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Diaphragm injury in chronic respiratory disease MacGowan, Nori A.

Abstract

Diaphragm injury may occur in chronic respiratory disease due to factors which increase the workload, cause weakness, or reduce the efficiency of the ventilatory pump. Diaphragm injury has been shown in many animal models of respiratory overload, but similar research in humans is limited. The purpose of this thesis was to investigate diaphragm injury in individuals who may experience diaphragm overload due to chronic respiratory disease. Diaphragm biopsies were obtained from twenty-one individuals going for thoracotomy surgery, and from thirty-three individuals post-mortem. In the thoracotomy study, biopsies were quick frozen (n=18) or formalin-fixed (n=3). Thick sections (10 μm) were stained with H & E. Macrophages were identified in thin sections (6 μm) using immunohistochemistry and monoclonal antibodies (Ber- MAC3, DAKO Canada Corp.). In the post-mortem study, biopsies were fixed in 10% formalin, then stained with H & E and Masson's trichrome. Area fractions of normal muscle, abnormal muscle and connective tissue were determined by point counting diaphragm cross-sections from both thoracotomy and post-mortem subjects. Image analysis was used to determine the number of macrophages in diaphragm cross-sections from thoracotomy subjects. Subjects in the thoracotomy study had airflow obstruction ranging from mild to severe, and had relatively homogeneous clinical characteristics. This study showed an inverse relationship between the proportion of abnormal muscle and the % predicted FEV₁ (r = -0.53, p < 0.01), and a direct relationship between the proportion of normal muscle and the % predicted FEV₁ (r = 0.37, p < 0.05). There was no relationship between the number of macrophages and the % predicted FEV₁. Subjects in the post-mortem study were heterogeneous in their clinical characteristics. This study showed a trend towards a direct relationship between the proportion of abnormal muscle and the presence of chronic respiratory disease (p=.065), and no relationship between the proportion of abnormal muscle and other clinical factors (gender, age, body mass index, presence of acute respiratory disease). We conclude from the first study that abnormal morphology is present in the diaphragm and is related to the severity of airflow obstruction in a fairly homogeneous sample of individuals going for thoracotomy surgery. We conclude from the second study that further study with a larger sample of individuals who have died of various causes may provide evidence of a relationship between abnormal diaphragm morphology and the presence of chronic respiratory disease.

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