Neural Respiratory Drive and Neuromuscular Coupling During CO2 Rebreathing in Patients with Chronic Interstitial Lung Disease

doi:10.1378/chest.96.4.824

Chest

Volume 96, Issue 4, October 1989, Pages 824-830

https://doi.org/10.1378/chest.96.4.824 Get rights and content

In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd ( $\bar{X}$ P/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P_0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P_0.1, and both EMGd and EMGint were significantly greater in patients. During a CO₂ rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P_0.1 responses to increasing PETCO₂ than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (Δ $\bar{X}$ P/TI/Δ PETCO₂), the average P_0.1 response slope (ΔP_0.1/APETCO₂) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (ΔP_0.1/Δ $\bar{X}$ P/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength.

Section snippets

MATERIAL AND METHODS

We studied 12 patients with biopsy-proved interstitial lung disease (seven men and five women, mean age 57.3 years ± 12, SD) and 18 normal subjects (eight men and ten women, mean age 50 years ± 16.9, SD; range, 25 to 78 years) who served as controls. Informed consent was obtained from each subject. Anthropometric and clinical data of the patients are shown in Table 1. Patients 6, 9, and 12 had progressive systemic sclerosis, and patient 10 had rheumatoid arthritis. In the remaining cases

RESULTS

Functional data of the 12 patients are shown in Table 2. All but two patients (3 and 12) exhibited a significant decrease in static pulmonary volumes (predicted — 1SD × 1.64): on average, the VC was 68.9 percent; RV, 62.1 percent; FRC, 67.1 percent; and TLC, 67.3 percent of the predicted values; the FEV₁ was significantly decreased in all patients but two (3 and 8) (mean =66.2 percent of predicted), and the FEV₁/VC ratio was normal in all patients but one (9) (mean = 82.85 percent). Diffusing

DISCUSSION

Our data show a shallower and faster breathing in patients than in normal subjects. In fact, a lower VT and Ti and a greater f were observed in patients during room air breathing and chemically stimulated breathing. These data are consistent with those of Di Marco et al⁴ and Savoy et al⁶ in patients with CILD. As in other studies,4, 5, 6 the VT/Ti was greater in patients, and the value of this increase was slightly greater than that calculated by Di Marco et al⁴ and Renzi et al.⁵ The reasons

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Cited by (21)

