Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids While on Monoclonal Antibody Therapy: Protocol for a Prospective Observational Study (BOOST)

Imran Howell; Mahdi Mahdi; Mona Bafadhel; Timothy S.C. Hinks; Sanjay Ramakrishnan; James Melhorn; Maisha Jabeen; Ian D. Pavord

doi:10.2196/46741

Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids While on Monoclonal Antibody Therapy: Protocol for a Prospective Observational Study (BOOST)

Imran Howell^*, Mahdi Mahdi, Mona Bafadhel, Timothy S.C. Hinks, Sanjay Ramakrishnan, James Melhorn, Maisha Jabeen, Ian D. Pavord

^*Corresponding author for this work

Peter Gorer Department of Immunobiology

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

6 Citations (Scopus)

Abstract

Background: Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. Objective: The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. Methods: BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. Results: The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. Conclusions: We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed.

Original language	English
Article number	e46741
Journal	JMIR research protocols
Volume	12
DOIs	https://doi.org/10.2196/46741
Publication status	Published - 2023

Keywords

adult
asthma
asthma attack
inflammatory response
monoclonal antibodies
monoclonal antibody
oral steroid
prednisolone treatment
quality of life
steroids
treatment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2196/46741

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@article{69b442c9b5104ae89a513708e6c7f393,

title = "Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids While on Monoclonal Antibody Therapy: Protocol for a Prospective Observational Study (BOOST)",

abstract = "Background: Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. Objective: The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. Methods: BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. Results: The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. Conclusions: We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed.",

keywords = "adult, asthma, asthma attack, inflammatory response, monoclonal antibodies, monoclonal antibody, oral steroid, prednisolone treatment, quality of life, steroids, treatment",

author = "Imran Howell and Mahdi Mahdi and Mona Bafadhel and Hinks, {Timothy S.C.} and Sanjay Ramakrishnan and James Melhorn and Maisha Jabeen and Pavord, {Ian D.}",

note = "Publisher Copyright: {\textcopyright}Imran Howell, Mahdi Mahdi, Mona Bafadhel, Timothy S C Hinks, Sanjay Ramakrishnan, James Melhorn, Maisha Jabeen, Ian D Pavord.",

year = "2023",

doi = "10.2196/46741",

language = "English",

volume = "12",

journal = "JMIR research protocols",

issn = "1929-0748",

publisher = "JMIR Publications Inc.",

}

TY - JOUR

T1 - Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids While on Monoclonal Antibody Therapy

T2 - Protocol for a Prospective Observational Study (BOOST)

AU - Howell, Imran

AU - Mahdi, Mahdi

AU - Bafadhel, Mona

AU - Hinks, Timothy S.C.

AU - Ramakrishnan, Sanjay

AU - Melhorn, James

AU - Jabeen, Maisha

AU - Pavord, Ian D.

N1 - Publisher Copyright: ©Imran Howell, Mahdi Mahdi, Mona Bafadhel, Timothy S C Hinks, Sanjay Ramakrishnan, James Melhorn, Maisha Jabeen, Ian D Pavord.

PY - 2023

Y1 - 2023

N2 - Background: Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. Objective: The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. Methods: BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. Results: The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. Conclusions: We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed.

AB - Background: Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. Objective: The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. Methods: BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. Results: The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. Conclusions: We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed.

KW - adult

KW - asthma

KW - asthma attack

KW - inflammatory response

KW - monoclonal antibodies

KW - monoclonal antibody

KW - oral steroid

KW - prednisolone treatment

KW - quality of life

KW - steroids

KW - treatment

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U2 - 10.2196/46741

DO - 10.2196/46741

M3 - Article

AN - SCOPUS:85163817097

SN - 1929-0748

VL - 12

JO - JMIR research protocols

JF - JMIR research protocols

M1 - e46741

ER -

Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids While on Monoclonal Antibody Therapy: Protocol for a Prospective Observational Study (BOOST)

Abstract

Keywords

UN SDGs

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