We have reviewed evidence that hypoxic chemosensitivity is variable and that this variation may be both endowed, partly through genetic mechanisms, and acquired, and may reflect fundamental changes in carotid body function. This variation may influence the nature and effectiveness of adaptation to high altitude and to hypoxic disease states such as chronic obstructive pulmonary disease. High chemosensitivity seems to be the choice for coping with the casual exposure to hypoxia; but fundamental, highly effective adaptations, presumably at the level of peripheral tissue, seem to be the strategy of choice for professionally adapted species.

Bronchopleural fistulas are associated with high morbidity and mortality and are particularly challenging in the ventilated patient. Familiarity with both basic and more technical medical management techniques may lessen morbidity and improve survival. Prompt recognition of BPFs and appropriate placement of a chest tube with an adequate suction device are crucial to prevent potential tension pneumothorax and to drain an infected pleural space. The chest tube may be used therapeutically to decrease BPF air leak and to promote fistula repair. Appropriate conventional ventilator manipulations aimed at decreasing fistula air leak and maintaining adequate oxygenation and ventilation may fail and necessitate a trial of HFV. Definitive therapy by the bronchoscopic application of a sealing agent to occlude the fistula site can be used, particularly in the poor surgical candidate.

Although commonly found at autopsy, leukemic infiltration of the lung is rarely recognized as a cause of respiratory symptoms or roentgenographic densities. Previously reported cases of patients who had symptomatic or roentgenographic acute leukemic lung diseases invariably presented with diffuse pulmonary infiltrates. We describe three patients with leukemic involvement of the lung who presented with cough, fever, and localized roentgenographic infiltrates suggestive of bacterial pneumonia. In each case, the diagnosis was made by transbronchial biopsy specimen and confirmed by complete response to chemotherapy. In common with the other reported cases, all of our patients had peripheral blast counts above 40 percent (greater than 6,000 blasts per ml3) at the time the pulmonary diagnosis was made. Leukemic invasion of the lung should be considered in patients with acute leukemia who develop lung infiltrates--whether diffuse or focal--in association with a high peripheral blast count.

Recent research suggests that anxiety disorders are more common in asthmatic patients than in the population as a whole. There are a variety of biologic, psychologic, and social factors that suggest that the disorder of asthma may in itself be anxiogenic and that simply having asthma may give patients an increased vulnerability toward the development of anxiety disorders. These issues are reviewed and emphasis is placed on the need for further research into the apparent biologic areas of overlap between psychiatric disorders and asthma. It is hypothesized that a "lactate challenge test" may be used in asthmatics to see if they are predisposed to panic and suggested that a therapeutic trial of tricyclic antidepressants in anxious asthmatics is indicated. Research into the psychobiologic aspects of asthma is likely to clarify the role of "emotional" factors in asthma and may well have significant implications for the management of this disorder.

