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Inspiratory Capacity (IC) is a variable closely linked to functionality and physical exercise, in Chile there are reference values for IC that may over or underestimate this condition in users. Thus, the objective of this research was to determine the local values of IC for the construction of reference equations. A total of 305 volunteers participated in the evaluations, of which 161 (53 %) were women and 144 (47 %) men, from March 2019 to February 2020. All complied with the requirements of the scientific ethics committee and signed the consent; the IC was evaluated on a body plethysmograph according to American Thoracic Society and the European Respiratory Society (ATS/ERS) recommendations. The highest IC values were found in the 18-25 age range with 3.24+0.36 L for women and 4.16+0.49 L for men, respectively. The IC had a critical inflection from the range of 46 to 55 years of age (women; p=0.026 and men; p=0.012), decreasing steadily. The measured IC showed differences with respect to the values of Lisboa et al. (2007) and Roca et al. (1998) (p<0.0001 and p<0.0001 in women and p=0.0028 and p=0.0107 in men). Predictive equations were obtained for both sexs, which showed significant differences with currently used values, thus, improving the diagnosis, control, and follow-up with reference values located will allow a more appropriate management in the Maule region, Chile. [ABSTRACT FROM AUTHOR]

Respiratory Muscle Training (RMT) has become an alternative approach to boost athletic performance by improving respiratory function and delaying inspiratory muscle fatigue. The objective of the present study is to synthesise recent works on the benefits of RMT regarding muscle strength, respiratory system function and exercise performance in athletes and healthy individuals. The reviewed studies suggest that RMT can significantly increase pulmonary function parameters; however, the impact of RMT on these parameters remains inconsistent across studies. Regarding exercise performance, RMT has been shown to improve endurance, as evidenced by increased time to exhaustion, VO2 max, Repeated Sprint Ability (RSA) and postural control in some studies. This author aimed to analyse the different studies on respiratory training with the aforementioned outcomes. A thorough search of studies were conducted using various databases. The review included studies published in English, which were peer-reviewed and focused on RMT interventions in sports players. The following keywords were used as search strategies: RMT, Inspiratory Muscle Training (IMT), pulmonary function, Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP), exercise performance, VO2 max and endurance training. All 10 studies were extracted based on their research design, including randomised controlled trials, pre-post experimental studies, randomised sham-controlled trials and randomised group factorial designs and were synthesised and analysed qualitatively. The activation of the metaboreflex mechanism and improved blood flow distribution to working muscles during exercise are proposed as potential underlying mechanisms for these performance benefits. However, the additive effects of RMT when combined with regular strength and endurance training remain debatable. The present analysis identified a suitable metric that could substantiate the evidence supporting the enhancement of athletic performance through RMT.

Abstract Background Dry powder inhalers (DPIs) rely on both internal resistance and patients’ inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity. Methods The accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland–Altman graphical analysis. Results PF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P

Background and Purpose: Diabetic polyneuropathy is a long‐standing microvascular complication of diabetes that affects the postural control and functional mobility of patients. There are other microvascular complications, including pulmonary complications that reduce lung function. Multifactorial Inspiratory Muscle Training (IMT) can act as a home‐based technique targeted to affect both these complications. This study aims to determine the effects of IMT on respiratory and functional parameters in diabetic polyneuropathy patients. Methods: This is a Pre‐Test Post‐Test Randomized Controlled Trial (NCT#04947163) with 62 diabetic polyneuropathy patients. Each was randomly assigned to the IMT or sham‐IMT group. Both the groups performed OTAGO exercises , with the sham‐IMT group performing IMT at 15% of baseline maximal inspiratory pressure (MIP), whereas IMT were trained at 50% of baseline MIP as an initial intensity, which was increased as per the tolerance of patients. Both groups performed training for 12 weeks. The study investigated diaphragmatic strength, pulmonary function, functional capacity through 6MWT, 30s sit to stand test and anterior trunk muscle endurance tested through sit up test as outcome variables. Data was analysed on SPSS v26 at the significance level of 0.0.5. Results: The IMT group significantly improved diaphragmatic strength, pulmonary function, 6MWT and anterior trunk muscle endurance when compared to the sham‐IMT group. Conclusion: The study concluded that home‐based IMT can improve pulmonary parameters including diaphragmatic strength and lung function as well as functional parameters including functional capacity in patients with diabetic polyneuropathy. The study was registered at ClinicalTrials.gov, NCT#04947163. [ABSTRACT FROM AUTHOR]

Background: Dry powder inhalers (DPIs) rely on both internal resistance and patients' inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity. Methods: The accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland–Altman graphical analysis. Results: PF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland–Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients. Conclusions: In-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits. [ABSTRACT FROM AUTHOR]

This cross-sectional study aimed to investigate the role of peak inspiratory flow rate (PIFR) in the management of inhalation therapy for patients with chronic obstructive pulmonary disease (COPD). Conducted in the Department of Pulmonary Medicine at a tertiary care institute from July 2021 to January 2022, this study included a total of 351 patients who were clinically diagnosed with stable COPD and currently receiving inhaler therapy. Participants underwent comprehensive assessments that included demographic data collection, the use of the ABCD assessment tool to evaluate disease severity, the COPD Assessment Test (CAT) for quality of life measurement, and assessments for adherence to inhaler therapy and inhaler technique proficiency. The primary focus was on determining the prevalence of suboptimal PIFR and identifying associated demographic and clinical factors. The results indicated that 45% of the patients exhibited suboptimal PIFR, which is critical for effective medication delivery in COPD management. Analysis revealed several significant predictors of suboptimal PIFR: female gender, lower CAT scores, the type of inhaler device used, and a Modified Medical Research Council grade of ≥2, which indicates increased levels of breathlessness. These findings underscore the importance of assessing PIFR in COPD patients to ensure effective drug delivery. The study suggests that personalized inhaler device prescriptions tailored to individual PIFR can enhance treatment efficacy and improve overall management outcomes for COPD patients. By addressing factors contributing to suboptimal PIFR, healthcare providers can optimize inhalation therapy and ultimately improve patient quality of life.

Background The use of compression garments in the postoperative period of abdominoplasty seems to be a consensus, but the incidents of complications arising from this have been described, related to an increase in intraabdominal pressure and reduction of the femoral vein blood flow that may facilitate thromboembolic events. There are no studies that have evaluated the isolated effect of postoperative compression garments on respiratory function. Objectives The purpose of this study was to evaluate the effect of compression garments on respiratory function after abdominoplasty. Methods Thirty-four female patients who underwent standard abdominoplasty were divided into 2 groups, the garment group (n = 18) and the no garment group (n = 16). Respiratory function assessment (with spirometry and manovacuometry) was performed in the preoperative and postoperative periods. Results Forced vital capacity assessment revealed a greater ventilatory restriction in the garment group. Forced expiratory volume in 1 second (FEV1) showed differences between the evaluation time points in the garment group; the intergroup comparisons showed that the no garment group had a lower FEV1. Slow vital capacity was evaluated with no significant differences found on both intergroup comparisons. The inspiratory capacity was reduced in the garment group, representing ventilatory restriction. Measurements of the maximum inspiratory pressure showed no significant differences between the groups. The maximum expiratory pressure showed significantly lower values on postoperative day 7 in the garment group. Conclusions The use of compression garments after abdominoplasty impairs ventilatory function. Not wearing this type of garment can improve ventilation, decreasing the risk of pulmonary complications. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]

BackgroundDespite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death).MethodsPatients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison.ResultsThe adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls.ConclusionsBreath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.

One of the most debilitating symptoms of chronic obstructive pulmonary disease (COPD) is breathlessness, which leads to avoidance of physical activities in daily living and hastens clinical deterioration. Treatment of patients with COPD with inhaled long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination therapy improves airflow limitation, reduces breathlessness compared with LAMA or LABA monotherapies, and improves health status and quality of life. A large clinical trial programme focusing on the effects of tiotropium/olodaterol combination therapy demonstrated that this LAMA/LABA combination improves lung function and reduces hyperinflation (assessed by serial inspiratory capacity measurements) compared with either tiotropium alone or placebo in patients with COPD. Tiotropium/olodaterol also increases exercise endurance capacity and improves patient perception of the intensity of breathlessness compared with placebo. In this narrative review, we focus on the relationship between improving symptoms during activity, the ability to remain active in daily life and how this may impact quality of life. We consider the benefits of therapy optimisation by means of dual bronchodilation with tiotropium/olodaterol, and present new data from meta-analyses/pooled analyses showing that tiotropium/olodaterol improves inspiratory capacity compared with placebo and tiotropium and improves exercise endurance time compared with placebo after 6 weeks of treatment. We also discuss the importance of taking a holistic approach to improving physical activity, including pulmonary rehabilitation and exercise programmes in parallel with bronchodilator therapy and psychological programmes to support behaviour change.

Background: Cervical spinal cord injury (CSI) often leads to impaired respiratory function, affecting the overall well-being of patients. This study aimed to investigate the influence of rib cage motion on inspiratory capacity in CSI patients. Methods: We conducted a study with 11 CSI patients, utilising respiratory inductance plethysmography (RIP). We measured ventilatory volume by spirometry concurrently with RIP. Participants were instructed to perform maximal inspiratory efforts. Inspiratory capacity (IC) was calculated from spirometry waveforms. We converted the respiratory waveforms of the chest and abdomen into inspiratory volume measured by a spirometer. The inspiratory volume measured by the chest sensor was defined as VRIP-rib cage (VRIP-rc), and the inspiratory volume measured by the abdominal sensor was defined as VRIP-abdomen (VRIP-ab). Subsequently, the relationships of IC with VRIP-rc and VRIPab were assessed. Results: The mean IC was 1.828 ± 0.459 L, with the mean VRIP-rc at 1.343 ± 0.568 L and the mean VRIP-ab at 0.485 ± 0.427 L. A significant correlation was observed between IC and VRIP-rc (r = 0.67, p = 0.02), indicating that rib cage motion significantly influences IC in CSI patients. Conclusion: This study highlights the importance of rib cage motion in assessing inspiratory capacity in patients with CSI.

Incentive spirometry is one of the most common methods used for respiratory rehabilitation in the early period after cardiac surgery. Inspiratory capacity values, obtained by a patient using spirometer, are not reliably trusted.Objectives. To compare volumetric parameters measured with incentive spirometer and results obtained with bedside ultrasound-based spirometer to assure the feasibility of the use of incentive spirometry to assess the inspiratory capacity and effectiveness of postoperative respiratory rehabilitation.Materials and methods. The study included 50 patients after elective cardiac surgery. Pulmonary rehabilitation involved the use of various respiratory therapy methods. Spirography was performed before and after each session. Both approaches were used simultaneously to obtain the spirometry maximum inspiratory capacity (SMIC) with a bedside ultrasonic spirography and maximum inspiratory capacity (MIC) index using an incentive spirometer. Patient’s discomfort and adverse events during the procedures were recorded.Results. The absolute values of the MIC measured before and after each session by the two methods were dissimilar, however, the average increment values (6) did not show statistically significant differences. The correlation analysis revealed a strong positive statistically significant relationship between 6 SMIC and 6 MIC (R = 0.74 before the session, R = 0.79 after the session, R = 0.77 across the whole data set, P < 0.01), also consistent with the Bland–Altman analysis, evidencing that more than 95% of all values fell within ± 1.96 SD of the mean difference. The inspiratory spirometry method showed good diagnostic accuracy (sensitivity 87%, specificity 85%, area under the curve (AUC) 0.8 (95% CI: [0.76; 0.83]), P < 0.001). Refusals of procedure were more often documented with ultrasonic spirography.Conclusion. The increment in the inspiratory capacity index measured with incentive spirometer shows good agreement with ultrasonic spirography measurements. Therefore, incentive spirometry can be reliably used to assess the effectiveness of respiratory rehabilitation interventions in cardiac surgery patients during early postoperative period.

Home-based lung function measurements can be used to capture day-to-day variations in symptoms in patients with chronic obstructive pulmonary disease (COPD). Although dynamic hyperinflation (DH) is clinically relevant, existing home-based measurements do not include its assessment. DH can be measured through inspiratory capacity (IC) measurements before and after metronome-paced tachypnea test (MPT). The goal of this study is to determine the accuracy of unsupervised home-based IC and DH measurements in COPD. Sixteen COPD patients performed IC and DH measurements during 4 home visits. Visit 1 was considered a training session. During all visits supervised and unsupervised IC at rest (ICREST) and after MPT (ICMPT) were measured. DH was calculated as the difference between ICREST and ICMPT, and as a percentage of ICREST. Bland-Altman analyses and ANOVA tests were performed to determine the effect of supervision and repeated measures over time. The biases between supervised and unsupervised ICREST, ICMPT, ΔIC and ΔIC% were 0.007 L, 0.007 L, 0 mL and −0.09% in the last visit, respectively. Limits of agreement of ICREST and ΔIC% decreased from ±0.261 mL to ±0.201 mL, and from ±13.84% to ±10.81% between visit 1 and 4, respectively. No significant effect of supervision or over time was found. After a robust training and a learning phase, COPD patients are able to perform IC measurements in an accurate manner in both rest and after MPT. This yield accurate assessment of DH, in an unsupervised home-based setting.

