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Respiratory muscle training in neuromuscular disease: long-term effects on strength and load perception

GOZAL, DAVID; THIRIET, PATRICE

Medicine & Science in Sports & Exercise: November 1999 - Volume 31 - Issue 11 - p 1522
Clinical Sciences: Clinically Relevant

GOZAL, D., and P. THIRIET. Respiratory muscle training in neuromuscular disease: long-term effects on strength and load perception. Med. Sci. Sports Exerc., Vol. 31, No. 11, pp. 1522–1527, 1999.

Purpose: Deterioration of respiratory muscle function in patients with neuromuscular disorders is primarily responsible for the high morbidity and mortality associated with these diseases.

Methods: The potential benefit of respiratory muscle training (RMT) on preservation of respiratory muscle strength and respiratory load perception (RLP) was examined in 21 children (mean age: 12.2 ± 1.8 yr [SD], 16 male) with Duchenne’s muscular dystrophy or spinal muscular atrophy type III, and in 20 age-, weight-, and sex-matched controls. Subjects were randomly allocated to undergo incremental RMT with resistive inspiratory and expiratory loads for a period of 6 months (trained group, TR) or to perform similar exercises with no load (NT). Maximal static inspiratory (Pimax) and expiratory (Pemax) pressures and RLP (modified Borg visual analog scale 0–10) were assessed on two separate occasions before beginning of the training protocol, monthly throughout RMT duration, and every 3–6 months upon cessation of RMT for 1 yr.

Results: In controls, no significant changes in maximal static pressures or load perception occurred during RMT or thereafter. Training in neuromuscular disorder (NMD) patients was associated with improvements in Pimax (mean Δmax: +19.8 ± 3.8 cmH2O in TR vs +4.2 ± 3.6 cmH2O in NT;P < 0.02) and in Pemax (mean Δmax: +27.1 ± 4.9 cmH2O in TR vs −1.8 ± 3.4 cmH2O in NT;P < 0.004). Similarly, RLP significantly decreased during the RMT period in TR (mean Δ: 1.9 ± 0.3;P < 0.01) but did not change in NT (−0.2 ± 0.2). In addition, with cessation of RMT, static pressures returned to pretraining values in TR within ∼3 months. However, RLP was still improved after 12 months.

Conclusions: We conclude that in children with NMD, although RMT-induced increases in expiratory muscle strength are rapidly reversible, long-lasting improvements in RLP occur and could be associated with decreased respiratory symptoms.

Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Section of Pediatric Pulmonology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112; and Centre de Recherche et d’Innovation sur le Sport, Unité de Formation et de Recherche en Activité Physique et Sportive, Université Claude Bernard, Lyon 1, Villeurbanne, FRANCE

Submitted for publication October 1998.

Accepted for publication March 1999.

Address for correspondence: David Gozal, M.D., Section of Pediatric Pulmonology, SL-37, Tulane University School of Medicine 1430 Tulane Avenue, New Orleans, LA 70112; E-mail: dgozal@tmcpop.tmc.tulane.edu.

One of the most common causes of death among patients afflicted with a neuromuscular disorder (NMD) is respiratory insufficiency. Respiratory failure may present either acutely, as a result of pneumonia, or may develop more chronically as a result of progressive respiratory decompensation.

Measurement of respiratory muscle strength is an important component in the clinical evaluation of NMD patients. Normative values of static maximal pressures have been derived for children and show that after the first year of life they are quite similar to those found in adults, ranging between 80 and 120 cmH2O (11,34).Maximal inspiratory (Pimax) and expiratory mouth pressures (Pemax) are most frequently reported in the literature regarding NMD patients and are usually found to be reduced (1,2,33).

Because the primary component affecting lung function in NMD children consists of respiratory muscle weakness, several investigators have attempted to preserve or improve respiratory muscle strength by regular respiratory muscle training (RMT) schedules. The effects of inspiratory muscle training in NMD patients may vary (7,21,29,32,35). However, although most studies reported no changes in vital capacity (VC), significant improvements in maximal static or sustainable inspiratory pressures were usually observed within ≥ 6 wk of RMT at least in less severely affected patients, and no deleterious effects of training were apparent (35). It is therefore possible that depending on the outcome variable measured during and after RMT, results may reflect the clinical stage at which training was begun and/or be contingent upon the type and duration of the training protocol rather than truly indicate an impaired capacity of the NMD respiratory muscles to respond to a given protocol. In addition, it remains so far unclear whether regular RMT in NMD patients will decrease respiratory morbidity, reduce dyspnea, provide a buffer for developing respiratory failure during an acute pulmonary infection, or increase exercise tolerance and overall physical activity and well-being.

