Characterization and Mortality Risk of Impaired Left Ventricular Filling in COPD.

BACKGROUND: In COPD, impaired left ventricular (LV) filling might be associated with coexisting HFpEF or due to reduced pulmonary venous return indicated by small LV size. We investigate the all-cause mortality associated with small LV or HFpEF and clinical features discriminating between both patterns of impaired LV filling. METHODS: We performed transthoracic echocardiography (TTE) in patients with stable COPD from the COSYCONET cohort to define small LV as LVEDD below the normal range and HFpEF features according to recommendations of the European Society of Cardiology. We assessed the E/A and E/e' ratios, NT-pro-BNP, hs-Troponin I, FEV1, RV, DLCo, and discriminated patients with small LV from those with HFpEF features or no relevant cardiac dysfunction as per TTE (normalTTE). The primary outcome was all-cause mortality after four and a half year. RESULTS: In 1752 patients with COPD, the frequency of small LV, HFpEF-features, and normalTTE was 8%, 16%, and 45%, respectively. Patients with small LV or HFpEF features had higher all-cause mortality rates than patients with normalTTE, HR: 2.75 (95% CI: [1.54 - 4.89]) and 2.16 (95% CI: [1.30 - 3.61]), respectively. Small LV remained an independent predictor of all-cause mortality after adjusting for confounders including exacerbation frequency and measures of RV, DLCo, or FEV1. Compared to normalTTE, patients with small LV had reduced LV filling, as indicated by lowered E/A. Yet in contrast to patients with HFpEF-features, patients with small LV had normal LV filling pressure (E/e') and lower levels of NT-pro-BNP and hs-Troponin I. CONCLUSION: In COPD, both small LV and HFpEF-features are associated with increased all-cause mortality and represent two distinct patterns of impaired LV filling.

Lung Hyperinflation as Treatable Trait in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Lung hyperinflation (LH) is a common clinical feature in patients with chronic obstructive pulmonary disease (COPD). It results from a combination of reduced elastic lung recoil as a consequence of irreversible destruction of lung parenchyma and expiratory airflow limitation. LH is an important determinant of morbidity and mortality in COPD, partially independent of the degree of airflow limitation. Therefore, reducing LH has become a major target in the treatment of COPD over the last decades. Advances were made in the diagnostics of LH and several effective interventions became available. Moreover, there is increasing evidence suggesting that LH is not only an isolated feature in COPD but rather part of a distinct clinical phenotype that may require a more integrated management. This narrative review focuses on the pathophysiology and adverse consequences of LH, the assessment of LH with lung function measurements and imaging techniques and highlights LH as a treatable trait in COPD. Finally, several suggestions regarding future studies in this field are made.

Spontaneous Intragastric Balloon Hyperinflation: Two Cases and Outcomes.

Endoscopic bariatric therapies can provide treatment options for obesity in non-surgical candidates, as a part of combination or serial treatment plans, and for the reduction of obesity-related comorbidities. Several complications of intragastric balloons have been documented, but spontaneous hyperinflation is a risk that has not been well reported previously. We describe two cases of spontaneous intragastric balloon hyperinflation and their outcomes.

Long COVID symptoms after 8-month recovery: persistent static lung hyperinflation associated with small airway dysfunction.

BACKGROUND: Limited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially dyspnea and fatigue. METHODS: 64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes. RESULTS: SLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue. CONCLUSION: SAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC.

Dynamic inflation prevents and standardized lung recruitment reverts volume loss associated with percutaneous tracheostomy during volume control ventilation: results from a Neuro-ICU population.

