Are morning headaches part of obstructive sleep apnea syndrome?

To determine whether morning headaches are a consistent symptom in sleep apnea, we reviewed clinical and polysomnographic data of 304 patients with sleep apnea and compared the findings with normal control subjects and with three other groups of patients seen at a sleep disorders center. Eighteen percent of patients with sleep apnea had frequent morning headaches compared with 21% to 38% in the other groups of patients and 6% of control subjects. In patients with sleep apnea, morning headaches were most common in those with mild predominantly nonobstructive apnea. Polysomnographic characteristics of patients with moderate to severe sleep apnea did not significantly differ between patients with frequent headaches and those without such headaches. Frequent morning headaches are a nonspecific symptom in patients with sleep disorders and are not a consistent or reliable symptom of sleep apnea syndrome.

Preliminary findings in the treatment of obstructive sleep apnea with transtracheal oxygen.

The effects of continuous low flow oxygen via transtracheal oxygen delivery (TTOD) were assessed in four patients with obstructive sleep apnea (OSA) and daytime hypersomnolence who were unable to tolerate continuous positive nasal airway pressure (CPAP). The overall quality of sleep, sleep fragmentation, pattern of respiration, and nocturnal oxygen saturations were evaluated with the patients receiving 2 to 3 L/min of oxygen by TTOD, and the results were compared to polysomnograms with and without nasal cannula oxygen. The mean respiratory disturbance index (apneas plus hypopneas/hour of sleep) was improved by TTOD compared to no therapy or nasal cannula oxygen, and improvement in sleep disturbance was associated with improvement in overall nocturnal oxygen saturation. The mean apnea duration was not increased by TTOD and the duration of the longest apneic spells was decreased by 33 to 85% with this therapy. These improvements in respiratory status were accompanied by symptomatic improvement in daytime sleepiness, and there were no significant side effects. These findings suggest that TTOD may be a safe and effective alternative treatment of OSA for some patients who are unable to tolerate nasal CPAP therapy.

Conventional mechanical ventilation.

Mechanical ventilation has become a very common and well-accepted practice in modern intensive care units. The use of the mechanical ventilator has progressed from being a support system during surgery and for acutely ill patients to being used in both moderate and long-term life support in patients with inadequate ventilation. The sophistication of modern ventilators and the ability of trained respiratory therapists and nursing personnel have permitted this technology to explode. This is occurring at a time when there are still many controversies about the relative benefits and modes of action of conventional ventilation. As newer techniques are developed, it is mandatory that the application of these techniques be tempered with controlled clinical trials, documenting their effectiveness. The beneficial effects of new modalities must be documented as mechanical ventilation expands from use in the intensive care unit to use in standard medical wards and the patient's home. In these latter two settings, the vigilance of an intensive care unit is absent and the simplest method will be preferable. The requirement to demonstrate efficacy of new techniques with adequate studies is especially necessary now as the economics of health delivery have come under increasing scrutiny. Even more important than new technologies may be the efficacy of prolonged mechanical ventilation. A recent study by Spicher and White evaluated the outcome in 250 patients ventilated for 10 days or more at the Hershey Medical Center (Pennsylvania State University). The mortality, morbidity, and disability in patients in this study population requiring prolonged ventilation were extremely high. As these studies have pointed out, further evaluations of predictors of meaningful survival are necessary to avoid unnecessary human suffering and to best use limited resources.

Protein kinase C activation modulates arachidonic acid metabolism in cultured alveolar epithelial cells.

Cultured alveolar type II cells can liberate esterified arachidonic acid (AA) and metabolize it predominantly via the cyclooxygenase pathway, and their capacity to do so increases as they alter their phenotype over time in culture. Little is known, however, about the regulation of AA metabolism in alveolar pneumocytes. We have examined the effects of protein kinase C (PKC) activation on arachidonate metabolism in primary cultures of rat alveolar epithelial cells studied at 2 and 7 days following isolation. The potent PKC activator phorbol myristate acetate (PMA) stimulated dose-dependent increases in free AA levels in both day 2 and day 7 cultures, with optimal stimulation at 50 nM. Greater stimulation was demonstrated for day 7 cells, and this was associated with greater prostanoid synthesis in response to PMA by day 7 than by day 2 cells. The capacity of PMA to "prime" epithelial cells for augmented AA liberation and metabolism in response to calcium ionophore A23187 (5 microM) was examined also. Significant priming by PMA was observed in both day 2 and day 7 cells; once again, augmentation of both free AA levels as well as prostaglandin E2 levels was greater for day 7 cells than for day 2 cells. That the capacity of PMA to modulate AA metabolism was mediated by activation of PKC was confirmed by demonstrating that (1) phorbol didecanoate, which lacks the ability to activate PKC, failed to activate AA metabolism; (2) pretreatment for 18 h with 1 microM PMA, which depletes cellular PKC, abolished subsequent AA metabolism activated by 50 nM PMA; and (3) the PKC inhibitor staurosporine abrogated increases in the quantities of both free AA and prostaglandin E2 in response to PMA. We conclude that activation of PKC increases the availability of AA for prostanoid synthesis in alveolar pneumocytes, and that this effect is more evident as type II cell differentiation is modeled during prolonged cultivation.

