Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase^® until 2016. Depression was reported most frequently in the whole population to the global database VigiBase^® (reporting odds ratio (ROR) 6.93; 95% CI: 6.5–7.4). In the VigiBase^®, aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5–32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61–3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase^®. These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.

Purpose of review: In 2013, the association between T-Box factor 4 (TBX4) variants and pulmonary arterial hypertension (PAH) has first been described. Now – in 2020 – growing evidence is emerging indicating that TBX4 variants associate with a wide spectrum of lung disorders. Recent findings: TBX4 variants are enriched in both children and adults with PAH. The clinical phenotype associated with a TBX4 variant seems to be milder than that in other PAH-associated gene mutations. Further, TBX4 variants have increasingly been associated with a variety of clinical and histopathological phenotypes, including lethal developmental parenchymal lung diseases such as not only acinar dysplasia in neonates, but also less outspoken parenchymal lung diseases in children and adults. Summary: The clinical phenotype of a TBX4 variant has recently been recognised to expand from bone disorders to different types of lung diseases. Recent data suggest that variants of TBX4, a transcription factor known to be an important regulator in embryonic development, are not rare in both children and adults with PAH and/or developmental parenchymal lung diseases.

Treatment strategies in paediatric pulmonary arterial hypertension (PAH) have evolved over the last years, but survival is still poor. Recently, in adults with severe PAH, upfront triple combination therapy (uTCT) from diagnosis has been reported to show significant clinical improvement and excellent long-term outcome. This retrospective, observational study aimed to assess the efficacy of uTCT in paediatric PAH.Children diagnosed with PAH between 2010 and 2019 and started with uTCT were included. World Health Organization Functional Class (WHO-FC), haemodynamics, echocardiography, 6-min walking distance and serum level ofN-terminal pro-brain-natriuretic-peptide were assessed at baseline, after 3 and 6 months and at last available follow-up. Events were defined as death, lung transplantation or Potts shunt.21 children (median age 4.8 years (2.5–12.8), 57% females) were included. All children except one were in WHO-FC III or IV (28% and 67%, respectively). After 3 months, one child had died and one child had received a Potts shunt. The remaining 19 children showed clinical and echocardiographic improvement, which persisted at 6 months. Children with idiopathic and heritable PAH showed one-, two- and three-year transplant-free survival estimates of 100%, 94% and 87%, albeit 47% of them receiving a Potts shunt during follow-up.Children with severe PAH, but not pulmonary veno-occlusive disease, improved significantly with uTCT and showed beneficial up to 3-year survival rates, albeit 47% of them receiving a Potts shunt during follow-up. The role of a Potts shunt in conjunction to uTCT in paediatric PAH needs to be further established.

Since the discovery of the TBX4 gene, the phenotypical spectrum of human TBX4 mutations is rapidly expanding from syndromes with skeletal dysplasia, to pulmonary hypertension to developmental lung diseases, all associated with disrupted organ developmenthttp://bit.ly/2MvYful