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 This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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.

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.

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.

From pressure to tension: a model of damaging inflation stress.

Although the stretch that generates ventilator-induced lung injury (VILI) occurs within the peripheral tissue that encloses the alveolar space, airway pressures and volumes monitor the gas within the interior core of the lung unit, not its cellular enclosure. Measured pressures (plateau pressure, positive end-expiratory pressure, and driving pressure) and tidal volumes paint a highly relevant but incomplete picture of forces that act on the lung tissues themselves. Convenient and clinically useful measures of the airspace, such as pressure and volume, neglect the partitioning of tidal elastic energy into the increments of tension and surface area that constitute actual stress and strain at the alveolar margins. More sharply focused determinants of VILI require estimates of absolute alveolar dimension and morphology and the lung's unstressed volume at rest. We present a highly simplified but informative mathematical model that translates the radial energy of pressure and volume of the airspace into its surface energy components. In doing so it elaborates conceptual relationships that highlight the forces tending to cause end-tidal hyperinflation of aerated units within the 'baby lung' of acute respiratory distress syndrome (ARDS).

Impact of bronchoscopic lung volume reduction with endobronchial valves on dynamic hyperinflation: Results from the PIERCE study.

BACKGROUND AND OBJECTIVE: Dynamic hyperinflation (DH) is a major marker of exertional dyspnoea in severe emphysema. We hypothesized that bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBVs) decreases DH. METHODS: In this prospective bi-centre study from both Toulouse and Limoges Hospitals, we assessed DH during an incremental cycle ergometry before and 3 months after EBVs treatment. The primary objective was to observe the change in inspiratory capacity (IC) at isotime. Target lobe volume reduction (TLVR) and changes in residual volume (RV), forced expiratory volume in one-second (FEV1 ), mMRC, 6 minutes walking distance (6MWD), BODE and other dynamic measures like tele-expiratory volume (EELV) were also analysed. RESULTS: Thirty-nine patients were included, of whom thirty-eight presented DH. IC and EELV at isotime significantly improved (+214 mL, p = 0.004; -713 mL, p Ë‚ 0.001, respectively). Mean changes were +177 mL for FEV1 (+19%, p < 0.001), -600 mL for RV (p < 0.0001), +33 m for 6MWD (p < 0.0001), respectively. Patients who responded on RV (>430 mL decrease) and FEV1 (>12% gain) had better improvements compared to non-responders (+368 mL vs. +2 mL; +398 mL vs. -40 mL IC isotime, respectively). On the opposite, in patients who responded on DH (>200 mL IC isotime increase), changes in TLV (-1216 mL vs. -576 mL), FEV1 (+261 mL vs. +101 mL), FVC (+496 mL vs. +128 mL) and RV (-805 mL vs. -418 mL) were greater compared to non-responders. CONCLUSIONS: DH decreases after EBVs treatment, and this improvement is correlated with static changes.

The cumulative effect of methacholine on large and small airways when deep inspirations are avoided.

BACKGROUND AND OBJECTIVE: The effect of serial incremental concentrations of methacholine is only slightly cumulative when assessed by spirometry. This limited cumulative effect may be attributed to the bronchodilator effect of deep inspirations that are required between concentrations to measure lung function. Using oscillometry, the response to methacholine can be measured without deep inspirations. Conveniently, oscillometry can also dissociate the contribution of large versus small airways. Herein, oscillometry was used to assess the cumulative effect of methacholine in the absence of deep inspirations on large and small airways. METHODS: Healthy and asthmatic volunteers underwent a multiple-concentration methacholine challenge on visit 1 and a single-concentration challenge on visit 2 using the highest concentration of visit 1. The maximal response was compared between visits to assess the cumulative effect of methacholine. The lung volume was also measured after the final concentration to assess hyperinflation. RESULTS: In both healthy and asthmatic subjects, increases in resistance at 19 Hz (Rrs19 ), reflecting large airway narrowing, did not differ between the multiple- and the single-concentration challenge. However, increases in resistance at 5 Hz (Rrs5 ) minus Rrs19 , reflecting small airway narrowing, were 117 and 270% greater in the multiple- than the single-concentration challenge in healthy (p = 0.006) and asthmatic (p < 0.0001) subjects, respectively. Hyperinflation occurred with both challenges and was greater in the multiple- than the single-concentration challenge in both groups. CONCLUSION: Without deep inspirations, the effect of methacholine is cumulative on small airways but not on large airways. Lung hyperinflation and derecruitment may partially explain these different responses.