Efficiency of neural drive during exercise in patients with COPD and healthy subjects
2010, Chest
Citation Excerpt :
However, it has been shown that increase in neural drive as assessed by P0.1, a marker of overall respiratory drive, is coincident with increased EMGdi during exercise.14 Moreover, it has been pointed out that the diaphragm is the main contributor to the ventilation both during quiet breathing and at high levels of ventilation effort,15 despite severe pulmonary hyperinflation.16 Therefore, we believe that the EMGdi is a suitable tool for assessment of neural drive in both normal subjects and patients with COPD.4,5,8,11,12,17,18
It is unknown whether efficiency of neural drive as expressed by a ratio of ventilation to the diaphragm electromyogram (EMGdi) in patients with COPD differs from that of healthy subjects during exercise and whether maximal neural drive is exhibited at the point of exercise termination.
We studied 12 male patients with COPD (mean ± SD age, 62.8 ± 10.3 years; FEV₁, 28.1 ± 10.2% predicted) and 12 age- and sex-matched healthy subjects (age, 61.1 ± 7.2 years, FEV₁, 101.5 ± 11.9% predicted). EMGdi was recorded from a multipair esophageal electrode during a constant work (80% of maximal oxygen consumption derived from a previous incremental exercise test) treadmill exercise. Minute ventilation and oxygen consumption were also measured.
Root mean square (RMS) of the EMGdi increased initially and reached a plateau at submaximal drive during constant load exercise in both patients with COPD and healthy subjects. The ratio of ventilation to EMGdi remained stable during exercise in healthy subjects from beginning to the end (100% ± 70% at the beginning and 100% ± 39% at the end, P > .05), whereas the ratio decreased gradually during exercise in patients with COPD (from 85% ± 66% to 42% ± 13%, P < .05).
Efficiency of neural drive decreases in patients with COPD during treadmill exercise. Neural respiratory drive reached a submaximal plateau during constant load exercise in both healthy subjects and patients with COPD, indicating that it may not be the only factor determining exercise capacity.
Do obstructive and restrictive lung diseases share common underlying mechanisms of breathlessness?
2010, Respiratory Medicine
Citation Excerpt :
Although the hypothesis of restricted volume expansion and disrupted neuromuscular coupling appears to be an appealing one, the impact of chemoreceptor activation on dyspnea as a result of arterial hypercapnia, hypoxia, or early metabolic acidosis has not been disproved.42 One of the characteristic features of ILD is a reduction in lung compliance and lung volumes.74,77–80 The mechanical response of the respiratory system is similarly restricted in patients with ILD as in those with COPD: inspiratory capacity is reduced, tidal volume expansion is constrained, which results in greater reliance on an increase in breathing frequency to increase ventilation.74,77–79
This review tries to answer two main questions: (i) What are the neurophysiological underpinnings of the most commonly selected cluster descriptors which define the qualitative dimension of dyspnea in patients? (ii) How do mechanical constraints affect dyspnea? (iii) Do obstructive and restrictive lung diseases share some common underlying mechanisms? Qualitative dimensions of dyspnea, which allude to increased respiratory work/effort breathing, reflect a harmonious coupling between increased respiratory motor output and lung volume displacement in healthy subjects. Descriptors that allude to unsatisfied inspiration are the dominant qualitative descriptors in patients with a variety of respiratory diseases. It is possible that sensory feedback from a multitude of mechanoreceptors throughout the respiratory system (in the muscle, chest wall, airways and lung parenchyma) collectively convey information to the consciousness that volume/flow or chest wall displacement is inadequate for the prevailing respiratory drive. The data would lend support to the idea that: (i) an altered afferent proprioceptive peripheral feedback signals that ventilatory response is inadequate to the prevailing motor drive, reflecting neuromechanical uncoupling (NMU), (ii) mechanical constraints on volume expansion (dynamic restriction) play a pivotal role in dyspnea causation in patients with a variety of either obstructive or restrictive respiratory disorders, and (iii) all of the physiological adaptations that optimize neuromechanical coupling in obstructive and restrictive disorders are seriously disrupted so that an NMU underpins cluster descriptors of dyspnea which are similar in obstructed and in restricted patients.
Mechanism of CO<inf>2</inf> retention in patients with neuromuscular disease
2000, Chest
In many studies of patients with muscle weakness, chronic hypercapnia has appeared to be out of proportion to the severity of muscle disease, indicating that factors other than muscle weakness are involved in CO₂ retention. In patients with COPD, the unbalanced inspiratory muscle loading-to-strength ratio is thought to trigger the signal for the integrated response that leads to rapid and shallow breathing and eventually to chronic hypercapnia. This mechanism, although postulated, has not yet been assessed in patients with muscular dystrophy.
Twenty consecutive patients (mean age, 47.6 years; range, 23 to 67 years) were studied: 11 patients with limb-girdle dystrophy, 3 with Duchenne muscular dystrophy, 1 with Charcot-Marie-Tooth syndrome, 1 with Becker muscular dystrophy, 1 with myotonic dystrophy, 1 with facioscapulohumeral dystrophy, and 2 with amyotrophic lateral sclerosis, without any respiratory complaints. Seventeen normal subjects matched for age and sex were studied as a control group.
Routine spirometry and arterial blood gases, maximal inspiratory and expiratory muscle pressures (MIP and MEP, respectively), and pleural pressure during maximal sniff test (Pplsn), were measured. Mechanical characteristics of the lung were assessed by evaluating lung resistance (RL) and dynamic elastance (Eldyn). Eldyn was assessed as absolute value and as percent of Pplsn; Eldyn (%Pplsn) indicates the elastic load per unit of inspiratory muscle force. Breathing pattern was assessed in terms of time (inspiratory time [Ti]; respiratory frequency [Rf]) and volume (tidal volume [Vt]) components of the respiratory cycle.
A rapid shallow breathing pattern, as indicated by a greater Rf/Vt ratio and a lower Ti, was found in study patients compared to control subjects. Eldyn was greater in study patients, while MIP, MEP, and Pplsn were lower. Paco₂ inversely related to Vt, Ti, and Pplsn (p = 0.012, p = 0.019, and p = 0.002, respectively), whereas it was directly related to Rf, Rf/Vt, Eldyn, and Eldyn (%Pplsn) (p < 0.004 to p < 0.0001). Also Eldyn (%Pplsn) inversely related to Ti, and the latter positively related to Vt. In other words, increase in Eldyn (%Pplsn) was associated with decrease in Ti, and the latter was associated with lower Vt and greater Paco₂. Mechanical and breathing pattern variables were introduced in a stepwise multiple regression that selected Eldyn (%Pplsn) (p < 0.0001; r² = 0.62) as a unique independent predictor of Paco₂.
The present study shows that in patients with neuromuscular disease, elastic load and respiratory muscle weakness are responsible for a rapid and shallow breathing pattern leading to chronic CO₂ retention.
Measurement of respiratory muscle strength
1995, Respiratory Medicine
Control of breathing in a subset of patients with systemic lupus erythematosus
1995, Chest
Inspiratory muscle weakness and abnormalities in breathing pattern and in respiratory drive have been reported in patients with multisystem disorders. In patients with systemic lupus erythematosus (SLE), data on respiratory muscle strength and control of breathing are scarce.
We studied a subset of nine female patients with SLE with no major findings of cardiovascular, renal, or neurologic involvement, and with a normal routine chest radiograph. An age- and sex-matched normal group was also studied as a control. We evaluated lung volumes, diffusing lung properties (TLco, TLCO/VA), maximal inspiratory (MIP) and expiratory (MEP) pressures, end-tidal carbon dioxide tension (Pco₂), and breathing pattern: ventilation (VE), tidal volume (VT), inspiratory time (TI), and respiratory frequency (Rf). Neural respiratory drive, assessed in terms of mean inspiratory flow (VT/TI), mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (Edi) and intercostal (Eps) muscles was also evaluated.
As a whole, patients exhibited mild decrease in MIP; vital capacity was slightly reduced in two patients and TLCO/VA was moderately reduced in three. During a hypercapnic rebreathing test, ΔVT/ΔPCO₂ was lower, ΔP0.1/ΔPCO₂ was normal, while ΔEdi/ΔPCO₂ and ΔEps/ΔPCO₂ were higher in patients compared with normal control subjects. ΔVT/ΔPCO2 significantly related to MIP. At 60 mm Hg of PCO₂ patients maintained the rapid and shallow pattern of breathing (RSB) exhibited during room-air breathing: lower VT, shorter Ti, and greater Rf, with VE, VT/TI, and Edi being greater compared with the normal control subjects.
These data seem to indicate that in this SLE subset, mild decrease in respiratory muscle strength may accompany an increased respiratory drive, and contribute to a qualitatively abnormal ventilatory response (RSB) to carbon dioxide stimulation.
Respiratory center activity during mechanical ventilation
1991, Journal of Critical Care

