Physiological predictors of morbidity and mortality in COPD: the relative importance of reduced inspiratory capacity and inspiratory muscle strength.

Low resting inspiratory capacity (IC) and low maximal inspiratory pressure (MIP) have previously been linked to exertional dyspnea, exercise limitation, and poor survival in chronic obstructive pulmonary disease (COPD). The interaction and relative contributions of these two related variables to important clinical outcomes are unknown. The objective of the current study was to examine the interaction between resting IC and MIP (both % predicted), exertional dyspnea, exercise capacity, and long-term survival in patients with COPD. Two hundred and eighty-five patients with mild to advanced COPD completed standard lung function testing and a cycle cardiopulmonary exercise test. Multiple regression determined predictors of the exertional dyspnea-ventilation slope and peak oxygen uptake (V̇o2peak). Cox regression determined predictors of 10-year mortality. IC was associated with the dyspnea-ventilation slope (standardized ß = -0.42, P < 0.001), whereas MIP was excluded from the regression model (P = 0.918). IC and MIP were included in the final model to predict V̇o2peak. However, the standardized ß was greater for IC (0.43) than MIP (0.22). After adjusting for age, sex, body mass index, cardiovascular risk, airflow obstruction, and diffusing capacity, resting IC was independently associated with 10-year all-cause mortality (hazard ratio = 1.25, confidence interval5%-95% = 1.16-1.34, P < 0.001), whereas MIP was excluded from the final model (all P = 0.829). Low resting IC was consistently linked to heightened dyspnea intensity, low V̇o2peak, and worse survival in COPD even after accounting for airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important physiological biomarker closely linked to key clinical outcomes in COPD.NEW & NOTEWORTHY To our knowledge, this study is the first to show an independent association between low resting inspiratory capacity (IC) and, severe exertional dyspnea, exercise limitation, and increased mortality risk, after accounting for the severity of airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important independent physiological biomarker closely linked to key clinical outcomes in COPD.

A reappraisal of inspiratory capacity in chronic obstructive pulmonary disease: clinical correlates and role of long-acting muscarinic antagonists and long-acting ß2 agonists.

INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), static and dynamic hyperinflation, together with expiratory flow limitation and gas exchange abnormalities, is one of the major causes of dyspnea, decreased exercise performance and ventilatory failure. An increase in functional residual capacity (FRC) is accompanied by a decrease in inspiratory capacity (IC), which is a volume readily available, repeatable, and simple to measure with any spirometer. Changes in IC and FRC after bronchodilation, contrary to changes in FEV1, have been closely associated with improvements in dyspnea and exercise performance. We systematically searched PubMed and Embase databases for clinical trials that assessed the effects of dual bronchodilation on inspiratory capacity in patients with COPD. AREAS COVERED: Despite their pivotal role in COPD, IC and static volumes have rarely been considered as primary outcomes in randomized clinical trials assessing the efficacy of bronchodilators. Available studies on dual bronchodilation have shown a significant and persistent positive impact on IC focusing mainly on patients with moderate-to-severe COPD, whereas dynamic hyperinflation is also present at milder disease stages. EXPERT OPINION: This narrative review discusses the pathophysiological and clinical importance of measuring IC in patients with COPD and how IC can be modified by maximizing bronchodilation combining long-acting muscarinic antagonists and long-acting ß2 agonists.

The relationship between peak inspiratory flow and hand grip strength measurement in men with mild chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) decreases quality of life and muscular strength. Inspiratory flow is important for inhalants in the bronchi but is complicated to measure in routine practice. We hypothesized that hand grip strength (HGS) would correlate with inhalation rate in patients with mild COPD. METHODS: The COPD patients were recruited at the St. Marianna University School of Medicine, Yokohama Seibu Hospital, from 2015 to 2018. We measured peak inspiratory flow (PIF) through an In-Check flow meter attached with Diskus [PIF(D)] and Turbuhaler [PIF(T)] inhalers. The 6-min walking test (6MWT), and the fraction of exhaled nitric oxide (FENO), spirometry, HGS, or forced oscillation technique (FOT) parameters were measured. RESULTS: Forty-four subjects were enrolled. All were men, with a mean age (± SD) of 77.8 ± 9.36 years. Thirty-nine patients had mild COPD. PIF(D) was 110 (80, 140) L/min (median, interquartile range), PIF(T) was 80 (70, 90) L/min, and HGS was 28.7 (13.8, 43.6) kgf. PIF(D) and PIF(T) were significantly correlated (r = 0.443, p = 0.003). PIF(D) was significantly correlated with age (r = - 0.327, p = 0.030) and HGS (r = 0.326, p = 0.031). PIF(T) was significantly correlated with age (r = - 0.328, p = 0.030), FVC (r = 0.351, p = 0.019), 6MWT distance (r = 0.392, p = 0.011), and HGS (r = 0.328, p = 0.030). CONCLUSION: HGS might be more useful for predicting PIF than other parameters. Also, elderly COPD patients need to be taught inhaled methods carefully.

Bilevel Noninvasive Ventilation During Exercise Reduces Dynamic Hyperinflation and Improves Cycle Endurance Time in Severe to Very Severe COPD.

BACKGROUND: During exercise, dynamic hyperinflation (DH), measured by a reduction in inspiratory capacity (IC), increases exertional dyspnea and reduces functional capacity in many patients with severe COPD. Although noninvasive ventilation (NIV) during exercise can improve exercise duration, the effect on DH is unclear. RESEARCH QUESTIONS: In people with COPD, resting hyperinflation, and evidence of DH during exercise, does bilevel NIV during exercise reduce DH and increase endurance time compared with exercise with no NIV, and does NIV with an individually titrated expiratory positive airway pressure (T-EPAP) reduce DH and increase exercise endurance time more than NIV with standardized EPAP (S-EPAP) of 5 cm H2O? STUDY DESIGN AND METHODS: A randomized crossover trial in which investigators and participants were blinded between NIV interventions was performed. Participants (N = 19; FEV1 of 1.02 ± 0.24 L (39% ± 6% predicted) completed three constant work rate endurance cycle tests in random order-no NIV, NIV with S-EPAP, and NIV with T-EPAP-during exercise. Primary outcomes were isotime IC and exercise endurance time. Outcome measures from each intervention were compared at isotime and at end exercise by using a linear mixed-model analysis. RESULTS: Compared with no NIV, isotime IC and endurance time were greater with both NIV with S-EPAP (mean difference: 95% CI, 0.19 L [0.10-0.28]; 95% CI, 153 s [24-280], respectively) and T-EPAP (95% CI, 0.22 L [0.13-0.32]; 95% CI, 145 s [28-259], respectively). There was no difference between NIV with S-EPAP and NIV with T-EPAP. INTERPRETATION: In people with COPD and DH during exercise, NIV during exercise reduced DH and increased cycle endurance time. An S-EPAP of 5 cm H2O was adequate to obtain these benefits. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; No.: ACTRN12613000804785; URL: http://www.anzctr.org.au.

Comparison of Multiple Diagnostic Tests to Measure Dynamic Hyperinflation in Patients with Severe Emphysema Treated with Endobronchial Coils.

PURPOSE: For this study, we aimed to compare dynamic hyperinflation measured by cardiopulmonary exercise testing (CPET), a six-minute walking test (6-MWT), and a manually paced tachypnea test (MPT) in patients with severe emphysema who were treated with endobronchial coils. Additionally, we investigated whether dynamic hyperinflation changed after treatment with endobronchial coils. METHODS: Dynamic hyperinflation was measured with CPET, 6-MWT, and an MPT in 29 patients before and after coil treatment. RESULTS: There was no significant change in dynamic hyperinflation after treatment with coils. Comparison of CPET and MPT showed a strong association (rho 0.660, p < 0.001) and a moderate agreement (BA-plot, 202 ml difference in favor of MPT). There was only a moderate association of the 6-MWT with CPET (rho 0.361, p 0.024). CONCLUSION: MPT can be a suitable alternative to CPET to measure dynamic hyperinflation in severe emphysema but may overestimate dynamic hyperinflation possibly due to a higher breathing frequency.

Peak In- and Expiratory Flow Revisited: Reliability and Reference Values in Adults.

BACKGROUND: While peak in- and expiratory flow rates offer valuable information for diagnosis and monitoring in respiratory disease, these indices are usually considered too variable to be routinely used for quantification in clinical practice. OBJECTIVES: The aim of the study was to obtain reproducible measurements of maximal inspiratory flow rates and to construct reference equations for peak in- and expiratory flows (PIF and PEF). METHOD: With coaching for maximal effort, 187 healthy Caucasian subjects (20-80 years) performed at least 3 combined forced inspiratory and expiratory manoeuvres, until at least 2 peak inspiratory flow measurements were within 10% of each other. The effect on PIF preceded by a slow expiration instead of a forced expiration and PIF repeatability over 3 different days was also investigated in subgroups. Reference values and limits of normal for PIF, mid-inspiratory flow, and PEF were obtained according to the Lambda-Mu-Sigma statistical method. RESULTS: A valid PIF could be obtained within 3.3 ± 0.6(SD) attempts, resulting in an overall within-test PIF variability of 4.6 ± 3.2(SD)%. A slow instead of a forced expiration prior to forced inspiration resulted in a significant (p < 0.001) but small PIF increase (2.5% on average). Intraclass correlation coefficient for between-day PIF was 0.981 (95% CI: 0.960-0.992). Over the entire age range, inter-subject PIF variability was smaller than in previous reports, and PIF could be predicted based on its determinants gender, age, and height (r2 = 0.53). CONCLUSIONS: When adhering to similar criteria for the measurement of effort-dependent portions of inspiratory and expiratory flow-volume curves, performed according to current ATS/ERS standards, it is possible to obtain reproducible PIF and PEF values for use in routine clinical practice.

Effects of inspiratory muscle training on resting breathing pattern in patients with advanced lung disease.

AIM: The aim of this study was to evaluate the effects of interval high intensity inspiratory muscle training (IMT) on resting breathing pattern in patients with advanced lung disease. METHODS: IMT was performed daily and training load set at 50 % of the maximal inspiratory pressure. Participants were evaluated at pre-IMT, post 8 weeks of IMT and follow-up (3 months after the end of IMT). Breathing pattern (volume and time variables as well as percentages of contribution to tidal volume) was evaluated by Optoelectronic Plethysmography at rest. Friedman test was used to verify the differences between the three time-points (p < 0.05). RESULTS: Nineteen patients (54 ± 16 years old; 5 males) were evaluated at pre-IMT and post-IMT and fourteen were assessed at follow-up. There was no significant difference (p > 0.05) in any comparison for all evaluated breathing pattern variables at the three time-points. CONCLUSION: Resting breathing pattern was not significantly changed after 8 weeks of IMT in patients with advanced lung disease.

Normative Cardiopulmonary Exercise Test Responses at the Ventilatory Threshold in Canadian Adults 40 to 80 Years of Age.

BACKGROUND: Physiologic and symptom responses at the ventilatory threshold (Tvent) during incremental cardiopulmonary exercise testing (CPET) can provide important prognostic information. RESEARCH QUESTION: This study aimed to develop an updated normative reference set for physiologic and symptom responses at Tvent during cycle CPET (primary aim) and to evaluate previously recommended reference equations from a 1985 study for predicting Tvent responses (secondary aim). STUDY DESIGN AND METHODS: Participants were adults 40 to 80 years of age who were free of clinically relevant disease from the Canadian Cohort Obstructive Lung Disease. Rate of oxygen consumption (V˙O2) at Tvent was identified by two independent raters; physiologic and symptom responses corresponding to V˙O2 at Tvent were identified by linear interpolation. Reference ranges (5th-95th percentiles) for responses at Tvent were calculated according to participant sex and age for 29 and eight variables, respectively. Prediction models were developed for nine variables (oxygen pulse, V˙O2, rate of CO2 production, minute ventilation, tidal volume, inspiratory capacity, end-inspiratory lung volume [in liters and as percentage of total lung capacity], and end-expiratory lung volume) using quantile regression, estimating the 5th (lower limit of normal), 50th (normal), and 95th (upper limit of normal) percentiles based on readily available participant characteristics. The two one-sided test of equivalence for paired samples evaluated the measured and 1985-predicted V˙O2 at Tvent for equivalence. RESULTS: Reference ranges and equations were developed based on 96 participants (49% men) with a mean ± SD age of 63 ± 9 years. Mean V˙O2 at Tvent was 50% of measured V˙O2 peak; the normal range was 33% to 66%. The 1985 reference equations overpredicted V˙O2 at Tvent: mean difference in men, -0.17 L/min (95% CI, -0.25 to -0.09 L/min); mean difference in women, -0.19 L/min (95% CI, -0.27 to -0.12 L/min). INTERPRETATION: A contemporary reference set of CPET responses at Tvent from Canadian adults 40 to 80 years of age is presented that differs from the previously recommended and often used reference set from 1985. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00920348; URL: www.clinicaltrials.gov.

Dynamic hyperinflation induced by the 6-minute pegboard and ring test in hospitalized patients with exacerbated COPD.

BACKGROUND: The six-minute pegboard and ring test (6-PBRT) has been used to evaluate functional capacity of the upper limbs in stable chronic obstructive pulmonary disease (COPD) patients. To the best of our knowledge, no studies have evaluated dynamic hyperinflation (DH) during exercise with upper limbs in the hospital setting. The aim of this study was to evaluate physiological responses and DH induced by 6-PBRT in hospitalized patients with acute exacerbation of COPD (AECOPD). METHODS: A cross-sectional study was conducted in a tertiary hospital enrolling patients who were hospitalized due to AECOPD. All included participants underwent an evaluation of lung function and 6-PBRT when they reached minimum clinical criteria. Ventilatory and hemodynamics parameters were monitored during 6-PBRT and until 6 minutes of rest after the test. Symptoms of dyspnea and upper limb fatigue were also measured. RESULTS: Eighteen patients (71.3±5.1 years) with a mean FEV1 of 43.2±18.3% were included in the study (11 females). Prevalence of DH after 6-PBRT was 50% (considering the drop of 150 ml or 10% of inspiratory capacity, immediately after the end of the test). There was a significant increase in respiratory rate, minute volume, dyspnea, and upper limb fatigue after the end of 6-PBRT (p<0.05). Dyspnea recovered more precociously than the perception of fatigue, being reestablished within four minutes of rest. An increase in heart rate, systolic and diastolic blood pressures was also induced by 6-PBRT (p<0.05), requiring 6 minutes of recovery to return to baseline. No adverse events were observed during 6-PBRT. We concluded that 6-PBRT induces physiological changes during its execution, at safe levels, requiring a maximum of 6 minutes for recovery. Finally, the test proved to be safe and applicable for patients hospitalized due to AECOPD.

Double and multiple cycling in mechanical ventilation: Complex events with varying clinical effects / Doble y múltiples ciclados en ventilación mecánica: eventos complejos con diferentes significado clínico

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Effects of Chronic and Acute Pulmonary Hyperinflation on Phrenic Nerve Conduction in Patients with COPD.

In patients with moderate-to-severe Chronic Obstructive Pulmonary Disorder (COPD), pulmonary hyperinflation can occur at rest and increase during episodes of exacerbation. Among other mechanical constraints, changes in position and configuration of the diaphragm are also induced by increased end-expiratory lung volume. Both descent and flattening of diaphragm might damage the phrenic nerves by stretching their fibers. The study aimed to investigate the phrenic nerve conduction in COPD patients in stable conditions and during COPD exacerbation. In a group of 11 COPD patients without relevant comorbidities in stable conditions and subsequently in another group of 10 COPD patients during in-hospital COPD exacerbation and recovery, measurements of functional respiratory parameters and assessment of phrenic nerves motor conduction by bilateral electric stimulation were performed concurrently. Significant increase in phrenic nerves latency (p < 0.05), but similar amplitude of motor compound muscle action potential (cMAP) was observed in stable COPD patients vs. matched controls (p < 0.05). However, in COPD patients with resting pulmonary hyperinflation as reliably detected by substantial Inspiratory Capacity reduction (<80% pred.), the mean bilateral latency was longer vs. COPD patients without pulmonary hyperinflation (p < 0.02). During COPD exacerbation, in contrast with mean latency, the mean amplitude of phrenic nerves cMAP improved at discharge when compared with in-hospital admission (p < 0.05). In stable COPD patients the velocity of phrenic nerve conduction was impaired mostly in the presence of pulmonary hyperinflation, while during COPD exacerbation where dynamic pulmonary hyperinflation abruptly occurs, the reversible decrease of cMAP amplitude does suggest a temporary, acute axonal damage of phrenic nerves, potentially contributing to diaphragmatic dysfunction in these circumstances.

Estudio descriptivo sobre la influencia de la metodología en la medición de la fuerza inspiratoria máxima en nariz (SNIP) en población sana / Descriptive Study of the Effect of Methodology in the Measurement of Sniff Nasal Inspiratory Pressure (SNIP) in a Healthy Population

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The Repeatability of Inspiration Performance Through Different Inhalers in Patients with Chronic Obstructive Pulmonary Disease and Control Volunteers.

