| [Background]Chronic obstructive pulmonary disease (COPD), one of the most common respiratory diseases, is a leading cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. Conventionally, the main therapy for COPD is pharmacologic treatment. Recently, pulmonary rehabilitation has established itself as an important component of COPD management. In previously reported studies, noninvasive positive pressure ventilation (NPPV) as a form of pulmonary rehabilitation was usually applied to COPD patients with respiratory failure rather than those without respiratory failure. However, COPD is a progressive diaease and it may accelerate the deterioration due to frequent exacerbations if not given timely treatment and control. Notably, COPD is charactered by persistent expiratory flow limitation (EFL) which contributes to the mechanism of dynamic pulmonary hyperinflation (DPH) and intrinsic positive end-expiratory pressure (PEEPi). DPH and PEEPi have been described to increase inspiratory threshold load on the inspiratory muscle and work of breathing, and reduce the efficiency and mechanical advantage of diaphragm. They could lead to impaired respiratory neural drive and mechanics, resulting in increased dyspnea. Therefore, we hypothesised that, for non-hypoxemic individuals with stable COPD, early intervention of continuous positive airway pressure (CPAP) may alleviate the PEEPi, rectify the abnormal pathophysiologic changes and help postpone the disease progression. In other words, CPAP therapy may be one of effective means of pulmonary rehabilitation, but it lacks evidence on evaluating the pathophysiological changes of COPD during CPAP.[Objective]We aim to investigate the effects of increasing CPAP on repiratory mechanics and neural drive in a group of subjects with stable COPD. Futher, we would like to explore whether CPAP therapy could be an effective form of pulmonary rehabilitation, and assist decision-making in large clinical trials.[Methods]From January 12015 to December 2015, patients with moderate-to-severe COPD in Zhujiang Hospital, Southern Medical University were consecutively enrolled in this study. Basic information and clinical data were collected from those who met the inclusion criteria and exclusion criteria. Some tests such as lung function testing, six-walking distance and respiratory muscle strength were also performed. Before experiment, all the participants were trained to practice some manoeuvres, including slow deep respiratory manoeuvre and strength part (Sniff, MIP and TLC). After being in a stable breathing pattern, the subjects received NPPV with CPAP model. CPAP began with 4 cmH20 and increased in increments of 1 cmH2O to a maximum of 10 cmH2O. Each pressure level lasted for 5 to 10 minutes. During rested tidal breathing and during different levels of CPAP, we monitored respiratory pressure indices [including mouth (Pmo), esophageal (Pes) and gastric pressure (Pga)], flow and diaphragm electromyogram (EMGdi), as well as subjective dyspnea, end tidal carbon dioxide pressure (PetCO2) and SpO2. Pes and Pga were measured with balloon-tipped catheters in place and EMGdi were measured with multi-pair esophageal electrodes. Dyspnoea was evaluated with the Borg score. Flow was monitored by a differential pressure sensor and those volume parameters such as Vt, Ve and IC were obtained by electrical integration of flow. The change in the end expiratory lung volume (EELV) was assessed by the change in IC.Data acquisition was performed using PowerLab 16sp hardware and software. Statistical calculations were performed using Statistical Package for Social Sciences (SPSS 20.0, Chicago, IL, USA). Data were expressed as mean values±standard deviation. Between-group differences were compared using unpaired t-test. Analysis of variance of repeated measurement data was used to assess the quantitative differences among different CPAP levels and least significant difference was used to detect inter-point differences. Person correlation analysis was used to study correlations between different indices. P<0.05 was considered to be statistically significant.[Results]1. Descriptive characteristics of the patientsWe recruited 22 participants in the study.3 participants had adverse reactions in the positioning of esophageal electrodes and we had to stop the experiment. Herein, we extract data for further analysis from the the remaining 19 patients who successfully completed the experiment. Descriptive characteristics are summarized as following:all males, age:62.16±8.526(year); height:165.11±5.43(cm); body weight: 59.53±7.66(kg); smoking history:30.37±12.28 (year), smoking index: 616.32±420.01(year·n); course of disease:5.66±3.08(year); frequency of acute exacerbation in the last year:1.32±1.20; lung function parameters:FVC 2.72±0.56L, FEV11.39±0.47L, FEV,%Pred 49.76±13.14(%), FEV1/FVC 51.36±10.47(%); Breathing difficulties assessment (mMRC):1.26±0.87(points); COPD symptom assessment test (CAT):9.00±3.23 (points); 6MWD:450.00±129.02 (m); Borg score during exercise:2.84±1.01; St. George’s respiratory questionnaire score (SGRQ): 15.36±4.22 (points); BODE:2.28±1.60. COPD classification according to GOLD 2006:moderate (11 cases), severe (7 cases), very severe (1 case); COPD classification according to GOLD 2011:Group A (7 cases), Group B (1 