Sleep-disordered breathing and hypotension.

We investigated the presence of low blood pressure (BP) in 4,409 subjects referred for overnight polysomnography. A low resting arterial BP (systolic BP < 105 mm Hg, diastolic BP < 65 mm Hg) was present in 101 subjects (2.3%). Low BP was more prevalent in subjects with upper airway resistance syndrome (UARS) (23%) than in subjects with obstructive sleep apnea syndrome (OSAS) (0.06%), parasomnia (0.7%), restless leg syndrome (0.9%), or psychological insomnia (0.9%). In order to investigate BP homeostasis, we conducted polysomnography followed by tilt-table testing on 15 subjects with orthostatic intolerance (OI) and UARS, five normotensive subjects with UARS, five subjects with insomnia and low BP, 15 subjects with OSAS, and 15 healthy control subjects. Fifteen subjects with UARS and OI and 15 healthy controls also underwent 24-h ambulatory BP monitoring. Subjects with OI and UARS had lower mean daytime systolic (119 +/- 28 mm Hg) and diastolic (75 +/- 18 mm Hg) BP than did control subjects (131 +/- 35 mm Hg and 86 +/- 19 mm Hg, respectively) (p < 0.05). During tilt-table testing, subjects with UARS and a history of OI had a greater decrease in systolic BP (27 +/- 3 mm Hg) than did control subjects (7.5 +/- 1.6 mm Hg), subjects with OSAS (6.8 +/- 1.2 mm Hg), normotensive subjects with UARS (7.2 +/- 0.84 mm Hg), or hypotensive insomniacs (7.4 +/- 1.1 mm Hg) (p < 0.01). We conclude that approximately one fifth of subjects with UARS have low BP and complain of OI. Tilt-table testing may be indicated to confirm orthostatic intolerance in subjects with UARS.

Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death.

This study investigates the presence of CD8(+) T lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. Postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease (control subjects). Using immunohistochemical techniques, the CD8(+) cytotoxic T-cell population in peribronchial tissue was characterized in three patient groups. The percentage of CD8(+) cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 +/- 1.92% versus 3.93 +/- 1.63% and 1.09 +/- 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 +/- 1.5%) compared with 1.39 +/- 0.9; 1.8 +/- 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN-gamma) by CD8(+) T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-gamma/IL-4 ratio in the AD group was less than half that of the control group (1.46 +/- 0.2 versus 3.2 +/- 0.1; p = 0.02). Using polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in lung tissue from three of the seven cases in the AD group. Two of these cases also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was detected in five of the AUC group and in one of these cases, RV was also detected. No viral genome was detected in the lungs of the control group. In conclusion, this study provides novel evidence of an aberrant CD8(+) T-cell population, possibly in response to viral infection in subjects who die of acute asthma.

40-O-(2-hydroxyethyl)-rapamycin attenuates pulmonary arterial hypertension and neointimal formation in rats.

Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/kg/d, by gavage): Group PMR(5-35) from Day 5 to Day 35, Group PMR5-14 from Day 5 to Day 14, and Group PMR15-35 from Day 15 to Day 35. By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (Ppa = 41 +/- 3 mm Hg) (p < 0.001), right ventricular systolic pressures (Prv,s = 45 +/- 2 mm Hg) (p < 0.01), and right ventricle/(left ventricle plus septum) (0.55 +/- 0.05) (p = 0.028) than rats in Groups PMR5-35 (Ppa = 25 +/- 3 mm Hg, Prv,s = 32 +/- 7 mm Hg, RV/LV&S = 0.42 +/- 0.06) and PMR5-14 (Ppa = 29 +/- 4 mm Hg, Prv,s = 30 +/- 5 mm Hg, RV/LV&S = 0.43 +/- 0.07). Pulmonary arterial neointimal formation (quantified by a vascular occlusion score) was more severe in vehicle-treated rats (1.93 +/- 0.03) than in Groups PMR5-14 (1.56 +/- 0.27) and PMR(5-35) (1.57 +/- 0.1) (p < 0.01). RAD attenuates the development of MCT-induced pulmonary arterial hypertension in the pneumonectomized rat.

