Silence of the lungs: comparing measures of slow and noncommunicating lung units from pulmonary function tests with computed tomography.

Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of underventilated lung units (UVLU). In addition, we used two previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P < 0.0001) and sensitivity (79%). Bland-Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (-249 mL [95% CI -10,796; 580 mL] and -203 mL [95% CI -997; 591 mL], respectively). Parameters from both spirometry and body plethysmography were suboptimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared with the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF.NEW & NOTEWORTHY We consider the term "trapped air" either in the use of imaging or pulmonary function testing, something of a misnomer that can lead to an inaccurate assessment of an important physiological feature. Instead, we propose the term underventilated lung units (UVLU). Of the many pulmonary function methods we used in this study, we found that the use of multiple breath washout with short extension (MBWShX) to be the best nonimaging method.

Lung Volumes in a Mouse Model of Pulmonary Allergic Inflammation.

PURPOSE: Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation. METHODS: Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure-volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses. RESULTS: HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains. CONCLUSION: Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans.

Assessment of Treatment Response in Patients With Severe Asthma Using Visual and Quantitative Analysis of Chest CT.

OBJECTIVE: To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma. MATERIALS AND METHODS: Korean participants enrolled in a prospective multicenter study, named the Precision Medicine Intervention in Severe Asthma study, from May 2020 to August 2021, underwent baseline and follow-up chest CT scans (inspiration/expiration) 10-12 months apart, before and after biologic treatment. Two radiologists scored bronchiectasis severity and mucus plugging extent. Quantitative parameters were obtained from each CT scan as follows: normal lung area (normal), air trapping without emphysema (AT without emph), air trapping with emphysema (AT with emph), and airway (total branch count, Pi10). Clinical parameters, including pulmonary function tests (forced expiratory volume in 1 s [FEV1] and FEV1/forced vital capacity [FVC]), sputum and blood eosinophil count, were assessed at initial and follow-up stages. Changes in CT parameters were correlated with changes in clinical parameters using Pearson or Spearman correlation. RESULTS: Thirty-four participants (female:male, 20:14; median age, 50.5 years) diagnosed with severe asthma from three centers were included. Changes in the bronchiectasis and mucus plugging extent scores were negatively correlated with changes in FEV1 and FEV1/FVC (ρ = from -0.544 to -0.368, all P < 0.05). Changes in quantitative CT parameters were correlated with changes in FEV1 (normal, r = 0.373 [P = 0.030], AT without emph, r = -0.351 [P = 0.042]), FEV1/FVC (normal, r = 0.390 [P = 0.022], AT without emph, r = -0.370 [P = 0.031]). Changes in total branch count were positively correlated with changes in FEV1 (r = 0.349 [P = 0.043]). There was no correlation between changes in Pi10 and the clinical parameters (P > 0.05). CONCLUSION: Visual and quantitative CT parameters of normal, AT without emph, and total branch count may be effective for evaluating treatment response in patients with severe asthma.

Detection of dynamic lung hyperinflation using cardiopulmonary exercise testing and respiratory function in patients with stable cardiac disease: a multicenter, cross-sectional study.

BACKGROUND: Many patients with heart disease potentially have comorbid chronic obstructive pulmonary disease (COPD); however, there are not enough opportunities for screening, and the qualitative differentiation of shortness of breath (SOB) has not been well established. We investigated the detection rate of SOB based on a visual and qualitative dynamic lung hyperinflation (DLH) detection index during cardiopulmonary exercise testing (CPET) and assessed potential differences in respiratory function between groups. METHODS: We recruited 534 patients with heart disease or patients who underwent simultaneous CPET and spirometry (369 males, 67.0 ± 12.9 years) to scrutinize physical functions. The difference between inspiratory and expiratory tidal volume was calculated (TV E-I) from the breath-by-breath data. Patients were grouped into convex (decreased TV E-I) and non-convex (unchanged or increased TV E-I) groups based on their TV E-I values after the start of exercise. RESULTS: Among the recruited patients, 129 (24.2%) were categorized in the convex group. There was no difference in clinical characteristics between the two groups. The Borg scale scores at the end of the CPET showed no difference. VE/VCO2 slope, its Y-intercept, and minimum VE/VCO2 showed no significant difference between the groups. In the convex group, FEV1.0/FVC was significantly lower compared to that in the non-convex group (69.4 ± 13.1 vs. 75.0 ± 9.0%). Moreover, significant correlations were observed between FEV1.0/FVC and Y-intercept (r=-0.343), as well as between the difference between minimum VE/VCO2 and VE/VCO2 slope (r=-0.478). CONCLUSIONS: The convex group showed decreased respiratory function, suggesting a potential airway obstruction during exercise. A combined assessment of the TV E-I and Y-intercept of the VE/VCO2 slope or the difference between the minimum VE/VCO2 and VE/VCO2 slopes could potentially detect COPD or airway obstruction.

Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis.

Background: Previous studies found high but very variable levels of tetranor-PGEM and PGDM (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF). This study aims to assess the role of cyclooxygenase COX-1 and COX-2 genetic polymorphisms in PG production and of PG metabolites as potential markers of symptoms' severity and imaging findings. Methods: A total of 30 healthy subjects and 103 pwCF were included in this study. Clinical and radiological CF severity was evaluated using clinical scoring methods and chest computed tomography (CT), respectively. Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. Variants in the COX-1 gene (PTGS1 639 C>A, PTGS1 762+14delA and COX-2 gene: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were also analyzed. Results: PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Conclusions: These results suggest that urinary PG level testing can be used as a biomarker of CF severity. COX genetic polymorphisms are not involved in the variability of PG production.

