Airways SCM is induced by a wide variety of noxious agents that perturb but do not kill the epithelial cells. Discharge of mucus soon after first exposure to a noxious agent is frequently observed, but discharge of mucus may or may not be followed by development of SCM. Treatment with steroidal and nonsteroidal antiinflammatory agents protects against development of SCM in some models, such as tobacco smoke-induced SCM, but not in others, such as enzyme-induced SCM. In general, SCM regresses slowly or not at all spontaneously. Recovery of some models, such as tobacco smoke-induced SCM, is hastened by nonsteroidal antiinflammatory agents. Experimental protection against induction of enzyme-induced SCM by secretory leukocyte protease inhibitor, which is secreted by airways secretory cells, suggests that such protection may be the in vivo role of that antiprotease. The response of the airways to injury is heterogeneous, with patterns of response of the secretory cells varying according to agent, species, and longitudinal localization of epithelial cells in the airways. The longitudinal heterogeneity of response of secretory epithelial cells to injury is summarized in Table 1. Anatomic heterogeneity of epithelial cells may make a minor contribution to longitudinal variation in response of secretory cells to injury. Molecular heterogeneity of the cellular milieu seems the more likely explanation for this variation in cellular response.

This article has reviewed the anatomic, compliance, reflex, and respiratory muscle variables that affect upper airway caliber and abnormalities which may precipitate upper airway collapse during sleep. One or more of these variables may be important in the mechanism of OSA in any given patient. First, anyone with anatomic narrowing of the upper airway is susceptible to OSA. However, we do know if anatomic narrowing of the upper airway is necessary for the development of OSA. Surely, heavy snoring produces pharyngeal trauma and possibly edema or inflammation, which in turn may narrow the upper airway. Submucosal adipose tissue or cervical adipose tissue may compress the airway when the tonic electrical activity of the pharyngeal muscles decreases with sleep onset. Data reviewed support the idea that the upper airway of OSA patients may be more collapsible than the upper airway of nonapneic subjects. Intrinsic tissue abnormalities have not been demonstrated that might be responsible for this collapsibility. Changes in collapsibility found are consistent with, and may be due to, changes in tonic and phasic contraction of upper airway muscles. Abnormalities in reflexes affecting upper airway size surely might exist in OSA. Edema or inflammation of pharyngeal tissues might not only narrow the upper airway but might also impair normal function of the receptors responsible for initiating protective reflexes. We propose the fluctuation between a low- and a high-drive state contributes to upper airway collapse in OSA. With this fluctuation the balance of forces and critical pressure concepts discussed above come into play (Fig 6). By stimulating upper airway inspiratory muscles, CO2 eliminates the hypoapneic, low-drive, high-resistance periods and thereby reduces the number of apneas. In addition, preferential stimulation of upper airway muscle activity dilates the upper airway per se. If the relative value of each of these factors can be determined diagnostically, perhaps therapy can be made more specific. By being more specific, therapy should be more successful than the present practice of prescribing a particular therapy, regardless of the specific mechanism responsible for the OSA in a given patient.

Pulmonary hypertension may be primary (idiopathic) or secondary. While the etiologies for secondary pulmonary hypertension are diverse, infection with the human immunodeficiency virus (HIV) has not been included. To date there have been 16 reported cases of pulmonary hypertension in the HIV-infected population. Plexogenic arteriopathy was the most common pathologic finding. We report two HIV-infected patients who were concomitantly found to have pulmonary hypertension with plexogenic arteriopathy. One patient had lymphocytic interstitial pneumonitis, an entity not previously associated with pulmonary hypertension. We review the 16 previous cases of pulmonary hypertension and HIV infection and discuss this association.

The purpose of this article is to assess critically the evidence for a causal relationship between gastric colonization by Gram-negative bacilli and nosocomial pneumonia in the intensive care unit. Articles were found using MEDLINE search and citations in relevant articles. Nine diagnostic tests of causation were applied and analysis showed that the major tests were satisfied. The strongest evidence comes from randomized controlled trials of selective gut decontamination and stress ulcer prophylaxis in intensive care units. These studies confirm that the incidence of nosocomial pneumonia correlates directly with the rate of gastric colonization by Gram-negative bacilli. Further support comes from other tests of causation such as strength and consistency of association, temporal relationship, and dose-response gradient. The data reviewed suggest that gastric colonization with Gram-negative bacilli plays a causal role in the development of nosocomial pneumonia in the intensive care unit patient. This relationship impacts on future studies of pathogenesis and prevention of this potentially lethal infection.

The major determinants of VO2 resp and, thus, diaphragmatic endurance are the tension-time index, work rate and lung volume. Changes in breathing pattern that adversely affect any of these factors can impair diaphragmatic endurance. A TTdi above 0.15-0.18 indicates a potentially fatiguing pattern of contraction. However, fatigue may occur at a TTdi below 0.15 if the work rate is sufficiently high or the Pdimax is not measured at the prevailing lung volume. Inspiratory muscle fatigue usually elicits an increase in minute ventilation and respiratory rate and to a lesser degree a reduction in tidal volume. However, fatigue may not always be accompanied by changes in breathing pattern. Furthermore, fatigue may sometimes result in a reduction rather than an increase in motor outflow to the respiratory muscles. Finally, abdominal paradox initially considered to be characteristic clinical sign of inspiratory muscle fatigue appears to be due to increases in respiratory load rather than to muscle fatigue.

Pulmonary embolus-in-transit represents an important cause of morbidity and mortality in the critically ill patient. Unexplained shock and acute pulmonary hypertension were evaluated with echocardiography. Standard transthoracic echocardiography failed to identify a large embolism-in-transit that was easily visualized by transesophageal imaging. A review of the literature involving emboli-in-transit suggests that early intervention in these patients may be beneficial.

The adult respiratory distress syndrome (ARDS) continues to demonstrate high mortality. This syndrome is frequently observed as a remote complication of another disease process and is characterized by a significant inflammatory component. The purpose of this review is to compare and contrast published research on the use of anti-inflammatory agents, steroidal and nonsteroidal, in animal models of acute lung injury. Emphasis is given to the nature of the experimental pulmonary injury, infusion (ie, oleic acid and zymosan-activated plasma) or bacteriologically (ie, endotoxin and live bacteria) induced and the timing of drug administration relative to induction of the insult. The clinical data available on the use of these drugs in ARDS are discussed, and a rationale is presented for future clinical trials in these patients.