The present study was therefore conducted based on the hypothesis that RMT in children with NMD would be associated with improvements in maximal static pressures and concurrent alterations in respiratory load perception (RLP).

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SUBJECTS AND METHODS

Subjects.

A total of 21 children with Duchenne muscular dystrophy (DMD) or spinal muscular atrophy (SMA) and 20 age- and sex-matched controls were recruited to participate in the study. The diagnoses of DMD and SMA type III were based on standard clinical and laboratory criteria (9,30). All NMD patients were wheelchair bound corresponding to functional capacity stage 9, based on the criteria of Inkley et al. (14).

Four study groups were randomly selected and consisted of NMD patients who underwent RMT (NMD-TR) or trained with no respiratory loads (NMD-NT) and their matched controls (CO-TR, and CO-NT). The NMD-TR group consisted of 11 subjects, 7 male, and ages ranged from 7 to 17 yr (mean 12.7 ± 2.2 yr [SD]). For NMD-NT (N = 10), mean age was 13.2 ± 2.6 yr and 6 were male. Similarly, in 10 CO-TR, mean age was 12.9 ± 2.4 yr (6 male), and in CO-NT, mean age was 13.0 ± 2.9 yr (6 males). After institutional approval, informed consent was obtained from each subject and his or her parent or guardian.

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Pulmonary function tests.

Pulmonary function studies were performed in the laboratory, located near sea level (mean atmospheric pressure 761 mm Hg). The best forced vital capacity (VC), forced expiratory volume in 1 s (FEV1), mean forced expiratory flow during the middle half of forced vital capacity (FEF25%−75%) and maximal expiratory flow volume curves were obtained from forced expiration into the wedge spirometer (Collins, DSIIa, Braintree, MA) and corrected for body temperature, pressure saturated (BTPS). Functional residual capacity was measured with a body pressure plethysmograph (Sensormedics 2800 Autobox, Yorba Linda, CA) by the method of DuBois et al. (8). Individual test results were considered abnormal if they were greater than ± 2 SD of the predicted means and were expressed as a percentage of predicted based on available reference values and regression equations (6,26). For NMD patients, armspan was used as an estimate of height (15).

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Maximal respiratory static pressures.

Measurements were performed using the technique previously described by Nickerson and Keens (25). Briefly, subjects were seated, wearing noseclips, and breathing via a mouthpiece. The mouthpiece was connected directly to a manifold with a safety port that could easily be occluded. The manifold included a 1.5-mm hole to help keep the glottis open, thereby preventing the subject from generating additional positive or negative pressures with facial and pharyngeal muscles. The manifold was connected to a pressure gauge (Inspiratory Force meter, model 4101, Boehringer Laboratories, Norristown, PA) via an isolation kit that separates the meter from the patient and uses an 18-inch internal diameter surgical tube (Tygon) with 1/16-inch wall thickness (Performance Plastics, Akron, OH). The calibrated pressure gauge measures pressures from −150 cmH2O to + 150 cmH2O in increments of 2 cmH2O.

Pimax was always measured from residual volume (RV), whereas Pemax was measured from total lung capacity (TLC). Before testing, the subjects underwent detailed instructions of the maneuvers, instructed how to inhale to TLC or exhale to RV, how to occlude the safety port, and then inhale or exhale maximally. Subjects were also instructed not to use their cheek and mouth muscles to generate additional pressure. Demonstration of the maneuvers was provided as needed. Subjects were allowed to practice the maneuver until one of the investigators was convinced that the appropriate technique was being employed, at which time measurements were started. Visual feedback as well verbal encouragements were provided to optimize performance. In an effort to minimize the biasing effect of learning during maximal pressure measurements, at least 20 maneuvers were performed by each subject for both Pemax and Pimax, and the average of the three highest values with ≤ 5% variability from all recorded maneuvers was retained as recently recommended (36).

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Load perception.

Subjects were seated comfortably in a sound-muffled chamber which was separated by a plexiglas partition from the experimenter and measuring apparati. Subjects breathed through a mouthpiece and nonrebreathing valve (Hans Rudolph, Kansas City, MO), and particular care was taken to secure the valve such that the only requirement on the subject was to maintain an airtight seal. The resistive loads consisted of regulatable inspiratory and expiratory pressure devices (Threshold IMT and Threshold PEP, Healthdyne, Cedar Grove, NJ) that were calibrated before the experimental procedure using a pressure transducer and were covered with a black cloth such that the various pressure settings were invisible to the subjects. A series of five test loads including the highest load (25 cmH2O) and lowest load (7 cmH2O) were initially presented in practice sessions to familiarize the subjects with the range of loads. Loads were then presented in random order at 0, 7, 10, 15, and 20 cmH2O at least 10 times for each load with 6–10 unloaded breaths being allowed between loads. A red light signal cue was given immediately before each loaded breath that the subject needed to evaluate, and the subject then provided the appropriate feeling descriptor of the estimate of the load according to a Borg category scale ranging from 0–10 (3). The average score for the 15-cmH2O load was retained for subsequent analysis.

