Aging increases vulnerability to obstructive sleep apnea (OSA), but the underlying mechanisms remain unclear. Recent data in awake healthy volunteers show a decrease in the genioglossus negative pressure reflex and anatomic compromise with increasing age, suggesting an age-related predisposition to pharyngeal collapse. However, aging effects on pharyngeal collapsibility have not been studied extensively during sleep. We tested the hypotheses that upper airway closing pressure (PCLOSE) and the increase in pharyngeal resistance during sleep (primary outcomes) as well as measures of arousal threshold (secondary outcomes) increase with age.

Postobstructive pulmonary edema is a well-recognized complication of upper airway obstruction. The mechanisms of edema formation are unclear and may be due to increased hydrostatic forces generated by high negative inspiratory pressure or by increased permeability of the alveolar capillary membrane. Measurement of the edema fluid/plasma protein ratio and the rate of net alveolar fluid clearance are two well-validated methods for classifying the underlying mechanism of edema formation. The goal of the current study was to investigate the mechanisms of pulmonary edema formation in patients with postobstructive pulmonary edema by serial sampling of undiluted pulmonary edema fluid.

Over the past decade, advances in the ventilatory management of acute lung injury (ALI) and ARDS have improved outcomes; however, until recently the search for other therapies has been less fruitful. Recently, the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial reported that a conservative fluid management strategy, compared with a fluid liberal strategy, increased the mean (+/- SE) number of ventilator-free days in patients with ALI (14.6 +/- 0.5 vs 12.1 +/- 0.5 days, respectively; p < 0.001). In addition to this beneficial effect on outcomes, the study found that the conservative fluid strategy did not increase the incidence of renal failure or the development of shock. Other studies have demonstrated that albumin and furosemide therapy may be beneficial in hypoproteinemic patients with lung injury, though data on outcomes is still lacking. Although several pharmacologic therapies, such as corticosteroids, surfactant, and nitric oxide, have been demonstrated to be ineffective in improving outcomes, several promising new treatments are being investigated in ongoing or upcoming clinical trials. This article reviews these developments and other recent research on the optimal nonventilatory management of patients with ALI.

Pulmonary hypertension is a common finding in patients with idiopathic pulmonary fibrosis (IPF), and is associated with increased morbidity and mortality. Therapy with sildenafil has been shown to decrease pulmonary vascular resistance in patients with pulmonary fibrosis and may improve functional status. Patients with IPF and documented pulmonary hypertension were followed up in an open-label study of sildenafil. The 6-min walk test distance (6MWD) was obtained before and after 3 months of sildenafil therapy. Fourteen patients were followed up in the study; 11 patients completed both 6-min walk tests. The mean improvement in walk distance was 49.0 m (90% confidence interval, 17.5 to 84.0 m). When all 14 patients were dichotomized into groups of "responders" (ie, >/= 20% improvement in 6MWD) or "nonresponders" (ie, < 20% change or unable to complete), 57% were classified as responders. Sildenafil is a promising and well-tolerated therapeutic agent for use in patients with IPF and pulmonary hypertension, and should be studied in a large, well-controlled trial.

Chronic lung diseases like COPD, severe progressive pulmonary hypertension (PH), and interstitial lung diseases all have a lung vascular disease component. Cellular and molecular mechanisms of pulmonary vascular remodeling have been experimentally explored in many animal models, and it is now clear that microvessels are involved. In emphysema patients, there is a loss of lung microvessels, and in many forms of severe PH there is obliteration of precapillary arterioles by angioproliferation. Thus, COPD/emphysema and severe angioproliferative PH are on the opposite ends of a spectrum of vascular biology responses. Animal experiments have provided insight regarding some of the initiating events that shape the various forms of pulmonary vascular remodeling. In pulmonary fibrosis and in the postinjury phase of acute lung injury, the angiogenic/angiostatic balance is also affected. This review will therefore discuss angiogenesis in several chronic lung diseases and will speculate on how altered vascular homeostasis may contribute to lung disease development.

Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several beta-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF.

