Background

Asthma is an increasingly serious cause of morbidity and mortality in the United States. There are approximately 12 million asthmatics and the disease affects both sexes and impacts all racial and ethnic groups. It is now recognized that asthma is a complex disease of varied etiology triggered by a number of factors such as allergens, drugs, chemicals, exercise, cold air, infections, and emotions, making asthma therapy difficult and sometimes complicated. Multiple drugs are often required, including medications to treat and control symptoms (bronchodilator agents such as beta-adrenergic agonists, theophylline, and anticholinergics), as well as drugs thought to control underlying airway inflammation (inhaled and systemic corticosteroids, cromolyn sodium, and nedocromil). Despite major advances in understanding the etiology and pathophysiology of asthma and the development of new therapeutic modalities, the prevalence, severity, and mortality from asthma have increased over the past decade in all age groups. Mortality rates are disproportionately high in urban and rural minority populations. Hospitalizations for asthma have doubled in adults and increased five-fold for children over the past twenty years, and asthma continues to place a heavy burden on patients and their families, the health care system, and society as a whole. Therefore, new approaches are needed to help alleviate this growing problem. A particularly important need at this juncture is a mechanism for the rapid evaluation of new and existing therapeutic approaches for asthma and for the dissemination of laboratory and clinical findings to the health care community. The Asthma Clinical Research Network program seeks to accomplish this through the development of a network of interactive asthma clinical groups that conduct clinical trials employing common protocols in a coordinated and multidisciplinary setting. This will ensure ready access to an adequate number of well characterized patients from diverse populations and age groups, and will bring together and coordinate the necessary clinical expertise and administrative resources to conduct multiple therapeutic trials. Centralized protocols will promote high quality design, decrease the variability in supportive modalities, and reduce the redundant utilization of resources required for rapidly conducting multiple independent clinical studies. The separate data coordinating center supports protocol and questionnaire development, sample size calculations, complete data analysis, and overall study coordination. The initiative was developed by the Pulmonary Diseases Advisory Committee working group, approved by the full committee at the February 1992 meeting, and given concept clearance by the National Heart, Lung, and Blood Advisory Council in May 1992.

Background

Asthma is one of the most common illnesses that complicates pregnancy. Asthma complicates at least 4 percent of all pregnancies; however, because at least 10 percent of the population appears to have nonspecific airway hyper-responsiveness, the true prevalence may be much higher. Asthma can produce serious maternal and fetal complications. A number of investigators have reported an increased incidence of pre-eclampsia, gestational hypertension, hyperemesis gravidarum, vaginal hemorrhage, toxemia, and induced and complicated labor. Fetal complications include increased risk of perinatal mortality, prematurity, low birth weight, and neonatal hypoxia. In contrast, several studies have failed to confirm some or all of these previous observations. Patients with severe asthma may have the greatest risk for complications during pregnancy, in addition to the risk of maternal morbidity from the asthma. For example, it has been shown that reduced pulmonary function in asthmatic women is associated with an increased likelihood of intrauterine growth retardation. On the other hand, studies in which asthma was successfully controlled have resulted in pregnancy outcomes similar to the general population. The mechanisms by which asthma may have adverse perinatal effects are not well known. Poor control of asthma leading to chronic or episodic fetal hypoxia is thought to be important. Medications used in asthma treatment may also play a role, although the limited data suggests minimal or no effects. In addition, it is possible that extrapulmonary autonomic nervous system abnormalities, such as uterine muscle hyperreactivity, could contribute to pre-term delivery or gestational hypertension independent of asthma control or therapy. Unfortunately, previous studies have been limited by relatively small numbers. Few studies have controlled for factors known to affect infant birth weight, such as maternal race, height, weight, parity, nutrition, and cigarette smoking. Particularly, race may be an important contributing factor in assessing the relationship between asthma and pregnancy outcomes, since Blacks of both sexes are twice as likely to be hospitalized from asthma and three times as likely to die from asthma as whites. Under the auspices of the National Asthma Education Program (NAEP), a Working Group on Asthma and Pregnancy developed a statement regarding the treatment of asthma during pregnancy. In its deliberations, the Working Group noted the paucity of data on the relative contributions of biological, social, and environmental factors on asthma in pregnant women, as well as the lack of data on the efficacy and safety of commonly used asthma therapies in pregnancy.