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Participants who were at an increased risk for lung cancer were enrolled in a trial to determine whether CT screening reduces mortality from lung cancer. In this study, volume measurements and volume doubling times were used to evaluate the noncalcified lung nodules that were detected by CT scanning at baseline and at years 1, 2, and 4 of the trial. With the use of these volumetric methods, the authors found that the chances of finding lung cancer by CT scanning 1 and 2 years after a negative baseline test were 1 in 1000 and 3 in 1000, respectively. With the use of volumetric methods, the authors found that the chances of finding lung cancer by CT scanning 1 and 2 years after a negative baseline test were 1 in 1000 and 3 in 1000, respectively. The use of multidetector computed tomography (CT) has increased the chance of finding noncalcified pulmonary nodules, 1 , 2 and as a result, clinicians often face the problem of deciding on the best course of action with respect to such nodules when they are found in asymptomatic subjects who have an increased risk for lung cancer. 3 This difficulty is especially evident in CT-based screening programs for lung cancer. The current practice is to refer participants in these programs for additional diagnostic evaluation if they have a noncalcified nodule that is larger than 5 mm in diameter. 4 – 9 In designing the Dutch–Belgian randomized . . .

Smokers with more than a 10-pack-year history of smoking who were part of an ongoing study had CT scans and lung-function tests. Approximately 1 in 12 had interstitial abnormalities; these patients had less emphysema and lower total lung capacities than did patients without such changes. The relationship between exposure to tobacco smoke and chronic obstructive pulmonary disease (COPD) is well described. 1 Two manifestations of COPD include emphysematous destruction of the lung parenchyma and elevated measures of total lung capacity. 2 However, there is increasing awareness that smoking may also result in areas of increased lung density — termed interstitial lung abnormalities — on high-resolution computed tomography (HRCT). 3 , 4 The extent to which interstitial lung abnormalities may be associated with a lesser amount of emphysema and lower measures of total lung capacity than anticipated on the basis of known smoking exposure is unclear. We determined the relationship . . .

The Third National Health and Nutrition Examination Survey (NHANES III) reference is currently recommended for interpreting spirometry results, but it is limited by the lack of subjects younger than 8 years and does not continuously model spirometry across all ages. By collating pediatric data from other large-population surveys, we have investigated ways of developing reference ranges that more accurately describe the relationship between spirometric lung function and height and age within the pediatric age range, and allow a seamless transition to adulthood. Data were obtained from four surveys and included 3,598 subjects aged 4-80 years. The original analyses were sex specific and limited to non-Hispanic white subjects. An extension of the LMS (lambda, mu, sigma) method, widely used to construct growth reference charts, was applied. The extended models have four important advantages over the original NHANES III analysis as follows: (1) they extend the reference data down to 4 years of age, (2) they incorporate the relationship between height and age in a way that is biologically plausible, (3) they provide smoothly changing curves to describe the transition between childhood and adulthood, and (4) they highlight the fact that the range of normal values is highly dependent on age. The modeling technique provides an elegant solution to a complex and longstanding problem. Furthermore, it provides a biologically plausible and statistically robust means of developing continuous reference ranges from early childhood to old age. These dynamic models provide a platform from which future studies can be developed to continue to improve the accuracy of reference data for pulmonary function tests.

