The Effect of High Flow Nasal Cannula Therapy in Exercised-Induced Asthma of Children
Round 1
Reviewer 1 Report
Authors wish to study the effect of HFNC in the treatment of asthma attack of children. At this aim they design a randomized prospective crossover trial recruiting children who show a decrease of FEV-1 of ≥ 30% during an exercise challenge. The time of fully recovered FEV-1 within 10% of the baseline after peak fall has been compared with and without HFNC therapy. Secondary outcome was the pressure used by the HFNC-device to deliver the constant high flow , as Authors think that a relation between the measured pressure and the degree of recovery may reveal a working mechanism of HFNC.
The research question is interesting, but the study design is adequate to investigate the effect of HFNC on exercise induced asthma and not spontaneous severe asthma attack. There is a profound difference between severe asthma attack, where mucus plugging may play a major role, particularly in children, and exercise induced asthma, which resolves spontaneously generally in 20-40 minutes!
Critical points
Authors should change the title in The effect of HFNC in exercise-induced asthma of children.
They should also provide the ratio why HFNC should be useful in EIA. HFFNC is particularly useful in mobilizing mucus plugged in narrowed airways, a condition observed in status asthmaticus, but not in EIA.
Author Response
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Authors should change the title in The effect of HFNC in exercise-induced asthma of children. |
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Answer |
The authors agree that “The effect of HFNC in exercise-induced asthma of children” is a more appropriate title. |
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They should also provide the ratio why HFNC should be useful in EIA. HFFNC is particularly useful in mobilizing mucus plugged in narrowed airways, a condition observed in status asthmaticus, but not in EIA. |
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Answer |
Altered introduction: “In asthmatic children inflammatory cells, residing in their airways, will shrink due to the osmotic stimulus, leading to the release of proinflammatory mediators[8,9]. These mediators induce bronchoconstriction, airway wall edema and excessive mucus production resulting in airway narrowing and the classic asthmatic symptoms of wheezing, cough and dyspnea. Exercise induced asthma (EIA) symptoms are usually short-lived, resolving in 15-30 minutes, as the provoking stimulus is transient. During an asthma attack the same inflammatory mediators are released as in EIA, and the airway narrowing is similarly reversible to bronchodilators. Imaging studies in EIA showed ventilation defects as is known from asthma attacks, probably also due to mucus plugged in constricted airways. An exercise challenge test is therefore a suitable method to investigate mechanisms of asthma[10].” |
Reviewer 2 Report
In the manuscript the authors through prospective crossover trial intend to investigate in asthmatic children whether HFNC therapy accelerates the recovery of lung function in children undergoing an exercise challenge test, which is an innovative approach. The effect of HFNC has been mainly investigated in asthmatics during acute asthma exacerbation. Therefore, the title of the trial is too general, and does not reflect the planned research and does not emphasize its innovativeness.
The introduction should also be refined, and emphasize the difference between exercise induced bronchoconstriction (EIB) and asthma, as well as the reason for choosing the climate controlled chamber (dry and cold air) as a standard for exercise challenge test and whether the choice of types of exercise (running on a treadmill or jumping in an inflatable bouncing castle) affect the repeatability of measurements and the comparability of results.
The inclusion criteria should be more clearly defined, eg stated “Children with a suspicion or diagnosis of asthma by a paediatrician...(86th line)
The endpoints of the trial are the recovery of lung function assessed with spirometry measurements and the duration to fully recovered lung function after ECT within 10% of baseline FEV1 in patient with or without HFNC, and the pressure values during HFNC therapy. As numerous other parameters are monitored during ECT as well, it is suggested to indicate where other potential changes are expected in patients on HFNC therapy, eg .heart rate, respiration rate, CO2 concentration, arterial blood pressure, oxygen uptake ...
Author Response
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The effect of HFNC has been mainly investigated in asthmatics during acute asthma exacerbation. Therefore, the title of the trial is too general, and does not reflect the planned research and does not emphasize its innovativeness |
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The authors wish to change the title into “The effect of HFNC in exercise-induced asthma of children” as suggested by the other reviewer. |
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The introduction should also be refined, and emphasize the difference between exercise induced bronchoconstriction (EIB) and asthma, |
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The introduction is modified, where the difference between EIB and asthma is now mentioned. EIB is short lived as the provoking stimulus is transient. |
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as well as the reason for choosing the climate controlled chamber (dry and cold air) as a standard for exercise challenge test |
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2The mechanism of exercise-induced asthma is …, September 2000, Journal Allergy Clinical Immunology: “There are different theories behind the driving mechanisms of EIA. The osmotic and thermal theories come together by considering that inspiration of cold air nog only cools the airways but also increases the numbers of airway generations becoming dehydrated in the humidifying process”2 Introduction altered: “During intensive prolonged exercise in cold, dry air a large number of airway generations become transiently dehydrated. In asthmatic children inflammatory cells, residing in their airways, will shrink due to the osmotic stimulus, leading to the release of pro-inflammatory mediators[8,9].” |
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and whether the choice of types of exercise (running on a treadmill or jumping in an inflatable bouncing castle) affect the repeatability of measurements and the comparability of results. |
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Most children will run on the treadmill, in the clinic we only use the bouncing caste for children who are too young to run on the treadmill. Regarding comparability all patients exercise the same amount of time with maximum effort. During the exercise the heart rate will be monitored to check whether the heart rates are comparable during both tests. On the treadmill the speed and angle can be adjusted to alter the intensity of the exercise. On the bouncing castle children can be motivated to jump intenser. Regarding comparability only children with a severe FEV1 labiltity (≥ 30%) are included in this study. |
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The inclusion criteria should be more clearly defined, eg stated “Children with a suspicion or diagnosis of asthma by a paediatrician...(86th line) |
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Adjustment: “Children that previously performed a standard ECT with a FEV1 lability of ≥ 30% are included in this study” |
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The endpoints of the trial are the recovery of lung function assessed with spirometry measurements and the duration to fully recovered lung function after ECT within 10% of baseline FEV1 in patient with or without HFNC, and the pressure values during HFNC therapy. As numerous other parameters are monitored during ECT as well, it is suggested to indicate where other potential changes are expected in patients on HFNC therapy, eg .heart rate, respiration rate, CO2 concentration, arterial blood pressure, oxygen uptake ... |
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To minimize the burden for the patient we designed the study so that the standard ECT is part of the study. During the standard ECT only the FEV1 is measured. |
Round 2
Reviewer 1 Report
The revised manuscript has been changed according to criticisms and suggestions.
