Abstract
It is well established that inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD), asthma and interstitial lung diseases (ILD). A wide variety of triggers may induce the recruitment and activation of inflammatory cells in the airways and stimulate both innate and adaptive immune mechanisms. Airway inflammation is implicated in many of the clinical characteristics of both entities. Basal levels of inflammatory mediators are often elevated during exacerbations, as a manifestation of the underlying process. Idiopathic pulmonary fibrosis (IPF) is a life-threatening variant of ILD. In IPF chronic injury and excessive apoptosis of alveolar epithelial type II (AECII) cells occurs, leading to permanently perturbed epithelial homeostasis. Treatment modalities aiming to attenuate epithelial injury are currently in early pre-clinical development and may reach the clinical arena in only a few years.
This review will focus on four drugs: pirefendinone, penicillamine, chloroquine, and chlorambucil. These agents have demonstrated immunomodulatory effects through different pathways. We will describe their mechanisms of action, side effects, and their potential use in various pulmonary diseases based on available clinical data. Unfortunately their current use is restricted due to limited efficacy, paucity of randomized clinical trials, and side effects resulting in a relatively narrow therapeutic index. Future trials will determine their exact role in the management of the various pulmonary diseases under discussion.
Keywords: Chlorambucil, chloroquine, interstitial lung diseases, penicillamine, pirfenidone.
Graphical Abstract
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