Spontaneous hemothorax. Report of 6 cases and review of the literature.

We present 6 cases of spontaneous hemothorax and comprehensively review the medical literature on this subject. We categorize the reported causes and offer a rational diagnostic approach to patients with nontraumatic hemothorax. We recommend specific treatments for specific etiologies, and emphasize the importance of well-established surgical principles for the treatment of hemothorax. Our suggestions should enable physicians to accurately diagnose and expeditiously treat patients with spontaneous hemothorax.

Graded comprehensive cardiopulmonary exercise testing in the evaluation of dyspnea unexplained by routine evaluation.

The evaluation of dyspnea is problematic when a cause is inapparent after initial diagnostic studies. We examined the results and role of cardiopulmonary exercise testing (CPET) in 50 patients with a mean 23 months of dyspnea and normal FEV1 and FVC. The CPET studies were interpreted by a panel and a consensus reached. Subsequent tests ordered by the primary physician were reviewed, and a final diagnosis was agreed on by the panel. Seven of 50 patients had cardiac limitation, 17 of 50 had pulmonary limitation, 14 of 50 had obesity and/or deconditioning, 1 of 50 had gastroesophageal reflux, and 16 of 50 had either psychogenic dyspnea or no identifiable disease. Five patients had more than one clinical diagnosis accounting for 55 diagnoses in the 50 patients. Those with a normal CPET had a higher VO2max and O2 pulse than those with cardiac disease, deconditioning, or hyperactive airways disease (HAD) (p < 0.05). Electrocardiographic changes identified cardiac disease while studies demonstrating ventilatory limitation identified a pulmonary process. In 24, deconditioning could not be distinguished from cardiac limitation. Of these, 14 responded to exercise training and/or weight loss, whereas 3 had cardiac disease, 7 had HAD, and 4 had psychogenic dyspnea (4 had more than one clinical diagnosis). In the 13 patients with normal CPET results, one had gastroesophageal reflux, two had HAD, four had psychogenic dyspnea, and six had no identifiable disease. We conclude that a diagnosis can be made in most patients with chronic dyspnea; however, further studies including bronchoprovocation are often required. Cardiopulmonary exercise testing is useful in identifying a cardiac or pulmonary process, but it is insensitive in distinguishing cardiac disease from deconditioning.

Dyspnea in a patient years after severe poliomyelitis. The role of cardiopulmonary exercise testing.

Dyspnea after polio can occur for a variety of reasons, including neuromuscular disease and upper airway abnormalities resulting from prolonged intubation, including tracheal stenosis, tracheomalacia, and vocal cord paralysis. Routine studies such as spirometry and maximum voluntary ventilation (MVV) measurements can give similar results in these conditions. We present a 50-year-old woman who as a child developed poliomyelitis that required tracheostomy and negative pressure ventilation. Thirty-nine years later, she developed breathlessness with normal spirometry but decreased MVV. The flow volume loop showed flattening of the inspiratory and expiratory limbs, consistent with a fixed upper airway obstruction or neuromuscular weakness. Exercise testing with measurement of exercise flow volume loops and respiratory pressures was performed. The patient was ventilatory limited with increasing end-expiratory lung volume through exercise. Flow volume loops confirmed flow limitation. Respiratory pressures did not change after maximal exercise. Further evaluation confirmed left vocal cord paralysis and tracheomalacia. This patient demonstrates that the causes of dyspnea after poliomyelitis can be multifactorial, and that routine evaluation may fail to elucidate the limiting factor. In this case, exercise testing provided valuable insight into the limiting factor for this patient and provided useful data for counseling and for further management.

Cardiopulmonary exercise testing following allogeneic lung transplantation for different underlying disease states.

