However, others have demonstrated down-regulation of leptin/leptin receptor system in bronchial epithelial cells of proximal airways of mild-to-severe COPD patients, when compared to tissues obtained from non-smoking subjects [48], while immunohistochemical studies show that leptin expression is increased in bronchial epithelial cells and alveolar macrophages in the peripheral lung of COPD patients (GOLD stage 4) [8]. This evidence concerns the gene LEPR and chronic obstructive pulmonary disease.