ACUTE AND DAILY EFFECTS OF REPEATED VOLUNTARY HYPERPNEA ON PULMONARY FUNCTION IN HEALTHY ADULTS

Abstract

Purpose

Hyperpnea training has been used as a method for both improving exercise performance in healthy persons and improving ventilatory capacity in patients with pulmonary disease. However, voluntary hyperpnea causes acute declines in pulmonary function, but the effects of repeated days of hyperpnea on airway function are not known. The purpose of this study was to determine the effects of repeated normocapnic hyperpnea on daily and post-hyperpnea pulmonary function in healthy adults.

Methods

Ten healthy adults (21 years; 170 cm; 66 kg) completed ten hyperpnea training sessions within 17-days (TR). Training sessions consisted of 20-minutes of normocapnic hyperpnea with gradually increased minute ventilation over the ten days. Spirometry was assessed at baseline and serially following hyperpnea during each experimental day. A control group (24 years; 171 cm; 66 kg) completed ten days of spirometry with no hyperpnea training (CON).

Results

In both CON and TR subjects, baseline pulmonary function was unchanged during the ten days. In TR subjects, pulmonary function was decreased at five-minutes after hyperpnea but thereafter increased to pre-hyperpnea values by 30-minutes. Furthermore, these changes in pulmonary function were consistent during the ten training days. In TR subjects, maximal voluntary ventilation decreased by 10.4 ± 8.9% (168 to 150 L·min⁻¹) over the ten days (P < 0.05), whereas it was unchanged in CON subjects.

Conclusions

These findings demonstrate that voluntary hyperpnea acutely decreases airway function in healthy subjects. However, there does not appear to be a cumulative effect of repeated hyperpnea, as daily pulmonary function was unchanged.

INTRODUCTION

Voluntary hyperpnea training, sometimes known as respiratory muscle endurance training, has been studied as a method for improving aerobic exercise performance in healthy people (Boutellier, Buchel et al. 1992; Keramidas, Debevec et al. 2010) and as a way to improve functional and ventilatory capacity in several clinical populations (Keens, Krastins et al. 1977; Scherer, Spengler et al. 2000). Such studies implicitly assume that repeated hyperpnea will not have any deleterious effects on airway structure or function. In support of this, previous publications demonstrate a combination of either unchanged or improved pulmonary function after a period of hyperpnea training in healthy populations (Leddy, Limprasertkul et al. 2007; Verges, Renggli et al. 2009; Keramidas, Debevec et al. 2010; Uemura, Lundgren et al. 2012). On the other hand, few studies have reported the acute effects of hyperpnea on pulmonary function during the immediate post-hyperpnea period (Verges, Renggli et al. 2009; Illi, Hostettler et al. 2011; Eichenberger, Kurzen et al. 2019). In all three reports, pulmonary function was reduced immediately after hyperpnea. Only one of these studies reported spirometry at multiple timepoints (up to 60-minutes) after hyperpnea (Eichenberger, Kurzen et al. 2019), showing a gradual improvement in pulmonary function throughout the recovery period. However, the effect of repeated, daily bouts of such hyperpnea on acute airway function is not known. If one attributes the reversible decrease in airway function to minor airway damage consequent to the sustained increases in airflow (Kippelen and Anderson 2012), it is not unreasonable to suspect that a repeated hyperpneic stimulus might cause a gradually more severe airway response over time.

Any effects of hyperpnea training on pulmonary function must be interpreted relative to the characteristics of the protocol used. For example, both tidal volume (VT) and breathing frequency (fb) have been controlled in nearly all previous publications of hyperpnea training. In general, VT is set at 50–60% of vital capacity while fb is calculated to achieve a particular minute ventilation (${\dot{\mathrm{V}}}_{\mathrm{E}}$); in practice, fb is usually approximately 30 breaths·min⁻¹. In contrast, in one of the first studies of hyperpnea training, subjects selected their own ventilatory pattern (Bradley and Leith 1978). Interestingly, the subjects adopted a very high fb between 51 and 137 breaths·min⁻¹, significantly higher than obtained with the controlled ventilatory patterns used in most studies. Although controlling VT and fb adds consistency to the hyperpneic intervention, it forces subjects to assume a constrained breathing pattern that is likely very different from the pattern that would occur if subjects were allowed to select their own VT and fb. Indeed, allowing subjects to choose their own breathing pattern during volitional hyperpnea should generate insights into ventilatory control and mechanics under circumstances of voluntarily increased ventilation.

