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.

Enteral tube feeding is an attractive alternative to intravenous alimentation for nutritional support. As previously used nasogastric tubes have been replaced with narrow-bore nasogastric tubes, the spectrum of complications seen with these devices has changed. We report a previously undescribed event associated with narrow-bore nasogastric tube feeding, review the literature, noting predisposing factors and complications, and suggest guidelines to avoid pitfalls of insertion and the ensuing adverse effects.

Successful aerosol therapy generally depends on the small percentage (typically 10 percent) of the drug dose delivered to the lungs from metered-dose inhalers (MDIs), nebulizers, and dry powder inhalers. Deposition of therapeutic aerosols occurs by inertial impaction (in the oropharynx and large conducting airways) and by gravitational sedimentation (in the small conducting airways and alveoli) and is determined by the mode of inhalation, particle or droplet size, and the degree of airway obstruction. Deposition of metered-dose aerosols in the lungs can be enhanced by using MDIs correctly (aerosol release coordinated with slow, deep inhalation, followed by a period of breath-holding); many patients have poor inhaler technique. Extension devices (spacers and holding chambers) make MDIs easier to use and may increase lung deposition to levels achieved by a correctly used MDI while substantially reducing oropharyngeal deposition. Optimal use of air-driven (jet) nebulizers depends primarily on the choice of nebulizers with relatively small droplet size and on the volume fill and compressed gas flow rate.

Inspiratory muscle function is impaired in many patients with severe COPD. This functional impairment often leads to hypercapnic respiratory failure via inspiratory muscle fatigue. Factors responsible for this functional impairment are: (1) an excessive mechanical load (high resistance and low compliance) for the inspiratory muscles to overcome; (2) the low, flat configuration of the diaphragm owing to lung hyperinflation; (3) reduced inspiratory muscle blood flow relative to the increased respiratory work requirement; and (4) tachypnea which increases the duty cycle (TI/Ttot) for inspiratory muscles, increases hyperinflation, wastes ventilation, and otherwise causes deterioration of gas exchange. Therapy is directed toward improving inspiratory muscle function and has three strategic goals: (1) to reduce the load imposed on the inspiratory muscles and reduce their mechanical disadvantage; (2) to improve the contractile characteristics of the inspiratory muscles; and (3) if goals 1 and 2 cannot be attained otherwise, to rest the inspiratory muscles using mechanical ventilation. Inspiratory muscle training offers promise as a means of preventing hypercapnic respiratory failure. Available data suggest that some COPD patients benefit from it. To be determined are which patients will benefit from it and which will not, as well as which training regimens are most effective.

Theophylline is a widely used bronchodilator, but only recently have its positive cardiovascular actions been recognized in patients with chronic obstructive pulmonary disease (COPD). Intravenous aminophylline acutely reduces pulmonary artery pressures and pulmonary vascular resistance and increases both right and left ventricular ejection fraction. Oral long-acting theophylline produces a similar and chronic improvement in biventricular performance. Postulated mechanisms by which theophylline enhances right and left ventricular systolic pump performance include reduction in ventricular afterload and positive effects of the drug on ventricular inotropy. Theophylline may be particularly valuable in patients with a combination of COPD, pulmonary artery hypertension, and right or left heart failure.

Theophylline has emerged as a major prophylactic agent for controlling the symptoms of chronic asthma, but it provides little if any relief of pulmonary symptoms caused by irreversible chronic airways obstruction. Although in vitro it inhibits phosphodiesterase and antagonizes adenosine receptors, theophylline's mechanism of action in asthma is unknown. Often, 10 to 20 micrograms/ml is used as the range of serum concentrations where there is the greatest likelihood of obtaining maximal benefit safely. Slow-release products have the potential to provide more stable serum concentrations with longer dosing intervals. However, clinically important differences in rate and sometimes extent of absorption exist between the 15 formulations sold under 29 brand names in this country. In patients with more rapid elimination, few products have sufficiently slow absorption to allow twice-daily use. Often these formulations must be administered every eight hours to prevent breakthrough in asthmatic symptoms despite promotional claims to the contrary. In patients with slower elimination, differences among products are unlikely to be clinically important with 12-hour dosing intervals. Current products approved for "once-a-day" dosing are clinically inadequate because of erratic absorption or excessive serum concentration fluctuations. Moreover, food induces dose dumping of potentially toxic amounts of theophylline from Theo-24, greatly increases the extent of absorption of theophylline from Uniphyl, decreases extent of absorption from Theo-dur-Sprinkle capsules, but has no clinically important effect on Theo-Dur tablets, Theobid, Slo-Bid, or Somophyllin-CRT. The effects of food or other factors that alter gastrointestinal physiology on theophylline absorption are unknown for most other products.

