Acute and chronic responses of the upper airway to inspiratory loading in healthy awake humans: An MRI study

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Abstract

We assessed upper airway responses to acute and chronic inspiratory loading. In Experiment I, 11 healthy subjects underwent T2-weighted magnetic resonance imaging (MRI) of upper airway dilator muscles (genioglossus and geniohyoid) before and up to 10 min after a single bout of pressure threshold inspiratory muscle training (IMT) at 60% maximal inspiratory mouth pressure (MIP). T2 values for genioglossus and geniohyoid were increased versus control (p < 0.001), suggesting that these airway dilator muscles are activated in response to acute IMT. In Experiment II, nine subjects underwent 2D-Flash sequence MRI of the upper airway during quiet breathing and while performing single inspirations against resistive loads (10%, 30% and 50% MIP); this procedure was repeated after 6 weeks of IMT. Lateral narrowing of the upper airway occurred at all loads, whilst anteroposterior narrowing occurred at the level of the laryngopharynx at loads ≥30% MIP. Changes in upper airway morphology and narrowing after IMT were undetectable using MRI.

Introduction

During inspiration, contraction of the thoracic inspiratory muscles creates a negative pressure within the intra- and extra-thoracic airways. To prevent upper airway collapse during inspiration, the pharyngeal muscles contract prior to the onset of neural activity to the thoracic inspiratory muscles (Strohl et al., 1980). According to the “balance of pressures” concept, upper airway occlusion occurs when the positive dilating pressure from the upper airway musculature is unable to resist the negative intraluminal pressure caused by inspiratory effort (Brouillette and Thach, 1979). Another approach to understanding airway collapse has been to consider the airway as a collapsible tube. According to this model, the intrinsic properties of the pharyngeal wall determine the collapsibility of the airway (Isono et al., 1997). It is known that chronic training increases the passive stiffness of locomotor muscles, independent of increases in either muscle mass or force output (Lindstedt et al., 2002). Thus, if it were possible to impose a training stimulus upon the upper airway dilator muscles, it is reasonable to suppose that there would be a reduced tendency of the upper airway to collapse due to an increase in the active (neural) tone, an increase in the passive (intrinsic) stiffness of the pharyngeal dilators, or both.

Pressure threshold inspiratory muscle training (IMT) is a method of applying a quantifiable external load to the inspiratory muscles. When applied daily over a period of up to 6 weeks, IMT has been shown to improve the function of the thoracic inspiratory muscles (Romer and McConnell, 2003) and to stimulate adaptive changes, including an increase in the percentage of fatigue resistant Type I fibres and an increase in the size of Type II fibres (Ramirez-Sarmiento et al., 2002). We propose that the skeletal muscles regulating the upper airway are also subjected to a training stimulus during IMT. Specific evidence in support of this postulate is twofold. First, electromyographic (EMG) activity of genioglossus (GG) is increased during inspiratory flow resistive loading (Malhotra et al., 2000, Pillar et al., 2001) and when a negative pressure is applied externally to the upper airway (Aronson et al., 1989, Horner et al., 1991, Pillar et al., 2001). Second, in rodents the hyperpnoea of exercise training has been shown to elicit a fast to slow shift in myosin heavy chain phenotype, and an increase in oxidative and antioxidant capacity, in both the diaphragm and upper airway muscles (Vincent et al., 2002).

There are three pieces of evidence in support of the notion that IMT may enhance the function of the upper airway dilator muscles. First, 4 weeks of voluntary isocapnic hyperpnoea training was found to reduce the incidence of snoring in otherwise healthy subjects (Furrer et al., 1998), whilst 4 months of didgeridoo playing improved sleep-related outcomes in patients with obstructive sleep apnoea (OSA; Puhan et al., 2006). In addition, 8 weeks of tongue-muscle training by intraoral electrical neurostimulation was found to reduce the incidence of snoring in patients with OSA (Randerath et al., 2004). Finally, a number of case study reports show that pressure threshold IMT is effective in treating vocal cord dysfunction (Sapienza et al., 1999, Baker et al., 2003a, Baker et al., 2003b, Mathers-Schmidt and Brilla, 2005). These findings suggest that IMT activates the upper airway muscles in a way that enhances function.