To determine how percutaneous tracheostomy (PT) impacts on respiratory system compliance (Crs) and end-expiratory lung volume (EELV) during volume control ventilation and to test whether a recruitment maneuver (RM) at the end of PT may reverse lung derecruitment. This is a single center, prospective, applied physiology study. 25 patients with acute brain injury who underwent PT were studied. Patients were ventilated in volume control ventilation. Electrical impedance tomography (EIT) monitoring and respiratory mechanics measurements were performed in three steps: (a) baseline, (b) after PT, and (c) after a standardized RM (10 sighs of 30 cmH2O lasting 3 s each within 1 min). End-expiratory lung impedance (EELI) was used as a surrogate of EELV. PT determined a significant EELI loss (mean reduction of 432 arbitrary units p = 0.049) leading to a reduction in Crs (55 ± 13 vs. 62 ± 13 mL/cmH2O; p < 0.001) as compared to baseline. RM was able to revert EELI loss and restore Crs (68 ± 15 vs. 55 ± 13 mL/cmH2O; p < 0.001). In a subgroup of patients (N = 8, 31%), we observed a gradual but progressive increase in EELI. In this subgroup, patients did not experience a decrease of Crs after PT as compared to patients without dynamic inflation. Dynamic inflation did not cause hemodynamic impairment nor raising of intracranial pressure. We propose a novel and explorative hyperinflation risk index (HRI) formula. Volume control ventilation did not prevent the PT-induced lung derecruitment. RM could restore the baseline lung volume and mechanics. Dynamic inflation is common during PT, it can be monitored real-time by EIT and anticipated by HRI. The presence of dynamic inflation during PT may prevent lung derecruitment.

Detection of dynamic lung hyperinflation using cardiopulmonary exercise testing and respiratory function in patients with stable cardiac disease: a multicenter, cross-sectional study.

BACKGROUND: Many patients with heart disease potentially have comorbid chronic obstructive pulmonary disease (COPD); however, there are not enough opportunities for screening, and the qualitative differentiation of shortness of breath (SOB) has not been well established. We investigated the detection rate of SOB based on a visual and qualitative dynamic lung hyperinflation (DLH) detection index during cardiopulmonary exercise testing (CPET) and assessed potential differences in respiratory function between groups. METHODS: We recruited 534 patients with heart disease or patients who underwent simultaneous CPET and spirometry (369 males, 67.0 ± 12.9 years) to scrutinize physical functions. The difference between inspiratory and expiratory tidal volume was calculated (TV E-I) from the breath-by-breath data. Patients were grouped into convex (decreased TV E-I) and non-convex (unchanged or increased TV E-I) groups based on their TV E-I values after the start of exercise. RESULTS: Among the recruited patients, 129 (24.2%) were categorized in the convex group. There was no difference in clinical characteristics between the two groups. The Borg scale scores at the end of the CPET showed no difference. VE/VCO2 slope, its Y-intercept, and minimum VE/VCO2 showed no significant difference between the groups. In the convex group, FEV1.0/FVC was significantly lower compared to that in the non-convex group (69.4 ± 13.1 vs. 75.0 ± 9.0%). Moreover, significant correlations were observed between FEV1.0/FVC and Y-intercept (r=-0.343), as well as between the difference between minimum VE/VCO2 and VE/VCO2 slope (r=-0.478). CONCLUSIONS: The convex group showed decreased respiratory function, suggesting a potential airway obstruction during exercise. A combined assessment of the TV E-I and Y-intercept of the VE/VCO2 slope or the difference between the minimum VE/VCO2 and VE/VCO2 slopes could potentially detect COPD or airway obstruction.

Chronic obstructive pulmonary disease (COPD) and COPD-like phenotypes.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Historically, two COPD phenotypes have been described: chronic bronchitis and emphysema. Although these phenotypes may provide additional characterization of the pathophysiology of the disease, they are not extensive enough to reflect the heterogeneity of COPD and do not provide granular categorization that indicates specific treatment, perhaps with the exception of adding inhaled glucocorticoids (ICS) in patients with chronic bronchitis. In this review, we describe COPD phenotypes that provide prognostication and/or indicate specific treatment. We also describe COPD-like phenotypes that do not necessarily meet the current diagnostic criteria for COPD but provide additional prognostication and may be the targets for future clinical trials.

