Utility of positive bronchoalveolar lavage in predicting respiratory failure after hematopoietic stem cell transplantation: a retrospective analysis.

Pulmonary complications occur frequently after hematopoietic stem cell transplantation (HSCT) and account for considerable mortality when associated with respiratory failure. Bronchoalveolar lavage (BAL) is commonly used in the diagnostic evaluation of pulmonary infiltrates in HSCT patients. Although the yield of BAL is well established in this setting, the impact on outcome is controversial. In addition, respiratory failure in HSCT patients is associated with high mortality. To determine if positive BAL predicted less respiratory failure and better survival, a retrospective review (between 1992 and 1998) of all HSCT patients who had bronchoscopy with BAL as part of their diagnostic evaluation for new pulmonary infiltrates was performed. Twenty-one patients met the inclusion criteria. Eleven patients (52%) had a positive BAL, defined as the isolation of infectious microorganisms or pulmonary hemorrhage in the lavage specimen. Most of the positive findings were pathogenic organisms (bacterial, fungal, and viral). Respiratory failure (defined as need for both intubation and mechanical ventilation) occurred in 11 of 21 patients (52%)-8 of 11 (73%) who had positive BAL compared with 3 of 10 (30%) who had negative BAL (P = .09). The overall mortality rate was 11 of 21 patients (52%). All deaths except one occurred as a direct result of respiratory failure. Although this study confirmed the high mortality rate in HSCT patients with respiratory failure, the BAL results were not predictive of outcome.

Etanercept therapy for late-onset idiopathic pneumonia syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation.

Idiopathic pneumonia syndrome (IPS) is a noninfectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (AHSCT), which usually develops within the first 100 days after transplantation. Donor T-cell-derived tumor necrosis factor-alpha (TNF-alpha) may play a crucial role in the pathogenesis of IPS, and inhibition of TNF-alpha has been used as a therapeutic option. We report two patients who had late-onset IPS about day 150 after nonmyeloablative AHSCT (NMA-AHSCT). They responded well to etanercept in combination with standard immunosuppressive drugs. Both patients had relapses and responded to retreatment with etanercept-based therapy. One patient was alive at 30 months after the initial diagnosis on long-term maintenance therapy with etanercept. The second patient was lost to follow-up at our institution but died 13 months after the onset of IPS. Our two cases showed that IPS could develop late after NMA-AHSCT and inhibition of TNF-alpha activity can be therapeutically effective.

Effect of pramipexole in treatment of resistant restless legs syndrome.

OBJECTIVE: To report the results of an open-label trial with a dopaminergic agent, pramipexole, in patients with treatment-resistant restless legs syndrome (RLS). MATERIAL AND METHODS: We studied the response to pramipexole in a consecutive series of 16 patients with symptomatic RLS who had previously experienced failure with other dopaminergic therapies. Patients assessed their posttreatment change in symptoms of RLS on a visual analog scale and indicated drug-related side effects with use of a checklist. RESULTS: With a mean dose of pramipexole of 0.3 mg, most patients reported clinically significant improvement. From 2 to 3 months after initiation of pramipexole therapy, nocturnal leg restlessness, involuntary leg movements, and insomnia had decreased in 12, 10, and 11 patients, respectively. The most frequent adverse effects were fatigue and stiffness, which occurred in a third of the patients. Overall, the drug was well tolerated. CONCLUSION: On the basis of these findings, we propose that pramipexole, a D2 subgroup receptor agonist, is an effective agent for treatment of RLS.

Fast-computed tomographic evaluation of the effect of route of breathing on upper airway size and function in normal men.

