Search

Cryptogenic organizing pneumonia is an idiopathic form of organizing pneumonia (also known as bronchiolitis obliterans organizing pneumonia). Because cryptogenic organizing pneumonia is considered an inflammatory disease, it characteristically responds to the broad-spectrum antiinflammatory corticosteroids, although relapse is common on discontinued use. Additionally, long-term use of corticosteroids has many side effects. In severe cases in which corticosteroids have failed, either cytotoxic therapy or macrolide therapy is used. Because of the toxicity and adverse effects of cytotoxic therapy (e.g., cyclophosphamide), this therapy option cannot be used long term in refractory cases. Macrolide therapy has been shown to be an effective antiinflammatory agent that is relatively safe when used on a long-term basis in patients with cryptogenic organizing pneumonia.

The shortage of lung donors for clinical transplantation could be significantly alleviated if lungs could be retrieved from cadavers hours after death. However, the time course of loss of lung viability after circulatory arrest and organism death remains unclear. To determine postmortem adenine nucleotide tissue levels in the lung and their relationship to lung viability, Sprague-Dawley rats were sacrificed and then ventilated with 100% oxygen (n = 50, O2) or 100% nitrogen (n = 40, N2) or left nonventilated (n = 50). Lungs from control rats (n = 20) were retrieved immediately after sacrifice. Lungs in the three study groups were retrieved at successive intervals postmortem. Adenine nucleotides (ATP, ADP, and AMP) and hypoxanthine and xanthine metabolites of adenosine were extracted from lung tissue and measured using high-performance liquid chromatography. Pulmonary parenchymal cell viability was quantified by pulmonary artery infusion of trypan blue vital dye in the contralateral lung of each animal. By 4 hr postmortem, viability was 85 +/- 1% in the O2-ventilated cadaver rat lungs, significantly higher than in the N2-ventilated (43 +/- 8%) and in the nonventilated (48 +/- 4%) lungs, where the percentage of viable cells was similar. All of the groups showed a time-dependent decrement in ATP levels and total adenine nucleotide (TAN) levels after death, but this was markedly attenuated in O2-ventilated cadaveric rat lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonicates of freshly isolated Clara cells produced thromboxane B2 (TxB2), prostaglandin (PG) D2, PGE2, PGF2 alpha, hydroxyheptadecatrienoic acid (HHT), and 12-hydroxyeicosatetraenoic acid (12-HETE) as detected using high-performance liquid chromatography (HPLC). Sonicates of Clara cells cultured on collagen matrices produced the same metabolites. Rates of [3H]arachidonic acid metabolism increased in culture, but the changes were not associated with changes in cell number. Sonicates of freshly isolated tracheal cells produced mainly 12-HETE. Cyclooxygenase products were not produced consistently. Sonicates of tracheal cultures produced significant quantities of TxB2, PGD2, PGE2, PGF2 alpha, and HHT, but 12-HETE remained the major metabolite. Equivalent short-circuit current (Ieq) across cultured Clara cell epithelia was unaffected by bilateral exposure to TxB2, PGD2, PGE2, PGF2 alpha, HHT, or 12-HETE. A minor (1%) decrease in transepithelial resistance (Rt) followed exposure to PGD2. Indomethacin had no significant effect on Rt or Ieq, but exposure of indomethacin-pretreated preparations to PGE2 revealed a minor (2%) increase in Ieq. In contrast, tracheal cell epithelia exhibited significant changes in Rt and Ieq in response to PGF2 alpha, PGE2, and HHT. These results indicate that Clara cells metabolize arachidonic acid to biologically active eicosanoids, but the resulting products do not play a major role in regulation of transepithelial ion transport by this cell type.