Evaluation of Clinical Data and Mortality among COPD Patients Receiving Domiciliary NIMV Therapy

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1 Turk Thorac J 2014; 15: DOI: /ttd ORIGINAL INVESTIGATION Evaluation of Clinical Data and Mortality among COPD Patients Receiving Domiciliary NIMV Therapy Tacettin Örnek, Fatma Erboy, Figen Atalay, Bülent Altınsoy, Hakan Tanrıverdi, Fırat Uygur, Meltem Tor Department of Chest Diseases, Bülent Ecevit University Faculty of Medicine, Zonguldak, Turkey Abstract OBJECTIVES: Domiciliary non-invasive mechanical ventilation (NIMV) is presumed to decrease hospital admissions and mortality in very severe chronic obstructive pulmonary disease (COPD) patients. This study was aimed to investigate the clinical data and mortality among COPD patients receiving domiciliary NIMV treatment. MATERIAL AND METHODS: A total of 40 COPD patients who were prescribed domiciliary NIMV at discharge between January 2010 and December 2011 were contacted by phone regarding their current health status, and the electronic patient charts of 34 patients who used NIMV regularly were retrospectively reviewed. RESULTS: The mean age of the patients was 67±15 years and 59% of them were females. The mean length of hospital stay was 14.5±6.82 days. Rate of admission to intensive care unit and use of invasive mechanical ventilation was 56% and 27%, respectively. The median follow up duration was 17 months. The 6-months, 1-year, 2-years and overall mortality rates were 24%, 38%, 50% and 56%, respectively. For patients surviving at least one year after domiciliary NIMV initiation (n=21), the mean number of hospitalizations in the year before-and after-nimv initiation were 1.38±1.28 and 0.57±0.93 (p=0.003), respectively. Mean daily NIMV use was 8.91±4.46 hours. Mean daily NIMV use of the patients with a lifespan 2 years was higher than that of the patients with a lifespan >2 years (11.82±4.02 hours/day versus 6.0±2.62 hours/day, respectively) (p<0.001). Long term oxygen was prescribed for the first time to 62% of the patients using NIMV. CONCLUSION: Domiciliary NIMV may have numerous beneficial effects such as decreasing hospital admissions for acute COPD exacerbations and related costs. It is very important in the battle against COPD, a disease with significant morbidity, mortality and economic burden. Key words: COPD, non-invasive mechanical ventilation, mortality Received: Accepted: INTRODUCTION Chronic obstructive pulmonary disease (COPD) is one of the diseases in which non-invasive mechanical ventilation (NIMV) is most frequently used. Domiciliary NIMV treatment is recommended in selected patients despite contradictory results of the studies conducted on domiciliary NIMV in stable patients with severe COPD. Providing that COPD and underlying disease have been treated in an optimum period; domiciliary NIMV therapy is recommended in patients with symptoms (fatigue, dyspnoea, morning headache, etc.) or 55 mmhg or =50-54 mmhg and nocturnal desaturation or =50-54 mmhg and a history of hospitalization at least twice a year due to hypercapnic respiratory failure [1]. It is also recommended for patients who cannot be separated from the ventilator after successful treatment of acute respiratory failure with NIMV [2]. Although acute effects of NIMV therapy have been clearly demonstrated in patients with chronic obstructive pulmonary disease, there are limited number of studies on the long-term outcomes and benefits [3]. In this study, we aimed to investigate the clinical data, number of hospitalizations and mortality in COPD patients receiving domiciliary NIMV therapy. MATERIAL AND METHODS All patients, who were discharged from our hospital between January 2010 and December 2011 with domiciliary NIMV, were retrospectively reviewed using the medical board records of the Department of Chest Diseases, and 45 patients who were discharged with domiciliary NIMV were identified. The study included only patients that were prescribed domi- 112 This study was presented as an oral presentation during the 15 th Annual Congress of Turkish Thoracic Society, April 2012, Antalya, Turkey: SS-036. Address for Correspondence: Tacettin Örnek, Department of Chest Diseases, Bülent Ecevit University Faculty of Medicine, Zonguldak, Turkey Phone: tacettinornek@yahoo.com Copyright 2014 by Turkish Thoracic Society - Available online at

