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.>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 <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. 

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 > 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 FEV₁ 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 FEV₁ <80% of predicted value (Quanjer et al., 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.

Study design

In a randomised cross-over design participants attended the laboratory on five occasions (figure 1): Visit 1: Peak oxygen uptake (V̇O₂ 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_2-agonists (LABA): 48 hrs; inhaled short-acting β₂-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.

Visit details

Visit One

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 et al. 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.

Visit Two

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.

Visits Three to Five

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 et al. 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 FEV₁ 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 FEV₁ 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 et al., 1999; Ansley et al., 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 et al. 2006; Birring et al. 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 et al. 2008). Cough data was analysed via a cough detection software based on the Hidden Markov model as described by (Birring et al. 2008). Participants completed an additional VAS 24 hours following the EX.

Statistical analysis

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 FEV₁ and coughs per hour 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 <0.05.

Spearman's rank correlation coefficient was used to investigate the relationship between VAS score and cough per hour, % fall in FEV₁ and coughs per hour 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 <0.05.