Objective monitoring tools for improved management of childhood asthma.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.

Social determinants of respiratory health from birth: still of concern in the 21st century?

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Development and validation of the international pediatric sleep endoscopy scale (IPSES).

OBJECTIVES: To develop and validate a consensus international pediatric sleep endoscopy scale (IPSES) for pediatric drug-induced sleep endoscopy (DISE). METHODS: Existing published DISE ratings scales were reviewed in order to develop a consensus rating scale synthesizing the most common features and adding new elements to address areas of controversy. Samples of 30 de-identified DISE video recordings were reviewed to develop and refine the scale. After the consensus scale was defined, a separate sample of 25 de-identified DISE videos were scored with the new consensus scale by the development group and a panel of independent raters. A weighted kappa statistic was used to quantify the inter-rater and intra-rater reliability of the consensus scale at each anatomic level. RESULTS: Among all raters, intra-rater reliability was most variable for the nasal airway (kappa range 0.33-0.94) and best for the lateral oropharynx (kappa range 0.68-0.95). Inter-rater reliability ranged from 0.43 for the nasal airway to 0.57 at the soft palate. CONCLUSION: The IPSES is a reliable consensus scale that reflects the most common features of existing scales and can be adopted as a universal scoring scale for pediatric DISE.

Applicability of the Global Lung Function Initiative prediction equations in Hong Kong Chinese children.

BACKGROUND AND OBJECTIVE: This study aimed to assess the applicability of the Global Lung Function Initiative (GLI) prediction equations for spirometry in Hong Kong children and to develop prediction equations based on the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) modeling. METHODS: Healthy Chinese children and adolescents aged 6-17 years old were recruited from randomly selected schools to undergo spirometry. The measurements were transformed to z-score according to the GLI-2012 equations for South East (SE) Asians and the GLI-2022 global race-neutral equations. Prediction equations for spirometric indices were developed with GAMLSS modeling to identify predictors. RESULTS: A total of 886 children (477 boys) with a mean age of 12.5 years (standard deviation [SD] 3.3 years) were included. By the GLI-2012 SE Asian equations, positive mean z-scores were observed in forced expiratory volume in 1 s (FEV1 ) (boys: 0.138 ± SD 0.828; girls: 0.206 ± 0.823) and forced vital capacity (FVC) (boys: 0.160 ± 0.930; girls: 0.310 ± 0.895) in both sexes. Negative mean z-scores were observed in FEV1 /FVC ratio (boys: -0.018 ± 0.998; girls: -0.223 ± 0.897). In contrast, negative mean z-scores in FEV1 and FVC, and positive mean z-scores in FEV1 /FVC were observed when adopting the GLI-2022 race-neutral equations. The mean z-scores were all within the range of ±0.5. By GAMLSS models, age and height were significant predictors for all four spirometric indices, while weight was an additional predictor for FVC and FEV1 . CONCLUSION: Our study provided data supporting the applicability of the GLI prediction equations in Hong Kong Chinese children. The GLI-2012 equations may underestimate FEV1 and FVC, while the GLI-2022 equations may overestimate the parameters, but the differences lie within the physiological limits. By GAMLSS modeling, weight was an additional predictor for FVC and FEV1 .

International Pediatric Otolaryngology Group (IPOG) consensus on scoring of pediatric Drug Induced Sleep Endoscopy (DISE).

OBJECTIVES: To develop consensus statements for the scoring of pediatric drug induced sleep endoscopy in the diagnosis and management of pediatric obstructive sleep apnea. METHODS: The leadership group identified experts based on defined criteria and invited 18 panelists to participate in the consensus statement development group. A modified Delphi process was used to formally quantify consensus from opinion. A modified Delphi priori process was established, which included a literature review, submission of statements by panelists, and an iterative process of voting to determine consensus. Voting was based on a 9-point Likert scale. Statements achieving a mean score greater than 7 with one or fewer outliers were defined as reaching consensus. Statements achieving a mean score greater than 6.5 with two or fewer outliers were defined as near consensus. Statements with lower scores or more outliers were defined as no consensus. RESULTS: A total of 78 consensus statements were evaluated by the panelists at the first survey - 49 achieved consensus, 18 achieved near consensus, and 11 did not achieve consensus. In the second survey, 16 statements reached consensus and 5 reached near consensus. Regarding scoring, consensus was achieved on the utilization of a 3-point Likert scale for each anatomic site for maximal observed obstructions of <50% (Score 0, no-obstruction), ≥ 50% but <90% (Score 2, partial obstruction), and ≥ 90% (Score 3, complete obstruction). Anatomic sites to be scored during DISE that reached consensus or near-consensus were the nasal passages, adenoid pad, velum, lateral pharyngeal walls, tonsils (if present), tongue base, epiglottis, and arytenoids. CONCLUSION: This study developed consensus statements on the scoring of DISE in pediatric otolaryngology using a modified Delphi process. The use of a priori process, literature review, and iterative voting method allowed for the formal quantification of consensus from expert opinion. The results of this study may provide guidance for standardizing scoring of DISE in pediatric patients.

