Current treatment options for asthma in adults.

Asthma is a common disorder with an increasing prevalence in the developed world. It is a serious health problem affecting health care costs, lost productivity, and death. Unfortunately, uncontrolled asthma is common and often unrecognized by physicians; of equal concern, uncontrolled asthma is accepted by asthmatic patients as they are uneducated as to what to expect from asthma therapy. Many learn to live with the limitations of daily activity and to overuse their rescue inhalers and yet when asked by their physicians, ''How's your asthma?'' the answer is ''okay''. The pursuit of more revealing questions regarding frequency in the use of rescue medications, nocturnal symptoms, activity limitations, and compliance with controller medications may be then overlooked. To achieve the goal of normal life on as few medications as possible will start with a well-educated patient. Understanding intermittent from persistent asthma and then tailoring the best regimen for each patient is imperative. The treatment options and the advances in the understanding of the pathophysiology of asthma in the past 3 decades have been remarkable. There are increasing resources for both physicians and patients available to facilitate a better understanding of asthma management and the several treatment options. Currently established guidelines are an excellent starting point for initiating therapy for intermittent and mild, moderate, and severe persistent asthma. The short-acting beta 2 agonists are first-line therapy for intermittent asthma, exercise-induced asthma, and acute exacerbations. Long-acting Beta 2 agonists, cromolyn and nedocromil, and leukotriene modifiers may also be used for exercise. Systemic corticosteroids may be needed for acute exacerbations. The treatment of choice for persistent asthma is ICS and, depending on the severity, add-on therapy with long-acting beta 2 agonists, theophylline, and leukotriene modifiers are next. Lastly, omalizumab, anti-IgE therapy, will make an important place for its use in certain persistent moderate and severe asthma. This will be particularly true if the cost of the medication is reduced in the future. Asthma control, morbidity, and mortality will improve with a careful and comprehensive medical regimen using the current multiple treatment options.

Staphylococcus aureus and human platelets cause pulmonary hypertension and thromboxane generation in isolated saline-perfused rabbit lungs.

The potential contributions of bacterial-platelet interactions to the development of acute edematous lung injury, such as that seen in the adult respiratory distress syndrome (ARDS), remains unknown. We found that the addition of Staphylococcus aureus, 502A to isolated rabbit lungs perfused with saline, and human platelets rapidly decreased the number of circulating platelets, increased pulmonary artery perfusion pressures, and generated thromboxane B2, the stable derivative of thromboxane A2. In contrast, increases in perfusion pressures or thromboxane levels did not occur when platelets treated with acetylsalicylic acid (ASA) were used, even though ASA-treated platelets disappeared from the perfusates. The results suggest that activation of platelets by bacteria may account for thrombocytopenia, platelet microemboli, and/or contribute to increases in pulmonary artery pressures seen in some patients with ARDS.

Unexplained pulmonary infiltrates in the compromised patient. An invasive investigation in a consecutive series.

A series of 51 consecutive unexplained pulmonary infiltrates were reviewed retrospectively, in a group of 48 patients in whom invasive procedures were performed. Fifty-two percent of these patients had leukemia or lymphoma and 40% had solid tumors. All patients had lung tissue obtained premortem either by transbronchial biopsy through the flexible fiberoptic bronchoscope or by open lung biopsy. There was a 27% complication rate in these invasive procedures including bleeding, pneumothorax, and ventilatory support. Infectious agents were found in only 13 cases (25%) with a mortality rate of 62%. The pathologic finding of the underlying malignant disease or organizing pneumonia portended a poor prognosis with 100% and 80% mortality, respectively. Twenty-one patients had biopsy tissue revealing only nonspecific pathologic changes and were associated with the lowest mortality (19%). It was found that 50% of the solid tumor patients with unexplained pulmonary infiltrates had nonspecific pathologic changes. The biopsy findings resulted in a change in the therapy in 29% of the cases and in 19% of the cases the subsequent change in therapy resulted in marked improvement. The lung biopsy is useful to diagnose treatable infectious disease, as well as for prognostic guidance in caring for critically ill compromised patients.

Mepacrine but not methylprednisolone decreases acute edematous lung injury after injection of phorbol myristate acetate in rabbits.

A good model of the adult respiratory distress syndrome (ARDS) is intravenously injected phorbol myristate acetate (PMA), which causes pulmonary sequestration of neutrophils and a neutrophil-dependent acute edematous lung injury in rabbits. In the present study, pretreatment of rabbits with the antimalarial agent, mepacrine, prevented lung edema after injection of PMA without altering initial accumulations of neutrophils in the lung. Mepacrine also decreased oxygen radical production and degranulation by neutrophils stimulated by PMA in vitro. In contrast, pretreatment with methylprednisolone did not decrease edematous lung injury in rabbits given PMA nor did it inhibit O2 radical production or degranulation by neutrophils treated with PMA in vitro. Our results suggest that agents that modify neutrophil function may be useful in decreasing lung injury after PMA treatment and, perhaps, in treating patients with ARDS.

Acetyl glyceryl ether phosphorylcholine-stimulated human platelets cause pulmonary hypertension and edema in isolated rabbit lungs. Role of thromboxane A2.

Macrophages, neutrophils, and platelets may play a role in acute edematous lung injury, such as that seen in the adult respiratory distress syndrome (ARDS), but their potential actions and interactions are unclear. Because stimulated human macrophages and neutrophils can release acetyl glyceryl ether phosphorylcholine (AGEPC), a potent platelet activator, we hypothesized that in ARDS, leukocyte release of AGEPC might stimulate platelets to release thromboxane A2 (TXA2), which then produces pulmonary hypertension and lung edema. In support of this premise, we found that pulmonary hypertension and edema occurred in isolated rabbit lungs perfused with human platelets and AGEPC, but not with platelets or AGEPC alone. Infusion of a vasodilator (nitroglycerin) to maintain base-line pulmonary artery pressures in lungs perfused with platelets and AGEPC prevented the development of lung edema suggesting that platelet and AGEPC-induced edema was hydrostatic in nature. Additional experiments suggested that the increased pressure was a result of TXA2 release from platelets stimulated by AGEPC. Specifically, preincubation of platelets with imidazole, a thromboxane synthetase blocker, prior to infusion with AGEPC significantly diminished pulmonary hypertension and prevented lung edema. Furthermore, pretreating lung preparations with 13-azaprostanoic acid, a TXA2 antagonist, before infusion of AGEPC and untreated platelets also reduced the pulmonary hypertension and blocked the lung edema. The role of TXA2 was further suggested when perfusates from lungs infused with platelets and AGEPC developed high levels of TXA2, whereas perfusates from controls did not. These results suggest that platelet aggregation induced by AGEPC may contribute to ARDS by releasing TXA2, which raises microvascular pressure and increases edema formation, especially when an underlying permeability defect is present.