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.

A number of important mechanisms have been identified by which viruses can provoke asthma. From the data available, there does not appear to be one single mechanism available to explain virus-induced asthma. The relationship between viral URIs and asthma is complex and involves many organ systems: airway epithelium, autonomic nervous system control, and the immediate hypersensitivity system. Identifying the effects of respiratory viruses on airway function remains an important undertaking as we try to better understand and control this precipitant of asthma.

Ca2+ ions are critical to the functions of the various cells involved in the pathogenesis of asthma. Interest has developed regarding the potential use of Ca2+ antagonists in the management of asthma and allergic diseases. The information accumulated to date suggests that Ca2+ entry blockers may decrease airway smooth muscle responses to contractile agonists and may also reduce chemical mediator release from mast cells. Both processes would be expected to modify favorably the pathophysiology of asthma. This seems to have been demonstrated with the findings that certain Ca2+ entry blockers may inhibit exercise-induced bronchospasm and cold air- and antigen-induced airway narrowing. In several but not all experiments a direct bronchodilating effect of nifedipine was found in some subjects. In asthmatic patients with coexistent cardiovascular disease requiring beta-blocker therapy, it would be appropriate to use drugs such as the currently available Ca2+ entry blockers in place of the contraindicated beta-blocking agents. It appears that the currently available Ca2+ entry blockers have not provided a breakthrough class of therapeutic agents for the treatment of asthma. However, it seems highly likely that new Ca2+ antagonist drugs can be expected which will have greater specificity for airway smooth muscle and perhaps other cell types involved in the pathogenesis of asthma.

There is no solid evidence that pregnancy has an adverse effect on tuberculosis. With early diagnosis and prompt, adequate chemotherapy, the outcome of pregnancy in a woman with tuberculosis is likely to be good. Routine therapeutic abortion is not indicated. Data in the literature do not support the notion that pregnancy is a major risk factor for the development of tuberculosis, although no well-designed studies have been conducted. Screening of pregnant patients for tuberculosis should be based on consideration of other proved risk factors not on the fact of pregnancy. Preventive therapy should be given during the second and third trimesters of pregnancy to selected patients at high risk of progressive disease developing. Treatment of disease should be instituted promptly when disease is detected. The preferred regimens are INH-EMB, INH-RIF, or INH-EMB-RIF, although other drugs may be needed if the disease is recurrent or if there is resistance to these primary drugs. Mothers taking antituberculosis drugs can nurse their infants with little risk. With proper medical management, both tuberculosis and pregnancy can be expected to reach a happy conclusion in virtually all cases.