Pulmonary function in patients with transfusion-dependent thalassemia and its associations with iron overload.

In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.

Level of urinary catecholamine in children with Sleep Disordered Breathing: A systematic review and meta-analysis.

OBJECTIVE: To compare the levels of different urinary catecholamines amongst paediatric patients with and without sleep-disordered breathing (SDB). METHODS: Literature searches were conducted on PubMed and EMBASE until 25/06/2022. Inclusion criteria were original human studies, English language, paediatric subjects diagnosed with SDB/obstructive sleep apnoea (OSA). The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The registered number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42022332939. The main outcome measured was standardised mean difference (SMD) of urinary catecholamine between subjects with and without SDB, between those with and without OSA, and also between subjects with mild OSA and those with moderate/ severe OSA. Sensitivity analyses were performed to avoid bias. RESULTS: 9 studies (8 cross-sectional and 1 cohort study) with a total of 838 subjects, were included in the quantitative analysis. Urine level of noradrenaline was higher in patients with SDB, which included primary snoring (PS), when compared to controls: SMD = 0.86 (95%CI=0.32-1.41; I2=85%, P=0.002). The levels of urinary noradrenaline and adrenaline were higher in children with OSA when compared to controls: SMD = 1.45 (95%CI=0.91-2.00; I2=75%, P < 0.001); SMD = 1.84 (0.00-3.67; I2=97%, P=0.05). Urine level of noradrenaline was higher in subjects with moderate/severe OSA compared to the mild OSA: SMD = 0.55 (95%CI=0.10-1.00; I2=0%, P=0.02). Urinary dopamine was not associated with SDB regardless of severity. CONCLUSIONS: Urinary noradrenaline was higher in all patients with SDB. Subjects with OSA, a more severe form of SDB, had higher urine levels of noradrenaline and adrenaline. Hence, noradrenaline and adrenaline may be markers of sympathetic overtone in patients with SDB and could potentially act as surrogate markers for SDB complications. Further studies are needed to assess this association.

Inferior endothelial function improved following optimisation of asthma control in children.

Association between asthma control and cardiovascular disease (CVD) remains highly plausible as the two are related to chronic systemic inflammation. Children with physician-diagnosed asthma and matched healthy controls underwent endothelial function assessment. Repeat measurements were performed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS), compared to those with well-controlled asthma without ICS therapy. We found that children with uncontrolled asthma had inferior endothelial function compared to matched healthy controls. Enhancement in endothelial function, lung function and symptom control was observed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS). These results provided further evidence of a likely relationship between asthma control and cardiovascular health.

Validation of the Sonographic Measurement of Lateral Parapharyngeal Wall Thickness in Childhood Obstructive Sleep Apnea.

Background: Lateral parapharyngeal wall (LPW) thickness is a potentially useful anatomical marker of childhood obstructive sleep apnea (OSA). Measuring LPW thickness by ultrasonography (USG) is technically feasible but its use in children has not been validated. Therefore, this study aimed to assess the intra- and inter-operator reliability of the sonographic measurements of LPW thickness in children and to assess its validity against magnetic resonance imaging (MRI) measurements. Methods: Prepubertal children aged 6-11 years suspected to suffer from OSA were recruited. Repeated measurements of LPW thickness by USG were conducted to evaluate the intra- and inter-operator reliability, examined by intraclass correlation coefficient (ICC). LPW thickness was measured as the distance between the internal carotid artery and the echogenic surface of the pharynx in an oblique coronal plane by USG. LPW thickness was measured by MRI at the retropalatal level. The agreement between the LPW thickness measured by USG and MRI was assessed by ICC and Bland-Altman plot. Results: Thirty-four children (mean age: 8.66 ± 1.61, 26 male) were recruited. The intra- and inter-operator reliability of the LPW thickness by USG was good (ICC = 0.84 and 0.82, respectively). The agreement between the USG-measured and MRI-measured LPW thickness was moderate (ICC = 0.72). he Bland-Altman plot demonstrated a mean difference of 0.061 cm and a 95% limit of agreement from 0.91 to 1.12 cm. Conclusion: In this study, we demonstrated that ultrasonography is a valid and reliable method to assess LPW thickness in children. This study was supported by the Direct Grant for Research from the Research Committee of the Chinese University of Hong Kong (Project no. 2020.073).

