DOI: 10.5061/dryad.gf1vhhmkm
title: The impact of a heat and moisture exchange mask on respiratory symptoms and airway response to exercise in asthma

description: Respiratory symptoms, including cough are prevalent in asthmatic
 individuals when exercising. This study investigates whether a heat and
 moisture exchanger (HME) face mask is effective in modulating exercise
 induced bronchoconstriction (EIB) and post exercise cough in a cold, dry
 environment in asthmatic individuals. Twenty-six participants diagnosed
 with asthma (20 males, 6 females) completed three cycling exercise
 challenges (EX) at 8 oC and 24% relative humidity (RH) in a randomised
 order. Participants wore either an HME mask (MASK), sham mask (SHAM), or
 no mask (CON). Following a 3-min warm-up participants completed 6-min
 cycling at 80% peak power output. Before and after EX, maximal flow volume
 loops were recorded. Post EX cough was monitored with a Leicester Cough
 Monitor (LCM) for 24-hours.  Results were analysed using repeated
 measures ANOVA and Friedman’s tests and data presented as the mean ± SD or
 median (IQR). Eleven participants failed to demonstrate EIB
 (i.e.&gt;10% fall in FEV1 post EX) and were removed from analysis. The
 % fall in FEV1 following EX in CON was greater than MASK (MASK: -6.0
 (7.0), SHAM: -11.0 (11.0), CON: -13.0 (9.0) %; p &lt;0.01). No
 difference was found between EX in cough count per hour over the 24-hour
 monitoring period or the number of coughs in the first hour post EX. HME
 masks can attenuate EIB when exercising in cold, dry environments. The
 SHAM mask may not have been entirely inert demonstrating the challenges of
 running randomised control trials utilising control and SHAM
 conditions. 
description: This
 study is registered on ClinicalTrials.gov (Identifier: NCT04302610).
 Following approval from the Faculty of Sciences Research Ethics Advisory
 Group for Human Participants, University of Kent (0881516) thirty-four
 recreationally active participants exercising &gt;
 twice per week (6 ± 2 hours) provided written informed consent to
 participate. All participants had a clinician-based diagnosis of asthma
 however participants who didn’t have a fall in FEV<sub>1</sub>
 of ≥10% at two consecutive time points following at least one of the
 exercise challenges (see below) were not included in subsequent analysis.
 i.e. no evidence of exercise-induced bronchoconstriction. Participants
 were excluded if they used of oral corticosteroid daily, were hospitalised
 due to asthma in the six months prior to study commencement and/or resting
 FEV<sub>1</sub> &lt;80% of predicted value (Quanjer
 <i>et al</i>., 1994). All participants were free from illness
 in the two weeks prior to assessment. Participants were instructed to
 maintain their usual diet for the duration of the study, to avoid exercise
 and caffeine for 24 hrs and 4 hrs respectively before each visit and
 arrive at the laboratory at least 2 hrs postprandial. <b>Study
 design </b> In a
 randomised cross-over design participants attended the laboratory on five
 occasions (figure 1): Visit 1: Peak oxygen uptake
 (V̇O<sub>2</sub> peak) test on a cycle
 ergometer. Visit 2): Familiarisation. Visits 3-5): Standardised cycle
 exercise challenge (EX) in a cold, dry environment. During the EX,
 participants wore either an HME mask (MASK) (ColdAvenger® expedition balaclava, USA,
 www.coldavenger.com), a sham mask (SHAM) which was the same
 HME mask with holes cut across the entire ventilator cup and the
 ventilator removed (figure 2), or no mask (CONT) wearing only the
 balaclava to which the mask is attached.  
 The EXs
 were completed in a randomised order but at the same time of day. The time
 between each visit was dependant on the participant’s current medication;
 participants previously prescribed inhaler medication for asthma / EIB
 withheld medication prior to each assessment (inhaled corticosteroids
 (ICS): 72 hours; inhaled long-acting β<sub>2-</sub>agonists
 (LABA): 48 hrs; inhaled short-acting β<sub>2</sub>-agonists
 (SABA): the day of the test (Anderson and Kippelen, 2013). Following each
 trial, participants had the same amount of time back on their medication
 before once again stopping treatment before their next EX. Participants
 who were not taking any asthma medication, had a minimum of 48 hrs between
 trials.  
