Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study)

Mosaic Study Investigator Group; Yvan Vandenplas; Zheng-Yan Zhao; Rajat Mukherjee; Christophe Dupont; Philippe Eigenmann; Mikael Kuitunen; Carmen Ribes Koninckx; Hania Szajewska; Andrea von Berg; Kateřina Bajerová; Rosan Meyer; Silvia Salvatore; Raanan Shamir; Anette Järvi; Ralf G Heine

doi:10.1136/bmjopen-2021-056641

Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study)

Mosaic Study Investigator Group, Yvan Vandenplas, Zheng-Yan Zhao, Rajat Mukherjee, Christophe Dupont, Philippe Eigenmann, Mikael Kuitunen, Carmen Ribes Koninckx, Hania Szajewska, Andrea von Berg, Kateřina Bajerová, Rosan Meyer, Silvia Salvatore, Raanan Shamir, Anette Järvi, Ralf G Heine

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Abstract

OBJECTIVES: The MOSAIC study aimed to evaluate if the Cow's Milk-related Symptom Score (CoMiSS) can be used as a stand-alone diagnostic tool for cow's milk protein allergy (CMPA).

DESIGN: Single-blinded, prospective, multicentre diagnostic accuracy study.

SETTING: 10 paediatric centres in China.

PARTICIPANTS: 300 non-breastfed infants (median age 16.1 weeks) with suspected CMPA.

INTERVENTIONS: After performing the baseline CoMiSS, infants commenced a cow's milk protein elimination diet with amino acid-based formula for 14 days. CoMiSS was repeated at the end of the elimination trial. Infants then underwent an open oral food challenge (OFC) with cow's milk-based formula (CMF) in hospital. Infants who did not react during the OFC also completed a 14-day home challenge with CMF. A diagnosis of CMPA was made if acute or delayed reactions were reported.

PRIMARY OUTCOME MEASURES: A logistic regression model for CoMiSS to predict CMPA was fitted and a receiver-operator characteristic (ROC) curve generated. An area under the curve (AUC) of ≥0.75 was deemed adequate to validate CoMiSS as a diagnostic tool (target sensitivity 80%-90% and specificity 60%-70%).

RESULTS: Of 254 infants who commenced the OFC, 250 completed both challenges, and a diagnosis of CMPA made in 217 (85.4%). The median baseline CoMiSS in this group fell from 8 (IQR 5-10) to 5 (IQR 3-7) at visit 2 (p<0.000000001), with a median change of -3 (IQR -6 to -1). A baseline CoMiSS of ≥12 had a low sensitivity (20.3%), but high specificity (87.9%) and high positive predictive value (91.7%) for CMPA. The ROC analysis with an AUC of 0.67 fell short of the predefined primary endpoint.

CONCLUSIONS: The present study did not support the use of CoMiSS as a stand-alone diagnostic tool for CMPA. Nevertheless, CoMiSS remains a clinically useful awareness tool to help identify infants with cow's milk-related symptoms.

TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.

Original language	English
Article number	e056641
Number of pages	8
Journal	BMJ Open
Volume	12
Issue number	2
DOIs	https://doi.org/10.1136/bmjopen-2021-056641
Publication status	Published - 17 Feb 2022

Bibliographical note

Keywords

allergy
community child health
paediatric dermatology
paediatric gastroenterology

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Mosaic Study Investigator Group, Vandenplas, Y., Zhao, Z-Y., Mukherjee, R., Dupont, C., Eigenmann, P., Kuitunen, M., Ribes Koninckx, C., Szajewska, H., von Berg, A., Bajerová, K., Meyer, R., Salvatore, S., Shamir, R., Järvi, A., & Heine, R. G. (2022). Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study). BMJ Open, 12(2), [e056641]. https://doi.org/10.1136/bmjopen-2021-056641

Mosaic Study Investigator Group ; Vandenplas, Yvan ; Zhao, Zheng-Yan ; Mukherjee, Rajat ; Dupont, Christophe ; Eigenmann, Philippe ; Kuitunen, Mikael ; Ribes Koninckx, Carmen ; Szajewska, Hania ; von Berg, Andrea ; Bajerová, Kateřina ; Meyer, Rosan ; Salvatore, Silvia ; Shamir, Raanan ; Järvi, Anette ; Heine, Ralf G. / Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy : a prospective, multicentre study in China (MOSAIC study). In: BMJ Open. 2022 ; Vol. 12, No. 2.