A Prototype Implantable Artificial Bronchus Reduces Lung Hyperinflation in Recently Deceased Patients with Emphysema.

BACKGROUND: Several minimally invasive treatments have been offered to patients with severe emphysema over the last two decades. Currently, endobronchial valves (EBVs) are the only approved therapeutic option, but this method has drawbacks: only a few can undergo this therapy and the incidence of pneumothorax remains high. A minimally invasive technique, appropriate for a broader patient population and posing fewer risks, would represent a desirable alternative to improve lung function in these patients. OBJECTIVE: The objective of this study was to demonstrate whether a new prototype implantable artificial bronchus (IAB) releases trapped air from the lungs of recently deceased patients with emphysema. METHOD: Seven recently deceased patients with emphysema were mechanically ventilated and the respiratory rate increased from 12 bpm (resting) to 30 bpm (exercise), inducing air trapping and dynamic hyperinflation. This protocol was performed twice, before and after IAB placement. Ventilation parameters and the fraction of inspired oxygen were similar in all patients. Respiratory system plateau pressure (Pplat,rs) and intrinsic positive end-expiratory pressure (iPEEP) were measured. RESULTS: IAB implantation significantly reduced Pplat,rs (p = 0.017) in 6 of 7 deceased patients with emphysema and iPEEP (p = 0.03) in 5 of 7 patients. CONCLUSIONS: Placement of one or two IABs in segmental bronchi (up to 15th generation) proved to be feasible and improved lung function. These findings should provide a basis for subsequent clinical studies to assess the safety and efficacy of IAB in patients with emphysema, as well as identify short- and long-term effects of this innovative procedure.

Reduction of Lung Hyperinflation Improves Cardiac Preload, Contractility, and Output in Emphysema: A Clinical Trial in Patients Who Received Endobronchial Valves.

Rationale: Pulmonary hyperinflation in patients with chronic obstructive pulmonary disease has been related to smaller cardiac chamber sizes and impaired cardiac function. Currently, bronchoscopic lung volume reduction (BLVR) with endobronchial valves is a treatment option to reduce pulmonary hyperinflation in patients with severe emphysema. Objectives: We hypothesized that reduction of hyperinflation would improve cardiac preload in this patient group. In addition, we investigated whether the treatment would result in elevated pulmonary artery pressures because of pulmonary vascular bed reduction. Methods: We included patients with emphysema and severe hyperinflation (defined by a baseline residual volume >175% of predicted) who were eligible for BLVR with endobronchial valves. Cardiac magnetic resonance imaging was obtained one day before treatment and at 8-week follow-up. Primary endpoint was cardiac preload, as measured by the right ventricle end-diastolic volume index. As secondary endpoints, we measured indexed end-diastolic and end-systolic volumes of the right ventricle, left atrium, and left ventricle; pulmonary artery pressures; cardiac output; ejection fraction; and strain. Measurements and Main Results: Twenty-four patients were included. At 8-week follow-up, right ventricle end-diastolic volume index was significantly improved (+7.9 ml/m2; SD, 10.0; P = 0.001). In addition to increased stroke volumes, we found significantly higher ejection fractions and strain measurements. Although cardiac output was significantly increased (+0.9 L/min; SD, 1.5; P = 0.007), there were no changes in pulmonary artery pressures. Conclusions: We found that reduction of hyperinflation using BLVR with endobronchial valves significantly improved cardiac preload, myocardial contractility, and cardiac output, without changes in pulmonary artery pressures. Clinical trial registered with www.clinicaltrials.gov (NCT03474471).

