Editorial [Hot Topic: (Guest Editor: Allan R. Brasier)]

Inflammation is a common pathological process underlying the most prevalent airway diseases worldwide. This process is characterized by abnormal leukocyte infiltration producing release of factors that induce vascular leakage, edema, smooth muscle cell contraction, mucous production, and generation of reactive oxygen species. Depending on the chemotactic factors produced by resident cells and the subtypes of T helper lymphocyte populations present, the infiltrating leukocytic cell types are quite distinct. Presently we understand that the initiation, maintenance and termination of airway inflammation involves intracellular innate signaling, expression of secreted bioactive proteins and effects of oxidation that affect resident cells within the pulmonary tissue. Here, proteomics technologies offer the potential for major new insights into these clinical syndromes. We have selected airway inflammation as the focus for this hot topic review because of the potential impact that proteomics approaches can have on the multiple facets of this complex clinical problem. The three major types of inflammatory airway disease discussed here are epidemic childhood wheezing (bronchiolitis), reactive airways disease (atopic asthma), and chronic obstructive pulmonary disease (COPD). Bronchiolitis is a lower respiratory tract infection of children, caused by the ubiquitous paramyxovirus, Respiratory Syncytial Virus. This virus causes acute mononuclear inflammation and may be an etiological factor in recurrent wheezing in childhood. Atopic asthma is a highly prevalent disease affecting up to 10% of the population in Western countries and accounts for >$3B annually in health care costs; this disease is characterized by eosinophilic inflammation and episodes of reversible obstruction provoked by non-specific allergen or viral infections. A specific form of asthma characterized by distinct neutrophilic inflammatory state is associated with a relative resistance to anti-inflammatory treatment. This syndrome is termed “severe” or “glucocorticoid resistant” asthma, and accounts for a disproportionately large share of asthma-related hospitalizations and significant reductions in quality of life. Finally, chronic obstructive pulmonary disease (COPD) is characterized by neutrophilic airways inflammation and/or alveolar destruction. In this hot topic issue, we will illustrate current approaches (and future directions) of relevant discovery proteomics, detection of post-translational modifications, methods for analysis of large scale proteomic datasets, and approaches for focused biomarker assay development that are relevant to airway disease. The first review (Brasier) will review salient clinical features, mechanisms of innate signaling and highlight distinct types of inflammatory processes seen in these three types of airway disease. Critical to the proteomics-based exploration of these disease states is an understanding of the utility and limitations in the currently available sampling strategies for airway cells and proximal fluids. The second review (Wiktorowicz) will review important recent developments in discovery approaches and significant advances in protein quantification, including novel methods for detection of protein cysteinyl oxidation, increasingly recognized as the result of inflammatory, oxidative damage. The third review (Pazdrak) will discuss the insights gleaned into proteomics in the major leukocyte populations known to be important in the initiation and maintenance of asthma. The fourth review (Sadygov) will update the rapidly changing bioinformatics tools available for global (“bottoms-up”) mass spectrometry experiments including stable isotopic labeling and label-free proteomics. Finally, the fifth review (Zhao) will discuss methods for biomarker assay development using selective reaction monitoring. Properly applied, these proteomics approaches will extend our understanding of the mechanisms, as well as impact therapy by identification of physiological distinct subsets of airway inflammatory disease.