Bronchiectasis is characterised by chronic bacterial airway infection that drives the inflammatory response responsible for this condition. A large number of aetiologies have been identified, however for many patients this disease may arise in the context of multiple risk factors as may occur with coronary artery disease. Young children with their immature immune systems are at higher risk of developing airway infection, particularly if they are malnourished. Children are heavily exposed to recurrent viral infections, but the role of viruses in the development of bronchiectasis in the paediatric population is poorly understood; this editorial reviews three potential mechanisms.

Viral infections may cause severe acute lung damage with the development of bronchiectasis and the most commonly listed example in the literature is measles, which was prevalent prior to vaccination. Measles may cause pneumonia in children and has characteristic clinical features such as a rash. A South African study diagnosed bronchiectasis on the basis of bronchoscopy in 57 children and in 20 of these subjects, respiratory symptoms had started immediately after a clinical diagnosis of measles; this cohort had low socioeconomic status with prevalent malnutrition.1 The same group also performed autopsies in 21 children who had died of measles and found the presence of bronchiectasis and in half the cohort there was evidence of superadded adenovirus or herpes virus infection with severe necrosis of the bronchi and bronchioles. Two studies assessed an adenovirus outbreak in New Zealand in 25 patients who required hospitalisation2,3; all subjects had significant clinical disease and on follow up 15 subjects had chronic respiratory symptoms. Of these children, 5 had evidence of bronchiectasis diagnosed 5 weeks to 5 years after the initial date of hospitalisation and pathology samples (1 post-mortem, 3 lobe/lung) demonstrated evidence of severe lung damage with obstructive bronchiolitis and fibrosis in addition to bronchiectasis. A prominent feature of this cohort was the presence of malnutrition. Influenza especially in pandemics may cause severe lung disease and has often been listed as a cause of bronchiectasis but there do not appear to be any studies based on radiology or pathology confirming this association that have been published. Respiratory syncytial virus (RSV) may cause significant illness in the first 2 years of life with bronchiolitis and emerging literature highlights its potential role in the development of asthma, but there appears to be no convincing evidence of a link to the development of bronchiectasis.

Chronic bronchial infection with a virus could potentially cause excessive inflammation and result in bronchial dilatation as occurs with bacteria; however, the published literature supporting this contention is minimal. Adenoviruses may persistently infect the upper4 and lower5 respiratory tracts in children with asthma. Wurzel et al. have demonstrated the presence of adenovirus in 10% of a cohort of children with persistent bacterial bronchitis (PBB) and bronchiectasis from bronchoscopy samples, which appear to have been taken at baseline state and therefore may represent chronic colonisation.6 The presence of adenovirus was also associated with the isolation of bacteria from the lower respiratory tract and younger age was an important risk factor. Cytomegalovirus (CMV) is an opportunistic pathogen and remains a major problem in lung transplantation with bronchiolitis obliterans syndrome and graft rejection. Persistent CMV infection also appears to cause a diffuse necrotising pneumonitis with fibrosis, in both immunocompromised and preterm infants and, less frequently in immunocompetent infants.7 CMV could well be relevant to the development of bronchiectasis in early childhood but there appear to be no published studies in this regard.

Viral infections of the lower respiratory tract may result in secondary bacterial infection and potentially persistent bacterial airway colonisation. There is now an extensive body of literature demonstrating that viral infections may trigger exacerbations in patients with established chronic lung disease, including bronchiectasis.8,9 One of the most convincing studies demonstrating this association was performed by Mallia et al.,10 who infected subjects with established COPD with rhinovirus (RV); in 60% these subjects this induced a bacterial exacerbation and the RV impaired innate immunity. Whether viral infections can lead to the establishment of bronchiectasis with secondary bacterial involvement has not been confirmed in the literature although this is certainly plausible. Fig. 1 demonstrates a potential pathway as to how this could occur. It is well established that viral infections can impair host immunity in the lower respiratory tract and perhaps the most recognised example occurred in the 1918 Spanish influenza pandemic in which there was widespread epithelial destruction; as highlighted by Mallia et al. there are a variety of other ways in which viruses can impair host immunity. This effect then leaves the lower respiratory tract vulnerable to the migration of bacteria from the upper respiratory tract microbiome such as nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae. These pathogens have a variety of mechanisms which may allow them to adapt to the lower respiratory tract including the ability to invade into lung tissue and facultative anaerobic metabolism.11 There have been a large number of factors identified which may impair the host immune response to bacteria in the lung of which the most prevalent in young children worldwide are an immature immune response (particularly the adaptive immune response) and malnutrition. The interaction between the bacteria and host immune response determines whether the pathogen is cleared from the lower respiratory tract or alternatively bacterial airway colonisation occurs. Colonisation may then result in persistent inflammation which may predominantly occur with exacerbations or more frequently and result in symptoms of PBB and if severe enough/adequate duration, develop into bronchiectasis.12

Fig. 1

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The increasing utilisation of viral detection techniques including rapid antigen testing and polymerase chain reaction has highlighted the potential role of viral infections as a trigger for the development of bronchiectasis in children. Prospective studies and the use of bronchoscopy with serial collection samples are likely to provide significant insights into this association and the mechanisms involved. Broadening viral detection techniques to cover pathogens such as CMV may be useful. Importantly, the proposed pathway of virus-triggered bronchiectasis as illustrated in Fig. 1 is potentially amenable to treatment, particularly in high-risk subjects such as those with prematurity or identified immune deficiency. Vaccination and emerging anti-viral agents could be considered for the treatment of these individuals. In patients with early stage bronchitis/PBB the appropriate use of antibiotics could conceivably eradicate colonising bacteria and prevent the progression to bronchiectasis. Studying the initial interaction between viruses and bacteria whilst challenging, has the potential to transform outcomes in paediatric bronchiectasis.