The Validity of Static Lung Compliance in Asbestos-induced Diseases

Background

Pulmonary compliance can be viewed as an indicator of distensibility of the lungs, not only in asbestos-induced pulmonary disorders but also in visceral pleural fibrosis extending into the lung parenchyma. In this study we evaluated static compliance measurements in asbestos-derived diseases, especially in patients with parietal pleura plaques. Lung function analyses, especially static lung compliance, were correlated with high-resolution computer tomography examinations.

Methods

Sixty-three patients with parietal pleural plaques, 10 with visceral pleural fibrosis, 39 with parenchymal pulmonary asbestosis together with parietal pleural plaques, and 42 with parenchymal pulmonary asbestosis together with visceral pleural fibrosis were enrolled in the study.

Results

In comparison with patients having only parietal pleural plaques, those having asbestosis and visceral pleural fibrosis showed significant decreases in static lung compliance, diffusing capacity, and vital capacity. Visceral pleural thickening was also associated with significantly reduced FEV₁, MEF₅₀, and FEV₁/FVC ratios. Multiple regression analyses indicated that the existence of visceral pleural fibrosis (p?=?0.017) is the most important factor accounting for a decrease in static compliance. Reference values of static lung compliance differ notably. In comparison with mean reference values, the sensitivity of detecting reduced lung compliance was calculated to be between 9.7 and 45.5?%. Other respiratory function variables failed to show any significant differences.

Conclusion

Our data indicate that the measurement of static compliance is not sufficient for early detection of pulmonary function impairment in patients with parietal pleural plaques.     

CD34(+)/CD38(-) stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin

Background

CD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias.

Design and Methods

We analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targeting drug, gemtuzumab/ozogamicin, were examined.

Results

As assessed by flow cytometry, stem cell-enriched CD34⁺/CD38⁻/CD123⁺ leukemic cells expressed significantly higher levels of CD33 compared to normal CD34⁺/CD38⁻ stem cells. Moreover, highly enriched leukemic CD34⁺/CD38⁻ cells (>98% purity) displayed higher levels of CD33 mRNA. In chronic phase patients, CD33 was found to be expressed invariably on most or all stem cells, whereas in accelerated or blast phase of the disease, the levels of CD33 on stem cells varied from donor to donor. The MDR1 antigen, supposedly involved in resistance against ozogamicin, was not detectable on leukemic CD34⁺/CD38⁻ cells. Correspondingly, gemtuzumab/ozogamicin produced growth inhibition in leukemic progenitor cells in all patients tested. The effects of gemtuzumab/ozogamicin were dose-dependent, occurred at low concentrations, and were accompanied by apoptosis in suspension culture. Moreover, the drug was found to inhibit growth of leukemic cells in a colony assay and long-term culture-initiating cell assay. Finally, gemtuzumab/ozogamicin was found to synergize with nilotinib and bosutinib in inducing growth inhibition in leukemic cells.

Conclusions

CD33 is expressed abundantly on immature CD34⁺/CD38⁻ stem cells and may serve as a stem cell target in chronic myeloid leukemia.