Mucosal Antibody Response to SARS-CoV-2 in Paediatric and Adult Patients: A Longitudinal Study.

BACKGROUND: SARS-CoV-2 enters the body through inhalation or self-inoculation to mucosal surfaces. The kinetics of the ocular and nasal mucosal-specific-immunoglobulin A(IgA) responses remain under-studied. METHODS: Conjunctival fluid (CF, n = 140) and nasal epithelial lining fluid (NELF, n = 424) obtained by paper strips and plasma (n = 153) were collected longitudinally from SARS-CoV-2 paediatric (n = 34) and adult (n = 47) patients. The SARS-CoV-2 spike protein 1(S1)-specific mucosal antibody levels in COVID-19 patients, from hospital admission to six months post-diagnosis, were assessed. RESULTS: The mucosal antibody was IgA-predominant. In the NELF of asymptomatic paediatric patients, S1-specific IgA was induced as early as the first four days post-diagnosis. Their plasma S1-specific IgG levels were higher than in symptomatic patients in the second week after diagnosis. The IgA and IgG levels correlated positively with the surrogate neutralization readout. The detectable NELF "receptor-blocking" S1-specific IgA in the first week after diagnosis correlated with a rapid decline in viral load. CONCLUSIONS: Early and intense nasal S1-specific IgA levels link to a rapid decrease in viral load. Our results provide insights into the role of mucosal immunity in SARS-CoV-2 exposure and protection. There may be a role of NELF IgA in the screening and diagnosis of SARS-CoV-2 infection.

Iron status of full-term infants in early infancy is not associated with maternal ferritin levels nor infant feeding practice.

Iron deficiency (ID) in early life is associated with morbidities. Most fetal iron required for infant growth is acquired in the third trimester from maternal iron store. However, how prenatal iron level affects ferritin level in early infancy remains controversial. This study aimed to examine the associations between maternal ferritin levels and cord blood serum ferritin (CBSF) and to compare the ferritin levels between different feeding practices in early infancy. Healthy Chinese mothers with uncomplicated pregnancy and their infants were followed up at 3 months post-delivery for questionnaire completion and infant blood collection. Infants who were predominantly breastfed and those who were predominantly formula fed were included in this analysis. Serum ferritin levels were measured in maternal blood samples collected upon delivery, cord blood and infant blood samples at 3 months of age. Ninety-seven mother-baby dyads were included. Maternal ID is common (56 %) while the CBSF levels were significantly higher than maternal ferritin levels. Only three infants (3 %) had ID at 3 months of age. There were no significant correlations between maternal ferritin levels with CBSF (r 0·168, P = 0·108) nor with infant ferritin levels at 3 months of age (r 0·023, P = 0·828). Infant ferritin levels at 3 months were significantly and independently associated with CBSF (P = 0·007) and birth weight (P < 0·001) after adjusting for maternal age, parity, maternal education, infant sex and feeding practice. In conclusion, maternal ID was common upon delivery. However, maternal ferritin levels were not significantly associated with CBSF concentrations nor infant ferritin concentrations at 3 months of age.

Natural History of REM-OSA in Children and Its Associations with Adverse Blood Pressure Outcomes: A Longitudinal Follow-Up Study.

PURPOSE: Most respiratory events in childhood obstructive sleep apnea (OSA) take place during rapid-eye-movement (REM) sleep. This study aimed to describe the characteristics and natural history of childhood REM-OSA and to evaluate the associations between OSA subtypes and blood pressure (BP) outcomes. PARTICIPANTS AND METHODS: This was a prospective 10-year follow-up study of a cohort established for a childhood OSA epidemiologic study. All subjects from the original cohort were invited to undergo a polysomnography (PSG) and 24-hour ambulatory blood pressure (ABP) monitoring. REM-OSA was defined with a ratio of obstructive apnea hypopnea index (OAHI) during REM sleep (OAHIREM) to OAHI during non-REM sleep (OAHINREM) ≥ 2. Natural history was observed and linear mixed models were used to assess the associations between OSA subtypes and BP outcomes. RESULTS: A total of 610 participants from baseline were included to study the epidemiology of REM-OSA in childhood. Among children with OSA, 65% had REM-OSA. At 10-year follow-up, 234 were included in the analysis. REM-OSA was more common at both baseline (58/92, 63%) and 10-year follow-up (34/58, 59%). For those with REM-OSA at baseline and persistent OSA at follow-up, the majority (72%) remained to have REM-OSA. Compared to those without OSA, subjects with REM-OSA had significantly higher nocturnal SBP (mean difference 2.19 mmHg, 95% confidence interval (CI): 0.12, 4.26; p = 0.039) and DBP (mean difference 1.58 mmHg, 95% confidence interval (CI): 0.11, 3.04; p = 0.035), and less nocturnal SBP dipping (mean difference -1.84%, 95% CI: -3.25, -0.43; p = 0.011), after adjusting for potential confounders. This significant association between REM-OSA and nocturnal SBP dipping was observed at baseline visit only. CONCLUSION: REM-OSA was found to be a stable phenotype through childhood to young adulthood, and REM-OSA was associated with higher nocturnal BP and a lesser degree of nocturnal SBP dipping in children.