The primary purpose of this study was to assess the acute and daily effects of a ten day period of repeated volitional hyperpnea on pulmonary function in healthy adults. Moreover, ventilatory pattern was not controlled, such that subjects were free to adopt any combination of VT and fb they thought best. We hypothesized that the repeated periods of high airflow would decrease pulmonary function during the training period. We also hypothesized that subjects would assume a significantly more tachypneic breathing pattern than seen in traditional hyperpnea training protocols.

METHODOLOGY

Subject selection

Adult males and females were recruited through advertisements posted in the community and by word-of-mouth. All participants were non-smokers between the ages of 18–45 years, had a negative history for cardiovascular disease and other chronic illness and an absence of respiratory infection during the 6-weeks prior to participation. Prior to participation, subjects were fully informed of the procedures, risks, and benefits of the study. All subjects provided consent by signing the informed consent document. This study was approved by the Northern Vermont University-Johnson Institutional Review Board for research involving human subjects.

Experimental design

A control group (CON) and a hyperpnea training group (TR) completed ten experimental visits to the exercise physiology lab. In all subjects, the visits were completed within seventeen days [12.4 ± 2.2 (range, 10–15 days) and 14.6 ± 1.7 days (SD) (range, 13–17 days) for CON and TR groups, respectively, P=n.s.]. CON subjects completed spirometry during each of the ten visits. TR subjects completed pre-hyperpnea spirometry, a hyperpnea training session, and post-hyperpnea spirometry at multiple timepoints (5, 10, 15, 20, and 30-minutes) during each of the ten visits. Every effort was made to study each individual subject at the same time of the day. Subjects were asked to maintain a similar behavioral routine throughout the entire period of participation.

Spirometry

Spirometry was performed using an automated spirometer (MGC Diagnostics). All tests were completed in the seated, upright position according to recommendations by the American Thoracic Society and European Respiratory Society (Miller, Hankinson et al. 2005). During all ten visits, subjects in both groups completed the following maneuvers upon arrival to the lab: 1) maximal voluntary ventilation (MVV)-12 seconds; 2) forced vital capacity; 3) slow vital capacity. During each visit, subjects performed two MVV maneuvers and the higher of the two values was selected for analysis. Post-hyperpnea spirometry in TR subjects included forced and slow vital capacity maneuvers; MVV was not performed after hyperpnea. Forced vital capacity (FVC), forced expiratory volume in 1.0 second (FEV₁), and peak expiratory flow (PEF) were obtained from the forced vital capacity whereas vital capacity (SVC) and inspiratory capacity (IC) were obtained from the slow vital capacity maneuvers. Predicted values for the measures derived from the forced vital capacity and slow vital capacity are from Hankinson et al. (Hankinson, Odencrantz et al. 1999). Predicted values for MVV are from Taylor et al. (Taylor, Rehder et al. 1989).

Hyperpnea training

Each hyperpnea session was 20-minutes in duration with the target ventilation (${\dot{\mathrm{V}}}_{\mathrm{E}}$) set as follows: days 1–4, 70% MVV; days 5–7, 75% MVV; days 8–10, 80% MVV. For each subject, the MVV obtained on the first training day was used to assign target ${\dot{\mathrm{V}}}_{\mathrm{E}}$ throughout the ten days of training. Subjects were instructed to select their own breathing pattern during the hyperpnea sessions. Thus, subjects’ only goal was to do their best to reach and maintain the target ${\dot{\mathrm{V}}}_{\mathrm{E}}$; they were not provided any instructions regarding VT or fb. During each hyperpnea training session, subjects were seated comfortably in a chair with a computer monitor placed at eye-level. Real-time ${\dot{\mathrm{V}}}_{\mathrm{E}}$ was displayed on the monitor and subjects voluntarily titrated their breathing to match the target as closely as possible.

