Abstract
BACKGROUND: The ventilatory mechanics of patients with COPD and obesity-hypoventilation syndrome (OHS) are changed when there is air trapping and auto-PEEP, which increase respiratory effort. P0.1 measures the ventilatory drive and, indirectly, respiratory effort. The aim of the study was to measure P0.1 in subjects with COPD or OHS on treatment with positive pressure and to analyze their changes in P0.1 after treatment.
METHODS: With a prospective design, subjects with COPD and OHS were studied in whom positive airway pressure was applied in their treatment. P0.1 was determined at study inclusion and after 6 months of treatment.
RESULTS: A total of 88 subjects were analyzed: 56% were males, and the mean age of 65 ± 9 y old. Fifty-four (61%) had OHS, and 34 (39%) had COPD. Fifty (56%) had air trapping, with an initial P0.1 value of 3.0 ± 1.3 cm H2O compared with 2.1 ± 0.7 cm H2O for subjects who did not have air trapping (P = .001). After 6 months of treatment, subjects who had air trapping had similar P0.1 as those who did not: 2.3 ± 1.1 and 2.1 ± 1 cm H2O, respectively (P = .53). In subjects with COPD, initial P0.1 was 2.9 ± 1.4 cm H2O and at 6 months 2.2 ± 1.1 cm H2O (P = .02). In subjects with OHS, initial P0.1 was 2.4 ± 1.1 cm H2O and at 6 months 2.2 ± 1.0 cm H2O (P = .28).
CONCLUSIONS: COPD and air trapping were associated with greater P0.1 as a marker of respiratory effort. A decrease in P0.1 indicates lower respiratory effort after treatment.
Introduction
The ventilatory mechanics of individuals with disorders such as COPD or obesity-hypoventilation syndrome (OHS) are altered, and there may be air trapping and auto-PEEP,1,2 defined as positive airway pressure at the end of expiration. In the course of the disease, hypercapnic respiratory failure can appear and occasionally requires treatment with devices that provide positive pressure in the airway in different ways, either in the form of noninvasive ventilation (NIV) or CPAP. During mechanical ventilation, especially if the expiration time is shortened, lung emptying is more difficult, air trapping is provoked, and an increase in pressure at the end of expiration (auto-PEEP) increases respiratory work; induces patient-ventilator asynchronies, hemodynamic changes; and compromises the effectiveness of ventilation.3 The treatment in this situation is to provide an external PEEP that counteracts auto-PEEP, and this aspect, widely studied in invasive mechanical ventilation, is less known in NIV or CPAP due to the difficulty in measuring it in routine clinical practice.3 In addition, the titration of the expiratory positive airway pressure (EPAP) and/or CPAP is usually oriented toward the correction of the obstruction in the upper airway and could be set at suboptimal or excessive levels for the correction of auto-PEEP.
On the other hand, the ventilatory pattern will be the expression of the adjustment of the respiratory center to the different functional situations, among which is the presence of air trapping. In this sense, and in the context of invasive mechanical ventilation, the measurement of P0.1 has been studied as a marker of respiratory effort to titrate the external PEEP level necessary to counteract auto-PEEP.4 Since P0.1 is an indirect marker of auto-PEEP, we wanted to analyze its possible changes in patients undergoing positive airway pressure treatment. The aim of the study was to measure the P0.1 values in subjects with COPD and/or OHS, establish the relationship of these values with the presence of air trapping, and analyze the changes in these values after treatment with positive-pressure devices.
QUICK LOOK
Current Knowledge
Individuals with air trapping and auto-PEEP secondary to COPD or obesity-hypoventilation syndrome (OHS) have an increase in respiratory work. The P0.1 value is a measurement of the ventilatory drive and, indirectly, respiratory effort.
What This Paper Contributes to Our Knowledge
In subjects with COPD and OHS with chronic hypercapnic respiratory failure treated with positive pressure at home, 56% of them had air trapping, and their baseline P0.1 values were elevated. The value of P0.1 decreased significantly after treatment with positive pressure.