Benefits and risks of ventilator hyperinflation in mechanically ventilated intensive care patients: A systematic review and meta-analysis.

OBJECTIVES: Patients requiring mechanical ventilation in the intensive care unit (ICU) have diminished respiratory defences and are at high risk of respiratory compromise, leading to an increased risk of pulmonary infection and prolonged ventilation. Ventilator hyperinflation (VHI) is an airway clearance technique used by physiotherapists and is suggested to improve respiratory mechanics. The objective of this study was to review the evidence for the benefits and risks of VHI in intubated and mechanically ventilated patients in the ICU. REVIEW METHOD USED: We conducted a systematic review. DATA SOURCES: We searched PubMed, Embase, CINAHL, CENTRAL, and Scopus from inception to 31st May 2022 for all randomised control trials evaluating VHI in intubated and mechanically ventilated adults in the ICU. REVIEW METHODS: Two authors independently performed study selection and data extraction. Individual study risk of bias was assessed using the Physiotherapy Evidence Database scale, and certainty in outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework. RESULTS: We included 10 studies enrolling 394 patients. Compared to standard care, VHI had significant effects on sputum clearance (Standardise mean difference: 0.36, 95% confidence interval [CI]: 0.12 to 0.61; very low certainty), static pulmonary compliance (mean difference [MD]: 4.77, 95% CI: 2.40 to 7.14; low certainty), dynamic pulmonary compliance (MD: 1.59, 95% CI: 0.82 to 2.36; low certainty) and oxygenation (MD: 0.28, 95% CI: 0.01 to 0.55; low certainty). No significant adverse events or immediate side effects relating to VHI were reported. There is a paucity of data available on the effects of VHI on clinical outcomes including mechanical ventilation duration, ICU length of stay, and mortality. CONCLUSIONS: Our findings suggest VHI has potential short-term respiratory benefits including increased secretion clearance, pulmonary compliance, and oxygenation, with no immediate adverse effects in intubated and mechanically ventilated ICU patients. However, there remains limited data on the longer term influence of VHI on clinical outcomes, and further research to inform clinical practice is needed. REGISTRATION: This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022341421).

Association of air pollution exposure with exercise-induced oxygen desaturation in COPD.

BACKGROUND: There is a link between exposure to air pollution and the increased prevalence of chronic obstructive pulmonary disease (COPD) and declining pulmonary function, but the association with O2 desaturation during exercise in COPD patients with emphysema is unclear. Our aims were to estimate the prevalence of O2 desaturation during exercise in patients with COPD, and determine the association of exposure to air pollution with exercise-induced desaturation (EID), the degree of emphysema, and dynamic hyperinflation (DH). METHODS: We assessed the effects of 10-year prior to the HRCT assessment and 7 days prior to the six-minute walking test exposure to particulate matter with an aerodynamic diameter of < 10 µm (PM10) or of < 2.5 µM (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in patients with emphysema in this retrospective cohort study. EID was defined as a nadir standard pulse oximetry (SpO2) level of < 90% or a delta (△)SpO2 level of ≥ 4%. Ambient air pollutant (PM2.5, PM10, O3, and NO2) data were obtained from Taiwan Environmental Protection Administration (EPA) air-monitoring stations, usually within 10 km to each participant's home address. RESULTS: We recruited 141 subjects with emphysema. 41.1% of patients with emphysema exhibited EID, and patients with EID had more dyspnea, worse lung function, more severe emphysema, more frequent acute exacerbations, managed a shorter walking distance, had DH, and greater long-term exposure to air pollution than those without EID. We observed that levels of 10-year concentrations of PM10, PM2.5, and NO2 were significantly associated with EID, PM10 and PM2.5 were associated with the severity of emphysema, and associated with DH in patients with emphysema. In contrast, short-term exposure did not have any effect on patients. CONCLUSION: Long-term exposure to ambient PM10, PM2.5 and NO2, but not O3, was associated with EID.

Sex differences in the ventilatory responses to exercise in mild to moderate obesity.