Classification of chronic airflow obstruction may be based on the site of the obstructing lesions. It is seldom that only one type of lesion is present, but one may often dominate. In chronic bronchitis, the major disease of large airways, chronic mucus hypersecretion, is reflected by an increase in size of bronchial mucous glands. This may be a factor in airway narrowing, especially with coexisting edema of the airway wall. Excess intralumenal mucus compounds the obstruction. Increased airways reactivity is present in 15 to 70 percent of patients with chronic airflow obstruction. Increased airway muscle and cartilage atrophy are features of chronic bronchitis, but the association of increased muscle with increased airway reactivity is poor. Inflammation of the small airways (bronchiolitis) is a significant complication for cigarette smokers and is an important cause of mild chronic airflow obstruction. Goblet cell metaplasia is a reflection of chronic small airways inflammation and, together with intralumenal mucus, is an important feature. Permanent narrowing of the small airways presumably results from inflammation with consequent fibrosis, while functional narrowing results from release of mediators of inflammation. Increased muscle mass is present in some cases. Distortion and irregularity of small airways related to emphysema are major factors in severe obstruction. Lesser degrees of emphysema may be associated with a diminished number of alveolar attachments and mild chronic airflow obstruction. Emphysema, the dominant lesion in patients with severe chronic airflow obstruction, results from parenchymal lesions. Centrilobular emphysema, in which the respiratory bronchioles are selectively or dominantly involved, is the most common form.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical views in the United States on the effects of smoking have shifted dramatically since the published evidence in 1958 established the link between smoking and fatal disease. Today's physician should be a nonsmoking role model, whose workplace both directly and indirectly teaches smoking cessation skills. Publications on smoking cessation techniques from the National Institutes of Health along with intervention tools such as patient smoking history questionnaires are available free of charge to physicians. Patient histories are critical to the intervention process, for they provide essential clues and information about which stage in cessation of smoking the patient has already reached: precontemplation, contemplation, action, and maintenance. Different approaches and techniques are required at each stage. The most important objective for the physician with a patient at the stage of contemplating quitting is to initiate a conversation leading to a directive to quit, with benefits of quitting stressed as reinforcement. Actively motivated patients committed to quit dates may need both educational and pharmacologic support; issues such as nicotine dependence and withdrawal symptoms must be addressed. Pharmacologic therapy at this time may consist of substitution of nicotine-containing gum (nicotine polacrilex) for cigarettes. Used in sufficient, regular dosages, the nicotine gum has been found to help diminish withdrawal symptoms following smoking cessation. Other drug therapies are currently under study. For now, nicotine replacement therapy (where indicated) is to be used for at least three months, the period of greatest chance of relapse. The physician should continue to encourage patients who have quit smoking to forestall relapses, while tacitly understanding that the incidence of relapse is high in first-time quitters. Hospital inpatients provide an opportunity to initiate bedside smoking cessation programs. The hope is that, in the future, hospitals will involve the entire health team in comprehensive smoking cessation programs.

Chronic obstructive pulmonary disease (COPD) is extremely common; all primary care physicians should be able to manage this disorder. Probably 30 million Americans are afflicted with some stage of the disease. Assessment of COPD is based on symptoms and simple spirometric measurements that primary care physicians can perform in their offices. Early identification and intervention are vital to controlling COPD. Smoking cessation is most important. Aggressive pharmacologic therapy is also required. Bronchoactive drugs are more successful in improving airflow in patients in early stages of the disease than those with more advanced stages. The National Mucolytic Study Investigators' Meeting, focusing on the usage of iodinated glycerol (Organidin) in patients with moderate-to-advanced airflow obstruction from chronic bronchitis, has concluded that symptoms of the disease were improved in treated patients compared with patients receiving placebo. These results, based on a major double-blind, controlled clinical trial, will usher in a new approach to the treatment of patients with mucus clearance problems. It is now time to develop a nationwide strategy for involving all primary care physicians in the identification and treatment of patients with COPD.

The fifth leading cause of death in the United States, chronic obstructive respiratory conditions, cannot be cured but can be considerably ameliorated by appropriate management. Many patients with COPD have a combination of chronic bronchitis, asthma, and emphysema. While the damage due to emphysema is permanent, many of the pathophysiologic changes of asthma and bronchitis can be reversed to some extent, and such reversal should be a goal of therapy. Smoking cessation will help the patient more than any other medical treatment. Bronchodilator therapy is best given by inhalation from a metered dose inhaler and on a maintenance basis. Be sure to check inhaler technique. An anticholinergic agent, eg, ipratropium bromide, is probably most effective, but many patients prefer a beta 2-selective adrenergic agent. Xanthines are currently third choice but are very useful to cover nocturnal dyspnea. Corticosteroids are usually only used in acute exacerbations and then only for short courses. If prolonged use is required, however, the inhalation route minimizes side effects to which these patients are particularly prone. Antibiotics are also usually only used in exacerbations, but one can be liberal with them. Use the less expensive broad-spectrum options for ten days. Some clinicians believe that hydration is an effective expectorant. Mucolytic therapy is extensively used outside the United States. The appropriate role of mucolytic therapy in the treatment of bronchitis remains to be more fully explored. Low-flow oxygen is only used in the prevention or treatment of cor pulmonale when the PaO2 is persistently at or below 55, or with a rising hematocrit and right-sided cardiac changes. If used, oxygen is helpful only when given long term for at least 18 h per day, not on a prn basis. Cardiac glycosides are probably of little benefit, but diuretics have an important role in treatment of fluid retention. Pulmonary vasodilator therapy is still experimental, as is almitrine. Prophylaxis with pneumococcal vaccine and annual influenza vaccine is rational but has not been proven to be of value. Exercise and activity should be encouraged for all except those with frank congestive heart failure. The role of "breathing exercises" is currently being reevaluated. Surgery has almost no place in the management of COPD. Anesthesia often results in postoperative complications in this disease. Avoid all sedatives and tranquilizers.

