Prevalence of scoliosis and impaired pulmonary function in patients with type III osteogenesis imperfecta.

PURPOSE: Osteogenesis Imperfecta (OI) is a rare group of congenital genetic disorders that consists of a collagen synthesis defect. The most severe phenotype is type III OI. Characterized by progressive bone deformity, fragility and pulmonary impairment, causing significant morbidity and mortality. Also, multilevel spine deformities are observed, such as scoliosis. The literature on the pathophysiology of pulmonary impairment in relation to scoliosis in these patients is scarce and conflicting. This study aims to determine the prevalence of scoliosis and its relation to pulmonary function in type III OI patients. METHODS: This retrospective cohort study took place between April 2020 and November 2021. Forty-two patients with type III OI were included. Anterior-posterior spine radiographs were evaluated for scoliosis. Pulmonary function was assessed using spirometry and partial pressure of carbon dioxide. RESULTS: All 42 patients had scoliosis, with a mean curve of 66° (95% CI of range). Vital lung capacity was decreased, compared to a non-OI population (mean 1.57 L). This was correlated to the degree of scoliosis (st. ß - 0.40, P = 0.03), especially in increasing thoracic curves. Restrictive lung pathophysiology was shown in our study population with a mean FEV1/FVC ratio of 0.85. CONCLUSIONS: Increasing thoracic scoliosis was correlated with decreased vital lung capacity in our study population of type III OI patients. High FEV1/FVC ratios found in this study population show restrictive lung pathophysiology. Therefore, it is plausible that the pulmonary impairment found in type III OI patients is a combined issue, partly associated to scoliosis and partly intrinsic to OI.

Effects of exercise training in patients with idiopathic pulmonary arterial hypertension.

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH). In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise training programme for the duration of 12 weeks. Maximal capacity, endurance capacity and quadriceps function were assessed at baseline and after 12 weeks. In 12 patients, serial quadriceps muscle biopsies were obtained. 6-min walk distance and peak exercise capacity did not change after training. However, endurance capacity improved significantly after training, demonstrated by a shift of the anaerobic threshold to a higher workload (from 32+/-5 to 46+/-6 W; p = 0.003) together with an increase in exercise endurance time (p<0.001). Moreover, exercise training increased quadriceps strength by 13% (p = 0.005) and quadriceps endurance by 34% (p = 0.001). Training enhanced aerobic capacity of the quadriceps, by increasing capillarisation (1.36+/-0.10 to 1.78+/-0.13 capillaries per muscle fibre; p<0.001) and oxidative enzyme activity, especially of the type-I (slow) muscle fibres. No changes were found in cross-sectional area and fibre type distribution. Exercise training in iPAH improves exercise endurance and quadriceps muscle function, which is also reflected by structural changes of the quadriceps.

A stable model of respiratory distress by small injections of oleic acid in pigs.

OBJECTIVE: Development of a stable model of respiratory distress in pigs with oleic acid, fulfilling clinical criteria of the adult respiratory distress syndrome (ARDS). DESIGN: Eight pigs (9.1 +/- 0.7 kg) were anesthetized with pentobarbital, paralyzed with tubocurarine and mechanically ventilated with an FIO2 of 0.6, an I:E ratio of 2:3 and a PEEP of 0.2 kPa. Oleic acid (dissolved 1:1 in 96% alcohol) was administered in a series of multiple injections of 0.1 ml until PaO2 was lower than 8 kPa. MEASUREMENTS AND RESULTS: Careful titration of the oleic acid injections on guidance of the PaO2 established a reproducible respiratory distress (PaO2 = 7.3 +/- 0.8 kPa), in which gas exchange and hemodynamic variables were stable for at least 4 h. The number of oleic acid injections (22 +/- 11, mean and SD) varied between the animals. CONCLUSIONS: With the use of multiple injections of oleic acid, a stable model of early respiratory distress in pigs can be achieved, in spite of individual differences in sensitivity. Such a stable model allows for a diversity of studies on early respiratory distress.

Pulmonary vasoconstriction in oleic acid induced lung injury. A morphometric study.

Distribution and severity of active vasoconstriction of muscular pulmonary arteries were morphometrically assessed in anaesthetized, paralysed and mechanically ventilated pigs with respiratory distress, induced by oleic acid. Vasoconstriction was deduced from the medial thickness which was measured and expressed as a percentage of external diameter. Six pigs received oleic acid (0.12 +/- 0.07 ml/kg), dissolved 1:1 in 96% alcohol, in multiple injections of 0.1 ml. Six pigs were used as controls. After the oleic acid injections a stable hypoxaemia (PaO2 = 57 +/- 8 mmHg, at an inspiratory oxygen fraction of 0.6) and pulmonary hypertension (mean Ppa = 36 +/- 2 mmHg) were obtained for several hours. Electron microscopy revealed swelling of endothelial cells with signs of degeneration. Medial thickness was far greater in the oleic acid group than in the control group; overall mean values were 8.1 +/- 3.2 and 3.8 +/- 1.7% respectively (P < 0.001). Arteries with prominent vasoconstriction were lying in clusters. This pattern was the same in dependent and non-dependent regions. We concluded that in oleic acid induced respiratory distress active vasoconstriction of muscular pulmonary arteries is an important factor in the development of pulmonary hypertension. Besides vasoconstriction, endothelial swelling and intravascular clotting may contribute to the development of pulmonary hypertension.

Pulmonary granulocyte influx and impaired alveolar macrophage adenylyl cyclase responsiveness in developing respiratory distress.

Alveolar macrophages have recently been postulated as being involved in the aetiology of adult respiratory distress syndrome (ARDS). To evaluate their role, basal cyclic AMP levels and responsiveness of adenylyl cyclase alveolar macrophages were determined at four intermediate stages of developing respiratory distress in piglets using a protocol with repeated lung lavage. Examination of alveolar cells recovered from the subsequent lavages reveals an influx of granulocytes (neutrophils and eosinophils) within 1 h of two intensive lung lavages. During the developing respiratory distress the basal cyclic AMPlevel of alveolar macrophages increases and adenylyl cyclase responsiveness to prostaglandin E(2) (PGE(2)) and isoprelanaline diminishes. The previously observed impairment of macrophage activity can then be explained at a subcellular level.