A stratified random sample of a large state (Michigan) was studied by respiratory questionnaire, medical history, and physical examination. Data were obtained on 1,169 white adults. The prevalence of chronic bronchitis and chronic wheezing varied with sex (greater in men) and smoking history (greatest in current smokers). The prevalence of chronic bronchitis varied depending on whether it was (1) defined simply as chronic production of sputum, (2) diagnosed by the examining physician, or (3) previously diagnosed by a physician. Dyspnea was more common in women; in men, it was least common in nonsmokers but was of similar prevalence in ex-smokers and current smokers. Angina was more commonly reported by women, but previously diagnosed heart attack was consistently more common in men. Wheezing was by far the most common physical sign, present in 5.1 percent of the total population and 9.2 percent of male current smokers. Clubbing and rales were each noted in 1.2 percent of the total population. The prevalences of clinical findings in this cross section of a large state should be useful for comparison with other populations.

We reviewed the literature evaluating pediatric asthma education interventions to assess their impact on morbidity (school absences and health care utilization). Thirteen studies were analyzed, most of which reported favorable outcomes. Of the ten studies reporting on school absences, only seven used tests of statistical significance when reporting on postintervention reductions, and of those, only two found a significant decrease in absenteeism. Similarly, among the studies reporting on utilization, not all used tests of statistical significance when reporting on postintervention decreases in physician visits, ER visits, and hospitalization. Only four of the ten studies used adequate sample sizes to detect a 20 percent reduction in school absences, and stratification of the sample by severity of asthma suggests that some programs do reduce health care utilization among those children with more severe disease. We conclude that the effectiveness of asthma educational programs on reducing school absences and health care utilization may be small. These programs are best directed toward children with moderate or severe disease. Finally, it is important for pediatricians, children with asthma, and their families to have realistic expectations about what these programs may accomplish.

A report of pulmonary edema following acute upper airway obstruction in an adult is presented, and the literature involving 25 additional cases is reviewed. This form of pulmonary edema appears to be related to markedly negative intrathoracic pressure due to forced inspiration against a closed upper airway resulting in transudation of fluid from pulmonary capillaries to the interstitium. Postanesthetic laryngospasm is the most common cause of pulmonary edema in adults (11/26 cases). The edema usually clears rapidly with supportive care. Aggressive diagnostic and therapeutic interventions may be avoided if the syndrome is recognized. Maintenance of oxygenation and a patent airway are the mainstays of treatment.

A 15 1/2-year-old boy died suddenly while swimming. He had a family history of sudden death involving three consecutive generations, including a brother. The patient had a history of exercise-related syncope, for which he was being treated with nadolol. Autopsy showed enlarged heart, normal coronary arteries, right ventricular septal hypertrophy, quadricuspid pulmonary valve, accessory tricuspid valve, and a moderately elongated and thickened mitral valve. Conduction system revealed that the penetrating bundle was pushed to the left side of the summit of the ventricular septum by the right ventricular septal hypertrophy; it was lobulated and showed fatty-fibrous changes. These findings extended throughout the beginning of the bundle branches. We conclude that in this patient with familial sudden death and normal QT interval, the abnormal right ventricular septal hypertrophy altered the course and produced degenerative changes in the conduction system, which may have caused sudden death.

Pyrazinamide is an antituberculosis drug synthesized in the 1950s and formerly used only as salvage therapy. Recent developments have elevated it to a central role in tuberculosis chemotherapy as the essential addition to isoniazid and rifampin which makes it possible to successfully complete treatment in six months. This is accomplished with no increase in hepatotoxicity. The only substantial side effect of this drug given at the dosage and for the duration used in these six-month regimens is a polyarthralgia which is only bothersome and not sufficient to warrant interruption of therapy. More rarely, acute gout is produced. The early history and pharmacology of this now first line antituberculosis drug are reviewed herein.

Patients with cystic fibrosis (CF) show abnormal aminoglycoside pharmacokinetics. After a conventional dose, the serum concentrations in CF patients are lower than those in nonCF patients. The lower serum concentrations in CF might be explained by increased total body clearance and/or a larger volume of distribution. The therapeutic range of aminoglycosides is narrow due to oto- and nephrotoxicity. The changed pharmacokinetics and the narrow therapeutic range make it difficult to ensure that patients with CF are adequately and safely treated with aminoglycosides. The mode of administration of aminoglycosides influences the antibacterial effect of these agents on Pseudomonas aeruginosa and the development of possible side effects. The therapeutic implications of these facts are discussed.

