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1 Introduction Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disorder with a global prevalence of 10.3% and an estimated 392 million patients worldwide ( Cigarette smoking is the major risk factor for COPD in the Western world ( The lung harbors different subsets of macrophages, including interstitial macrophages that are present in the lung interstitium between blood vessels and alveoli whereas alveolar macrophages (AM) are found in the alveolar space and airspace ( Single-cell genomics technologies, particularly single-cell RNA-sequencing (scRNA-seq), now allows a detailed characterization of such complex cell communities and their molecular mechanisms