CPAP suppression of awake right-to-left shunting through patent foramen ovale in a patient with obstructive sleep apnoea.

The prevalence of an echocardiographically visible patent foramen ovale (PFO) is higher in patients with obstructive sleep apnoea syndrome (OSAS) than in normal controls. We report a patient who presented with OSAS and right-to-left shunting (RLS) through the PFO in whom the RLS disappeared after treatment for 1 week with nocturnal continuous positive airway pressure (CPAP). This case shows the role of OSA in generating an awake RLS through a PFO and its possible reversibility by CPAP. The mechanism of reversible awake RLS through PFO in OSAS is discussed.

Association of oral almitrine and medroxyprogesterone acetate: effect on arterial blood gases in chronic obstructive pulmonary disease.

Almitrine (A) and medroxyprogesterone acetate (MA) given separately improve arterial blood gases in some patients with chronic obstructive pulmonary disease (COPD); the aim of this study was to assess the effect of the two drugs given together. Forty-eight patients with irreversible COPD and hypoxaemia were prospectively enrolled into a 14-day run-in period and received single-blind oral treatment with double placebo. Patients whose PaO2 remained stable (less than 10% change; n = 29, 25 males, mean age 65.6 years) were included in a 14-day active treatment period and randomly assigned to three groups. They received double-blind oral treatment with: A (50 mg bid, group A, n = 10); MA (20 mg tid, group MA, n = 9); A (50 mg bid) and MA (20 mg tid, group A+MA, n = 10). Anthropometric and spirometric measurements were similar in the three groups and so were the arterial blood gas values at the beginning and the end of the run-in period. At the end of the active treatment period, blood gas changes (mean+/-SE) were significantly different between groups (P<0.05, Kruskal-Wallis test), with improvement in both hypoxaemia and hypercapnia in group A+MA only: delta PaO2 = 7.4+/-1.9 mmHg, delta PaCO2 = -5.1+/-1.7 m mHg (P<0.05, Wilcoxon test). In short-term treatment, the association of A and MA is more efficient than either drug alone at improving arterial blood gases in COPD patients.

Supine hypoxemia following nebulizated salbutamol in patients with chronic airway obstruction.

Inhaled beta-adrenergic agonists can decrease arterial oxygen tension (PaO2). A decrease in PaO2 can also be observed with supine posture. We assessed the effect on PaO2 of supine posture following salbutamol nebulization inpatients with chronic airflow obstruction. Twelve patients (10 males, 2 females mean age 60 yr) with FEV1/FVC = 0.65 (mean 0.54) and resting PaO2 = 60 mm Hg while breathing room air (mean 76.5 mm Hg) were included in a prospective randomized double-blind double crossover study conducted for 2 consecutive days. On each study day, each patient successively underwent baseline PaO2 measurement; nebulization of either salbutamol (0.5% solution, 1 cm3) or saline; two supervised 30-min periods in the supine or seated posture, with PaO2 measurement at the end of each period. PaO2 values were compared with analysis of variance for repetitive measurements (6 values for each patient). PaO2 values (mean +/- SD; mm Hg) were similar at baseline (day 1: 76.5 +/- 8.1; day 2: 76.6 +/- 8.6), after saline + seated (74.8 +/- 7.2), after saline + supine (74.9 +/- 7.5), and after salbutamol + seated (74.3 +/- 7.3). In contrast, PaO2 after salbutamol + supine (70.8 +/- 10.1) was significantly lower than all other values (p <0.05), six patients exhibited large PaO2 decreases (from 9 to 21 mm Hg). Hypoxemia induced by the combination of nebulized salbutamol and supine posture may represent a potential hazard of bronchodilator therapy.

Left atrial and ventricular filling in chronic obstructive pulmonary disease. An echocardiographic and Doppler study.

Abnormal left ventricular (LV) diastolic function has frequently been reported in patients with chronic obstructive pulmonary disease (COPD). In the present work, diastolic function was studied by a combined analysis of pulmonary venous and mitral blood flow velocities in 34 patients with COPD clinically stable and without history of heart disease, and 20 control subjects. We confirmed the increased contribution of the atrial contraction to the LV filling in COPD patients in comparison with control subjects; furthermore, a decreased left atrial (LA) filling during the ventricular systole was observed. Changes in LV filling were not the consequence of a systolic dysfunction, because LV systolic function was normal. Doppler indices indicated that LA pressure was below 15 cm H(2)O in all the patients with COPD and control subjects. Several factors can be put forward to explain these changes; the first one is tachycardia. In addition to hypoxemia and medications, echocardiography suggested that a decreased LV preload participated in increased heart rate. Analysis of Doppler transmitral and pulmonary venous flows demonstrated the role of the ventricular interdependence because a correlation existed between LA and LV filling pattern and right ventricle pressure and diameter.