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Experimental protocol.

Lung function was assessed immediately before initiation of the study (T0), upon completion of the training period of 6 months (T6), and at the end of the follow-up period (T18). Maximal static respiratory pressures (Pimax and Pemax) as well as RLP were evaluated 3 months before initiation of the study (T3), at T0, during RMT (T3 and T6), and after discontinuation of RMT (T9, T12, and T18).

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Respiratory muscle training at home.

The training protocol consisted of using individual expiratory and inspiratory breathing resistors (Threshold IMT and Threshold PEP, Healthdyne) twice daily. The use of the training devices was demonstrated to each subject by one of the investigators, and subjects practiced as long as required until the appropriate technique was achieved. Subjects started by breathing via each of the two devices at the lowest pressure (7 cmH2O) for 1 min followed by 1-min rest periods and increased the pressure by 2 cmH2O until they reached their targeted maximal training pressures (at least 30% of the Pimax or Pemax). In addition to weekly telephone reminders, diaries of the daily performances in each training session were filled by the subjects or their parents and mailed to the investigators on a weekly basis in prestamped envelopes. The training technique was further reassessed at the designated follow-up times (T3 and T6).

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Data analysis.

Data are presented as mean ± SD. Two-way analyses of variance (ANOVA) for repeated measures followed by Neuman Keuls post hoc tests or paired Student t-tests were employed to determine statistical differences for Pimax, Pemax, and RLP over time among the various experimental groups. A P-value of < 0.05 was considered to achieve statistical significance.

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RESULTS

The pulmonary function characteristics of the subjects in the four study groups are shown in Table 1. NMD patients had evidence of restrictive lung involvement and reduced expiratory flows compared with controls. In addition, significant decreases in Pimax and Pemax were present in all NMD subjects compared to the control groups (P < 0.01).

Table 1

Table 1

Improvements in Pimax and Pemax occurred with respiratory muscle training in NMD-TR but not in NMD-NT or in any of the two control groups. The improvements in maximal static pressures lasted throughout the duration of the training period (Figs. 1 and 2;P < 0.02), whereas no changes occurred in NMD-NT or in the trained or untrained control groups. When changes in Pimax were expressed as the maximal difference in Pimax from T0 or ΔPimax, NMD-TR increased by +19.8 ± 3.8 cmH2O versus +4.2 ± 3.6 cmH2O in NMD-NT (P < 0.02). Similarly, mean ΔPemax was significantly larger in NMD-TR (+27.1 ± 4.9 cmH2O) compared with NMD-NT (−1.8 ± 3.4 cmH2O;P < 0.004). However, despite improved maximal static pressures, no significant changes in lung function occurred at the end of the training period.

Figure 1

Figure 1

Figure 2

Figure 2

Upon discontinuation of RMT, Pimax returned to pretraining values after 3 months and similarly, Pemax was back to baseline values within 3 months (Figs. 1 and 2). In contrast, no significant reduction in lung function occurred in any of the groups one yr after cessation of RMT.

The categorical load perception scores assigned to a standard inspiratory load of 15 cmH2O were markedly higher in both NMD-TR and NMD-NT before and at initiation of the RMT period (Fig. 3). However, although no changes in RLP occurred in NMD-NT, CO-NT, and CO-TR over time, marked decreases in RLP were already present after 3 months of training. Indeed, RLP significantly decreased during the RMT period in NMD-TR (mean ΔRLP: 1.9 ± 0.3) but did not change in NMD-NT (−0.2 ± 0.2). The improvements in RLP persisted for at least 12 months after discontinuation of RMT in NMD-TR, such that no significant changes in RLP from the values measured at the end of the training period occurred over time even at completion of the experimental protocol in the NMD-TR group (RLP at T6 vs T9, T12, and T18:P-value, not significant;Fig. 3). Qualitatively similar findings occurred for all loads examined during RLP tests but group differences were particularly prominent for the higher loads (i.e., 15 and 20 cmH2O).

Figure 3

Figure 3

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DISCUSSION

Our study shows that 6 months training of respiratory muscles in NMD patients was associated with improvements in Pimax and Pemax, which rapidly return to pretraining levels once training is discontinued. However, the reduction in respiratory load perception scores that accompanies training-induced increases in maximal static pressures persists well after maximal pressures have returned to baseline untrained values.