case), Group C (6 cases), Group D (5 cases).2. Respiratory physiological parameters at rest condition:At rest condition parameters are shown as following. Pmo:-0.63±0.50cmH2O; Pes:-11.63±4.09cmH2O; Pga:19.44±5.66cmH2O; Pdi:30.13±7.83cmH2O; Vt: 0.717±0.24 L; Ve:11.86±3.85L/min; RMS:79.77±14.96μV; Ve/RMS: 0.157±0.069L/min/μV; Raw:14.09±6.96 cmH2O/L/s; pressur-time product of transdiaphragmatic pressure (PTPdi):13.34±5.26cmH2O·s; pressur-time product of Pes (PTPes):9.01±2.52 cmH2O·s; CL:0.24±0.03 L/cmH2O; Ccw:0.25±0.04 L/cmH2O. PEEPi, stat:2.58±1.51 cmH2O. PImax:-68.15±30.30cmH2O; Pes, max:-69.46±26.40cmH2O; Pdi,max:108.03±37.48cmH2O; RMS,max:183.93±27.02μV.3. Effects of CPAP on respiratory physiological parameters:Breathing patterns:After application of 4 cmH20 CPAP, respiratory rate (RR) increased from 17.43±4.83 beat/min to 21.15±6.68 beat/min, and it increased gradually as CPAP incresed, but there were no significant differences among 4～10cmH2O groups. Ttot and Ti decreased gradually as the increment of CPAP level, but there were no significant differences among different groups. In comparison with at rest condition, Vt,Ve and Vt/Ti all increased sigficantly at 4 cmH2O. As CPAP increased, Vt and Ve increased first and then fell, whereas Vt/Ti first fell and then increased; no marked differences were found among 4-10 cmH20 groups.Respiratory pressure parameters:As CPAP increased, Pmo increased from-0.63±0.5cmH2O to 2.88±2.35cmH2O, and Pes increased from-11.63±4.09cmH2O to-2.88±2.35cmH2O. Pga remained stable in different CPAP levels. Pdi decreased gradually, but no significant differences were detected among different groups. Ater CPAP was applied, Pes/Pdi decreased from-38.85±9.30% to-32.74±16.10%, and it went on to fall as the increment of CPAP level, especially over 8 cmH2O. To minimize the individual differences, Pdimax and PImax were used to correct Pdi and Pes, but no differences were detected.Raw and inspiratory work:Ater CPAP was applied, Raw, PTPdi, and PTPes decreased first and then increased after 7 cmH2O, but there were no marked differences among 5～10 cmH2O groups (all P>0.05).Lung hyperinflation, PEEPi, dyn and PEEPi, stat:As CPAP increased, IC increased from 2.33±0.46 L to 2.50±0.58 L, but it decreased gradually at 7 cmH2O. In contrast, △EELV and △EELV/ICx first fell and then increased gradually. On the whole, both PEEPi,dyn and PEEPi,stat decreased gradually, but increased at 10 cmH2O.Central drive and respiratory efficiency:As CPAP increased, RMS increased from 79.77±14.96μv to 91.03±29.14μv, but there were no marked differences among different groups.Ve/RMS increased as the increment of CPAP level, but it decreased at 8 cmH2O. To minimize the individual differences, RMS,max was used to correct RMS and Ve/RMS, but no differences were detected. In addition, Ve/Pes increased as the the increment of CPAP level, but it decreased at 7 cmH20.Dyspnea, PetCO2, and SpO2:Ater CPAP was applied, Borg score increased gradually, which is due to the patient’s contact discomfort at 4-6 cmH2O and due to the increased expiratory dyspnea over 7cmH2O. SpO2 remained stable in the experiment. As CPAP increased, PetCO2 decreased gradually, but no marked differences were among different groups.Differences in relevant indices between moderate group and severe group:During eupnea, there were significant differences in FVC、FEV1, FEV1% pre, FEV1/FVC (%), Ti, PImax, and Pes,max between moderate group and severe group (all P<0.05). During CPAP, no significant differences in Raw, PTPes, PTPdi, IC, △EELV, △EELV/IC (%), RMS, and Ve/RMS were found between two groups (all P >0.05). In addition, for moderate group, no significant differences in the above indices were found among different levels; for severe group, significant differences in IC, △EELV, and △EELV/IC (%) were found among different levels.4. Correlation analysisRMS correlated positively with Ve, Borg and Ve/Pdi, correlated negatively with Ve/RMS, PTPes, PTPdi and PEEPi, dyn (allP<0.05). IC correlated negatively with △EELV%, Borg, PTPes and PTPdi (all P<0.05).Ve correlated negatively with Raw, PTPdi and PEEPi, dyn (all P<0.05), indicating that the reduction of airway resistance, inspiratory efforts and PEEPi contributed to the increased ventilation. Borg was positively associated with Ve/Pdi and Ve/Pes, but negatively with PEEPi,dyn. Moreover, there is significantly positive correlation between PTPdi and PEEPi,dyn, negative correlation between Raw and Ve/Pdi (or Ve/Pes).[Conclusion]1. In COPD patients, appropriate application of CPAP (4-7cmH2O) can decrease PEEPi, airway resistance and work of breathing, as well as reducing lung hyperinflation and increasing minute ventilation. Though CPAP can not decrease neural respiratory drive, it could improve the ventilation-drive coupling in COPD.2. The degree of airflow limitation does not influence the change of different respiratory parameters during CPAP.3. In this exploratory study, we investigate the physiological role of CPAP in COPD patients without respiratory failure and the results support our hypothesis that CPAP may be promising as an effective form of pulmonary rehabilitation. However, the clinical efficacy of CPAP should be further verified in prospective randomized controlled clinical trials. |
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