Hyperpnea training apparatus

Subjects breathed through a two-way, non-rebreathing valve with a nose clip in place. Inspired airflow was measured with a pneumotachograph (Hans-Rudolph) and the signal was integrated to determine breath-by-breath VT, which was multiplied by fb to calculate ongoing ${\dot{\mathrm{V}}}_{\mathrm{E}}$ during the training sessions. Carbon dioxide was continuously sampled at the mouth to determine breath-by-breath end-tidal CO₂ (ETCO₂) (Vacumed). Prior to hyperpnea, four minutes of resting, eupneic breathing was used to determine resting ETCO₂. External dead-space was then added to maintain ETCO₂ close to the resting level during each hyperpnea session. The initial volume of dead space was estimated by the target ${\dot{\mathrm{V}}}_{\mathrm{E}}$ and application of the alveolar air equation. Subsequently, 0.5 liter increments of dead space were added or subtracted from the breathing circuit if ETCO₂ was below, or above, eupneic levels, respectively. In some cases, subjects’ breathing patterns changed over the course of the training sessions; in these instances, dead space was added and subtracted as necessary.

Statistical analysis

Descriptive characteristics and baseline pulmonary function values were compared between CON and TR subjects with a two-tailed independent t-test. The spirometric measures were compared between the CON and TR groups and across experimental days using a two-way [GROUP (CON and TR) x TIME (Day 1 – Day 10)] repeated measures analysis of variance. When significant main effects were found, Bonferroni-corrected pairwise comparisons were employed for post-hoc analysis. In TR subjects, hyperpnea training variables were analyzed using one-way repeated measures analysis of variance with Bonferroni-corrected comparisons for post-hoc analysis. Data in figures are presented as mean ± standard error of mean whereas data in tables are presented as mean ± standard deviation. Significance was set at α ≤ 0.05. The statistical software program SYSTAT was used to analyze all data (SYSTAT 12).

RESULTS

Subject characteristics (table 1)

Table 1.

Descriptive characteristics and baseline spirometry in control and hyperpnea training subjects

Variable	Control	Hyperpnea
Male/female	5/3	5/5
Age, yr	24.4 ± 4.4	20.8 ± 1.0
Height, m	1.7 ± 0.1	1.7 ± 0.1
Weight, kg	66.1 ± 11.1	65.6 ± 13.2
SVC, % normal	106 ± 11.7	101 ± 8.6
FVC, % normal	102 ± 8.8	99.4 ± 9.6
FEV1, % normal	105 ± 11.9	97.2 ± 10.1
FEV1/FVC	86.3 ±− 5.8	83.8 ± 6.8
PEF, % normal	112 ± 12.3	102 ± 14.2
MVV, % normal	115 ± 20.7	107 ± 16.6

SVC, vital capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume 1 second; PEF, peak expiratory flow; MVV, maximal voluntary ventilation. There were no significant differences between groups. Values are means +/− standard deviation.

Subjects in the CON and TR groups were well-matched for age, height, and weight. Pulmonary function was normal in both subject groups, and there were no differences in any of the spirometric variables between the two groups. All subjects in both groups had a negative history for reactive airways disease. No subject was prescribed any medication that might influence airway function (e.g., inhaled β₂-agonist; leukotriene blockers; anti-histamines; inhaled corticosteroids).

Pulmonary function

Results for baseline SVC, FVC, FEV₁ and PEF in CON and TR subjects during the ten experimental days are shown in table 2. In both CON and TR subjects, all spirometric measures remained unchanged at baseline across the ten training days. Moreover, there were no differences between the CON and TR groups in any of the measures.

Table 2.

Daily pulmonary function results during ten experimental days in control and hyperpnea training subjects