Methods
Using a repeated-measurements prospective design, a study was conducted on a group of subjects with chronic hypercapnic respiratory failure (daytime PCO2 > 50 mm Hg) in whom positive airway pressure was applied for their treatment. We provide a standardized adaptation process to NIV on our unit. We used the S/T mode in all subjects, with inspiratory positive airway pressure, EPAP, and breathing frequency programmed on an out-patient basis to achieve comfort and effectiveness. Clinical appropriateness was verified by nocturnal oximetry, daytime gasometry (diurnal PCO2 < 50 mm Hg), and built-in software analysis, specifically apnea-hypopnea index (AHI) and the appearance of patient-ventilator asynchronies.5
Subjects in stable condition (no exacerbations documented 4 weeks before inclusion) were included consecutively in an ambulatory setting between June 2017–January 2020. Subjects with a diagnosis of COPD or OHS were included, and patients who had neuromuscular diseases or chest wall disorders were excluded as well as those who required a medical assessment or therapeutic changes due to an exacerbation of respiratory cause during the 4 weeks prior to inclusion. The COPD diagnosis was based on the Global Initiative for Chronic Obstructive Lung Disease6 criteria: FEV1/FVC < 70 after bronchodilator treatment. For the diagnosis of OHS, the usual criteria were used (body mass index [BMI] > 30 kg/m2, diurnal PCO2 > 45 mm Hg, and exclusion by any other cause). Subjects with COPD received treatment with bronchodilators (long-acting muscarinic antagonist + long-acting β agonist) before their inclusion in the study, and no substantial changes were made.
The following variables were initially obtained: age; sex; BMI; and diurnal values of PaO2, PaCO2, and HCO3. Nocturnal respiratory polygraphy was performed at home, and the following data were collected: the AHI and percentage of nocturnal time with an SpO2 < 90%. Lung function studies were performed, which included spirometry, static lung volumes, and the measurement of P0.1.
The treatment between NIV or CPAP was decided at the time of inclusion, depending on the clinical situation, level of hypercapnia, and AHI value, following the established criteria.7,8 Subjects were assessed after at least 6 months of treatment through a clinical interview, diurnal blood gas assessment, nocturnal pulse oximetry, a reading the build-in software of the ventilators, and a further P0.1 measurement. At that time, nonadherent subjects (< mean of 4 h of use/d), those who had exacerbations in the previous month, and those in which a second determination of P0.1 could not be obtained 6 months after starting treatment were excluded. The P0.1 values obtained in a previous study carried out by our group with the same methodology were used as values for a control group.5
A Micro 5000 HypAir (Medisoft, Sorinnes, Belgium) spirometer and a BodyBox 5500 (Medisoft) plethysmograph were used in the lung function studies. The analysis included FEV1, total lung capacity (TLC), and residual volume (RV) (expressed as an absolute value and a percentage of its theoretical value). Spirometry was performed following the protocols and reference values recommended by Spanish Society of Pulmonology and Thoracic Surgery.9 Body plethysmography was performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines using ERS reference values.10 The existence of air trapping was established when the RV/TLC was ≥ 50, with an RV > 120% of its reference value.11 The value of P0.1 was determined using the HypAir compact + Muscle Study (Medisoft) device, measuring the occlusion pressure in the first 100 ms of inspiration from functional residual capacity with the airway occluded and breathed at tidal volume. Five maneuvers were performed, disregarding the highest and lowest values, and the average of the remaining 3 values was obtained.12
The quantitative variables are presented as the mean and SD, and the qualitative variables are presented as percentages. The Kolmogorov-Smirnov test was used to check that quantitative variables were normally distributed. The quantitative variables were analyzed using bivariate Pearson correlation and comparisons of the mean (Student t test). For qualitative variables, we used the chi-square test; a value of P < .05 was considered significant. We estimated the sample size over the number of subjects with COPD and OHS who receive NIV at home and considered a confidence level of 90% with an error of 8% the necessary sample would be 85 cases. For the analyses, the subjects were divided into 2 groups depending on whether there was air trapping. An analysis was also carried out according to etiologies, comparing subjects with COPD with subjects with OHS, and according to treatment, comparing those who received treatment with NIV with those who received treatment with CPAP. The study was approved by the research ethics committee of our site (No. 2020.123), and written informed consent was obtained from all subjects included in the study.
Results
A total of 101 patients were initially assessed, of whom 13 were excluded: 3 had recent exacerbations; another 4 had low adherence, and 6 were not considered evaluable due to not having completed the studies (Fig. 1). The final sample was 88 subjects, of whom 49 (56%) were males, with a mean age of 65 ± 9 y; 54 (61%) had a diagnosis of OHS, and 34 (39%) had COPD. Of the total subjects, 50 (56%) had air trapping. In 51 (58%), the treatment was NIV, and the rest was treated with CPAP. In 26 COPD (76%) and 25 OHS subjects (46%), NIV was used (P = .003); 28 of the subjects with COPD (82%) and 22 of those with OHS (40%) showed air trapping (P = .001). The clinical and functional characteristics of the whole series are shown in Table 1.
