Breastfeeding, lung volumes and alveolar size at school-age

Background: Previous studies found larger lung volumes at school-age in formerly breastfed children, with some studies suggesting an effect modification by maternal asthma. We wanted to explore this further in children who had undergone extensive lung function testing. The current study aimed to assess whether breastfeeding was associated with larger lung volumes and, if so, whether all compartments were affected. We also assessed association of breastfeeding with apparent diffusion coefficient (ADC), which measures freedom of gas diffusion in alveolar-acinar compartments and is a surrogate of alveolar dimensions. Additionally, we assessed whether these effects were modified by maternal asthma.Methods: We analysed data from 111 children and young adults aged 11–21 years, who had participated in detailed lung function testing, including spirometry, plethysmography and measurement of ADC of 3Helium (3He) by MR. Information on breastfeeding came from questionnaires applied in early childhood (age 1–4 years). We determined the association between breastfeeding and these measurements using linear regression, controlling for potential confounders.Results: We did not find significant evidence for an association between duration of breastfeeding and lung volumes or alveolar dimensions in the entire sample. In breastfed children of mothers with asthma, we observed larger lung volumes and larger average alveolar size than in non-breastfed children, but the differences did not reach significance levels.Conclusions: Confirmation of effects of breastfeeding on lung volumes would have important implications for public health. Further investigations with larger sample sizes are warranted

Clinical features and management of children with primary ciliary dyskinesia in England

Objective In England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children seen in this Service and compare lung function to children with cystic fibrosis (CF). Design Multi-centre service evaluation of the English National Management PCD Service. Setting Four nationally commissioned PCD centres in England. Patients 333 children with PCD reviewed in the Service in 2015; lung function data were also compared to 2970 children with CF. Results Median age at diagnosis for PCD was 2.6 years, significantly lower in children with situs inversus (1.0 vs 6.0 years, p<0.0001). Compared with national data from the CF Registry, mean (SD) %predicted FEV1 76.8% in PCD (n=240) and 85.0% in CF, and FEV1 was lower in children with PCD up to the age of 15 years. Approximately half of children had some hearing impairment, with 26% requiring hearing aids. Children with a lower BMI had lower FEV1 (p<0.001). One third of children had positive respiratory cultures at review, 54% of these grew Haemophilus influenzae. Conclusions We provide evidence that children with PCD in England have worse lung function than those with CF. Nutritional status should be considered in PCD management, as those with a lower BMI have significantly lower FEV1. Hearing impairment is common but seems to improve with age. Well designed and powered randomised controlled trials on management of PCD are needed to inform best clinical practice

The Impact on Parents of Diagnosing PCD in Young Children

Primary ciliary dyskinesia (PCD) is an incurable, rare, inherited, chronic condition. Treatment includes the regular clearing of airway mucus, aggressive treatment of infections and management of hearing loss. Caregiver burden has not been explored, hence we interviewed 18 mothers and 6 fathers of children under 6 years to understand the impact of diagnostic testing and implications of a positive diagnosis. Interviews were transcribed and thematically analysed and five key themes were identified. These included the parents’ experiences following child’s diagnosis, impact of child’s treatment regimen on parent, impact of child’s health status on parent, parent’s coping strategies, and parental concerns for the future. Parents described their diagnostic journey, with the findings revealing how a lack of awareness among clinicians of the PCD symptom pattern can lead to a delayed diagnosis. Parents discussed the emotional and practical impact of a PCD diagnosis and the coping strategies employed to deal with challenges arising following a diagnosis. Parents use a variety of different lifestyle changes to accommodate their child’s treatment regimen and to cope with disruptive life events such as the COVID-19 pandemic. This study provides valuable insights into parental adjustment and adaptation to a PCD diagnosis and management regimen. Going forward, this research highlights the need for integrated social care for PCD patients and their families

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients

Assessment of lung alveolar development in childhood and adolescence using 3-helium magnetic resonance

The major functional units of the lung called alveoli, are located in the periphery of the lung. Despite their functional importance, it has been difficult to evaluate their structure and development. Until the advent of 3-Helium magnetic resonance (3HeMR), it was not possible to directly assess peripheral lung structure in a living individual. When this study commenced, the prevailing hypothesis was that human alveolarization was complete by 3 years. It was believed that preterm birth would lead to persisting alveolar damage. The role of other factors affecting human lung development were not clearly understood. In this work, I describe the use of 3HeMR to : 1. Examine the current hypothesis regarding normal alveolar development, 2. Determine whether birth at very preterm gestation leads to long-term alveolar damage and 3. Evaluate factors affecting human alveolar development. First, we determined alveolar size using 3HeMR in healthy subjects aged 7 to 21 years. Alveolar dimensions did not increase by the expected rate over this age range, despite lung capacity increasing nearly fourfold. The only plausible explanation is new alveoli forming throughout the period of lung growth. Then, we compared alveolar size between children born very prematurely (<32 weeks gestation), including survivors of neonatal chronic lung disease (CLD) with term born children and children born mildly preterm (33-36 weeks gestation). Alveolar dimensions were nearly identical suggesting alveolar catch up growth in the very preterm groups. In the third part of the study, we investigated the relationship between various risk factors and alveolar dimensions. Exposure to environmental tobacco smoke (ETS) was found to be consistently associated with larger alveoli, suggesting its detrimental effect on alveolar development. Our results imply that developing lungs have the potential to recover from early life insults. Conversely, the window for adverse environmental exposures to affect alveolar development may be wider than previously believed

An Association of Purple Urine Bag Syndrome with Intussusception - A Case Report

An Association of Purple Urine Bag Syndrome with Intussusception - A Case Repor

Case presentation: persistent adenovirus B3 infections associated with bronchiolitis obliterans treated with cidofovir in a child with mosaic tetrasomy 9p.

BACKGROUND: Adenoviruses (AdV) are non-enveloped, double-stranded DNA viruses with multiple serotypes, which cause a variety of end-organ disease in both immunocompetent and immunocompromised individuals. Some adenoviruses can become latent in the mucosa-associated lymphoid tissue (e.g. adenoids and tonsils), with the potential to reactivate sporadically, leading to upper or lower respiratory tract infection and disease. Bronchiolitis Obliterans (BO) is a rare chronic lung disorder which usually follows a severe insult to the respiratory tract. In children, it is a complication of severe infections (as post-infectious BO), typically manifesting after a severe respiratory infection, in previously healthy pre-school children. Symptoms and signs of air trapping (hyperinflated chest, expiratory wheeze) with persistent oxygen requirement are characteristic. The presence of the unusual mosaic tetrasomy 9p genotype in this case, despite standard cidofovir therapy for persistent or chronic adenovirus infection, may have impacted on the child's long-term clinical outcomes. CASE PRESENTATION: We present a case of persistent AdV B3 infection in a 14-month old boy with mosaic tetrasomy 9p, which persisted for 10 weeks, resulting in radiologically-confirmed BO, requiring cidofovir to control the persistent AdV B3 infection and standard therapy with pulsed steroids. We argue that in the presence of the mosaic tetrasomy 9p, earlier antiviral therapy may have decreased the severity of BO, as this mutation is known to be associated with some degree of immune dysregulation. CONCLUSIONS: Adenovirus infections are common in children and may persist as latent infections, with subsequent reactivations during loss of immune control, related to systemic illness arising from other causes. In chronic, reactivated AdV infection with pneumonia, BO is a recognised complication. However, in this case, with the presence of the mosaic tetrasomy 9p mutation, earlier antiviral therapy may have reduced such longer term complications, due to the immune dysregulatory nature of this mutation

Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance

The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals