Chronic Hypercapnic COPD Patients Research Articles

Long-term home non-invasive ventilation in chronic hypercapnic chronic obstructive pulmonary disease patients: Real-world impact on lung function, acute exacerbations and survival.

Although long-term home non-invasive ventilation (H-NIV) has been used among chronic hypercapnic COPD patients, its clinical benefit is still on debate. We aim to assess the impact of H-NIV in chronic hypercapnic COPD patients. COPD patients who initiated H-NIV between January 2010 and December 2017 were included. Patients with concomitant respiratory disorders were excluded. Acute exacerbation (AE) before and 2years after H-NIV initiation was assessed as main outcome. Secondary outcomes included lung function and gas exchange parameters. Survival since H-NIV initiation was determined, and factors related with survival were explored. Seventy-two patients were enrolled. A decrease in partial pressure of carbon dioxide (PaCO2 ) in arterial blood (p < 0.001) and an improvement of partial pressure of oxygen (PaO2 ) (p < 0.001) were achieved using a high-intensity H-NIV. Regarding lung function, residual volume (RV) reduced (p = 0.010) and forced-expiratory volume in 1s (FEV1 ) improved (p = 0.043) after H-NIV initiation. No significant differences in 6-min walking test (6MWT) were found. Compared with the year before H-NIV initiation, the number of AE diminished in the first and in the second years of follow-up (p < 0.001). The median survival was 79.0months (95% confidence interval [CI], 52.9-105.1), and the covered distance in 6MWT predicted survival (hazard ratio [HR] = 0.026, p = 0.003) in the multivariate analysis. High-intensity H-NIV significantly improved FEV1 and hyperinflation, decreased frequency of AEs and led to a remarkable median survival, which was independently predicted by the walking distance in 6MWT.

Portable NIV for patients with moderate to severe COPD: two randomized crossover trials

BackgroundLong-term non-invasive ventilation (NIV) is as an established treatment option for chronic hypercapnic COPD patients. Beneficial effects have also been shown during exercise, but this is restricted to rehabilitation programs. New portable NIV (pNIV) devices may now enable NIV application during walking at home.Study design and methodsIn two randomized crossover trials, the impact of pNIV on dyspnea and endurance capacity was investigated in patients with moderate to severe COPD. Participants performed a standardized 6-min walking test, with and without pNIV, using a pre-set inspiratory/expiratory positive airway pressure of 18/8 cmH2O. The first study was performed in NIV-naïve patients (Study I), while the second study was performed in those already established on long-term NIV (Study II).Results38 patients (66.9 ± 7.4 years, mean FEV1: 30.3 ± 8%pred) and 23 patients (67.6 ± 8.7 years, mean FEV1: 29.8 ± 10.4%pred) participated in Study I and II, respectively. In Study I, the mean difference in the Borg Dyspnea Scale (BDS, primary outcome) score following walking was 3.2 (IQR 2–4) without pNIV, compared to 2.6 (IQR 1–4) with pNIV (ΔBDS 0.65, P = 0.04), while walking distance increased from 311.8 m (95%CI 276.9–346.6 m) to 326.3 m (95%CI 291.5–361.2 m) (P = 0.044) when pNIV was used. Accordingly, in Study II, the mean difference in BDS was 4.4 (IQR 3–6) without pNIV, compared to 4.5 (IQR 3–6) with pNIV (ΔBDS 0.09, P = 0.54), while walking distance decreased from 291.5 m (95%CI 246.1–336.9 m) to 258.4 m (95%CI 213–303.8 m) (P ≤ 0.001).InterpretationThe use of a pNIV device during walking can improve dyspnea and walking distance in patients with moderate to severe COPD. Patients who do not already receive long-term NIV therapy are more likely to benefit compared to those undergoing long-term NIV. Careful patient selection is mandatory.Clinical Trial Register: DRKS00013203; DRKS00012913 registered October 20th 2017 and October 16th 2017; https://www.drks.de/drks_web/

European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD.

While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients. The European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients. The task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode. Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

Prospective cross-sectional multicenter study on domiciliary noninvasive ventilation in stable hypercapnic COPD patients.

BackgroundDomiciliary noninvasive ventilation (NIV) use in stable hypercarbic COPD is becoming increasingly widespread. However, treatment compliance criteria and factors related to compliance remain to be defined.MethodsThis research was designed as a prospective, cross-sectional, multicenter real-life study. Chronic hypercapnic COPD patients who were using domiciliary NIV for at least 1 year and being followed up in 19 centers across Turkey were included in the study. The patients who used NIV regularly, night or daytime and ≥5 hours/d, were classified as “high-compliance group,” and patients who used NIV irregularly and <5 hours/d as “low-compliance group.”ResultsTwo hundred and sixty-six patients with a mean age of 64.5±10.3 years were enrolled, of whom 75.2% were males. They were using domiciliary NIV for 2.8±2 years. Spontaneous time mode (p<0.001) and night use (p<0.001) were more frequent in the high-compliance group (n=163). Also, mean inspiratory positive airway pressure values of the high-compliance group were significantly higher than the low-compliance group (n=103; p<0.001). Cardiac failure (p=0.049) and obesity (p=0.01) were significantly more frequent in the high-compliance group. There were no difference between 2 groups regarding hospitalization, emergency department and intensive care unit admissions within the last year, as well as modified Medical Research Council dyspnea and COPD Assessment Test scores. With regard to NIV-related side effects, only conjunctivitis was observed more frequently in the high-compliance group (p=0.002).ConclusionDetermination of the patients who have better compliance to domiciliary NIV in COPD may increase the success and effectiveness of treatment. This highly comprehensive study on this topic possesses importance as it suggests that patient and ventilator characteristics may be related to treatment compliance.

Home noninvasive ventilatory support for patients with chronic obstructive pulmonary disease: patient selection and perspectives.

Long-term or home mechanical noninvasive ventilation (Home-NIV) has become a well-established form of therapy over the last few decades for chronic hypercapnic COPD patients in European countries. However, meta-analyses and clinical guidelines do not recommend Home-NIV for COPD patients on a routine basis. In particular, there is ongoing debate about Home-NIV in chronic hypercapnic COPD regarding the overall effects, the most favorable treatment strategy, the selection of eligible patients, and the time point at which it is prescribed. The current review focuses on specific aspects of patient selection and discusses the various scientific as well as clinical-guided perspectives on Home-NIV in patients suffering from chronic hypercapnic COPD. In addition, special attention will be given to the topic of ventilator settings and interfaces.

Home noninvasive positive pressure ventilation with built-in software in stable hypercapnic COPD: a short-term prospective, multicenter, randomized, controlled trial.

BackgroundThe benefits of noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic COPD are controversial. It is presumed that methodology and appropriate use of NIV ventilator might be crucial for the outcomes. With the new built-in software, the performance of NIV can be monitored at home, which can guarantee the compliance and appropriate use. This study investigated effects of home use of NIV in hypercapnia in COPD patients using the NIV ventilator with built-in software for monitoring.MethodsThe current multicenter prospective, randomized, controlled trial enrolled patients with stable GOLD stages III and IV hypercapnic COPD. Patients were randomly assigned via a computer-generated randomization sequence, with a block size of four patients, to continue optimized treatment (control group) or to receive additional NPPV (intervention group) for 3 months. The primary outcome was arterial carbon dioxide pressure (PaCO2). Data were derived from built-in software and analyzed every 4 weeks. Analysis was carried out with the intention to treat. This study is registered with ClinicalTrials.gov, number NCT02499718.ResultsPatients were recruited from 20 respiratory units in China from October 1, 2015, and recruitment was terminated with a record of the vital statistics on May 31, 2016. A total of 115 patients were randomly assigned to the NPPV group (n=57) or the control group (n=58). Patients complied well with NPPV therapy (mean [± standard deviation] day use 5.6±1.4 h). The mean estimation of leaks was 37.99±13.71 L/min. The changes in PaCO2 (−10.41±0.97 vs −4.32±0.68 mmHg, P=0.03) and 6-min walk distance (6MWD) (38.2% vs 18.2%, P=0.02) were statistically significant in the NPPV group versus the control group. COPD assessment test (CAT) showed a positive trend (P=0.06) in favor of the NPPV group. Pulmonary function and dyspnea were not different between groups.ConclusionVentilators equipped with built-in software provided methodology for monitoring NIV use at home, which could facilitate the improvement of compliance and quality control of NIV use. It was shown that three months use of NIV at home could reduce the PaCO2 and improve exercise tolerance (6MWD) in chronic hypercapnic COPD patients.

Prevention of Emphysema‐Induced Reductions in Diaphragm Muscle Mass

Chronic hypercapnic COPD patients have an unfavorable prognosis. Respiratory muscle atrophy and weakness may lead to CO2 retention and ultimately respiratory failure. Therefore, the purpose of this investigation was to determine whether PG‐873637, a corticotrophin‐releasing factor 2 receptor‐selective agonist, would ameliorate diaphragm atrophy and/or induce hypertrophy.To establish the time course of emphysema induced diaphragmatic atrophy, costal diaphragm mass was measured at 4 and 8 months following saline (control) or elastase (emphysema) instillation in hamsters. Subsequently, after demonstration of atrophy, control and emphysema hamsters were treated with either saline (vehicle) or PG‐873637 (treatment) for 1 or 5 months prior to sacrifice.Excised lung volume increased (&gt;140%) with emphysema at all time points. PG‐873637 treatment increased diaphragm muscle mass at both time points in emphysema animals (1‐month = 13% and 5‐month = 12%). These data demonstrate that PG‐873637 is efficacious as a treatment to preserve mass or induce hypertrophy in the emphysematous diaphragm.

Survival of Chronic Hypercapnic COPD Patients Is Predicted by Smoking Habits, Comorbidity, and Hypoxemia

Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (P(I(max))), decreased maximum expiratory mouth pressure (P(E(max))), and low hypercapnic ventilatory response (HCVR), could be related to survival. Other parameters, such as arterial blood gas values, airway obstruction (FEV1), body mass index (BMI), current smoking status, and the presence of comorbidity were studied as well. A cohort of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3 weeks) in our institute was followed up for 3.8 years on average. Survival was analyzed using a Cox proportional hazards model. The risk factors considered were analyzed, optimally adjusted for age and gender. At the time of analysis 18 patients (10 male) were deceased. After adjusting for age and gender, P(I(max)), P(E(max)), and HCVR were not correlated with survival within this hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7 to 18.7) were associated with increased mortality. A higher Pa(O2) affected survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Pa(CO2) tended to be lower in survivors, but this did not reach statistical significance (HR, 2.0 per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related with survival in hypercapnic COPD patients. In patients with chronic hypercapnia, only smoking status, the presence of comorbidity, and Pa(O2) level are significantly associated with survival. Airway obstruction, age, and BMI are known to be predictors of survival in COPD patients in general. However, these parameters do not seem to significantly affect survival once chronic hypercapnia has developed.

Ventilation therapy for patients with COPD

Acute ventilatory failure in COPD is caused by impaired respiratory mechanics and an imbalance of capacity and load of the respiratory muscles. Continuous positive airway pressure (CPAP), pressure support ventilation (PSV), proportional assist ventilation (PAV) or controlled mechanical ventilation (CMV) are effective in unloading the respiratory pump. CPAP reduces the inspiratory pressure time product by reducing the elastic work of breathing due to intrinsic PEEP (PEEPi). PSV and PAV reduce the work of breathing and additionally improve alveolar ventilation and CO2 elimination. In spontaneous breathing patients these modes of ventilation should be applied non invasively by using a face mask. In CMV, hyperinflation should be avoided by choice of low tidal volumes and long exspiratory times (low respiratory rate, I:E ratio 1:3, 1:4). In the weaning from CMV, PSV or PAV and CPAP is used. There seems to be a beneficial effect in nocturnal intermittent nonivasive ventilation (NPPV) in chronic hypercapnic stable COPD patients with documented hypoventilation during the night, which is reversible by NPPV.

Effects of Acetazolamide and Furosemide on Ventilation and Cerebral Blood Volume in Normocapnic and Hypercapnic Patients With COPD

Effects of chronic metabolic alkalosis and acidosis and their relation to central chemoregulation may differ between normocapnic and chronic hypercapnic patients with COPD. The relationship between responses of inspired ventilation (VI), mouth occlusion pressure (P(0.1)), and cerebral blood volume (CBV), to short-term changes in arterial PCO(2) was measured. Seventeen patients with chronic hypercapnia and COPD (PaCO(2) > 6.0 kPa) and 16 normocapnic patients with COPD (PaCO(2) < or = 6.0 kPa) [FEV(1) 27% predicted] were studied under baseline metabolic conditions and after 1 week of treatment with oral furosemide, 40 mg/d, or acetazolamide, 500 mg/d. Hypercapnia (change in end-tidal carbon dioxide > 1 kPa) was induced by administering adequate amounts of carbon dioxide in the inspired air. CBV was measured using near-infrared spectroscopy. Compared with baseline metabolic condition, chronic metabolic acidosis and alkalosis did not change ventilatory (Delta VI/Delta PaCO(2)) and cerebrovascular (Delta CBV/Delta PaCO(2)) reactivity. Base excess (BE) decreased by 6.8 +/- 1.1 mEq/L and 6.9 +/- 1.6 mEq/L, respectively, in the normocapnic and chronic hypercapnic COPD groups during metabolic acidosis, resulting in a not-quite-significant leftward shift of both the ventilatory and cerebrovascular carbon dioxide response curve. BE increased by 2.3 +/- 1.2 mEq/L and 1.2 +/- 1.3 mEq/L, respectively, during chronic metabolic alkalosis in both COPD groups, without concomitant shift. Poor correlations between ventilatory and cerebrovascular carbon dioxide responsiveness (Delta CBV/Delta PaCO(2) and Delta VI/Delta PaCO(2), Delta CBV/Delta PaCO(2) and Delta P(0.1)/Delta PaCO(2), respectively) were found irrespective of baseline, respiratory condition, and induced metabolic state. Normocapnic and chronic hypercapnic COPD patients have the same ventilatory and cerebrovascular carbon dioxide responsiveness irrespective of induced metabolic state.