Clinical Outcome And Mechanism Of A Novel Breathing Training Manoeuvre In Patients With Stable COPD

Background:Chronic obstructive pulmonary disease (COPD) is characterised by incompletely reversible airflow limitation and dyspnea. As the disease progresses, systemic manifestations occur in majority of the patients, which include exercise limitation, respiratory muscle and peripheral muscle dysfunction and malnutrition. Recent guidelines for the management of COPD emphasize the importance of pulmonary rehabilitation (PR) as part of an integrated multidisciplinary approach. PR programs have been shown to improve exercise capacity, health related quality of life and dyspnea. Breathing training is considered an important component of PR for individuals with COPD. Several breathing training manoeuvre have been reported in the literature, which included slow and deep breathing, pursed lips breathing and diaphragmatic breathing. However, diaphragmatic breathing may be difficult for the patients to employed and accompany increased asynchronous and paradoxical breathing movements when it is used during dyspnea. Pursed lips breathing is difficult to learn for majority of the patients. This self-designed novel breathing training is based on the expiratory airflow limitation and impaired inspiratory muscle function in COPD patients with rapid deep inspiration and prolonged expiration. We hypothesized that this novel breathing training manoeuvre can provide effective inspiratory muscle training, alleviate dynamic hyperinflation during breathing training and improve dyspnea.Objective:A prospective, randomized, controlled study was conducted to evaluate the clinical effects and potential mechanisms of this novel breathing training manoeuvre with the following outcomes: (1) improvement of dyspnea and exercise tolerance. (2) respiratory mechanical mechanisms related to the improvement of dyspnea and exercise tolerance after breathing training. Part one. Clinical outcomes of a novel breathing training manoeuvre in patients with COPDSubjects and methods:Stable moderate to severe COPD patients were enrolled in the out-patient clinics of The First Affiliated Hospital of Guangzhou Medical College from April 2010 to December 2010. The COPD diagnosis was confirmed with clinical presentation and spirometric testing. The subjects inclusion criteria were as following: (1)aged≥50yrs; (2)post–bronchodilator FEV₁<80% predicted and FEV₁/FVC ratio<70%; (3)Subjects had neither acute exacerbation nor systemic use of glucocorticosteroids in the past 4 weeks; (4)no history or diagnosis of bronchial asthma; (5)ex-smokers. Exclusion criteria included:(1) history of participating in pulmonary rehabilitation program; (2)complicated with respiratory failure;(3)disorders involving pleural cavity, thoracic wall, bone and joint or neurological or muscular system;(4)history or diagnosis major disorders including cardiac, hepatic or renal disorders or tumor; (5)psychological or cognitional abnormality; (6)incompliance or refusing to sign informed consent.All the patients were randomized to receive one of the three groups: group A with novel breathing training; group B with diaphragmatic breathing training and group C as control. The manoeuvre of novel breathing training consist of a fast forceful deep inspiration to total lung capacity and hold for a short period with total inspiratory time of 0.8¹.0 second, then follows with relaxed expiration for 3⁴ seconds. The manoeuvre of diaphragmatic breathing for group B is as described in the literature. The breathing training was instructed and supervised by researcher in hospital until the patient can follow the breathing manoeuvre. Then patients underwent a 15-minute training at home for 3 times a day with daily diary record for eight weeks. The group C was managed with stable pharmacological therapy and follow up for eight weeks. Measurements at Baseline and post-training are as following: MRC scale of dyspnea, 6 minutes walking distance, pulmonary function, respiratory muscle strength (MIP and MEP) and quality of life (St George's Respiratory Questionnaire, SGRQ), as well as BODE index.Results:1. Baseline demographic and