 months, 10.0 months, 10.1 months, respectively), p = 0.32. The 2-year survival rates were 15%, 3%, and 11%, respectively. Grade 3 and 4 leukopenia occurred more frequently in the IFN arms than in the CT alone arm and resulted in dose reductions. Antibodies occasionally developed to recombinant IFN. We conclude that IFN-alpha can be administered concomitantly with chemotherapy but is probably better kept for maintenance therapy so that optimal full doses of induction CT can be given.

Irradiation of brain metastases from lung cancer: a retrospective study.

A total of 94 patients with brain metastases from lung carcinomas were treated with irradiation of their brain metastases. Two fractionation schedules were applied, a non-conventional one (76 patients) mixing hypofractionation and accelerated hyperfractionation to a total dose of 47 Gy and a conventional one (18 patients), with 3 Gy once a day to a total dose of 30 or 36 Gy. No benefit was found for the non-conventional treatment schedule over the conventional one. A difference in survival was demonstrated between patients whose brain metastases originated from adenocarcinoma or squamous cell carcinoma of the lung with a median survival of 3.5 and 1.9 months, respectively (P = 0.006). Median survival of patients with brain metastases from small cell lung cancer (SCLC) was 2.8 months, and when compared with the squamous cell carcinoma group, there was no statistically improved survival (P = 0.12). There were indications of a better palliative effect in adenocarcinomas compared with squamous or large cell carcinomas. In a few patients (1/22 adenocarcinoma and 7/32 SCLC), the patients were free from malignant cells in the brain at autopsy, demonstrating that irradiation of brain metastases might be efficient in certain patients.

Pleural fluid interferon-gamma and tumour necrosis factor-alpha in tuberculous and rheumatoid pleurisy.

Tuberculous and rheumatoid pleural effusions show features suggesting a strong local cellular immune response. Pleural fluid (Pf) from patients with tuberculosis, rheumatoid arthritis (RA) and other diseases were compared with respect to interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Immunoassays were used to determine Pf-IFN-gamma and Pf-TNF-alpha in 102 patients, including 11 with RA, 31 with verified tuberculosis, 23 with suspected tuberculosis, 11 with pneumonia, 14 with lung cancer and 12 with congestive heart failure. Measurable Pf-IFN-gamma occurred exclusively in patients with verified (median 1.8 ng x mL-1; 95% confidence interval (95% CI) 0.63-4.0 ng x mL-1) or suspected (0.37 ng x mL-1; 95%CI 0-0.7 ng x mL-1) tuberculosis. The highest median Pf-IFN-gamma was observed in those patients who showed a positive pleural fluid culture for Mycobacterium tuberculosis. In pleural effusions due to other diseases, including RA, IFN-gamma was undetectable. The highest Pf-TNF-alpha occurred in verified tuberculosis (median 198 ng x L-1; 95% CI 169-222 ng x L-1) and RA (210 ng x L-1; 95% CI 147-231 ng x L-1). Pleural fluid interferon-gamma is a highly useful marker for diagnosing tuberculous pleurisy. Although tuberculous and rheumatoid pleural effusions share several biochemical features, they are strikingly different with respect to interferon-gamma.

Similar pleural fluid findings in pleuropulmonary tularemia and tuberculous pleurisy.

Biochemical and cellular characteristics of pleural fluid from two patients with pleuropulmonary tularemia and 39 patients with tuberculous pleurisy were compared. High pleural fluid concentrations of adenosine deaminase, lysozyme, and beta 2-microglobulin occurred in both diseases. As is the case with tuberculous pleural effusions, pleural fluid in tularemia showed an abundance of lymphocytes, predominantly CD4-positive T lymphocytes. The similar pleural fluid findings suggest analogous local pathogenetic mechanisms in tularemia and tuberculosis. In the diagnostic evaluation of a lymphocyte-rich exudative pleural effusion with a high adenosine deaminase concentration, a possible cause to consider is tularemia.

Pleural fluid beta-2-microglobulin and angiotensin-converting enzyme concentrations in rheumatoid arthritis and tuberculosis.

