Development of an ex vivo human-porcine respiratory model for preclinical studies.

Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures "pleural" depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with 81mKrypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies.

Bronchoalveolar lavage in hypersensitivity pneumonitis: a series of 139 patients.

Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis, classically delineated by an increase of CD8+ lymphocytes, with an inversion of the CD4+/CD8+ ratio. The aim of this study is both to describe the yield and cell bronchoalveolar lavage (BAL) profile and to revisit the assumption of low BAL CD4/CD8 ratio in the diagnosis of HP. A multicentric study was conducted on 139 patients who fulfilled the standardized diagnostic criteria of HP, mainly affected by farmer's lung. Mean total cell count in BAL fluid was 594 ± 401.10(3) cells /ml. Prominent absolute lymphocytic alveolitis, moderate neutrophilia, and mild eosinophilia and mastocytosis were found. Mean CD4/CD8 ratio was 3.8 ± 6.1 (median 2.1). Thirty four percent of the patients showed lymphocytic CD8 alveolitis (ratio < 1). The CD4/CD8 ratio was not different between forms, etiologies of HP, and time elapsed since last antigen exposure, but was higher in women (p=0.02). BAL in HP shows high total cell and lymphocyte counts, moderate neutrophilia, and mild eosinophilia and mastocytosis. An absence of low CD4/CD8 ratio should not at all exclude diagnosis.