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.

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.

Bronchodilator effects of antiasthmatic cigarette smoke (Datura stramonium).

In 12 asthmatic patients with mild airway obstruction we have measured the effect on specific airway resistance (sRaw) of inhaling the smoke of one Datura stramonium cigarette. In 11 patients sRaw decreased substantially after the cigarette, the mean maximal decrease being 40% at the 30th minute. In seven patients the subsequent inhalation of 200 micrograms salbutamol caused no further decrease in sRaw. In the remaining four patients salbutamol induced a larger decrease in sRaw than the cigarette smoke. The inhalation, however, of a synthetic anticholinergic agent (SCH 1000, 600 micrograms) proved as effective as salbutamol in these patients. In one patient the cigarette smoke and SCH 1000 produced only a negligible amount of bronchodilatation whereas the bronchial obstruction was reversible with salbutamol. Minor side effects were observed in six patients after the cigarette.

[Bronchial asthma and the beta adrenergic system]. / Asma bronquial y sistema simpático beta

The relationship between bronchial asthma and the beta adrenergic system is considered both from the physiopathologic and therapeutic point of view. A brief analysis of the sympathetic system is performed. The sympathetic nervous system is responsible for bronchodilation mediated through its beta-receptors. To evaluate this activity, beta adrenergic blockers such as propanolol are used. When this agent is administered, a descent of conductance is observed. On this condition, vagal stimulation brings about bronchoconstriction. At bronchial level, it seems that the beta-adrenergic system antagonizes vagal effect. From the physiopathologic point of view, Szentivanyi (1968) suggested a spontaneous beta block in the asthmatic. Other theories refer to a pathologic sensitivity of the peripheral bronchial receptors. The natural beta-adrenergics and the beta-adrenergic drugs enhance the synthesis of cAMP by stimulating the adenil cyclase system. This effect brings about relaxation of the bronchial smooth muscle. Considering the therapeutic effects, a comparative study of bronchodilators is performed. From all, Salbutamol has an intense broncholytic effect with little effect on heart dynamics. When sympathomimetics are bound to use in asthma, drugs such as Salbutamol and Terbutalina should be preferred because of its low cardiogenic effects. Its administration per os has rendered doubtful results.