2 ciliary NIMV for COPD. Patients who were prescribed NIMV for obesity hypoventilation syndrome or sleep apnoea syndrome were excluded. Therefore, 5 patients who were prescribed the device because of reasons other than COPD (restrictive lung disease due to scoliosis [n=1], interstitial pulmonary disease [n=2], obesity hypoventilation syndrome [n=2]) were excluded from the study (Figure 1). In April 2013, the patients were contacted using their phone numbers recorded in the electronic file system of the hospital and their consents were obtained after they were informed about the study. They were questioned whether they regularly used the device, daily duration of device use and death date if they died (information about dead patients were obtained from their legal representatives). Three patients who could not be reached and three patients who did not use the device regularly or used the device for less than 4 hours daily were excluded. The remaining 34 patients were considered as the study group. Clinical data of these patients were retrospectively reviewed using electronic patient files. Number of patients receiving domiciliary NIMV=45 Without COPD NİMV=5 NIMV=40 Could not be reached=3 NIMV=37 Noncompliant =3 Study group=34 Figure 1. Flowchart illustrating the number of dropouts and the reasons COPD: Chronic obstructive pulmonary disease; NIMV: non-invasive mechanical ventilation Table 1. Clinical data of the patients receiving domiciliary NIMV Turk Thorac J 2014; 15: Statistical Analysis Data were analysed using the Statistical Package for the Social Sciences (SPSS) version 16.0 (Chicago, USA) package program. Normality of distribution was tested using the Kolmogorov-Smirnov test. The means of two dependent groups was compared by Wilcoxon Signed-rank test in case the distribution of the groups was not normal, and the Paired- Samples T test (Student T test) was used in case of normal distribution. The means of two independent groups were compared by Mann-Whitney U test when the distribution of the groups was not normal, whereas categorical variables were compared using the chi-square test and, if appropriate, by Fisher s Exact Probability test. Survival analysis was performed using Kaplan-Meier method. P<0.05 was considered statistically significant. RESULTS The mean age of the patients was 68±15 (range, 34-87) years and 59% (n=20) were females. All females had a history of biomass exposure, whereas 45% (n=9) had a history of cigarette smoking. Of the males, 86% (n=12) had a history of cigarette smoking and the 2 non-smoker males were retired coal mine workers. Of the patients included in the study, 53% (n=18) were house wives and 24% (n=8) were retired coal mine workers. Clinical data of the patients are summarized in Table 1. As was expected, there was a significant difference between the blood gas values obtained at hospital admission and at hospital discharge in patients receiving domiciliary NIMV (Table 2). According to the Global Obstructive Lung Disease (GOLD) criteria, 35% were Stage 4, 24% were Stage 3, and 41% were Stage 2 patients [4]. None of the patients had GOLD Stage 1 disease. Mortality in patients receiving domiciliary NIMV therapy is presented in Table 3 and the survival curve is demonstrated in Figure 2. The mean age and the mean duration of daily NIMV use of patients with a lifespan 2 years after domiciliary NIMV prescription were significantly higher (n=17) as compared to that of the patients with a lifespan>2 years (n=17) (Table 4). Smoking status Never smoked, n (%) 13 (38.2) Quitted smoking, n (%) 20 (58.8) Currently smoking, n (%) 1 (2.9) Number of cigarettes, 25.86±20.36 (2-60) The median follow-up period of study participants was 17 Mean packs -year±sd (range) (range, 1-39) months. The number of patients that survived Body mass index, mean±sd (range) 24.65±3.89 (18-36) for at least 1 year after the initiation of NIMV therapy was 21 Duration of hospital stay, mean day±sd (range) Rate of intensive care unit stay, n (%) 14.5±6.82 (5-38) 19 (55.9) (62%). In these patients, the mean number of hospitalizations before and after domiciliary NIMV therapy was 1.38±1.28 and 0.57±0.93, respectively (p=0.003). Rate of IMV application, n (%) 9 (26.9) The mean daily duration of domiciliary NIMV use was Percentage of predicted FEV ± ±4.46 hours. Thirty eight percent (n=13) of the patients mean±sd (range) ( ) had been receiving long-term oxygen therapy (LTOT) previously. LTOT was commenced for the first time in 62% (n=21) IPAP* mean cmh 2 O±SD (range) 