Abstract Purpose This document addresses aspects of the performance and interpretation of spirometry that are particularly important in the workplace, where inhalation exposures can affect lung function and cause or exacerbate lung diseases, such as asthma, chronic obstructive pulmonary disease, or fibrosis. Methods Issues that previous American Thoracic Society spirometry statements did not adequately address with respect to the workplace were identified for systematic review. Medline 1950–2012 and Embase 1980–2012 were searched for evidence related to the following: training for spirometry technicians; testing posture; appropriate reference values to use for Asians in North America; and interpretative strategies for analyzing longitudinal change in lung function. The evidence was reviewed and technical recommendations were developed. Results Spirometry performed in the work setting should be part of a comprehensive workplace respiratory health program. Effective technician training and feedback can improve the quality of spirometry testing. Posture-related changes in FEV1 and FVC, although small, may impact interpretation, so testing posture should be kept consistent and documented on repeat testing. Until North American Asian–specific equations are developed, applying a correction factor of 0.88 to white reference values is considered reasonable when testing Asian American individuals in North America. Current spirometry should be compared with previous tests. Excessive loss in FEV1 over time should be evaluated using either a percentage decline (15% plus loss expected due to aging) or one of the other approaches discussed, taking into consideration testing variability, worker exposures, symptoms, and other clinical information. Conclusions Important aspects of workplace spirometry are discussed and recommendations are provided for the performance and interpretation of workplace spirometry.

Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]). Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema. Broncus Technologies.

BackgroundRates of preterm birth have increased in most industrialised countries but data on later lung function of late preterm births are limited. A study was undertaken to compare lung function at 8–9 and 14–17 years in children born late preterm (33–34 and 35–36 weeks gestation) with children of similar age born at term (≥37 weeks gestation). Children born at 25–32 weeks gestation were also compared with children born at term.MethodsAll births from the Avon Longitudinal Study of Parents and Children (n=14 049) who had lung spirometry at 8–9 years of age (n=6705) and/or 14–17 years of age (n=4508) were divided into four gestation groups.ResultsAt 8–9 years of age, all spirometry measures were lower in the 33–34-week gestation group than in controls born at term but were similar to the spirometry decrements observed in the 25–32-week gestation group. The 35–36-week gestation group and term group had similar values. In the late preterm group, at 14–17 years of age forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were not significantly different from the term group but FEV1/FVC and forced expiratory flow at 25–75% FVC (FEF25–75%) remained significantly lower than term controls. Children requiring mechanical ventilation in infancy at 25–32 and 33–34 weeks gestation had in general lower airway function (FEV1 and FEF25–75) at both ages than those not ventilated in infancy.ConclusionsChildren born at 33–34 weeks gestation have significantly lower lung function values at 8–9 years of age, similar to decrements observed in the 25–32-week group, although some improvements were noted by 14–17 years of age.

Background: A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal lung function more readily than spirometry in children and teenagers with CF, but its relationship to structural lung abnormalities is unknown. A study was undertaken to determine the agreements between LCI and spirometry, respectively, with structural lung disease as measured by high-resolution computed tomography (HRCT) in children and teenagers with CF. Methods: A retrospective study was performed in 44 consecutive patients with CF aged 5–19 years (mean 12 years). At an annual check-up inspiratory and expiratory HRCT scans, LCI and spirometric parameters (forced expiratory volume in 1 s (FEV1) and maximal expiratory flow when 75% of forced vital capacity was expired (FEF75)) were recorded. Abnormal structure was defined as a composite HRCT score of >5%, the presence of bronchiectasis or air trapping >30%. Abnormal lung function was defined as LCI above the predicted mean +1.96 residual standard deviations (RSD), or FEV1 or FEF75 below the predicted mean −1.96 RSD. Sensitivity/specificity assessments and correlation analyses were done. Results: The sensitivity to detect abnormal lung structure was 85–94% for LCI, 19–26% for FEV1 and 62–75% for FEF75. Specificity was 43–65% for LCI, 89–100% for FEV1 and 75–88% for FEF75. LCI correlated better with HRCT scores (Rs +0.85) than FEV1 (−0.62) or FEF75 (−0.66). Conclusions: LCI is a more sensitive indicator than FEV1 or FEF75 for detecting structural lung disease in CF, and a normal LCI almost excludes HRCT abnormalities. The finding of an abnormal LCI in some patients with normal HRCT scans suggests that LCI may be even more sensitive than HRCT scanning for detecting lung involvement in CF.

Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. We aimed to build on previous models by collating existing reference data in young children (aged 3-7 yr), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. The Asthma UK Collaborative Initiative was established to collate lung function data from healthy young children aged 3 to 7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (lambda, micro, sigma) method and extend previously published equations down to 3 years of age. The Asthma UK centile charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n = 3,777) from 15 centers across 11 countries and provide a continuous reference with a smooth transition into adolescence and adulthood. These equations improve existing pediatric equations by considering the between-subject variability to define a more appropriate age-dependent lower limit of normal. The collated data set reflects a variety of equipment, measurement protocols, and population characteristics and may be generalizable across different populations. We present prediction equations for spirometry for preschool children and provide a foundation that will facilitate continued updating.

Abstract Rationale Lung clearance index (LCI) is a more sensitive measure of lung function than spirometry in cystic fibrosis (CF) and correlates well with abnormalities in high-resolution computed tomography (HRCT) scanning. We hypothesized LCI would be equally sensitive to lung disease in primary ciliary dyskinesia (PCD). Objectives To test the relationships between LCI, spirometry, and HRCT in PCD and to compare them to the established relationships in CF. Methods Cross-sectional study of 127 patients with CF and 33 patients with PCD, all of whom had spirometry and LCI, of which a subset of 21 of each had HRCT performed. HRCT was scored for individual features and these features compared with physiological parameters. Measurements and Main Results Unlike in CF, and contrary to our hypothesis, there was no correlation between spirometry and LCI in PCD and no correlation between HRCT features and LCI or spirometry in PCD. Conclusions We show for the first time that HRCT, spirometry, and LCI have different relationships in different airway diseases and that LCI does not appear to be a sensitive test of airway disease in advanced PCD. We hypothesize that this results from dissimilarities between the components of large and small airway disease in CF and PCD. These differences may in part lead to the different prognosis in these two neutrophilic airway diseases.

Accurate characterization of asthma severity is difficult due to the variability of symptoms. Hyperpolarized helium-3 MRI (H(3)HeMR) is a new technique in which the airspaces are visualized, depicting regions with airflow obstruction as \"ventilation defects.\" The objective of this study was to compare the extent of H(3)HeMR ventilation defects with measures of asthma severity and spirometry. Patients with a physician diagnosis of asthma and normal control subjects underwent H(3)HeMR. For each person, the number and size of ventilation defects were scored and the average number of ventilation defects per slice (VDS) was calculated. The correlations of the imaging findings with measures of asthma severity and spirometry were determined. There were 58 patients with asthma (mild-intermittent, n = 13; mild-persistent, n = 13; moderate-persistent, n = 20; and severe-persistent, n = 12) and 18 control subjects. Mean +/- SE VDS for asthmatics was significantly greater than for control subjects (0.99 +/- 0.15 vs 0.26 +/- 0.22, p = 0.004). Among asthmatics, VDS was significantly higher for the group with moderate-persistent and severe-persistent disease than for the group with mild-intermittent and mild-persistent disease (1.37 +/- 0.24 vs 0.53 +/- 0.12, p < 0.001). VDS correlated significantly with FEV(1)/FVC (r = - 0.51, p = 0.002), forced expiratory flow between 25% and 75% from the beginning of FVC (FEF(25-75%)) percentage of predicted for height, sex, and race (%predicted) [r = - 0.50, p = 0.001], and FEV(1) %predicted (r = - 0.40, p = 0.002), but not with FVC %predicted (r = - 0.26, p = 0.057) and peak expiratory flow %predicted (r = - 0.16, p = 0.231). Many asthmatics had an elevated VDS, but their spirometric indexes, except FEF(25%-75%), were normal. Most ventilation defects were < 3 cm in size for all asthmatics. In the group of patients with moderate-to-severe persistent asthma, there were more defects > or =3 cm than in the group with mild-intermittent and mild-persistent disease (p = 0.021). Regional changes of airflow obstruction in asthmatics depicted by H(3)HeMR correlate with measures of asthma severity and spirometry.