Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper.

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Aspergillus antigen detection in bronchoalveolar lavage fluid from patients with invasive aspergillosis and aspergillomas.

Improved diagnostic techniques have been needed for pulmonary aspergillosis, a common opportunistic fungal infection with a high mortality rate. Radioimmunoassay was used in this study to detect Aspergillus antigen in bronchoalveolar lavage fluid. In four patients with invasive aspergillosis or aspergillomas, Aspergillus antigen was detected in bronchoalveolar lavage fluid. In two patients, results of fungal cultures were negative or delayed. The specificity of antigen detection in bronchoalveolar lavage fluid was 91 percent in 35 control patients with a variety of pulmonary disorders. The technique or radioimmunoassay detection of microbial antigen in bronchoalveolar lavage fluid appears promising for the diagnosis of aspergillosis.

Diagnosis of nosocomial bacterial pneumonia in acute, diffuse lung injury.

Nosocomial bacterial pneumonia as a complication of acute, diffuse lung injury may be difficult to distinguish clinically from other pathologic processes. To determine the reliability of findings commonly used to diagnose pneumonia in this setting, we compared clinical predictions of bacterial pneumonia with postmortem histology. Pneumonia was present histologically in 58 percent of the study patients, 36 percent of whom had been thought to have only lung injury. Among patients who had only diffuse lung injury histologically, 20 percent were thought to have pneumonia by clinical evaluation. Overall, 29 percent of cases were misdiagnosed. Improved diagnostic techniques will be required before the efficacy of preventive or therapeutic measures for pneumonia in the setting of acute, diffuse lung injury can be accurately determined.

Pleural effusions: meeting the diagnostic challenge.

Etiologies of complicated pleural effusions include infections, malignancies, and rheumatologic disorders. Appropriate diagnostic studies are determined by specific clinical situations. Possible causes of benign pleural effusions should be considered first. Commonly overlooked diagnoses include chronic effusions initially due to transudative processes, benign asbestos effusions, and traumatic effusions.

Immunodiagnosis of invasive pulmonary aspergillosis in rabbits. Fungal antigen detected by radioimmunoassay in bronchoalveolar lavage fluid.

To improve antemortem diagnosis of invasive pulmonary aspergillosis, we used a radioimmunoassay to detect an Aspergillus fumigatus antigen in bronchoalveolar lavage fluid (BALF) and evaluated this technique in a model of disseminated aspergillosis. Antigen was detected in 91% of BALF samples obtained from 11 rabbits with major pulmonary aspergillosis. In an additional 10 rabbits with only minor pulmonary involvement, antigen was detected in 40% of concentrated lavage samples. In contrast, antigenlike activity was found in only 1 of 17 BALF samples from control animals with systemic candidiasis, in none of 9 control animals with staphylococcal pneumonia and in none of 10 normal control animals. Although antigen was present in the serum of 76% of animals infected with Aspergillus, 27% of those with major pulmonary involvement had antigen detected in BALF alone. We found that an extracellular microbial antigen can be detected in BALF and that this technique in the disseminated aspergillosis model is both sensitive and specific for invasive pulmonary disease.

Hypersensitivity pneumonitis treated with an electrostatic dust filter.

A 60-year-old woman had had recurrent acute migratory pneumonias for 9 months. The results of an evaluation, which included tests for serum precipitins, a transbronchial biopsy, and a bronchial provocation, confirmed a diagnosis of hypersensitivity pneumonitis caused by an Aspergillus species. The findings from gravity air cultures in the home showed a heavy infestation of mold. The installation of electrostatic dust filters in the return ducts of the central air conditioning system resulted in the lowering of mold colony counts to normal levels. This change in the environment enabled the patient to live at home without having the signs and symptoms of hypersensitivity pneumonitis, or a need for medication. Thirty months after the electrostatic dust filters were installed, total mold colony counts were still normal, the patient remained free of the signs and symptoms of hypersensitivity pneumonitis, and serum precipitins could no longer be demonstrated. The results of a bronchial challenge to Aspergillus species, however, remained positive; these positive results suggest that long-term memory immune mechanisms may play an important role in the pathogenesis of hypersensitivity pneumonitis and lessen the importance of precipitins in establishing a diagnosis. We report that electrostatic dust filters may be an effective treatment for patients with hypersensitivity pneumonitis when avoidance of the causative antigen cannot be easily and rapidly achieved.

Acute pulmonary edema associated with use of low-molecular weight dextran for prevention of microvascular thrombosis.

Low-molecular weight dextran is commonly used to prevent thrombosis after microvascular procedures; however, the potential complications of this drug are not well known. We report a case of acute pulmonary edema in a healthy person after elective microsurgery for treatment of a malignant tumor of the forearm. The mechanism of action of dextran and the pathophysiology of two potential adverse reactions to this drug are discussed. It is thought that in this patient pulmonary edema was caused by dextran toxicity.