14.74±1.77 (12-18) of the patients together with NIMV. EPAP mean cmh 2 O±SD (range) 6.29±0.72 (6-8) DISCUSSION Systolic pulmonary artery pressure, 44.41±16.24 (20-70) mean mmhg±sd In the present study, we discussed the clinical data and mortality of COPD patients that were discharged with domiciliary NIMV in the light of literature. The present study demon- *Inspiratory positive airway pressure adjusted on NIMV device at hospital discharge. Expiratory positive airway pressure adjusted on NIMV device at hospital strated that annual mortality in COPD patients receiving discharge domiciliary NIMV therapy was 38.2%. NIMV: non-invasive mechanical ventilation; IMV: invasive mechanical ventilation; FEV 1 : forced expiratory volume in one second; IPAP: Although NIMV therapy is frequently used for the treatment inspiratory positive airway pressure; EPAP: expiratory positive airway of chronic hypercapnic respiratory failure, data on the longterm efficacy of domiciliary NIMV therapy in COPD patients pressure 113

3 Örnek et al. Domiciliary NIMV in COPD Cumulative survival rate Table 3. Mortality in patients receiving domiciliary NIMV Duration Mortality n 6-month 23.5% 8 1-year 38.2% 13 2-year 50% 17 Within the follow-up period 55.9% 19 NIMV: non-invasive mechanical ventilation Duration of Survival (months) Figure 2. Survival curve of the patients included in the study Table 2. Blood gas values of patients receiving domiciliary NIMV on At Hospital Blood gas Admission Discharge p ph- mean±sd (range) 7.29± ±0.04 <0.001 PaO 2 - mean±sd (range) 58.09± ± mean±sd (range) 79.40± ±9.30 <0.001 SpO 2 - mean±sd (range) 81.92± ±10.31 <0.001 NIMV: non-invasive mechanical ventilation; ph: hydrogen ion concentration; PaO 2 : partial arterial oxygen pressure; : partial arterial carbon dioxide pressure; SpO 2 : oxygen saturation are confusing [5-7]. In one of the initial studies conducted to investigate the efficacy of domiciliary NIMV therapy in COPD patients, Casonova et al. [8] have concluded that NIMV therapy does not change the natural course of COPD and has no notable benefit in case of stable disease. In that prospective randomized study, patients that receive domiciliary NIMV for COPD (n=20) were compared with a control group and it was found that the number of hospital admissions within 3 months was decreased in the group that received NIMV (5% vs. 15%), but there was no difference in terms of the number of hospital admissions within 6 months (18% vs. 19%) and one-year. The same study found no significant difference between the two groups in terms of oneyear mortality (15%). The higher mean values of our patients (Table 2) as compared to the vales (50.7±7.9) of the patients in the above-mentioned study indicate that participants of this present study had more severe COPD. We think that, this could partially explain the high mortality rate found in the present study. In a study comparing 72 hypercapnic COPD patients receiving non-invasive mechanical ventilation +LTOT with 72 hypercapnic COPD patients receiving LTOT alone, 5-year mortality was found to be 20% and 25%, respectively, with no statistically significant difference between the groups [9]. Nevertheless, it was observed that the mean survival time in the group receiving NIMV (40.27±3.56 months) was significantly higher than that of the group not receiving NIMV (27.35±3.68 months). Although domiciliary NIMV therapy Table 4. Comparison of the factors that could influence two-year mortality Lifespan Lifespan> Factor 2 years 2 years p Age (year) mean±sd 73.88± ± Female gender, n (%) 11 (64.7) 9 (52.9) Smoking history, n (%) 8 (47.1) 13 (76.5) Body mass index (kg/m 2 ) 24.06± ± mean±sd Number of hospitalizations 1.94± ± in the last year* Rate of staying at intensive 9 (52.9) 10 (58.8) care unit, n (%) Rate of İMV application, n (%) 4 (23.5) 5 (29.4) 1.0 Percentage of predicted 39.74± ± FEV 1, mean±sd Duration of daily 11.82± ±2.62 <0.001 domiciliary NIMV use, Mean hour±sd - mean±sd 66.16± ± IPAP mean cmh 2 O±SD 14.35± ± EPAP mean cmh 2 O±SD 6.24± ± Systolic pulmonary artery 51± ± pressure- mean mmhg±sd *number of hospitalizations in the year before NIMV prescription Arterial blood gas values during hospital discharge Inspiratory positive airway pressure adjusted on NIMV device during hospital discharge Expiratory positive airway pressure adjusted on NIMV device during hospital discharge IMV: invasive mechanical ventilation; FEV 1 : forced expiratory