Nasal obstruction is associated with increased sleep disordered breathing (SDB), even in normal subjects. This increase in SDB may result from narrowing of the orohypopharyngeal (OHP) or retroglossal segment of the upper airway (UA) due to retropositioning of the jaw and tongue base as the mouth is opened and route of breathing changed from nasal to oral. It is postulated that significant narrowing of the OHP occurs with oral breathing even in the awake state. To ascertain the effect of route of breathing on the UA, fast-CT was used to study the UA response to the route of breathing in 30 normal, awake men, with each subject breathing via the nasal and oral routes under the following conditions: end-inspiration during tidal breathing (VTei) and functional residual capacity (FRC). In the velopharyngeal (VP) or retropalatal segment of the UA, minimum (Amin) and mean (Amean) cross-sectional areas (CSA) decreased 49 +/- 11 percent and 16 +/- 6 percent, respectively, with oral compared with nasal breathing at FRC. In the OHP, Amin at FRC increased by 26 +/- 15 percent with oral compared with nasal breathing with no significant change in Amean. Similar changes in CSA of both the VP and OHP were observed at VTei. Genioglossal electromyographic (EMGgg) activity increased from 12 +/- 1 microV breathing nasally to 27 +/- 4 microV breathing orally at FRC. Although the CSA of the VP segment decreased with conversion from nasal to oral breathing, Amin of the OHP segment was unexpectedly observed to increase with oral breathing. The doubling of EMGgg activity with oral breathing suggests that active contraction of the genioglossus may function to increase the patency of the OHP segment during oral breathing in supine, awake, normal subjects.

Fast-CT evaluation of the effect of lung volume on upper airway size and function in normal men.

The present study was performed to evaluate the regional changes in pharyngeal cross-sectional area (CSA) that occur with changes in lung volume in normal men. Fast-CT and genioglossal electromyogram (EMGgg) were used to study upper airway (UA) size and dilator muscle activity at TLC, lung volume at end-tidal inspiration (VTei), FRC, and residual volume (RV) in 30 men with a mean age of 46 +/- 3 yr and no significant sleep-disordered breathing, mean AHI = 4 +/- 1 per hour. Compared with values at FRC, minimum CSA (Amin) increased 154 +/- 31% at TLC (p = 0.0001), 19 +/- 10% at VTei (p = 0.03), and there was a trend toward a decrease of 31 +/- 12% at RV (p = 0.07). Similar but smaller changes were observed in mean CSA (Amean), with an increase of 69 +/- 14% at TLC (p = 0.0001), 8 +/- 5% at VTei (p = 0.01), and a decrease of 17 +/- 7% at RV (p = 0.01). Both the velopharyngeal (VP) and orohypopharyngeal (OHP) segments of the UA increased in size with increasing lung volume. Both Amin and Amean of the OHP segment at TLC were larger (55 +/- 19 and 38 +/- 14%, respectively) than the respective measurements in the VP segment. EMGgg activity doubled from 12 +/- 1 microV at FRC to 25 +/- 1 microV at TLC (p = 0.006). There was no change in EMGgg with tidal ventilation or with exhalation to RV. Changes in CSA directly paralleled changes in lung volume in this group of normal awake nonobese men.(ABSTRACT TRUNCATED AT 250 WORDS)

Fast-computed tomography evaluation of age-related changes in upper airway structure and function in normal men.

The reasons for the increase prevalence of snoring and sleep-disordered breathing in elderly adults are not clear. We hypothesized that age-related reductions in upper airway (UA) size, increased UA collapsibility, and/or inadequate compensatory action of the UA dilator muscles were contributory factors. Fast-computed tomography (CT) was used to examine UA size at FRC and atmospheric pressure, as well as its collapsibility and distensibility in response to negative and positive UA pressures actively generated by the subjects at FRC. The electromyographic activity of the genlogiossal muscle group (EMGgg) was recorded to assess UA dilator muscle response. Thirty adult men with normal overnight polysomnography (mean AHI = 4 +/- 1/h) were studied, and three subgroups of 10 subjects each, young (20-39), middle-age (40-59), and old (60-79), were compared. Unexpectedly, minimal UA cross-sectional area (Amin) at FRC and atmospheric pressure was larger in the old group than in the young group (73 +/- 9 versus 49 +/- 7 mm2, p = 0.04). In response to negative UA pressures of -10 and -50 cm H2O, there were no significant age group differences in Amin, indicating that no age-related increase in UA collapsibility was present. Although no significant difference in tonic EMGgg activity at FRC and atmospheric pressure was detected between groups, the old group demonstrated greater EMGgg activity than did the younger age groups in response to negative UA pressure loading (p less than 0.05). This finding indicated increased compensatory UA dilator muscle activity in response to negative pressures in the older subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Upper lobe pulmonary parenchymal calcification in a patient with AIDS and Pneumocystis carinii pneumonia receiving aerosolized pentamidine.