BackgroundCOPD exacerbations occur more frequently with disease progression and are associated with worse prognosis and higher healthcare expenditure.PurposeTo utilize a networked system, optimized with statistical process control (SPC), for remote patient monitoring (RPM) and to identify potential predictors of COPD exacerbations.MethodsSeventeen subjects, mean (SD) age of 69.7 (7.2) years, with moderate to severe COPD received RPM. Over 2618 patient-days (7.17 patient-years) of monitoring, we obtained daily symptom scores, treatment adherence, self-reported activity levels, daily spirometry (SVC, FEV1, FVC, PEF), inspiratory capacity (IC), and oxygenation (SpO2). These data were used to identify predictors of exacerbations defined using Anthonisen and other criteria.ResultsAfter implementation of SPC, concordance analysis showed substantial agreement between FVC (decrease below the 7-day rolling average minus 1.645 SD) and self-reported healthcare utilization events (κ=0.747, P1.645 SD below the 7-day rolling average) and self-reported healthcare utilization events (κ=0.475, P

BACKGROUND: COPD is characterized by progressive and irreversible air flow limitations. Single-inhaler therapies (SITTs) incorporating an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β2-agonist have been shown to effectively alleviate symptoms and improve lung function. Fluticasone-furoate/umeclidinium/vilanterol (F/U/V) and budesonide/glyco-pyrronium/formoterol (B/G/F) are available as SITT in Japan. However, the clinical differences between these 2 combinations and the predictors of their proper use have not been established. This study aimed to identify the subject characteristics that could predict the effectiveness of inhaler therapy. METHODS: We assessed the pulmonary function test results of subjects with COPD before and one month after using F/U/V and B/G/F as SITT. Subjects with a difference of 100 mL or more in the FEV1 after treatment with pre-SITT were extracted and divided into the F/U/V effect and no-effect group and B/G/F effect and no-effect group to examine the factors associated with positive outcomes with each inhaler. RESULTS: F/U/V and B/G/F significantly improved the inspiratory capacity (IC), %IC, FVC, and %FEV1 when compared to pre-inter-vention values (P < .001, P = .001, P = .007, P = .009, respectively, for F/U/V; and P = .006, P = .008, P = .038, P = .005, respectively, for B/G/F). Factors associated with FEV1 improvement in F/U/V included lower %IC (odds ratio 0.97 [95% CI 0.94-0.99], P = .03) and a higher modified Medical Research Council (mMRC) dyspnea score (2.36 [1.27-4.70], P < .01). In addition, a higher %IC (1.03 [1.00-1.06], P = .02) and lower mMRC dyspnea score (0.55 [0.28-0.99], P = .041) were predictors for the effectiveness of B/G/F. CONCLUSIONS: Our results showed that SITT significantly improved the IC, %IC, FVC, and %FEV1 when compared to pre-inter-vention and that F/U/V was more effective in subjects with severe symptoms, whereas B/G/F was more effective in subjects with mild symptoms. [ABSTRACT FROM AUTHOR]

The article reports on the impact of an expiratory positive airway pressure (EPAP) device on tolerance of high-intensity exercise in subjects with chronic obstructive pulmonary disease (COPD). Topics discussed include dynamic lung hyperinflation, pulmonary function tests, and EPAP without inspiratory resistance.

Background and Study Aim. To assess the effects of Anulom Vilom Pranayama (AVP) or alternative nostril breathing and Rope Mallakhamb Training (RMT) on respiratory parameters among university females with athletic backgrounds. Material and Methods. A quasi experimental study was performed on thirty-six, university female students from the Department of Physical Education (T), Guru Nanak Dev University, Amritsar, Punjab, India. The subjects were divided in three groups. The groups were subjected to 4-weeks of intervention including: Group A (n1=12) subjected to AVP, Group B (n2=12) subjected to RMT, and Group C: (n3=12) no training or control. Respiratory parameters were measured twice, pre and post intervention using a wet spirometer. All measurements were performed three times and the average values were recorded for analysis. Results. 4-weeks of AVP resulted in positive increases for respiratory parameters measured including Tidal Volume (VT) 25.7%, Inspiratory Reserve Volume (IRV) 29.4%, Expiratory Reserve Volume (ERV) 27.1%, Vital Capacity (VC) 33.2%, and Inspiratory Capacity (IC) 31.6% compared to the control group. Also, 4-weeks of RMT had a positive impact on respiratory parameters including (VT) 19.8%, (IRV) 22%, (ERV) 19.4%, (VC) 32 % and (IC) 28.1% compared to the control group. Conclusions. Both AVP and RMT had a positive impact on respiratory parameters. Also, AVP training has a more positive impact on respiratory parameters than RMT and may also contribute to the enhancement of concentration-based performance and voluntary control of breathing among young females from athletic backgrounds. As a result, AVP training can be more beneficial for a competitive edge in order to improve the athletes' primary need for respiratory endurance.

ObjectiveBronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV1 (BDRFEV1) as a measure reflecting the change in flow and in FVC (BDRFVC) reflecting the change in volume.MethodsWe analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.ResultsA majority of COPD participants exhibited BDR (52.7%). BDRFEV1 occurred more often in earlier stages of COPD, while BDRFVC occurred more frequently in more advanced disease. When defined by increases in either FEV1 or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDRFVC was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDRFVC was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV1.ConclusionWith advanced airflow obstruction in COPD, BDRFVC is more prevalent in comparison to BDRFEV1 and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV1, BDRFVC itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.Clinical trials registrationClinicalTrials.gov: NCT01969344T4.

