Intranasal Spray an Effective First-Line Treatment for Pediatric Sleep-Disordered Breathing

While the recommended treatment for pediatric sleep-disordered breathing is often a tonsillectomy, could there be a quicker, easier, and less painful first-line treatment administered in a primary care setting?

Neurology Learning Network spoke with Kristen P. Perrett, associate professor, Department of Pediatrics, University of Melbourne, Australia, and Gillian M. Nixon, associate professor, Department of Pediatrics, Monash University, Australia, about their study “Effectiveness of Intranasal Mometasone Furoate vs Saline for Sleep-Disordered Breathing in Children: A Randomized Clinical Trial,” recently published in JAMA Pediatrics.

In Part 1 of this interview, Drs Perrett and Nixon explain the background behind the study, their methods and most significant findings, and the practical implications for clinicians treating sleep disorders.

Find Part 2 of this interview here, and then visit our Sleep Disorders Excellence Forum for more expert insights for your practice.

Editor’s Note: This interview has been lightly edited for length and clarity.

Brionna Mendoza, Associate Digital Editor, Neurology Learning Network (NLN): What led you and your colleagues to investigate intranasal mometasone furoate versus saline for the treatment of obstructive sleep-disordered breathing in children?

Drs. Kristen P. Perrett and Gillian M. Nixon: Snoring and difficulty breathing during sleep affects about 12 per cent of children and can cause significant long-term issues impacting cognitive function, behavior and cardiovascular health. The most common treatment is removing the tonsils and adenoids.

Alongside collaborators at the Melbourne Clinical Trials Centre, we looked at a “top-down approach” and asked what were the biggest health issues for the Royal Children’s Hospital, Melbourne, and Monash Health. Waitlists for children with sleep-disordered breathing (SDB) were unacceptable with children often referred to multiple departments, including both medical and surgical.

To help, we wanted to find out if these children could be initially managed in the primary care setting – by their GP – before requiring a specialist referral, as currently recommended.

Small randomized controlled trials have previously demonstrated improvement in polysomnography (PSG) parameters for children with obstructive sleep apnea (OSA) when treated with an intranasal steroid, but these studies relied on PSG metrics as both inclusion criteria and outcomes. Given that many children who snore and have breathing problems in sleep worldwide do not have access to PSG, we wanted to design a study that focused on symptoms so the results would be directly translatable to primary care.

The MIST Trial investigated if a six-week course of intranasal mometasone furoate (an anti-inflammatory steroid nasal spray) was more effective than intranasal saline (a salt water nasal spray) for the treatment of symptoms of obstructive SDB in children.

Mendoza, NLN: Please walk us through the study methods and most significant findings.

Perrett and Nixon: The MIST Trial was a multicenter, randomized, double-blind, placebo-controlled recruiting participants from 8 June 2018 to 13 February 2020. The trial involved 276 children, aged 3 to 12 years, referred to a specialist for significant SDB symptoms. Exclusion criteria encompassed previous adenotonsillectomy, body mass index greater than the 97th percentile and severe SDB.

The trial was carried out at The Royal Children's Hospital, Melbourne, and Monash Children's Hospital, with  randomization stratified by site. Data were analyzed on an intention-to-treat basis between 28 October 28 2020 and 25 September 2022.

Each child received one spray in each nostril per day of either the saline nasal spray or the anti-inflammatory steroid nasal spray for 6 weeks.

Resolution of significant SDB symptoms (to a level no longer requiring referral to a specialist as per American Academy of Pediatrics guidelines) occurred in 44% in the mometasone group and 41% in the saline group (risk difference 4% [95% CI -8– 16] p=0.51).

We concluded there was no difference in treatment effect between intranasal mometasone and saline for management of SDB symptoms, with substantial rates of SDB symptom improvement after 6 weeks with both nasal sprays. The results suggest that almost half of children with SDB could be initially managed in the primary care setting, and may not require referral to specialist services, as currently recommended.

Mendoza, NLN: Which other sleep disorders, if any, might your findings apply to? Are there any implications for adult patients?

Perrett and Nixon: Our results apply to children’s health only – in this study, participants were aged between 3 and 12. It’s important to remember that adults often snore for different reasons to children, such as being overweight or obese or having anatomical abnormalities. This means that these sprays may not be effective in adults.

Mendoza, NLN: What are the practical applications of your findings for clinicians that treat sleep disorders?

Perrett and Nixon: Clinicians managing children aged between t3 and 12 years with SDB could consider a 6-week trial of intranasal saline or steroid spray as a first line management option, which may resolve symptoms in almost half of children.

At this stage, we don’t yet know which agent should be the first choice and whether the effect is sustained. Our MIST+ follow-up study, which is currently recruiting, is looking into this.

If families are concerned about a child’s snoring or breathing difficulties while they sleep, we recommend they visit their GP first to discuss the possibility of using a nasal spray.

Associate Professor Gillian Nixon, MBChB, FRACP, MD, Grad Cert Hlth Serv Mt, is a pediatric respiratory and sleep physician with both academic and clinical appointments. Her clinical practice as Deputy Director of the Melbourne Children’s Sleep Centre at Monash Children’s Hospital is centered on the management of children with respiratory and sleep disorders, placing her in an ideal situation to both raise clinical questions for research and to translate research into practice directly. A/Prof Nixon's academic appointment is in the Department of Paediatrics, Monash University. She is also the Head of Paediatric Sleep Research in the Melbourne Children’s Sleep Centre. A/Prof Nixon's research is focussed on improvements in the diagnostic and treatment pathway for snoring and obstructive sleep apnoea in children, including developing simplified diagnostic tools and driving improvements in evidence-based treatment pathways. She has recently held a Translating Research into Practice fellowship from the National Health and Medical Research Council to support this research. She has a postgraduate qualification in Health Service Management and is focussed on improving care for children through improvements in health care systems. She has built cross-disciplinary collaborations and worked with state government 2018-2020 on related quality improvement projects regarding the management of the large number of children with snoring and obstructive sleep apnoea, a condition with significant negative effects on learning and development.

Associate Professor Kirsten Perrett, MBBS (Hons), FRACP, PhD, is Group Leader of the Population Allergy Group and Deputy Directory of the Melbourne Children’s Trials Centre at the Murdoch Children’s Research Institute (MCRI). She is also Director of the National Allergy Centre of Excellence (NACE) and the Centre for Food & Allergy Research (CFAR), hosted at MCRI; Paediatric Allergist and Vaccinologist at The Royal Children's Hospital, Melbourne and an Honorary Principal Fellow at The University of Melbourne. For more than 15 years, A/Prof Perrett has spear-headed Investigator-led and industry-sponsored vaccine and food allergy clinical trials and is a highly sought-after trials expert and food allergy clinician scientist. warded a 2022-26 National Health and Medical Research Council (NHMRC) Investigator Award and 2018-2027 Melbourne Children’s Clinician-Scientist Fellowship, A/Prof Perrett has also received more than $47.5 million in competitive, government, philanthropic and industry research funding and has more than 100 peer-reviewed publications, including 85 in the past five years. Her research has helped shape world-wide changes to food allergy prevention, diagnosis and management. A/Prof Perrett’s current program of clinical trials research focuses on investigating novel strategies for the prevention and early intervention/treatment of food allergy, eczema and atopic disease. She is also involved in research investigating immunological mechanisms underlying allergic disease pathogenesis and exploring strategies to improve the diagnostic accuracy of minimally invasive tests for food allergy diagnosis.