Before we discuss the implications of our study, several issues regarding the compromise of respiratory function in NMD need to be addressed because respiratory impairment is often an early sign of progressive disease. Decreases in TLC and VC are usually closely linked to the degree of muscular weakness, such that declines in VC will occur over time with disease progression and with age (14,16,31). In addition, the restrictive element introduced by development and progression of scoliosis (19), reductions in chest wall compliance in older NMD patients that are independent of scoliosis (10,22), and decreases in pulmonary compliance that occur as a result of widespread microatelectatic changes (12) will further compound the decrease in TLC and VC of NMD children. Despite the reduction in lung volumes, an increase in RV may be frequently observed in NMD patients, most likely reflecting the disproportionate weakness of expiratory muscles in these patients, such that a close curvilinear relationship was found between RV/TLC and Pemax (4,14,37). Thus, the pulmonary findings in our NMD patients are concordant with previous studies assessing lung function in such populations.

The values of Pimax and Pemax in the control groups were similar to those reported for normal children (11,34), and as expected such measurements were significantly reduced in NMD subjects. In the present study, RMT was associated with significant improvements in both Pimax and Pemax, and our findings are similar to those previously reported by several investigators (7,21,29,32,35). However, Wanke et al. (35) found that the improvements in Pimax were substantially preserved even 6 months after discontinuation of an inspiratory muscle training period of 6 months duration. In contrast, return of maximal static pressures to pretraining values occurred within 3 months in the NMD-TR group. The explanation for such disparate findings is unclear because the duration of RMT was identical in the current study and in Wanke et al. study (35). Furthermore, similar load approaches were employed during the training protocol and have been shown to be effective in patients with chronic obstructive lung disease (20).

The mechanisms underlying perception of resistive respiratory loads assign a preponderant role to parenchymal and airway components with lesser contributions from chest wall activity (27). RLP is lower in children compared with adults and appears to be correlated to intrinsic respiratory system resistance (23). Furthermore, the magnitude of RLP is positively correlated to ventilatory drive (5), and similar pathways appear to be involved in perception of inspiratory and expiratory resistive loads (24). Evidence for increased baseline respiratory drive in NMD patients as found by Baydur (1) and Gigliotti et al. (13) would therefore suggest that RLP is increased in patients with NMD and could induce large disproportionate increases in air hunger when small respiratory loads are added. Thus, changes in the ability to estimate the magnitude of a respiratory load may be of clinical importance in NMD. For example, decreased RLP scores were reported in both children and adults with severe asthma (17,18) and were postulated to contribute to delays in therapeutic intervention thereby facilitating the development of near-fatal or fatal asthmatic events (17,18). Conversely, disproportionate increases in load perception in relation to a given increase in respiratory load as might occur during a mild upper respiratory tract infection (URI) in patients with respiratory muscle weakness could lead to marked respiratory distress and air hunger leading to the need for earlier implementation of endotracheal intubation and mechanical ventilatory support, clearly undesired courses of action in this patient population. Thus, reductions in respiratory load perception in NMD patients could lead to improved tolerance to intercurrent illnesses such as URI. Incidentally, parental reports in 7 of the 11 NMD-TR indicated that these children appeared more physically active and displayed less respiratory difficulty or fatigue with their usual daily activities. No such reports occurred in the NMD-NT group.

The mechanisms underlying the persistence of reduced respiratory load perception over time despite the return of maximal static pressures to pretraining values are unknown. It is possible that the persistent effect of RMT on RLP could represent a long-lasting plasticity of respiratory sensation such as that described by Revelette and Wiley (28). Indeed, these investigators found that after 2-min period in which subjects were required to breathe through a high resistive load, the perceptual scores for a loading protocol were markedly reduced compared with those before high-resistance breathing. This study did not explore however the duration of such plasticity changes in load sensation (28). It is therefore possible that a long-duration training period as used in the present study could be associated with prolonged effects on the magnitude estimates of a standard resistive load.

In summary, we have shown that respiratory muscle training will enhance maximal respiratory pressures and reduce the magnitude estimate of a standard resistive respiratory load. However, although the effect on respiratory muscle strength will rapidly abate if training is stopped, the reduction in respiratory load perception is long-lasting. Further studies are clearly necessary to establish the mechanisms and potential long-term benefits of RMT on respiratory morbidity and quality of life in patient with neuromuscular weakness.

We thank the respiratory technicians who performed the pulmonary functions tests and the subjects and families for their participation and enthusiastic cooperation. D.G. was supported in part by grants from the National Institute of Health (HD-01072), the Maternal and Child Health Bureau (MCJ-229163), and a Career Development Award from the American Lung Association (CI-002-N).

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Keywords:

RESPIRATORY PERCEPTION; RESISTIVE LOAD; SPINAL MUSCULAR ATROPHY; MUSCULAR DYSTROPHY; LOADED BREATHING

© 1999 Lippincott Williams & Wilkins, Inc.