Control subjects	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Day 8	Day 9	Day 10
SVC, L	5.1 ± 1.0	5.0 ± 0.9	5.2 ± 0.9	5.1 ± 1.0	4.9 ± 0.9	5.0 ± 1.0	5.0 ± 0.9	5.0 ± 1.0	5.0 ± 1.0	4.9 ± 1.0
FVC, L	4.9 ± 1.2	4.9 ± 1.1	5.0 ± 1.1	4.9 ± 1.1	4.8 ± 1.1	5.0 ± 1.0	4.9 ± 1.0	4.8 ± 1.0	4.9 ± 0.9	4.8 ± 1.0
FEV1, L	4.3 ± 1.1	4.2 ± 1.0	4.2 ± 1.0	4.2 ± 1.0	4.1 ± 1.0	4.2 ± 0.9	4.1 ± 1.0	4.1 ± 0.9	4.2 ± 0.9	4.2 ± 1.0
FEV1/FVC	.86 ± .06	.86 ± .05	.86 ± .06	.85 ± .05	.85 ± .04	.85 ± .05	.85 ± .06	.85 ± .06	.85 ± .07	.86 ± .06
PEF, L·sec−1	9.8 ± 2.2	10.2 ± 2.4	10.0 ± 2.5	9.8 ± 2.7	10.2 ± 2.8	10.0 ± 2.6	10.0 ± 2.5	9.9 ± 2.5	10.1 ± 2.3	10.0 ± 2.5
MVV, L·min−1	186 ± 61	186 ± 53	184 ± 54	182 ± 54	185 ± 56	181 ± 56	183 ± 55	186 ± 61	188 ± 57	187 ± 65
MVV, % change	-	1.4 ± 9.7	−0.2 ± 5.6	−1.3 ± 7.4	0.02 ± 8.3	−2.2 ± 9.8	−0.9 ± 8.2	−0.1 ± 8.5	2.0 ± 11.0	−0.02 ± 10.2
Training subjects
SVC, L	4.8 ± 1.2	4.7 ± 1.2	4.7 ± 1.2	4.7 ± 1.2	4.7 ± 1.2	4.7 ± 1.2	4.7 ± 1.2	4.7 ± 1.2	4.7 ± 1.3	4.7 ± 1.3
FVC, L	4.7 ± 1.2	4.7 ± 1.2	4.6 ± 1.2	4.7 ± 1.3	4.7 ± 1.2	4.7 ± 1.3	4.6 ± 1.3	4.6 ± 1.3	4.6 ± 1.3	4.6 ± 1.3
FEV1, L	3.9 ± 0.9	3.9 ± 0.8	3.8 ± 0.9	3.9 ± 1.0	3.9 ± 0.9	3.9 ± 0.9	3.8 ± 1.0	3.8 ± 0.9	3.8 ± 0.9	3.8 ± 0.9
FEV1/FVC	.83 ± .07	.86 ± .1	.83 ± .1	.83 ± .1	.84 ± .1	.83 ± .1	.83 ± .1	.83 ± .1	.84 ± .1	.84 ± .1
PEF, L·sec−1	8.6 ± 2.0	8.6 ± 1.9	8.4 ± 1.8	8.5 ± 2.0	8.7 ± 2.0	8.5 ± 1.9	8.4 ± 2.0	8.5 ± 1.9	8.4 ± 2.1	8.3 ± 1.8
MVV, L·min−1	168 ± 38	161 ± 39	163 ± 35	160 ± 33	159 ± 36*	159 ± 37	156 ± 37	156 ± 36	151 ± 37*	150 ± 35
MVV, % change	-	−4.1 ± 6.1	−2.4 ± 5.4	−4.0 ± 3.4	−5.3 ± 4.5	−4.9 ± 6.0	−6.8 ± 6.9	−6.9 ± 5.7	−9.8 ± 7.6	−10.4 ± 8.9

SVC, slow vital capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume 1.0 sec; PEF, peak expiratory flow; MVV, maximal voluntary ventilation

^*P<0.05 vs. Day 1

In TR subjects, the acute effects of hyperpnea on pulmonary function was assessed with spirometry measured serially after each training session. In all variables (FVC, FEV₁, PEF, SVC), repeated measures ANOVA revealed a significant main-effect of time (i.e., pre-hyperpnea, 5-, 10-, 15-, 20-, 30-minutes post-hyperpnea) but no effect of training day. Therefore, each variable was averaged over the ten days for each subject. There was a significant main-effect of time in all four variables (P < 0.05) that was dominated by a similar pattern of a decrease at 5-minutes after hyperpnea followed by a gradual increase during the remainder of recovery (figure 1A–D). Of the four variables, PEF decreased the most and also recovered the least following hyperpnea. Nadir post-hyperpnea values were also analyzed for each variable. Compared with pre-hyperpnea values, FVC, FEV₁, and PEF decreased by −4.4% [−0.19 L (P < 0.001)], −3.4% [−0.12 L (P = 0.005)], and −9.4% [−0.80 L·sec⁻¹ (P < 0.001)] after hyperpnea training. The nadir values occurred most frequently at 5-minutes following hyperpnea (61% of the time), followed by 10-minutes (22% of the time) and 15-minutes (11% of the time) after hyperpnea.