volume in one second; NIMV: non-invasive mechanical ventilation; : partial arterial carbon dioxide pressure; IPAP: inspiratory positive airway pressure; EPAP: expiratory positive airway pressure has been demonstrated to increase the overall health quality in two studies including patients with short-term follow-up (8- and 12-week, respectively), it was observed in this longterm study, different from the literature, that overall health and mental state were much worsened in the group receiving NIMV [10,11]. The same study found no significant difference between the groups in terms of mean levels obtained at 6 and 12 months. The exclusion of the patients aged over 80 years and the patients with concomitant diseases, domiciliary NIMV therapy being indicated at >46, and the patients who participated having milder COPD in the above mentioned study as compared to the

4 Turk Thorac J 2014; 15: present study, may explain the quite high mortality rates found in the present study. In the present study, the daily duration of NIMV use was significantly higher in patients with a shorter lifespan as compared to those with a longer lifespan after being given domiciliary NIMV. Kurtar et al. [12] found that mortality rate was significantly increased in COPD patients using domiciliary oxygen concentrator for longer than 15 hours/day as compared to those using the device for a shorter time. This unexpected effect observed with domiciliary NIMV therapy, similar to domiciliary oxygen concentrator suggests that patients using the device for longer times are more severe cases and thus expected mortality rate is higher. In the present study, the higher mean age of patients with a shorter lifespan was an expected finding. In another multicentre study, 43 stable hypercapnic patients receiving domiciliary NIMV therapy together with LTOT were compared with 47 controls receiving LTOT alone [13]. The patients were followed up for 2 years in 3-month intervals; it was found that health-related quality of life was improved, and carbon dioxide accumulation and resting dyspnoea decreased in the group receiving NIMV together with LTOT, but no significant difference was found between the groups in terms of mortality rate (18% and 17% respectively) and the number of annual hospital admissions (1.4±2.3 and 0.9±1.2 respectively). Whilst that study with a different design demonstrated some benefits of domiciliary NIMV therapy, it was observed, contrarily with the present study, that the rate of hospital admissions was not changed. In a small-scale randomized study that compared the patients receiving domiciliary NIMV together with LTOT and the patients receiving LTOT alone, improvement was observed in and PaO 2 values (even during daytimes when not receiving NIMV therapy) and a significant increase was observed in the quality of life of patients receiving domiciliary NIMV therapy together with LTOT [11]. Tsuboi et al. [14], in their study on patients receiving domiciliary NIMV, found that the patients with values lower than 60 at 6-months had a significantly higher number of fatal attacks within the first year as compared to the patients with value 60 or higher. Tuggey et al. [15] compared the clinical parameters and patient costs of 13 COPD patients with multiple hospital admissions due to acidotic attacks before and after domiciliary NIMV therapy. They found that annual cost after treatment decreased to 4013 from 12495, total duration of hospital stay decreased to 25 days from 78 days, number of hospital admissions decreased to 2 from 5, and the number of days in intensive care unit decreased to 4 from 25. In that study, although the inclusion of patients that seriously benefited from therapy and the creation of the study group from extremely selected patients have decreased the reliability of data, especially the decrease observed in hospital admissions supports the results of this present study. In a study on patients who had been recommended domiciliary NIMV therapy due to chronic respiratory failure, the patients were divided into two groups as those regularly using the device (n=32) and those that never used the device due to various reasons (n=24), and the groups were compared [16]. It was demonstrated that there was no significant difference between the groups in terms of hospital and intensive care unit admissions. In the present study, only three patients out of 37 were non-compliant with the device suggesting that