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While lung diseases have traditionally been defined by objective clinical characteristics, these characteristics usually do not predict outcome, response to therapy and morbidity and mortality. To realize the promise of personalized medicine, the current diagnostic approaches to chronic lung diseases should be modified to include both information on the genetics, epigenetics and microbiome of the individual and the diseased organ as well dynamic molecular information that can more precisely define the etiology, stage, and the biological activity of the disease process.