Biomedical ethics and the withdrawal of advanced life support.

It is common for health care providers to deal with the complex and difficult issue of withdrawing advanced life support. The patient is always the key source of authority in these decisions. The most important ingredient in end-of-life decision making is effective communication. It is important to try to ascertain what the patient thought about quality-of-life values before surrogate decisions can be made on the patient's behalf. The concepts of beneficence, nonmaleficence, autonomy, and justice are the foundation of ethical decision making. Numerous legal precedents have laid the groundwork for end-of-life decision making. Most state courts have supported withholding and withdrawing life support from patients who will not regain a reasonable quality of life. The recent Patient Self-Determination Act encourages patients to fill out advance directives that state their desires. When continued intensive care is futile, advanced life support should be withdrawn. However, a narrow definition of futility in this situation is the key, since the concept of futility could lead to inappropriate decisions. It is best to consider a situation futile when the patient is terminally ill, the condition is irreversible, and death is imminent. During the withdrawal of advanced life support, terminal or rapid weaning is preferable to extubation. Combinations of opiates, benzodiazepines, and other agents help provide comfort to patients who are suffering.

Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats.

This paper reports the effect of triptolide (a diterpenoid triepoxide) on the development of monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague- Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Rats received therapy from Day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml of ethanol/cremophor intraperitoneally, every other day, n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmonary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 versus 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significantly less right ventricular hypertrophy (RVH) and pulmonary arterial neointimal formation. In a rescue experiment, rats initiated therapy on Day 21. At Day 35, vehicle-treated rats (n = 4) had higher mPAP (40 +/- 9 mm Hg), greater RVH, and more severe pulmonary arterial neointimal formation than rats that received triptolide (0.25 mg/kg every other day, n = 7, mPAP 30 +/- 4 mm Hg) and rats that received triptolide (0.2 mg/kg daily, n = 7, mPAP 25 +/- 5 mm Hg, p < 0.01). In pneumonectomized rats that receive MCT, triptolide attenuates the development of pulmonary hypertension and RVH, and promotes regression of pulmonary arterial neointimal formation.

Influenza pneumonia in a paediatric lung transplant recipient.

Although a common cause of morbidity and mortality in the general population, influenza infections are uncommon in lung transplant recipients and, to date, have only been associated with transient declines in pulmonary function and a relatively benign clinical course. This paper describes severe influenza pneumonia in a 13-year-old paediatric lung transplant recipient (5 months after double lung transplantation). Influenza pneumonia was diagnosed by direct fluorescent antibody testing and viral culture of bronchoalveolar lavage fluid. The patient required mechanical ventilation for 2 days due to respiratory failure and fatigue. Since his recovery from this pneumonia, he has developed obliterative bronchiolitis and currently awaits re-transplantation.

The surgical management of severe gastroparesis in heart/lung transplant recipients.

This article describes the use of gastric bypass surgery for severe gastroparesis in two lung transplant recipients. In addition to feeding intolerance, both our patients suffered from severe erosive esophagitis, transfusion-dependent upper GI hemorrhage, and recurrent aspiration pneumonia. They responded poorly to promotility agents and were eventually treated with Roux-en-Y esophagojejunostomy-one patient with subtotal gastrectomy, and one with gastric bypass without distal gastric resection. Both cases were improved by surgery. Early surgical referral may be indicated in the management of lung transplant recipients with severe symptomatic gastroparesis in whom medical management has failed. On the basis of our experience, gastric bypass with esophagojejunostomy is a worthwhile option in lung transplant recipients with severe gastroparesis.

Vascular reactivity in obstructive sleep apnea syndrome.

The obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular disease and systemic hypertension. Because systemic arterial blood pressure is proportional to venodilation and venous return to the heart, we hypothesized that altered vascular responsiveness might exist in the veins of subjects with OSAS. We therefore investigated venodilator responses in awake, normotensive subjects with and without OSAS, using the dorsal hand vein compliance technique. Dose-response curves to bradykinin and nitroglycerin were obtained from 12 subjects with OSAS and 12 matched control subjects. Maximal dilation (E(max)) to bradykinin was significantly lower in the OSAS group (62.1% +/- 26.1%) than in the control group (94.3% +/- 10.7%) (p < 0.005). Vasodilation to nitroglycerin tended to be lower in the OSAS group (78.6% +/- 31.8%) than the control group (100.3% +/- 12.9%), but this effect did not reach statistical significance. When six of the OSAS subjects were retested after 60 d of treatment with nasal continuous positive airway pressure (CPAP), E(max) to bradykinin rose from 60.3% +/- 20. 3% to 121.4% +/- 26.9% (p < 0.01). Vasodilation to nitroglycerin also increased, but this effect did not reach statistical significance. These results demonstrate that a blunted venodilatory responsiveness to bradykinin exists in OSAS. This effect appears to be reversible with nasal CPAP therapy.

The reproducibility of repeat measures of airway inflammation in stable atopic asthma.

Measures of airway inflammation are increasingly being used as outcome measures in asthma intervention studies. Meaningful interpretation of observed changes in bronchial mucosal cell numbers should depend, in part, on the reproducibility of repeat measures over time. We wanted to investigate the reproducibility of immunopathologic and physiologic parameters after short and long measurement intervals. We therefore performed spirometry, bronchial provocation challenge, and fiberoptic bronchoscopy with endobronchial biopsy (always right upper lobe second-generation bronchus) at baseline, after 2 wk, and again after 8 wk on nine subjects with stable atopic asthma (receiving inhaled placebo and beta-agonist therapy only). Numbers of T cells, memory T cells (CD45Ro(+)), macrophages (CD68(+)), and eosinophils (EG1(+) and EG2(+)) on immunohistochemical stains of bronchial biopsies were quantified by computerized image analysis. Intraclass correlation coefficients (ICCs) of reproducibility were calculated for repeat measures of each parameter and a high ICC (greater than 0.6) was interpreted as "highly reproducible." Repeat measures of FEV(1), FEF(25-75%), and PC(20) were highly reproducible after short (2-wk) and long (8-wk) intervals. Only repeat measures of EG2(+) had an ICC greater than 0.6 after 8 wk. Repeat measures of CD45Ro(+), EG2(+), and T cell numbers (but not CD68(+) and EG1(+) cells) are highly reproducible and reliable parameters of asthmatic airway inflammation after a 2 wk interval.

Constrictive pericarditis due to coccidiomycosis.

Coccidiomycosis is a fungal infection that rarely causes cardiac disease. Constrictive pericarditis in the setting of disseminated coccidiomycosis can be fatal, despite antifungal therapy and pericardiectomy. We report on a patient with constrictive pericarditis due to localized infection by Coccidioides immitis. The patient underwent successful surgical pericardiectomy and antifungal chemotherapy, and remains well 1 year later.

Endobronchial stenting for severe airway obstruction in relapsing polychondritis.

Airway complications of relapsing polychondritis (RP), including tracheobronchial stenosis, can be fatal. This paper describes a life-saving technique (placement of multiple metallic endobronchial stents under conscious sedation) to prevent life-threatening airway closure in a 50-year-old woman with RP. Using fluoroscopic and bronchoscopic guidance, a tracheal stent and three endobronchial metallic stents were deployed in the central airways, with good functional outcome. There were no complications. In critical airway compromise caused by RP, the insertion of endobronchial stents can result in improved symptoms, pulmonary function, and a return to daily activities, without the use of tracheotomy and mechanical ventilation.