OBJECTIVES: To assess the exercise response to single lung transplantation in chronic airflow obstruction (CAO), idiopathic pulmonary fibrosis (IPF), and pulmonary vascular disease (PVD) vs double lung transplantation at well-defined time points after transplantation, and to define the change in exercise response in SLT and DLT over the first year after transplantation. DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENTS: Fourteen stable SLT recipients (6 with CAO, 4 with IPF, 4 with PVD) and 11 stable DLT recipients. MEASUREMENTS: Spirometry, lung volumes, diffusion lung capacity for carbon monoxide (DLco) and MVV measured prior to exercise at 3 months (n = 25) then at 3-month intervals up to a maximum of 12 months post-transplantation (n = 18 [12 SLT and 6 DLT]). Symptom-limited cardiopulmonary exercise tests at same time points (n = 25 at 3 months, n = 18 [12 SLT and 6 DLT] at 3-month intervals up to 12 months). Breathlessness was estimated by visual analogue scale prior to exercise and at peak exercise. RESULTS: At 3 months, FEV1 percent predicted was lower for SLT-CAO and SLT-IPF vs DLT (p < or = 0.05). Mean FEV1/FVC was lower for SLT-CAO vs all other groups (p < or = 0.05). The FVC, MVV, and DLco/VA were similar for all groups. The TLC and RV were higher for the SLT-CAO group compared with all others. The TLC was lower for SLT-PVD compared with DLT. Exercise responses were similar in all groups studied without a statistically significant difference in achieved VO2, work rate, O2 pulse, anaerobic threshold, heart rate response, respiratory rate, VE/MVV, and VT/VC. The change in O2 saturation during exercise was the least in recipients of DLT. Maximal achieved VO2 rose from 3 to 6 months after SLT but dropped by 9 to 12 months after transplantation. Maximal achieved VO2 trended up from 3 to 6 months after DLT but dropped by 9 to 12 months after transplantation. Maximal achieved work rate rose in both SLT and DLT from 3 to 9 to 12 months after transplantation. There was no significant difference in breathlessness at rest and peak exercise measured between recipients of SLT or DLT. CONCLUSIONS: Minor differences in pulmonary function and change in O2 saturation occur between recipients of SLT and DLT during the first posttransplant year. These differences are most pronounced when comparing SLT-CAO with DLT. However, there is no significant difference in exercise capacity between SLT for CAO, IPF, PVD, and DLT. The rise in maximum achieved VO2 over the first 6 months after transplantation may reflect the effects of exercise training and should be taken into account when examining aerobic response after transplantation.

Pulmonary function in single lung transplantation for chronic obstructive pulmonary disease.

The primary determinants of pulmonary function after heart-lung or double lung transplantation are the volume and compliance of the recipient's thoracic cage. This study evaluated the influence of recipient chest wall factors on static and dynamic lung volumes after single lung transplantation for chronic obstructive pulmonary disease. Fourteen patients with chronic obstructive pulmonary disease received 15 single lung transplants (one retransplant). Posttransplantation follow-up data at 3 and 6 months, in the absence of infection or rejection, were available in nine patients. Overall pulmonary function at 6 months improved from preoperative levels to 55% to 65% of predicted values (forced vital capacity 38% to 55%, forced expiratory volume at 1 second 18% to 55%, maximum voluntary ventilation 21% to 65%), and allograft-specific pulmonary function improved to nearly normal predicted single-lung values (forced vital capacity 89%, forced expiratory volume at 1 second 90%, maximum voluntary ventilation 105%). Postoperative pulmonary function in these patients correlated significantly with preoperative thoracic volume measured by planimetry of chest radiographs. No correlation between postoperative pulmonary function was demonstrated with either the estimated volume of donated lung tissue or relative donor-to-recipient size matching. These findings support the concept that recipient chest wall factors determine postoperative pulmonary function in patients undergoing single lung transplantation for chronic obstructive pulmonary disease. Furthermore, the allograft lung functions at a normal level for the recipient and does not appear to be constrained by hyperinflation of the contralateral lung.

Limitations of spirometry in detecting rejection after single-lung transplantation.

Pulmonary function testing has been extensively studied in the heart-lung transplant (HLT) population and has been advocated as a screening test for rejection or infection; however, few data are available in the single-lung transplant (SLT) population. The effect of acute episodes of infection, rejection, and bronchiolitis on the pulmonary function of 30 SLT patients with varying underlying disease states was prospectively evaluated. The native disease process was obstructive in 17 (SLT-OBS), restrictive in six (SLT-IPF), and pulmonary vascular in seven (SLT-PVD). Rejection was associated with a drop in FVC from 71 +/- 15 to 62 +/- 14% of predicted, with a significant drop seen in all three subgroups. Statistically significant drops in FEV1 were also seen in the SLT-OBS and SLT-PVD subgroups but not in the SLT-IPF subgroup. A drop in FEV25-75% was seen only in SLT-PVD. The greatest fall in FVC, FEV1, and FEF25-75% was seen with bronchiolitis, followed by acute rejection. The sensitivity and specificity of spirometry as a predictor of infection or rejection were significantly lower than those previously reported for HLT, with SLT-PVD having the most and SLT-OBS the least clinically useful values. We conclude that a fall in spirometry is seen in infection and rejection in SLT and that the underlying disease state has a significant influence on the diagnostic utility of specific spirometric indices.

Lung mechanics and dyspnea after lung transplantation for chronic airflow obstruction.