A Review of Management of Congenital Sublobar Hyperinflation at a Single Institution.

There has been an increased recognition of a subset of congenital lobar emphysema (CLE), termed congenital sublobar hyperinflation (CSLH), which may affect only a segment of lung as opposed to an entire lobe. This is an uncommon variant for which there is a paucity of information in published literature. The majority of CLE are managed surgically. Current literature suggests non-operative management for CSLH. However, there has been slow adoption of non-operative management and there is not a well-established observation pathway. A retrospective review of all pediatric patients diagnosed with CSLH at a single institution was performed from 2017 to 2023 to determine if this variant may be safely managed with observation. A total of 10 patients were identified. Of these, three patients had consolidation on cross-sectional imaging; therefore, operative intervention was undertaken given diagnostic uncertainty. All patients managed observationally remained asymptomatic. This case series validates non-operative management for patients with asymptomatic CSLH.

Dynamic hyperinflation is a risk factor for mortality and severe exacerbations in COPD patients.

OBJECTIVE: To assess if dynamic hyperinflation is an independent risk factor for mortality and severe exacerbations in COPD patients. METHODS: A cohort of 141 patients with stable COPD and moderate to very severe airflow limitation, treated according to conventional guidelines, was followed for a median of 9 years. Clinical characteristics were recorded and arterial blood gases, pulmonary function tests, 6-min walk and incremental exercise test with measurement of respiratory pattern and operative lung volumes were performed. Endpoints were all-cause mortality and hospitalization for COPD exacerbation. RESULTS: 58 patients died during the follow-up period (1228 patients x year). The mortality rate was higher in patients with dynamic hyperinflation (n = 106) than in those without it (n = 35) (14.6; 95% CI, 14.5-14.8 vs. 7.2; 95% CI, 7.1-7.4 per 1000 patients-year). After adjusting for sex, age, body mass index, pack-years and treatment with inhaled corticosteroids, dynamic hyperinflation was associated with a higher mortality risk (adjusted hazard ratio [aHR], 2.725; 95% CI, 1.010-8.161), and in a multivariate model, comorbidity, peak oxygen uptake and dynamic hyperinflation were retained as independent predictors of mortality. The time until first severe exacerbation was shorter for patients with dynamic hyperinflation (aHR, 3.961; 95% CI, 1.385-11.328), and dynamic hyperinflation, FEV1 and diffusing capacity were retained as independent risk factors for severe exacerbation. Moreover, patients with dynamic hyperinflation had a higher hospitalization risk than those without it (adjusted incidence rate ratio, 1.574; 95% CI, 1.087-2.581). CONCLUSION: In stable COPD patients, dynamic hyperinflation is an independent prognostic factor for mortality and severe exacerbations.

Relationship Between Lung Volumes and Heterogeneity in the Response to Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Lung Disease.