Fig. 1A-B.

(A) FEV₁, (B) FVC, (C) PEF, and (D) SVC at baseline and at multiple timepoints after hyperpnea in ten hyperpnea training subjects. The values represent the mean responses over ten days of hyperpnea training. All variables decreased immediately after hyperpnea training and progressively increased until 30-minutes after hyperpnea.

FEV₁, forced expiratory volume 1 sec; FVC, forced vital capacity; PEF, peak expiratory flow; SVC, slow vital capacity. *, P<0.05 vs. 5 minutes post-hyperpnea; †, P<0.05 vs. BL; ‡, P<0.05 vs. 15 minutes post-hyperpnea

Figure 2A–B depicts both individual subject and group mean results for MVV during the ten days for CON and TR subjects. In CON subjects, MVV did not change during the ten days. In CON subjects, MVV was higher on day ten than day one in three subjects whereas it was lower on day ten compared with day one in five subjects. In TR subjects, MVV decreased by −10.4 ± 8.9% (SD) between day one and day ten [168 ± 38 vs. 150 ± 35 L·min⁻¹ (SD) for day one vs. day ten; P=0.008]. Moreover, MVV decreased during the ten training days in nine out of the ten subjects, and six TR subjects had a greater than 10% decrease in MVV on the final training day compared with the first day. Additional results for MVV are shown in table 2.

Fig. 2A-B.

Individual subject and group mean maximal voluntary ventilation (MVV) during ten experimental days in control (A) and hyperpnea training (B) subjects. In control subjects, MVV did not change across the experimental days. In training subjects, MVV decreased progressively across the ten experimental days.

MVV, maximal voluntary ventilation. *, P<0.05 vs. day 1

Hyperpnea training results (table 3)

Table 3.

Selected variables during ten hyperpnea training sessions (n=10 subjects)

Variable	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Day 8	Day 9	Day 10
${\dot{\mathrm{V}}}_{\mathrm{E}}$, L·min−1	109 ± 23	115 ± 26	117 ± 25	117 ± 26	120 ± 26*	123 ± 23*	124 ± 24*	126 ± 28*	124 ± 26*	125 ± 26*
Vt, L·breath−1	1.8 ± 0.6	1.8 ± 0.7	1.8 ± 0.7	1.7 ± 0.6	1.7 ± 0.6	1.6 ± 0.4	1.6 ± 0.4	1.6 ± 0.5	1.5 ± 0.5	1.5 ± 0.5
fb, breath·min−1	63 ± 20	65 ± 21	65 ± 22	68 ± 24	71 ± 25	76 ± 19	78 ± 18	79 ± 18	81 ± 19*	83 ± 18*
${\dot{\mathrm{V}}}_{\mathrm{E}}$	0.66 ± 0.06	0.68 ± 0.06	0.69 ± 0.05	0.69 ± 0.07	0.71 ± 0.06*	0.73 ± 0.06*	0.74 ± 0.09*	0.75 ± 0.11	0.74 ± 0.09*	0.74 ± 0.08*
Vt/VC	0.39 ± 0.1	0.39 ± 0.1	0.40 ± 0.1	0.37 ± 0.1	0.38 ± 0.1	0.35 ± 0.1	0.34 ± 0.1	0.35 ± 0.1	0.33 ± 0.1	0.32 ± 0.1
IC BL, Liter	2.85 ± 0.82	2.77 ± 0.86	2.89 ± 0.76	2.92 ± 0.80	2.98 ± 0.88	2.83 ± 0.82	2.87 ± 0.76	2.98 ± 0.75	2.87 ± 0.83	2.89 ± 0.88
IC hyp, Liter	2.79 ± 0.75	2.77 ± 0.78	2.80 ± 0.71	2.73 ± 0.64	2.77 ± 0.68	2.58 ± 0.57	2.52 ± 0.61	2.70 ± 0.69	2.55 ± 0.71	2.55 ± 0.62
IC (Δ BL), Liter	−0.05 ± 0.4	0.01 ± 0.4	−0.08 ± 0.4	−0.20 ± 0.4	−0.21 ± 0.5	−0.25 ± 0.5	−0.35 ± 0.4	−0.33 ± 0.5	−0.32 ± 0.5	−0.34 ± 0.5
Vt/IC	0.65 ± 0.1	0.66 ± 0.2	0.67 ± 0.2	0.64 ± 0.1	0.64 ± 0.1	0.63 ± 0.1	0.64 ± 0.1	0.60 ± 0.1	0.62 ± 0.1	0.60 ± 0.1
ETCO2 BL, mmHg	34.5 ± 5.8	33.7 ± 6.1	35.5 ± 5.8	34.1 ± 5.5	35.0 ± 5.2	34.2 ± 6.4	34.2 ± 6.0	34.5 ± 5.8	34.2 ± 5.5	34.6 ± 5.6
ETCO2 hyp, mmHg	36.8 ± 5.9	37.5 ± 7.2	37.0 ± 7.2	36.0 ± 6.4	35.1 ± 6.4	36.6 ± 6.8	37.7 ± 6.1	36.4 ± 7.4	36.4 ± 5.8	37.4 ± 5.8
ETCO2 (Δ BL), mmHg	+2.2 ± 2.9	+3.8 ± 3.8	+1.5 ± 3.1	+1.8 ± 2.8	+0.1 ± 3.8	+2.4 ± 3.2	+3.5 ± 4.6	+1.9 ± 3.9	+2.3 ± 2.7	+2.8 ± 3.0
HR, beats·min−1	115 ± 18	119 ± 19	119 ± 16	120 ± 17	122 ± 18	122 ± 23	122 ± 14	122 ± 18	120 ± 18	122 ± 16