Bacterial infections determine life expectancy in the hereditary disease cystic fibrosis (CF). The dominant pathogens are Staphylococcus aureus and Pseudomonas aeruginosa, which persist in the patient's respiratory tract. Current explanations of the chronicity of the infections in the apparently immunocompetent host are based on defective opsonophagocytosis. This may be caused by (1) bacterial exopolysaccharide production, leading to cryptic infection types; (2) cleavage of immunoglobulin, complement, and surface receptors on immunocompetent cells by host proteases; and (3) a change from opsonic to nonopsonic antibody isotypes. Continuous antigenic stimulation of the immune system leads to local immune complex formation and a high chronic hypersensitivity reaction as well as to temporary immune unresponsiveness. Progressive tissue damage caused by lysosomal enzymes and oxygen radicals from polymorphonuclear leukocytes is thought to be ultimately responsible for respiratory failure and death in CF. Besides antibiotic treatment, anti-inflammatory therapy is therefore currently considered beneficial.

Increasing evidence from case control surveys, population studies and allergen avoidance studies suggest inhalant allergy plays an important role in the etiology of asthma. Recent studies in hospital emergency rooms have compared the prevalence of serum IgE antibodies to common allergens (mite, cat, cockroach, rye grass and ragweed pollen) in patients admitted with acute asthma attacks and in unselected age-matched control subjects. These studies, carried out in central Virginia and northern California, showed a highly increased prevalence of IgE antibodies to inhaled allergens among asthmatic patients, and suggest that the development of allergen specific IgE antibody responses is a major risk factor for emergency room admission with asthma. Presentation at the emergency room appeared to be related to patients' exposure to specific allergens: in central Virginia, in the fall, dust mite was the predominant allergy, whereas in northern California, in May-June, most asthmatic patients (greater than 90 percent) were allergic to rye grass. New immunoassay technology, based on the use of monoclonl antibodies, has been developed to measure the quantities of "indoor" allergens (mite, cat, cockroach) in asthmatic patients' houses. It is now possible to propose tentative levels of mite allergens which should be considered both as a risk for IgE antibody sensitization (2micrograms allergen/g dust) and as a risk for acute asthma attacks (10micrograms allergen/g dust). Future management of asthma will require analysis of indoor allergens and the development of efficient allergen avoidance procedures. Further research is necessary to investigate the relationship between airborne allergen levels, particle size and the precipitation of asthma attacks and also to investigate immunologic mechanisms which may cause bronchial hyperreactivity.

It is now recognized that the basic reason for airway obstruction in asthma is chronic airway inflammation. The hyperresponsiveness and "bronchospasm" are, in part at least, a consequence of the inflammation. Optimum patient care needs to focus on preventing inflammation when possible and using anti-inflammatory drugs when prevention is not possible. When chronic asthma is mild, aerosol glucocorticoids or cromolyn suffice. Acute exacerbations that do not respond fully to bronchodilator drugs usually should be treated by a course of oral glucocorticoids. A few patients with severe disease require oral glucocorticoid therapy indefinitely.

Heightened airway reactivity is a cardinal feature of asthma and correlates with many clinical features of the illness, such as the acute response to bronchodilator drugs, the magnitude of diurnal fluctuations in lung function, and the amount of therapy required to control symptoms. Data have accumulated indicating that a reduction in airway reactivity can decrease asthma morbidity, and many advocate treating asthmatic patients prophylactically to prevent acute exacerbations from developing, rather than responding to them after they have occurred. This approach is particularly effective if it is used when the airways are being exposed to stimuli to which they are sensitive. A number of drugs have been purported to reduce airway reactivity, but the most convincing evidence supports the effects of cromolyn and inhaled and oral steroids. Although each type of drug has its own advantages and disadvantages and different modes of action, the common denominator is believed to be a reduction in the state of airway inflammation.

Late inflammatory sequelae following allergen (and occupational low molecular weight sensitizing chemical) exposure, including the late asthmatic response and increased nonallergic airway responsiveness, are now felt to be more important in the pathogenesis of atopic allergic and occupational asthma than are the early bronchospastic responses. These late sequelae can be inhibited by sodium cromoglycate and by corticosteroids but not by bronchodilators. Recognition that allergic and occupational (and likely all forms of) asthma are inflammatory conditions underscores the rationale for the early use of anti-inflammatory therapeutic strategies in the management of asthma. Such "anti-inflammatory" therapeutic strategies include environmental control, sodium cromoglycate, and both inhaled and oral corticosteroids.