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.

Nasal Polyps in Children: The Early Origins of a Challenging Adulthood Condition.

Nasal polyps (NPs) are benign inflammatory masses causing chronic nasal obstruction, usually associated with underlying chronic rhinosinusitis (CRS), which are rarely reported in childhood. The interest in NPs has recently increased due to new therapeutic options, namely biological agents, such as dupilumab, and an update of the European position paper on this topic was released in 2020, providing a detailed classification for these lesions and also discussing diagnostic and therapeutic approaches also in children. In childhood, NPs usually represent red flags for systemic diseases, such as cystic fibrosis and immunodeficiencies. This review outlines the recent data on NPs in childhood, focusing on predisposing factors for CRS as well as on the potential endotypes in this particular age group, for which further studies are required in order to better clarify their pathogenesis and to identify molecular biomarkers that could help achieve more personalized treatments.

Breast milk: more than just nutrition!

From an evolutionary and nutritional standpoint, exclusive human milk feeding for the first 6 months of life, with continued breastfeeding for 1 to 2 years of life, is recognized as the gold standard nourishment for the infant: it is a species-specific food, with a composition designed by nature to better respond to the biological and psychological needs of the newborn/infant. Human milk contains many hundreds of bioactive molecules that protect newborn against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Compared with formula feeding, breastfeeding has been associated with decreased morbidity and mortality in infants and to lower incidence of gastrointestinal infections and inflammatory, respiratory and allergic disease. Here, we briefly review the nutritional and functional composition of human milk and provide an overview of its varied bioactive factors.

The Virome and Its Major Component, Anellovirus, a Convoluted System Molding Human Immune Defenses and Possibly Affecting the Development of Asthma and Respiratory Diseases in Childhood.

The microbiome, a thriving and complex microbial community colonizing the human body, has a broad impact on human health. Colonization is a continuous process that starts very early in life and occurs thanks to shrewd strategies microbes have evolved to tackle a convoluted array of anatomical, physiological, and functional barriers of the human body. Cumulative evidence shows that viruses are part of the microbiome. This part, called virome, has a dynamic composition that reflects what we eat, how and where we live, what we do, our genetic background, and other unpredictable variables. Thus, the virome plays a chief role in shaping innate and adaptive host immune defenses. Imbalance of normal microbial flora is thought to trigger or exacerbate many acute and chronic disorders. A compelling example can be found in the respiratory apparatus, where early-life viral infections are major determinants for the development of allergic diseases, like asthma, and other non-transmissible diseases. In this review, we focus on the virome and, particularly, on Anelloviridae, a recently discovered virus family. Anelloviruses are major components of the virome, present in most, if not all, human beings, where they are acquired early in life and replicate persistently without causing apparent disease. We will discuss how modulation of innate and adaptive immune systems by Anelloviruses can influence the development of respiratory diseases in childhood and provide evidence for the use of Anelloviruses as useful and practical molecular markers to monitor inflammatory processes and immune system competence.