Strategies to minimize dynamic hyperinflation (DH) and dyspnea, such as slow chest compression (SCC), are relevant in people with chronic obstructive pulmonary disease (COPD). To analyze the acute effects of SCC after exercise on DH and dyspnea in people with COPD and to identify responders to the technique. This is a cross-over study with 40 patients. Two six-minute step tests (6MSTs) were performed followed by a one-minute application of SCC (6MSTSCC) or rest (6MSTCONTROL), at random. End-expiratory lung volume (EELV) and dyspnea were assessed. A difference ≥76 ml in ΔEELV between SCC and control characterized the responders. The performance in 6MSTSCC and 6MSTCONTROL were similar. There was a greater reduction in EELV after 6MSTSCC compared to 6MSTCONTROL (124 ± 193 ml vs. 174 ± 183 ml; p =.049), while there was no difference in change in dyspnea between the SCC and control groups. Twenty-one participants were SCC responders and had higher functional residual capacity [FRC: 5.36 ± 1.09 vs. 4.58 ± 0.94; p =.02; cutoff point: 4.56; sensitivity = 76%; specificity = 53%; AUC = 0.71 (95%CI: 0.54 to 0.87); p =.02]. SCC applied immediately after exercise reduced DH, but did not reduce dyspnea in people with COPD. The technique is beneficial only for some patients and FRC can help to identify them. [ABSTRACT FROM AUTHOR]

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 (...O2peak). Cox regression determined predictors of 10-year mortality. IC was associated with the dyspnea-ventilation slope (standardized β = -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 VO2peak. However, the standardized β 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 ...O2peak, 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. [ABSTRACT FROM AUTHOR]

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler. Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).295 and 291 patients were treated in MORACTO 1 and 2, respectively. Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p

This document reviews 1) the measurement properties of commonly used exercise tests in patients with chronic respiratory diseases and 2) published studies on their utilty and/or evaluation obtained from MEDLINE and Cochrane Library searches between 1990 and March 2015.Exercise tests are reliable and consistently responsive to rehabilitative and pharmacological interventions. Thresholds for clinically important changes in performance are available for several tests. In pulmonary arterial hypertension, the 6-min walk test (6MWT), peak oxygen uptake and ventilation/carbon dioxide output indices appear to be the variables most responsive to vasodilators. While bronchodilators do not always show clinically relevant effects in chronic obstructive pulmonary disease, high-intensity constant work-rate (endurance) tests (CWRET) are considerably more responsive than incremental exercise tests and 6MWTs. High-intensity CWRETs need to be standardised to reduce interindividual variability. Additional physiological information and responsiveness can be obtained from isotime measurements, particularly of inspiratory capacity and dyspnoea. Less evidence is available for the endurance shuttle walk test. Although the incremental shuttle walk test and 6MWT are reliable and less expensive than cardiopulmonary exercise testing, two repetitions are needed at baseline. All exercise tests are safe when recommended precautions are followed, with evidence suggesting that no test is safer than others.

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Silvia Uccelli,1 Laura Pini,1 Damiano Bottone,1 Piera Ranieri,2 Nicla Orzes,1 Claudio Tantucci1 1Respiratory Medicine Unit, Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy; 2Department of Internal Medicine and Rehabilitation, Istituto Clinico Sant’Anna, Brescia, ItalyCorrespondence: Laura Pini Email laura.pini@unibs.itRationale: Patients with chronic obstructive pulmonary disorder (COPD) complain of various COPD-related symptoms with different daily frequencies. During the night-time and at early morning, dyspnea is often reported and may predict an increased risk of COPD exacerbation and hospitalization and all-cause mortality. The aim of the study was to assess the underlying mechanisms of this symptom, seeking functional biomarkers of its occurrence.Methods: Stable COPD patients with moderate-to-severe airflow obstruction and without confounding comorbidities underwent extensive baseline function respiratory tests. Spirometry, maximal flow-volume curves, lung volumes, and lung diffusion capacity parameters were obtained. Inspiratory capacity was also measured both in seated and supine positions. Forced oscillation technique (FOT) and negative expiratory pressure (NEP) method were used to establish the presence of tidal expiratory flow limitation (EFL) during recumbency. Questionnaires for recording COPD-related symptoms were administered. Sleep-related disturbances reported by the patients were also registered.Results: Forty-two consecutive COPD patients aged 65± 9 completed the protocol. They were divided, according to the absence (NFL) or presence (FL) of supine EFL, in NFL group (n=17) and FL group (n=25). FL COPD patients had more severe airflow obstruction (FEV1= 46.4± 19.4 vs 65.1± 12.5% pred., p< 0.01) and they showed no increase of supine IC in contrast with NFL COPD patients (ΔIC= 0.080± 0.18 vs 0.390± 0.28 L, p< 0.01). Dyspnea either during night-time and at early morning was significantly more reported in FL COPD patients than in NFL COPD patients (p< 0.05) and in those with less than 10% increase in supine IC (p< 0.05).Conclusion: Supine EFL is frequently associated with both night-time and early morning dyspnea, suggesting that the development of recumbent dynamic pulmonary hyperinflation, heralded by the lack of increment of IC in supine position, is a pivotal mechanism of this symptom. No or trivial increase in supine IC may indicate the occurrence of dyspnea under these conditions.Keywords: COPD, expiratory flow limitation, pulmonary hyperinflation, dyspnea, nocturnal symptoms, symptoms in the early morning, inspiratory capacity

Home-based lung function measurements can be used to capture day-to-day variations in symptoms in patients with chronic obstructive pulmonary disease (COPD). Although dynamic hyperinflation (DH) is clinically relevant, existing home-based measurements do not include its assessment. DH can be measured through inspiratory capacity (IC) measurements before and after metronome-paced tachypnea test (MPT). The goal of this study is to determine the accuracy of unsupervised home-based IC and DH measurements in COPD. Sixteen COPD patients performed IC and DH measurements during 4 home visits. Visit 1 was considered a training session. During all visits supervised and unsupervised IC at rest (ICREST) and after MPT (ICMPT) were measured. DH was calculated as the difference between ICREST and ICMPT, and as a percentage of ICREST. Bland-Altman analyses and ANOVA tests were performed to determine the effect of supervision and repeated measures over time. The biases between supervised and unsupervised ICREST, ICMPT, ΔIC and ΔIC% were 0.007 L, 0.007 L, 0 mL and −0.09% in the last visit, respectively. Limits of agreement of ICREST and ΔIC% decreased from ±0.261 mL to ±0.201 mL, and from ±13.84% to ±10.81% between visit 1 and 4, respectively. No significant effect of supervision or over time was found. After a robust training and a learning phase, COPD patients are able to perform IC measurements in an accurate manner in both rest and after MPT. This yield accurate assessment of DH, in an unsupervised home-based setting. [ABSTRACT FROM AUTHOR]

BackgroundForced expiratory volume in 1 second (FEV1) grades severity of COPD and predicts survival. We hypothesize that the inspiratory capacity/total lung capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may have a significant association with survival in an emphysematous phenotype of COPD.ObjectivesTo access the association between IC/TLC and survival in an emphysematous phenotype of COPD.MethodsWe performed a retrospective analysis of a large pulmonary function (PF) database with 39,050 entries, from April 1978 to October 2009. Emphysematous COPD was defined as reduced FEV1/forced vital capacity (FVC), increased TLC, and reduced diffusing capacity of the lungs for carbon monoxide (DLCO; beyond 95% confidence intervals [CIs]). We evaluated the association between survival in emphysematous COPD patients and the IC/TLC ratio evaluated both as dichotomous (≤25% vs >25%) and continuous predictors. Five hundred and ninety-six patients had reported death dates.ResultsUnivariate analysis revealed that IC/TLC ≤25% was a significant predictor of death (hazard ratio [HR]: 2.39, P

A suboptimal peak inspiratory flow rate (PIFR) in dry-powder inhaler (DPI) users can lead to insufficient therapeutic effects in the treatment of chronic obstructive pulmonary disease (COPD). However, few data on the prevalence of and factors associated with suboptimal PIFR in Korean patients with COPD are available. We conducted a cross-sectional study of patients with COPD who had been using DPIs for more than three months. PIFR was measured using an In-Check DIAL G16 device. Suboptimal PIFR was defined as below the resistance-matched threshold. Multivariable logistic regression analysis was used to determine factors associated with suboptimal PIFR. Of 444 DPI users with COPD, the rate of suboptimal PIFR was 22.0 % (98/444). In a multivariable analysis, significant factors associated with suboptimal PIFR were age (adjusted odds ratio [aOR] = 1.06 by 1-year increase; 95 % confidence interval [CI] = 1.02–1.09), male sex (aOR = 0.28; 95 % CI = 0.11–0.73), body mass index (BMI) (aOR = 0.91 by 1 kg/m2 increase; 95 % CI = 0.85–0.99), post-bronchodilator forced vital capacity (FVC) %pred (aOR = 0.97 by 1%pred increase; 95 % CI = 0.95–0.99), and In-Check DIAL R2-type inhaler [medium-low resistance] use (aOR = 3.70 compared with R1-type inhalers [low resistance]; 95 % CI = 2.03–7.03). In Korea, more than one-fifth of DPI users with COPD had a suboptimal PIFR. The factors associated with suboptimal PIFR were age, female gender, low BMI, low FVC, and R2-type inhaler use. Therefore, clinicians should carefully evaluate the possibility of suboptimal PIFR when prescribing DPIs. [ABSTRACT FROM AUTHOR]

Igor Z Barjaktarevic,1 Russell G Buhr,1,2 Xiaoyan Wang,3 Scott Hu,1 David Couper,4 Wayne Anderson,4 Richard E Kanner,5 Robert Paine III,5 Surya P Bhatt,6 Nirav R Bhakta,7 Mehrdad Arjomandi,7 Robert J Kaner,8 Cheryl S Pirozzi,5 Jeffrey L Curtis,9,10 Wanda K O’Neal,4 Prescott G Woodruff,7 MeiLan K Han,9 Fernando J Martinez,8 Nadia Hansel,11 James Michael Wells,6 Victor E Ortega,12 Eric A Hoffman,13 Claire M Doerschuk,4 Victor Kim,14 Mark T Dransfield,6 M Bradley Drummond,4 Russell Bowler,15 Gerard Criner,14 Stephanie A Christenson,7 Bonnie Ronish,5 Stephen P Peters,12 Jerry A Krishnan,16 Donald P Tashkin,1 Christopher B Cooper1 On behalf of the NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS)1Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; 2Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA; 3Department of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, CA, USA; 4Department of Medicine, University of North Carolina, Chapel Hill, NC, USA; 5Department of Medicine, University of Utah, Salt Lake City, UT, USA; 6Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 7Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; 8Department of Medicine, Weill Cornell Weill Cornell Medical Center, New York, NY, USA; 9Department of Medicine, University of Michigan, Ann Arbor, MI, USA; 10Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; 11Department of Medicine, John Hopkins University, Baltimore, MD, USA; 12Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 13Department of Medicine, University of Iowa, Iowa City, IA, USA; 14Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; 15Department of Medicine, National Jewish Health Systems, Denver, CO, USA; 16Department of Medicine, University of Illinois at Chicago, Chicago, IL, USACorrespondence: Christopher B CooperDepartments of Medicine and Physiology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, 37-131 CHS, Los Angeles, CA 90095, USAEmail ccooper@mednet.ucla.eduObjective: Bronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV1 (BDRFEV1) as a measure reflecting the change in flow and in FVC (BDRFVC) reflecting the change in volume.Methods: We analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.Results: A majority of COPD participants exhibited BDR (52.7%). BDRFEV1 occurred more often in earlier stages of COPD, while BDRFVC occurred more frequently in more advanced disease. When defined by increases in either FEV1 or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDRFVC was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDRFVC was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV1.Conclusion: With advanced airflow obstruction in COPD, BDRFVC is more prevalent in comparison to BDRFEV1 and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV1, BDRFVC itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.Clinical trials registration: ClinicalTrials.gov: NCT01969344T4.Keywords: bronchodilator responsiveness, inspiratory capacity, FVC, FEV1, SPIROMICS

Study objective. To assess the association between intracardiac hemodynamics and airway obstruction with pulmonary hyperinflation in patients with chronic obstructive pulmonary disease.Materials and methods. Ninety-six patients with chronic obstructive pulmonary disease, aged 40 to 75 years, without concomitant cardiovascular disease, were examined and divided into 4 groups according to the severity of the disease. The patients underwent general clinical examination, spirometry, 24-hour pulse oximetry and echocardiography with assessment of linear and volumetric parameters, as well as diastolic function of left and right ventricles.Results. Linear and volumetric parameters of the left ventricle, LV myocardial mass and geometry in the examined patients with chronic obstructive pulmonary disease matched threshold values. The progression of the severity of chronic obstructive pulmonary disease was accompanied by decrease of the end-diastolic size of the left ventricle, ratio of peak early to late diastolic filling velocity for the left ventricle (E/A) without significant changes in the left ventricle isovolumetric relaxation time (IVRT). Moderate correlations of the inspiratory capacity with the end-diastolic size of the left ventricle (r=0.612; p=0.001) and the left ventricle E/A (r=0.464; p=0.001); forced expiratory volume in 1 second (FEV1) with the left ventricle E/A (r=0.600; p=0.011) were established. As a result of the logistic regression performed, the predictor value of the inspiratory capacity was confirmed (Wald χ2 — 5.795; р=0.024). Impairment of left ventricular diastolic function of grade I was revealed in 12 (31.6 %) patients in group 2, in 7 (24.1 %) patients in group 3, and in 9 (56.2 %) patients in group 4.Conclusion. Airway obstruction severity and pulmonary hyperinflation progression in patients with chronic obstructive pulmonary disease and without concomitant cardiovascular disease is associated with a decrease of left ventricular size and diastolic filling, contributes to the development of the left ventricular diastolic dysfunction, predominantly due to the decrease in filling velocity parameters.

Alejandra Ramírez-Venegas,1 Mónica Velázquez-Uncal,1 Adrián Aranda-Chávez,1 Nicolás Eduardo Guzmán-Bouilloud,1 María Eugenia Mayar-Maya,2 José Luis Pérez Lara-Albisua,1 Rafael de Jesus Hernández-Zenteno,3 Fernando Flores-Trujillo,3 Raúl H Sansores41Department of Tobacco Smoking and COPD Research, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosió Villegas”, Mexico City, Mexico; 2Department of Medical Attention, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosió Villegas”, Mexico City, Mexico; 3Obstructive Disease Ward, Pulmonary Obstructive Diseases Clinical Service, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico; 4Department of Respiratory Medicine, Medica Sur Clinic & Foundation, Mexico City, MexicoIntroduction: The efficacy of long-acting bronchodilators for COPD associated with biomass (BE-COPD) has not been properly evaluated.Objective: To determine the acute effect of indacaterol (IND) 150 μg q.d and tiotropium (TIO) 18 μg q.d. on lung hyperinflation, walking distance (WD) and dyspnea during the six-minute walking test (6MWT) in moderate BE-COPD at 30, 60 and 240 mins post-drug administration.Design: Randomized, controlled, open-level, crossover noninferiority clinical trial. Forty-two women with BE-COPD were randomly assigned to a bronchodilator sequence: IND–TIO or vice versa.Results: There were statistically significant changes over time in inspiratory capacity (IC) (p

Yong Suk Jo,1 Sung Kyoung Kim,2 Seoung Ju Park,3 Soo-Jung Um,4 Yong-Bum Park,5 Ki Suck Jung,6 Deog Kyeom Kim,7 Kwang Ha Yoo8 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Division of Pulmonology, St Vincent’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; 4Department of Internal Medicine, Division of Pulmonology, Dong-A University Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 6Department of Internal Medicine, Division of Pulmonary Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 7Department of Internal Medicine, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 8Department of Internal Medicine, Division of Pulmonary and Allergy Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: FEV1 is the gold standard for assessment of COPD. We compared efficacy of FEV1, inspiratory capacity (IC), and IC to total lung capacity (TLC) ratio in the evaluation of COPD and their association with exacerbation.Methods: We analyzed the association of dyspnea severity, quality of life status, and lung function with lung function measurements and exacerbation risk in 982 patients enrolled in the Korea COPD Subgroup Registry and Subtype Research study. Exacerbation and longitudinal lung function change were evaluated in 3 years’ follow-up.Results: The FEV1, IC, and IC to TLC ratio showed comparable negative correlations with dyspnea severity and quality of life status, and positive correlation with exercise capacity. In patients with >2 events/year, annual rate of change in FEV1 and IC tended to decline more rapidly in those with FEV1 50% (-14.46±19.40 mL/year vs 12.29±9.24 mL/year, P=0.213; -4.75±17.28 mL/year vs -78.05±34.16 mL/year, P=0.056 for FEV1 and IC, respectively), without significance.Conclusion: Longitudinal changes in IC and FEV1 were not significantly associated with exacerbation risk. Keywords: COPD, exacerbation, FEV1, inspiratory capacity

New Findings: What is the central question of this study?The study aimed to establish a novel model to study the chronic obstructive pulmonary disease (COPD)‐related cardiopulmonary effects of dynamic hyperinflation in healthy subjects.What is the main finding and its importance?A model of expiratory resistance breathing (ERB) was established in which dynamic hyperinflation was induced in healthy subjects, expressed both by lung volumes and intrathoracic pressures. ERB outperformed existing methods and represents an efficacious model to study cardiopulmonary mechanics of dynamic hyperinflation without potentially confounding factors as present in COPD. Dynamic hyperinflation (DH) determines symptoms and prognosis of chronic obstructive pulmonary disease (COPD). The induction of DH is used to study cardiopulmonary mechanics in healthy subjects without COPD‐related confounders like inflammation, hypoxic vasoconstriction and rarefication of pulmonary vasculature. Metronome‐paced tachypnoea (MPT) has proven effective in inducing DH in healthy subjects, but does not account for airflow limitation. We aimed to establish a novel model incorporating airflow limitation by combining tachypnoea with an expiratory airway stenosis. We investigated this expiratory resistance breathing (ERB) model in 14 healthy subjects using different stenosis diameters to assess a dose–response relationship. Via cross‐over design, we compared ERB to MPT in a random sequence. DH was quantified by inspiratory capacity (IC, litres) and intrinsic positive end‐expiratory pressure (PEEPi, cmH2O). ERB induced a stepwise decreasing IC (means (95% CI): tidal breathing: 3.66 (3.45–3.88), ERB 3 mm: 3.33 (1.75–4.91), 2 mm: 2.05 (0.76–3.34), 1.5 mm: 0.73 (0.12–1.58) litres) and increasing PEEPi (tidal breathing: 0.70 (0.50–0.80), ERB 3 mm: 11.1 (7.0–15.2), 2 mm: 22.3 (17.1–27.6), 1.5 mm: 33.4 (3.40–63) cmH2O). All three MPT patterns increased PEEPi, but to a far lesser extent than ERB. No adverse events during ERB were noted. In conclusion, ERB was proven to be a safe and efficacious model for the induction of DH and might be used for the investigation of cardiopulmonary interaction in healthy subjects. [ABSTRACT FROM AUTHOR]

Assessment of the ventilatory response to exercise is important in evaluating mechanisms of dyspnea and exercise intolerance in chronic cardiopulmonary diseases. The characteristic mechanical derangements that occur during exercise in chronic respiratory conditions have previously been determined in seminal studies using esophageal catheter pressure-derived measurements. In this brief review, we examine the emerging role and clinical utility of conventional assessment of dynamic respiratory mechanics during exercise testing. Thus, we provide a physiologic rationale for measuring operating lung volumes, breathing pattern, and flow–volume loops during exercise. We consider standardization of inspiratory capacity-derived measurements and their practical implementation in clinical laboratories. We examine the evidence that this iterative approach allows greater refinement in evaluation of ventilatory limitation during exercise than traditional assessments of breathing reserve. We appraise the available data on the reproducibility and responsiveness of this methodology. In particular, we review inspiratory capacity measurement and derived operating lung volumes during exercise. We demonstrate, using recent published data, how systematic evaluation of dynamic mechanical constraints, together with breathing pattern analysis, can provide valuable insights into the nature and extent of physiological impairment contributing to exercise intolerance in individuals with common chronic obstructive and restrictive respiratory disorders.

Wilfried De Backer,1 Jan De Backer,2 Wim Vos,3 Ilse Verlinden,3 Cedric Van Holsbeke,3 Johan Clukers,1 Bita Hajian,1 Shahid Siddiqui,4 Martin Jenkins,5 Colin Reisner,4,6 Ubaldo J Martin4 1Department of Respiratory Medicine, University of Antwerp, Antwerp, Belgium; 2FLUIDDA, Los Angeles, CA, USA; 3FLUIDDA, Kontich, Belgium; 4AstraZeneca, Gaithersburg, MD, USA; 5AstraZeneca, Cambridge, UK; 6Pearl – A member of the AstraZeneca Group, Morristown, NJ, USA Background: Functional respiratory imaging (FRI) uses high-resolution computed tomography (HRCT) scans to assess changes in airway volume and resistance. Patients and methods: In this randomized, double-blind, 2-week, crossover, Phase IIIB study, patients with moderate-to-severe COPD received twice-daily glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler (GFF MDI, 18/9.6 µg) and placebo MDI, formulated using innovative co-suspension delivery technology. Co-primary endpoints included the following: specific image-based airway volume (siVaw) and specific image-based airway resistance (siRaw) at Day 15, measured using FRI. Secondary and other endpoints included the following: change from baseline in post-dose forced expiratory volume in 1 second (FEV1) and inspiratory capacity (IC; spirometry) and ratio to baseline in post-dose functional residual capacity (FRC) and residual volume (RV; body plethysmography). Results: Twenty patients (46–78 years of age) were randomized and treated; of whom 19 completed the study. GFF MDI treatment increased siVaw by 75% and reduced siRaw by 71% vs placebo MDI (both P

Masakazu Ichinose,1 Yoshiaki Minakata,2 Takashi Motegi,3 Jun Ueki,4 Yasuhiro Gon,5 Tetsuo Seki,6 Tatsuhiko Anzai,7 Shuhei Nakamura,6 Kazuto Hirata8 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, 2Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital, Wakayama, 3Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, 4Clinical Research Unit of Respiratory Pathophysiology, Juntendo University Graduate School of Health Care and Nursing, Chiba, 5Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 6Medical Division, Nippon Boehringer Ingelheim Co., Ltd, 7Clinical Information Division Data Science Center, Statistics Analysis Department 1, EPS Corporation, Tokyo, 8Osaka City University, Osaka, Japan Purpose: This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD.Patients and methods: A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II–IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa. The primary endpoint was inspiratory capacity (IC) at peak post-dose.Results: Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p

The coefficients of a quantile regression model are one-to-one functions of the order of the quantile. In standard quantile regression (QR), different quantiles are estimated one at a time. Another possibility is to model the coefficient functions parametrically, an approach that is referred to as quantile regression coefficients modeling (QRCM). Compared with standard QR, the QRCM approach facilitates estimation, inference and interpretation of the results, and generates more efficient estimators. We designed a penalized method that can address the selection of covariates in this particular modelling framework. Unlike standard penalized quantile regression estimators, in which model selection is quantile-specific, our approach permits using information on all quantiles simultaneously. We describe the estimator, provide simulation results and analyse the data that motivated the present article. The proposed approach is implemented in the qrcmNP package in R. [ABSTRACT FROM AUTHOR]

Approximately 20% of chronic obstructive pulmonary disease (COPD) patients have been considered to have a "nonhyperinflator phenotype." However, this judgment depends on patients making a fully maximal inspiratory capacity (IC) maneuver at rest, since the IC during exercise is compared with this baseline measurement. We hypothesized that IC maneuvers at rest are sometimes submaximal and tested this hypothesis by measuring IC and associated neural respiratory drive at rest and during inhalation of CO2 and exercise in patients with COPD. Twenty-six COPD patients [age 66 ± 6 yr, mean forced expiratory volume in 1 s (FEV1) 40 ± 11% predicted] and 39 healthy subjects (age 39 ± 14 yr, FEV1 98 ± 12% predicted) were studied. IC and the diaphragm electromyogram (EMGdi) associated with it (EMGdi-IC) and forced inspiratory vital capacity (FIVC) and its corresponding EMGdi (EMGdi-FIVC) were measured during inhalation of 8% CO2 (8% CO2-92% O2) and room air. Incremental exhaustive cycle ergometer exercise was also performed in both patients with COPD and healthy subjects. IC, EMGdi-IC, FIVC, and EMGdi-FIVC during breathing 8% CO2 were significantly greater than those during breathing room air in both patients with COPD and healthy subjects (all P < 0.001). EMGdi-IC in patients with COPD constantly increased during exercise from 145 ± 40 V at rest to 185 ± 52 μV at the end of exercise but change in IC was variable. Neural respiratory drive and its relevant IC increased during hypercapnia. Exercise-related hypercapnia in patients with COPD raises neural respiratory drives, which compensate for IC reduction, leading to underestimation of dynamic hyperinflation measured by IC at rest breathing room air. [ABSTRACT FROM AUTHOR]

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Lung hyperinflation or air trapping is the hallmark of COPD and the primary cause of dyspnea, poor quality of life, and advertent disease prognosis associated with the disease. Debates continue to rise against the use of forced expiratory volume 1 as the single-main evaluative parameter for patients with COPD. Inspiratory capacity (IC) together with spirometry on the other hand has been shown to be a dependable parameter that can indicate the presence and management of lung hyperinflation. Patients and Methods: This cross-sectional study included fifty patients of COPD presenting to the department of respiratory medicine. All patients underwent spirometry and 6-min walk test (6MWT). They were grouped according to the GOLD guidelines for airflow limitation, body mass index (BMI), 6MWT, BODE index, number of exacerbations (NoEs), COPD “ABCD” assessment tool, and IC. t-test and one-way analysis of variance were applied. Results: There were 37 males and 13 females. A positive correlation was found between IC and 6MWT and BMI (coefficient of 0.678 and 0.149, respectively). There was a negative correlation between IC and NoEs and BODE index (coefficient of − 0.257 and − 0.631, respectively). IC correlated strongly with the GOLD classification for airflow limitation and combined assessment of COPD. A statistically significant difference between pre- and post-IC values showed IC as the predictor of lung hyperinflation. Conclusion: IC can be used along with 6MWT, BMI, BODE index and NoE for the prognostication and management of COPD.

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DLCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DLCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (VO2), DLCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DLCO [i.e., CO was associated with peak VO2 (P = 0.006), peak work-rate (P = 0.005), and dyspnea/VO2 slope (P < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV1 and IC tertiles, peak VO2 and work rate were lower (P = 0.05) in low versus normal DLCO groups. Across all tertiles, low DLCO groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal DLCO group (all P < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, DLCOCO. The higher dyspnea ratings and earlier exercise termination in low DLCO groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. NEW & NOTEWORTHY Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (DLCO) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal DLCO. [ABSTRACT FROM AUTHOR]

Objective: Chronic Obstructive Pulmonary disease (COPD) is a disease characterized by progressive airflow limitation, which is not fully reversible. Expiratory flow limitation (EFL) is the most common cause of dynamic hyperinflation (DH) and increased respiratory workload in COPD. In our study, the relationship between negative expiratory pressure (NEP) and all pulmonary function tests, especially inspiratory capacity (IC), was investigated in the examination of DH in COPD patients. Methods: Thirty four COPD patients with a mean forced expiratory volume in one second (FEV1) of 38.9±12.7% and 15 healthy subjects were included in the study. Pulmonary function tests and NEP were performed in all COPD patients. Results: In 16 COPD patients (47.1%), EFL was positive with NEP. When pulmonary function tests of EFL positive and EFL negative patients were compared, significant differences were found only in obstruction parameters such as FEV1 and forced expiratory flow 25-75, but no difference was found with lung volumes and diffusion test. However, there was a statistically significant correlation between IC and FVC (mL and % predicted), FEV1 (% predicted) and lung volumes (mL and % predicted) and FRC (mL) (p<0.05). There was a negative but statistically insignificant correlation between IC and presence of flow limitation (p>0.05). Conclusion: We think that NEP application in COPD patients does not provide additional information about DH and that IC is the best predictor of DH. [ABSTRACT FROM AUTHOR]

Background: A simple technique to measure dynamic hyperinflation (DH) in patients with chronic obstructive pulmonary disease (COPD) is the metronome-paced tachypnea test (MPT). Earlier studies show conflicting results about the accuracy of the MPT compared to cardiopulmonary exercise testing (CPET). Objectives: The focus was to investigate the diagnostic accuracy of MPT to detect DH in a prospective and clinical study. Methods: COPD patients were included; all underwent spirometry, CPET, and MPT. DH (ΔIC) was calculated as the difference in % between inspiratory capacity (IC) at the start and end of the test divided by IC at the start. A subject was identified as a hyperinflator, if ΔIC (% of ICrest) was smaller than –10.2 and –11.1% in CPET and MPT, respectively. With these values, sensitivity and specificity were calculated. Bland-Altman plots were made of ΔIC (% of ICrest). Results: In the prospective and clinical study, 107 and 48 patients were included, respectively. Sensitivity of the MPT was 85% in both studies. The specificities were 33 and 27%, respectively. In the prospective study, B = +2.6%, L = 30.6, and –25.6%. In the clinical study, B = +0.8%, L = 31.0, and –29.1%. Conclusion: MPT seems to be a good replacement for CPET in group studies. The mean amount of DH was not different between CPET and MPT. On an individual level, MPT cannot be used to identify hyperinflators; it should be kept in mind that MPT overdiagnoses DH. The amount of DH should not be interchanged between CPET and MPT. [ABSTRACT FROM AUTHOR]

Long-acting bronchodilators are the cornerstone of pharmacologic treatment of chronic obstructive pulmonary disease (COPD). Spiolto® or Stiolto® is a fixed-dose combination (FDC) containing two long-acting bronchodilators, the long-acting muscarinic receptor antagonist tiotropium (TIO) and the long-acting β2-adrenoceptor agonist olodaterol (OLO), formulated in the Respimat® Soft Mist™ inhaler. A total of 13 large, multicentre studies of up to 52 weeks' duration have documented its efficacy in more than 15,000 patients with COPD. TIO/OLO 5/5 µg FDC significantly increases pulmonary function compared with placebo and its respective constituent mono-components TIO 5 µg and OLO 5 µg. TIO/OLO 5/5 µg also results in statistically and clinically significant improvements in patient-reported outcomes, such as dyspnoea, use of rescue medication, and health status. Addition of OLO 5 µg to TIO 5 µg reduces the rate of moderate-to-severe exacerbations by approximately 10%. Compared with placebo and TIO 5 µg, TIO/OLO 5/5 µg significantly improves exercise capacity (e.g. endurance time) and physical activity, the latter increase being reached by a unique combination behavioural modification intervention, dual bronchodilatation and exercise training. Overall, the likelihood for patients to experience a clinically significant benefit is higher with TIO/OLO 5/5 µg than with its constituent mono-components, which usually yield smaller improvements which do not always reach statistical significance, compared with baseline or placebo. This supports the early introduction of TIO/OLO 5/5 µg in the management of patients with symptomatic COPD. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the relationship between slow and forced vital capacity (SVC-FVC) difference with dynamic lung hyperinflation (DH) during the 6-min walking test (6MWT) in subjects with chronic obstructive pulmonary disease (COPD). Twenty-four subjects with COPD (12 males; 67 ± 6 years; forced expiratory volume in first second [FEV1] 56 ± 18% predicted) performed lung function tests by spirometry and plethysmography. DH was assessed by serial measurements of inspiratory capacity (IC) performed during the 6MWT and defined as ∆IC ≥ 150 mL or 10%. IC decrease significantly during the 6MWT (ΔCI: − 0.48 ± − 0.40 L; P < 0.0001), and 18 individuals (75%) presented DH. There was significant difference when comparing IC measured at rest with the other serial IC measurements (P < 0.0001). Correlation between the SVC-FVC difference and DH during the 6MWT was r = − 0.38; P = 0.06. The SVC-FVC difference presented only weak correlation with the development of DH during the 6MWT in patients with COPD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Measurements of inspiratory capacity (IC) and vital capacity (VC) are used to recognize dynamic hyperinflation, but appropriate reference values are required to achieve accurate clinical interpretations. Altitude above sea level is a potential determining factor for lung volumes, including IC and VC. OBJECTIVE: To describe IC and VC for healthy people who live in Mexico City at an altitude of 2,240 m above sea level. METHODS: Healthy subjects ages 9--81 y completed slow spirometry by following 2005 American Thoracic Society/European Respiratory Society standards. Once associations were explored, linear regression models were constructed and values were compared with those from previously published equations. RESULTS: A total of 441 healthy subjects (55.1% women) participated. The mean age was 32 y (minimum age, 9 y; maximum age, 81 y). IC and VC measurements were associated with sex, age, height, and weight. An accelerated increase in IC and VC was evident from 9 to 20 y of age, followed by a gradual decrease in both sexes. In general, IC was higher in our population than predicted by previously published reference equations. CONCLUSIONS: IC in healthy people at 2,240 m above sea level was higher than that of previous reports about European and Latin-American subjects of the same height, sex, and age who were at sea level. The present study provided robust reference values for persons who lived at a moderate altitude. [ABSTRACT FROM AUTHOR]