Concentrations of beta 2-microglobulin (B2M) and angiotensin-converting enzyme (ACE) were measured in pleural fluid (Pf) and serum (S) of 364 patients with pleural effusions. Eleven patients had rheumatoid arthritis (RA), 36 verified tuberculosis (TB), 15 suspected TB, 120 cancer, 21 empyema, 34 pneumonia, 33 various defined diseases, 67 effusions of unknown aetiology and 27 congestive heart failure. The median concentrations of Pf-B2M and Pf-ACE were significantly higher in patients with RA than in patients with any other disease (p < 0.005). Tuberculous effusions contained higher Pf-ACE concentrations than any other type of non-rheumatoid effusion (p < 0.05). With sensitivities of 91%, the specificity of Pf-B2M and Pf-ACE for the diagnosis of RA was 86% and 55%, respectively. Local cellular immune events probably account for the abundance of B2M and ACE in rheumatoid and tuberculous pleural effusions. Pf-B2M and Pf-ACE determinations may aid in the differentiation of rheumatoid and tuberculous pleurisy from other types of pleural disease.

Neurone-specific enolase levels in pleural effusions in patients with rheumatoid arthritis.

BACKGROUND: High pleural fluid levels of neurone-specific enolase (NSE) have been reported, not only in patients with small cell lung cancer but also in those with chronic inflammatory diseases. METHODS: NSE concentrations were determined in pleural fluid and serum from 342 patients with pleural effusions including 17 with rheumatoid arthritis. RESULTS: The median NSE concentration in pleural fluid was higher in rheumatoid effusions than in any other condition studied. The median pleural fluid:serum NSE ratio was highest in patients with rheumatoid arthritis (11.6) and about unity in all other diseases including small cell lung cancer (0.9). In patients with rheumatoid arthritis pleural fluid concentrations of NSE correlated inversely with pleural fluid glucose concentrations and the pH of the pleural fluid. CONCLUSIONS: A high pleural fluid:serum NSE ratio was found consistently in pleural effusions from patients with rheumatoid disease.

Effect of early vs late intervention with inhaled corticosteroids in asthma.

One hundred five consecutive patients with mild or moderate asthma not earlier treated with inhaled corticosteroids and with a need of an inhaled bronchodilator of three or more doses a week, and/or asthma symptoms during day or night, and/or peak expiratory flow (PEF) or FEV1 less than 75% of predicted normal values were given an inhaled corticosteroid for 2 years (budesonide delivered via an inspiratory flow-driven multidose dry powder inhaler [Turbuhaler]). According to duration of symptoms, they were divided into six groups; from a duration less than 6 months up to a duration more than 10 years. PEF and FEV1 were measured before and after treatment for 3 months, 1 year, and 2 years. In the groups of patients with a duration of symptoms less than 2 years, mean FEV1 and PEF were significantly higher at all time points as compared with the baseline and as compared with the groups of patients with a longer duration of asthma symptoms. The maximum effects were usually seen after 1 year's treatment with maintained control during the second year. A significant negative correlation was found between duration of symptoms and maximum increases in PEF (r = -0.34; p = 0.0006) and FEV1 (r = -0.32; p = 0.0012), a correlation remaining also after correcting for baseline airway function. No correlation was found between the age of the patients or earlier regular use of beta 2-agonists and improvements in airway function. The results give some evidence that early treatment of asthma with an inhaled steroid may prevent patients from developing chronic airway obstruction. They also support current asthma treatment guidelines advocating early introduction of inhaled anti-inflammatory drugs.

Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol.

Inhaled formoterol is a potent selective beta 2-agonist with rapid onset and at least 12-h duration of bronchodilation. The aim of the study was to compare the bronchodilating effect of inhaled formoterol dry powder (dp) 12 micrograms b.i.d. with salbutamol dp 400 micrograms q.i.d. and placebo in patients with reversible obstructive airway disease (ROAD). The study design consisted of a closed 12-week double-blind, placebo-controlled, multicenter trial followed by an open noncomparative, multicenter, 12-month follow-up trial, in which the tolerability of formoterol dp was assessed. A total of 304 patients (146 men, 158 women) aged 18-79 years, ill during 0.1-64 years, were randomized. No demographic or baseline differences were found among the different treatment groups. The bronchodilating effect of formoterol, assessed by morning premedication PEFR, was significantly superior to placebo (P < 0.0001) and salbutamol (P < 0.0001). Efficacy was maintained during the open follow-up study with 12 micrograms b.i.d. in most of the patients. A few patients, however, needed 24 micrograms b.i.d. to control their ROAD. Formoterol 12 micrograms b.i.d. significantly reduced morning and evening asthma symptoms and sleep disturbances, and reduced significantly the need for rescue medication. The tolerability of the three treatment groups was comparable. In conclusion, formoterol 12 micrograms dp b.i.d. was significantly superior to both salbutamol 400 micrograms dp q.i.d. and placebo, and reduced asthma symptoms significantly. Overall, formoterol showed a tolerability profile comparable to that of salbutamol, and no tachyphylaxis was observed during 1 year of treatment.

