Plethysmographic Lung Volumes Research Articles

Feasibility of dynamic chest radiography to calculate lung volumes in adult people with cystic fibrosis: a pilot study

IntroductionDynamic chest radiography (DCR) is a novel, low-dose, real-time digital imaging system where software identifies moving thoracic structures and can automatically calculate lung areas. In an observational, prospective, non-controlled, single-centre...

Computed Tomography Registration-Derived Regional Ventilation Indices Compared to Global Lung Function Parameters in Patients With COPD.

CT registration-derived indices provide data on regional lung functional changes in COPD. However, because unlike spirometry which involves dynamic maximal breathing maneuvers, CT-based functional parameters are assessed between two static breath-holds, it is not clear how regional and global lung function parameters relate to each other. We assessed the relationship between CT-density change (dHU), specific volume change (dsV), and regional lung tissue deformation (J) with global spirometric and plethysmographic parameters, gas exchange, exercise capacity, dyspnoea, and disease stage in a prospective cohort study in 102 COPD patients. There were positive correlations of dHU, dsV, and J with spirometric variables, DLCO and gas exchange, 6-min walking distance, and negative correlations with plethysmographic lung volumes and indices of trapping and lung distension as well as GOLD stage. Stepwise regression identified FEV1/FVC (standardized β = 0.429, p < 0.0001), RV/TLC (β = −0.37, p < 0.0001), and BMI (β = 0.27, p=<0.001) as the strongest predictors of CT intensity-based metrics dHU, with similar findings for dsV, while FEV1/FVC (β = 0.32, p=<0.001) and RV/TLC (β = −0.48, p=<0.0001) were identified as those for J. These data suggest that regional lung function is related to two major pathophysiological processes involved in global lung function deterioration in COPD: chronic airflow obstruction and gas trapping, with an additional contribution of nutritional status, which in turn determines respiratory muscle strength. Our data confirm previous findings in the literature, suggesting the potential of CT image-based regional lung function metrics as the biomarkers of disease severity and provide mechanistic insight into the interpretation of regional lung function indices in patients with COPD.

Lung Function of Adults Born at Very Low Birth Weight

J Yang, RA Kingsford, J Horwood. Pediatrics. 2020;145(2):e20192359 To assess the lung function in adults who were very low birth weight (VLBW) infants in comparison with controls and to assess if bronchopulmonary dysplasia (BPD) added further insult to their underlying pulmonary function. The study population consisted of 226 adults, aged 26 to 30 years, selected from the 1986 New Zealand VLBW cohort (birth weight <1500 g). One hundred adults born at term in 1986 who did not require NICU admission served as age-matched controls. In this retrospective cohort analysis, participants …

Lung Function of Adults Born at Very Low Birth Weight.

Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without. At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN2). An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN2. The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV1, FEV1/FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN2, versus subjects without. The differences remained after adjustment for confounders. Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function.

Correlation of bronchoalveolar lavage lymphocyte count with the extent of lung fibrosis and with plethysmographic lung volumes in patients with newly recognized hypersensitivity pneumonitis.

IntroductionHypersensitivity pneumonitis (HP) is an increasingly recognized interstitial lung disease, presenting with elevated total cell counts and high percentage of lymphocytes in bronchoalveolar lavage fluid (BALF). Despite many publications, there is no consensus in the literature concerning BALF cellular composition in patients with prolonged course of HP.AimThe aim of the present retrospective study was to investigate the influence of disease duration, smoking habits, and the extent of lung fibrosis on BALF cells’ population in patients with newly recognized HP.Material and methodsIn total, 94 patients (49 females, 45 males), mean age 52 (±12) years, with HP recognized according to recently proposed criteria, were enrolled into the present study. Chest CT scans were retrospectively reviewed by two independent radiologists. BALF evaluation was performed as a part of routine diagnostics according to recent recommendations.ResultsPercentage of lymphocytes in BALF was significantly lower in patients with lung fibrosis (stage 1 and 2) comparing to those without lung fibrosis (stage 0). Significant correlation was also found between the percentage of BALF lymphocytes and plethysmographic lung volumes, but not with lung transfer capacity for carbon monoxide (TLCO% pred). Smoking did not influence BALF results in our study group.ConclusionsBALF lymphocytosis correlated with the presence and the extent of lung fibrosis on chest CT as well as with plethysmographic lung volumes but did not with TLCO and smoking habits in newly recognized HP pneumonitis.