Single lung transplantation (SLT) is widely used to treat chronic airflow obstruction (CAO). During exercise the native lung should increase end-expiratory lung volume (EELV) and result in a different respiratory sensation compared with double lung transplantation (DLT). Eight SLT recipients and 12 DLT recipients demonstrated a similar maximal work load and achieved VO2. VEmax/MVV was 67.2 +/- 4.0% in SLT recipients and 48.5 +/- 3.6% in DLT recipients (p = 0.003). All SLT recipients demonstrated an increase in EELV during exercise, which was seen in only three of 12 DLT recipients. The change in absolute EELV from rest to peak exercise was different between SLT recipients (+0.37 +/- 0.10 L) and DLT recipients (-0.10 +/- 0.06, p = 0.0002). Tidal flow volume loop analysis demonstrated encroachment of the expiratory limb in four of seven SLT patients but in only one of 12 DLT recipients. A lesser peak breathlessness in DLT recipients approached statistical significance (p = 0.051), although the relation of respiratory sensation versus VE or VO2% predicted did not differ between the two groups. EELV increases in SLT recipients at peak exercise, although overall aerobic response is preserved and respiratory sensation is similar.

Cytokine-induced neutrophil-derived interleukin-8.

During acute inflammation, the first line of cellular response for host defense is the neutrophil. In addition to the historic role of the neutrophil as a phagocyte, recent studies have identified this cell as an important source of a number of cytokines. In this study, we provide evidence that the neutrophil is a significant source of interleukin-8 (IL-8). Neutrophils freshly isolated from whole blood were not found to constitutively express IL-8 mRNA. In contrast, when these leukocytes were cultured on plastic they were activated, leading to the significant expression of de novo steady-state levels of IL-8 mRNA. In addition, when neutrophils were treated with cycloheximide, there was evidence for "superinduction" of steady-state levels of IL-8 mRNA and inhibition of antigenic IL-8 production. Neutrophils were subsequently stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha, or interleukin-1-beta and were found to express IL-8 mRNA and antigen in both a time- and dose-dependent manner. Furthermore, neutrophils stimulated with traditional chemotactic/activating factors, such as the split product of the fifth component of complement (C5a), formylmethionyleucylphenylalanine (fMLP), and leukotriene B4 (LTB4) in a dose-dependent manner did not produce significant antigenic IL-8, as compared with unstimulated controls. In contrast, when neutrophils were exposed to either of these neutrophil agonists in the presence of LPS, the production of antigenic IL-8 was significantly elevated, as compared with either of the stimuli alone, suggesting a synergistic response. These data would suggest that the neutrophil can no longer be viewed as only a phagocyte or warehouse for proteolytic enzymes, but is a pivotal effector cell that is able to respond to mediators in its environment and generate cytokines. This latter neutrophil response may be important for either the elicitation of additional neutrophils or to orchestrate the conventional immune response at sites of inflammation.

Regulation of neutrophil-derived IL-8: the role of prostaglandin E2, dexamethasone, and IL-4.

Historically, the neutrophil has been perceived as a terminally differentiated leukocyte with limited ability to produce de novo proteins. Furthermore, in the context of acute inflammation the activated neutrophil has been appreciated only for its ability to release various proteases, reactive oxygen, and arachidonic acid metabolites. Recently, the neutrophil has been shown to have the capacity to produce a number of cytokines that may be instrumental in orchestrating the progression of acute inflammation to a more chronic and specific immune response. These cytokines include IFN-alpha, M-CSF, G-CSF, TNF, IL-1, and IL-6. Our laboratory and others have shown that neutrophils produce IL-8 in response to LPS or a phagocytic challenge. Although these studies have shown the induction of IL-8 from polymorphonuclear neutrophils (PMN), relatively little is known regarding the regulation of PMN-derived IL-8. Because PMN and monocytes share the same stem cell, and monocyte-derived IL-8 is regulated by prostaglandin E2 (PGE2), glucocorticoids (dexamethasone; DEX) and the T-Lymphocyte-derived IL-4, we postulated that PMN-derived IL-8 production may be regulated in a similar manner. To test this hypothesis, PMN were isolated (> 99% pure) from peripheral blood and cultured in media with 5% FCS in the presence or absence of LPS (10 ng/ml; a concentration of LPS that induced the half-maximal production of PMN-derived IL-8) and in the presence or absence of DEX (10(-6) M to 10(-10) M), PGE2 (10(-6) M to 10(-10) M), or IL-4 (100 ng/ml to 100 pg/ml). PMN-derived IL-8 was measured using a specific sandwich ELISA. DEX and IL-4 in the presence of LPS were found to inhibit PMN-derived IL-8 in both a dose- and time-dependent fashion. DEX and IL-4 in concentrations of 10(-6) M and 10 ng/ml resulted in maximal inhibition of LPS-induced PMN-derived IL-8, respectively. Moreover, both DEX and IL-4 administration could be delayed 4 hr post-stimulation with LPS and result in significant suppression of PMN-derived IL-8. Interestingly, in contrast to the regulation of monocyte-derived IL-8 by PGE2, PGE2 treatment of PMN failed to inhibit the generation of LPS-induced IL-8. Northern blot analysis of steady-state IL-8 mRNA demonstrated that both DEX and IL-4 treatment of PMN resulted in a 40 and 52% reduction in LPS-stimulated PMN-derived IL-8 mRNA, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Endobronchial ultrasound-guided needle aspiration of mediastinal adenopathy.

