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Recent multi-centre studies have shown that high doses of Almitrine (100-200 mg per day), lead to a significant improvement in the hypoxaemia of patients presenting with chronic airflow obstruction, but that a high blood level (greater than 500 ng/ml) is often seen after 1 year, sometimes associated with signs of peripheral neuropathy. In order to maintain Almitrine blood levels in the range 200-300 ng/ml we have used an intermittent regime (with a "window" of 1 month every 3 months) and a dose limited to 100 mg per day. 102 hypoxic patients with chronic airflow obstruction, who were in a stable state were included. 65 patients were in the Almitrine group (A) and 37 patients in the placebo group (P). The treatment lasted for 1 year. In addition there was a 3 monthly follow up with arterial blood gases and spirometry, a clinical neurological examination and also electrophysiology, initially and after 6 and 12 months. 43% of patients in group A and 32% of patients in group P, left the study, most often due to poor cooperation, but sometimes as a result of side effects. After 12 months the PaO2 rose significantly in group A from 59.1 +/- 0.7 to 65.8 +/- 1.6 mmHg (p less than 0.001) whilst it was not changed in group P. The PaCO2 did not change in either group. On the other hand there was a significant fall in the subgroup of patients with hypercapnia in group A (p less than 0.001). The outcome of the neurological and electrophysiological assessments did not show any significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The main results obtained, in healthy or unhealthy man, with the inert gas method are gathered together. The major factor at the source of hypoxemia is the uneven distribution of VA/Q ratios. The fall in the partial pressure of oxygen in mixed venous blood amplifies this effect. Only hypoxemia, during muscular exercise, in patients with interstitial lung diseases could be explained, in part, by a decrease in membrane diffusion and a reduction in the transit time of blood in pulmonary capillaries. The differences between the methods used to analyse pulmonary gas exchange are discussed.