© 2004 American Thoracic Society
Forces in EmphysemaNewtonian v Quantum MechanicsTo the Editor:We read with great interest the recent review of the pathobiology of emphysema by Suki and colleagues (1). In it the authors addressed classic hypotheses regarding the etiologic factors of emphysema—for example, protease–antiprotease, inflammation, mechanical forces, and collagen deposition. We were particularly interested in the authors' position on the role of mechanical forces as merely having blunt physical effects on the lung parenchyma, which overlooks a growing body of evidence that shows how physical forces can have specific molecular physiologic or pathophysiologic effects on the developing and adult lung (2). Workers in our laboratory (3) and others (2) are studying the influence of mechanical forces on normal lung morphogenesis and its possible role in lung pathology. Suki and colleagues (1) have taken the more conservative position that physical forces merely dissect the tissue as if it were a hank of rope under tension (their analogy). We prefer to think of physical forces "molding" the lung during normal morphogenesis, and perhaps explaining how varying tension can explain both ventilation–perfusion matching and the cause of emphysema. The bases for such speculation are myriad: lung morphogenesis is highly plastic, literally being "molded" by amniotic fluid distension in utero (4); postnatally, lung structure/function are influenced by physical forces that allow the alveolar wall of the lung to remodel under the influences of distension and contraction, through a common paracrine mechanism; and perhaps even wedge resection for the treatment of emphysema represents a means by which the remaining healthy, but restricted parenchyma, can be salvaged by allowing it to "stretch." Parathyroid hormone–related protein (PTHrP) is a stretch-regulated paracrine hormone that is necessary for normal lung development; knocking out this gene causes stage-specific failure of lung morphogenesis (5). Recent studies from our laboratory have demonstrated the importance of PTHrP signaling between epithelium and interstitium for alveolar homeostasis (6); in the absence of PTHrP signaling, both the interstitial and epithelial cells readapt in a manner mimicking fibrosis. We acknowledge that this is a minority position, but one that offers the possibility that chronic lung disease is part of the continuum of development, homeostasis, and repair (7), and that as such it may be a reversible (i.e., treatable) process.
Harbor-UCLA Medical Center Research and Education Institute Torrance, California FOOTNOTES Conflict of Interest Statement: J.S.T. and V.K.R. have no declared conflict of interest. Dr. Suki was given the opportunity to respond to this letter but declined to do so. REFERENCES
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