Associations between lung and endothelial function in early middle age.

Chronic lung disease is associated with impaired endothelial function and this may be a risk factor for poor cardiovascular health. It is unknown if there is an association between lung and endothelial function in the general population. We investigated associations between lung and endothelial function in a population-based cohort of 38-year-old men and women. Systemic endothelial function was measured using peripheral arterial tonometry to calculate the Framingham reactive hyperaemia index. Lung function was assessed using spirometry, plethysmographic lung volumes, airway conductance and gas transfer. Associations between lung and endothelial function were assessed with and without adjustment for potential confounding factors using regression analyses. Sex modified the association between lung and endothelial function. Among women, lower values of pre- and post-bronchodilator spirometry, total lung capacity and functional residual capacity (FRC) were associated with worse endothelial function (P < 0.05). These associations persisted after adjustment for smoking, asthma diagnoses, fitness and body mass index. Associations were weaker among men: only FRC, airway conductance and post-bronchodilator forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) ratios were associated with endothelial function. Endothelial function was not associated with gas transfer in either sex. Lower lung volumes and airflow obstruction are associated with endothelial dysfunction among women. There is weaker evidence for an association between airway and endothelial function in men. These findings may partly explain the increased risk of cardiovascular disease among people with poor lung function, but suggest that there are sex differences in this association.

Relation of Indices of Lung Hyperinflation to Dyspnea in Patients with Chronic Obstructive Pulmonary Disease: A Physiologic Assessment and Discussion

Background: The severity of COPD is commonly assessed by the reduction in forced expiratory volume at one second (FEV1), although more recently prognostic factors influencing survival have also incorporated functional capacity, degree of breathlessness on exertion, and body mass index. Increasingly, the reliability of physiological parameters such as FEV1 to predict patient-centered outcomes has been brought into question. Objectives: To evaluate the relationship between dyspnea as assessed by the Modified Medical Council Dyspnea (MMRC) scale, the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) staging and indices of lung hyperinflation and spirometry. Methods: Data were retrospectively analyzed at a 600-bed tertiary care center including spirometry, plethysmographic lung volumes, single breath carbon monoxide diffusion capacity and dyspnea graded according to MMRC, and GOLD staging. Results: Data for 331 patients were analyzed. Differences amongst FEV1, IC, IC/TLC, FRC and RV/TLC were significant between GOLD I/II and GOLD III/IV groups. The closest relationship to GOLD staging was seen with FEV1, FVC and slow vital capacity (SVC). FEV1/FVC, IC, and IC/TLC were inversely associated with MMRC score, while RV/TLC exhibited a positive relation with MMRC score. Conclusions: Indices of lung hyperinflation are closely associated, with dyspnea as assessed by MMRC grading with TLC, RV/TLC and IC exhibiting the closest relations, more so than FEV1. GOLD staging also shows strong correlations with lung volume subdivisions (weakly with TLC), more so than with FEV1. That TLC changed little between GOLD stages can be explained by the presence of collateral interalveolar channels and population characteristics different from those of other studies. These findings further support the concept that more than a reduction in FEV1, lung hyperinflation contributes to the sensation of dyspnea in airflow limitation.

Impact of neurological level and spinal curvature on pulmonary function in adults with spina bifida.

To describe pulmonary function and determine the impact of neurological level, scoliosis, and obesity on pulmonary function in people with spina bifida (SB). Participants with SB (N= 29) (15 females; age, 30 ± 12 years) completed spirometry and body plethysmographic lung volume testing. Univariate and multivariate regression analyses were used to describe the factors associated with pulmonary function in people with SB. Distribution of category of impairment in pulmonary function was: 55% (n= 16) restricted, 6.9% (n= 2) spirometric restricted, 1 combined obstructed and restricted, and 35.5% (n= 10) normal. In univariate analyses, neurological level was negatively associated with pulmonary function parameters, i.e., forced vital capacity (FVC) (p= 0.005), forced expiratory volume in 1 second (FEV1) (p= 0.008), total lung capacity (TLC) (p= 0.001), and degree of scoliosis were inversely associated with FVC (p= 0.005), FEV1 (p= 0.003), and TLC (p= 0.004). In multivariate models, level of lesion and degree of scoliosis independently contributed to the degree of lung function impairment. Restrictive pulmonary function was observed in 9/10 (90%) of those with thoracic neurological levels and was associated with decreased inspiratory capacity (IC) and expiratory reserve volume (ERV). Lumbar level lesions were associated with either normal lung function or an isolated reduction in FVC due to reduction in only ERV and preserved TLC representing spirometric restriction. High prevalence of restrictive pulmonary physiology is present in people with SB, with more rostral neurological levels and greater degree of scoliosis associated with a higher degree of pulmonary function impairment.