Background: Inhalation therapy is a cornerstone of treating patients with chronic obstructive pulmonary disease (COPD). Inhaler types and through-device inhalation parameters influence airway drug delivery. We aimed to measure the repeatability of inhalation performance through four different commercially available inhalers. Methods: We recruited control subjects (n = 22) and patients with stable COPD (S-COPD, n = 16) and during an acute exacerbation (AE-COPD, n = 15). Standard spirometry was followed by through-device inhalation maneuvers using Ellipta®, Evohaler®, Respimat®, and Genuair®. Through-device inspiratory vital capacity (IVCd) and peak inspiratory flow (PIFd), as well as inhalation time (tin) and breath hold time (tbh), were recorded and all measurements were repeated in a random manner. Results: There was no difference in forced expiratory volume in 1 second (FEV1) between patients (S-COPD: 39 ± 5 vs. AE-COPD: 32% ± 5% predicted, p > 0.05). In controls, the IVCd was significantly reduced by all four devices in comparison with the slight reduction seen in COPD patients. In all subjects, PIF was lowered when inhaling through the devices in order of decreasing magnitude in PIFd: Evohaler, Respimat, Ellipta, and Genuair. The Bland-Altman analysis showed a highly variable coefficient of repeatability for IVCd and PIFd through the different inhalers for all COPD patients. Based on the intermeasurement differences in patients, Respimat and Genuair showed the highest repeatability for IVCd, while Genuair and Ellipta performed superior with regard to PIFd. Conclusions: Our study is the first to compare repeatability of inhalation performances through different inhalers in COPD patients, showing great individual differences for parameters influencing lung deposition of inhaled medication from a given device. Our data provide new insight into the characterization of inhaler use by patients with COPD, and might aid the selection of the most appropriate devices to ensure the adequate and consistent delivery of inhaled drugs.

Incentive spirometry inspiratory capacity changes and predictors after open heart surgery: a 5-day prospective study.

INTRODUCTION: Incentive spirometry (IS) is commonly used for increasing postoperative IS inspiratory capacity (ISIC) after open heart surgery (OHS). However, little is known about the serial changes in ISIC and their predictive factors. OBJECTIVE: The aim of this study is to identify the postoperative ISIC changes relative to preoperative ISIC after OHS, and determine their predictors, including patient characteristics factors and IS performance parameters such as inspiration volumes (ISv) and frequencies (ISf). METHODS: This is a prospective study with blinding procedures involving 95 OHS patients, aged 52.8±11.5 years, whose ISIC was measured preoperatively (PreopISIC) until fifth postoperative day (POD), while ISv and ISf monitored with an electronic device from POD1-POD4. Regression models were used to identify predictors of POD1 ISIC, POD2- POD5 ISIC increments, and the odds of attaining PreopISIC by POD5. RESULTS: The ISIC reduced to 41% on POD1, increasing thereafter to 57%, 75%, 91%, and 106% from POD2-POD5 respectively. Higher PreopISIC (B=-0.01) significantly predicted lower POD1 ISIC, and, together with hyperlipedemia (B=11.52), which significantly predicted higher POD1 ISIC, explained 13% of variance. ISv at relative percentages of PreopISIC from POD1-POD4 (BPOD1=0.60, BPOD2=0.56, BPOD3=0.49, BPOD4=0.50) significantly predicted ISIC of subsequent PODs with variances at 23%, 24%, 17% and 25% respectively, but no association was elicited for ISf. IS performance findings facilitated proposal of a postoperative IS therapy target guideline. Higher ISv (B=0.05) also increased odds of patients recovering to preoperative ISIC on POD5 while higher PreopISIC (B=- 0.002), pain (B=-0.72) and being of Indian race (B=-1.73) decreased its odds. CONCLUSION: ISv appears integral to IS therapy efficacy after OHS and the proposed therapy targets need further verification through randomized controlled trials.

Prevalence and predictors of suboptimal peak inspiratory flow rate in COPD patients.