Pulmonary arteriovenous malformations: lung transplantation as a therapeutic option.

Multiple pulmonary arteriovenous malformations (PAVM) constitute an uncommon cause of respiratory disability. They may lead to severe hypoxaemia via right-to-left shunts and are sources of substantial mortality and morbidity. Conservative surgical resection has been proposed as the treatment of choice. More recently, percutaneous balloon or coil embolization of the feeding vessels offered an efficacious and safe alternative therapy for patients whose fistulas are too numerous to excise. This study reports an unusual case of respiratory disability in a patient with multiple and microscopic pulmonary arteriovenous malformations who failed to respond to embolotherapy and who received a double lung transplantation with good initial outcome.

Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease.

Unexplained weight loss is common in chronic obstructive pulmonary disease (COPD). Blood levels of tumor necrosis factor-alpha (TNF-alpha), a cytokine causing cachexia in laboratory animals, are elevated in various human diseases associated with weight loss. We therefore prospectively measured TNF-alpha serum levels (immunoradiometric assay) in patients with clinically stable COPD (n = 30; all male; mean age, 65 yr) whose weight was less (Group I; n = 16) or more (Group II; n = 14) than the lower limit of normal taken from Metropolitan Life Insurance Company tables. The patients had no cause known to elevate TNF-alpha serum levels; notably, they were not infected. Group I patients had unintentionally lost weight during the previous year, whereas the weight of Group II patients had not changed during the same period. The two groups had similar chronic airflow obstruction and arterial blood gas impairment; hyperinflation and reduction in diffusing capacity were more pronounced in Group I, but differences were not significant. TNF-alpha serum levels (pg/ml; mean [SD]) were significantly higher in Group I than in Group II (70.2 [100.0] versus 6.7 [6.4]; p < 0.001). Group II TNF-alpha serum levels did not differ significantly from those of healthy subjects (7.8 [3.9]), whereas those of Group I were significantly higher (p < 0.001). Because renal function was in the normal range, we conclude that increased TNF-alpha production--and not decreased TNF-alpha clearance--is a likely cause of weight loss in patients with COPD.

Left lung asthma.

The chest radiograph of a woman with acute asthma showed signs of obstructive emphysema of the left lung. Fiberoptic bronchoscopy excluded obstruction of a large bronchus. The signs disappeared after antiasthmatic treatment, suggesting that they were caused by airway closure. In usual asthma, airway closure affects both lungs; the reason for the unilateral predominance we observed is unknown.

Manufacturer's information insert and subjective theophylline side-effects.

In Western Europe medicine packages contain an insert prepared by the manufacturer which enumerates the drug side-effects. We investigated the influence of this insert on alleged theophylline side-effects. Forty literate adult asthmatics were randomly allocated into two groups (n = 20 each): theophylline packages contained the manufacturer's insert in group A but not in group B. Theophylline was prescribed (10 mg.kg-1 body weight qd) for one week. During this period the patients filled a diary grading 13 different symptoms from 0 to 3; 5 of these symptoms were listed on the insert as theophylline side-effects. On the eighth day the patients were interviewed and theophylline blood levels measured. Theophylline side-effects were significantly more marked in group A than in group B, whereas the other symptoms were of similar magnitude. Eight patients prematurely stopped their treatment in group A vs 3 in group B, because of alleged intolerance. Theophylline blood levels did not differ significantly in the two groups; neither did they in the subgroup which stopped treatment and in the one which complied to prescription. We conclude that side-effects were suggested to the patients by the insert and/or that the insert increased their awareness of side-effects, with a subsequent detrimental influence upon compliance to therapy.

Attenuation of bronchofiberscopy-induced cough by an inhaled beta 2-adrenergic agonist, fenoterol.

We investigated the antitussive effect of fenoterol in 40 patients (34 males) undergoing bronchofiberscopy for diagnostic purposes. The patients were randomly allocated into two groups, one receiving two puffs (400 micrograms) of fenoterol and the other two puffs of placebo, from a metered-dose inhaler in a double-blind fashion. The following procedure was used: premedication with 0.5 mg atropine sulfate and 100 mg hydroxyzine administered intramuscularly; 50 min later, aerosol administration; 10 min after aerosol administration, a standardized topical anesthesia was performed. As soon as the bronchofiberscope had entered the trachea, sounds were recorded for a 5-min period, while the tracheobronchial tree was systematically inspected. Additional lidocaine (2% solution, 2 ml boluses) was injected into the airways if troublesome cough occurred. The two groups did not differ significantly in terms of age, sex ratio, and smoking history. In contrast, both the number of coughs and the volume (ml) of additional lidocaine were significantly smaller in the fenoterol group than in the placebo group: m +/- SEM: 35.0 +/- 5.5 versus 51.6 +/- 6.5, p less than 0.01 and 1.9 +/- 0.5 versus 3.3 +/- 0.4, p less than 0.01, respectively. Thus, fenoterol exhibits antitussive properties and can usefully be administered before bronchofiberscopy.

