Celiprolol--review of airways studies.

Celiprolol was compared with chlorthalidone in a double-blind randomized placebo-controlled study of 30 hypertensive or anginal patients with reversible bronchial obstruction. The study consisted of a 4-week placebo run-in period and a 12-week titration period during which the dose of both drugs was increased at 4-week intervals if blood pressure was not reduced adequately. The doses of celiprolol were 200, 400 or 600 mg once daily, whereas those for chlorthalidone were 12.5, 25 or 37.5 mg once daily. Entry criteria were a diastolic blood pressure between 90 to 115 mm Hg, forced expiratory volume in 1 second between 40 and 80% of predicted value, increasing by 15% or more after salbutamol inhalation and the need for occasional bronchodilator therapy. Prophylactic medication for asthma was given at a constant dosage for 1 month before the study and throughout the study. Clinical variables were not significantly changed by either drug, and neither celiprolol nor chlorthalidone had any significant effect on forced expiratory volume in 1 second.

Effects of a beta adrenergic drug and a secretolytic agent on regional mucociliary clearance in patients with COLD.

The effect of clenbuterol, a beta adrenergic drug, and ambroxol, a secretolytic agent, on regional mucociliary clearance and pulmonary radioaerosol distribution was investigated in two groups of 15 patients with COLD in a double-blind cross-over trial with placebo. Clearance rates of inhaled 99mTc-labelled human serum albumin minimicrospheres (HAMM) were determined over upper, middle, lower, central, and peripheral anterior lung regions. Additionally, an index was employed for quantitative analysis of initial pulmonary aerosol distribution in order to detect changes in the site of particle deposition caused by the drugs. Regional measurement of tracheobronchial particle clearance showed clenbuterol to have a significant (P less than 0.05) stimulating effect in 4 of 5 tested pulmonary zones resulting in significantly accelerated whole lung clearance. Ambroxol was effective in only 1 of 5 tested lung areas and did not prove to enhance whole lung clearance significantly. The secretolytic agent was associated with significant (P less than 0.05) improvement of lung aerosol distribution in obstructive emphysematous patients, whereas no significant change in lung deposition of the inhaled particles was encountered in the patients with chronic obstructive bronchitis after either drug regimen.

Nedocromil sodium is more effective than cromolyn sodium for the treatment of chronic reversible obstructive airway disease.

In a multicenter, double-blind, group comparative trial, the efficacy of nedocromil sodium (nedocromil, 4 mg, four times daily [qid]), cromolyn sodium (2 mg, qid), and placebo was compared in patients receiving inhaled beta 2-agonists and inhaled corticosteroids for the treatment of chronic reversible obstructive airway disease. After a 2-week baseline period, 132 patients (8 centers) between the ages of 20 and 75 years entered a 4-week run-in period in which the dose of inhaled corticosteroid was reduced by 50 percent. During the run-in phase, deterioration of symptoms (total symptom score) by ten points qualified patients to enter the 6-week drug trial period. Patients in the nedocromil treatment group showed the most robust and consistent improvements over placebo and cromolyn sodium for all daily dairy variables. Statistically significant improvements over placebo were noted for both active treatment groups for daytime, nighttime, and total symptom score. Symptom scores for nedocromil were statistically significantly improved over both cromolyn sodium and placebo for both daytime and nighttime asthma. Patients treated with nedocromil also demonstrated a significant reduction in the use of nighttime as needed (prn) beta 2-agonists as compared with either the placebo- or cromolyn sodium-treated groups. Only nedocromil-treated patients demonstrated a statistically significant improvement in morning peak expiratory flow rate (PEFR) as compared with placebo. Both nedocromil and cromolyn sodium groups demonstrated statistically significant improvements in afternoon and evening PEFRs. Collectively, the improvements in nighttime symptoms, decreased bronchodilator use, and improved morning PEFR show that patients treated with nedocromil had improved nocturnal symptoms. Pulmonary function tests (FEV1, FVC, PEFR) demonstrated no statistically significant differences between the two active treatments, although trends favored nedocromil for both FEV1 and PEFR. Although symptoms improved in patients treated with cromolyn sodium, the level of symptom control was less than that achieved by nedocromil. As compared with baseline control (regular dose of inhaled steroids), patients treated with nedocromil plus the 50 percent reduced dosage of inhaled corticosteroid consistently demonstrated comparable or better symptom control. Although both active drugs reduced symptoms, nedocromil proved to be more effective than cromolyn sodium for treatment of reversible obstructive airway disease in patients normally well maintained on regimens of low to moderate doses of inhaled corticosteroids.