BACKGROUND: The effects of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory outcomes for people with cystic fibrosis (CF) were demonstrated by several clinical trials, mainly based on simple spirometry. However, gains in lung function may vary greatly between patients, and predictors of FEV1 change after treatment are still missing. RESEARCH QUESTION: Which ventilatory parameters are involved in the heterogeneity of FEV1 change after 12-month ETI treatment in people with CF with advanced lung disease? STUDY DESIGN AND METHODS: This was a multicenter, observational, prospective cohort study at two major CF centers in Italy. We enrolled 47 adults with CF and advanced lung disease (FEV1 < 40% or actively listed for lung transplant) who started ETI treatment between December 2019 and December 2021. At treatment initiation and after 12 months, patients underwent body plethysmography. Values were compared at the two time points. To assess the relationship between baseline plethysmography measurements and treatment-induced changes in FEV1, we used the Spearman rank correlation coefficient (r) and median quantile regressions. RESULTS: After 12 months of ETI treatment, there was a significant increase in FEV1 % predicted from a median value of 36.0 (25th-75th percentile, 33-39) to 52 (25th-75th percentile, 43-61) (P < .001). Inspiratory capacity/total lung capacity (TLC) ratio also increased from 32.0 (25th-75th percentile, 28.6-36.9) to 36.3 (25th-75th percentile, 33.4-41.3) (P < .001). Specific airway resistance decreased from 263 (25th-75th percentile, 182-405) to 207 (25th-75th percentile, 120-258) (P < .001). Functional residual capacity/TLC ratio decreased from 68.2 (25th-75th percentile, 63.3-71.9) to 63.9 (25th-75th percentile, 58.8-67.1) (P < .001), and residual volume (RV)/TLC ratio decreased from 53.1 (25th-75th percentile, 48.3-59.4) to 45.6 (25th-75th percentile, 39.4-49.8) (P < .001). Changes in FEV1 % predicted negatively correlated with baseline functional residual capacity/TLC ratio (r = -0.38, P = .009) and RV/TLC ratio (r= -0.42, P = .004). After adjustment for age at treatment initiation and cystic fibrosis transmembrane conductance regulator genotype, we estimated that for each 10-unit increase in baseline RV/TLC ratio, the expected median change in FEV1 decreased by 2.3 (95% CI, -5.8 to -0.8). INTERPRETATION: ETI was associated with improvements in both static and dynamic volumes in people with CF and advanced lung disease. Heterogeneity in FEV1 % predicted change after 12 months of treatment may be predicted by the severity of hyperinflation at baseline.

Impact of biologics on lung hyperinflation in patients with severe asthma.

BACKGROUND: In asthma, inflammation affects both the proximal and distal airways and can cause significant hyperinflation, which is thought to be a major cause of dyspnea. METHODS: This is a retrospective observational study evaluating the effect of three months of treatment with different biologic drugs (benralizumab, dupilumab and omalizumab) on pulmonary hyperinflation in a cohort of patients with severe asthma already receiving regular triple inhaled therapy. Changes in RV, RV/TLC ratio, FRC and FRC/TLC ratio were the primary efficacy measures. Secondary outcomes included FEV1, FVC, FEV1/FVC ratio, IC, IC/TLC ratio, asthma control test, the percentage of eosinophils in the blood and fractional FENO. RESULTS: Benralizumab led to significant changes (p < 0.001) in RV, RV/TLC, FRC, and FRC/TLC. Dupilumab demonstrated a notable reduction in RV (p = 0.017) and RV/TLC (p = 0.002), but the decreases in FRC and FRC/TLC were merely numerical and not as pronounced as those induced by benralizumab. Omalizumab's positive impact on RV (p = 0.057) and RV/TLC (p = 0.085), as well as FRC (p = 0.202) and FRC/TLC (p = 0.096), was also predominantly numerical, with a tendency towards efficacy, albeit excluding the effect on FRC. Treatment with biologics resulted in improvements in all other lung function parameters assessed and a decrease in FENO levels. CONCLUSION: This study, although limited by small sample size, lack of a placebo control, and unbalanced group sizes, suggests that biological agents are effective in reducing lung hyperinflation even after a relatively short treatment.

The Impact of Positive Expiratory Pressure Therapy on Hyperinflation in Patients With COPD.

