An international clinical trial on the efficacy and safety of roxithromycin in 40,000 patients with acute community-acquired respiratory tract infections.

An ongoing eight-country study is being conducted in an unprecedented number of general practice patients with acute upper and lower respiratory tract infections to compare the efficacy and tolerance of roxithromycin 150 mg b.i.d. for 7-14 days with the data acquired in the prelaunch studies of these same parameters. The target population is 40,000 (to be achieved by the end of 1991) and we report the interim results from 32,405 patients, 18,020 with upper and 14,385 with lower respiratory tract infections. In acute pharyngitis/tonsillitis sinusitis, and otitis, clinical resolution or improvement has been achieved in 97%, 96%, and 96% of cases, respectively. The figures for bronchitis, exacerbation of chronic bronchitis, and pneumonia are 97%, 94%, and 95%. Side effects have been reported in only 4% of patients to date, 75% consisting of moderate gastrointestinal upsets. Of the patients, 1% withdrew from treatment because of side effects. These interim figures confirm the data from the prelaunch, controlled comparative trials and show roxithromycin to be an appropriate choice of first-line antibiotic therapy in the management of respiratory tract infections in general practice.

Inhaled beta adrenergic agonists and inhaled steroids in the treatment of asthma.

In summary, inhaled steroids are the treatment to be preferred for patients requiring maintenance therapy with steroids, since they cause a dramatic fall in sensitivity and reactivity of bronchial response, improve lung function to normal, reduce the diurnal variation in peak expiratory flow rates, and markedly reduce symptoms. Nevertheless they must be given at adequate dosage for a long time, associated with inhaled beta-agonists, and in more severe asthma with short courses of oral steroids.

Elevation of the bronchoalveolar concentration of angiotensin I converting enzyme in sarcoidosis.

The concentration of angiotensin converting enzyme (ACE) and that of albumin (AIb) were assayed in the serum (SACE, SAlb) and in bronchoalveolar lavage fluid (LACE, LAlb). Three groups of patients were studied: 14 healthy volunteers (Group I), 45 patients with active sarcoidosis (Group II), and 7 patients with sarcoidosis in remission (Group III). The SACE in Group II (4,466 +/- 2,202 U/100 ml, mean +/- SD) was higher (p less than 0.001) than in Group I (2,470 +/- 547 U/100 ml) or in Group III (2,640 +/- 610 U/100 ml); LACE was higher in Group II (65.2 +/- 48.4 U/100 ml, p less than 0.001) than in Group I (21.1 +/- 14.7 U/100 ml), or in Group III (25.7 +/- 14.6 U/100 ml). The SAlb was found to be, respectively, 3,908 +/- 385 mg/100 ml, 3,982 +/- 965 mg/100 ml, and 3.613 +/- 222 mg/100 ml in Groups I, II, and III. The LAlb in Group II (8.2 +/- 6.2 mg/100 ml) was higher (p less than 0.01) than in Group I (2.5 +/- 1.4 mg/100 ml) or in Group III )4.1 +/- 1.0 mg/100 ml). The LACE in Group II increased with the number of alveolar lymphocytes, in nonsmokers (4 = + 0.56, df = 34, p less than 0.001) and in smokers (4 = + 0.88, df = 7, p less than 0.01). In the smokers in this group, LACE was higher with respect to the number of lymphocytes than in the nonsmokers. We conclude from this study (1) that the permeability of the alveolocapillary membrane to albumin and to ACE is increased in active pulmonary sarcoidosis, (2) that LACE increases during sarcoidosis and returns to normal when the disease is cured, and (3) that the concentration of ACE in alveolar fluid increases with tobacco use.

[Increased concentration of angiotensin I converting enzyme in the alveolar fluid of patients with sarcoidosis]. / Augmentation de la concentration de l'enzyme de conversion de l'angiotensine I dans le fluide alvéolaire de sujets sarcoidiens.

Angiotensin converting enzyme (ACE) was assayed both in serum (SACE) and in bronchoalveolar fluid lavage (LACE) in 14 healthy controls and in 45 patients with sarcoidosis with mediastinal and pulmonary involvement. Concentration of SACE was 4466 +/- 2202 U x 100 ml-1 (mean +/- SD) in sarcoidosis and 2470 +/- 547 U x 100 ml-1 (chi +/- SD) in sarcoidosis and 2470 +/- 547 U . 100 ml-1 in controls. Concentrations of LACE were 65.2 +/- 48.4 U . 100 ml-1 and 21.1 +/- 14.7 U . 100 ml-1 respectively in sarcoidosis and in controls. These results are in favor of an intraalveolar secretion of ACE in sarcoidosis. LACE could be a better criterium than SACE for the evaluation of the pulmonary activity of sarcoidosis.

Bronchoalveolar cells in advanced pulmonary sarcoidosis.

We performed bronchoalveolar lavage (BAL) in 120 subjects: 94 patients with sarcoidosis, 11 patients with idiopathic pulmonary fibrosis (IPF), and 15 normal volunteers. By counting cells and comparing the results with those from control subjects, we found a high percentage of lymphocytes in BAL fluid from all patients with sarcoidosis and a high percentage of neutrophils (NE) in BAL fluid from patients with IPF. In addition, we observed a significantly higher proportion of NE in the 14 patients with advanced sarcoidosis (i.e., fibrosis and bullous radiological patterns), than was seen in the 80 patients with early stages of involvement (i.e., bilateral hilar lymphadenopathy and/or pulmonary infiltrations) (p less than 0.001). The NE count exceeded the normal value of 3.5% in 9 of the 14 patients with advanced sarcoidosis but only in 1 of the 80 patients with early disease (p less than 0.001). We believe that advanced sarcoidosis is one of the conditions in which a simultaneous increase in both NE and lymphocytes in BAL fluid can be observed. The NE count in bronchoalveolar fluid in patients with sarcoidosis, as in patients with IPF, may indicate evolution of the granulomatous process toward pulmonary fibrosis. These phenomena point out the potential practical value of iterative BAL in patients with sarcoidosis in assessing the prognosis of their disease.