MRI and CT in the differential diagnosis of pleural disease.

STUDY OBJECTIVE: To explore the role of MRI in the differential diagnosis of pleural disease. PATIENTS: Forty-two patients with pleural disease were included. METHOD: Retrospective study. All patients were examined with both CT and MRI. The morphologic features of pleural lesions and magnetic resonance signal intensity on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted images were evaluated. RESULTS: Mediastinal pleural involvement, circumferential pleural thickening, nodularity, irregularity of pleural contour, and infiltration of the chest wall and/or diaphragm were most suggestive of a malignant cause both on CT and MRI. Pleural calcification on CT was suggestive of a benign cause. Contrary to what has been previously reported in the literature, neither on CT nor on MRI, pleural thickness >1 cm revealed significant difference between malignant and benign pleural disease (p>0.05, chi(2) test). High signal intensity in relation to intercostal muscles on T2-weighted and/or contrast-enhanced T1-weighted images was significantly suggestive for a malignant disease. Using morphologic features in combination with the signal intensity features, MRI had a sensitivity of 100% and a specificity of 93% in the detection of pleural malignancy. CONCLUSION: When signal intensity and morphologic features are assessed, MRI is more useful and therefore superior to CT in differentiation of malignant from benign pleural disease.

Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group.

This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients with mild to moderate asthma. All patients (n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation.

Therapeutic advantage of unequal dosing of theophylline in patients with nocturnal asthma.

Two theophylline treatments were compared in a randomized, multiple-dose, crossover study on 20 patients present with nonallergic bronchial asthma. Both products (E = Euphyllin CR, A = Afonilum Retard) were capsules containing micropellets. They were administered according to the recommendations of the manufactures and differed in the total daily theophylline dose (642 mg versus 500 mg), the partition of this dose (1/3 in the morning and 2/3 in the evening versus equal amounts in the morning and evening) and the timing of the evening dose (2200 hr versus 2000 hr). The patients were off oral theophyllines at least 2 days prior to study onset and no other drugs were allowed to be administered during the testing periods. On the 4th day of each study period, serum theophylline concentrations (STC) and peak expiratory flow rate (PEF) were determined every 2 hr. Compared with the 24-hr PEF reference profile taken prior to study onset, both theophylline treatments produced a significantly higher 24-hr PEF average (mesor). Treatment E resulted in significantly higher mesor than A; in addition, the PEF amplitude relative to the mesor was reduced by treatment E when compared with placebo.

Radioaerosol lung imaging in chronic obstructive airway disease.

Inhalation radioaerosol lung imaging was performed in 22 patients with chronic obstructive lung disease (COLD) and in 8 healthy subjects. Aerosol deposition pattern within the right lung, as recorded by a gamma camera, was expressed by means of the aerosol distribution index (ADI). The degree of airway obstruction as measured by airways resistance (Raw) was significantly correlated with ADI. Differing stages of COLD are characterized by differing radioaerosol images, which may resemble each other in end-stage disease. The readily available radioaerosol technique can disclose the location and magnitude of bronchitic airway alterations and be useful for clinical inhalation lung imaging in multiple views.

[Quantitative radioaerosol lung imaging in healthy subjects and in patients with chronic obstructive lung disease (author's transl)]. / Quantitative Inhalationsszintigraphie bei Lungengesunden und Patienten mit chronisch obstruktiver Atemwegserkrankung.

