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Three hundred and fourteen elderly subjects admitted to chronic medical centers were given either RU 41740 (n = 155) or a placebo (n = 159) at the rate of one course per month during three months. RU 41740 was administered in doses of 2 mg per day during 8 days in the first course and 1 mg per day during 8 days in the second and third courses. The subjects were followed up and regularly examined every three months for one year. The incidence of acute infectious episodes was evaluated in both groups. Compared to those patients who received the placebo, the number of subjects without infection was significantly higher in the treated group during the 0-6 months and the 0-9 months periods and during the 12 months of observation. The number of infectious episodes was reduced during the 0-3 months and 0-9 months periods and throughout the 12 months of the trial. The mean duration of pulmonary infections that occurred during the 0-6 and 0-9 months periods was reduced. Finally, there was a significant decrease in the duration of antibiotic therapy during the 0-3, 0-6, 0-9 months periods and during the 12 months of observation. The drug was well tolerated. This study showed that RU 41740 is effective in protecting elderly and therefore fragile subjects against respiratory infections.

RU 41740 is an immunomodulator of organic origin acting on cells of the immune system (B cells, T cells, phagocytic cells) and on mediators IL1-CSF). Its mode of action has been explored by means of experimental infections. The types of defence involved differ according to whether the experimental infection is caused by an extracellular or intracellular micro-organism. Candida albicans and Saccharomyces cerevisiae were used to produce fungal infections, while bacterial infections were obtained with Staph. aureus, E. coli, Strep. pneumoniae and other organisms. The influenza virus was used to produce a viral infection. In these experimental models, RU 41740 increased the survival time of the infected animals and reduced bacterial, fungal and viral proliferation. These effects were observed even in immunocompromised mice. These in vitro and in vivo studies have demonstrated that RU 41740 is effective whatever the type of body defence involved.

In both adults and children RU 41740 exerts an immunomodulating effect and prevents recurrent respiratory infections. Patients with such infections frequently consult for acute episodes, and it was deemed necessary to evaluate the safety of the drug given concomitantly with antibiotic in acute infections. Three double-blind, drug versus placebo studies were conducted in fragile institutionalized or hospitalized patients. Antibiotics were administered simultaneously with RU 41740 in one group and with a placebo in another group. The studies performed by Albarede and Ollivier showed that in acute respiratory infections RU 41740 was well tolerated and resulted in a more rapid improvement of severity score. Grassi and al. studied chronic bronchitis patients admitted for acute on chronic episode. RU 41740 produced a more rapid improvement in the most severely ill patients, and it was well tolerated. It is concluded that RU 41740 can be initiated safely in acute episodes occurring in subjects with recurrent respiratory infections, and that it results in a faster improvement of clinical symptoms.

Several double-blind drug versus placebo trials have been carried out to evaluate the effectiveness of RU 41740 in the treatment of recurrent respiratory infections in children. The compound was administered in doses of two tablets per day for one week during the first month and one tablet per day for one week during the second and third months. Effectiveness was assessed 1, 3 and 6 months after the end of the treatment period. These trials have shown that RU 41740 is well tolerated both clinically and biochemically and that it decreases the number, duration and complications of respiratory infections, as well as the consumption of antibiotics during the infectious episodes. It therefore appears that this compound is particularly useful to prevent recurrent respiratory infections in children.

RU 41740 is an immunomodulator of organic origin to be used preventively against recurrent respiratory infections in both adults and children. The immunological safety of the drug was first studied on NZB-NZW mice which spontaneously develop a disease resembling lupus erythematosus. The survival rate of these mice and the amounts of protein excreted in the urine were not modified by the compound. Clinically, RU 41740 was well tolerated by the adult mice and their offspring. Studies on immunological safety were also conducted in human adults and children. Compared with pre-treatment values, there were no pathological changes in blood count and differential, erythrocyte sedimentation rate, immunoglobulins E, A, M and G levels, apolipoproteins, haptoglobin, haemolytic complement, antinuclear factors, rheumatic serology and anti-red cell antibodies. In addition, the drug was well tolerated by atopic subjects.

Chronic bronchitis is responsible for 20,000 deaths per annum in France, i.e. 5 per cent of the overall mortality rate. Infection of the bronchi and lung tissue is a frequent cause of death in these patients. Acute on chronic bronchitis ranks fifth among the causes of disablement and admission to hospital. Pneumococci and Haemophilus influenza are the organisms most frequently isolated. the incidence and potential severity of acute episodes of infection account for the repeated use of antibiotics which carries a risk of promotion bacterial resistance. RU 41740 is a non-specific immunomodulator agent which reinforces the non-specific means of the respiratory tract against infections. Three double-blind, drug versus placebo and therefore reliable therapeutic trials have shown that the drug is effective in preventing airway infection. In patients with moderately advanced chronic bronchitis, RU 41740 reduces the number and duration of acute infectious episodes as well as antibiotic consumption. This positive effect persists in patients with chronic respiratory failure, including those who present with extensive bronchial dystrophy. RU 41740 is particularly effective in patients with numerous previous episodes of infection, but it also acts at all stages of chronic bronchitis.