A Simple Measure to Assess Hyperinflation and Air Trapping: 1-Forced Expiratory Volume in Three Second / Forced Vital Capacity.

Background:Several recent studies have suggested that 1 minus-forced expiratory volume expired in 3 seconds / forced vital capacity (1-FEV3/FVC) may be an indicator of distal airway obstruction and a promising measure to evaluate small airways dysfunction.Aims:To investigate the associations of 1-FEV3/FVC with the spirometric measures and lung volumes that assess small airways dysfunction and reflects hyperinflation and air trapping.Study Design:Retrospective cross-sectional study.Methods:Retrospective assessment of a total of 1110 cases who underwent body plethysmographic lung volume estimations between a time span from 2005 to 2012. Patients were assigned into two groups: firstly by FEV1/FVC (FEV1/FVC <70% vs. FEV1/FVC ≥70%); secondly by FEV3/FVC < lower limits of normal (LLN) (FEV3/FVC < LLN vs. FEV3/FVC ≥ LLN). Spirometric indices and lung volumes measured by whole-body plethysmography were compared in groups. Also the correlation of spirometric indices with measured lung volumes were assessed in the whole-study population and in subgroups stratified according to FEV1/FVC and FEV3/FVC.Results:Six hundred seven (54.7%) were male and 503 (45.3%) were female, with a mean age of 52.5±15.6 years. Mean FEV3/FVC and 1-FEV3/FVC were 87.05%, 12.95%, respectively. The mean 1-FEV3/FVC was 4.9% in the FEV1/FVC ≥70% group (n=644) vs. 24.1% in the FEV1/FVC <70% group (n=466). A positive correlation was found between 1-FEV3/FVC and residual volume (r=0.70; p<0.0001), functional residual capacity-pleth (r=0.61; p<0.0001), and total lung capacity (r=0.47; p<0.0001). 1-FEV3/FVC was negatively correlated with forced expiratory flow25-75 (r=−0.84; p<0.0001). The upper limit of 95% confidence interval for 1-FEV3/FVC was 13.7%. 1-FEV3/FVC showed significant correlations with parameters of air trapping and hyperinflation measured by whole-body plethysmography. Importantly, these correlations were higher in study participants with FEV1/FVC <70% or FEV3/FVC < LLN compared to those with FEV1/FVC ≥70% or FEV3/FVC ≥ LLN, respectively.Conclusion:1-FEV3/FVC can be easily calculated from routine spirometric measurements. 1-FEV3/FVC is a promising marker of air trapping and hyperinflation. We suggest that 1-FEV3/FVC is complementary to FEV1/FVC and recommend clinicians to routinely report and evaluate together with FEV1/FVC during spirometry.

The relationship between body fat and respiratory function in young adults.

The relationship between adiposity and respiratory function is poorly understood. Most studies investigating this have used indirect measures of body fat and few have assessed how changes in adiposity influence lung function.Body fat measured by bio-electrical impedance analysis, body mass index, waist circumference, spirometry, body plethysmography and transfer factor were measured at ages 32 and 38 years in 361 non-smoking, non-asthmatic participants from a population-based birth cohort.Higher percentage body fat was associated with lower spirometric and plethysmographic lung volumes, but not with airflow obstruction, or transfer factor at 32 years. Changes in adiposity between ages 32 and 38 years were inversely associated with changes in lung volumes. These associations were generally stronger in men than women, but an association between increasing adiposity and lower airway function (forced expiratory volume in 1 s/forced vital capacity) was only found in women. Similar associations were found for body mass index and waist circumference.Higher percentage body fat is associated with lower lung volumes. Direct and indirect measures of adiposity had similar associations with lung function. Adiposity had a greater effect on lung volumes in men than women but was associated with airway function only in women. There was little evidence that adiposity influenced transfer factor.

Efficacy of Tiotropium Bromide and Rehabilitation Treatment on Pulmonary Function of Patients With Sulfur Mustard Lung Injury.

Background:Chronic pulmonary complication is the most common delayed toxic effect of sulfur mustard (SM) and it has no treatment so far.Objectives:To evaluate short-term therapeutic effects of inhaled tiotropium bromide and pulmonary rehabilitation on pulmonary function of patients with SM induced lung injury.Patients and Methods:In a randomized clinical trial, using convenient sampling method, 54 patients with chronic lung disease due to SM exposure were recruited in Baqiyatallah General Hospital, Tehran, Iran for a period of 2-month study. They were randomly divided into 3 groups of 18 participants each. Group 1 received routine drugs (Serevent, Flixotide), pulmonary rehabilitation 30 minutes/2 times a week, and tiotropium bromide 18 µg/day. Group 2 was treated with routine drugs and pulmonary rehabilitation and group 3 was only on the routine drugs. cardiopulmonary exercise test (CPET), plethysmographic measurements, and respiratory symptoms evaluation were performed before and after medical intervention.Results:In group 1, compared to group 3, significant differences were found with regard to symptoms of cough ([difference between the first and last visit in group 1: Diff 1] = -1.6, Diff 3 = -0.3, P = 0.01) and nocturnal dyspnea (Diff 1 = -1.9, Diff 3 = 0.0, P = 0.01), likewise, compared to group 2, significant differences were found with regard to lung function parameters of forced vital capacity (Diff 1 = 3.0, Diff 2 = -3.5, P = 0.03), forced expiratory volume in one second (Diff 1 = 3.9, Diff 2 = -5.6, P = 0.009), maximal mid-expiratory flow rate 25% - 75% (Diff 1 = 1.5, Diff 2 = -3.2, P = 0.007) and peak expiratory flow (Diff 1 = -2.06, Diff 2 = -4.3, P = 0.04). Total lung capacity (Diff 2 = 9.28, Diff 3 = -12.07, P = 0.02) and residual volume (Diff2 = 32.1, Diff3 = -27.6, P = 0.04) were increased in group 2 compared to group 3. There were no significant differences with regard to CPET results among all groups (P > 0.05).Conclusions:Inhalation of tiotropium bromide in combination with pulmonary rehabilitation could improve some plethysmographic lung volumes and clinical outcomes in patients with chronic pulmonary disease due to SM. Short-term prescription of pulmonary rehabilitation has no effect on CPET of patients.

The continuum of physiological impairment during treadmill walking in patients with mild-to-moderate COPD: patient characterization phase of a randomized clinical trial.

BackgroundTo have a better understanding of the mechanisms of exercise limitation in mild-to-moderate chronic obstructive pulmonary disease (COPD), we compared detailed respiratory physiology in patients with COPD and healthy age- and sex-matched controls.MethodsData were collected during the pre-treatment, patient characterization phase of a multicenter, randomized, double-blind, crossover study. Patients with COPD met Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 spirometric criteria, were symptomatic, and had evidence of gas trapping during exercise. All participants completed pulmonary function and symptom-limited incremental treadmill exercise tests.ResultsChronic activity-related dyspnea measured by Baseline Dyspnea Index was similarly increased in patients with GOLD 1 (n = 41) and 2 (n = 63) COPD compared with controls (n = 104). Plethysmographic lung volumes were increased and lung diffusing capacity was decreased in both GOLD groups. Peak oxygen uptake and work rate were reduced in both GOLD groups compared with controls (p<0.001). Submaximal ventilation, dyspnea, and leg discomfort ratings were higher for a given work rate in both GOLD groups compared with controls. Resting inspiratory capacity, peak ventilation, and tidal volume were reduced in patients with GOLD 2 COPD compared with patients with GOLD 1 COPD and controls (p<0.001).ConclusionsLower exercise tolerance in patients with GOLD 1 and 2 COPD compared with controls was explained by greater mechanical abnormalities, greater ventilatory requirements, and increased subjective discomfort. Lower resting inspiratory capacity in patients with GOLD 2 COPD was associated with greater mechanical constraints and lower peak ventilation compared with patients with GOLD 1 COPD and controls.Trial RegistrationClinicalTrials.gov: NCT01072396