Treatment of brain metastases of lung cancer with high doses of etoposide (VP16-213). Cooperative study from the Groupe Franais Pneumo-Cancérologie.

To study the efficacy of etoposide in brain metastases of lung carcinoma, etoposide was given during 3 consecutive days. The total dose of 1500 mg/m2 was divided into six 1 h perfusions delivered over 3 days to 19 patients having squamous (7), large cell (3), small cell (5) or adenocarcinoma (4). Response to chemotherapy was assessed by means of computerized tomography (CT) before and 15-30 days after the last course of chemotherapy (course interval = 28 days, maximum of four courses). Severe myelotoxicity was observed in nine patients with seven patient deaths resulting from infection. Efficacy could be evaluated in 13 patients. Failure was observed in seven cases. An objective response was observed in six patients (4/14 NSCLC and 2/5 SCLC), two patients having a complete regression. Average survival time was 10 weeks.

Attenuation of hyperventilation-induced bronchospasm by terfenadine: a new antihistamine.

The effect of terfenadine, a selective H1-receptor antagonist devoid of central nervous system side effects, was evaluated on hyperventilation-induced bronchospasm in 11 adult subjects with asthma in a double-blind, placebo-controlled, crossover study. Increases in specific airway resistance (SRaw) were induced by isocapnic hyperventilation with dry air on two occasions, 7 days apart. Before the tests, the subjects received oral terfenadine (120 mg, twice daily) or placebo for 3 days with the last dose administered 3 hours before the test. Baseline SRaw and spirometric values (vital capacity and FEV1) were similar for the two tests. Terfenadine yielded a significant (p less than 0.001) parallel shift to the right of the stimulus (hyperventilation)-response (SRaw) curve; 100% increases in SRaw occurred at ventilation rates of 44 L/min after placebo treatment and 64 L/min after terfenadine treatment. These data suggest that histamine release plays a role in hyperventilation-induced bronchospasm despite the fact that increase in plasma histamine has not been found in this situation, in contrast to exercise-induced bronchospasm.

[Medical history of severe respiratory insufficiency]. / Histoire médicale des insuffisants respiratoires graves.

To evaluate retrospectively health care in severe chronic respiratory failure, we interviewed 38 patients, admitted for the first time to a pulmonary intensive care unit for an acute episode. A standardised questionnaire was devoted to establishing if the patients were aware of chronic respiratory disease prior to admission, if they had visited a general practitioner or a chest clinic, and had undergone a lung function evaluation. Six patients were unaware of any respiratory disease prior to the acute episode. Six others realised they had suffered from a respiratory disease, but had failed to visit a physician. Among the remaining 26 patients, two-thirds had visited a chest physician. Fourteen of them had undergone spirometry and arterial blood gas measurements. One third had visited a general practitioner but spirometry was performed in only 3 and arterial blood gas analysis in only 1. Thus, chronic respiratory failure is sometimes ignored, and most of the time diagnosed with delay and inadequately evaluated.

Cholinergic responsiveness of respiratory and vascular tissues in two different rat strains.

The airway and systemic arterial smooth muscle responsiveness to cholinergic agents of two strains of rats, Rat Albino (RA) and Brown Norway (BN), was compared in vivo and in vitro. In vivo, we measured the doses of carbachol that induced a 100% increase in lung resistance (PD100 RL), a 50% decrease in dynamic lung compliance (PD50 Cdyn), and the value of systolic blood pressure at the carbachol dose of 10 micrograms (Pa 10 micrograms). In vitro airway smooth muscle and systemic arterial smooth muscle responsiveness was assessed by measuring the maximal response to acetylcholine, the slope of the linear portion of the dose-response curve, and the negative logarithm of the molar concentration of acetylcholine producing 50% of the maximal response (pD2). PD100 and PD50 were about four times greater in BN rats than in RA rats. In contrast, Pa 10 micrograms was 1.5 lower in the BN rats. These differences persisted after bivagotomy. Tracheal pD2 was 25% greater in the RA than in the BN strain. The mean dose-response curve of parenchymal strips of RA rats was situated upward and to the left of the BN curve, but the reverse was observed for aortic smooth muscle dose-response curves. Thus 1) airway smooth muscle responsiveness to cholinergic agents is greater in RA strain than in BN, but the reverse is true for systemic arterial smooth muscle responsiveness; and 2) these differences are not due to factors extrinsic to the smooth muscle, since they occurred in vitro and may depend on different densities of muscarinic receptors.