The aim of this study was to determine prevalence and possible clinical predictors of suboptimal peak inspiratory flow rate (PIFR) with different dry powder inhalers. PIFR was measured across all resistance ranges of In-Check Dial® in 180 chronic obstructive pulmonary disease (COPD) subjects before hospital discharge. COPD subjects were defined as suboptimal if measured PIFR was suboptimal with any resistance representative of specific inhalers (R1-R5). Demographics and clinical data were collected, including COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) scores, Global Initiative for Obstructive Lung Disease (GOLD) stage spirometry by Spirodoc® and peak flow meter measurements with portable peak inspiratory and expiratory flow meters. All were correlated with In-Check Dial PIFRs. Suboptimal PIFR was 44.44% prevalent in COPD subjects. 55% of the suboptimal cohort was female which represent 57.14% of the total female population in the study. The distribution of suboptimal PIFR included 43.75% with R1, 67.5% with R2, 100% with R3, 13.75% with R4, and 21.25% with R5. In the suboptimal cohort, CAT score was significantly higher and spirometry demonstrated significantly lower lung function results compared to the optimal cohort (p < 0.05). The only parameter to show strong and moderate correlation with In-Check Dial PIFRs was PIFR measured by peak flow meter (p < 0.001). Suboptimal PIFR is common among COPD subjects at hospital discharge. Female gender and peak flow meter PIFR was the only predictor of suboptimal PIFR. Inhaler therapy for COPD patients must be personalized based on simple routine measurement of In-Check Dial PIFRs or peak flow meter PIFR to optimize clinical benefits .

The role of inspiratory flow in selection and use of inhaled therapy for patients with chronic obstructive pulmonary disease.

Inhalation therapy is the mainstay of chronic obstructive pulmonary disease management, and inhaler selection can have a profound impact on drug delivery and medication adherence, as well as on treatment outcomes. Although multiple delivery systems, such as pressurized metered-dose inhalers, dry powder inhalers, slow-mist inhalers, and nebulizers, are available, clinical benefits achieved by patients rely on effective delivery of the inhaled medication to the airways. Among several factors influencing drug deposition, inspiratory flow is one of the most important. Inspiratory flow impacts drug delivery and subsequent clinical efficacy, making it necessary to adequately train patients to ensure correct inhaler use. Peak inspiratory flow is the maximal airflow generated during a forced inspiratory maneuver. Health care professionals need to select the appropriate delivery system after carefully considering patient characteristics, including lung function, optimal inspiratory flow, manual dexterity, and cognitive function. Herein, the role of inspiratory flow in the selection and use of inhaled therapy in patients with COPD is reviewed.

5-Year Survival after Endobronchial Coil Implantation: Secondary Analysis of the First Randomised Controlled Trial, RESET.

BACKGROUND: Lung volume reduction surgery is a proven treatment for emphysematous patients with hyperinflation, but the precarious health of candidates has prompted development of less invasive approaches. Bronchoscopic implanted endobronchial coils, shape-memory nitinol filaments, shrink emphysematous lung tissue to restore elastic recoil and to tether airways to maintain patency. Studies have demonstrated an acceptable safety profile and improvements in lung function, exercise capacity, and quality of life out to 3 years. Volume reduction is key. However, data for longer-term survival are limited. OBJECTIVE: The aim of this study was to establish the 5-year overall and transplant-free survivals of subjects whose procedure in the first randomized controlled trial, RESET, achieved clinically meaningful reduction in residual volume (RV). METHODS: Patients and their primary care doctors were contacted to confirm vital status and history of additional interventions. Death certificates were acquired via the General Registry Office. Survival time was calculated for responders achieving a reduction of ≥10% in RV compared to non-responders. RESULTS: 39 patients completed the planned bilateral sequential treatments. Six patients received unilateral implants. At 5 years, 22 patients had died. The overall survivals at 1, 2, 3, 4 and 5 years were 88.9, 88.9, 77.8, 64.4 and 50.6%, respectively. Two patients underwent lung transplantation at 52 and 59 months and were alive at 5 years. The transplant-free (TF) survivals at 1, 2, 3, 4 and 5 years were 88.9, 88.9, 77.8, 64.4 and 46.7%, respectively. Volume reduction responders (n = 18) at 3 months had a 5-year TF survival of 66.7% compared to 36.4% for non-responders (n = 22; p = 0.07). Higher baseline inspiratory capacity (HR 0.13, 95% CI 0.02-0.73; p = 0.02) and partial pressure of oxygen (pO2) (HR 0.57, 95% CI 0.38-0.86; p < 0.01) values were predictive of survival for the entire cohort and were not influenced by age. CONCLUSIONS: Endobronchial coil implantation appears to confer a 5-year survival advantage for those who achieved a 10% reduction in RV at 3 months. Ongoing trials are designed to clarify the mechanisms of action of coils and to refine patient selection.