Short-term effects of Mediterranean diet on nutritional status in adults affected by Osteogenesis Imperfecta: a pilot study.

BACKGROUND: Osteogenesis Imperfecta (OI) is a heterogeneous group of connective tissue disorders, characterized by varying degrees of skeletal fragility. Patients experience a range of comorbidities, such as obesity, cardiovascular, and gastrointestinal complications, especially in adulthood. All aspects that could benefit from dietary intervention. The aim of this study was to evaluate the effects of a 6-months restricted Mediterranean Diet (rMD) on nutritional status in adult patients affected by OI. We carried out a 6-months longitudinal pilot study. 14 adults (median age: 35 years; 7 women; 7 OI type III) where recruited in 2019 among the members of As.It.O.I., the Italian Association of Osteogenesis Imperfecta. As.It.O.I. All the evaluations were performed at the University of Milan, Italy. The rMD provided a reduction of 30% from daily total energy expenditure. 45% of calories derived from carbohydrates, 35% from fat and 0.7-1.0 g/kg of body weight from proteins. Comparisons of continuous variables after 6 months of intervention were performed by the paired t-test. All P-values were two-tailed, and p < 0.05 was considered significant. RESULTS: Patients showed significant improvement in anthropometric measurements (BMI = 30.5 vs 28.1 kg/cm2, p < 0.001; Body Fat % = 32.9 vs 29.9, p = 0.006; Waist circumferences = 83.6 vs 79.6 cm; p < 0.001; Arm Fat Area = 29.8 vs 23.07 cm2; p < 0.011) and energy expenditure (REE/kg = 27.2 vs 29.2 kcal/kg, p < 0.001). Glucose and lipid profiles improved (Δglycemia = - 8.6 ± 7.3 mg/dL, p = 0.003; ΔTC = - 14.6 ± 20.1 mg/dL, p = 0.036; ΔLDL = - 12.0 ± 12.1 mg/dL, p = 0.009). Adherence to the MD significantly increased, moving from a moderate to a strong adherence and reporting an increased consumption of white meat, legumes, fish, nuts, fruits and vegetables. CONCLUSION: A rMD was effective in improving nutritional status and dietary quality in adults with OI. These results underscores the need to raise awareness of nutrition as part of the multidisciplinary treatment of this disease.

Pulmonary and chest wall function in obese adults.

Obesity is frequently associated with breathing disorders. To investigate if and how the highest levels of obesity impact respiratory function, 17 subjects with obesity (median age: 49 years; BMI: 39.7 kg/m2, 8 females) and 10 normal-weighted subjects (49 years; 23.9 kg/m2, 5 females) were studied. The abdominal volume occupied 41% in the obese group, being higher (p < 0.001) than the normal-weighted group (31%), indicating accumulation of abdominal fat. Restrictive lung defect was present in 17% of subjects with obesity. At rest in the supine position, subjects with obesity breathed with higher minute ventilation (11.9 L/min) and lower ribcage contribution (5.7%) than normal weighted subjects (7.5 L/min, p = 0.001 and 31.1%, p = 0.003, respectively), thus indicating thoracic restriction. Otherwise healthy obesity might not be characterized by a systematic restrictive lung pattern. Despite this, another sign of restriction could be poor thoracic expansion at rest in the supine position, resulting in increased ventilation. Class 3 obesity made respiratory rate further increased. Opto-electronic plethysmography and its thoraco-abdominal analysis of awake breathing add viable and interesting information in subjects with obesity that were complementary to pulmonary function tests. In addition, OEP is able to localize the restrictive effect of obesity.

Physiology of respiratory disturbances in muscular dystrophies.

Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. KEY POINTS: A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination.In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia.Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness.Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase.The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. EDUCATIONAL AIMS: To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy.To understand the impact of respiratory disturbances in patients with muscular dystrophy.To provide a brief description of the main forms of muscular dystrophy with their respiratory implications.

Correlated variability in the breathing pattern and end-expiratory lung volumes in conscious humans.

In order to characterize the variability and correlation properties of spontaneous breathing in humans, the breathing pattern of 16 seated healthy subjects was studied during 40 min of quiet breathing using opto-electronic plethysmography, a contactless technology that measures total and compartmental chest wall volumes without interfering with the subjects breathing. From these signals, tidal volume (VT), respiratory time (TTOT) and the other breathing pattern parameters were computed breath-by-breath together with the end-expiratory total and compartmental (pulmonary rib cage and abdomen) chest wall volume changes. The correlation properties of these variables were quantified by detrended fluctuation analysis, computing the scaling exponenta. VT, TTOT and the other breathing pattern variables showed α values between 0.60 (for minute ventilation) to 0.71 (for respiratory rate), all significantly lower than the ones obtained for end-expiratory volumes, that ranged between 1.05 (for rib cage) and 1.13 (for abdomen) with no significant differences between compartments. The much stronger long-range correlations of the end expiratory volumes were interpreted by a neuromechanical network model consisting of five neuron groups in the brain respiratory center coupled with the mechanical properties of the respiratory system modeled as a simple Kelvin body. The model-based α for VT is 0.57, similar to the experimental data. While the α for TTOT was slightly lower than the experimental values, the model correctly predicted α for end-expiratory lung volumes (1.045). In conclusion, we propose that the correlations in the timing and amplitude of the physiological variables originate from the brain with the exception of end-expiratory lung volume, which shows the strongest correlations largely due to the contribution of the viscoelastic properties of the tissues. This cycle-by-cycle variability may have a significant impact on the functioning of adherent cells in the respiratory system.

Postural effects on lung and chest wall volumes in late onset type II glycogenosis patients.

Respiratory failure associated with diaphragmatic weakness is the first cause of death in late-onset type II glycogenosis (LO-GSDII). We aim to identify predictive factors of diaphragmatic weakness and investigate the pathophysiology of respiratory muscles impairment. Pulmonary function and chest wall volumes were measured in ten patients and eight controls (supine and seated). According to the change in forced vital capacity in supine (ΔFVC) we considered patients with (DW, ΔFVC>25%) and without (noDW, ΔFVC<25%) diaphragmatic weakness. Postural change made the supine abdominal contribution to tidal volume (%VAB) of DW to fall and the ribcage to increase and good correlation was found between %VAB and ΔFVC (R=0.776). Patients showed reduced chest wall and abdominal inspiratory capacity (ICCW and ICAB) (p<0.001) and low abdominal expiratory reserve volume (p<0.01). Passing to supine DW did not increase ICCW and ICAB. ΔFVC occurs in LO-GSDII due to weakened diaphragm and abdominal muscles while intercostals are preserved. %VAB represents a new reliable index to detect diaphragmatic weakness.

Concomitant ventilatory and circulatory functions of the diaphragm and abdominal muscles.

Expulsive maneuvers (EMs) caused by simultaneous contraction of diaphragm and abdominal muscles shift substantial quantities of blood from the splanchnic circulation to the extremities. This suggests that the diaphragm assisted by abdominal muscles might accomplish ventilation and circulation simultaneously by repeated EMs. We tested this hypothesis in normal subjects by measuring changes (Δ) in body volume (Vb) by whole body plethysmography simultaneously with changes in trunk volume (Vtr) by optoelectronic plethysmography, which measures the same parameters as whole body plethysmography plus the volume of blood shifts (Vbs) between trunk and extremities: Vbs = ΔVtr-ΔVb. We also measured abdominal pressure, pleural pressure, the arterial pressure wave, and cardiac output (Qc). EMs with abdominal pressure ~100 cmH(2)O for 1 s, followed by 2-s relaxations, repeated over 90 s, produced a "stroke volume" from the splanchnic bed of 0.35 ± 0.07 (SD) liter, an output of 6.84 ± 0.75 l/min compared with a resting Qc of 5.59 ± 1.14 l/min. Refilling during relaxation was complete, and the splanchnic bed did not progressively empty. Diastolic pressure increased by 25 mmHg during each EM. Between EMs, Qc increased to 7.09 ± 1.14 l/min due to increased stroke volume and heart rate. The circulatory function of the diaphragm assisted by simultaneous contractions of abdominal muscles with appropriate pressure and duration at 20 min(-1) can produce a circulatory output as great as resting Qc, as well as ventilation. These combined functions of the diaphragm have potential for cardiopulmonary resuscitation. The abdominal circulatory pump can act as an auxiliary heart.

The abdominal circulatory pump.

Blood in the splanchnic vasculature can be transferred to the extremities. We quantified such blood shifts in normal subjects by measuring trunk volume by optoelectronic plethysmography, simultaneously with changes in body volume by whole body plethysmography during contractions of the diaphragm and abdominal muscles. Trunk volume changes with blood shifts, but body volume does not so that the blood volume shifted between trunk and extremities (Vbs) is the difference between changes in trunk and body volume. This is so because both trunk and body volume change identically with breathing and gas expansion or compression. During tidal breathing Vbs was 50-75 ml with an ejection fraction of 4-6% and an output of 750-1500 ml/min. Step increases in abdominal pressure resulted in rapid emptying presumably from the liver with a time constant of 0.61+/-0.1SE sec. followed by slower flow from non-hepatic viscera. The filling time constant was 0.57+/-0.09SE sec. Splanchnic emptying shifted up to 650 ml blood. With emptying, the increased hepatic vein flow increases the blood pressure at its entry into the inferior vena cava (IVC) and abolishes the pressure gradient producing flow between the femoral vein and the IVC inducing blood pooling in the legs. The findings are important for exercise because the larger the Vbs the greater the perfusion of locomotor muscles. During asystolic cardiac arrest we calculate that appropriate timing of abdominal compression could produce an output of 6 L/min. so that the abdominal circulatory pump might act as an auxiliary heart.