In light of these observations we aimed to quantify the acute and chronic responses of the upper airway to inspiratory loading in healthy awake subjects, before and after 6 weeks of IMT. In Experiment I, we measured the nuclear magnetic resonance (MR) transverse relaxation time (T2) of muscle water (Fleckenstein et al., 1988, Patten et al., 2003) to determine whether specific upper airway dilator muscles are activated in response to an acute bout of pressure threshold IMT. The GG and geniohyoid (GH) were chosen due to their putative role in maintaining upper airway patency (Series, 2002) and because they can be identified clearly on MR images (Ryan et al., 1991, Schotland et al., 1996). In Experiment II, we determined whether there was a dose–response relationship between the magnitude of inspiratory loading and narrowing of the upper airway as assessed using 2D-Flash MR imaging. In addition, we examined the effect of 6 weeks of IMT on this relationship. We hypothesised that a dose–response relationship would be present, whereby larger negative pressures would result in greater narrowing of the airway. Further, we predicted that after IMT, airway narrowing would be attenuated at each level of inspiratory loading.

Section snippets

Subjects

Eleven healthy subjects volunteered for Experiment I and nine individuals volunteered for Experiment II, including five of the subjects from Experiment I. The local Research Ethics Committee approved all experimental procedures and each subject provided written informed consent. All of the subjects had pulmonary function within normal limits, as inferred from maximum flow-volume loops. Descriptive characteristics of the subjects are shown in Table 1.

Pulmonary function

Maximum flow-volume loops were assessed at

Experiment I

The T2 values were not different between the two baseline scans for either GH or GG (Fig. 3). Immediately after the acute bout of IMT, T2 values were elevated above baseline for GG (p < 0.001) and GH (p < 0.001) (Fig. 3). These increases in T2 represented 111 ± 6% and 116 ± 9% of baseline for GG and GH, respectively. In the subgroup of seven subjects, T2 values immediately after acute IMT were elevated, but did not differ from baseline after 5 and 10 min of recovery (Fig. 4).

Experiment II: acute effects

Actual mouth pressure did

Main findings

The main finding of Experiment I was that selected upper airway dilator muscles (GG and GH) were activated in response to an acute bout of pressure threshold IMT, as demonstrated by prolongation of T2 relaxation times. In Experiment II there was a substantial reduction in upper airway cross-sectional area at relatively low inspiratory resistive loads (10% MIP) that did not worsen at higher loads (30% and 50% MIP). The majority of airway narrowing in the axial plane occurred in the lateral

Acknowledgements

We thank Mr. Ari Lingeswaran for technical assistance and Dr. Karl Schmidt for valuable advice regarding the ImageJ software. SCH is supported by a bursary provided by Gaiam Ltd. The authors are also grateful to Gaiam Ltd. for providing the modified POWERbreathe for use in the MRI scanner.

References (51)

  • G.R. Adams et al.

    Mapping of electrical muscle stimulation using MRI

    J. Appl. Physiol.

    (1993)
  • R.M. Aronson et al.

    Upper airway and respiratory muscle responses to continuous negative airway pressure

    J. Appl. Physiol.

    (1989)
  • ATS/ERS

    ATS/ERS statement on respiratory muscle testing

    Am. J. Respir. Crit. Care Med.

    (2002)
  • R.T. Brouillette et al.

    A neuromuscular mechanism maintaining extrathoracic airway patency

    J. Appl. Physiol.

    (1979)
  • I.G. Brown et al.

    Pharyngeal cross-sectional area in normal men and women

    J. Appl. Physiol.

    (1986)
  • M.S. Conley et al.

    Noninvasive analysis of human neck muscle function

    Spine

    (1995)
  • P.R. Eastwood et al.

    Heterogeneous activity of the human genioglossus muscle assessed by multiple bipolar fine-wire electrodes

    J. Appl. Physiol.

    (2003)
  • M.J. Fisher et al.

    Direct relationship between proton T2 and exercise intensity in skeletal muscle MR images

    Invest. Radiol.

    (1990)
  • J.L. Fleckenstein et al.

    Acute effects of exercise on MR imaging of skeletal muscle in normal volunteers

    Am. J. Roentgenol.

    (1988)
  • J.L. Fleckenstein et al.

    ARRS executive council award. Exercise-enhanced MR imaging of variations in forearm muscle anatomy and use: importance in MR spectroscopy

    Am. J. Roentgenol.

    (1989)
  • J.L. Fleckenstein et al.

    Finger-specific flexor recruitment in humans: depiction by exercise-enhanced MRI

    J. Appl. Physiol.

    (1992)
  • P.L. Flicker et al.

    Lumbar muscle usage in chronic low back pain. Magnetic resonance image evaluation

    Spine

    (1993)
  • E. Furrer et al.

    Treatment of snoring by training of the upper airway muscles

    Am. J. Respir. Crit. Care Med.

    (1998)
  • R.A. Green et al.

    A pilot study using magnetic resonance imaging to determine the pattern of muscle group recruitment by rowers with different levels of experience

    Skeletal Radiol.

    (2000)
  • R.L. Horner et al.

    Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man

    J. Physiol.

    (1991)
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