Alveolar lavage fluid (ALF) of normal volunteer subjects: cytologic, immunocytochemical, and biochemical reference values.

OBJECTIVE: Pooled bronchoalveolar lavage fluid (BALF), the return of lavage, contains both bronchial and alveolar material which differ from each other. Artifacts may be created by filtering, centrifuging and washing cells before cytopreparation. This study presents reference values of healthy volunteers for the alveolar sample, ALF, cytopreparation being performed without filtration or centrifugation. METHODS: Eighteen healthy, non-smoking volunteers underwent a standard bronchoalveolar lavage using 10 aliquots of 20 ml of saline. Excluding the return of the first and second aliquots, the rest were pooled and examined cytologically, immunocytochemically and biochemically. The mean, standard deviation, and 95% confidence limits were calculated for the following variables: amount of return, estimated content of epithelial lining fluid (ELF), total and differential cell counts on filter and cytocentrifuge (CCF) preparations, computed cell counts per unit volume of ALF, distribution of lymphocyte subgroups CD3+CD2, CD4, CD8, CD19, CD25 and CD57, and the ratio of CD4 to CD8, the amounts of lymphocytes in the same subgroups per volume of ALF, and the concentrations of total protein, albumin, immunoglobulins A, G and M, hyaluronic acid, eosinophilic cationic protein (ECP), procollagen III aminoterminal propeptide (PCP) and beta 2-microglobulin in ALF and in ELF, as well as the ratios of the concentrations of the solutes in ALF to the same in serum. RESULTS: The 95% confidence limits of means for the most important variables were as follows: estimated ELF content 0.42-0.74%; total cells in ALF 76.6-143.0 x 10(6) l-1; distribution of inflammatory cells on filter and CCF slides: macrophages 74.9-83.6 and 81.4-90.1%, lymphocytes 13.1-22.5 and 8.1-16.4%, and neutrophils 1.0-4.1 and 0.7-2.7%, respectively; distribution of lymphocyte subsets: CD3+CD2 85.6-90.6%, CD4 44.3-53.1%, CD8 26.9-35.8%; concentration of solutes in ALF: total protein 44.8-61.3 mg l-1, albumin 15.4-22.2 mg l-1, IgA 1.8-3.4 mg l-1, IgG 3.1-6.1 mg l-1, IgM 0.05-0.26 mg l-1, hyaluronic acid 8.8-11.1 micrograms l-1, ECP 0.19-0.77 micrograms l-1, PCP 0.005-0.58 micrograms l-1, beta 2-microglobulin 62.2-81.5 micrograms l-1. CONCLUSIONS: Our results show that excluding the bronchial sample from ALF of volunteer subjects and omitting filtering and washing before cytopreparation produces cytologic, immunocytochemical and biochemical reference values with reasonable 95% confidence limits to be used in clinical settings.

Clinical efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI with volumatic spacer. A 2-year randomized study in 102 asthma patients.

A total of 102 patients had their asthma treatment with beclomethasone dipropionate (BDP) optimized in order to achieve the best possible control of symptoms. Thereafter, the BDP doses were gradually reduced over a 2-year period (1988-90) to the lowest possible without deterioration of their asthmatic condition. In the beginning of 1990, treatment was changed in 76 patients (group A) to the nearest possible dose of budesonide delivered via Turbuhaler. Twenty-six randomly selected patients (25% of the study population; group B) continued treatment with BDP. In both groups, dose reductions were tried during 1990-2 every third month as long as the patients remained symptom-free and without significant decreases in FEV1 or PEF. In group A, the maintenance dose could be reduced from 1003.9 +/- 325.4 micrograms BDP (mean +/- SD) to 602.9 +/- 454.4 micrograms budesonide Turbuhaler (P < 0.001). In group B, no significant dose reduction was possible; the mean dose was +/- SD 1067.3 +/- 36.6 micrograms in 1990, and 1019.2 +/- 324.7 micrograms in 1992. The results indicate that, in efficacy, 0.6 mg budesonide Turbuhaler corresponds to approximately 1.0 mg BDP with volumatic spacer. This difference is probably due to an improved pulmonary delivery of budesonide with Turbuhaler.

Local side-effects during 4-year treatment with inhaled corticosteroids--a comparison between pressurized metered-dose inhalers and Turbuhaler.