Central sleep apnea (CSA) is characterized by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas exchange. These nighttime breathing disturbances can lead to important comorbidity and increased risk of adverse cardiovascular outcomes. There are several manifestations of CSA, including high altitude-induced periodic breathing, idiopathic CSA, narcotic-induced central apnea, obesity hypoventilation syndrome, and Cheyne-Stokes breathing. While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. This brief review summarizes the underlying physiology and modulating components influencing ventilatory control in CSA, describes the etiology of each of the various forms of CSA, and examines the key factors that may exacerbate apnea severity. The clinical implications of improved CSA pathophysiology knowledge and the potential for novel therapeutic treatment approaches are also discussed.

This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations.

Estimating the clinical probability of malignancy in patients with a solitary pulmonary nodule (SPN) can facilitate the selection and interpretation of subsequent diagnostic tests.

With the increasing incidence of asthma, there is increasing concern over environmental exposures that may trigger asthma exacerbations. Blooms of the marine microalgae, Karenia brevis, cause red tides (or harmful algal blooms) annually throughout the Gulf of Mexico. K brevis produces highly potent natural polyether toxins, called brevetoxins, which are sodium channel blockers, and possibly histamine activators. In experimental animals, brevetoxins cause significant bronchoconstriction. In humans, a significant increase in self-reported respiratory symptoms has been described after recreational and occupational exposures to Florida red-tide aerosols, particularly among individuals with asthma.

For patients with acute lung injury, positive pressure mechanical ventilation is life saving. However, considerable experimental and clinical data have demonstrated that how clinicians set the tidal volume, positive end-expiratory pressure, and plateau airway pressure influences lung injury severity and patient outcomes including mortality. In order to better identify ventilator-associated lung injury (VALI), clinical investigators have sought to measure blood-borne and airspace biological markers of VALI. At the same time, several laboratory-based studies have focused on biological markers of inflammation and organ injury in experimental models in order to clarify the mechanisms of ventilator-induced lung injury (VILI) and VALI. This review summarizes data on biological markers of VALI and VILI from both clinical and experimental studies with an emphasis on markers identified in patients and in the experimental setting. This analysis suggests that measurement of some of these biological markers may be of value in diagnosing VALI and in understanding its pathogenesis.

The influence of the clinical syndromes of pulmonary embolism (PE) on clinical outcome has not been evaluated.

Patients with obstructive sleep apnea (OSA) are characterized by deranged cardiovascular variability, a well-established marker of cardiovascular risk. While long-term treatment with continuous positive airway pressure leads to a significant improvement of cardiovascular variability, little is known of the possibility of achieving the same results with other therapeutic approaches. The aim of our study was to investigate the responses of autonomic indexes of neural cardiac control to another type of OSA treatment based on an oral jaw-positioning appliance.

Exacerbations of asthma and COPD are major causes of morbidity, mortality, and health-care costs. Over the last decade, studies using new molecular diagnostic techniques have established that respiratory viruses are a major cause of exacerbations of both asthma and COPD. The most prevalent viruses detected during exacerbations are the rhinoviruses. Despite the burden of disease associated with exacerbations, little is known about the mechanisms of virus-induced exacerbations of airway diseases. Exacerbations are associated with increased airway inflammation in patients with both asthma and COPD, but many questions remain unanswered regarding the key inflammatory cells and mediators involved. Identifying the key inflammatory mediators involved in exacerbations holds the promise of developing diagnostic and prognostic markers of exacerbation. In addition, such studies can identify new therapeutic targets for the development of novel drugs for the prevention and treatment of exacerbations.

Optical coherence tomography (OCT) is an evolving technology that is capable of delivering real-time, high-resolution images of tissues. The purpose of this study was to evaluate the feasibility of using OCT for detecting airway pathology in a septic animal model.

Patients with respiratory infections often require the use of supplemental oxygen via oxygen masks, which, in the hospital, may become sources of aerosolized infectious pathogens. To assess this risk, a human lung model (respiration rate, 12 breaths/min) was designed to test the potential for a simple oxygen mask at a common setting (4 L/min) to disperse potentially infectious exhaled air into the surrounding area. A laser sheet was used to illuminate the exhaled air from the mask, which contained fine tracer smoke particles. An analysis of captured digital images showed that the exhaled air at the peak of simulated exhalation reached a distance of approximately 0.40 m.

Health-care workers are concerned about the risk of acquiring contagious diseases such as severe acute respiratory syndrome and avian influenza after recent outbreaks. We studied exhaled air and particle dispersion through an oronasal mask attached to a human-patient simulator (HPS) during noninvasive positive-pressure ventilation (NPPV).