The Mucosal and Serological Immune Responses to the Novel Coronavirus (SARS-CoV-2) Vaccines.

Background: Although the serological antibody responses induced by SARS-CoV-2 vaccines are well characterized, little is known about their ability to elicit mucosal immunity. Objectives: This study aims to examine and compare the mucosal and systemic responses of recipients of two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac). Methods: Serial blood and nasal epithelial lining fluid (NELF) samples were collected from the recipients of either Comirnaty or CoronaVac. The plasma and NELF immunoglobulins A and G (IgA and IgG) specific to SARS-CoV-2 S1 protein (S1) and their neutralization effects were quantified. Results: Comirnaty induced nasal S1-specific immunoglobulin responses, which were evident as early as 14 ± 2 days after the first dose. In 64% of the subjects, the neutralizing effects of NELF persisted for at least 50 days. Moreover, 85% of Comirnaty recipients exhibited S1-specific IgA and IgG responses in plasma by 14 ± 2 days after the first dose. By 7 ± 2 days after the booster, all plasma samples possessed S1-specific IgA and IgG responses and were neutralizing. The induction of S1-specific plasma antibodies by CoronaVac was IgG dominant, and 83% of the subjects possessed S1-specific IgG by 7 ± 2 days after the booster, with neutralizing effects. Conclusion: Comirnaty induces S1-specific IgA and IgG responses with neutralizing activity in the nasal mucosa; a similar response is not seen with CoronaVac. Clinical Implication: The presence of a nasal response with mRNA vaccine may provide additional protection compared with inactivated virus vaccine. However, whether such widespread immunological response may produce inadvertent adverse effects in other tissues warrants further investigation.

Impact of Snoring on Telomere Shortening in Adolescents with Atopic Diseases.

Atopic diseases can impose a significant burden on children and adolescents. Telomere length is a cellular marker of aging reflecting the impact of cumulative stress exposure on individual health. Since elevated oxidative stress and inflammation burden induced by chronic atopy and snoring may impact telomere length, this study aimed to investigate whether snoring would moderate the relationship between atopic diseases and telomere length in early adolescence. We surveyed 354 adolescents and their parents. Parents reported the adolescents' history of atopic diseases, recent snoring history as well as other family sociodemographic characteristics. Buccal swab samples were also collected from the adolescents for telomere length determination. Independent and combined effects of atopic diseases and snoring on telomere length were examined. Among the surveyed adolescents, 174 were reported by parents to have atopic diseases (20 had asthma, 145 had allergic rhinitis, 53 had eczema, and 25 had food allergy). Shorter TL was found in participants with a history of snoring and atopic diseases (ß = -0.34, p = 0.002) particularly for asthma (ß = -0.21, p = 0.007) and allergic rhinitis (ß = -0.22, p = 0.023). Our findings suggest that snoring in atopic patients has important implications for accelerated telomere shortening. Proper management of atopic symptoms at an early age is important for the alleviation of long-term health consequences at the cellular level.

Effect of surgical intervention for mild childhood obstructive sleep apnoea on attention and behavioural outcomes: A randomized controlled study.