BACKGROUND: Lung hyperinflation is a typical clinical feature of patients with COPD. Given the association between breathing at elevated lung volumes and the manifestation of severe debilitating symptoms, therapeutic interventions such as positive expiratory pressure (PEP) therapy and its variations (temporary, oscillatory) have been devised to mitigate lung hyperinflation. However, the efficacy of these interventions remains to be conclusively demonstrated. METHODS: A systematic review with meta-analysis of randomized trials was conducted following the PRISMA guidelines. Seven databases were screened with no date or language restriction. Two authors independently applied eligibility criteria and assessed the risk of bias of included studies using the Cochrane risk-of-bias tool. Outcomes were lung hyperinflation measures detected through changes in inspiratory capacity (IC), functional residual capacity (FRC), total lung capacity (TLC), and residual volume (RV), as well as FEV1, FVC, dyspnea, and physical capacity. Pooled standardized mean differences (SMDs) or mean differences (MDs) and 95% CI were calculated using a random-effects model. RESULTS: Seven trials, all with a high risk of bias, were included. Compared to control group, RV significantly decreased (4 studies, n = 231; SMD -0.42 [95% CI -0.77 to -0.08], P = .02), dyspnea improved (n = 321, SMD -1.17 [95% CI -1.68 to -0.66], P < .001), and physical capacity increased (5 studies, n = 311; MD 30.1 [95% CI 19.2-41.0] m, P < .001) with PEP therapy. There was no significant difference between PEP therapy and the control group in TLC, FVC, or FEV1. Only one study reported changes in inspiratory capacity as well as FRC. CONCLUSIONS: In patients with COPD, the effect of PEP therapy on lung hyperinflation is unclear owing to the non-consistent change in lung hyperinflation outcomes, insufficient data, and lack of high-quality trials. Dyspnea and physical capacity might improve with PEP therapy.

Critical Care Management of Severe Asthma Exacerbations.

Severe asthma exacerbations, including near-fatal asthma (NFA), have high morbidity and mortality. Mechanical ventilation of patients with severe asthma is difficult due to the complex pathophysiology resulting from severe bronchospasm and dynamic hyperinflation. Life-threatening complications of traditional ventilation strategies in asthma exacerbations include the development of systemic hypotension from hyperinflation, air trapping, and pneumothoraces. Optimizing pharmacologic techniques and ventilation strategies is crucial to treat the underlying bronchospasm. Despite optimal pharmacologic management and mechanical ventilation, the mortality rate of patients with severe asthma in intensive care units is 8%, suggesting a need for advanced non-pharmacologic therapies, including extracorporeal life support (ECLS). This review focuses on the pathophysiology of acute asthma exacerbations, ventilation management including non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV), the pharmacologic management of acute asthma, and ECLS. This review also explores additional advanced non-pharmacologic techniques and monitoring tools for the safe and effective management of critically ill adult asthmatic patients.

Lung Ultrasound Assessment of Lung Hyperinflation in Patients with Stable COPD: An Effective Diagnostic Tool.

Purpose: To evaluate the degree of lung hyperinflation (LH) in patients with stable chronic obstructive pulmonary disease (COPD) by lung ultrasound score (LUS) and assess its value. Patients and Methods: We conducted a study of 149 patients with stable COPD and 100 healthy controls recruited by the Second Affiliated Hospital of Fujian Medical University. The pleural sliding displacement (PSD) was measured, the sliding of the pleura in different areas was observed, and LUS was calculated from both of them. The diaphragm excursion (DE), residual capacity (RV), total lung capacity (TLC), inspiratory capacity (IC) and functional residual capacity (FRC) were measured. We described the correlation between ultrasound indicators and pulmonary function indicators reflecting LH. Multiple linear regression analysis was used. The ROC curves of LUS and DE were drawn to evaluate their diagnostic efficacy, and De Long method was used for comparison. Results: (1) The LUS of patients with stable COPD were positively correlated with RV, TLC, RV/TLC and FRC and negatively correlated with IC and IC/TLC (r1=0.72, r2=0.41, r3=0.72, r4=0.70, r5=-0.56, r6=-0.65, P < 0.001). The correlation was stronger than that between DE at maximal deep inspiration and the corresponding pulmonary function indices (r1=-0.41, r2=-0.26, r3=-0.40, r4=-0.43, r5=0.30, r6=0.37, P < 0.001). (2) Multiple linear regression analysis showed that LUS were significantly correlated with IC/TLC and RV/TLC. (3) With IC/TLC<25% and RV/TLC>60% as the diagnostic criterion of severe LH, the areas under the ROC curves of LUS and DE at maximal deep inspiration for diagnosing severe LH were 0.914 and 0.385, 0.845 and 0.543, respectively (P < 0.001). Conclusion: The lung ultrasound score is an important parameter for evaluating LH. LUS is better than DE at maximal deep inspiration for diagnosing severe LH and is expected to become an effective auxiliary tool for evaluating LH.