Flow chart.
Characteristics of Subjects Included in the Study
The initial P0.1 values showed significant differences between the subjects with air trapping, 3.0 ± 1.3 cm H2O, compared to 2.1 ± 0.7 cm H2O in those who did not have air trapping (P = .001). After treatment, the group with air trapping had P0.1 values equal to those of the group without air trapping and significantly lower than the initial values. The value of P0.1 in the group without air trapping did not change after the treatment period (Table 2). The value of P0.1 in the control group was 2.1 ± 0.7 cm H2O, with no significant differences from the value of P0.1 in subjects without air trapping or the value of P0.1 at 6 months of treatment.
Comparison of Subjects With and Without Air Trapping
In the correlation study, a relationship was detected between baseline P0.1 and FEV1 (r = −0.45, P = .001) and the RV/TLC (r = −0.38, P = .001). No relationship was detected between baseline P0.1 and the other clinical and functional parameters. There was also no relationship found between P0.1 at 6 months of treatment and functional clinical data, the ventilatory parameters, or AHI.
If we compared the subjects who received CPAP with those treated with NIV, we observed that the tendency was to treat the subjects with more severe sleep apnea syndrome with CPAP. The CPAP level employed was superior to that used in the NIV; however, the initial P0.1 value and the P0.1 value after treatment, as well as the rest of the data, were not significantly different between the 2 groups (Table 3). Comparing etiological groups, subjects with COPD had a greater tendency for air trapping; their initial P0.1 value was higher, and their AHI was lower than subjects with OHS (Table 4).
Comparison Between Subjects Treated With Noninvasive Ventilation Versus Those Treated With CPAP
Comparison Between COPD and OHS Subjects
In the group of subjects without air trapping, there were no subjects who reached the mean value of P0.1 of the group with air trapping. At 6 months of treatment, 36 of the 50 subjects with air trapping (72%), 26 of the 34 subjects with COPD (76%), and 26 of the 54 with OHS (48%) reduced their P0.1 value.
In the group of subjects with air trapping (n = 49), 29 had COPD with mean P0.1 = 3.2 ± 1.4 cm H2O, and 20 had OHS with mean P0.1 = 2.7 ± 1.1 cm of H2O (P = .68). At 6 months of treatment, subjects with COPD had a mean P0.1 = 2.37 (1.1) cm of H2O and those with OHS a mean P0.1 = 2.13 ± 0.90 cm of H2O (P = .45). In the group of subjects with COPD (n = 34), the initial value of P0.1 was 2.98 ± 1.40 cm H2O and at 6 months of treatment 2.2 ± 1.1 cm H2O (P = .02). In the group of subjects with OHS (n = 54), the initial value of P0.1 was 2.4 ± 1.1 cm H2O and at 6 months of treatment 2.2 ± 1.0 cm H2O (P = .28). In the group of subjects with COPD and air trapping, the initial value of P0.1 was 3.2 ± 1.5 cm H2O; subjects with COPD without air trapping had 2.1 ± 0.3 cm H2O (P = .003); in the group of subjects with OHS and air trapping, the initial value of P0.1 was 2.9 ± 0.8 cm H2O; subjects with OHS without air trapping had 2.0 ± 0.7 cm H2O (P = .007).
Discussion
In our series of subjects with hypercapnic respiratory failure treated with CPAP or home NIV, those with COPD and those with air trapping showed elevated baseline P0.1 value. The value of P0.1 decreased significantly after treatment with positive pressure. Taking into account that P0.1 is a measurement of the ventilatory drive and has shown a good correlation with respiratory effort,13 we could consider that this drop reflects a decrease in respiratory work.
Air trapping is a phenomenon of great relevance in COPD and is associated with symptoms such as dyspnea or a decrease in exercise capacity.14 Air trapping and auto-PEEP phenomena have been described in OHS in relation to anomalies in the distribution of ventilation and the closure of small airways.1,2 In our series of subjects with OHS and COPD, we found that more than half of them had air trapping and probably an increase in airway pressure and the end of expiration (auto-PEEP). If we compare according to etiology, subjects with COPD had a greater tendency for air trapping than those with OHS. We believe that this has to be taken into account when establishing therapy and monitoring.