Effect of salbutamol on the measurement of single‐breath diffusing capacity

The bronchodilation and cardiovascular effects of bronchodilators may alter alveolar ventilation and perfusion distribution, which could subsequently affect single-breath diffusing capacity of the lungs for carbon monoxide (DL ,CO) measurements. The aim of this study was to investigate the effect of salbutamol on DL ,CO in subjects with and without airway obstruction and reversibility. Sixty subjects were investigated with 20 in each of the three groups: normal spirometry; irreversible obstruction; and reversible obstruction. Baseline spirometry, plethysmographic lung volumes, DL ,CO, pulse rate and arterial blood gases were measured. The same testing sequence was repeated after administration of a placebo inhaler and again after 400 μg salbutamol. Salbutamol did not affect the mean alveolar volume (VA ) (P > 0.05), transfer coefficient for carbon monoxide (DL ,CO/VA , KCO) (P > 0.05) or DL ,CO (P > 0.05) in the normal and irreversible obstruction groups. In the reversible obstruction group, salbutamol caused an increase in the mean VA compared with placebo (P < 0.001). However, the mean KCO was reduced (P < 0.001). The mean change in DL ,CO was not significant (P > 0.05). A considerable reduction in DL ,CO was found after salbutamol in four subjects in the reversible group as a result of a minor increase in VA and substantial decrease in KCO. No statistical difference in pulse rate or arterial blood gases values was detected. Salbutamol had no effect on the mean DL ,CO in any group. However, salbutamol may considerably reduce DL ,CO in some individuals with reversibility secondary to its effects on VA and KCO.

Impact of ethnicity and extreme prematurity on infant pulmonary function

The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi-ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRCpleth) and forced expired volume (FEV0.5) were obtained at ∼12 months post-term age in 52 extremely preterm (EP) infants (median [range] gestational age [GA]: 26 [23–27] weeks; 40% White mothers; 79% with BPD), 41 PTC (GA:35 [30–36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37–42] weeks; 86% White mothers). Using reference equations based on identical equipment and techniques, results were expressed as z-scores to adjust for age, sex and body size. FEV0.5 was significantly lower in EP infants when compared with PTC (mean difference [95% CI]: −1.02[−1.60; −0.44] z-scores, P < 0.001), as was forced vital capacity (FVC) but there were no significant differences in FRCpleth or FEV0.5/FVC ratio. FEV0.5, FVC, and FEV0.5/FVC were significantly lower in both preterm groups when compared with fullterm controls. On multivariable analyses of the combined preterm dataset: FEV0.5 at ∼1 year was 0.11 [0.05; 0.17] z-scores higher/week GA, and 1.28 (0.49; 2.08) z-scores lower in EP infants with prior BPD. Among non-white preterm infants, FEV0.5 was 0.70 (0.17; 1.24) z-scores lower, with similar reductions in FVC, such that there were no ethnic differences in FEV0.5/FVC. Similar ethnic differences were observed among fullterm infants. These results confirm the negative impact of preterm birth on subsequent lung development, especially following a diagnosis of BPD, and emphasize the importance of taking ethnic background into account when interpreting results during infancy as in older subjects.

Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants

RationaleNewborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end...

S34 Lung Function in Children with Sickle Cell Disease

IntroductionSickle Cell Disease (SCD) is one of the most prevalent genetic diseases with an incidence of ∼1 in 200 Afro-Caribbean children in the UK (WHO; 2006). Since SCD can result...

Health Status Assessment in Routine Clinical Practice: The Chronic Obstructive Pulmonary Disease Assessment Test Score in Outpatients

Background: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a simple, self-completion questionnaire developed to measure health status in patients with COPD, which is potentially suitable for routine clinical use. Objectives: The purpose of this study was to establish the determinants of the CAT score in routine clinical practice. Methods: Patients attending the clinic completed the CAT score before being seen. Clinical data, including, where available, plethysmographic lung volumes, transfer factor and arterial blood gas analysis, were recorded on a pro forma in the clinic. Results: In 224 patients (36% female), mean forced expiratory volume in 1 s (FEV₁) was 40.1% (17.9) of predicted (%pred); CAT score was associated with exacerbation frequency [0–1/year 20.1 (7.6); 2–4/year 23.5 (7.8); >4/year 28.5 (7.3), p < 0.0001; 41/40/19% in each category] and with Medical Research Council (MRC) dyspnoea score (r² = 0.26, p < 0.0001) rising approximately 4 points with each grade. FEV₁ %pred had only a weak influence. Using stepwise regression, CAT score = 2.48 + 4.12 [MRC (1–5) dyspnoea score] + 0.08 (FEV₁ %pred) + 1.06 (exacerbation rate/year)] (r² = 0.36, p < 0.0001). The CAT score was higher in patients (n = 54) with daily sputum production [25.9 (7.5) vs. 22.2 (8.2); p = 0.004]. Detailed lung function (plethysmography and gas transfer) was available in 151 patients but had little influence on the CAT score. Conclusion: The CAT score is associated with clinically important variables in patients with COPD and enables health status measurement to be performed in routine clinical practice.

