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Background: Resting pulmonary diffusing capacity of the lung for carbon monoxide (DLCO )i s known to be the best predictor of arterial desaturation during exercise in patients with sarcoidosis. However, the relative contribution of each of the two components of DLCO—alveolar membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc)—remains unclear. Study objectives: To evaluate which component is responsible for the decrease of resting DLCO in patients with sarcoidosis, and to determine which resting pulmonary function test, including Dm and Vc, is the best predictor of gas exchange abnormalities during submaximal exercise. Design: Prospective analysis of patients referred to our department of respiratory medicine. Patients: Twenty four patients with pulmonary sarcoidosis were separated into two groups according to chest radiographic findings: group 1, stages 2 and 3 (n 15); group 2, stage 4 (n 9). All the patients completed pulmonary function tests (flows, volumes, single-breath DLCO, transfer coefficient [Ka], Dm, Vc) and submaximal exercise (two steady-state levels of mild and moderate exercise corresponding respectively to a target oxygen consumption of approximately 10 to 15 mL/min/kg). Results: DLCO was reduced in the two groups (group 1, 63 16% of predicted; group 2, 64 16% of predicted). Dm was severely decreased (group 1, 58 24% of predicted; group 2, 51 15% of predicted), whereas Vc was unchanged or only mildly decreased (group 1, 81 18% of predicted; group 2, 85 28% of predicted). Whatever the group of patients and the exercise level, Dm and DLCO were the strongest predictors (p < 0.001) of gas exchange abnormalities. Ka or volumes were weak predictors, and Vc or flows were not related with exercise gas exchange. Conclusions: This study demonstrates that a decrease in Dm mostly accounts for resting DLCO reduction, and that Dm as well as DLCO are highly predictive of gas exchange abnormalities at exercise in patients with sarcoidosis. (CHEST 2004; 125:2061–2068)

Study objective: Airway obstruction (AO) in sarcoidosis is reported to be associated with respiratory symptoms, increased morbidity, and an increased mortality risk. Because AO in sarcoidosis may result from several causes, the therapeutic benefit of corticosteroids is difficult to determine. The aim of this study was to evaluate the therapeutic response of AO attributable to sarcoid granulomas in the bronchial wall. Patients: We selected 11 patients who had sarcoidosis with AO (defined as FEV1/vital capacity [VC] < 70%) associated with sarcoid granulomas on an endobronchial biopsy. Exclusion criteria were history of asthma, smoker or exsmoker, stage 4 disease, evidence of extrinsic compression by enlarged lymph nodes, and localized endobronchial stenosis seen during fiberoptic bronchoscopy. Interventions: We compared the results of pulmonary function tests and clinical, radiologic, and biological findings at baseline with those obtained at the time of the last pulmonary function tests available, between the sixth and 12th months of treatment. Eight patients took oral corticosteroids (20 to 60 mg/d initially), one received IV methylprednisolone pulses, another took oral hydroxychloroquine, and the last one received IM methotrexate. Measurements and results: With treatment, FEV1 and FEV1/VC significantly improved in eight patients (72%), normalized in four patients, and was unchanged in the remaining three patients. The mean FEV1 increased from 60.8 6 10.8% to 76 6 13.7% of the predicted value (p < 0.02). VC did not change significantly. FEV1/VC increased from 76.1 6 6.4% to 87.6 6 10.7% of the predicted value (p < 0.01). Dyspnea on exertion and other clinical findings were attenuated in 10 patients; the chest radiograph improved in 9 patients, and normalized in 5 patients. The mean serum angiotensin-converting enzyme level decreased from 112 6 48 to 58 6 40 IU/mL (p < 0.05), and normalized in four patients. Conclusion: The present study indicates that AO caused by sarcoid granulomas in the bronchial wall can be either partially or completely reversed by treatment with a concomitant attenuation of pulmonary symptoms. (CHEST 1999; 116:1194 ‐1199)

The presence of Na + -coupled sugar transport in rat trachea was investigated using the nonmetabolizable glucose analogs methyl α-glucopyranoside and 3- O -methylglucose. The rates of disappearance from tracheal instillates and the tissue uptake of these analogs were compared with those of l -glucose. Experiments were performed in vivo, using a cross-circulation preparation, and in vitro, on tracheal strips. The analog methyl α-glucopyranoside was removed in vivo from the tracheal lumen faster than l -glucose. The cellular uptake in vivo or in vitro was determined by lysing the cells lining the tracheal lumen with detergents. This uptake was inhibited by luminal glucose, phloridzin and Na + substitution with choline. The transport rate of 3- O -methylglucose was very low and thus discouraged inhibition experiments. These results indicate the presence of a Na + /sugar cotransport system in rat trachea. The effects of luminal interactions suggest that the cotransport is located in the apical membrane of the tracheal epithelium. It resembles that previously described in the rat alveolar epithelium, but apparently differs from that found in the fetal sheep lung in which a significant 3- O -methylglucose cotransport with Na + has been described.

Propranolol, a beta-blocking agent, has been proposed in the prevention of gastro-intestinal bleeding in cirrhotic patients, and is known for its bronchoconstrictive effects. Since hypoxemia is a frequent finding in patients with cirrhosis, this work was undertaken to study the effects of intravenous propranolol on pulmonary function and on gas exchange in these patients. The 10 patients studied had cirrhosis associated with an increase in the alveolar arterial O2 difference, (A-a)DO2, an index of arterial oxygenation impairment. Their 1-s forced expiratory volume/forced vital capacity (FEV1/FVC) was normal, but in most a reduction of the forced expiratory flow of 25-75% of vital capacity was observed (FEF 25-75), suggestive of some degree of small airway obstruction. Although propranolol induced a significant decrease of FEF 25-75 from 67.7 +/- 19.3% to 55.4 +/- 21.5% (P less than 0.01), suggesting a bronchoconstriction of the small airways, there was no significant decrease in mean arterial oxygen partial pressure (PaO2) (74.1 +/- 6.4 mmHg before and 77.0 +/- 6.5 mmHg after propranolol). Indeed, a slight but significant improvement of the (A-a)DO2 was observed, from 39.1 +/- 5.9 mmHg to 34.4 +/- 4.9 mmHg (P less than 0.02). Although the mechanism of this beneficial effect remains to be elucidated, we conclude that in spite of its bronchoconstrictive action, propranolol is not contra-indicated in cirrhotic patients with hypoxemia who have normal expiratory flow.

This study compares the effects of 2 α 2 -adrenergic agonists, rilmenidine (S 3341) and clonidine, on histamine-induced bronchoconstriction (HIB) in guinea pigs. Clonidine has previously been shown to potentiate HIB in guinea pigs. The study was conducted in anesthetized, paralyzed and ventilated guinea pigs. Six groups of at least 6 guinea pigs were pretreated with saline, rilmenidine (0.1, 0.3 and 1 mg/kg intravenously) or clonidine (0.01 and 0.03 mg/kg intravenously), respectively. Conductance, dynamic compliance and static compliance of the respiratory system were measured before and during histamine infusion (80 ng/kg/s) and expressed as percent variation. Clonidine potentiated HIB as previously reported. In contrast, rilmenidine potentiated HIB only at the dose of 1 mg/kg. As it is well known that HIB is influenced by adrenergic outflow, these results suggest that rilmenidine has less inhibitory effect than clonidine on adrenal secretion.