Auto-PEEP has a negative effect on mechanical ventilation, and to neutralize this negative effect, an external EPAP is programmed at an adequate level that could counteract it. However, the titration of this EPAP is complex in clinical practice in patients on NIV.3 Although our work does not provide information on the value of auto-PEEP or its titration, we believe that the relationship between P0.1 and the presence of air trapping makes it possible to hypothesize a relationship between the decrease in P0.1 after the treatment and the value of EPAP or CPAP selected; however, we have not demonstrated this association in our study. In this sense, the determination of P0.1 has been used in subjects on invasive mechanical ventilation to adjust the value of the PEEP as well as to guide extubation or to establish the level of pressure support.4,15,16 However, there are fewer studies in the context of NIV. Although with a different hypothesis, in a study on 35 subjects with OHS, Heinemann et al17 found baseline values of RV/TLC > 50 and a P0.1 value of 4.0 cm H2O. At 12 months of treatment with positive pressure, a drop was detected in the RV/TLC value and in P0.1, which showed a mean of 3.2 cm H2O. The authors concluded that treatment with positive pressure has an effect on lung volumes. Our findings demonstrate the presence of significant air trapping in subjects with OHS and elevated values of P0.1 and may suggest that P0.1 could be an indirect marker of respiratory work. We highlight that the subjects with no air trapping had a significantly lower P0.1 value that was not modified with the treatment, showing values nearer to those that we consider reference values.12 At the current time, there are no references in any of the clinical practice guidelines or consensus documents that address that the presence of auto-PEEP and/or air trapping may have a relevant effect on patients on long-term NIV.15,16
Subjects with COPD had a lower AHI and BMI but a higher RV/TLC and initial P0.1 value than subjects with OHS. At 6 months of treatment, the P0.1 value was the same in both groups. On the other hand, the subjects treated with CPAP presented a higher AHI, and their CPAP was titrated at a higher value than the subjects treated with NIV; however, there were no differences in the initial or final P0.1 values or in the RV/TLC. Although bronchodilator treatment may influence the P0.1 value in subjects with COPD,18 in our series, there were no changes in the treatment that could influence the P0.1 measurements. We want to highlight that in the analysis by diagnostic subgroups subjects with COPD were more likely to be treated with NIV than subjects with OHS and to show a high P0.1 value that decreased significantly after treatment with positive pressure; this phenomenon also occurs when there is air trapping. These data lead us to hypothesize that the value of P0.1 may be related to the existence of air trapping and may be used as an evolution marker.
A strong point of our study is that its findings relate air trapping with respiratory work in subjects on NIV, especially in a large group of subjects with OHS. Our study has some limitations such as (1) not having a second lung volume determination available, which would allow P0.1 after treatment to be correlated with the air-trapping level; (2) P0.1 is not a specific marker of air trapping and may be influenced by other factors that could be present in the subjects included in the study; and (3) we opted to jointly study subjects with COPD and OHS, who, although they may have different physiopathological characteristics, have in common the presence of air trapping, which is a subject of our hypothesis. To explore the clinical usefulness of our findings, longitudinal studies that would provide information regarding the relationships among the changes in lung volumes, P0.1, and parameters are necessary.
In our series of subjects with hypercapnic respiratory failure, initial P0.1 measurements were increased in those with COPD and/or air trapping, and these values decreased after treatment with positive pressure. We believe these findings indicate a decrease in respiratory work and that P0.1 values are suitable for adjusting ventilation treatment. Budweiser et al19 demonstrated in a group of subjects with chronic respiratory failure undergoing treatment with NIV that the value of P0.1 could predict mortality. If we consider that a decrease in respiratory effort is one of the objectives of NIV, we could say that, with the measurement of P0.1, we would be indirectly monitoring a marker of great relevance. The design of works that incorporate complete studies of lung function can provide us with information to classify our patients and measure the impact of treatments that we administer.
Conclusions
Subjects with COPD and subjects with air trapping and chronic hypercapnic respiratory failure on treatment with positive pressure at home had evlevated baseline P0.1 values. This value decreased significantly after treatment with positive pressure.
Footnotes
- Correspondence: Ramón Fernández Álvarez, Servicio de Neumología, Hospital Universitario Central de Asturias, Avda de Roma s/n 33011 Oviedo, Asturias, Spain. E-mail: enelllano{at}gmail.com
The authors have disclosed no conflicts of interest.
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