Absence of dynamic hyperinflation during exhaustive exercise in severe COPD reflects submaximal IC maneuvers rather than a nonhyperinflator phenotype.

Approximately 20% of chronic obstructive pulmonary disease (COPD) patients have been considered to have a "nonhyperinflator phenotype." However, this judgment depends on patients making a fully maximal inspiratory capacity (IC) maneuver at rest, since the IC during exercise is compared with this baseline measurement. We hypothesized that IC maneuvers at rest are sometimes submaximal and tested this hypothesis by measuring IC and associated neural respiratory drive at rest and during inhalation of CO2 and exercise in patients with COPD. Twenty-six COPD patients [age 66 ± 6 yr, mean forced expiratory volume in 1 s (FEV1) 40 ± 11% predicted] and 39 healthy subjects (age 39 ± 14 yr, FEV1 98 ± 12% predicted) were studied. IC and the diaphragm electromyogram (EMGdi) associated with it (EMGdi-IC) and forced inspiratory vital capacity (FIVC) and its corresponding EMGdi (EMGdi-FIVC) were measured during inhalation of 8% CO2 (8% CO2-92% O2) and room air. Incremental exhaustive cycle ergometer exercise was also performed in both patients with COPD and healthy subjects. IC, EMGdi-IC, FIVC, and EMGdi-FIVC during breathing 8% CO2 were significantly greater than those during breathing room air in both patients with COPD and healthy subjects (all P < 0.001). EMGdi-IC in patients with COPD constantly increased during exercise from 145 ± 40 µV at rest to 185 ± 52 µV at the end of exercise but change in IC was variable. Neural respiratory drive and its relevant IC increased during hypercapnia. Exercise-related hypercapnia in patients with COPD raises neural respiratory drives, which compensate for IC reduction, leading to underestimation of dynamic hyperinflation measured by IC at rest breathing room air.NEW & NOTEWORTHY Inspiratory capacity measured during hypercapnia is higher than that during eucapnia. Thus total lung capacity is not always be achieved by a standard inspiratory capacity maneuver, leading to risk of underestimation of dynamic hyperinflation in patients with severe chronic obstructive pulmonary disease after exhaustive exercise.

Coexistence of OSA may compensate for sleep related reduction in neural respiratory drive in patients with COPD.

BACKGROUND: The mechanisms underlying sleep-related hypoventilation in patients with coexisting COPD and obstructive sleep apnoea (OSA), an overlap syndrome, are incompletely understood. We compared neural respiratory drive expressed as diaphragm electromyogram (EMGdi) and ventilation during stage 2 sleep in patients with COPD alone and patients with overlap syndrome. METHODS: EMGdi and airflow were recorded during full polysomnography in 14 healthy subjects, 14 patients with OSA and 39 consecutive patients with COPD. The ratio of tidal volume to EMGdi was measured to indirectly assess upper airway resistance. RESULTS: Thirty-five patients with COPD, 12 healthy subjects and 14 patients with OSA completed the study. Of 35 patients with COPD, 19 had COPD alone (FEV1 38.5%±16.3%) whereas 16 had an overlap syndrome (FEV1 47.5±16.2%, AHI 20.5±14.1 events/hour). Ventilation (VE) was lower during stage 2 sleep than wakefulness in both patients with COPD alone (8.6±2.0 to 6.5±1.5 L/min, p<0.001) and those with overlap syndrome (8.3±2.0 to 6.1±1.8 L/min). Neural respiratory drive from wakefulness to sleep decreased significantly for patients with COPD alone (29.5±13.3% to 23.0±8.9% of maximal, p<0.01) but it changed little in those with overlap syndrome. The ratio of tidal volume to EMGdi was unchanged from wakefulness to sleep in patients with COPD alone and healthy subjects but was significantly reduced in patients with OSA or overlap syndrome (p<0.05). CONCLUSIONS: Stage 2 sleep-related hypoventilation in COPD alone is due to reduction of neural respiratory drive, but in overlap syndrome it is due to increased upper airway resistance.

Neural Respiratory Drive and Arousal in Patients with Obstructive Sleep Apnea Hypopnea.

STUDY OBJECTIVES: It has been hypothesized that arousals after apnea and hypopnea events in patients with obstructive sleep apnea are triggered when neural respiratory drive exceeds a certain level, but this hypothesis is based on esophageal pressure data, which are dependent on flow and lung volume. We aimed to determine whether a fixed threshold of respiratory drive is responsible for arousal at the termination of apnea and hypopnea using a flow independent technique (esophageal diaphragm electromyography, EMGdi) in patients with obstructive sleep apnea. SETTING: Sleep center of state Key Laboratory of Respiratory Disease. PATIENTS: Seventeen subjects (two women, mean age 53 ± 11 years) with obstructive sleep apnea/hypopnea syndrome were studied. METHODS: We recorded esophageal pressure and EMGdi simultaneously during overnight full polysomnography in all the subjects. MEASUREMENTS AND RESULTS: A total of 709 hypopnea events and 986 apnea events were analyzed. There was wide variation in both esophageal pressure and EMGdi at the end of both apnea and hypopnea events within a subject and stage 2 sleep. The EMGdi at the end of events that terminated with arousal was similar to those which terminated without arousal for both hypopnea events (27.6% ± 13.9%max vs 29.9% ± 15.9%max, P = ns) and apnea events (22.9% ± 11.5%max vs 22.1% ± 12.6%max, P = ns). The Pes at the end of respiratory events terminated with arousal was also similar to those terminated without arousal. There was a small but significant difference in EMGdi at the end of respiratory events between hypopnea and apnea (25.3% ± 14.2%max vs 21.7% ± 13.2%max, P < 0.05]. CONCLUSIONS: Our data do not support the concept that there is threshold of neural respiratory drive that is responsible for arousal in patients with obstructive sleep apnea.