${\dot{\mathrm{V}}}_{\mathrm{E}}$, minute ventilation; Vt, tidal volume; fb, breathing frequency; MVV, maximum voluntary ventilation; IC, inspiratory capacity; ETCO₂, end-tidal CO₂; HR, heart rate; hyp, hyperpnea; BL, baseline.

^*P < 0.05 vs. Day 1

The ${\dot{\mathrm{V}}}_{\mathrm{E}}$ obtained during hyperpnea training increased progressively by 15.4 ± 11.1% (SD) during the first eight training days (P < 0.05) but plateaued on the final two days. As well, ${\dot{\mathrm{V}}}_{\mathrm{E}}$ /MVV increased significantly from 0.66 ± 0.06 to 0.75 ± 0.11 over the first eight training days. Overall, subjects assumed a progressively more tachypneic breathing pattern over the ten training days; group mean fb increased by 37 ± 30% from day 1 to day 10 [63 ± 20 to 83 ± 18 breaths·min⁻¹ (SD); P < 0.05]. Tidal volume decreased non-significantly by 14 ± 16% (−0.29 ± 0.30 L) from the first to tenth training session (P > 0.05). Group mean VT/VC decreased slightly from 0.39 ± 0.1 to 0.32 ± 0.1 (−14%) over the ten training days (P=>0.05). Similarly, VT/IC decreased non-significantly from 0.65 to 0.60 between the first and tenth training day. During the first three training days, hyperpnea IC was not different from the resting value; however, hyperpnea IC decreased by 200 to 350 ml from rest during the remaining seven training days (main-effect F= 3.87, P < 0.0001). ETCO₂ was well-maintained during the training sessions; on average, hyperpnea ETCO₂ was 2.2 ± 2.2mmHg (SD) higher than baseline values (P = ns).

DISCUSSION

We assessed pulmonary function during ten days of high-intensity volitional hyperpnea in healthy adults. Subjects selected their own ventilatory pattern during the training sessions, representing an important methodological difference from the vast majority of hyperpnea training studies. In CON subjects, pulmonary function did not change during the ten experimental days. In TR subjects, measures of forced exhalation and SVC consistently decreased after hyperpnea during the ten training sessions but thereafter increased to baseline values by 30-minutes following hyperpnea. However, all such measures were unchanged before hyperpnea during the ten training days. In contrast, MVV decreased progressively during the ten training days in nine out of the ten TR subjects, whereas it was unchanged in CON subjects. These findings provide evidence that repeated voluntary hyperpnea does not impair daily airway function in healthy adults. However, the progressive decrease in MVV with the training does merit further research.

