Pulmonary Complications and Lung Function Abnormalities in Children with Sickle Cell Disease

The pulmonary complications of sickle cell disease (SCD) have a high morbidity and mortality. Fatal pulmonary complications occur in 20% of adults; those with sickle chronic lung disease (SCLD) and pulmonary hypertension have a significantly increased mortality. Treatment of SCLD is only supportive. Recurrent acute chest syndrome (ACS) episodes are the major risk factor for SCLD, and ACS is the leading cause of death. Adults with SCD tend to have restrictive lung function abnormalities, whereas, in children, obstructive abnormalities are more frequent. Lung function abnormalities are common even in young children and may reflect their chronic anaemia and increased pulmonary capillary blood volume, which increases airway obstruction and may be responsible for their increased wheezing. Whether more aggressive treatment of anaemia would improve lung function and long-term outcomes merits testing. Children with SCD experience a decline in lung function, which is most rapid in younger children in whom ACS episodes are most common highlighting the importance of identifying effective strategies to prevent and optimally treat ACS

Neonatal ventilatory techniques – which are best for infants born at term?

Few studies have examined ventilatory modes exclusively in infants born at term. Synchronous intermittent mandatory ventilation (SIMV) compared to intermittent mandatory ventilation (IMV) is associated with a shorter duration of ventilation. The limited data on pressure support, volume targeted ventilation and neurally adjusted ventilatory assist demonstrate only short term benefits in term born infants. Favourable results of high-frequency oscillatory ventilation (HFOV) in infants with severe respiratory failure were not confirmed in the two randomised trials. Nitric oxide (NO) in term born infants, except in those with congenital diaphragmatic hernia (CDH), reduces the combined outcome of death and requirement for extracorporeal membrane oxygenation (ECMO). In infants with severe refractory hypoxaemic respiratory failure, ECMO, except in infants with CDH, reduced mortality and the combined outcome of death and severe disability at long-term follow-up. Randomised studies with long term outcomes are required to determine the optimum modes of ventilation in term born infants

PPAR Gamma Receptor: A Novel Target to Improve Morbidity in Preterm Babies

Worldwide, three-quarters of a million babies are born extremely preterm (&lt;28 weeks gestation) with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopulmonary dysplasia (BPD), and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal period. In newborn animal models, pioglitazone has been shown to be protective against BPD, necrotising enterocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelopment. Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema, seen rarely in adults, may be avoided with a short treatment course. The other effects of pioglitazone, including improved glycaemic control and lipid metabolism, may provide added benefit in the context of prematurity. Currently, there is no formulation of pioglitazone suitable for administration to preterm babies. A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns.</p

Predictors of outcome of prematurely born infants with pulmonary interstitial emphysema

Aim: To determine how oxygenation, ventilation efficiency and tidal volume requirements changed with the development of pulmonary interstitial emphysema (PIE) and whether in affected patients a composite gas exchange index predicted death or bronchopulmonary dysplasia (BPD). Methods: Infants who developed PIE from 2010 to 2016 were identified. The oxygenation index (OI), ventilation efficiency index (VEI), ventilation to perfusion ratio and inspiratory tidal volume were calculated before radiological evidence of PIE (pre-PIE) and at the worst PIE radiographic appearance (PIE-worst). Results: Thirty infants, median (IQR) gestational age of 24.6 (24.3–26.7) weeks were assessed. Their age at pre-PIE was 11 (6–19) days and 23 (13–42) days at PIE-worst. Compared to pre-PIE, at PIE-worst, the OI was higher [14.5 (10.7–19.2) vs 4.8 (3.1–6.1), respectively, p 11.4 at PIE-worst predicted death or BPD with 80% sensitivity and 100% specificity. Conclusion: Development of PIE was associated with poorer oxygenation and ventilation efficiency despite increased tidal volumes. The OI at PIE-worst predicted death or BPD