Ventilatory Drive at Rest and Perception of Exertional Dyspnea in Severe COPD

doi:10.1378/chest.115.5.1293

Chest

Volume 115, Issue 5, May 1999, Pages 1293-1300

https://doi.org/10.1378/chest.115.5.1293 Get rights and content

Background

The reasons for exertional dyspnea in severe COPD are not well established, but they are not solely related to the mechanical load. We tested the hypothesis that breathlessness may be determined, in part, by the response of an individual's central output.

Methods

In 26 patients with severe COPD (FEV₁ < 50% predicted) and 22 matched control subjects, we assessed at rest the ventilatory and mouth occlusion pressure (P_0.1) response to hyperoxic progressive hypercapnia. At rest and during a symptom-limited exercise test, routine cardiopulmonary variables were measured, and respiratory muscle function was evaluated using esophageal and gastric pressure. Dyspnea was assessed with a visual analog scale.

Results

Dyspnea with or without leg discomfort limited exercise in 73% of patients. Peak exercise dyspnea correlated only with dyspnea at rest (r = 0.5, p < 0.008) and P_0.1 response to CO₂ (ΔP_0.1/Δ[end-tidal Pco₂]Petco₂) (r = 0.48, p = 0.02). Multiple regression analysis including resting and exercise data as independent variables revealed that 47% of the variance for dyspnea at peak exercise was explained by a model including dyspnea at rest andΔ P_0.1/ΔPetco₂. Again,Δ P_0.1/ΔPetco₂ was the only predictor for the change in dyspnea from rest to peak exercise (Δ Dyspnea, r² = 0.28, p = 0.005). There was no correlation between exercise dyspnea and any metabolic variable, pulmonary function, or respiratory muscle function test.

Conclusion

In severe COPD, exertional dyspnea is not simply related to respiratory muscle load or mechanical impairment, but also to an individual's central motoneural output to the respiratory system.

Section snippets

Subjects

This study population consisted of 26 consecutive men with stable COPD. All patients had a diagnosis of COPD according to the criteria of the American Thoracic Society.¹³ All were referred for evaluation of possible lung volume reduction surgery. They were studied under stable clinical and functional conditions and gave informed consent. The study was approved by the Human Studies Review Board at St. Elizabeth's Medical Center.

Pulmonary Function Tests

Spirometry was measured with a calibrated dry seal spirometer

Population Characteristics

Clinical and spirometric data of the patient and control groups are listed in Table 1. The age and anthropometric findings were similar. As expected, the FVC and FEV₁ were normal in the control subjects and showed severe airways obstruction in the COPD group. On plethysmography, most patients also manifested significant hyperinflation. As a group, the patients had normal blood gas values, but eight of them were hypoxemic (Pao₂ < 60 mm Hg) and nine were hypercapnic (Paco₂ > 45 mm Hg).

Control of Breathing

The

Discussion

The most important finding in this study is that the degree of exertional dyspnea in patients with severe COPD correlates with resting respiratory drive and the individual's response of the central output to increased central drive CO₂ stimuli. The value of the slope of the P_0.1 response to progressive hypercapnia (ΔP_0.1/ΔPetco₂) explained close to 30% of the change in the dyspnea the patients experienced from rest to peak exercise. Coupled with dyspnea at rest,Δ P_0.1/ΔPetco₂ also explained

