Does drug-induced emphysema exist?
Authors: Norbert F. Voelkel, Shiro Mizuno, Masanori Yasuo
Journal: European Respiratory Journal (2013)

Mechanisms whereby drugs directly, or in synergism with epigenetic control mechanisms, can destroy lung tissue http://ow.ly/p3n7MPulmonary physicians are well aware of drug-induced acute and chronic pulmonary toxicities; inhaled or systemically administered drugs can affect airway tone and cause cough, dyspnoea due to airspace disease, diffuse alveolar damage, pulmonary capillaritis or interstitial lung fibrosis, to name a few presentations and tissue manifestations.Well-studied drugs that cause pulmonary toxicity include methotrexate [1], bleomycin [2] and amiodarone [3], all of which can cause interstitial lung disease, platinum compounds which can generate pulmonary hypersensitivity reactions [4], or propylthiouracil which can cause antineutrophil cytoplasmic antibody positive vasculitis and nonspecific interstitial pneumonitis [5,6].Over the years a catalogue of drug-induced pulmonary toxicities has been assembled [7] and, more recently, druginduced respiratory disease in patients with haematological disorders [8] and toxicity related to the systemic treatment of nonsmall cell lung cancer [9] have been reviewed.In contrast, repeated PubMed research of the literature did not uncover a single clinical report of druginduced emphysema.This circumstance begs the question whether drugs do not cause toxicities that result in alveolar-capillary cell changes and emphysematous lung parenchyma destruction in humans, or whether drug-induced emphysema is simply not reported.Herein, we attempt to approach this topic with the appropriate caution, beginning with the statement that on theoretical ground, and based on data derived from animal studies, there ought to be drugs that cause emphysema in susceptible patients.It has been acknowledged that not all of the patients that develop emphysema are smokers; the estimate is that ,15% of emphysema patients are nonsmokers [10].Yet pathogenetic mechanisms that can explain emphysema in these patients are lacking after rare associations, like anorexia [11], cadmium exposure [12] or playing a wind instrument, have been ruled out.In the following editorial, we provide a rationale for our postulate of drug-induced emphysema, without speculating that in some cases emphysema in nonsmokers may be drug or diet related.The traditional concepts applied to explain the pathobiology of emphysematous lung tissue destruction focus on mediators, proteases and reactive oxygen species released from inflammatory cells, all targeting the building blocks of the alveolar structures; mostly epithelial and endothelial cells.In addition, some investigators consider that the alveolar structure cells themselves, for example endothelial cells, become activated and injured without requirement of injurious interactions with inflammatory cells.Regardless, injurious attacks on the alveolar gas exchange units can also be seen in the context of an impaired lung structure maintenance programme [13,14].The adult lung structure maintenance concept integrates genetic and epigenetic control mechanisms, operates with the principle of homeostatic balances, and provides a framework for our understanding of how inflammatory mechanisms are involved in emphysemagenesis.The lung structure maintenance concept also provides room for per se