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title = "Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study)",

abstract = "OBJECTIVES: The MOSAIC study aimed to evaluate if the Cow's Milk-related Symptom Score (CoMiSS) can be used as a stand-alone diagnostic tool for cow's milk protein allergy (CMPA).DESIGN: Single-blinded, prospective, multicentre diagnostic accuracy study.SETTING: 10 paediatric centres in China.PARTICIPANTS: 300 non-breastfed infants (median age 16.1 weeks) with suspected CMPA.INTERVENTIONS: After performing the baseline CoMiSS, infants commenced a cow's milk protein elimination diet with amino acid-based formula for 14 days. CoMiSS was repeated at the end of the elimination trial. Infants then underwent an open oral food challenge (OFC) with cow's milk-based formula (CMF) in hospital. Infants who did not react during the OFC also completed a 14-day home challenge with CMF. A diagnosis of CMPA was made if acute or delayed reactions were reported.PRIMARY OUTCOME MEASURES: A logistic regression model for CoMiSS to predict CMPA was fitted and a receiver-operator characteristic (ROC) curve generated. An area under the curve (AUC) of ≥0.75 was deemed adequate to validate CoMiSS as a diagnostic tool (target sensitivity 80%-90% and specificity 60%-70%).RESULTS: Of 254 infants who commenced the OFC, 250 completed both challenges, and a diagnosis of CMPA made in 217 (85.4%). The median baseline CoMiSS in this group fell from 8 (IQR 5-10) to 5 (IQR 3-7) at visit 2 (p<0.000000001), with a median change of -3 (IQR -6 to -1). A baseline CoMiSS of ≥12 had a low sensitivity (20.3%), but high specificity (87.9%) and high positive predictive value (91.7%) for CMPA. The ROC analysis with an AUC of 0.67 fell short of the predefined primary endpoint.CONCLUSIONS: The present study did not support the use of CoMiSS as a stand-alone diagnostic tool for CMPA. Nevertheless, CoMiSS remains a clinically useful awareness tool to help identify infants with cow's milk-related symptoms.TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.",

keywords = "allergy, community child health, paediatric dermatology, paediatric gastroenterology",

author = "{Mosaic Study Investigator Group} and Yvan Vandenplas and Zheng-Yan Zhao and Rajat Mukherjee and Christophe Dupont and Philippe Eigenmann and Mikael Kuitunen and {Ribes Koninckx}, Carmen and Hania Szajewska and {von Berg}, Andrea and Kate{\v r}ina Bajerov{\'a} and Rosan Meyer and Silvia Salvatore and Raanan Shamir and Anette J{\"a}rvi and Heine, {Ralf G}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2022",

month = feb,

day = "17",

doi = "10.1136/bmjopen-2021-056641",

language = "English",

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Mosaic Study Investigator Group, Vandenplas, Y, Zhao, Z-Y, Mukherjee, R, Dupont, C, Eigenmann, P, Kuitunen, M, Ribes Koninckx, C, Szajewska, H, von Berg, A, Bajerová, K, Meyer, R, Salvatore, S, Shamir, R, Järvi, A & Heine, RG 2022, 'Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study)', BMJ Open, vol. 12, no. 2, e056641. https://doi.org/10.1136/bmjopen-2021-056641

Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy : a prospective, multicentre study in China (MOSAIC study). / Mosaic Study Investigator Group ; Vandenplas, Yvan; Zhao, Zheng-Yan; Mukherjee, Rajat; Dupont, Christophe; Eigenmann, Philippe; Kuitunen, Mikael; Ribes Koninckx, Carmen; Szajewska, Hania; von Berg, Andrea; Bajerová, Kateřina; Meyer, Rosan; Salvatore, Silvia; Shamir, Raanan; Järvi, Anette; Heine, Ralf G.

In: BMJ Open, Vol. 12, No. 2, e056641, 17.02.2022.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy

T2 - a prospective, multicentre study in China (MOSAIC study)

