Lung Ultrasound for Infants' Swallowing Disorders (LUNCH)

Lung Ultrasound for Early Detection of Silent and Apparent aspiratioN in Infants and Young CHildren With Cerebral Palsy and Other Developmental Disabilities: a New Fast, Safe, Cost-effective Infant-friendly Imaging Tool to Easily Monitor Feeding , Improve Outcomes and Reduce Morbidities (LUNCH)

The aim is to test the effectiveness of lung ultrasound (LUS) in the dynamic assessment of aspiration related to abnormal swallowing in infants and young children with neurological impairment (cerebral palsy/developmental disabilities). Neither standardized measure is available, nor protocols for invasive fibre-optic endoscopic examination of swallowing (FEES) and x-Ray videofluoroscopic swallowing study (VFSS) to be used in such population. LUS offers several advantages: time saving for aspiration diagnosis; safeness (neither invasiveness nor radiation); repeatability with different meal consistencies or to monitor interventions efficacy; cost-effectiveness; savings of x-Ray exposition (compared to VFSS). All these advantages may lead infants to improve clinical behavioural and neurological outcomes and reduce stressful interactions with caregivers, and to reduce morbidities and hospitalization costs for respiratory and non-respiratory complications related to swallowing disorders.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Palsy; Developmental Disability; Pediatric Neurological Disorder
• Intervention / Treatment: Diagnostic test: Lung Ultrasound (LUS)-monitored feeding trial

Detailed Description

The dynamic use of LUS for monitoring feeding related aspiration can be effective in detecting meal-related pulmonary abnormalities in neurologically impaired infants and that LUS-management will improve medical/neurological/behavioural status, and reduce chronic pain/discomfort and stress for caregivers. LUS effectiveness is expected to reduce the need for x-Ray, invasive and more expensive techniques (VFSS and FEES). Results may be translated into clinical practice in the management of swallowing disorders in a very vulnerable population, by reducing invasiveness, possible x-Ray early exposition risks, costs, medical complications, and by assessing risk categories based on neuroimaging MRI markers, to rationalize prevention and intervention.

Preliminary data. LUS examinations have been performed on 6 infants with neurological impairment (mean age 15 ± 8 months; Gross Motor Function Classification System (GMFCS) range 2-5, median=4) and in 3 healthy infants (mean age 25 ± 3 months) before and right after a meal. A LUS score ranging from 0 to 18 was established, according to previous literature (0= normal pattern, 1= separated B-lines, 2= confluent B-lines or B-lines with pleural alterations, 3= consolidations; the score 0-3 was then calculated in all 6 thoracic scanning areas and summed up). In the 6 infants with neurological impairment, at paired sample t test, LUS score changed before and after meal (pre-meal 2.50±2.95 vs post-meal 5.17±3.25, p=0.01), with very large effect size (Cohen d=1.6). No change was detected in the control group. Changes in LUS score pre and post-meal correlated with GMFCS (p=0.03, r=0.64) and with adapted Eating and Drinking Ability Classification System (EDACS) scores (p=0.04, r=0.59), as more severe clinical pictures resulted in worse LUS scores. The LUS score pre- meal was worse in infants with neurological impairment compared to controls (2.50±2.95 vs 0.67±0.58, p=0.14). Results make LUS extremely promising as a tool to monitor pulmonary aeration changes in infants with neurological impairment. Feasibility of dorsal and ventral oromotor tract reconstruction has been tested in an infant with neurological impairment.

Specific Aim 1:

• To establish the feasibility and effectiveness of LUS-guided management in the detection of aspiration related to swallowing disorders in children with cerebral palsy and other developmental disabilities, determining advantages of LUS-guided management over standard care on medical (respiratory illness and growth rate) LUS findings themselves and behavioural/neurological outcomes
• To compare diagnostic accuracy of LUS versus X-ray VFSS and invasive FEES

Specific Aim 2:

- To determine specific parameters to estimate aspiration entity by LUS (eg cut-off values for the diagnosis of clinically significant silent or overt aspiration, responsiveness of LUS monitoring to medical, postural or food consistencies adaptation) and their relationship with standardised clinical feeding evaluation and medical/behavioural/neurological measures in order to define risk groups for aspiration

Specific Aim 3:

• To evaluate other applications/potentialities of LUS in children with cerebral palsy and other developmental disabilities.
• To uncover the impact of brain abnormalities detected by brain MRI on LUS findings, for establishing risk categories for unsafe swallowing disorders on early imaging markers, and potential clinical recommendations for early management.