A quantitative method for study of the penetration, deposition pattern and clearance of inhaled particles (O,5-micron-99Tc-labeled human serum millimicrospheres) in the lung is described. 10 healthy subjects and 15 patients with chronic obstructive lung disease (COLD) were studied. For both groups significant differences in the mean values of two indices describing peripheral particle penetration and particle distribution homogeneity were observed. Mucociliary efficiency has been assessed by evaluating aerosol clearance rates from the whole right lung and from upper, middle, lower, perihilar and peripheral zones of the right lung field. Whereas the total lung clearance of both groups showed no marked difference, there was a statistical significant clearance delay in the patient's group upper and peripheral lung area.

[Radioaerosol lung imaging in small airways disease (author's transl)]. / Inhalationsszintigraphische Befunde bei small airways disease.

Aerosol inhalation lung imaging was performed in 35 asymptomatic smokers who have been selected on the basis of abnormal findings in small airways pulmonary function tests. Qualitative (image inspection) and quantitative (aerosol distribution index = ADI) analysis of the radioaerosol lung patterns was accomplished. Compared to healthy subjects as well as to patients with chronic obstructive lung disease significant differences of mean aerosol distribution homogeneity were observed. A characteristic type of abnormal aerosol pattern, indicating peripheral airways obstruction, was found in 71% of the patients with small airways disease.

[Chronic obstructive respiration disorders imaged by inhalation scintigraphy. Differential diagnosis and early detection using radio-aerosols]. / Die chronisch obstruktive Ventilationsstörung im inhalationsszintigraphischen Bild. Differentialdiagnostik und Früherkennung mit der Radioaerosolmethode.

Inhalation radioaerosol lung imaging was performed in 86 patients with chronic obstructive lung disease (COLD) and in 45 asymptomatic smokers with small airways dysfunction. Within certain limits analysis of abnormal aerosol scans helped distinguish emphysematous from brochitic and asthmatic types of disease. Patients with asthma often responded to bronchodilator treatment and abnormal aerosol images reverted to near normal patterns. Besides a slight aerosol distribution inhomogeneity in the lung periphery, patients with small airways dysfunction showed significant hypodeposition of inhaled particles distal to the ciliated airways. Compared with small airways dysfunction, COLD was associated with an even more decreased aerosol penetrance to the alveoli.

[Alveolar deposition of inhaled radio-aerosol particles in central and peripheral airway obstruction. Methodologic conditions and clinical results]. / Alveoläre Deposition inhalierter Radioaerosolpartikel bei zentraler und peripherer Atemwegsobstruktion.

The degree of alveolar deposition of inhaled microparticles, which is affected by airway patency, was studied in 16 asymptomatic smokers with small airways disease. Compared to healthy subjects (n = 12) as well as to patients with chronic obstructive lung disease (COLD, n = 14) significant differences in mean alveolar particle deposition were encountered. The results indicate that in both patient groups the lower-lung regions were most affected by airway obstruction. In patients with peripheral airways disease there was no difference in the degree of right- and left-lung aerosol deposition whereas in patients with COLD obstructive airway alteration was found to affect preferably the right lung region.

[Comparative scintigraphic analysis of 99mTc aerosol inhalation and 81m Kr ventilation in chronic obstructive bronchial disease]. / Vergleichende szintigraphische Analyse der 99mTc-Aerosol-Inhalation und der 81mKr-Ventilation bei chronisch obstruktiver Bronchialerkrankung.

The usefulness of 99mTc-labelled serum albumin aerosol as a ventilation agent was compared to that of 81mKr gas in normal subjects and in patients with a wide range of pathological pulmonary function. In addition to visual analysis of the scintigrams, lung activity distribution was quantified by an index. In healthy subjects aerosol distribution was very similar to that of 81mKr gas. In patients with persistent obstruction of bronchial air flow, the aerosol tended to penetrate less well than 81mKr gas to the lung periphery and to show a more uneven pulmonary tracer distribution. Consequently the 81mKr gas technique resulted in underestimating bronchial obstructive defects compared with the radioaerosol method. The results indicate that unlike 81mKr gas imaging, small-particle aerosol scintigraphy provides a useful diagnostic technique for the detection of even mild air flow obstructions.

