Structural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia

RATIONALE: As more preterm infants recover from severe bronchopulmonary dysplasia (BPD), it is critical to understand the clinical consequences of this condition on the lung health of adult survivors.

OBJECTIVES: To assess structural and functional lung parameters in young adult BPD survivors and preterm and term controls Methods: Young adult survivors of BPD (mean age 24) underwent spirometry, lung volumes, transfer factor, lung clearance index and fractional exhaled nitric oxide measurements together with high-resolution chest tomographic (CT) imaging and cardiopulmonary exercise testing.

MEASUREMENTS AND MAIN RESULTS: 25 adult BPD survivors, (mean ± SD gestational age 26.8 ± 2.3 weeks; birth weight 866 ± 255 g), 24 adult prematurely born non-BPD controls (gestational age 30.6 ± 1.9 weeks; birth weight 1234 ± 207 g) and 25 adult term birth control subjects (gestational age 38.5 ± 0.9 weeks; and birth weight 3569 ± 2979 g) were studied. BPD subjects were more likely to be wakened by cough (OR 9.7, 95% CI: 1.8 to 52.6), p<0.01), wheeze and breathlessness (OR 12.2, 95%CI: 1.3 to 112), p<0.05) than term controls after adjusting for sex and current smoking. Preterm subjects had greater airways obstruction than term subjects. BPD subjects had significantly lower values for FEV1 and FEF25-75 (% predicted and z scores) than term controls (both p<0.001). Although non-BPD subjects also had lower spirometric values than term controls, none of the differences reached statistical significance. More BPD subjects (25%) had fixed airflow obstruction than non-BPD (12.5%) and term (0%) subjects (p=0.004). Both BPD and non-BPD subjects had significantly greater impairment in gas transfer (KCO % predicted) than term subjects (both p<0.05). Eighteen (37%) preterm participants were classified as small for gestational age (birth weight < 10th percentile for gestational age). These subjects had significantly greater impairment in FEV1 (% predicted and z scores) than those born appropriate for gestational age. BPD survivors had significantly more severe radiographic structural lung impairment than non-BPD subjects. Both preterm groups had impaired exercise capacity compared to term controls. There was a trend for greater limitation and leg discomfort in BPD survivors.

CONCLUSIONS: Adult preterm birth survivors, especially those who developed BPD, continue to experience respiratory symptoms and exhibit clinically important levels of pulmonary impairment.

Chronic inflammation in CF airways - a persistent issue for A20

Cystic Fibrosis (CF) is characterised by prolonged and exaggerated airways inflammation. Despite recent developments to overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to reduce the inflammatory response. The NF-kB regulator A20 is a key target to normalise the inflammatory response and is reduced in CF. Here, we describe the plethora of functions of A20 as they apply to innate immune function within the airways. Pharmacological compounds can enhance A20 mRNA and protein expression, but we observed a blunted effect in CF primary epithelial cells. In CF cells pre-treatment with gibberellic acid (GA3) shows anti-inflammatory effects only in some patients. We show that cells with higher basal p38 expression respond with an increase in pro-inflammatory cytokines. Furthermore, all CF PNECs show increased p38 mRNA when stimulated in the presence of GA3. Our results suggest that those patients may benefit from therapeutics targeting p38.

Congenital nasolacrimal duct obstruction:Comparison of two different treatment algorithms

Purpose: To clarify the most appropriate treatment regimen for congenital nasolacrimal duct obstruction (CNLDO). Methods: A retrospective observational analysis was performed of patients undergoing probing with or without intubation to treat CNLDO in a single institution (Royal Victoria Hospital, Belfast) from 2006 to 2011. Results: Based on exclusion criteria, 246 eyes of 177 patients (aged 0 to 9.8 years with a mean age of 2.1 years) were included in this study: 187 (76%) eyes had successful outcome at first intervention with primary probing, whereas 56 (23%) eyes underwent secondary intervention. There were no significant differences by gender, age, or obstruction complexity between the successful and unsuccessful patients with first intervention. For those patients requiring secondary intervention, 16 of 24 (67%) eyes had successful probing, whereas 22 of 24 (92%) had successful intubation. Patients with intubation as a secondary procedure were significantly more likely to have a successful outcome (P = .037). Statistical analysis was performed using the Fisher's exact test and Barnard's exact test. Conclusions: Primary probing for CNLDO has a high success rate that is not adversely affected by increasing age. This study also indicates that if initial probing is unsuccessful, nasolacrimal intubation rather than repeat probing yields a significantly higher success rate.