GLI-12 Reference Values versus Fixed 0.7 Ratio for the Detection of Airflow Obstruction in the Presence of Lung Hyperinflation.

Introduction: Airflow obstruction (AO) is evidenced by reduced forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) with the threshold for diagnosis often being set at <0.7. However, currently the ATS/ERS standards for interpretation of lung function tests recommend the lower limit of normal (LLN), calculated by reference equations of the Global Lung Initiative from 2012 (GLI-12), as a threshold for AO diagnosis. The present study aims to investigate phenotypes, with focus on hyperinflation, which influence AO prevalence defined by FEV1/FVC < LLN when compared to the fixed 0.7 threshold. Methods: Data from 3,875 lung function tests (56.4% men, aged 18-95) including 3,824 body plethysmography recordings performed from July 2021 to June 2022 were analysed. The difference between both classifiers was quantified, before and after stratification by sex, age, and hyperinflation. Results: AO diagnosis was significantly less frequent with the LLN threshold (18.2%) compared to the fixed threshold (28.0%) (p < 0.001) with discordance rate of 10.5%. In the presence of mild or moderate hyperinflation, there was substantial agreement (Cohen's kappa: 0.616, 0.718) between the classifiers compared to near perfect agreement in the presence of severe hyperinflation (Cohen's kappa: 0.896). In addition, subgroup analysis after stratification for sex, age, and hyperinflation showed significant differences between both classifiers. Conclusion: The importance of using the LLN threshold instead of the fixed 0.7 threshold for the diagnosis of AO is highlighted. When using the fixed threshold AO, misdiagnosis was more common in the presence of mild to moderate hyperinflation.

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Ventilator hyperinflation associated with flow bias optimization in the bronchial hygiene of mechanically ventilated patients.

BACKGROUND: Ventilation configurations are of great clinical importance for adequate outcomes in mechanically ventilated patients, and they may even be used as specific physical therapy techniques. OBJECTIVES: To compare the effectiveness of lung hyperinflation through mechanical ventilation (HMV) with HMV plus flow bias optimization regarding respiratory mechanics, hemodynamics, and volume of secretion. METHODS: Patients mechanically ventilated > 24 h were included in this randomized crossover clinical trial. The following techniques were applied: HMV alone (control group) and HMV plus flow bias optimization (intervention group). RESULTS: The 20 included patients underwent both techniques, totaling 40 collections. A total of 52 % were women, the mean age was 60.8 (SD, 15.7) years, and the mean mechanical ventilation time was 4.3 (SD, 3.0) days. The main cause of mechanical ventilation was sepsis (44 %). Expiratory flow bias in optimized HMV was higher. than conventional HMV (p < 0.001). The volume of tracheal secretions collected was higher during optimized than conventional HMV. (p = 0.012). Significant differences in peak flow occurred at the beginning of the technique and a there was a significant decrease in respiratory system resistance immediately and 30 min after applying the technique in the intervention group. CONCLUSIONS: The volume of tracheal secretions collected was higher during optimized HMV, and, HMV with flow bias optimization resulted in lower respiratory system resistance and flow peaks and produced expiratory flow bias.

Sustained Clinical Benefits of Spiration Valve System in Patients with Severe Emphysema: 24-Month Follow-Up of EMPROVE.

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Effect of a Conical-PEP Mask on Exercise in Subjects With COPD.