In our subjects, hyperpnea caused acute, rapidly-reversible decreases in pulmonary function that resolved by 30-minutes after the hyperpnea (Figure 1A–D). The most important new finding in this study is that acute, reversible decreases in airway function after volitional hyperpnea remain consistent across ten days of repeated hyperpnea. Thus, the changes in post-hyperpnea pulmonary function neither worsened nor improved over the training period. Previous work reported decreases in pulmonary function after one session of voluntary hyperpnea (Illi, Hostettler et al. 2011; Eichenberger, Kurzen et al. 2019) and the average post-hyperpnea decrease observed during 20 days of training (Verges, Renggli et al. 2009). Our finding of gradually improved airway function during the 30-minute recovery period is similar to the findings by Eichenberger et al. (Eichenberger, Kurzen et al. 2019). Thus, in contrast to our hypothesis, our findings suggest that repetitive increases in airflow during volitional hyperpnea training do not cause progressive alterations in airway or lung structure or function that determine forced expiratory flow and volume. Furthermore, our findings support the conclusion by others that the acute decreases in airway function after voluntary hyperpnea are small and not likely clinically significant (Wuthrich, Marty et al. 2015; Eichenberger, Kurzen et al. 2019)

The mechanisms for the transitory and modest decline in airway function are not known. The significant decrease in SVC suggests an early airway closure during the maximal exhalation. Potentially, the sustained high airflows during hyperpnea might have caused a small degree of peripheral airway inflammation leading to premature airway closure. It is also possible that the hyperpnea triggered a small amount of airway narrowing, either due to active airway smooth muscle contraction or plasma exudation and increased airway wall thickness (Anderson and Daviskas 2000). In patients with reactive airways disease (e.g., asthma), however, the maximum airway narrowing after voluntary hyperpnea and exercise occurs between 10 and 15-minutes after the stimulus (Haverkamp, Dempsey et al. 2005). In our subjects, the maximum decreases in airway function occurred most frequently 5-minutes after hyperpnea and recovered more rapidly than seen in asthma. Thus, the temporal pattern of the change in airway function after hyperpnea is not compatible with an inflammatory-based airway narrowing. Given the short duration of the reductions in spirometry, it is also reasonable to suggest that they might have been the result of either reduced recruitment, or decreased contractility, of the expiratory muscles during exhalation. The more sustained decrease in PEF (highly effort-dependent) than the other spirometric variables lends support to this hypothesis. Indeed, the hyperpnea required sustained and large increases in airflow exceeding levels maintained during all but the most intense whole-body exercise. On the other hand, a previous study showed that experimentally-induced expiratory muscle fatigue does not affect spirometry in healthy adults (Haverkamp, Metelits et al. 2001).

In contrast to the acute, reversible decreases in pulmonary function following hyperpnea, the training was not accompanied by daily changes in any of the measures of forced exhalation (table 2). Previous studies have been somewhat inconsistent regarding the effects of hyperpnea training on spirometry. Whereas several studies showed improvements in spirometry with hyperpnea training (Sonetti, Wetter et al. 2001; McMahon, Boutellier et al. 2002; Verges, Boutellier et al. 2008; Verges, Renggli et al. 2009; Uemura, Lundgren et al. 2012), others have not (Spengler, Roos et al. 1999; Stuessi, Spengler et al. 2001; Leddy, Limprasertkul et al. 2007; Verges, Lenherr et al. 2007; Keramidas, Debevec et al. 2010). Verges et. al. performed a re-analysis of nine training studies completed in their lab and found that SVC, FVC, and PEF were increased with hyperpnea training (Verges, Boutellier et al. 2008). This analysis must be interpreted with caution, inasmuch as all the studies analyzed took place in the same lab. In any case, in our subjects, the repeated hyperpnea did not have any obvious negative effects on the structural or functional properties of the tracheobronchial tree and lung parenchyma that determine maximal airflow and volumes during traditional spirometry.

Despite the lack of change in pre-hyperpnea spirometry during the training period, daily MVV decreased progressively in the TR subjects whereas it remained unchanged in CON subjects. Previous observations showed an increased MVV following hyperpnea training in normal subjects (Spengler, Roos et al. 1999; McMahon, Boutellier et al. 2002; Leddy, Limprasertkul et al. 2007; Verges, Boutellier et al. 2008; Verges, Renggli et al. 2009; Uemura, Lundgren et al. 2012). Although other studies found no change in MVV with repeated hyperpnea (Sonetti, Wetter et al. 2001; Stuessi, Spengler et al. 2001; Verges, Lenherr et al. 2007; Keramidas, Debevec et al. 2010), to the best of our knowledge the current study is the first report of a progressively decreased MVV with hyperpnea training. Our finding that MVV did not decrease in CON subjects provides evidence that the decreased MVV was not simply due to lack of effort related to repeated visits to the lab.

