Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity

Abstract

Purpose

Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema.

Patients and methods

We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests.

Results

In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity.

Conclusion

A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

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Keywords:

• lung
• pathology
• COPD
• pulmonary function
• pathogenesis

Acknowledgments

The authors thank Drs Harumi Ito at Fukui University, Lucian R Chirieac at Brigham and Women’s Hospital, Eugene J Mark at Massachusetts General Hospital, and Cesar A Moran at MD Anderson Cancer Center for critical discussions and advice. The schema of the lung that we edited and used in Figure 2 was designed by Dr Ryoko Egashira at Saga University. This study was partially supported by the Diffuse Lung Disease Research Group from the Ministry of Health, Labor, and Welfare, Japan.

Author contributions

JF is the guarantor of the content of the manuscript, including data collection and analysis. AY, SS, TT, and JF contributed to study design, data acquisition, data analysis, data interpretation, and drafting the manuscript. MH, YK, and HY contributed to interpretation of data and revision of the manuscript. TT, NY, and TN contributed to tissue acquisition and revision of the manuscript. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.