[Assessment of neural respiratory drive in humans].

OBJECTIVE: Assessment of neural respiratory drive is useful for diagnosis of dyspnea and respiratory failure with unknown causes. The purpose of the study was to compare the sensitivity of trandiaphragmatic pressure (Pdi) and diaphragm electromyogram (EMGdi) in assessment of neural respiratory drive. METHODS: A combined catheter with 10 electrodes and 2 balloons was used to record EMGdi and Pdi during CO2 rebreathing. Three different inspiratory maneuvers-inspiration from functional residual capacity to total lung capacity (TLC), deep inspiration from functional residual capacity against closed airway (MIP), and short sharp inspiration through the nose (Sniff) were performed. Ten healthy subjects [male 4 and female 6; age (26 ± 4) years] were studied. RESULTS: Linear relationship between EMGdi and end-tidal CO2 (r = 0.83-0.98, all P < 0.01) was better than that between Pdi and end-tidal CO2 (r = 0.48-0.96, all P < 0.01) during CO2 rebreathing, Z = -2.731, P < 0.05. The slope of linear relation between EMGdi and end-tidal CO2 (16.3-32.5) was significantly higher than that between Pdi and end-tidal CO2 (0.4-11.1), Z = -3.780, P < 0.01. The maximal EMGdi derived from TLC maneuver (211 ± 48) µV was larger than those from the MIP maneuver (161 ± 48) µV and the Sniff maneuver (145 ± 37) µV, F = 5.931, P < 0.05, whereas the maximal Pdi derived from TLC maneuver (58 ± 27) cm H2O (1 cm H2O = 0.098 kPa) was significantly lower than those from the MIP maneuver (92 ± 32) cm H2O and the Sniff maneuver (95 ± 27) cm H2O, F = 5.155, P < 0.05. CONCLUSION: EMGdi is more sensitive than Pdi in the assessment of neural respiratory drive.

[Neural respiratory drive and nocturnal hypoventilation in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To explore the effects of neural respiratory drive on ventilation in patients with chronic obstructive pulmonary disease (COPD) during sleep. METHODS: Diaphragm electromyogram (EMG) from a multipair esophageal electrodes and airflow derived from pneumotachography were recorded during overnight polysomnography in 13 patients with stable COPD recruited from outpatient clinic of First Affiliated Hospital of Guangzhou Medical College from May 2010 to May 2011. Changes in diaphragm EMG and ventilation during wakefulness and different sleep stages were observed. RESULTS: Diaphragm EMG decreased by 26% in non-rapid eye movement sleep (NREM) stage and 39% in rapid eye movement (REM) as compared with wakefulness. Coinciding with change in diaphragm EMG, ventilation (VE) (ml×min(-1)×kg(-1)) significantly decreased from wakefulness (156 ± 53) ml×min(-1)×kg(-1) to steady NREM stage (112 ± 35) ml×min(-1)×kg(-1) (P < 0.05) and further decreased from NREM stage to REM stage (95 ± 27) ml×min(-1)×kg(-1) (P < 0.05). Oxygen saturation also decreased significantly from 97.1% ± 1.8% in wakefulness to REM stage (94.0% ± 3.9%) (P < 0.01). CONCLUSION: Reduced neural respiratory drive contributes to nocturnal hypoventilation in COPD patients.

Effect of expiratory load on neural inspiratory drive.

BACKGROUND: Neural respiratory drive is usually measured during inspiration, even in patients with chronic obstructive pulmonary disease (COPD) in whom the primary physiological deficit is expiratory flow limitation. The purpose of the study was to test the hypothesis that inspiratory muscle neural respiratory drive could be used to assess expiratory load. METHODS: Ten healthy young men, (26 ± 4) years old, were asked to expire through a tube immersed in water where an expiratory load was required. The load was judged by the depth of the tube in water and the different loads (0 cmH2O, 10 cmH2O, 20 cmH2O and 30 cmH2O) were randomly introduced. Each expiratory load lasted for 3 - 5 minutes and inspiration was unimpeded throughout. Diaphragm electromyogram (EMG) and transdiaphragmatic pressure were recorded by a catheter with 10 metal coils and two balloons. Incremental cycle exercise with and without an expiratory load at 30 cmH2O was also performed. RESULTS: Neural drive during expiratory loaded breathing was larger than during unloaded breathing but neural drive did not increase proportionally with increasing expiratory load; neural drive during expiratory loading at 0, 10, 20 and 30 cmH2O was (10.1 ± 3.1) µV, (16.7 ± 7.3) µV, (18.4 ± 10.7) µV and (22.9 ± 13.2) µV, respectively. Neural drive as a percentage of maximum at the end of exercise with or without load was similar ((57.4 ± 11.0)% max vs. (62.7 ± 16.4)% max, P > 0.05). CONCLUSION: Neural respiratory drive measured at inspiration does not accurately quantify expiratory load either at rest or during exercise.