Lung function evolution in children with old and new type bronchopulmonary dysplasia: a retrospective cohort analysis.

Bronchopulmonary dysplasia (BPD) is one of the most important sequelae of premature birth. There is concern that in some patients, lung injuries early in life may have lifelong consequences. In this retrospective observational cohort study, lung function evolution in children with BPD was investigated from childhood to young adulthood. Data from 355 pulmonary function tests (PFT) in 24 patients were analyzed, with a median age at first PFT of 7.6 years and at last PFT 18.2 years. FEV1 and FEV1/FVC were below the 5th percentile in respectively 18 and 13/24 patients. Comparing first and last measurement, there was significant worsening in FEV1 from a mean of 71.3% pred (SD 18.3) to 66.7% pred (SD 21.7) (p < 0.05) and in FEV1/FVC from 85.4% pred (SD 15.2) to 79.8% pred (SD 17.3) (p = 0.01). Evaluation of the individual lung function changes with linear regression showed deterioration in FEV1, FVC, and FEV1/FVC in respectively 17, 13, and 17/24 patients. Total group analysis showed significant deterioration in FEV1 (- 0.7%/year, p = 0.002) and FEV1/FVC (- 0.5%/year, p = 0.01). None of the 11 patients born up to 1990 improved in FEV1 vs 7 of the 13 patients born after 1990 (p = 0.006).Conclusion: This points out to further deterioration of the lung function during childhood in this selected group of children with BPD.What is Known:• Data on longitudinal changes in lung function in children with BPD are scarce.What is New:• In children with BPD at the severe end of the disease spectrum, lung function does not improve over time. On the contrary, in two-thirds of the subjects studied FEV1and FEV1/FVC worsen over time.• Lung function evolution towards adulthood was somewhat more favorable in children born after 1990 compared with those born earlier, probably reflecting improvements in neonatal care in subjects with new type BPD.

Novel LMNA mutations cause an aggressive atypical neonatal progeria without progerin accumulation.

BACKGROUND: Progeroid syndromes are genetic disorders that recapitulate some phenotypes of physiological ageing. Classical progerias, such as Hutchinson-Gilford progeria syndrome (HGPS), are generally caused by mutations in LMNA leading to accumulation of the toxic protein progerin and consequently, to nuclear envelope alterations. In this work, we describe a novel phenotypic feature of the progeria spectrum affecting three unrelated newborns and identify its genetic cause. METHODS AND RESULTS: Patients reported herein present an extremely homogeneous phenotype that somewhat recapitulates those of patients with HGPS and mandibuloacral dysplasia. However, pathological signs appear earlier, are more aggressive and present distinctive features including episodes of severe upper airway obstruction. Exome and Sanger sequencing allowed the identification of heterozygous de novo c.163G>A, p.E55K and c.164A>G, p.E55G mutations in LMNA as the alterations responsible for this disorder. Functional analyses demonstrated that fibroblasts from these patients suffer important dysfunctions in nuclear lamina, which generate profound nuclear envelope abnormalities but without progerin accumulation. These nuclear alterations found in patients' dermal fibroblasts were also induced by ectopic expression of the corresponding site-specific LMNA mutants in control human fibroblasts. CONCLUSIONS: Our results demonstrate the causal role of p.E55K and p.E55G lamin A mutations in a disorder which manifests novel phenotypic features of the progeria spectrum characterised by neonatal presentation and aggressive clinical evolution, despite being caused by lamin A/C missense mutations with effective prelamin A processing.

Airway clearance techniques to treat acute respiratory disorders in previously healthy children: where is the evidence?

Airway clearance techniques are an important part of the respiratory management in children with cystic fibrosis, bronchiectasis and neuromuscular disease. They are also, however, frequently prescribed in previously healthy children with an acute respiratory problem with the aim to speed up recovery. The current review explores the evidence behind this use of airway clearance techniques in children without underlying disease. Few studies have been performed; many different techniques are available and the therapies used are often poorly specified. It is necessary to name the specific airway clearance technique used in treatment rather than to just state "chest physiotherapy," a term that is often confused with chest clapping or vibration plus postural drainage. There is little evidence that airway clearance techniques play a role in the management of children with an acute respiratory problem. Physicians routinely prescribing airway clearance techniques in previously healthy children should question their practice.