tural adaptations that occur in the diaphragm muscle of patients with chronic obstructive pulmonary disease (COPD), namely an increase in type I fibers and a decrease in type II fibers, have been explored in terms of the active contractile properties of the diaphragm. The aim of this study was to test the passive properties of the diaphragm by measuring the force response of relaxed diaphragm muscle fibers to stretching to determine the effect of COPD on these properties. Costal diaphragm biopsies were taken from patients with COPD and from controls with normal pulmonary function. From these biopsies, titin expression was assessed in diaphragm homogenates by gel electrophoresis, and the restoring force was measured by incremental stretching of single fibers in the relaxed state and measuring the force response to stretching. A quadratic model was used to illustrate the relationship between restoring force and muscle fiber length, and it revealed that COPD fibers generate significantly lower restoring forces than control fibers as judged by the area under the force-length curve. Furthermore, this finding applies to both type I and type II fibers. Gel electrophoresis revealed different titin isoforms in COPD and controls, consistent with the conclusion that COPD results not only in a change in muscle fiber-type distribution but in a structural change in the titin molecule in all muscle fiber types within the diaphragm. This may assist the muscle with the energetic changes in the length of the diaphragm required during breathing in COPD.titin; passive tension; chronic obstructive pulmonary disease CHRONIC OBSTRUCTIVE PULMONARY disease (COPD) is one of the leading causes of death and disability in the developed world (17,20) and is characterized by progressive airflow limitation, which is largely irreversible (20). Because of the increased resistance to airflow, pulmonary hyperinflation can develop (18), the consequence of which is a flattening of the diaphragm resulting in a loss of its natural, curved, anatomic shape. This decreases the zone of apposition of the diaphragm to the chest wall (2, 13), which is essential for development of transdiaphragmatic pressure, and so the capacity of the diaphragm to generate negative intrathoracic pressures decreases in pulmonary hyperinflation (13,27).It is has been documented that in COPD the diaphragm undergoes an adaptation to compensate for the mechanical stresses that pulmonary hyperinflation places on it. These changes involve an alteration in the myosin heavy chain (MHC) isoform expression (14), with an increase in the proportion of type I fibers, and there is evidence of structural change also occurring within the diaphragm fibers at a subcellular level. Studies have shown that in chronic hyperinflation the resting sarcomere length in human diaphragm muscle fibers decreases (23). In emphysematous rodent models, it has been proposed that the total number of sarcomeres available in the shortened muscle fiber may be fewer than in normal controls, due to a loss in their n...