We depicted the potential involvement of the miR-22-HDAC4-DLCO axis on the pathogenesis of COPD associated with tobacco smoke, contrasting with that due to biomass smoke inhalation, which may lead mechanistically to two phenotypes of COPD well-known to clinics from developing countries, COPD-BS and COPD-TS. The gene discussed is HDAC4; the disease is chronic obstructive pulmonary disease.