Evolving concepts in the pathogenesis of chronic obstructive pulmonary disease.

It is arguable that more biologic insight has been gained from the study of COPD than from any other pulmonary disorder. A vast knowledge of the biology of extracellular matrix proteins, proteinases, and proteinase inhibitors has largely stemmed from the elastase:anti-elastase hypothesis for the pathogenesis of emphysema. An equally compelling case could be made that interest in, and funding for, COPD research has been woeful, and investigators have made no significant medical breakthroughs in the treatment of this disorder, which, unfortunately, is becoming epidemic worldwide. Indeed, it cannot be argued that physicians have very little treatment to offer to the many patients with COPD. Humankind is rapidly approaching a time when all human genes will be sequenced, and genetic engineering will allow determination of the function of these proteins in vivo. Expression profiling and bioinformatics will allow clinicians to assess the spectrum of genes and proteins regulated in biologic processes, no longer limiting study to naïve candidate genes. These advances will allow investigators to decipher precise pathways of complex diseases, identify genetic and environmental interactions, and ultimately lead to specific (pre)diagnoses and rational treatment. Answers to the question as to why only a subset of smokers develop COPD will enhance the understanding of the disease process. Fortunately, there has been a resurgence of interest in COPD, led largely by the pharmaceutical industry, which has discovered the potential of this unmet need. Consequently, these state-of-the-art scientific techniques are being directly applied to COPD, lending hope for the future. Of even greater importance, the tide seems to be turning on the cigarette industry. Although difficult to imagine, perhaps cigarettes will disappear in this lifetime or at least the next generation won't be fooled by this deadly habit! Well ... the rational therapy thing could work.