NEW FINDINGS: What is the central question of the study? What are the sex differences in ventilatory responses during exercise in adults with obesity? What is the main finding and its importance? Tidal volume and expiratory flows are lower in females when compared with males at higher levels of ventilation despite small increases in end-expiratory lung volumes. Since dyspnoea on exertion is a frequent complaint, particularly in females with obesity, careful attention should be paid to unpleasant respiratory symptoms and mechanical ventilatory constraints while prescribing exercise. ABSTRACT: Obesity is associated with altered ventilatory responses, which may be exacerbated in females due to the functional consequences of sex-related morphological differences in the respiratory system. This study examined sex differences in ventilatory responses during exercise in adults with obesity. Healthy adults with obesity (n = 73; 48 females) underwent pulmonary function testing, underwater weighing, magnetic resonance imaging (MRI), a graded exercise test to exhaustion, and two constant work rate exercise tests; one at a fixed work rate (60 W for females and 105 W for males) and one at a relative intensity (50% of peak oxygen uptake, V ̇ O 2 peak ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ ). Metabolic, respiratory and perceptual responses were assessed during exercise. Compared with males, females used a smaller proportion of their ventilatory capacity at peak exercise (69.13 ± 14.49 vs. 77.41 ± 17.06% maximum voluntary ventilation, P = 0.0374). Females also utilized a smaller proportion of their forced vital capacity (FVC) at peak exercise (tidal volume: 48.51 ± 9.29 vs. 54.12 ± 10.43%FVC, P = 0.0218). End-expiratory lung volumes were 2-4% higher in females compared with males during exercise (P < 0.05), while end-inspiratory lung volumes were similar. Since the males were initiating inspiration from a lower lung volume, they experienced greater expiratory flow limitation during exercise. Ratings of perceived breathlessness during exercise were similar between females and males at comparable levels of ventilation. In summary, sex differences in the manifestations of obesity-related mechanical ventilatory constraints were observed. Since dyspnoea on exertion is a common complaint in patients with obesity, particularly in females, exercise prescriptions should be tailored with the goal of minimizing unpleasant respiratory sensations.

Small Airways: Not Just Air Ducts - Pathophysiological Aspects and Clinical Implications.

The airways smaller than 2 mm diameter are named small airways. They are essential for the transport and exchange of oxygen and carbon dioxide and at the same time play a relevant role in pulmonary mechanics, contributing to the subdivision of lung volumes. Measurement of small airway function is, therefore, crucial in patients with respiratory disease. This overview focuses on the physiological aspects of the small airways, considered as air ducts as well as determinants of pulmonary mechanics, the most common tools for evaluating their function and treatment implications.

Effects of Pulmonary Rehabilitation Including Inspiratory Muscle Training in Patients with Chronic Obstructive Pulmonary Disease after Stratification by the Degree of Static Hyperinflation.

BACKGROUND: Inspiratory muscle training (IMT) improves inspiratory muscle strength, exercise capacity and health status in patients with chronic obstructive pulmonary disease (COPD). However, there is no additional effect on top of comprehensive pulmonary rehabilitation (PR). It is unclear whether patients with different baseline degrees of static hyperinflation respond differentially to IMT as part of a PR program. Therefore, the aim was to study the effects of IMT as an add-on on PR after stratification for baseline degrees of static hyperinflation. METHODS: In this single center retrospective study data were extracted between June 2013 and October 2020 of COPD patients who participated in a comprehensive PR program including IMT. IMT was performed twice daily, one session consisted of 3 series of 10 breaths and training intensity was set initially at a load of approximately 50% of patients' maximal static inspiratory mouth pressure (MIP). The primary outcome measure was MIP. Secondary outcomes were the distance achieved on the 6-min walk test (6MWD), endurance cycling exercise capacity at 75% of the peak work rate (CWRT) and disease-specific health status using the COPD assessment test. RESULTS: 754 patients with COPD were screened for eligibility and 328 were excluded because of repeated PR programs, missing data or baseline residual volume (RV) > 350%. In total, 426 COPD patients were categorized into RV categories 50-130% (n = 84), 131-165% (n = 86), 166-197% (n = 86), 198-234% (n = 85) and 235-349% (n = 85). In the whole sample, MIP, endurance exercise capacity and health status improved significantly. The change in 6MWD was higher in the lowest baseline degree of static hyperinflation [+ 39 (9-92) m] compared with the baseline highest degree of static hyperinflation [+ 11 (- 18-54) m] (p < 0.05). CONCLUSIONS: IMT as part of a PR program in patients with COPD with different baseline degrees improved MIP irrespective of the degree of static lung hyperinflation. Improvement in functional exercise capacity was significantly higher in the group with the lowest degree of static hyperinflation compared with the patients with the highest degree of static hyperinflation.