Safety and efficacy of cefixime versus cefaclor in respiratory tract infections.

A randomized controlled study design was used to compare the efficacy of cefixime versus cefaclor in 30 patients suffering from lower respiratory tract infections. Patients were treated with a 10 to 11 day course of cefixime 200 mg b.i.d. or cefaclor 500 mg t.i.d. The overall clinical response (cured and improved) in the 13 evaluable patients of the cefixime group was 100%. 12 of the 14 patients of the cefaclor group were cured or improved. In the two other patients the symptoms remained unchanged. The bacteriological efficacy in both groups was comparable. Adverse effects were not reported during the study.

Bronchoneutral effects in hypertensive asthmatics--celiprolol versus chlorthalidone.

The actions of celiprolol and chlorthalidone on lung function were studied in a randomized double-blind study of 30 patients. At the end of a 4-week placebo run-in period each patient had a supine diastolic blood pressure between 90 and 115 mmHg, and a forced expiratory volume at the first second of expiration (FEV1) 50-80% of the predicted value in patients with bronchial asthma, and between 40% and 70% of the predicted value in patients with chronic airways obstruction. The active treatment period lasted 12 weeks during which patients received either celiprolol, 200-600 mg daily, or chlorthalidone 12.5-37.5 mg daily. Lung function, blood pressure and heart rate were measured and assessed every 2 weeks during active treatment. Systolic and diastolic blood pressures were reduced during treatment with both drugs, but FEV1, forced vital capacity and forced expiratory volume at 25-75% of vital capacity were not significantly altered. These results suggest that celiprolol does not adversely affect pulmonary function in hypertensive patients who also have chronic bronchial obstruction.

Influence of intrinsic sympathomimetic activity (ISA) during beta-adrenoceptor blockade in asthmatics.

1 Ten patients suffering from extrinsic bronchial asthma were examined. 2 In the pretreatment period, the histamine concentration required to produce a 20% decrease of forced expiratory volume in one second (FEV1) was 7.71 mg/ml. 3 Histamine provocation was repeated 2 h after administration of placebo, propranolol 40 mg, pindolol 5 mg or metoprolol 50 mg. After pindolol and metoprolol the histamine concentrations were slightly, but not significantly, lower than after placebo. After propranolol only 3.16 mg/ml histamine was necessary to reduce FEV1 by 20%. 4 This indicates that in equipotent cardiac beta-adrenoceptor blocking doses, in contrast to propranolol, neither pindolol nor metoprolol increased sensitivity to the bronchoconstrictor effects of inhaled histamine.

[Long-term study on a new beta2-sympathicomimetic agent and a combination of an oral theophylline-ethylenediamine with retard effect and hexoprenaline (author's transl)]. / Langzeituntersuchung mit einem neuen beta-2-Sympathikomimetikum (Hexoprenalin) und einer Kombination (orales Theophyllin-äthylendiamin-Präparat mit Retardwirkung + Hexoprenalin).

The effects of a treatment with a new beta2-adrenergic agent (hexoprenaline, Etoscol) as well as a combined therapy of theophylline (Euphylin retard) with the Etoscol on the total resistance were studied on two groups of patients. The therapy resulted in a significant decrease of the total resistance and the combined therapy showed an additional decrease of the resistance values.

Beta 1/beta 2-splitting of bisoprolol.

In an open study with 16 angina pectoris patients with concomitant chronic obstructive bronchitis, the effect of single oral doses of the beta-adrenoceptor antagonist bisoprolol (5, 10, 15, 20, 30, and 40 mg) on blood pressure (BP), heart rate (HR), airway resistance (AWR), and forced expiratory volume in 1 s (FEV1) was investigated. In the dose range between 5 and 20 mg, no increase in AWR and no decrease in FEV1 was observed. Thirty and 40 mg of bisoprolol produced an increase in AWR and a decrease in FEV1. A reduction in BP and HR was observed even after the lowest bisoprolol dose.