HDAC4 and chronic obstructive pulmonary disease: By examining the DNA methylation levels of CpG islands in the S1P pathway genes, it was found that the methylation levels at these sites in macrophages from COPD patients were significantly lower compared to the control group, with COPD at 8.60 ± 2.53% and the control group at 27.85 ± 5.48% (78).Assessment of circulating monocytes from healthy non-smokers, smokers, and COPD patients revealed that the expression of EP300, HDAC2, and HDAC3 in peripheral blood monocytes from COPD patients was significantly reduced, while HDAC4 expression was increased.