Prognosis of severely hypoxemic patients receiving long-term oxygen therapy.

Two hundred seventy severely hypoxemic (PaO2 < or = 55 mm Hg: mean +/- SD = 48 +/- 6) COPD patients (232 men) were selected for long-term oxygen therapy (LTOT). They were old (mean = 66 +/- 8 years), with severe airflow limitation (FEV1 = 30 +/- 12 percent of predicted), some CO2 retention (PaCO2 = 47 +/- 9 mm Hg), and compensated respiratory acidosis. Eighteen percent of the patients presented some complicating pleuropulmonary diseases (pleural thickening, sequelae of tuberculosis, etc). Overall survival proportion was poor: 70, 50, and 43 percent at 1, 2, and 3 years, respectively. The Cox model showed that the factors which independently reduced survival were lower CO transfer coefficient, smaller intrathoracic gas volume, more severe bronchial obstruction, the fact that oxygen administration did not increase PaO2 above 65 mm Hg, increasing age, and the presence of chest wall abnormalities. When the patients were divided into three groups according to mortality risk, the mean clinical and functional profile of the high-mortality risk group was consistent with the prevalence of emphysematous lesions. Moreover, the best survivors fitted better into the "bronchitic" type; they showed a higher mean PaCO2, suggesting that some degree of hypoventilation could delay muscular fatigue and improve survival. The difference in the proportion of "emphysematous" and "bronchitic" patients is a possible explanation for the variability of the mortality rate reported in literature.

Measurement of respiratory system resistance by forced oscillation in normal children: a comparison with spirometric values.

In 377 children, the commercially available Siregnost FD-5 was used to measure respiratory system resistance (Rrs) by forced oscillation at 10 Hz. The children were between 3 and 18 years of age and, by a detailed questionnaire and conventional pulmonary function testing in 335, they were shown to be representative of the normal pediatric population. There was a linear relationship between Rrs and height (Rrs = 13.9-0.064 x ht (cm), r = -0.87). Children less than 6 years of age had no trouble with using the forced oscillation technique. The smoking of tobacco in the house, the presence of carpets in the child's bedroom, or an atopic family history, alone or in combination, had no influence on Rrs or on any spirometric measure. Forced oscillation is useful in children too young to be able to cooperate with conventional pulmonary function testing.

CO transfer capacity as a determining factor of survival for severe hypoxaemic COPD patients under long-term oxygen therapy.

The transfer capacity for carbon monoxide is a commonly used method in clinical practice but is rarely considered as a prognostic factor for patients under long term oxygen therapy (LTOT). LTOT was applied to 217 stable, severely hypoxaemic (arterial oxygen tension (PaO2 less than 7.3 kPa or 55 mmHg) chronic obstructive pulmonary disease (COPD) patients, according to the usual recommendations. The average survival rate of this series is rather poor: 46% at 24 months. There is nevertheless an important difference between patients with a normal transfer coefficient and those with a decreased one (79% survival at 2 yrs as compared to 37%). On the other hand, the degree of airflow limitation has no prognostic value in the present series of very disabled patients. We can conclude that hypoxaemic COPD patients with a severely decreased transfer coefficient have a poor prognosis, even under LTOT, compared to patients with an equivalent impairment of airflow limitation and hypoxaemia but with a normal CO transfer factor/alveolar ventilation ratio (TLCO/VA).

Bronchodilating and density dependence effects of fenoterol, ipratropium bromide and Duovent in reversible chronic obstructive pulmonary disease.

The bronchodilating effect of Duovent (0.2 mg fenoterol +0.8 mg ipratropium bromide) was compared with that of each of its components at the same doses. Twenty patients were included in the trial. Maximum expiratory flow-volume curves with air and helium-oxygen, intrathoracic gas volume and airway conductance were used for assessing the bronchomotor tone before and 15, 30, 60, 240 and 360 min after drug administration. All the drugs showed a significant bronchodilating effect. No differences between Duovent and fenoterol or ipratropium bromide were observed except a slight but statistically significant greater decrease of ITGV with Duovent. When expressing the data as percentage variation of the initial values, Duovent induced a better effect than the other drugs. The evaluation of density dependence was highly disappointing, and no conclusion can be drawn.

Effect of medroxyprogesterone on ventilatory control and pulmonary gas exchange in chronic obstructive patients.

Chronic obstructive hypercapnic patients were monitored for blood gases and breathing pattern, before, during and after a 7-day treatment with 75 mg/day of medroxyprogesterone (MPA). In 9 out of the 15 patients the PaCO2 level decreased (+/- 8 mm Hg) significantly with return to nearly control values at stop. 4 subjects still continued to improve after cessation of therapy and were considered as not being stable. In 2 patients PaCO2 did not change. We were unable to find any significant difference between the control values of these three categories. The study of the breathing pattern in responsive subjects showed an increase in minute ventilation and tidal volume, with a small increase in mean inspiratory flow and no change in inspiratory time as a function of total respiratory cycle time. We conclude that MPA lowers the PaCO2 of hypercapnic chronic obstructive pulmonary disease patients through an increased tidal volume, which could result from an increased central nervous inspiratory output, or from better mechanical performance of the respiratory muscles due to the same central stimulation.

Nitroglycerin and isosorbide dinitrate in pulmonary hypertension of chronic obstructive pulmonary disease.