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We studied 243 consecutive children (age, 13.2 ± 2.1 years; 128 boys) with maximal cardiopulmonary exercise testing. All children had normal clinical examination and echocardiograms. In all children, the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO₂ slope) was calculated using both only data until the respiratory compensation point (VE/VCO_2RC) and using data until peak exercise (VE/VCO_2Peak).
The exercise test was maximal in all children (peak respiratory exchange ratio, 1.2 ± 0.1). For all the cohorts, VE/VCO_2Peak slope was 28.2 ± 3.7; and VE/VCO_2RC slope was 24.5 ± 3.0, whereas peak oxygen uptake was 94.6% ± 14.0% of predicted value. Baseline spirometric function was normal in all children (vital capacity, 100% ± 14% and forced expired volume in the first second 97% ± 13% of predicted). From the age of 10 to 16 years, we observed a progressive decrease in both VE/VCO_2Peak and VE/VCO_2RC slopes (−0.833 and −0.705 per each year), with the highest reduction observed in boys. Gender-specific percentiles for both VE/VCO_2Peak and VE/VCO_2RC slopes were constructed.
Ventilatory response to exercise expressed as VE/VCO₂ slope seems to decrease progressively in the second decade of life. Because of age-related changes, interpretation of VE/VCO₂ slopes in this age range should be based on the reported percentiles rather than on the absolute values.
Effects of interval exercise training on respiratory drive in patients with chronic heart failure
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Furthermore, the ventilatory response to exercise as assessed by VE/VCO2 slope, a significant prognosis indicator that also reflects interstitial pulmonary edema demonstrated a trend to improve.44 In patients with Chronic Obstructive Pulmonary Disease (COPD) the degree of exertional dyspnea correlates with resting respiratory drive and at similar mechanical load and similar levels of respiratory muscle dysfunction, dyspnea may result from an individual’s response of the central motor output.45 These data support the concept that exertional dyspnea is modulated by afferent output from central receptors.
Patients with chronic heart failure (CHF) suffer from ventilatory abnormalities. This study examined the effects of interval exercise training on the respiratory drive in CHF patients.
Forty-six clinically stable CHF patients (38 males/8 women, mean age = 53 ± 11 years) participated in an exercise rehabilitation program (ERP) 3 times/week, for 12 weeks by interval training modality with or without the addition of resistance training. All patients underwent symptom-limited cardiopulmonary exercise testing (CPET), and measurements of mouth occlusion pressure at 100 ms (P_0.1) and maximum inspiratory muscle strength (P_Imax) before and after ERP. Respiratory drive was estimated by mouth occlusion pressure P_0.1 and P_0.1/P_Imax ratio at rest, and the ventilatory pattern by resting mean inspiratory flow (V_T/T_I) and by V_T/T_I at identical CPET workloads, before and after ERP. We also studied a control non exercising group of 11 patients (8 men and 3 women).
P_0.1 at rest decreased from 3.04 ± 1.52 to 2.62 ± 0.9 cmH₂O (p = 0.015), P_0.1/P_Imax % at rest from 4.56 ± 3.73 to 3.69 ± 2.03 (p = 0.006), resting V_T/T_I from 0.44 ± 0.10 to 0.41 ± 0.10 l/s (p = 0.014), and V_T/T_I at identical work rate from 2.13 ± 0.59 to 1.93 ± 0.58 l/s (p = 0.001) after ERP. VO₂ at peak exercise increased from 16.3 ± 4.8 to 18.5 ± 5.3 ml/kg/min (p < 0.001) in the exercise group. No improvement was noted in the control group.
ERP by interval training improves the respiratory drive and ventilatory pattern at rest and during exercise in CHF patients.
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This study aimed to determine whether exercise testing, overbreathing and altered breathing pattern can reflect early respiratory impairment.
Twenty-four active ED male smokers aged 33–60 years, with no background of muscular, cardiac or respiratory disease, were compared to 31 healthy smokers (with no ED). Spirometry, plethysmography, ventilatory pattern and arterial blood gases were assessed in both groups and dyspnea was estimated using a Borg scale at every 30W/3 min step of incremental maximal exercise, starting with 40 W for 10 min.
Spirometry data was normal in both groups. Compared to healthy subjects, the respiratory pattern was significantly (p<0.001) more rapid and shallow with smaller tidal volume (VT) (p<0.001) and less alveolar ventilation ( ${\dot{V}}_{A} / {\dot{V}}_{E}$ ) and PaO₂ while ventilation ( ${\dot{V}}_{E}$ ), the ratio ${\dot{V}}_{E}$ /MVV, ventilatory frequency (fB), dead space ventilation (VD), lactic acidemia, and cardiac frequency (fC) were significantly higher (p<0.01) in the ED group. The significant differences (p<0.05) observed at rest were amplified during exercise and $\dot{V} O_{2}$ pico and maximal power load were 30% lower (p<0.001) in ED subjects.
Apparently healthy subjects, whose spirometry are normal, complain of exertional dyspnea associated with a combination of adverse effects of: increased central ventilatory demand, overbreathing, impairments of ventilatory pattern, hypoventilation, and severe reduction of the maximal levels of exercise. These changes are not often explored, although they are potentially susceptible to correction corrected with sophisticated respiratory physiotherapy and exercise training.
Severe respiratory insufficiency in a patient with chronic obstructive pulmonary disease following carbogen inhalation
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Citation Excerpt :
First, supplemental oxygen given to COPD patients with CO2 retention may result in worsening respiratory acidosis, an effect that is usually attributed to the loss of their hypoxic stimulus to breathe.3 Second, the degree of dyspnea in patients with severe COPD during carbogen inhalation correlates with their response to increased central drive CO2 stimuli.4,5 Hence carbogen imposes both an increased hypercapnic motoneural output to the respiratory system with the subjective feeling of shortness of breath and hyperoxic suppression of ventilatory drive that further worsens CO2 retention thus creating a viscous cycle.

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: Dr. Marin is the recipient of a fellowship from the Fondo de Investigaciones Sanitarias (FIS 96/5696) Spain.

^†: Currently at Universidad Central de Venezuela, Caracas, Venezuela.

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Chest

Clinical InvestigationsCONTROL OF BREATHINGVentilatory Drive at Rest and Perception of Exertional Dyspnea in Severe COPD

Background

Methods

Results

Conclusion

Section snippets

Subjects

Pulmonary Function Tests

Population Characteristics

Control of Breathing

Discussion

Chest

Chest

Pulmonary mechanics during exercise in subjects with chronic airflow obstruction

J Appl Physiol

Right ventricular performance during upright exercise in patients with chronic obstructive pulmonary disease

Am Rev Respir Dis

Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation

Am Rev Respir Dis

Dyspnea

Exertional breathlessness in patients with chronic airflow limitation: the role of lung hyperinflation

Am Rev Respir Dis

Chest wall mechanics during exercise in patients with severe chronic air-flow obstruction

Am Rev Respir Dis

Breathlessness and exercise in patients with cardiorespiratory disease

Am Rev Respir Dis

Respiratory muscle and cardiopulmonary function during exercise in very severe COPD

Am J Respir Crit Care Med

The measurement of breathlessness induced in normal subjects: individual differences

Clin Sci

Respiratory sensations and the voluntary control of breathing

Standard for the diagnosis and care of patients with COPD

Am J Respir Crit Care Med

Standardization of spirometry 1987 update. ATS statement

Am Rev Respir Dis

Spirometric standards for healthy nonsmoking adults

Am Rev Respir Dis

A clinical method for assessing the ventilatory response to carbon dioxide

Australas Ann Med

Normal standards for an incremental progressive cycle ergometer test

Am Rev Respir Dis

Clinical Investigations
CONTROL OF BREATHING
Ventilatory Drive at Rest and Perception of Exertional Dyspnea in Severe COPD