Cryptococcal antigen testing of lung tissue homogenate improves pulmonary cryptococcosis diagnosis: Two case reports.

BACKGROUND: Pulmonary cryptococcosis (PC) is an opportunistic infectious disease of the respiratory system. Lung tissue biopsies, culture of respiratory samples (e.g., sputum, lung tissue, pleural fluid, and bronchoalveolar lavage fluid), and cryptococcal antigen (CrAg) testing are helpful for a definitive diagnosis. However, these tests are sometimes falsely negative. PC is often misdiagnosed or underdiagnosed owing to the absence of obvert symptoms, poor imaging specificity, and false-negative laboratory tests. CASE SUMMARY: We report two female patients who underwent computed tomography-guided percutaneous needle pulmonary biopsy of a lung nodule for a confirmed diagnosis. In both patients, the CrAg test on the lung biopsy tissue homogenate was positive, while the serum CrAg test was negative. Combined with the lung tissue pathology, we made the diagnosis of PC. Antifungal therapy was effective in both patients. CONCLUSION: Given the findings of our cases and the literature review, lung tissue homogenate CrAg testing can be helpful in improving the diagnosis of PC.

Pulmonary delivery of a p38 α/ß MAP kinase inhibitor: bioanalytical method validation and biodistribution in rat plasma and respiratory tissues.

PF-03715455, an inhaled p38 α/ß mitogen-activated protein (MAP) kinase inhibitor (MAPK), has being identified as an agent with potential therapeutic action on lung diseases such as COPD and severe asthma. However, little is known about this MAPKs local and systemic pharmacokinetics after pulmonary delivery. Consequently, the aim of the present work was to develop and validate a method of extraction and quantification of PF-03715455 in rat plasma and lung tissues and to determine the drug biodistribution in plasma and respiratory tissues after intratracheal administration of the drug solution in rats. The method was validated in rat plasma samples and resulted selective and linear in the concentration range of 0.08-100 ng/ml. Then a partial validation was carried out on samples obtained by the extraction and quantification of PF-03715455 from rat lung homogenate in order to ascertain method applicability on lung tissue samples. The intratracheal administration of drug in solution to rats evidenced a rapid elimination from the plasma, while on the contrary a prolonged residence time in lung tissue was evidenced. In conclusion, a linear, accurate, precise and reproducible method has been developed and validated according to FDA and EMA guidelines to quantify plasmatic and tissue-associated concentrations of PF-03715455 in order to investigate this compound in pharmacokinetics pre-clinical studies in rats. The administration of drug solution evidenced a prolonged permanence of the drug in the lungs that could be related to a slow absorption/poor permeability of the drug across airways epithelia.