Experimental Design Aim 1:

Double-blinded randomized parallel-designed controlled trial (Consort checklist), with block randomization (blocks of size 4), in one of 2 groups: 1) LUS-monitored management (LUS-m); 2) Standard care management (SC-m). Both groups will undergo an experimental 6-months follow-up. In the first 3 months, participants will be evaluated a minimum of 1 time per month, in-hospital, for a total of 3 evaluations (T1, T2 and T3), plus baseline (T0). At any time point, they will undergo at least one LUS-monitored (before and after) feeding trial (different consistencies might be tested in separate repeated trials according to clinical evaluation). A further LUS evaluation will be performed at a distance of 3 hours, before the next meal to check for resolution of after-meal abnormalities. Both the clinicians who will perform and score LUS, and the patients' family will be blinded to randomization. The child neurologist and the speech and language pathologist (SLP) will be informed of the result of LUS only in the LUS-m group and will include that result to impact on feeding care (postural, thickening fluids or with drugs available for GERD). LUS results in the SC-m group will be available only at the time of data analyses. All meals will be monitored by pulse-oximetry and video recording. A further 6-months LUS-monitored and clinical assessment (T4) will be delivered for collecting outcome measures in both treatment groups. At T0, T3 and T4 time points, infants will perform standardized medical/behavioural/neurological, chronic pain/discomfort assessments. At T0 and T4, a blood sample will be collected, to evaluate general and nutritional status, and a quantitative ultrasound (QUS) will be performed to evaluate bone density. A parent stress questionnaire (Parenting Stress Index (PSI)) will be delivered (T0, T3 and T4). Between T0 and T4, parents will be asked to fill a respiratory infection-diary for respiratory illness rate calculation. VFSS and FEES data will be collected, compared in frequency of execution between groups, and their results will be compared to LUS findings. Primary and secondary outcome measures will be collected at both T3 (short-term) and T4 (long-term).

Experimental Design Aim 2:

Aim 2 is based on the same design as Aim 1. We will explore the frequency, severity and distribution of basal and feeding related LUS parameters and their relationship with clinical (feeding assessment/medical/behavioural/neurological/chronic pain) measures, interventions (postural, thickening fluids or with drugs available for GERD), inter- and intra- group at any time point.

Other possible applications of LUS in the enrolled population will be collected (e.g. pneumonia detection and monitoring).

Experimental Design Aim 3:

Brain MRI is a clinical procedure in the diagnostic approach to children with neurological impairment. Brain abnormalities and corticobulbar tract integrity for lips, tongue, larynx motor and sensory control will be checked to uncover the neural circuits that may underlay swallowing problems leading to silent or overt aspiration and pulmonary risk estimated by LUS. Brain lesions topography and severity will be assessed by using a standardized MRI acquisition protocol according to the diagnostic procedure in use at Stella Maris Scientific Institute MRI Lab. Diffusion-weighted Imaging (DWI) will be used with the aim of revealing structural integrity and connectivity along white matter tracts involved in swallowing.

Expected outcomes:

the LUS-m group having better outcomes, at short- and long-term, including: having lower rate of pulmonary illness, better growth curve, reduction of execution rate of VFSS/FEES. Also, better results at blood sample and bone metabolism, lower pain indices, better scores at neurological/behavioural clinical measures, and less stressful interaction with caregivers.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simona Fiori, MD, PhD; Phone Number: 0039 050886310; Email: s.fiori@fsm.unipi.it
• Study Contact Backup: Name: Elena Moretti, SLP; Phone Number: 0039 050886310; Email: e.moretti@fsm.unipi.it

Study Locations

• Italy
  • Pisa, Italy, 56128
    • Not yet recruiting
    • IRCCS Fondazione Stella Maris
    • Contact: Simona Fiori, MD, PhD; Phone Number: 0039 050886310; Email: s.fiori@fsm.unipi.it
    • Contact: Giovanni Cioni, MD; Phone Number: 0039 050886229; Email: dirscient@fsm.unipi.it
  • Toscana
    • Marina di Pisa-Tirrenia-Calambrone, Toscana, Italy, 56128
      • Recruiting
      • IRCCS Fondazione Stella Maris
      • Contact: Giovanni Cioni; Phone Number: 050886233; Email: gcioni@fsm.unipi.it
      • Contact: Giuseppina Sgandurra; Email: gsgandurra@fsm.unipi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 weeks to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• cerebral palsy or abnormal muscular tone at any age between 0-3 years of life due disorders other than cerebral palsy;
• motor developmental delay assessed by a quantitative scale for infants and young children development (<5 sd according to age)
• in absence of the previous clinical indices, if there is the clinical suspicion of GERD or dysphagia based on clinical symptoms
• a brain MRI acquisition done before or programmed prior the end of the study period as part of their diagnostic procedure.

