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.