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The search for COPD bio‑ markers
compared with 2DE, “LC/MS/MS gives an advantage in identifying extreme Breathing is a basic process that is all pI and molecular-weight values.” The too easy to take for granted. However, proteins identified in this work plus the for patients with chronic obstructive proteins reported in other proteomics pulmonary disease (COPD), just taking analyses form the basis of a pulmoa breath can be very difficult. nary-proteome “platform”, says IadaCOPD is a syndrome that includes rola. “Once this platform is definitely many lung diseases, such as chronic established, the identification of probronchitis (CB) and emphyteins over- or underexpressed sema. The most common cause as a function of inflammatory of COPD is cigarette smoking, processes should be easier,” he 10,000 NS 1000 but environmental or genetic says. 100 10 factors may be to blame in some Many differences were ob1 cases. “Still, we don’t have the served among the groups. For 4 5 6 7 8 9 10 11 12 pI entire picture of this disease,” example, more proteins were 10,000 says Begoña Casado, who is detected in the CB, COPD, and COPD 1000 100 now at the Nestlé Research COPD&E subjects than in either 10 Center (Switzerland). While control group. Iadarola says that 1 4 5 6 7 8 9 10 11 12 she was studying to earn her this finding suggests that cerpI 10,000 Ph.D. at Georgetown University, tain proteins are up-regulated in COPD&E 1000 Casado and her adviser, James response to cigarette smoke or 100 10 Baraniuk, collaborated with lung destruction. Alternatively, 1 4 5 6 7 8 9 10 11 12 Paolo Iadarola and colleagues some proteins may be released pI at the Universitá di Pavia, the by dying cells. He points out Universitá di Ferrara (both in that the detection of histone In the lungs. Theoretical 2D maps of the identified proteins for Italy), and the University of H4 and other histones (i.e., the (top) NS, (middle) COPD, and (bottom) COPD&E groups. South Alabama on a pilot project H2B and H1) at higher levels to discover biomarkers for these in COPD&E subjects than in processes. As they report in this issue of patients with different lung disorders. the others “suggests that chromatin JPR (pp 4615–4623), they found several The 56 subjects who participated in the is released during emphysema, and a interesting differences in the sputum study were divided into five groups. NS potential source of this material may be proteomes of patients with various and HS were in the two control groups. apoptosis or necrosis of alveolar cells,” stages of COPD compared with healthy Smokers who had a persistent cough he explains. Casado says that a few very smokers (HS) and healthy nonsmokers and produced phlegm, but did not have basic proteins that were identified in (NS). an obstructed airway, composed the the COPD&E group were missing from Although some researchers already CB group. Although CB technically is a the COPD samples. “That means that have conducted proteomics studies form of COPD, the investigators treated maybe these proteins are really the with COPD samples, they typically these patients as a separate group, key to distinguish between COPD and analyzed bronchoalveolar lavage fluid because CB is considered an early step COPD with emphysema,” she says. (BALF) with 2DE methods. To obtain in the development of the syndrome, Interesting proteins were detected, BALF, researchers insert a tube down Iadarola explains. The COPD group but no conclusive biomarkers have a subject’s throat and rinse the lungs included smokers who had a restricted been pinpointed yet. According to the with fluid. Iadarola points out that this airflow but no symptoms of emphyresearchers, this pilot study is only the process is invasive and that it could sema. Finally, smokers who had COPD beginning, and samples from many adalter the contents of the epithelial and with emphysema had the most severe ditional subjects must be examined in inflammatory cells. So, in the current symptoms and were placed in the future experiments. In the immediate study, the scientists analyzed sputum COPD&E category. future, however, the investigators plan by LC/MS/MS. To produce sputum, With LC/MS/MS, the researchers to perform a more extensive statistical subjects first inhale salbutamol, which identified 203 proteins in the sputum analysis of the data obtained in this dilates the airways. Then, increasing samples. Some overlap was observed study. Toward that end, they have colconcentrations of nebulized hyperbetween the proteins identified in lected exhaled breath condensate from tonic saline are administered until this study and those detected in BALF the subjects for evaluation. the subjects cough up enough sputum 2DE experiments. Casado notes that, —Katie Cottingham log MW (kDa)
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for analysis. Sputum is a tricky type of sample to analyze, however. “They are very sticky samples, and they are very rich in lipids,” says Casado. “You need to clean them a lot.” Whereas previous reports lumped patients with different types of COPD in one category, Casado, Iadarola, and colleagues made a distinction among
4544 Journal of Proteome Research • Vol. 6, No. 12, 2007
© 2007 American Chemical Society