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This research was supported by grants from the Ministero della Pubblica Istruzione of Italy.

Manuscript received August 8; revision accepted February 10.

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Chest

Clinical InvestigationsNeural Respiratory Drive and Neuromuscular Coupling During CO2 Rebreathing in Patients with Chronic Interstitial Lung Disease

Section snippets

MATERIAL AND METHODS

RESULTS

DISCUSSION

Respir Physiol

Chest

Am J Med

Respir Physiol

Mechanical impedance as determinant of inspiratory neural drive during exercise in humans

J Appl Physiol

Diaphragmatic EMG and occlusion pressure response to elastic loading during CO2 rebreathing in humans

J Appl Physiol

Occlusion pressure and breathing pattern in patients with interstitial lung disease

Am Rev Respir Dis

The pattern of breathing in diffuse lung fibrosis

Bull Eur Respir Physiol

Role of vagal airway reflexes in control of ventilation in pulmonary fibrosis

Clin Sci

Diaphragmatic response to isocapnic hypoxia and hyperoxic hypercapnia in humans

J Lab Clin Med

Control of breathing in normal subjects and in patients with chronic airflow obstruction

Bull Eur Physiopathol Respir

New height-weight tables; importance of new criteria

JAMA

Cardiopulmonary adaptation to exercise in coal miners

Arch Environ Health

Effects of inhaled histamine on occlusion pressure and breathing pattern in asthmatic patients

Clin Allergy

Electromyogram pattern of diaphragmatic fatigue

J Appl Physiol

Contribution electromyographique à l'étude de la mécanique et du controle nerveux des mouvements respiratoires de l'homme

Quantification of diaphragmatic EMG response to CO2 rebreathing in humans

J Appl Physiol

A clinical method for assessing ventilatory response to carbon dioxide

Aust Ann Med

Clinical Investigations
Neural Respiratory Drive and Neuromuscular Coupling During CO₂ Rebreathing in Patients with Chronic Interstitial Lung Disease