 <b>Visit
 details</b> <i>Visit
 One</i> Cough-specific
 health status was assessed with the Leicester Cough Questionnaire (LCQ),
 which is a self-administered 19-item tool (total score range 3-21; higher
 scores indicating better health status; Birring <i>et al.</i>
 2003).  Anthropometric measures were taken and performed a standardised
 incremental ramp test to volitional exhaustion to establish Peak Power on
 a cycle ergometer (Lode; Corival, Groningen, Netherlands) with
 simultaneous gas analysis (Cortex Metalyser 3b, CORTEX Biophysik GmbH,
 Germany). Heart rate was recorded throughout (Polar RS400; Polar Electro
 Oy, Kempele, Finland) and Peak Power Output (PPO) was recorded.
  
 <i>Visit
 Two</i> Participants
 remained on prescribed asthma therapy and completed the EX protocol as
 detailed below in a normal lab environment without a mask, as means of
 laboratory testing familiarisation.  
 <i>Visits Three to Five</i> Participants completed a cough 0-100mm visual analogue scale (VAS) (Spinou and Birring 2014). Airway inflammation was then assessed prior to each challenge by determining fraction of exhaled nitric oxide (FeNO) (NIOX VERO, NIOX, Aerocrine, Sweden) (Dweik <i>et al.</i> 2011). Resting lung function was then measured by maximal flow volume spirometry (Spiro-USB and MicroLab, CareFusion, Germany) in accordance with international standards (Miller et al., 2005). Maximal flow-volume loops were subsequently measured in duplicate at 3, 5, 7, 10- and 15-mins post challenge, with the highest value at each time point used for analysis. If there was a ≥10% fall in FEV<sub>1</sub> post challenge at two consecutive time points, 400 µg inhaled salbutamol was self-administered by the participant and maximal flow loops were repeated 15 minutes post administration to ensure FEV<sub>1</sub> had returned to within 10% of baseline. The EXs were conducted in an environmental chamber (TIS Services, Hampshire, UK) (8.6 ± 0.9 °C, 24.2 ± 4.2% RH) on a cycle ergometer (Lode; Corival, Groningen, Netherlands). The EX protocol required participants to complete 3-minutes of incremental cycling at a work rate of 60, 75 and 90% of their final target power for one minute at each power output. They then cycled for 6 minutes at 80% of their peak power (Crapo <i>et al</i>., 1999; Ansley <i>et al</i>., 2010). Heart rate was recorded throughout. Immediately after EX, cough frequency was assessed objectively over 24 hours with the validated Leicester Cough Monitor (LCM; Birring <i>et al.</i> 2006; Birring <i>et al.</i> 2008). The LCM is an ambulatory system, which comprises a MP3 recorder (ICD-PX333, Sony Corporation, Tokyo, Japan), a lapel free-field microphone (LFH9173, Philips, Amsterdam, Netherlands) and a semi-automated cough detection software. Coughs were detected as single events whether they occurred in isolation or in bouts (Birring <i>et al.</i> 2008). Cough data was analysed via a cough detection software based on the Hidden Markov model as described by (Birring <i>et al.</i> 2008). Participants completed an additional VAS 24 hours following the EX.   <b>Statistical analysis</b> Data are presented as mean ± SD unless otherwise stated. Shapiro-Wilk tests were used to test for normal distribution. Differences between the three EX conditions were examined using repeated measures ANOVA. Where data was not normally distributed, Friedman’s test was used with post hoc pairwise comparisons where appropriate. Spearman's rank correlation coefficient was used to investigate the relationship between VAS score and cough per hour, % fall in FEV<sub>1</sub> and coughs per hour<sub> </sub>after EX or LCQ score and cough count. All analysis was conducted using SPSS software, V.23 (SPSS, IBM, Armonk, NY, USA) with significance accepted at P &lt;0.05. Spearman's rank correlation coefficient was used to investigate the relationship between VAS score and cough per hour, % fall in FEV<sub>1</sub> and coughs per hour<sub> </sub>after EX or LCQ score and cough count. All analysis was conducted using SPSS software, V.23 (SPSS, IBM, Armonk, NY, USA) with significance accepted at P &lt;0.05.