Evidence of ventilatory constraints during exercise in hypermobile Ehlers-Danlos syndrome.

PURPOSE: Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder with many different symptoms such as pain, fatigue, dysautonomia, or respiratory symptoms. Among the respiratory manifestations described, the most frequent are exertional dyspnea and breathing difficulties. Mechanical ventilatory constraints during exercise could participate in these respiratory manifestations. The objective of this study was to explore the response of pulmonary flow-volume loops to exercise in patients with hEDS and to look for dynamic hyperinflation and expiratory flow limitation during exercise. METHODS: For this purpose, breathing pattern and tidal exercise flow-volume loops were recorded at two workloads (30% and 80% of the peak power output) of a constant load exercise test. RESULTS: Twelve patients were included (11 women, mean age 41 ± 14 years). The results showed a decrease (p = 0.028) in the inspiratory capacity (from 3.12 ± 0.49 L to 2.97 ± 0.52 L), an increase (p = 0.025) in the end-expiratory lung volume (from 0.73 ± 0.68 L to 0.88 ± 0.66 L, i.e., from EELV comprising 17 ± 12% to 21 ± 12% of forced vital capacity) between the two workloads in favor of dynamic hyperinflation, and half of the patients had expiratory flow limitations. CONCLUSION: This exploratory study provides evidence for mechanical ventilatory constraints during exercise in patients with hEDS, which may induce discomfort during exercise and could contribute to the respiratory symptomatology. TRIAL REGISTRATION NUMBER: This study is part of a larger clinical trial (ID: NCT04680793, December 2020).

Chronic obstructive pulmonary disease and atrial fibrillation: an interdisciplinary perspective.

Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ∼25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening.

Tidal volume expandability affected by flow, dynamic hyperinflation, and quasi-fixed inspiratory time in patients with COPD and healthy individuals.

Exertional dyspnea (ED) and impaired exercise performance (EP) are mainly caused by dynamic hyperinflation (DH) in chronic obstructive pulmonary disease (COPD) patients by constraining tidal volume expansion at peak exercise (VTpeak). As VTpeak is the product of inspiratory time (TIpeak) and flow (VT/TIpeak), it was hypothesized that VTpeak and VTpeak/total lung capacity (VTpeak/TLC) may be affected by TIpeak and VT/TIpeak. Hence, the study investigated the (1) effect of TIpeak and VT/TIpeak on VTpeak expansion, (2) factors associated with TIpeak, expiratory time (TEpeak), VT/TIpeak, and VTpeak/TLC, and (3) relationships between VT/TIpeak and VTpeak/TLC with ED and EP in COPD patients and controls. The study enrolled 126 male stable COPD patients and 33 sex-matched controls. At peak exercise, TIpeak was similar in all subjects (COPD versus controls, mean ± SD: 0.78 ± 0.17 s versus 0.81 ± 0.20 s, p = NS), whereas the COPD group had lower VT/TIpeak (1.71 ± 0.49 L/s versus 2.58 ± 0.69 L/s, p < .0001) and thus the COPD group had smaller VTpeak (1.31 ± 0.34 L versus 2.01 ± 0.45 L,p < .0001) and VTpeak/TLC (0.22 ± 0.06 vs 0.33 ± 0.05, p < .0001). TIpeak, TEpeak, and VT/TIpeak were mainly affected by exercise effort, whereas VTpeak/TLC was not. TEpeak, VT/TIpeak, and VTpeak/TLC were inversely changed by impaired lung function. TIpeak was not affected by lung function. Dynamic hyperinflation did not occur in the controls, however, VTpeak/TLC was strongly inversely related to DH (r = -0.79) and moderately to strongly related to lung function, ED, and EP in the COPD group. There was a slightly stronger correlation between VTpeak/TLC with ED and EP than VT/TIpeak in the COPD group (|r| = 0.55-0.56 vs 0.38-0.43). In summary, TIpeak was similar in both groups and the key to understanding how flow affects lung expansion. However, the DH volume effect was more important than the flow effect on ED and EP in the COPD group.

Immediate effects of manual hyperinflation on cardiorespiratory function and sputum clearance in mechanically ventilated pediatric patients: A randomized crossover trial.

Background: In developing countries, lower respiratory tract infection is a major cause of death in children, with severely ill patients being admitted to the critical-care unit. While physical therapists commonly use the manual hyperinflation (MHI) technique for secretion mass clearance in critical-care patients, its efficacy has not been determined in pediatric patients. Objective: This study investigated the effects of MHI on secretion mass clearance and cardiorespiratory responses in pediatric patients undergoing mechanical ventilation. Methods: A total of 12 intubated and mechanically ventilated pediatric patients were included in this study. At the same time of the day, the patients received two randomly ordered physical therapy treatments (MHI with suction and suction alone) from a trained physical therapist, with a washout period of 4 h provided between interventions. Results: The MHI treatment increased the tidal volume [ V t ; 1.2 mL/kg (95% CI, 0.8-1.5)] and static lung compliance [ C stat ; 3.7 mL/cmH2O (95% CI, 2.6-4.8)] immediately post-intervention compared with the baseline ( p < 0 . 05 ). Moreover, the MHI with suction induced higher V t [1.4 mL/kg (95% CI, 0.8-2.1)] and C stat [3.4 mL/cmH2O (95% CI, 2.1-4.7)] compared with the suction-alone intervention. In addition, the secretion mass [0.7 g (95% CI, 0.6-0.8)] was greater in MHI with suction compared with suction alone ( p < 0 . 05 ). However, there was no difference in peak inspiratory pressure, mean airway pressure, respiratory rate, heart rate, blood pressure, mean arterial blood pressure or oxygen saturation ( p > 0 . 05 ) between interventions. Conclusions: MHI can improve V t , C stat and secretion mass without inducing adverse hemodynamic effects upon the pediatric patients requiring mechanical ventilation.

Contamination of single fluid-filled intragastric balloons with orogastric fluid is not associated with hyperinflation: an ex-vivo study and systematic review of literature.

BACKGROUND: Spontaneous hyperinflation is reported to the Food and Drug Administration as a complication of intragastric balloons. It is postulated that orogastric contamination of the intragastric balloon may cause this phenomenon. We sought to investigate the effects of intentional balloon contamination with gastric contents on intragastric balloon perimeter and contents, whether methylene blue plays a role in preventing spontaneous hyperinflation, and review the available literature on spontaneous hyperinflation. METHODS: Four pairs of balloons with different combinations of sterile saline, orogastric contaminants, and methylene blue were incubated in a 37 °C water bath for six months to simulate physiological conditions with serial measurements of balloon perimeter. Our findings were compared against a systematic review across multiple databases to summarize the available literature. RESULTS: Balloon mean perimeter decreased from 33.5 cm ± 0.53 cm to 28.5 cm ± 0.46 cm (p < 0.0001). No significant differences were seen with the methylene blue group. Only 11 cases were found reported in the literature. CONCLUSIONS: Despite contaminating intragastric balloons with gastric aspirates, hyperinflation did not occur, and other factors may be in play to account for this phenomenon, when observed. Rates of hyperinflation remain under-reported in the literature. Further controlled experiments are needed.

Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema.

BACKGROUND: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. OBJECTIVE: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. METHOD: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score at 6 months. RESULTS: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by -10.6 [-15.9 to -5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. CONCLUSION: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.