We do not know why daily MVV decreased in our TR subjects; however, there are several possible explanations for the decrease. Reduced central drive to the ventilatory muscles or decreased contractile capacity (i.e., fatigue) could decrease MVV. The training sessions were challenging, and it is not altogether unlikely that our subjects became motivationally “fatigued” with the neuro-mechanical effort required for a maximal MVV. Unfortunately, we did not measure respiratory muscle function in these studies, but one study did document decreased diaphragm and expiratory muscle twitch pressure after 30-minutes of voluntary hyperpnea (Wuthrich, Marty et al. 2015). Airway narrowing due to some combination of bronchiolar smooth muscle contraction or altered airway wall thickness would be expected to decrease MVV. However, given the unchanged values for the measures of forced expiratory flow during the training period, we think that it is unlikely that airway narrowing contributed to the reduced MVV.

Experimental and methodological considerations

The hyperpnea apparatus and methods used in this study differ in several respects from the majority of hyperpnea training studies in the literature. Our subjects completed fewer training sessions but at higher ventilatory volumes than routinely performed. Importantly, our subjects selected their own breathing pattern during the hyperpnea sessions, and they elected to adopt a very tachypneic pattern in which fb averaged between 63 and 83 breaths·min⁻¹ over the ten training days. In a classic study by Bradley and Leith (Bradley and Leith 1978), subjects selected their own ventilatory pattern and chose a similarly very high fb between 51 and 137 breaths·min⁻¹. In contrast, VT was very low in our subjects, averaging ~35% of vital capacity during the final five days of training. Thus, our subjects ventilated at a significantly lower VT and higher fb than obtained with traditional hyperpnea training paradigms. Additionally, the decreased IC during hyperpnea indicates that our subjects hyperinflated during the training sessions (table 3), increasing the elastic work of breathing and adding to the total ventilatory work.

In most applications of voluntary hyperpnea, partial rebreathing systems are used to maintain normocapnia, whereas we added external dead space to maintain normocapnia. Temperature and water content of inspired air is increased in both systems; however, we did not measure conditions of the inspirate nor were we able to find values in the literature for partial rebreathing systems. The additional tubing increases both inspiratory and expiratory resistance, adding to the work of breathing. We estimated resistance of the external tubing by using a 3-liter syringe to mimic breathing at both different airflows and dead space volumes. On average, the tubing generated a resistance of 1 cmH₂0·L⁻¹·sec⁻¹. While the added resistance increased the training load on the ventilatory muscles, we have no reason to believe that it influenced airway function any differently than partial rebreathing systems. Collectively, however, given these differences in experimental design and methodology, our findings are not necessarily generalizable to traditional methods used for hyperpnea training.

Conclusions

Ten days of high airflow hyperpnea training did not affect daily spirometry, including FVC, FEV₁, PEF and SVC. However, the hyperpnea did cause acute, modest declines in pulmonary function that resolved by 30-minutes post-hyperpnea. Importantly, the acute reductions in airway function after hyperpnea neither improved, nor worsened, during the ten training days. This suggests that repetitive, sustained increases in airflow at levels higher than obtained during whole-body exercise does not cause cumulative detriments in the structural or functional properties of the airways that determine maximal airflow. Finally, MVV decreased progressively across the ten days of training in 90% of TR subjects. This finding warrants further research and also supports the recommendation for regular assessment of pulmonary function in studies of hyperpnea training.

ABBREVIATIONS

CON

Control group

ETCO₂

End-tidal CO₂

fb

Breathing frequency

FEV₁

Forced expiratory volume in 1.0 second

FVC

Forced vital capacity

IC

Inspiratory capacity

MVV

Maximal voluntary ventilation

PEF

Peak expiratory flow

SVC

Slow vital capacity

TR

Hyperpnea training group

VT

Tidal volume

${\dot{\mathrm{V}}}_{\mathrm{E}}$

Minute ventilation