Interpretation of pediatric lung function: Impact of ethnicity

To evaluate the appropriateness of spirometric and plethysmographic reference equations in healthy young children according to ethnic origin. Spirometry data were collated in 400 healthy children (214 Black and 186 White) aged 6-12 years. Of these children, 68 Black and 115 White children also undertook plethysmography. Results were expressed as percent predicted according to commonly used equations for spirometry and plethysmography. Black children had lower lung function for a given height compared to White children. The magnitude and direction of these differences varied according to specific outcome. In the studied age range (6-12 years) the ethnic-specific Wang equations were adequate for spirometry (mean results approximating 100% predicted in both ethnic groups). By contrast, significant differences were found between observed and % predicted plethysmographic lung volumes according to published equations derived from White children: Among the Black children, function residual capacity (FRC) and total lung capacity (TLC) were on average, 14 and 6% lower than predicted, whereas mean residual volume (RV) and RV/TLC were 4 and 10% higher. Among White children, the Rosenthal equations gave the best fit, with the exception of FRC which was, on average, 9% lower than predicted. Spirometry equations may suffice in Black children; however, interpretation of static lung volumes in Black children is limited due to inappropriate reference equations. More appropriate plethysmographic reference equations that are applicable to all ethnic groups across the entire age range are urgently needed.

Decline of Resting Inspiratory Capacity in COPD: The Impact on Breathing Pattern, Dyspnea, and Ventilatory Capacity During Exercise

To better understand the interrelationships among disease severity, inspiratory capacity (IC), breathing pattern, and dyspnea, we studied responses to symptom-limited cycle exercise in a large cohort with COPD. Analysis was conducted on data from two previously published replicate clinical trials in 427 hyperinflated patients with COPD. Patients were divided into disease severity quartiles based on FEV(1) % predicted. Spirometry, plethysmographic lung volumes, and physiologic and perceptual responses to constant work rate (CWR) cycle exercise at 75% of the peak incremental work rate were compared. Age, body size, and COPD duration were similar across quartiles. As the FEV(1) quartile worsened (mean, 62%, 49%, 39%, and 27% predicted), functional residual capacity increased (144%, 151%, 164%, and 185% predicted), IC decreased (86%, 81%, 69%, and 60% predicted), and peak incremental cycle work rate decreased (66%, 55%, 50%, and 44% predicted); CWR endurance time was 9.7, 9.3, 8.2, and 7.3 min, respectively. During CWR exercise, as FEV(1) quartile worsened, peak minute ventilation ($$\dot{\mathrm{V}}$$e) and tidal volume (Vt) decreased, whereas an inflection or plateau of the Vt response occurred at a progressively lower $$\dot{\mathrm{V}}$$e (P < .0005), similar percentage of peak $$\dot{\mathrm{V}}$$e (82%-86%), and similar Vt/IC ratio (73%-77%). Dyspnea intensity at this inflection point was also similar across quartiles (3.1-3.7 Borg units) but accelerated steeply to intolerable levels thereafter. Progressive reduction of the resting IC with increasing disease severity was associated with the appearance of critical constraints on Vt expansion and a sharp increase in dyspnea to intolerable levels at a progressively lower ventilation during exercise.

Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial

IntroductionExercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD). We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.MethodsPatients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout. Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.ResultsA total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted). Ninety-five patients completed the study. On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%. Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study. This was accompanied by inverse decreases in residual volume and functional residual capacity. NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime). The safety profile of NVA237 was similar to that of the placebo.ConclusionNVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1. This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea. Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance. (ClinicalTrials.gov Identifier: NCT01154127).