Exclusion Criteria:

• epileptic spasm
• drugs for muscle tone abnormalities or GERD introduced or modified less than 3 weeks before potential enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LUS-monitored management (LUS-m); In the first 3 months, participants will be evaluated a minimum of 1 time per month, in-hospital, for a total of 3 evaluations (T1, T2 and T3), plus baseline (T0). At any time point, they will undergo at least one LUS-monitored (before and after) feeding trial (different consistencies might be tested in separate repeated trials according to clinical evaluation). A further LUS evaluation will be performed at a distance of 3 hours, before the next meal to check for resolution of after-meal abnormalities.	Diagnostic test: Lung Ultrasound (LUS)-monitored feeding trial; LUS-monitored (before and after) feeding trial (different consistencies might be tested in separate repeated trials according to clinical evaluation). A further LUS evaluation will be performed at a distance of 3 hours, before the next meal to check for resolution of after-meal abnormalities. All pulmonary fields will be explored according to semeiotics and previous literature.
Sham Comparator: Standard care management (SC-m); Sham protocol with LUS performed at the same timepoints. LUS results in the SC-m group will be available only at the time of data analyses for comparison by investigators. They will not be used for clinical decisions.	Diagnostic test: Lung Ultrasound (LUS)-monitored feeding trial; LUS-monitored (before and after) feeding trial (different consistencies might be tested in separate repeated trials according to clinical evaluation). A further LUS evaluation will be performed at a distance of 3 hours, before the next meal to check for resolution of after-meal abnormalities. All pulmonary fields will be explored according to semeiotics and previous literature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
respiratory	respiratory illness rate (including pneumonia, wheezing, chronic cough, and apnoea rate)	long term (T4, at 6 months)
respiratory	respiratory illness rate (including pneumonia, wheezing, chronic cough, and apnoea rate)	short term (T3, at 3 months)
growth	growth rate	long term (T4, at 6 months)
growth	growth rate	short term (T3, at 3 months)
invasive diagnostic	VFSS/FEES execution rates	long term (T4, at 6 months)
invasive diagnostic	VFSS/FEES execution rates	short term (T3, at 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline laboratory exam at 6 months	blood cells count	baseline-long term (T4, at 6 months)
change from baseline laboratory exam at 6 months	reticulocytes count	baseline-long term (T4, at 6 months)
change from baseline laboratory exam at 6 months	total serum protein	baseline- long term (T4, at 6 months)
change from baseline laboratory exam at 6 months	ferritin	baseline- long term (T4, at 6 months)
chronic pain assessment	parents-report measure (Non-communicating Children's Pain Checklist, NCCPC), with scores ranging from 0 to 90, with higher scores corresponding to worse outcome	short term (T3, at 3 months)
chronic pain assessment	parents-report measure (Non-communicating Children's Pain Checklist, NCCPC), with scores ranging from 0 to 90, with higher scores corresponding to worse outcome	long term (T4, at 6 months)
parents' stress	Parenting Stress Index questionnaire (PSI), with scores ranging from 0 to 120 including 4 domains, with higher scores corresponding to worse outcome	long term (T4, at 6 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
neurological outcome	Hammersmith Infant Neurological Examination (HINE), with scores ranging from 0 to 78, with higher scores corresponding to better outcome	short term (T3, at 3 months) and long term (T4, at 6 months)

Collaborators and Investigators

• Sponsor: IRCCS Fondazione Stella Maris
• Collaborators: University of Pisa; Ministry of Health, Italy; Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
• Investigators: Principal Investigator: Simona Fiori, MD, PhD, IRCCS Fondazione Stella Maris

