We will collect clinical data and quality-of-life information about the children, test their lung function and take blood samples to analyze their immune response. 

The long-term goal is to uncover how respiratory infections during childhood affect long-term lung health and the development of chronic lung diseases in Nepal. In addition, we're going to investigate whether a short course of steroids given to children who are admitted to the hospital with respiratory tract infections can prevent the development of chronic lung diseases. 

The project will be realized by performing a clinical study with a related biobank to assess these major research questions: 

What are the main LRTI etiologies and how do they present clinically (in a semi-rural setting) in Nepal? 

The occurrence, risk factors, and clinical course of common respiratory viruses in children with LRTI have been incompletely assessed in a LMIC setting like Nepal.  

We will assess the etiology patterns in children with LRTI based on four important viruses: respiratory syncytial virus (RSV), human metapneumovirus (HMPV), Influenza, and SARS-CoV-2. For this, we will first establish diagnostics of viral LRTIs based on in-house real-time multiplex PCRs developed at the hospital in Molde, Møre og Romsdal Health Trust, Norway, and using nucleic acid extraction reagents developed at NTNU (now Lybe). By strengthening local molecular diagnostics and biobanking samples for retrospective viral tests, the basis for future surveillance capacity is also formed.  

Is Early life viral LRTI exposure a risk factor for later chronic lung disease development? 

In C-LUNG we will follow children after early-life LRTI, to assess the rate of recurrent LRTIs, wheezing episodes, and lung function, and compare to a control group of children without LRTI. We will extend traditional outcome assessments including family and child-related QoL effects. 

Can we prevent chronic lung disease development after early childhood wheezing LRTI?  

In C-LUNG we will include children in a RCT to determine the efficacy of a short (3 day) and affordable (1 USD/pr.d) corticosteroid course in preventing recurrent wheezing and asthma in a 12-month follow-up in children with first-time wheezing bronchiolitis caused by other viruses than RSV. 

Can we identify blood immune signatures associated with specific viral infections and the development of chronic lung disease in Nepali children? 

We have an incomplete understanding of how early-life viral LRTI contribute to lung disease such as asthma later in life. Our hypothesis is that some respiratory viruses cause dysregulated immune responses that predispose to lung disease. We will therefore assess blood samples from children with LRTIs upon admission to DH, one year later and at school age, with a goal to identify immune signatures associated with specific viral infections and the development of CLD.  

To address the described project objectives and research questions, the work has been structured into three work packages (WP). In WP1 we will establish viral diagnostics for viruses most clearly associated with LRTI and epidemics in the child population (RSV, HMPV, Flu, SARS-CoV-2), and a POCT for RSV. In WP2 we will perform a prospective clinical study in children with LRTI followed by an interventional study in the youngest non-RSV wheezing LRTIs. In WP3 a biobank will be established from the first-year prospective study and the interventional study with blood cells and serum for immunological profiling.