We conducted a randomized, controlled trial to prospectively confirm that ultrasound-directed transbronchial needle aspiration (USTBNA) results in: (1) improved sensitivity for detecting lymph nodes involved with neoplasm, and (2) a decreased number of aspirates needed to achieve a diagnosis as compared with standard transbronchial needle aspiration (TBNA). The study was conducted in a tertiary medical center on patients undergoing fiberoptic bronchoscopy in the evaluation of enlarged mediastinal lymph nodes. USTBNA or TBNA were followed by rapid, on-site cytopathology examination of the collected specimens. Measurements included the (1) age and sex of the patient, prior diagnosis of cancer, nodal short-axis diameter and node location as determined by computerized tomography (CT), and endobronchial abnormalities at bronchoscopy; (2) number, order, and location of transbronchial aspirates and results of on-site evaluation; (3) results of surgical exploration in patients with negative transbronchial needle aspiration; (4) sensitivity, specificity, and diagnostic accuracy of USTBNA and TBNA; (5) number of aspirates required for successful lymph node aspiration as well as for a diagnosis of cancer for both USTBNA and TBNA; and (6) multiple logistic regression analysis to determine the significance of combinations of clinical predictors and needle aspirate results. Eighty-two bronchoscopic examinations were performed on 80 patients. We found no significant difference between USTBNA and TBNA in sensitivity (82.6% versus 90.5%, respectively), specificity (100% for both), or diagnostic accuracy (86.7% versus 91.7%, respectively). The sensitivity, specificity, and diagnostic accuracy of USTBNA and TBNA were similarly high, regardless of node location (paratracheal or subcarinal). A decrease in the number of aspirates required for lymph node sampling approached statistical significance for all USTBNAs as compared with TBNAs (2.03 +/- 0.19 versus 2.62 +/- 0.25, p = 0.06), but this was not demonstrated for the number required to confirm cancer (1.95 +/- 0.47 versus 2.68 +/- 0.21, p = 0.17). The number of aspirates to successful lymph node aspiration decreased with USTBNA versus TBNA in paratracheal lymph nodes (2.00 +/- 0.20 versus 2.91 +/- 0.34, p = 0.03), but not to a diagnosis of cancer (1.93 +/- 0.25 versus 3.00 +/- 0.58, p = 0.11). No difference was seen in the number of aspirates for subcarinal nodes. The number of TBNA attempts for paratracheal lymph node sampling was inversely correlated with node size (r = 0.48, p = 0.02). No such relation was seen with USTBNA of paratracheal nodes (r = 0.09, p = 0.66), TBNA of subcarinal nodes, or USTBNA of subcarinal nodes. A similar relation was seen between the number of aspirates to a diagnosis of cancer. On multiple logistic regression analysis, a positive transbronchial aspirate was associated only with a larger lymph node and history of prior cancer. We conclude that: (1) in the setting of on-site cytopathology, transbronchial needle aspiration has a high sensitivity, specificity, and diagnostic accuracy in the evaluation of enlarged mediastinal lymph nodes suspected of harboring malignancy; (2) mediastinal anatomy, including vascular structures and lymph nodes, is clearly imaged with endobronchial ultrasonography; (3) a greater short-axis diameter of the mediastinal lymph node and history of a prior malignancy increase the likelihood of a positive transbronchial aspiration; (4) USTBNA exhibits a similarly high diagnostic yield to TBNA in the setting of rapid on-site cytopathology evaluation; (5) USTBNA decreases the number of aspirates required for paratracheal lymph node sampling, which may be particularly useful in sampling smaller paratracheal nodes or at institutions that do not utilize rapid on-site cytopathology evaluation.