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.

The question of whether chrysotile asbestos ever causes mesothelioma in man has become a major public and occupational health issue. Review of the literature suggests that only 53 acceptable cases of chrysotile-induced mesothelioma have ever been reported; of these, 41 cases have occurred in individuals exposed to chrysotile mine dust, all of it naturally contaminated with tremolite. Ten cases have occurred in secondary industry workers, but here the suspicion of amosite or crocidolite contamination is high. Analysis of lung asbestos content indicates that induction of mesothelioma by chrysotile requires, on average, as great a lung fiber burden as induction of asbestosis by chrysotile, whereas amphibole (amosite or crocidolite)-induced mesotheliomas appear at a several hundred-fold smaller lung burden. Tremolite alone has definitely produced mesothelioma in man, particularly when exposure has been to long, high aspect ratio, fibers. Analysis of tremolite:chrysotile fiber ratios in human lung suggests that some, but not all tremolite is removed in milling chrysotile ores. The low incidence of mesothelioma in secondary chrysotile users may reflect the small amount of tremolite left in the product. These observations indicate that although chrysotile asbestos can produce mesothelioma in man, the total number of such cases is small and the required doses extremely large. The data are consistent with the idea that mesotheliomas seen in chrysotile miners and some secondary industry workers are produced by the tremolite contained in the chrysotile ore, but that the short length and low aspect ratio of the tremolite make its carcinogenicity quite low. However, these data are very indirect, and a role for the chrysotile fiber itself is still possible.

The multifaceted nature of smoking includes its physiologic, social, and psychologic dimensions and its career features. It develops over time, through phases such as experimentation or conditioning. It also is given up over time, often after several unsuccessful attempts. Several repetitions of a sequence of considering cessation, attempting to quit, and relapsing are likely to precede permanent cessation. Those who are not ready to commit themselves to quitting may be reached by low-key information more than by too forceful exhortation. Those who are ready to quit may select from among a range of approaches, including group clinics, "self-help" manuals, and physician counseling. Maintenance requires as much attention as does cessation. Cooperation from those around the quitter, reminders to use skills for coping with stressors or temptations, and continued encouragement from the physician may all encourage long-term abstinence. Owing to the multifaceted nature of smoking and quitting and the multiple approaches to cessation and its maintenance, the physician may best be viewed as a catalyst for nonsmoking. If appropriate to his or her practice, this may include extended patient counseling, but those unable to provide this may still make great contributions through brief information on why it is important to quit, encouragement to do so, timely referral to other staff or to materials and programs available in the community, and continued expression of interest in the patient's efforts and/or success. All these may catalyze quitting without demanding excessive time or skills beyond those commonly employed by the physician. In catalyzing nonsmoking, the physician can also be an effective proponent of community or voluntary agency programs as well as institutional and governmental policies to limit smoking in health care facilities and public places. The American College of Chest Physicians' policy encouraging nonsmoking among its Fellows and in their offices is an excellent example of this catalyst role.