Publications and helpful links

General Publications

• Volpicelli G, Elbarbary M, Blaivas M, Lichtenstein DA, Mathis G, Kirkpatrick AW, Melniker L, Gargani L, Noble VE, Via G, Dean A, Tsung JW, Soldati G, Copetti R, Bouhemad B, Reissig A, Agricola E, Rouby JJ, Arbelot C, Liteplo A, Sargsyan A, Silva F, Hoppmann R, Breitkreutz R, Seibel A, Neri L, Storti E, Petrovic T; International Liaison Committee on Lung Ultrasound (ILC-LUS) for International Consensus Conference on Lung Ultrasound (ICC-LUS). International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012 Apr;38(4):577-91. doi: 10.1007/s00134-012-2513-4. Epub 2012 Mar 6.
• Erasmus CE, van Hulst K, Rotteveel JJ, Willemsen MA, Jongerius PH. Clinical practice: swallowing problems in cerebral palsy. Eur J Pediatr. 2012 Mar;171(3):409-14. doi: 10.1007/s00431-011-1570-y. Epub 2011 Sep 20.
• Gargani L, Volpicelli G. How I do it: lung ultrasound. Cardiovasc Ultrasound. 2014 Jul 4;12:25. doi: 10.1186/1476-7120-12-25.
• Srivastava R, Jackson WD, Barnhart DC. Dysphagia and gastroesophageal reflux disease: dilemmas in diagnosis and management in children with neurological impairment. Pediatr Ann. 2010 Apr;39(4):225-31. doi: 10.3928/00904481-20100318-07. No abstract available.
• Fitzgerald DA, Follett J, Van Asperen PP. Assessing and managing lung disease and sleep disordered breathing in children with cerebral palsy. Paediatr Respir Rev. 2009 Mar;10(1):18-24. doi: 10.1016/j.prrv.2008.10.003. Epub 2009 Jan 23.
• Arvedson J, Rogers B, Buck G, Smart P, Msall M. Silent aspiration prominent in children with dysphagia. Int J Pediatr Otorhinolaryngol. 1994 Jan;28(2-3):173-81. doi: 10.1016/0165-5876(94)90009-4.
• Blackmore AM, Bear N, Blair E, Gibson N, Jalla C, Langdon K, Moshovis L, Steer K, Wilson AC. Factors Associated with Respiratory Illness in Children and Young Adults with Cerebral Palsy. J Pediatr. 2016 Jan;168:151-157.e1. doi: 10.1016/j.jpeds.2015.09.064. Epub 2015 Oct 29.
• Pillai Riddell RR, Stevens BJ, McKeever P, Gibbins S, Asztalos L, Katz J, Ahola S, Din L. Chronic pain in hospitalized infants: health professionals' perspectives. J Pain. 2009 Dec;10(12):1217-25. doi: 10.1016/j.jpain.2009.04.013. Epub 2009 Jun 21.
• Benfer KA, Weir KA, Boyd RN. Clinimetrics of measures of oropharyngeal dysphagia for preschool children with cerebral palsy and neurodevelopmental disabilities: a systematic review. Dev Med Child Neurol. 2012 Sep;54(9):784-95. doi: 10.1111/j.1469-8749.2012.04302.x. Epub 2012 May 14. Erratum In: Dev Med Child Neurol. 2018 Jun;60(6):630.
• van den Engel-Hoek L, Erasmus CE, van Hulst KC, Arvedson JC, de Groot IJ, de Swart BJ. Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study. J Child Neurol. 2014 May;29(5):646-53. doi: 10.1177/0883073813501871. Epub 2013 Sep 9.
• Calvo I, Conway A, Henriques F, Walshe M. Diagnostic accuracy of the clinical feeding evaluation in detecting aspiration in children: a systematic review. Dev Med Child Neurol. 2016 Jun;58(6):541-53. doi: 10.1111/dmcn.13058. Epub 2016 Feb 9.
• Cichero J, Nicholson T, Dodrill P. Liquid barium is not representative of infant formula: characterisation of rheological and material properties. Dysphagia. 2011 Sep;26(3):264-71. doi: 10.1007/s00455-010-9303-3. Epub 2010 Sep 10.
• Novak I, Morgan C, Adde L, Blackman J, Boyd RN, Brunstrom-Hernandez J, Cioni G, Damiano D, Darrah J, Eliasson AC, de Vries LS, Einspieler C, Fahey M, Fehlings D, Ferriero DM, Fetters L, Fiori S, Forssberg H, Gordon AM, Greaves S, Guzzetta A, Hadders-Algra M, Harbourne R, Kakooza-Mwesige A, Karlsson P, Krumlinde-Sundholm L, Latal B, Loughran-Fowlds A, Maitre N, McIntyre S, Noritz G, Pennington L, Romeo DM, Shepherd R, Spittle AJ, Thornton M, Valentine J, Walker K, White R, Badawi N. Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment. JAMA Pediatr. 2017 Sep 1;171(9):897-907. doi: 10.1001/jamapediatrics.2017.1689. Erratum In: JAMA Pediatr. 2017 Sep 1;171(9):919.
