What is the meaning of these findings to the practicing chest physician? First, leukotrienes are potent airway constrictors; they are capable of reproducing the type of airway constriction observed in asthma. The role of leukotrienes in this regard has yet to be established, but experiments to test the importance of these agents in this setting are likely to be performed soon. Specifically, several leukotriene receptor antagonists or synthesis inhibitors have been identified and may provide the tools needed to test this crucial hypothesis. Second, the leukotrienes are unique bronchoactive agents in that the degree of hyperresponsiveness between normal and asthmatic subjects varies markedly with the bronchoconstrictor index used to assess response. When one compares normal subjects to asthmatic subjects, there is substantial overlap in leukotriene sensitivity among groups when V30-P is used as the bronchoconstrictor index. However, when the FEV1 is used as the bronchoconstrictor index, there is little overlap in sensitivity between normal and asthmatic subjects, and the separation between the two groups is even more clearly made than it is with histamine or methacholine challenge. Thus, LTD4 inhalation challenge may replace the histamine and methacholine challenges in the diagnosis of cryptic shortness of breath. Third, the differential sensitivity of various bronchoconstrictor indices in both normal and asthmatic subjects when leukotrienes are used may provide clues as to the locus of airway hyperresponsiveness in asthma. Thus, leukotrienes hold the promise of new ways to treat and diagnose asthma, as well as providing new insights into the pathobiology of the disease itself.

Although oxygen therapy has been used in the care of critically ill patients for many years, the recognition of pulmonary oxygen toxicity as an important clinical problem is relatively recent. The biochemical basis of oxygen toxicity is increased production of highly reactive, partially reduced metabolites of oxygen, including hydrogen peroxide and free radicals, by cells in hyperoxia. Enzymatic intracellular defense mechanisms exist which protect cells from the toxic effects of oxygen free radicals. The physiologic manifestations of oxygen toxicity include decreases in vital capacity, diffusing capacity, and lung compliance. The pathologic changes of oxygen toxicity are not specific and resemble those of the adult respiratory distress syndrome. Many drugs used in the care of patients, including bleomycin, nitrofurantoin, and corticosteroids, may exacerbate oxygen-induced lung injury. No effective pharmacologic means exist for lessening pulmonary oxygen toxicity in humans.

The classic diseases of dusty occupations may be on the decline, but this is not the case for chronic nonmalignant lung disease characterized by airflow limitation. This group of diseases, almost certainly multifactorial in etiology, occurs in those engaged in dusty occupations as well as in those who are not. Among the environmental factors concerned, cigarette smoking is clearly one of the most important, but occupational exposures are increasingly implicated. It is also clear that not all with similar exposures are affected, pointing to the importance of host or personal factors. Evidence is now accumulating in support of what has been called the Dutch hypothesis. This explanation of the natural history of chronic airflow limitation suggests that an "asthmatic tendency" is a necessary factor whether the putative exposure is to cigarettes or to other airborne pollutants. Further research should therefore be directed towards clarifying the relationships of acute and chronic airway dysfunction in response to airborne pollutants of all types.

The intrapulmonic accumulation of neutrophils is a relatively common finding in certain animal models of increased permeability pulmonary edema and in humans with the adult respiratory distress syndrome. The release of toxic oxygen radicals from these cells can result in acute lung injury. Whether these cells mediate the increased permeability in all models of increased permeability pulmonary edema remains controversial. This review will examine the role of the neutrophils in various models of increased permeability pulmonary edema.

Postural drainage has usually been shown to be an effective component of chest physical therapy; there is currently no data showing a beneficial effect of percussion or vibration; directed coughing may be as efficacious as postural drainage (Table 3); the forced expiration technique may increase sputum clearance with or without postural drainage (Table 4).

Breathlessness is a common symptom in patients with respiratory disorders and contributes significantly to functional disability. Recent studies of the psychophysics of respiratory sensation suggest that dyspnea is a function of the forces generated by the respiratory muscles during the act of breathing and may simply represent the intensity of the sense of effort arising from central respiratory motor command signals. It is important to recognize the multidimensional nature of respiratory sensations that include not only sensory aspects but also affective and cognitive components. At present there are no established satisfactory means of treating dyspnea. Efforts to minimize abnormalities in ventilatory system impedance are limited by the largely irreversible nature of most chronic lung diseases. Sedatives and narcotic agents have not proved to be effective in altering perceptual responses and may have an adverse effect, worsening respiratory failure. Physical measures to improve overall conditioning and respiratory muscle performance may be most effective in relieving breathlessness and improving exercise capacity in patients with chronic lung disease.