clinical characteristics81 subjects with COPD were enrolled in this study with 65 subjects completed the study. In group A, 22 (21 males and 1 female,65.18±6.25 years) completed the study and 8 drop out. In group B, 23 (22 males and 1 female, 66.52±6.90 years) completed the study and 6 drop out. In group C, 20 (19 males and 1 female, 67.55±7.50 years) completed the study and 2 drop out. Only those subjects completed the study were included in the following analysis. There was no significant difference in the baseline measurements including average age, BMI, pulmonary function, exercise capacity, dyspnea, respiratory muscle strength, quality of life and BODE index among the three groups (all P>0.05).2. Impact on dyspneaMRC scale declined significantly after 8 weeks compared to baseline values in group A and B (1.90±0.75 VS 2.77±1.06, 1.52±0.89 VS 2.39±0.94, respectively) (all P <0.01). At the end of 8 weeks, no significant change was observed in MRC scale in group C (P>0.05).ΔMRC:Significant decrease (P< 0.01) was present inΔMRC of group A and B compared with that of group C, with no statistical difference being shown between group A and B(P >0.05).3. Impact on exercise capacity6-MWD increased significantly after 8 weeks compared to baseline values in group A and B (475.77±107.15 m VS 424±101.77 m, 486.34±57.40 m VS 437.30±69.44 m, respectively) (all P <0.01). At the end of 8 weeks , no significant change was observed in 6-MWD in group C (P>0.05).Δ6-MWD: Significant increase (P< 0.01) was present inΔ6-MWD of group A and B compared with that of group C, with no statistical difference being shown between group A and B(P >0.05).4. Impact on pulmonary function(1)group A: IC and PIF increased significantly after 8 weeks compared to baseline values (1.91±0.56L VS 1.68±0.42L;4.45±1.27L/s VS 3.73±1.37L/s, respectively) (all P <0.01). No significant changes (all P>0.05) were found in other pulmonary function parameters, including FEV₁, FEV₁%pre, FEV₁/FVC, FVC, PEF and MVV. (2) group B: IC was the only parameter with significant increase after 8 weeks compared to baseline values (2.10±0.34L VS 2.10±0.34L) (P <0.01). No significant changes (all P>0.05) were found in other pulmonary function parameters, including FEV₁, FEV₁%pre, FEV₁/FVC, FVC, IF, PEF and MVV. (3)group C: At the end of 8 weeks, no significant changes were observed in all the pulmonary function parameters (all P>0.05). (4) Comparison of changes in pulmonary function among the three groups:It revealed no significant differences inΔFEV₁,ΔFEV₁%pre,ΔFEV₁/FVC,ΔFVC,ΔPEF andΔMVV among the three groups (all P>0.05).ΔIC:Significant increase (P<0.01) was present inΔIC of group A and B compared with that of group C, with no statistical difference being shown between group A and B(P >0.05).ΔPIF:Significant increase (P<0.01) was present inΔPIF of group A compared with that of group B and C.5. Impact on respiratory muscle functionMIP and MEP increased significantly after 8 weeks compared to baseline values in group A and B (85.20±22.59 cmH₂O VS 74.35±24.81cmH₂O, 80.26±19.32cmH₂O VS 70.29±18.98cmH₂O;129.60±39.07cmH₂O VS106.30±35.64cmH₂O, 127.98±32.61cmH₂O VS 113.56±31.04cmH₂O,respectively) (all P<0.01). At the end of 8 weeks, no significant changes were observed in all the variables of respiratory muscle function in group C (all P>0.05).ΔMIP:Significant increase (P< 0.01) was present inΔMIP of group A and B compared with that of group C, with no statistical difference being shown between group A and B(P >0.05).ΔMEP had the similar outcome withΔMIP.6. Impact on quality of lifeSGRQ total score decreased significantly after 8 weeks compared to baseline values in group A and B (35.40±12.98 VS 47.81±14.09;32.04±14.09 VS 44.56±12.42, respectively) (all P <0.01). At the end of 8 weeks , no significant changes were observed in all the variables of quality of life in group C (P>0.05).ΔSGRQ total score: Significant increase (P< 0.01) was present inΔSGRQ total score of group A and B compared with that of group C, with no statistical difference being shown between group A and B(P >0.05). SGRQ symptoms, activity and impact score had the similar outcomes with SGRQ total score.7. Impact on BODE indexBODE index declined significantly after 8 weeks compared to baseline values in group A and B (3.86±1.78 VS 4.86±2.35; 3.21±1.73 VS 4.21±1.83, respectively) (all P<0.01). At the end of 8 weeks , no significant change was observed in BODE index in group C (P>0.05).