Precision medicine is an emerging approach to disease treatment and prevention that considers individual gene variability, environment and lifestyle. In contrast to a one-size-fits-all approach, improved outcomes can be achieved with individually targeted health-care advice. This is especially powerful in oncology, with treatments based on the individual’s tumour genetics.
Otitis media (OM), rhinosinusitis, sleep disordered breathing (SDB) are common presentations. The sequelae include complaints of difficulty breathing, sleeping, feeding and hearing, subsequently affecting growth, mood, behaviour, learning, communication and development.
Genetics
Anecdotally, most children presenting to an ENT clinic have a parent who, as a child, also suffered recurrent tonsillitis or OM. Twins studies also show a strong heritable component in OM.
Co-researchers at the Telethon Kids Institute (TKI) have identified one gene and several genetic loci that may host candidate genes indicating risk of OM. Although gene therapy appears a long way off, injecting genes, via a viral vector, into the cochlea to treat hearing loss, is entering clinical trials.
Mannose binding lectin (MBL) is an integral part of the innate immune system. Unpublished data from a paediatric cohort at St John of God Hospital (SJGH) Subiaco, found approximately 35% of patients requiring surgical intervention for SDB were MBL deficient. A further 5-7% of patients had an immunoglobulin deficiency. None of these deficiencies can be directly corrected, apart from immunoglobulin replacement in severe cases.
Our research also shows that day-care attendance is correlated with increased risk for surgical intervention for OM. Armed with such data, for the high-risk patient, advice could be to minimise day-care attendance, encourage influenza and other vaccination, lower the threshold for antibiotic prescription etc.
Microbiology, immunology and nutrition
TKI co-researchers have also uncovered complex interactions between the immune system, the nasopharyngeal microbiome, nasopharyngeal and middle ear viral pathogens, bacterial pathogens (H. Influenzae) and biofilm formation, resulting in persistent disease.
These studies have led to two novel therapies in clinical trials: 1) Dornase Alpha (usually used to treat viscous secretions in cystic fibrosis) to dissolve the persistent middle ear biofilm and, 2) a nasal vaccine to replace the pathogenic nasopharyngeal microbiome with a healthy one. Our animal model shows markedly reduced rates of OM, indicating that these treatments could dramatically alter management in the future.
We found that in children with SDB, similar persistent infections within the tonsils and adenoid cause chronic inflammation and hypertrophy, presenting targets for future anti-microbial therapies to treat SDB.
Immune deficiency and atopy contribute to presentations of rhinitis, sinusitis and airway obstruction. Unlike adults, paediatric allergic rhinitis is strongly associated with SDB. Identifying rhinitis, aeroallergens, effective topical therapy, allergen avoidance and desensitisation, play an important primary and adjuvant role in treating SDB and rhinosinusitis in children.
Patients with adenotonsillar hypertrophy often present with dysphagia (especially meat). We found that most children undergoing adenotonsillectomy (SJGH cohort), were iron deficient. It is uncertain if diet alone is responsible. Eosinophilic oesophagitis and coeliac disease are often also identified in this dysphagic population.
Some of these children have persistent lethargy, despite sleep improvement after surgery, and can be counselled to increase iron-rich foods, or other supplements. In children presenting with restless sleep without snoring, but resultant periodic limb movement disorder, and/or behavioural and learning issues, iron supplements alone may be recommended.
Surgical outcomes and safety
Using validated questionnaires, our team demonstrated the efficacy of symptom-based targeting of surgery for sleep disordered breathing. Furthermore, we showed that in younger children, iron deficiency may cause persistent daytime lethargy and behavioural problems that may require supplementation.
Although adenotonsillectomy is highly effective to treat SDB in children (success rates in randomised controlled trials >85%), the risk of post-operative haemorrhage is a concern. The Perth Children’s Hospital (PCH) ENT department pioneered tranexamic acid use in secondary haemorrhage to reduce return to theatre rates (<1%).
Further improvements in technology and technique have resulted in the intra-capsular tonsillectomy for selected patients, reducing recovery times to a few days, and bleeding rates to near zero. In complex, non-obese, CPAP intolerant patients where adenotonsillectomy fails (e.g. trisomy 21), midline posterior glossectomy is effective.
Teams
The virtual or in-person meeting of medical, surgical, and allied health teams in the aero-digestive diseases arena was pioneered in Australia at Princess Margaret Hospital in 2006. This enabled the coordinated care of complex patients, in teaching hospitals and private practice. The Complex Airway Team at PCH is a multi-disciplinary group meeting frequently and communicating daily.
For example, a child with snoring, dysphagia, failure to thrive and chronic respiratory pathology will be discussed by the otolaryngologist, respiratory physician, gastroenterologist, speech pathologist and dietitian. Investigations (sleep studies, blood tests, lung function studies, contrast swallow assessment) and clinical findings are compared and communicated to the primary care team. If surgery is contemplated, a bronchoscopy, oesophagoscopy and adenotonsillectomy can be combined under one general anaesthetic, with concurrent multi-specialty opinions and treatment.
Targeted nutrition, feeding, sleep hygiene, day-care attendance, supplemental vaccination and allied health interventions all help to reduce the burden of disease and improve outcomes of medical and surgical interventions, and can be targeted to each child’s unique clinical and social picture.
Key messages
- Precision medicine enables better targeting of treatments
- Consider genetics, microbiome, immune status nutrition and lifestyle not just the organ system
- Individualised patient-centred, family focused healthcare can produce better outcomes with fewer complications.
– References available on request
Author competing interests – the author has been involved in some of the research described