BACKGROUND AND OBJECTIVE: We evaluated inattention and behavioural outcomes following surgery versus watchful waiting (WW) in school-aged children with mild obstructive sleep apnoea (OSA). METHODS: A prospective randomized controlled study was performed in pre-pubertal children aged 6-11 years with polysomnography (PSG)-confirmed mild OSA. They were assigned randomly to early surgical intervention (ES) or WW. The surgical intervention consisting of tonsillectomy with or without adenoidectomy and turbinate reduction was carried out within 4-6 weeks after randomization. Both groups underwent PSG, attention and behavioural assessment and review by an otorhinolaryngologist at baseline and 9-month follow-up. The primary outcome was omission T score from Conners' continuous performance test (CPT). Secondary outcomes were parent-reported behaviours, quality of life, symptoms and PSG parameters. RESULTS: A total of 114 participants were randomized. Data of 35 subjects from the ES and 36 from the WW group were available for final analysis. No significant treatment effect could be found in all CPT parameters and behavioural outcomes. Nevertheless, significantly greater reductions were seen in PSG parameters (obstructive apnoea-hypopnoea index [-1.4 ± 2.0 cf. +0.3 ± 4.1/h, p = 0.038] and arousal index [-1.3 ± 4.4 cf. +1.4 ± 4.5/h, p = 0.013]) and OSA-18 total symptom score (-17.3 ± 19.7 cf. -3.6 ± 14.1, p = 0.001) in the ES group. Subjects who underwent surgery also had significantly greater weight gain (+3.3 ± 2.1 cf. +2.2 ± 1.5 kg, p = 0.014) and increase in systolic blood pressure (+5.1 ± 12.4 cf. -1.2 ± 8.7 mm Hg, p = 0.016). CONCLUSION: Despite improvements in PSG parameters and parent-reported symptoms, surgical treatment did not lead to parallel improvements in objective attention measures in school-aged children with mild OSA.

Childhood bronchiolitis obliterans in Hong Kong-case series over a 20-year period.

BACKGROUND AND OBJECTIVE: Bronchiolitis obliterans (BO) is a rare but serious condition. The natural history and outcomes remain poorly understood. In this clinical review, we aimed to describe the clinical characteristics and outcomes of children diagnosed with BO in Hong Kong (HK). METHODS: This was a retrospective study of pediatric patients with BO under the care of six respiratory units in HK from January 1996 to December 2015. Information was retrieved from medical records. RESULTS: Fifty-six patients were included with a male predominance (67.9%). The median age at diagnosis was 1.98 years (interquartile range [IQR]: 0.84-4.99 years). Postinfectious BO (PIBO) was the commonest cause (64.3%) followed by posthematopoietic stem-cell transplant (21.4%). Adenovirus (63.2%) was the commonest causative pathogen among PIBO. The median follow-up duration was 9.7 years (IQR: 2.9-14.3 years). Twenty-five patients (44.6%) could achieve symptom-free recovery at the time of follow-up. Five (8.9%) and three (5.4%) were oxygen or ventilator dependent, respectively. There were two deaths, both had posttransplant BO. Patients who developed BO after transplant had significantly worse lung function than those with PIBO. There were no risk factors significantly associated with worse clinical outcomes (oxygen/ventilator dependence or death) by logistic regression. Among patients with PIBO, coinfection at presentation was significantly associated with persistent symptoms at follow-up (p = .028). CONCLUSIONS: The most common cause of childhood BO in HK is postinfectious and coinfection at presentation was associated with persistent symptoms at follow-up. Further studies are needed to better elucidate disease progression, treatment options and long term outcomes.

Economic evaluation of the introduction of rotavirus vaccine in Hong Kong.

BACKGROUND: Rotavirus is a common cause of severe gastroenteritis in young children in Hong Kong (HK) with a high economic burden. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into the HK Government's Childhood Immunisation Programme (CIP) and to include the potential protective effect of the vaccine against seizures. METHODS: A decision-support model was customised to estimate the potential impact, cost-effectiveness and benefit-risk of rotavirus vaccination in children below 5 years over the period 2020-2029 in HK. Two doses of Rotarix® and three doses of RotaTeq® were each compared to no vaccination. Rotavirus treatment costs were calculated from a governmental health sector perspective (i.e., costs of public sector treatment) and an overall health sector perspective (both governmental and patient, i.e., costs of public sector treatment, private sector treatment, transport and diapers). We ran probabilistic and deterministic uncertainty analyses. RESULTS: Introduction of rotavirus vaccination in HK could prevent 49,000 (95% uncertainty interval: ~44,000-54,000) hospitalisations of rotavirus gastroenteritis and seizures and result in ~50 (95% uncertainty interval: ~25-85) intussusception hospitalisations, over the period 2020-2029 (a benefit-risk ratio of ~1000:1), compared to a scenario with no public or private sector vaccine use. The discounted vaccination cost would be US$51-57 million over the period 2020-2029 based on per-course prices of US$72 (Rotarix®) or US$78 (RotaTeq®), but this would be offset by discounted treatment cost savings of US$70 million (government) and US$127 million (governmental and patient health sector). There was a greater than 94% probability that the vaccine could be cost-saving irrespective of the vaccine product or perspective considered. All deterministic 'what-if' scenarios were cost-saving from an overall health sector perspective (governmental and patient). CONCLUSIONS: Rotavirus vaccination is likely to be cost-saving and have a favourable benefit-risk profile in HK. Based on the assumptions made, our analysis supports its introduction into CIP.