ΔBODE index:Significant decrease (P< 0.01) was present inΔBODE index of group A and B compared with that of group C, with no statistical difference being shown between group A and B(P>0.05).8. Multiple regression analysis result(1)dyspnea: In a multiple regression analysis,ΔMRC served as dependent variable, ΔMIP andΔPIF were predictors ofΔMRC(all P<0.05)in improved variables such asΔIC,ΔMIP,ΔMEP,ΔFEV₁%pre,ΔFEV₁/FVC,ΔFVC,ΔPIF,ΔMVV andΔ6-MWD in group A.ΔFEV₁%pre was the only predictor ofΔMRC in group B(P<0.05).(2) exercise capacity: In a multiple regression analysis, 6-MWD served as dependent variable, none of parameters were predictors ofΔ6-MWD(all P>0.05)in improved variables such asΔIC,ΔMIP,ΔMEP,ΔFEV₁%pre,ΔFEV₁/FVC,ΔFVC,ΔPIF,ΔMVV andΔMRC in group A.ΔMEP andΔFEV₁/FVC were predictors ofΔ6-MWD in group B(all P<0.01).(3) respiratory muscle function: In a multiple regression analysis,ΔMIP andΔMIP served as dependent variable respectively,ΔIC was the only predictor ofΔMIP(P<0.05) in improved variables such asΔIC,ΔFEV₁%pre,ΔFEV₁/FVC,ΔFVC andΔMRC in group A. None of parameters were correlated withΔMIP in group A(all P>0.05). None of parameters were correlated withΔMEP in group A and B(all P>0.05).(4)quality of life: In a multiple regression analysis,ΔSGRQ total score served as dependent variable,ΔMRC was the only predictor ofΔSGRQ total score(P<0.05)in improved variables such asΔIC,ΔMIP,ΔMEP,ΔFEV₁%pre,ΔFEV₁/FVC,ΔFVC,ΔPIF,ΔMVV,Δ6-MWD andΔMRC in group A.ΔSGRQ symptom score had the same outcome withΔSGRQ total score.ΔMRC andΔPIF were predictors ofΔSGRQ activity score in group A(all P<0.05).ΔIC andΔPIF were predictors ofΔSGRQ impact score in group A(all P<0.05). None of parameters were correlated withΔSGRQ total, symptom, activity and impact score in group B(all P>0.05).Part two. The mechanism of a novel breathing training manoeuvre in patients with COPDSubjects and methods:The patients with COPD who had completed the first part of this study participated in the second part. Respiratory mechanical examinations were next performed in a certain proportion of subjects undergoing novel breathing training and diaphragmatic breathing program. The oesophageal electrode was introduced through the nose and swallowed into the oesophagus. EMGdi recordings were made from the crural diaphragm using multipair oesophageal electrode. Pleural pressure (Ppl) and gastric pressure (Pga) were measured using two balloon-tipped catheters that were passed transnasally. Airflow was measured through a mouthpiece connected in series to a pneumotachograph. First, pressure, flow, EMGdi and Borg scale were recorded during resting breathing, and then changes in parameters for breathing training were monitored dynamically.Results:1. Baseline demographic and clinical characteristics16 subjects with COPD were enrolled in this study. 8 male subjects completed the study in both groups. There was no significant difference of average age, pulmonary function,breathing pattern, EELV, inspiratory work, PEEPi, central drive, dyspnea, arterial oxygen saturation(SpO₂) betweent the two groups(all P>0.05).2. Impact on breathing pattern and EELV(1)group A: Vt, Te, Ttot and Vt/Ti increased significantly during breathing training compared to resting breathing (all P <0.01). However, RR, Vt/Te and Ti/Ttot decreased significantly during breathing training. No significant changes (all P>0.05) were found in other breathing pattern parameters, including VE and Ti. EELV also increased significantly during breathing training. (2) group B: Vt, Ti, Te and Ttot increased significantly during breathing training compared to resting breathing (all P <0.01). However, VE, RR, Vt/Te and Ti/Ttot decreased significantly during breathing training. Vt/Ti had no significant change(all P>0.05). EELV also increased significantly during breathing training. (3) comparison of changes in pulmonary function between the two groups: There was no significant difference ofΔVt,ΔVE,ΔRR,ΔTe,ΔTtot andΔVt/Te between the two groups (all P>0.05).