compliance with the device is very high in the present patient group. The high values in our patient group even at hospital discharge may have caused the patients to have a higher need for the device, which could partially explain the high compliance rates in our study. In the same study, a positive correlation was found between daily duration of NIMV therapy and lifespan. In that study, the significantly lower hospital and intensive care unit admissions and the higher mean values in the group not using the device versus the group using the device within the last year before NIMV was prescribed, indicate that the severity of chronic respiratory failure was not similar in the two groups and that the two groups compared were quite different. We think that this might explain why NIMV therapy failed to decrease the frequency of hospital admissions. Muir et al. [17] found that domiciliary NIMV therapy caused a 50% decrease in the total duration of hospital stay for one year and a significant improvement in symptoms. Consistent with the present study, that study demonstrated that NIMV therapy significantly decreased the number of hospital admissions. Different pressure values and different types of NIMV masks may influence treatment success [18]. In the present study, the mean IPAP was 14.74±1.77 cm H 2 O and the mean EPAP was 6.29±0.72 cm H 2 O. These values were close to those found in previous long-term prospective studies [9,13]. Getting higher benefit from treatment could be possible with higher IPAP values. A retrospective study comprising hypercapnic COPD patients with IPAP values changing between 17 and 40 cm H 2 O determined a decrease in, partial improvement in FEV and an increase in lifespan [19]. 1 Absence of a control group in this study reduces the reliability of benefits obtained with high pressures. Although the prevalence of COPD is higher in males versus females in Turkey, the ratio of females was higher in the present study. The limited number of patients included in the study and the fact that all drop outs (because of being not reached or being non-compliant) were males might have relatively increased the number of female patients. Moreover, we think that Zonguldak s, which is the residential province of the patients, ranking first in terms of air pollution as compared the other provinces of our country and that biomass exposure s being quite common in Zonguldak might have contributed to this situation [20,21]. One of the limitations of the present study is the small number of patients included in the study. This situation hindered the use of statistical methods that would give more accurate results. Moreover, absence of a control group including patients who have indication for domiciliary NIMV, but not using the device, is another limitation of the present study. 115

5 Örnek et al. Domiciliary NIMV in COPD In conclusion, despite the contradictory results reported from the small number of studies on the efficacy of domiciliary NIMV therapy in COPD patients, domiciliary NIMV therapy may have multiple benefits; decreased frequency of hospital admissions and cost, being in the first place. We think that this is important in the struggle against COPD, which is associated with significant morbidity and mortality and a rapidly increasing economic burden. Ethics Committee Approval: Ethics committee approval was received for this study from the ethics committee of Bülent Ecevit University Clinical Research Ethics Committee. Informed Consent: Written informed consent was obtained from patients who participated in this study. Peer-review: Externally peer-reviewed. Author Contributions: Concept - T.Ö., F.E., F.A., B.A., H.T., F.U., M.T.; Design - T.Ö., F.E., F.A., B.A., H.T., F.U., M.T.; Supervision - T.Ö., F.E., F.A., B.A., H.T., F.U., M.T.; Funding - T.Ö.; Materials - T.Ö.; Data Collection and/or Processing - T.Ö.; Analysis and/or Interpretation - T.Ö., M.T.; Literature Review - T.Ö., M.T.; Writer - T.Ö.; Critical Review - T.Ö., F.E., F.A., B.A., H.T., F.U., M.T. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. REFERENCES 1. National Association for Medical Direction of Respiratory Care (NAMDRC). Clinical indications for non-invasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation: A consensus conference report. Chest 1999;116: [CrossRef] 2. Antoniadis A. Long term home Non Invasive Mechanical Ventilation in COPD. 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