BACKGROUND: Dynamic hyperinflation (DH) is a major pathophysiology of COPD that is directly related to dyspnea and exercise intolerance. Positive expiratory pressure (PEP) might reduce DH and dyspnea during exercise, but at present, there is insufficient evidence to conclude whether it is beneficial for DH, dyspnea, and exercise capacity in COPD. METHODS: A randomized crossover trial with concealed allocation was conducted in 37 moderate to very severe subjects with COPD (34 males, age 66.6 ± 7.4 y, FEV1% of predicted 56.3 ± 13.7). The experimental condition was conical-PEP breathing with a PEP of around 5 cm H2O during a spot marching exercise at a constant speed, inducing 71 ± 9% age-predicted maximum heart rate to symptom limit or 25 min. The control condition was usual breathing. Exercise endurance time and end-exercise symptoms were recorded. Inspiratory capacity (IC) was measured pre-exercise and immediately post exercise. Cardiopulmonary function and breathlessness were monitored throughout the test and after 10 min of recovery. RESULTS: There were no complications or adverse effects during exercise with a conical-PEP mask. Conical-PEP showed longer exercise times than control (median 11.0 [interquartile range 7.7-17.0] min vs 8 [6.0-11.5] min, respectively, P < .001). Most stopped exercising because of breathlessness and leg fatigue. At the end of exercise, IC and breathlessness showed non-significant differences between the conditions, but breathlessness was significantly lower in conical-PEP (median 4 [1.5-5.0] than control 5 [3-6] on Borg scale at isotime for control [8 min]). CONCLUSIONS: Breathing with a 5 cm H2O conical-PEP mask improved exercise time (median 27.1% [0.6-52.9]) in subjects with COPD. The improvement in exercise with the conical-PEP mask was associated with slower development of breathlessness, possibly due to delays in DH development.

Reproducibility and responsiveness of airway impedance measures derived from the forced oscillation technique across different operating lung volumes.

BACKGROUND: The forced oscillation technique (FOT) enables non-invasive measurement of respiratory system impedance. Limited data exists on how changes in operating lung volume (OLV) impact FOT-derived measures of airway resistance (Rrs) and reactance (Xrs). OBJECTIVES: This study examined the reproducibility and responsiveness of FOT-derived measures of Rrs and Xrs during simulated changes in OLV. METHODS: Participants simulated breathing at six OLVs: total lung capacity (TLC), ∼50% of inspiratory reserve volume (IRV50), ∼two-times tidal volume (VT2), tidal volume (VT), ∼50% of expiratory reserve volume (ERV50), and residual volume (RV), on a commercially available FOT device. Each simulated OLV manuever was performed in triplicate and in random order. Total Rrs and Xrs were recorded at 5, 11, and 19 Hz. RESULTS: Twelve healthy participants (2 female) completed the study (weight: 76.5 ± 13.6 kg, height: 178.6 ± 9.7 cm, body mass index: 23.9 ± 3.1 kg/m2). Reproducibility of Rrs and Xrs at VT, VT2 and IRV50 was good to excellent (Range: ICC: 0.89-0.98, 95% confidence interval (CI): 0.70-0.98), while reproducibility at TLC, RV, and ERV50 was poor to excellent (Range: ICC: 0.60-0.98, 95% CI: 0.36-0.97). Rrs and Xrs were not different between VT and VT2 at any frequency (P > .05). With lung hyperinflation from VT to TLC, Rrs and Xrs decreased at all three frequencies (e.g., At 5 Hz Rrs: mean difference (MD): - 0.89, 95%CI: - 0.03 to - 1.75, P = .04; Xrs: MD: - 0.56, 95%CI: - 0.25 to - 0.86, P < .01). With lung hypoinflated from VT to RV, Rrs increased, and Xrs decreased for all frequencies (e.g., MD at 5 Hz, Rrs: MD: 2.31, 95%CI: 0.94-3.67, P < .01; Xrs: MD: -2.53, 95%CI: -4.02 to -1.04, P < .01). CONCLUSION: FOT-derived measures of airway Rrs and Xrs are reproducible across a range of OLV's, and are responsive to hyper- and hypo-inflation of the lung. To further understand the impact of lung hyper- and hypo-inflation on FOT-derived airway impedance additional study is required in individuals with pathological variations in operating lung volume.