AU - Mosaic Study Investigator Group

AU - Vandenplas, Yvan

AU - Zhao, Zheng-Yan

AU - Mukherjee, Rajat

AU - Dupont, Christophe

AU - Eigenmann, Philippe

AU - Kuitunen, Mikael

AU - Ribes Koninckx, Carmen

AU - Szajewska, Hania

AU - von Berg, Andrea

AU - Bajerová, Kateřina

AU - Meyer, Rosan

AU - Salvatore, Silvia

AU - Shamir, Raanan

AU - Järvi, Anette

AU - Heine, Ralf G

PY - 2022/2/17

Y1 - 2022/2/17

N2 - OBJECTIVES: The MOSAIC study aimed to evaluate if the Cow's Milk-related Symptom Score (CoMiSS) can be used as a stand-alone diagnostic tool for cow's milk protein allergy (CMPA).DESIGN: Single-blinded, prospective, multicentre diagnostic accuracy study.SETTING: 10 paediatric centres in China.PARTICIPANTS: 300 non-breastfed infants (median age 16.1 weeks) with suspected CMPA.INTERVENTIONS: After performing the baseline CoMiSS, infants commenced a cow's milk protein elimination diet with amino acid-based formula for 14 days. CoMiSS was repeated at the end of the elimination trial. Infants then underwent an open oral food challenge (OFC) with cow's milk-based formula (CMF) in hospital. Infants who did not react during the OFC also completed a 14-day home challenge with CMF. A diagnosis of CMPA was made if acute or delayed reactions were reported.PRIMARY OUTCOME MEASURES: A logistic regression model for CoMiSS to predict CMPA was fitted and a receiver-operator characteristic (ROC) curve generated. An area under the curve (AUC) of ≥0.75 was deemed adequate to validate CoMiSS as a diagnostic tool (target sensitivity 80%-90% and specificity 60%-70%).RESULTS: Of 254 infants who commenced the OFC, 250 completed both challenges, and a diagnosis of CMPA made in 217 (85.4%). The median baseline CoMiSS in this group fell from 8 (IQR 5-10) to 5 (IQR 3-7) at visit 2 (p<0.000000001), with a median change of -3 (IQR -6 to -1). A baseline CoMiSS of ≥12 had a low sensitivity (20.3%), but high specificity (87.9%) and high positive predictive value (91.7%) for CMPA. The ROC analysis with an AUC of 0.67 fell short of the predefined primary endpoint.CONCLUSIONS: The present study did not support the use of CoMiSS as a stand-alone diagnostic tool for CMPA. Nevertheless, CoMiSS remains a clinically useful awareness tool to help identify infants with cow's milk-related symptoms.TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.

AB - OBJECTIVES: The MOSAIC study aimed to evaluate if the Cow's Milk-related Symptom Score (CoMiSS) can be used as a stand-alone diagnostic tool for cow's milk protein allergy (CMPA).DESIGN: Single-blinded, prospective, multicentre diagnostic accuracy study.SETTING: 10 paediatric centres in China.PARTICIPANTS: 300 non-breastfed infants (median age 16.1 weeks) with suspected CMPA.INTERVENTIONS: After performing the baseline CoMiSS, infants commenced a cow's milk protein elimination diet with amino acid-based formula for 14 days. CoMiSS was repeated at the end of the elimination trial. Infants then underwent an open oral food challenge (OFC) with cow's milk-based formula (CMF) in hospital. Infants who did not react during the OFC also completed a 14-day home challenge with CMF. A diagnosis of CMPA was made if acute or delayed reactions were reported.PRIMARY OUTCOME MEASURES: A logistic regression model for CoMiSS to predict CMPA was fitted and a receiver-operator characteristic (ROC) curve generated. An area under the curve (AUC) of ≥0.75 was deemed adequate to validate CoMiSS as a diagnostic tool (target sensitivity 80%-90% and specificity 60%-70%).RESULTS: Of 254 infants who commenced the OFC, 250 completed both challenges, and a diagnosis of CMPA made in 217 (85.4%). The median baseline CoMiSS in this group fell from 8 (IQR 5-10) to 5 (IQR 3-7) at visit 2 (p<0.000000001), with a median change of -3 (IQR -6 to -1). A baseline CoMiSS of ≥12 had a low sensitivity (20.3%), but high specificity (87.9%) and high positive predictive value (91.7%) for CMPA. The ROC analysis with an AUC of 0.67 fell short of the predefined primary endpoint.CONCLUSIONS: The present study did not support the use of CoMiSS as a stand-alone diagnostic tool for CMPA. Nevertheless, CoMiSS remains a clinically useful awareness tool to help identify infants with cow's milk-related symptoms.TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.

KW - allergy

KW - community child health

KW - paediatric dermatology

KW - paediatric gastroenterology

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U2 - 10.1136/bmjopen-2021-056641

DO - 10.1136/bmjopen-2021-056641

M3 - Article

C2 - 35177461

VL - 12

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 2

M1 - e056641

ER -

Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study)

Abstract

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Keywords

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