If one includes all types of chronic generalized airways obstruction under the heading of "COPD," diagnosis of this condition requires only the demonstration of an obstructive ventilatory impairment on spirometric testing that persists despite maximum medical therapy. However, as generally used, the term COPD implies that upper airways obstruction and "specific" lung diseases that can produce an obstructive type of physiologic abnormality have been excluded. Examples of these exclusions include silicosis, sarcoidosis, and even advanced tuberculous disease. It is more difficult to determine the type of disease that is causing the chronic airways obstruction in patients with COPD as defined above. A severe and persistent form of asthma, sometimes called "chronic asthmatic bronchitis," can mimic the typical emphysematous form of COPD that is characteristic of heavy cigarette smokers. Since these types of chronic airflow obstruction differ in regard to their clinical courses, prognoses, and treatments, their distinction is clinically important. One should not be discouraged by the fact that some patients appear to have a mixed type of disorder. Features that help differentiate the various forms of chronic airways obstruction are described in this report, and recommendations are offered to help guide the practitioner in the workup indicated for patients thought to have any type of chronic airways obstruction. It is also emphasized that patients vary markedly in regard to the relative importance of readily reversible bronchospasm, airways inflammation, and mucus hypersecretion in producing their disability. Assessment of these factors is critical in determining clinical management.

Chronic bronchitis is characterized by mucociliary dysfunction resulting from structural and functional defects of cilia and the secretory apparatus. The combination of hypersecretion and ciliary impairment leads to disruption of mucociliary interaction and hence the accumulation of secretions in the lower airways. Cigarette smoke appears to play a critical role in the pathogenesis of chronic bronchitis-associated mucociliary dysfunction. While the excessive lower airway secretions may have only minor effects on the natural course of airflow obstruction, they could transiently compromise airway function during acute exacerbations. In addition, altered aerosol deposition in the airways resulting from excessive airway secretions could influence the airway responses to inhaled irritants and pharmacologic agents. There are currently no direct, non-invasive methods available to assess the quantity and distribution of airway secretions in vivo. Indirect indices such as cough frequency, sputum volume, respiratory function, and mucociliary clearance are nonspecific and subject to misinterpretation. The clinical utility of mucotropic pharmacologic agents and of physical maneuvers directed at removing excessive lower airway secretions is therefore difficult to evaluate objectively.

Sclerosing mediastinitis is an uncommon disease associated with a multiplicity of clinical syndromes. The cause of this disorder is probably an abnormal fibroproliferative response to an inflammatory stimulus, most commonly a granulomatous infection secondary to Histoplasma capsulatum. The pathophysiology of this disease is predicated on the encasement of mediastinal vital organ structures within a dense fibrotic mass. This mass appears to emanate from an invasive chronic inflammatory process causing erosion as well as external compression of these structures. The following case reports illustrate the diversity of this disease entity, representing a patient population from the Ohio River Valley, endemic for histoplasmosis. The purpose of this report is to elucidate the various clinical manifestations of sclerosing mediastinitis and to correlate the pathologic process with a rational approach to treatment.