The likelihood that the leukotriene products derived from the 5-lipoxygenase pathway mediate aspects of obstructive airways diseases is strongly suggested by their documented capacities to effect airway spasmogenicity, airway hyperreactivity, tissue edema formation, mucus secretion, and tissue infiltration by leukocytes. That the various leukotriene components of SRS-A have unique receptors on responding tissues and are recoverable from airway surfaces in several inflammatory lung diseases and that several resident and infiltrating cell types have significant potential for leukotriene biosynthesis lend further support to their postulated pathobiologic roles. To fulfill Koch's postulates for proof of leukotrienes' etiologic role, it remains to be shown that inhibition of their biosynthesis or specific antagonism at their end-organ receptors can greatly ameliorate these disease states.

This article reviews the multiple mechanisms by which glucocorticoids influence the pathophysiology of pulmonary disease. Particular emphasis is given to the influence of glucocorticoids on the release and action of mediators that promote inflammation and that modulate other pathophysiologic processes in the lung. The time course and mechanisms of action that contribute to glucocorticoid effects on pulmonary function are also discussed.

Bronchoalveolar lavage (BAL) is a powerful tool with which the immunology of the lung in health and disease can be studied. This technique has been successfully used to characterize localized humoral and cell-mediated responses in sarcoidosis and a number of other interstitial pneumonitides. In contrast, BAL in patients with lung cancer has resulted in some confusion regarding the extent and type of local and systemic immunity in these patients. This review summarizes some of the data obtained from these patients via BAL, but does not attempt to explain the reported discrepancies. The objective of this review is rather to identify gaps which exist in our knowledge of the environmental factors influencing pulmonary immunity in primary lung cancer.

Infants with respiratory failure in the first weeks of life may develop a chronic pulmonary condition called bronchopulmonary dysplasia. Their lungs have areas of atelectasis and areas of air trapping from variable obstruction of the airways. These infants may be dependent on supplemental oxygen or a ventilator and may require hospitalization for months, and have symptoms of airway obstruction which last for years. They require meticulous medical management to avoid a number of common complications such as patent ductus arteriosus, cor pulmonale, tracheal stenosis, recurrent aspiration, and death. The condition of most infants improves over the first two years. Preliminary studies suggest that their exercise and pulmonary function is usually close to normal by school-age. The long-term implications for the increasing number of children with this disease who will soon reach adulthood are still unknown.

Aspirin intolerance is particularly common in asthmatic patients who additionally have chronic rhinitis and/or nasal polyps. These individuals differ in several respects from patients who experience urticaria and/or angioedema after aspirin administration, and differing mechanisms may be involved. Data regarding the latter are indirect and incomplete, but suggest that ASA-sensitive asthma is most likely to be related in some manner to the capacity of ASA to inhibit cyclooxygenases, enhanced lipoxygenase metabolism perhaps playing a crucial role. Current research employing ASA "desensitization" may help to elucidate these enigmas.

Bone marrow transplantation (BMT) for hematologic disorders is potentially curative in selected persons. These patients may be immunocompromised for months after engraftment as a consequence of chemotherapy, irradiation, acute and chronic graft-vs-host disease (GVHD), and maturing recipient marrow. Pulmonary complications commonly occur during the early and late periods after BMT and are associated with significant morbidity and mortality. The leading early-onset complication is interstitial pneumonitis, most commonly associated with cytomegalovirus infection but also related to possible toxicities from chemotherapy and irradiation. Major late-onset problems include bacterial sinopulmonary infections and obstructive airway disease thought to be associated with chronic GVHD. The exact mechanisms of lung injury are probably quite complex, and unfortunately, often cause irreversible pulmonary disease, even in the patient who has had successful transplantation. Antimicrobial prophylaxis, modified chemotherapy and irradiation dosages, and antiviral immunization have been shown to reduce the incidence of early-onset pulmonary problems. Early recognition and treatment of late-onset problems will, it is hoped, minimize respiratory limitations.

