The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3–like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated. We quantified serum YKL-40 levels in three cohorts of patients with asthma — one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin — as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated. Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels. YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.

Smoke Gets in Your Lungs: Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, primarily caused by cigarette smoking. The chronic inflammation that leads to tissue damage and organ dysfunction in COPD is mediated in large part by neutrophils, a type of granulocytic immune cell. Snelgrove et al. (p. 90 , published online 2 September; see the Perspective by Barnes ) now provide an explanation for why neutrophils stick around in the lung during COPD. The neutrophil chemoattractant Pro-Gly-Pro (PGP) is a biomarker for COPD and promotes neutrophil accumulation. The enzyme leukotriene A ₄ hydrolase degrades PGP in mice, and its activity was reduced by cigarette smoke both in vivo and in vitro. In contrast, during acute influenza infection in mice, leukotriene A ₄ hydrolase functioned normally, allowing for PGP degradation and the resolution of inflammation. Thus, in COPD, cigarette smoking may lead to the accumulation PGP—which, in turn, could keep neutrophils in the lung to drive inflammation and subsequent lung damage and dysfunction.

Purpose: To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon‐129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects.Materials and Methods: A three‐dimensional, multi‐echo, radial‐trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue‐to‐gas, RBC‐to‐gas, and RBC‐to‐tissue) were calculated from the images for quantitative comparison.Results: Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior‐to‐posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole‐lung values of total dissolved Xe129 to gas, tissue‐to‐gas, and RBC‐to‐gas ratios in healthy subjects were significantly larger than those in diseased subjects.Conclusion: Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics. J. Magn. Reson. Imaging 2014;39:346–359. © 2013 Wiley Periodicals, Inc.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs that usually manifests late in life. Physiologic and immunologic changes that occur in COPD often mimic changes seen in the aging lung. This has led some to characterize COPD as an “accelerated aging phenotype.” At the molecular level, COPD and aging share common mechanisms and are associated with significant dysregulation of the immune systems. Aging and COPD are characterized by increases in proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, which are implicated in aging-related inflammatory diseases and correlate with degree of obstruction in COPD. There is an age-dependent decline in naïve T cells with oligoclonal expansion of CD8+ CD28null T cells from chronic antigenic stimulation. The increase in CD8+ CD28 null T regulatory cells inhibits antigen-specific CD4+ T cell responses, leading to a decline in adaptive immune response. To compensate for the decline in the adaptive immune function there is a paradoxical up-regulation of innate immune system resulting in a proinflammatory state. The dysregulated adaptive immune system with activated innate immune responses seen with aging results in recruitment and retention of neutrophils, macrophages, and CD4+ and CD8+ T cells in the lungs of smokers with COPD. Once the inflammation is triggered, there is a self-perpetuating cascade of inflammation and lung parenchymal damage. This review will focus on how the aging immune system may contribute to COPD development later in life in susceptible individuals.