In an effort to improve the delivery of a drug to the lungs, to correct problems of hand-lung discoordination, and to reduce local side effects such as oral candidiasis, a number of spacer devices have been developed to attach to metered-dose inhalers. Administration of bronchodilator drugs to patients with faulty techniques of inhalation has been improved with the addition of spacers. In adults and older children with a correct technique of inhaling bronchodilators, the spacer devices do not seem to have any advantage over the simple metered-dose inhalers. Young children (two to five years) can benefit from inhaled bronchodilators or corticosteroids by use of spacer devices with one-way valves. Older children and especially adults who suffer from dysphonia or thrush from inhaled corticosteroids can also benefit from spacers. In patients whose condition is well controlled with the usual inhaled doses of corticosteroids with no local side effects, spacer devices show promise, but more studies are needed.

The functional anatomy of the respiratory muscles and their actions and interactions are presented, particularly of the diaphragm. The large amount of blood flow to respiratory muscles and the determination of blood flow are reviewed, while the role these muscles play in the overall economy of the body in health and disease are discussed. Finally the failure of the respiratory muscles in the context of the development of hypercapnic respiratory failure is examined. It is argued that as the respiratory muscles become fatigued, afferent information from the respiratory muscles modifies the breathing pattern, which might be beneficial to respiratory muscle function, but it might compromise alveolar ventilation.

The likelihood that the leukotriene products derived from the 5-lipoxygenase pathway mediate aspects of obstructive airways diseases is strongly suggested by their documented capacities to effect airway spasmogenicity, airway hyperreactivity, tissue edema formation, mucus secretion, and tissue infiltration by leukocytes. That the various leukotriene components of SRS-A have unique receptors on responding tissues and are recoverable from airway surfaces in several inflammatory lung diseases and that several resident and infiltrating cell types have significant potential for leukotriene biosynthesis lend further support to their postulated pathobiologic roles. To fulfill Koch's postulates for proof of leukotrienes' etiologic role, it remains to be shown that inhibition of their biosynthesis or specific antagonism at their end-organ receptors can greatly ameliorate these disease states.

This article reviews the multiple mechanisms by which glucocorticoids influence the pathophysiology of pulmonary disease. Particular emphasis is given to the influence of glucocorticoids on the release and action of mediators that promote inflammation and that modulate other pathophysiologic processes in the lung. The time course and mechanisms of action that contribute to glucocorticoid effects on pulmonary function are also discussed.

Bronchoalveolar lavage (BAL) is a powerful tool with which the immunology of the lung in health and disease can be studied. This technique has been successfully used to characterize localized humoral and cell-mediated responses in sarcoidosis and a number of other interstitial pneumonitides. In contrast, BAL in patients with lung cancer has resulted in some confusion regarding the extent and type of local and systemic immunity in these patients. This review summarizes some of the data obtained from these patients via BAL, but does not attempt to explain the reported discrepancies. The objective of this review is rather to identify gaps which exist in our knowledge of the environmental factors influencing pulmonary immunity in primary lung cancer.

Infants with respiratory failure in the first weeks of life may develop a chronic pulmonary condition called bronchopulmonary dysplasia. Their lungs have areas of atelectasis and areas of air trapping from variable obstruction of the airways. These infants may be dependent on supplemental oxygen or a ventilator and may require hospitalization for months, and have symptoms of airway obstruction which last for years. They require meticulous medical management to avoid a number of common complications such as patent ductus arteriosus, cor pulmonale, tracheal stenosis, recurrent aspiration, and death. The condition of most infants improves over the first two years. Preliminary studies suggest that their exercise and pulmonary function is usually close to normal by school-age. The long-term implications for the increasing number of children with this disease who will soon reach adulthood are still unknown.

Aspirin intolerance is particularly common in asthmatic patients who additionally have chronic rhinitis and/or nasal polyps. These individuals differ in several respects from patients who experience urticaria and/or angioedema after aspirin administration, and differing mechanisms may be involved. Data regarding the latter are indirect and incomplete, but suggest that ASA-sensitive asthma is most likely to be related in some manner to the capacity of ASA to inhibit cyclooxygenases, enhanced lipoxygenase metabolism perhaps playing a crucial role. Current research employing ASA "desensitization" may help to elucidate these enigmas.