Local side-effects, such as hoarseness and oropharyngeal candidiasis, are often seen during treatment of patients with inhaled corticosteroids (ICS). We investigated whether changing from pressurized metered-dose inhalers (pMDI) to Turbuhaler influenced the type and frequency of local side-effects. Local side-effects were recorded for a 2-year period in which 154 patients used ICS pMDI with a spacer device. They were followed for an equally long period of time (26.2 +/- 5.7 months) while using Turbuhaler, as were 90 patients who received Turbuhaler as their first ICS preparation. After inhalation, all patients rinsed out their mouths with water. In experienced pMDI-users, the frequency of local side-effects decreased from 21% to 6%. The reduction was due to a lower incidence of hoarseness. Candidiasis or hoarseness was not seen in patients given Turbuhaler as their first ICS device. Our fear of an increased incidence of local side-effects when giving ICS in Turbuhaler was unwarranted.

Comparison of terbutaline and placebo from a pressurised metered dose inhaler and a dry powder inhaler in a subgroup of patients with asthma.

BACKGROUND: Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients. METHODS: Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler). RESULTS: Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%). CONCLUSIONS: Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown.

Pleural fluid soluble interleukin 2 receptor in rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To study local cellular immune reactions in the pleural fluid of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Using an immunoenzymometric assay, the concentration of soluble interleukin 2 receptor (sIL-2R) was measured in the pleural fluid of 13 patients with RA, 6 patients with SLE and 72 patients with pleural effusions of other etiologies, including tuberculosis, cancer, pneumonia and congestive heart failure. RESULTS: The mean pleural fluid sIL-2R concentration was significantly higher in patients with RA (593 pM, range 252-1558) than in patients with SLE (145 pM, range 94-236; p < 0.005), cancer (224 pM, range 98-521, p < 0.01), pneumonia (177 pM, range 60-343, p < 0.005) and congestive heart failure (139 pM, range 56-228, p < 0.005), but as high in patients with tuberculous pleurisy (mean 390 pM, range 151-512). The highest mean pleural fluid to serum sIL-2R ratios were observed in patients with RA and with tuberculosis. CONCLUSION: Measurement of sIL-2R in pleural fluid is useful for the differentiation of pleural effusions in RA from those occurring in SLE. High levels of sIL-2R associated with a local T cell mediated immune reaction may serve an immunoregulatory purpose in rheumatoid pleurisy.

Inhaled budesonide for maintenance treatment of pulmonary sarcoidosis.

Forty-seven patients with pulmonary sarcoidosis stage II-III, fulfilling clinical indications for starting treatment with corticosteroids, received oral methylprednisolone for 8 weeks in gradually decreasing doses (starting dose 48 mg per day). From week 5 onwards, they also received inhaled budesonide, 1.6 mg daily. Treatment was continued for 18 months and all patients have been followed for at least 3 years. At 18 months treatment could be discontinued in 38 patients, who had used individually adjusted doses of budesonide depending on the clinical response (reduced doses in 14, initial dose in 16, and increased doses in 8 patients). Budesonide treatment alone was satisfactory in 31 of these 38 cases. An additional seven patients could stop treatment after receiving supplementary courses of oral steroids for 3-12 months. Treatment is ongoing in 9 patients in which 6 have extrapulmonary manifestations requiring oral steroids. The chest radiograph became normal in 22 patients and improved in 14. Significant improvements were noted in FVC and DLco in relation to predicted normal values. Serum ACE, lysozyme and beta 2-microglobulin values decreased significantly. Transient cough was seen in 5 and hoarseness in 3 patients. No systemic side-effects were noted; one patient taking 2.4 mg budesonide daily had a plasma cortisol value below the normal range. Inhaled budesonide seems to offer an effective and safe alternative to oral steroids for long-term maintenance treatment of patients with pulmonary sarcoidosis.

High concentrations of eosinophil cationic protein and eosinophil protein X in eosinophilic pleural effusions.

To analyze the association of the eosinophil granulocyte with pleural effusions, we measured the concentrations of two eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), in pleural fluid and serum of 92 patients with pleural effusions of various causes. We observed significantly higher ECP and EPX concentrations in eosinophilic than in noneosinophilic pleural effusions (p < 0.001 and p < 0.05, respectively) and a positive correlation between the concentrations of both eosinophil proteins in pleural fluid and the total number of eosinophils in pleural fluid (ECP: r = 0.66, p < 0.0001; and EPX: r = 0.62, p < 0.0001). There was a positive correlation between the concentrations of ECP in pleural fluid and serum (r = 0.74, p < 0.0001) and between the concentrations of EPX in pleural fluid and serum (r = 0.41, p < 0.001). High ECP and EPX concentrations in pleural fluid indicated nonspecific etiology and not tuberculosis as the cause of the effusion. Our results suggest that eosinophils in pleural effusions release eosinophil proteins and probably actively participate in the local inflammatory reaction.