In patients with AIDS-related Pneumocystis carinii infection occurring during aerosolized pentamidine prophylaxis, roentgenographic findings may be atypical. Pulmonary parenchymal calcification due to P carinii is rare. In this case, extensive upper lobe pulmonary parenchymal, splenic, and nodal calcifications occurred after two years of monthly treatments with aerosolized pentamidine.

Pulmonary mechanics in lymphangioleiomyomatosis.

Standard pulmonary function and mechanics studies were done in eight female patients with lymphangioleiomyomatosis diagnosed by open-lung biopsy. Five patients were studied before hormone treatment. The mean age of the patients was 40 +/- 3 (SEM) years. Two of the eight had a smoking history of 10 pack-years or more, but all had quit smoking several years before evaluation. There was a trend toward increased total lung capacity (114 +/- 7% expressed as mean of percentage predicted +/- SEM) and increased residual volume (207 +/- 24%). Of the eight patients seven had expiratory obstruction as evidenced by the reduced forced expiratory volume in 1 s/forced vital capacity ratio [( FEV1/FVC] 61 +/- 6%). Steady-state diffusing capacity for carbon monoxide was reduced in seven of the patients (57 +/- 12%). Pulmonary mechanics studies performed in a body plethysmograph revealed a modest reduction in retractive force both at total lung capacity and at 90% total lung capacity (67 +/- 10 and 59 +/- 9%, respectively). Static compliance tended to be increased (128 +/- 19%). Pulmonary flow resistance was markedly elevated (266 +/- 46%). Maximal flow-static recoll curves revealed that in the seven patients with expiratory obstruction the cause was predominantly airway narrowing rather than loss of lung elastic forces. We conclude that in this group of patients with lymphangioleiomyomatosis there was no evidence for significant restriction. Although there was some decrease in retractive force consistent with emphysema, expiratory flows were reduced predominantly because of airway narrowing or obstruction rather than loss of pulmonary elastic recoil forces.

Nasal and oral flow-volume loops in normal subjects and patients with obstructive sleep apnea.

Because flow-volume loops (FVLs) are clinically useful in evaluating upper airway (UA) obstruction and the fact that patency of the nasopharyngeal ventilatory pathway is important to the prevention of obstructive sleep apnea (OSA), the present study examined the role of nasal compared with oral FVLs in evaluating patients with OSA. Fourteen obese male patients 56 +/- 3 yr of age with a mean apnea plus hypopnea index (AHI) of 51 +/- 9/h were studied along with 14 nonobese, healthy, age- and sex-matched control subjects whose mean AHI was 6 +/- 1/h. Nasal and oral FVLs obtained in the normal subjects indicated the nose behaved like a variable resistor, with flow limitation during inspiration but not during expiration. In the patient group, flow limitation was observed during expiration as well as inspiration indicating nondistensibility of the nasopharyngeal ventilatory pathway in the patients compared to the control subjects. A change in body position from upright to supine in the OSA group was associated with small reductions in expiratory but not inspiratory flow rates. The area under the nasal supine flow-volume loop (FVLANaSup) was found to be highly correlated with awake resting PaO2 (r = 0.80) and PaCO2 (r = -0.83) in the patient group. In addition, multiple linear regression analysis revealed that PaO2 and the area under the nasal FVLs independently contributed to the prediction of AHI with a multiple R of 0.89. These results suggest that limitations to ventilation via the nasopharynx may significantly influence both gas exchange and the frequency of sleep-disordered breathing in patients with OSA.(ABSTRACT TRUNCATED AT 250 WORDS)