Arachidonic acid metabolism by rat alveolar epithelial cells.

Arachidonic acid release and metabolism by stimulated cultures of rat type II alveolar epithelial cells (94 +/- 2% pure) were studied. As compared with unstimulated cultures, a marked increase in the release of [14C]arachidonic acid from prelabeled cells was observed when the cells were incubated with the calcium ionophore A23187. Radioimmunoassay of unlabeled cultures demonstrated significant increases in the production of prostaglandin E2 greater than 6-Keto-prostaglandin F1 alpha greater than prostaglandin F2 alpha greater than thromboxane B2 with A23187 stimulation. Reverse-phase high performance liquid chromatography of media from cells prelabeled with [14C]arachidonic acid confirmed the identities and relative amounts of these metabolites. As expected, the production of these cyclooxygenase products was inhibited by indomethacin. Stimulation with A23187 led to no increment in immunoreactive leukotriene C4 production, but yielded a statistically significant but quantitatively small increment in leukotriene B4 production; its production by small numbers of contaminating macrophages cannot be ruled out. Analysis by high performance liquid chromatography of media from prelabeled cells after 30 minutes stimulation revealed no peaks of radioactivity coeluting with the lipoxygenase products leukotriene B4, leukotriene C4, or 5-, 12-, or 15-hydroxy-6,8,11,14-eicosatetraenoic acid. The results indicate that rat alveolar epithelial cells have the capacity to release arachidonic acid and metabolize it to an array of cyclooxygenase products. However, after stimulation, little or no lipoxygenase products accumulated in media. Thus, the alveolar epithelium may be a source of bioactive eicosanoids with potentially important roles in pulmonary physiology and pathophysiology.

Rat alveolar macrophages synthesize leukotriene B4 and 12-hydroxyeicosatetraenoic acid from alveolar epithelial cell-derived arachidonic acid.

Although recent reports have described arachidonic acid metabolism of individual types of lung cells, the actual profile of eicosanoids that are produced in the lung may reflect interactions between different cell types. Because macrophages and epithelial cells are in close physical contact within the alveolus, we measured the eicosanoids produced by combined cultures of these cells. We found that the [14C]arachidonic acid that was released from previously labeled epithelial cells following A23187 stimulation was metabolized by alveolar macrophages to leukotriene B4 and 12-hydroxyeicosatetraenoic acid, which are products not normally produced by these epithelial cells. Simultaneously, there was a decrease in 6-keto-prostaglandin F1 alpha, the end product of prostacyclin metabolism and a major product of epithelial cell arachidonate metabolism but not macrophage arachidonate metabolism. A net increase in leukotriene B4 and a net decrease in 6-keto-prostaglandin F1 alpha were demonstrated by radioimmunoassay. Thus, the interaction of stimulated alveolar macrophages and epithelial cells alters the eicosanoid profile produced by each cell type alone in a manner that would tend to accentuate inflammatory processes within the alveolus.

Invasive techniques in the diagnosis of bacterial pneumonia in the intensive care unit.

Bacterial nosocomial pneumonia represents the greatest infectious risk for morbidity and mortality for patients requiring intensive care and mechanical ventilation. The occurrence of purulent respiratory secretions and new infiltrates on chest radiograph generally necessitates broad-spectrum antibiotic therapy due to the lack of a safe, reliable method of determining the presence or absence of bacterial pneumonia. This article reviews the currently available invasive techniques for the diagnosis of bacterial pneumonia in the intensive care patient, with particular emphasis on the bronchoscopic methods using protected specimen brushes and bronchoalveolar lavage. The reliability, risks, and techniques of the various procedures are compared and contrasted.

Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro.

Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung.