Faculty Bibliography

OBJECTIVE: To determine the frequency of unexplained reversible hypoxemia in patients with systemic lupus erythematosus and to assess the relation between hypoxemia and elevated plasma levels of complement split products. DESIGN: Cohort study. SETTING: Inpatient and outpatient facilities of the New York University Medical Center/Bellevue Hospital and the Hospital for Joint Diseases. PATIENTS: Case patients were 22 patients hospitalized with disease exacerbation and no evidence of parenchymal lung disease on chest roentgenogram. Four patients with stable disease were followed in the outpatient clinic, and five healthy normal volunteers served as controls. MEASUREMENTS: Plasma levels of complement split products (C3a, factor Bb fragment), alveolar-arterial (A-a) Po2 gradients, and pulmonary function were measured. MAIN RESULTS: Nine episodes of hypoxemia or hypocapnia (mean A-a gradient, 30.4 +/- 4.8 mm Hg) or both (despite normal chest roentgenogram results) were noted in six hospitalized patients (group 1). Gas exchange improved within 72 hours of steroid therapy (mean A-a gradient, 11.6 +/- 4.3 mm Hg; P less than 0.01). These patients had an elevated initial mean C3a level (938.4 +/- 246.8 ng/mL) that decreased within 72 hours (407.8 +/- 80.9 ng/mL; P less than 0.01), concomitant with improved oxygenation. Ventilation-perfusion scans, obtained for four of six group 1 patients, excluded pulmonary emboli. Four hospitalized patients (group 2) had a normal A-a gradient (mean, 7.5 +/- 2.7 mm Hg). The mean C3a level of this group (358.3 +/- 39.2 ng/mL) was lower than that of group 1 (P less than 0.05). Four patients with stable disease (group 3) had a mean A-a gradient and a mean C3a level of 3.3 +/- 2.7 mm Hg and 237.8 +/- 105.7 ng/mL, respectively, similar to values found in five normal volunteers, in whom the mean A-a gradient was 3.7 +/- 1.7 mm Hg and the mean C3a level was 124.8 +/- 9.2 ng/mL. CONCLUSION: A syndrome of reversible hypoxemia, unassociated with parenchymal lung disease, is unexpectedly common in acutely ill, hospitalized patients with systemic lupus erythematosus. The pathogenesis of this syndrome is unclear, although the data are compatible with the hypothesis that hypoxemia may be related to pulmonary leukoaggregation

Defense of ventilatory homeostasis against recurrent hypercapnia, hypoxia, and acidosis resulting from apnea in obstructive sleep apnea syndrome (OSAS) is dependent on compensatory mechanisms operative between episodes of airway obstruction. This investigation was designed to examine whether endogenous opiate activity modulates the compensatory ventilatory response to apnea in OSAS. Polysomnography and quantitative measurement of tidal volume was performed in 12 patients with moderate to severe OSAS during a morning nap study before and after intravenous administration of 10 mg of naloxone. Apnea index was not significantly altered. There was a small but significant shortening of apneas (postnaloxone apnea duration, 91.2% of prenaloxone; p = 0.002 by ANOVA). Tidal volume of the first postapnea breath and minute ventilation extrapolated from the first two postapnea breaths, but not frequency, increased significantly after naloxone (postnaloxone first breath volume, 112.7% of prenaloxone value [p = 0.03], with a similar increase for minute ventilation, 115.1% [p = 0.007]). The volume of the first postapnea breath was correlated with the duration of the previous apnea, both before (r = 0.59, p = 0.0001) and after naloxone. Despite this, analysis of covariance with apnea duration as the covariate confirmed a significant independent increase in postapnea breath volume after naloxone (p = 0.001). Naloxone also altered sleep architecture, increasing percent time awake during the study period (prenaloxone, 36.3 +/- 15.6%; postnaloxone, 56.7 +/- 22.4%; p = 0.0003) and decreasing total sleep time and percent time in Stage 1. Furthermore, naloxone increased continuity of awake periods (mean length of awake periods increased from 27.0 +/- 8.4 to 66.0 +/- 66.6 s after naloxone, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We compared ventilatory effects of the nonsedating anxiolytic buspirone with those of the sedating anxiolytic diazepam in nine normal men. Resting ventilatory parameters and ventilatory responses to CO2 rebreathing and inspiratory threshold loading were measured before and after placebo, diazepam, and buspirone. Placebo had no ventilatory effects. Diazepam had no effect on resting ventilation but depressed response to CO2. Buspirone had no effect on resting ventilation or CO2 response. During loading, buspirone did not alter the augmentation of mouth pressure; diazepam produced a trend toward less augmentation. Both anxiolytics altered the load compensation response for the group; in particular, an increase in ventilation during loading (seen in three of nine subjects) was suppressed by drug administration. Diazepam also markedly depressed one subject's loaded ventilation below unloaded ventilation. In summary, buspirone did not cause the depression of respiratory center chemosensitivity that was seen with diazepam and produced less depression of load compensation in normal subjects. This suggests that it may be a safer anxiolytic in patients with lung disease

Drugs used in the treatment of anxiety are frequently sedating and tend to be respiratory depressants. Buspirone, a nonbenzodiazepine anxiolytic agent, has little reported sedative effect. It has been shown to be a respiratory stimulant in an anesthetized, glomectomized cat model. In this study, we examined the effects of two intraperitoneal single doses (10 and 20 mg/kg) of buspirone on sleep and respiration in unanesthetized, intact, freely moving rats. Buspirone increased sleep latency (p less than 0.0001) and decreased total sleep (p less than 0.02) through reductions in both non-REM and REM sleep. Respiratory rate (p less than 0.0003) and ventilation (p less than 0.004) were significantly increased for 4 h after drug injection. The effects on respiration were independent of those on sleep; stimulation was evident in both waking and non-REM sleep. This study suggests that buspirone, in addition to being free of sedating and respiratory depressant side effects when prescribed for anxiety in humans, may be a respiratory stimulant whose effects persist in sleep

Relationships of lung mechanics and diffusion to lung volume were examined in 38 patients with interstitial lung disease to determine whether patterns of reduction relate to severity of disease, distinguish histologic characteristics or predict prognosis for reversibility. Normal volume-related values for both mechanics and diffusion were seen throughout the range of severity of disease. The ratio of mechanics to lung volume did not correlate with the ratio of diffusion to lung volume in the same patient. Volume relationships of mechanics and diffusion failed to distinguish pathologic predominance of fibrosis or inflammation/granulomas. These ratios failed to predict reversibility in patients who had repeated tests. These results suggest that in patients with interstitial lung disease the significance of 'volume-adjustment' of mechanics and diffusion should be viewed with caution; these parameters do not appear to contribute to the assessment of pathophysiology or correlate with clinical spectrum of interstitial lung diseases

Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment