No abstract

Idiopathic infantile arterial calcification (IIAC; OMIM 208000) is characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. We analyzed affected individuals from 11 unrelated kindreds and found that IIAC was associated with mutations that inactivated ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This cell surface enzyme generates inorganic pyrophosphate (PP(i)), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, may be associated with long-term airflow limitation. Survivors of BPD may develop asthma-like symptoms in childhood, with a variable response to beta(2)-agonists. However, the pathologic pathways underlying these respiratory manifestations are still unknown. The aim of this study was to measure exhaled nitric oxide (FE(NO)) and lung function in a group of 31 school-age survivors of BPD. They showed variable degrees of airflow obstruction (mean FEV(1) 77.8 +/- 2.3% predicted) unresponsive to beta(2)-agonists in 72% of the subjects. Their FE(NO) values (geometric mean [95% confidence interval]: 7.7 [+/- 1.1] ppb) were significantly lower than in a group of healthy matched control subjects born at term (10.7 [+/- 1.1] ppb, p < 0.05) and a group of preterm children without BPD (9.9 [+/- 1.1] ppb, p < 0.05). The children with BPD were also compared with a group of 31 patients with asthma with a comparable airflow limitation (FEV(1) 80.2 +/- 2.1% predicted) and showed FE(NO) values four times lower than in those with asthma (24.9 [+/- 1.2] ppb, p < 0.001). In conclusion, unlike children with asthma, school-age survivors of BPD have airflow limitation associated with low FE(NO) values and lack of reversibility to beta(2)-agonists, probably as a result of mechanisms related to early life structural changes in the airways.

To evaluate the physiologic course of pulmonary function in infants with bronchopulmonary dysplasia (BPD) weighing less than 1,250 g at birth, 24 infants with BPD underwent serial pulmonary function evaluations from birth until 2 yr of age. All infants were intubated at birth and the mean duration of mechanical ventilation was 38 +/- 4 d. Passive respiratory system compliance (Crs) and resistance (Rrs) were measured between 10 and 20 d of life during mechanical ventilation. Thereafter pulmonary mechanics and functional residual capacity (FRC) were evaluated at 3, 6, 9, 12, and 24 mo of postnatal age. Forced expiratory flow (Vmax,FRC) was measured at 2 yr of age. A severe alteration on Crs (50% of predicted) was found during the acute phase of BPD, associated with abnormal values of Rrs. A progressive improvement (ANOVA, p < 0.0001) occurred in the first year of life and, at 24 mo of age, Crs and Rrs reached the range of normalcy. FRC value was 86 +/- 7.5% of predicted at 3 mo and gradually increased to a mean value of 115 +/- 5% of predicted at 2 yr of age. In spite of the good resistance time course over the 2-yr evaluation, less favorable data of Vmax,FRC were found with individual values reduced more than 40% of predicted values in 70% of the children. In conclusion, although pulmonary mechanics of BPD survivors improves during the first years of life, reaching the range of normal values, at 2 yr of age they still present a substantial airway function impairment as revealed by the low forced expiratory flows.

Exercise tolerance and possible limitation in work capacity of asthmatic children is still a matter of debate. The aim of this study was to compare ventilation and gas exchange response to exercise of asthmatic children with that of healthy controls.Exercise performance was evaluated in 80 children with mild-to-moderate asthma, aged 7-15 yrs, and in 80 healthy controls matched for age, height, weight and habitual level of physical activity. The children performed a maximal exercise test on a treadmill, during which oxygen uptake (V 'O 2 ), carbon dioxide output (V 'CO 2 ) and minute ventilation (V 'E) were measured continuously. No premedication was given to the asthmatic children.Forced expiratory volume in one second (FEV1) at rest was 93±11% of predicted in asthmatic children and 95±9% pred in controls. After the run, the mean fall in FEV1 was 13.9% (range 0-57%) and 1.6% (0-9%), respectively (p<0.001). The two groups achieved similar maximum oxygen uptake (V 'O 2 ,max) ((mean±SD) 40.3± 8.4 and 42.6±9.6 mL·min -1 ·kg -1 in asthmatics and controls, respectively; NS) and maximum minute ventilation output (V 'E,max) (42.9±14.8 and 45.7±14.9 L·min -1 respectively; NS). The kinetics of V 'O 2 , V 'CO 2 and V 'E during the test revealed no differences between the two populations. Moreover, anaerobic threshold and oxygen pulse were the same in the two groups. Asthmatics showed a ventilatory pattern with lower respiratory frequencies and greater tidal volumes during the run.These results suggest that asthmatic children can achieve a level of exercise performance similar to that of healthy children, provided that they have a comparable level of habitual physical activity. The only difference found concerned the ventilatory pattern of the asthmatic children, which was characterized by a reduced respiratory frequency and greater tidal volume at the same minute ventilation. The level of physical conditioning was found to be the main determinant of exercise tolerance for children with controlled asthma.