Cromolyn sodium is a valuable agent in the pharmacologic management of asthma. In addition to its established effects of inhibiting mediator release, it now appears that it is a useful drug for diminishing the effects of reflex-mediated asthma, nonspecific bronchial hyperreactivity, and diurnal swings of bronchial lability. Because of these unique prophylactic properties, the availability of a nebulized aqueous solution delivery system and recent clinical reports showing that its efficacy is comparable to theophylline, cromolyn sodium should be reconsidered as a first-line antiasthmatic drug in the United States.

Asthma in children has many special features which deserve consideration. This disease is probably underdiagnosed and is often undertreated. Vague, persistent respiratory symptoms, especially chronic cough, may often be due to asthma. Chronic bronchitis is extremely rare in the pediatric patient and is a manifestation of reactive airway disease or cystic fibrosis. The absolute severity, the extent of the disease, responses to treatment, and long-term course should be evaluated by repeated pulmonary function tests. Fortunately, asthma responds well to pharmacologic and supportive therapy, and it is important to approach its management as that of a chronic rather than episodic illness. Therapy should include comprehensive, closely supervised drug therapy, health education, and a program of self-management. Asthma usually starts before youngsters enter school, and the majority get better as they get older. Nevertheless, many children with moderate or severe asthma will continue to be troubled by intermittent or chronic airway obstruction into adulthood, and they require long-term, anticipatory treatment programs. Comprehensive care will optimize the quality of life for the affected children and their families, and it will minimize the discomfort and restrictions to which some of them have been subjected unnecessarily. Asthma in childhood, especially when not well controlled, may constitute a risk factor for the development of chronic obstructive pulmonary disease in adulthood; however, this is as yet only suspected and not proved.

Several types of reactions to drugs and chemicals may precipitate or perpetuate asthmatic relapse. This review focuses on reactions to aspirin and sulfites. Approximately 40 percent of patients with rhinosinusitis, nasal polyps, and asthma and 5 to 10 percent of all asthmatic patients are sensitive to aspirin and aspirin-like nonsteroidal anti-inflammatory drugs at some time in their course. A prudent recommendation to all asthmatics is to substitute acetaminophen for aspirin. When aspirin/aspirin-like drug is essential for treatment of cardiovascular or musculoskeletal disorder, desensitization by cautious oral challenges with graded doses of aspirin can be accomplished. Treatment of the respiratory disorder per se by desensitization followed by daily therapeutic aspirin remains investigational. Sulfur dioxide and sulfites, commonly used as sanitizers and preservatives of foods and pharmaceuticals, may precipitate acute asthma in 5 percent or more of asthmatic patients. When the history suggests sulfite sensitivity, challenges can be used to confirm sensitivity and the patient counseled in avoidance of these chemicals.

Mast cell activation occurs in allergic asthma and may play a role in a variety of nonallergic asthmatic states. The defined mast cell constituent histamine has been identified in blood of antigen-sensitive challenged asthma patients, while other mediators, whose cell of origin is not fully defined, accompany this amine in blood (Table 1). Due to technical difficulty in accurate assessment, the rapid metabolism of various constituents, and the need for biologic rather than chemical assay of some mediators, it is not yet possible to assess blood constituents for the unequivocal attribution of asthma to activation of a particular cell type. Likewise, the usefulness of blood studies in the prediction of the course of asthma or as serial measurements to define the severity of asthma remains limited. However, it is only with analysis of the appropriate biologic fluids, blood and/or bronchoalveolar lavage materials, that it will be possible to define which potential mediators are, in fact, present and active in asthma. Until such analysis is completed, it is not possible to assign a function in this disease to the numerous potent inflammatory mediators known to be active in in vitro or in vivo models of asthma.

It is now recognized that, in addition to the preformed mast cell granule mediators, newly generated lipid compounds are likely to be exceedingly important in the mediation of allergic asthma and other atopic diseases. That the initiating event in allergic diseases evokes a far more complex set of biochemical events than those that only lead directly to the release of histamine and other preformed mediators, and that the functional efficacies of the leukotrienes, PGD2, and PAF are significant for allergic pathobiology mandate that the latter compounds will necessarily be subject to efforts for future therapeutic intervention in allergic patient populations.