Methods
Participants and study design
Within an explorative study design, all athletes consecutively referred for work-up of EIIS and diagnosed with EILO at the outpatient clinic at the Pediatric Department of Haukeland University Hospital in Western Norway between May 2012 and May 2014 were offered a structured treatment period with IMT, providing a device was available (ie, convenience-based inclusion within a given time frame). The inclusion criteria required that the severity scores of EILO obtained during a continuous laryngoscopy exercise (CLE) test16 were graded as two or more, either at the supraglottic level or at the vocal folds (ie, the glottic level)17 (regarding CLE scores, see figure 1). Moreover, there should be no evidence that EIB could explain the patient’s symptoms. Asthma per se was not an exclusion criterion, but in cases where asthma was present or suspected, EIB was excluded as cause of symptoms by performing a standardised test as described by Carlsen et al, either at our institution or by the referring institution.18 CLE scores, lung function and ergospirometry data were collected before and 2–4 weeks after the IMT treatment period, as were symptom scores obtained using a standardised questionnaire that also served to obtain demographic background variables. All athletes answered the question “When you are physically active, how much are you bothered by your breathing difficulties?”, using a numeric rating scale from 1 to 5 (1=nothing, 2=a bit, 3=pretty much, 4=a lot and 5=disabling). The study was approved by the Committee on Medical Research Ethics of Western Norway (REK number 2009/2111), and informed written consent was obtained from the participants.
Figure 1Grading system according to Maat et al
17 reproduced with permission.
CLE test
An integrated set-up for continuous video-recorded laryngoscopy throughout a maximal cardiopulmonary exercise test, coupled with video recordings of the upper part of the body and sound recordings, was applied as previously described.16
A transnasal flexible fiberoptic laryngoscope (Olympus ENF-P3, Tokyo, Japan), diameter 3.5 mm, was introduced after applying a decongestive nasal spray (Rhinox) and local anaesthesia (Xylocaine), and secured in a position allowing for a good view of the laryngeal entrance, including both supraglottic structures and the vocal folds. Continuous video recordings from the laryngoscope, a film of the upper part of the body and breath sounds were obtained simultaneously throughout the exercise test and stored in one single file for later evaluation. Laryngeal movements were scored as described previously17; at moderate (ie, when the test person changed from walking to running) and at maximal exercise intensity at glottic (labelled A and C, respectively) and supraglottic (labelled B and D, respectively) levels, and additionally a total sum score labelled E (figure 1). A CLE subscore of 1 (glottic or supraglottic) was regarded as normal.2 All assessments were done by two experienced raters (HHC and ODR) who were exposed to anonymised video recordings from all participants, blinded to the circumstances under which the video had been obtained, that is, if the video had been obtained before or after the treatment period. An uninvolved photographer presented the two films from each participant in random order. Disagreements were solved by consensus. Clinical symptoms during the CLE test were recorded in a questionnaire.
Pulmonary function and exercise test
Spirometry was performed with a Vmax 22 (SensorMedics, Yorba Linda, California, USA) according to guidelines,19 recording FVC, FEV1 and forced expiratory flow at 50% of FVC (FEF50%), and reported as percentages of predicted.20 Forced inspiratory volume in first second (FIV1) and forced inspiratory flow at 50% (FIF50%) of forced inspiratory volume capacity were recorded, and FEF50/FIF50 and FEV1/FIV1 were calculated and classified as abnormal if exceeding 1.5.8 The configuration of the flow-volume loops (FVL) was classified as normal or abnormal by an experienced respiratory physiologist (ODR), based on flattening or truncation of the inspiratory limbs.21 The patients ran on a treadmill (Woodway ELG 70, Weil am Rhein, Germany) using a computerised and modified Bruce protocol,22 increasing speed and/or elevation every minute, aiming to reach maximum exercise capacity after 6–12 min. Variables of gas exchange were measured breath by breath using a facemask (Hans Rudolph, Kansas City, Missouri, USA) connected to a Jaeger Oxycon Pro Cardiopulmonary Exercise testing system (Viasys Health Care, Yorba Linda, California, USA). The test was considered successful if the patient continued until exhaustion, preferably supported by a plateau in oxygen consumption and/or the heart rate response, or until stopped by respiratory distress. Duration and distance on treadmill running were recorded.
Inspiratory muscle training
Respifit S (Biegler GmbH, Mauerbach, Austria) was used to measure the maximal inspiratory mouth pressure (PImax), using the best value of 10 according to guidelines23 in order to provide exact settings of the resistance during the IMT sessions. The same device was used for the 6-week training sessions. To promote correct breathing technique, the participants were instructed to inhale using the diaphragm and to minimise movements of the shoulders in the cranial direction. Two modes of inspiratory muscle training were tested in accordance with the manual supplied by the manufacturer, that is, (1) inspiratory muscle strength training (IMST) with the resistance set to produce mouth pressures ≥80% of PImax and (2) moderate resistance or inspiratory muscle endurance training (IMET) with the resistance set at 60%–80% of PImax. In the IMST sessions, subjects performed five maximal inhalations repeated three times, separated by a 1 min break. In the IMET sessions, subjects were instructed to breathe in and out 12–16 times for 1 min. The frequency and power were guided by an animation program ensuring correct use of the device, and data from each training session were stored by a memory card measuring treatment compliance. The participants trained every day, in cycles of 2 days with IMET followed by 1 day of IMST, for a total of 6 weeks.
Statistical methods
This was a descriptive study, with main outcomes being the CLE scores and symptom scores obtained before versus after the IMT treatment period, compared using Gosset’s paired sample t-test.24 Means, SD, 95% CIs and ranges were calculated, as appropriate. The CLE scores are by nature ordinal and categorical, ranging from 0 to 3. Due to the few number of categories, the data were reported as mean values and mean differences with 95% CI, as this is considered to provide more information than medians and IQRs.25 Mixed linear model regression including interaction terms were applied to address if CLE-score changes (before vs after the treatment period) differed when obtained at moderate versus maximal exercise intensity and at the glottic versus supraglottic laryngeal level.26
All analyses were performed with SPSS V.24.