Enzymes of the blood coagulation and fibrinolytic cascades are prominent in both the vascular and alveolar compartments of the human lung. Important differences exist in the regulation of these enzyme activities between the vascular and the alveolar compartments, suggesting different functions of similar enzymes in the two compartments. In the vascular bed, endothelial cells provide a nonthrombogenic lining layer and release small amounts of tissue plasminogen activator into the circulation, maintaining patency of the vascular bed, whereas the alveolar epithelial surface is replete with active enzymes of the extrinsic pathway of coagulation as well as urokinase. The alveolar surface seems primed to localize and degrade any fibrin that has leaked into alveoli during hemorrhagic states. In addition, parenchymal lung cells such as resident macrophages are coated with urokinase, providing a mechanism for cellular migration and ongoing extracellular matrix metabolism. Amplification of the PA/plasmin system in the lung during chronic inflammation, eg, cigarette smoking, could accelerate connective tissue breakdown. Recent evidence indicates that in acute inflammation there is an enhancement of mediators of coagulation and suppression of fibrinolysis. These observations may partly explain prior pathologic observations regarding the deposition of hyaline membranes and persistence of alveolar fibrin/fibronectin deposits that may be stimulants for alveolar fibrosis. The assembly of clotting components on the surface of macrophages and the integral involvement of macrophages with fibrin deposits in the lung are likely mechanisms for macrophage immobilization and focal accumulation important to local clearance, host defense, effective chemotactic signalling, and possibly proliferation since thrombin has mitogenic properties for other lung cells. Newer methods focusing on the biology and biochemistry of the pulmonary architecture and its cellular components should further elucidate the importance of these pathways and suggest new therapeutic options.

From this review, it is apparent that the effects of respiratory viral infection on airway reactivity are multiple. Although virus-associated changes are many, we have at present no evidence to show that respiratory viruses cause intrinsic abnormalities in airway smooth muscle function. Rather, respiratory viruses influence bronchial smooth muscle function through a variety of other means: epithelial injury, PMN-dependent inflammation, and greater mediator release. These observations suggest that a common pathway to development of airway hyperreactivity during respiratory viral illnesses is to enhance those factors which participate in the inflammatory response. When the target of this enhanced inflammatory response becomes the airway, greater bronchial reactivity and obstruction result. Although many questions remain to be answered, we feel that future studies to evaluate the biology of respiratory virus effects on mechanisms of airway responsiveness will lead to a greater understanding of asthma pathogenesis.

Amiodarone represents an important new approach in the treatment of serious cardiac rhythm disturbances and is associated with significant pulmonary toxicity in approximately 5 to 10 percent of patients. The recognition of APT in patients receiving the drug early in the course of the disease will likely preclude the development of a permanent loss of pulmonary function in these patients. It is important for the clinician to individualize both the diagnostic and therapeutic approach to the patient receiving amiodarone who is thought to have pulmonary toxicity secondary to the drug. Several diagnostic and therapeutic decisions are available, and it is important to constantly reevaluate the risk-benefit ratios of the decision making process. Future studies may improve insight into the assessment of APT and may permit the clinician to diagnose this toxicity at an earlier and potentially more reversible stage of the disease process.

Prior to the development of ketoconazole, the treatment of systemic histoplasmosis and blastomycosis was limited to AMB. The convenience of oral dosing, combined with avoidance of the significant toxicities associated with AMB, make ketoconazole an attractive alternative for the treatment of selected forms of histoplasmosis and blastomycosis. Although high-dose (800 mg/day) ketoconazole is generally more effective than low-dose (400 mg/day), therapy should be initiated at the lower dose due to significantly more adverse effects at higher doses; the daily dose should be increased in patients with progressive disease. Caution should be exercised when ketoconazole is used to treat patients with GU tract disease and in patients with naturally occurring or pharmacologically induced achlorhydria. Thus, AMB remains the drug of choice for difficult to treat cases of histoplasmosis and blastomycosis; however, recent studies have established ketoconazole as the drug of choice in immunocompetent patients with non-life-threatening, non-meningeal H capsulatum and B dermatitidis disease.

The pulmonary vasculature responds to a multitude of constrictor and dilator mediators, but the exact physiologic and pathologic significance of such responsiveness is unknown. Further careful studies with specific mediator receptor blockers and synthesis inhibitors are required to determine if dilators play a role in maintaining the low vascular tone of the normal pulmonary circulation and if constrictors contribute to either the onset or the maintenance of the pulmonary hypertension associated with chronic airway hypoxia, lung injury, and pulmonary microembolism. It would be a mistake to summarily dismiss the possible involvement of vasoconstrictors in chronic pulmonary hypertension, but the apparent difficulty in establishing their importance emphasizes that mediators of vascular cell migration, proliferation, synthesis, and secretion may be at least as important in the etiology of the increased vascular resistance as the mediators of vascular tone.

Since the advent of angiotensin-converting enzyme inhibitors (captopril and enalapril), cough has been recognized sporadically as a side effect, but has received little attention in the pulmonary literature. To emphasize that angiotensin-converting enzyme (ACE) inhibitors should be considered among possible etiologies of cough, we report recent experience with two patients and review the available experience with ACE inhibitor-induced cough.

Respiratory failure is the leading cause of death in the neonatal period. The anatomic and functional basis for this, particularly in full-term infants, most often is persistent pulmonary hypertension of the neonate (PPHN). This condition is reversible but can cause very severe and unrelenting respiratory failure and ultimate death when uncontrolled. Recent technologic advances have expanded the scope of therapy available for PPHN, resulting in increasing therapeutic success for these critically ill infants. This article reviews the anatomic and functional anomalies of PPHN, as well as the methods of diagnosis and discusses current treatment.