The effects of sublingual isosorbide dinitrate (ISDN; 10 mg) or nitroglycerin (NTG; 1 mg) on pulmonary hemodynamics, gas exchange and pulmonary function were studied during right heart catheterization in two series of 27 patients with COPD. An immediate significant decrease of pulmonary arterial pressure, cardiac output and work of the right ventricle was obtained with both drugs, but NTG only was able to reduce the pulmonary vascular resistance. Arterial oxygen tension did not decrease, but venous O2 tension did, with no change in blood lactate. NTG had also a slight bronchodilating effect. After chronic use, no improvement of pulmonary function or gas exchange was observed but NTG lowered pulmonary vascular resistances significantly. The effects observed during the acute study were reproduced after six weeks with the same doses of both drugs. NTG appears effective in reducing pulmonary arterial hypertension mainly by vasodilation while the ISDN effect seems due only to the decreased cardiac output.

Comparison of the bronchodilating effect of two doses of a sustained release theophylline.

In order to assess the dose/response ratio of two different doses of theophylline, the effects of two periods of 4-day treatment with 300 and 450 mg sustained release anhydrous theophylline (Theodur, Astra, Sweden) b.i.d. in 16 in-patients with reversible chronic obstructive lung disease in a stable state were investigated in a double-blind randomized crossover study. On the 4th day in each treatment period, ventilatory function parameters (FEV1, FVC, PEFR, MEF25, MEF50), theophylline serum concentration and blood gases were measured. Asthma symptoms, beta 2-adrenergic aerosol use significantly different from its value before treatment: the mean FEV1 increase during the 300-mg period reached 12% and during the 450-mg period 15%. The mean difference in theophylline serum concentration between the periods of 300 and 450 mg reached approximately 2 micrograms/ml, but a significant difference could not be demonstrated between both treatment periods, neither in the mean ventilatory parameters, nor in the patients preference. In spite of the use of a sustained release preparation, variations of serum levels of theophylline were observed individually throughout a 12-hour observation period: the extent of those variations differs from one patient to another.

Influence of different extension-actuator tubes on the bronchodilation effect of a terbutaline sulfate aerosol.

The addition of a tube extension or of a pear-shaped spacer to a conventional metered-dose aerosol for delivering a bronchodilator drug, caused a slightly improved bronchodilation in 12 trained, adult patients with stable, reversible airways obstruction of moderate severity. Although statistically significant, the increase in bronchodilation effect does not appear to be clinically relevant in these patients. Continuous measurement of pulmonary resistance using the airflow interruption method did not reveal differences in the time of onset of the bronchodilation.

Early bronchodilating effect of oxitropium bromide in comparison with ipratropium bromide.

The bronchodilating effects of a metered aerosol dose of 40 micrograms ipratropium bromide and of 200 micrograms oxitropium bromide are similar 15 min. after administration. The bronc hodilating activity of ipratropium bromide appears earlier (i.e., 75-90 s after administration) than that of oxitropium bromide but later than that of ibuterol, a beta2-agonist. Ipratropium bromide administered at the close of 80 micrograms provokes a bronchodilation about double of that obtained with 40 micrograms. An adaptation of the usual dosage should be considered.

Controlled trial of the effect of repeated administration of ipratropium bromide on ventilatory function of patients with severe chronic airways obstruction.

A trial was designed to assess whether repeated administration of ipratropium bromide for two weeks produced greater improvement than was obtained after a single dose. The effect of ipratropium bromide was compared with that of a placebo during a double-blind cross-over randomized trial in patients with advanced chronic airways disease in a stable state. Ipratropium bromide and placebo were both administered by metered dose inhaler for 14 days. There was a slight statistically significant improvement of conductance, thoracic gas volume, FEV1 and VC after inhalation of ipratropium bromide, but repeated doses of the drug did not produce progressive improvement.

Evaluation of onset of bronchodilating effect by interruption of the air flow method.

The speed of onset of the bronchodilating effect of ibuterol, a derivative of terbutaline, was measured by the method of air flow interruptions, which enables an almost continuous study of lung resistance before and after the administration of a bronchodilator. In the double-blind comparison between ibuterol and placebo, the onset of action of the new beta 2-agonist has been shown to take place within 30-45 sec. This indicates that ibuterol is a bronchodilator with rapid onset of action.

[Differential diagnosis of chronic obstructive lung disease, A statistical analysis of the discriminating power of various lung function tests (author's transl)]. / Diagnostic différentiel des bronchopneumopathies obstructives chroniques. Etude statistique du pouvoir discriminatoire de diverses épreuves fonctionnelles respiratoires

Among 65 patients admitted to the hospital for chronic obstructive lung disease, the following pulmonary tests were systematically performed : spirometric vital capacity and total lung capacity, FEV1, functional residual capacity and total lung capacity measured by body plethysmography, airway resistance and specific conductance, CO diffusion capacity measured by single-breath test, N2 clearance by single breath oxygen dilution, and blood gases. The patients were divided into bronchitics, emphysematous and broncho-emphysematous, according to the clinical and radiological Nash's score, and to another personal score derived from the former. The simple and multiple correlations between the clinico-radiological score and the functional results are low. The clustering analysis groups the 65 patients into four clouds of points, around two principal axes : the volume axis and the overinflation axis. This study indicates that the most suggestive results for emphysema diagnosis are increased FRC and TLC and low Tlco/V'a. The clinical score is not dominant for the clustering of the patients into the dynamic clouds. Beneath the bronchitic, the broncho-emphysematous and the emphysematous groups, the clustering analysis individualizes a fourth group of cases characterized by chronic asthma, and which were not isolated by Nash's score.