• Uhm KE, Yi SH, Chang HJ, Cheon HJ, Kwon JY. Videofluoroscopic swallowing study findings in full-term and preterm infants with Dysphagia. Ann Rehabil Med. 2013 Apr;37(2):175-82. doi: 10.5535/arm.2013.37.2.175. Epub 2013 Apr 30.
• Raimondi F, Migliaro F, Sodano A, Umbaldo A, Romano A, Vallone G, Capasso L. Can neonatal lung ultrasound monitor fluid clearance and predict the need of respiratory support? Crit Care. 2012 Nov 14;16(6):R220. doi: 10.1186/cc11865.
• Raimondi F, Migliaro F, Sodano A, Ferrara T, Lama S, Vallone G, Capasso L. Use of neonatal chest ultrasound to predict noninvasive ventilation failure. Pediatrics. 2014 Oct;134(4):e1089-94. doi: 10.1542/peds.2013-3924. Epub 2014 Sep 1.
• Balk DS, Lee C, Schafer J, Welwarth J, Hardin J, Novack V, Yarza S, Hoffmann B. Lung ultrasound compared to chest X-ray for diagnosis of pediatric pneumonia: A meta-analysis. Pediatr Pulmonol. 2018 Aug;53(8):1130-1139. doi: 10.1002/ppul.24020. Epub 2018 Apr 26.
• Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR Am J Roentgenol. 2001 Feb;176(2):289-96. doi: 10.2214/ajr.176.2.1760289.
• Goh YR, Choi JY, Kim SA, Park J, Park ES. Comparisons of severity classification systems for oropharyngeal dysfunction in children with cerebral palsy: Relations with other functional profiles. Res Dev Disabil. 2018 Jan;72:248-256. doi: 10.1016/j.ridd.2017.12.002. Epub 2017 Dec 7.
• Pandis N, Chung B, Scherer RW, Elbourne D, Altman DG. CONSORT 2010 statement: extension checklist for reporting within person randomised trials. BMJ. 2017 Jun 30;357:j2835. doi: 10.1136/bmj.j2835.
• Liegeois FJ, Butler J, Morgan AT, Clayden JD, Clark CA. Anatomy and lateralization of the human corticobulbar tracts: an fMRI-guided tractography study. Brain Struct Funct. 2016 Jul;221(6):3337-45. doi: 10.1007/s00429-015-1104-x. Epub 2015 Sep 28.
• O'Rourke D. The measurement of pain in infants, children, and adolescents: from policy to practice. Phys Ther. 2004 Jun;84(6):560-70. No abstract available.
• Bouhemad B, Mongodi S, Via G, Rouquette I. Ultrasound for "lung monitoring" of ventilated patients. Anesthesiology. 2015 Feb;122(2):437-47. doi: 10.1097/ALN.0000000000000558. No abstract available.
• Fiori S, Scaramuzzo RT, Moretti E, Amador C, Controzzi T, Martinelli A, Filippi L, Guzzetta A, Gargagni L. LUNCH-Lung Ultrasound for early detection of silent and apparent aspiratioN in infants and young CHildren with cerebral palsy and other developmental disabilities: study protocol of a randomized controlled trial. BMC Pediatr. 2022 Jun 23;22(1):360. doi: 10.1186/s12887-022-03413-z.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Anticipated): September 15, 2023
• Study Completion (Anticipated): December 15, 2023

Study Registration Dates

• First Submitted: January 30, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 20, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: lung ultrasound; abnormal swallowing; infants and young children with neurological impairment; apparent aspiration; silent aspiration
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Brain Damage, Chronic; Neurodevelopmental Disorders; Cerebral Palsy; Nervous System Diseases; Developmental Disabilities
• Other Study ID Numbers: LUNCH-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No