ΔIC:There was no significant difference between group A and B(P >0.05). Significant decrease (P< 0.01) was present inΔTi of group A compared with that of group B; significant increases (all P< 0.01) were present inΔVt/Ti andΔTi/Ttot of group A compared with that of group B.3. Change in respiratory muscle activity(1)group A: Peso, Pgas and Pdi increased significantly during breathing training compared to resting breathing (all P <0.05). However, no significant change (P>0.05) was found in TTdi. (2) group B: Peso and Pdi increased significantly during breathing training compared to resting breathing (all P <0.05). Pgas and TTdi had no significant changes (all P>0.05). (3) comparison of changes in respiratory muscle function between the two groups: There was no significant difference ofΔPgas andΔTTdi between the two groups (all P>0.05). However, there were significant increases ofΔPeso andΔPdi of group A compared with that of group B (all P <0.01).4. Change in inspiratory work and PEEPi(1)group A: No significant changes (P>0.05) were found in PEEPi, PTPeso and PTPdi during breathing training compared to resting breathing (all P <0.05). (2) group B: PTPeso increased significantly during breathing training compared to resting breathing (all P <0.05). PEEPi and PTPdi had no significant changes (all P>0.05). (3) comparison of changes in inspiratory work and PEEPi between the two groups: There was no significant difference ofΔPEEP,ΔPTPeso andΔPTPdi between the two groups (all P>0.05).5. Change in central driveRMS and EMGdi%max increased significantly during breathing training compared to resting breathing in group A and B (all P <0.01). There was no significant difference ofΔRMS,ΔEMGdi%max between the two groups (all P>0.05).6. Impact on dyspnea and arterial oxygen saturationSpO₂ increased significantly during breathing training compared to resting breathing in group A and B(all P <0.05). However, no significant change (P>0.05) was found in BORG scale in group A and B(P <0.05). There was no significant difference ofΔBORG andΔSpO₂ between the two groups (all P>0.05).7. Multiple regression analysis result(1) dyspnea:In a multiple regression analysis,ΔMRC served as dependent variable, EMGdi%max was the only predictor ofΔMRC(P<0.05)in variables such as Vt, VE, RR, Ti, Te, IC, Peso, Pdi, PEEPi, PTPeso, PTPdi, RMS and EMGdi%max or the improved values in group A. IC was the only predictor ofΔMRC in group B(P<0.05).(2) exercise capacity:ΔEMGdi%max,ΔVT andΔPEEPi were predictors ofΔ6-MWD in group A(all P<0.05). Te andΔTe were predictors ofΔ6-MWD in group B(all P<0.01). (3) respiratory muscle function: PTPeso was the only predictor ofΔMIP in group A(P<0.05). None of parameters were correlated withΔMIP in group B(all P>0.05). PTPdi andΔPTPdi were the predictors ofΔMEP in group A(all P<0.05).ΔTi,ΔRR and Te were predictors ofΔMEP in group B(all P<0.05). (4) quality of life: PEEPi was the only predictor ofΔSGRQ total score in group A(P<0.05). None of parameters were correlated withΔSGRQ total score in group B(all P>0.05). Conclusion:1. Breathing training could improve dyspnea, exercise capacity, respiratory muscle function, and quality of life in patients with moderate to severe COPD. During breathing training, there were increases in tidal volume and oxygen saturation, as well as reduction in breathing frequency and lung volume at end expiration as compared with normal breathing. There was no significant difference between the novel breathing training and diaphragmatic breathing training.2. During the novel breathing training, there was no significant increase of average work of breathing due to prolongation of expiration. The improvement of dyspnea was related to the diaphragmatic activity during the training. On the other hand, diaphragmatic breathing training increased the average work of breathing, which might incur inspiratory muscles fatigue.3. The results prove the novel breathing training is an effective rehabilitation method, which is easy to learn for the patients and seems appropriate for the physiological abnormality of COPD patients and long term home rehabilitation.