Effect of twice daily inhaled albuterol on cardiopulmonary exercise outcomes, dynamic hyperinflation, and symptoms in secondhand tobacco-exposed persons with preserved spirometry and air trapping: a randomized controlled trial.

BACKGROUND: In tobacco-exposed persons with preserved spirometry (active smoking or secondhand smoke [SHS] exposure), air trapping can identify a subset with worse symptoms and exercise capacity. The physiologic nature of air trapping in the absence of spirometric airflow obstruction remains unclear. The aim of this study was to examine the underlying pathophysiology of air trapping in the context of preserved spirometry and to determine the utility of bronchodilators in SHS tobacco-exposed persons with preserved spirometry and air trapping. METHODS: We performed a double-blinded placebo-controlled crossover randomized clinical trial in nonsmoking individuals at risk for COPD due to exposure to occupational SHS who had preserved spirometry and air trapping defined as either a residual volume-to-total lung capacity ratio (RV/TLC) > 0.35 or presence of expiratory flow limitation (EFL, overlap of tidal breathing on maximum expiratory flow-volume loop) on spirometry at rest or during cardiopulmonary exercise testing (CPET). Those with asthma or obesity were excluded. Participants underwent CPET at baseline and after 4-week trials of twice daily inhalation of 180 mcg of albuterol or placebo separated by a 2-week washout period. The primary outcome was peak oxygen consumption (VO2) on CPET. Data was analyzed by both intention-to-treat and per-protocol based on adherence to treatment prescribed. RESULTS: Overall, 42 participants completed the entire study (66 ± 8 years old, 91% female; forced expiratory volume in 1 s [FEV1] = 103 ± 16% predicted; FEV1 to forced vital capacity [FVC] ratio = 0.75 ± 0.05; RV/TLC = 0.39 ± 0.07; 85.7% with EFL). Adherence was high with 87% and 93% of prescribed doses taken in the treatment and placebo arms of the study, respectively (P = 0.349 for comparison between the two arms). There was no significant improvement in the primary or secondary outcomes by intention-to-treat or per-protocol analysis. In per-protocol subgroup analysis of those with RV/TLC > 0.35 and ≥ 90% adherence (n = 27), albuterol caused an improvement in peak VO2 (parameter estimate [95% confidence interval] = 0.108 [0.014, 0.202]; P = 0.037), tidal volume, minute ventilation, dynamic hyperinflation, and oxygen-pulse (all P < 0.05), but no change in symptoms or physical activity. CONCLUSIONS: Albuterol may improve exercise capacity in the subgroup of SHS tobacco-exposed persons with preserved spirometry and substantial air trapping. These findings suggest that air trapping in pre-COPD may be related to small airway disease that is not considered significant by spirometric indices of airflow obstruction.

Longitudinal changes in respiratory reactance in patients with COPD: associations with longitudinal change in air-trapping, exacerbations, and mortality.

INTRODUCTION: Air-trapping affects clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and may be detected by reactance at 5 Hz (X5) on respiratory oscillometry because X5 sensitively reflects the elasticity of the chest wall, airway and lung. However, the longitudinal association between X5 and air-trapping remains to be explored. This study aimed to test whether longitudinal changes in X5 could be associated with air-trapping progression, exacerbations, and mortality in patients with COPD. METHODS: In this prospective COPD observational study, the follow-up period consisted of the first 4 years to obtain longitudinal changes in X5 and residual volume (RV) and number of exacerbations and the remaining years (year 4 to 10) to test mortality. Patients were divided into large, middle, and small X5 decline groups based on the tertiles of longitudinal change in X5, and mortality after 4 years was compared between the groups. RESULTS: Patients with COPD (n = 114) were enrolled. The large X5 decline group (n = 38) showed a greater longitudinal change in RV and more exacerbations compared with the small X5 decline group (n = 39) in multivariable models adjusted for age, sex, body mass index, and smoking history. Long-term mortality after the 4-year follow-up was higher in the large X5 decline group than in the small X5 decline group (hazard ratio [95 % confidence interval] = 8.37[1.01, 69.0]) in the multivariable Cox proportional hazard model. CONCLUSION: Longitudinal changes in respiratory reactance could be associated with progressive air-trapping, exacerbation frequency, and increased mortality in patients with COPD.

Sustained Clinical Benefits of Spiration Valve System in Patients with Severe Emphysema: 24-Month Follow-Up of EMPROVE.

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Use of Quantitative CT Imaging to Identify Bronchial Thermoplasty Responders.

BACKGROUND: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly. RESEARCH QUESTION: Do baseline radiographic and clinical characteristics exist that predict response to BT? STUDY DESIGN AND METHODS: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response. RESULTS: From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86). INTERPRETATION: To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01185275; URL: www. CLINICALTRIALS: gov.

A Novel Air Trapping Segment Score Identifies Opposing Effects of Obesity and Eosinophilia on Air Trapping in Asthma.

Rationale: Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments. Objectives: To apply a segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma. Methods: In each of 19 bronchopulmonary segments in CT lung scans from 199 patients with asthma, AT was categorized as present if lung attenuation was less than -856 Hounsfield units at expiration in ⩾15% of the lung area. The resulting AT segment score (0-19) was related to patient outcomes. Measurements and Main Results: AT varied at the lung segment level and tended to persist at the patient and lung segment levels over 3 years. Patients with widespread AT (⩾10 segments) had more severe asthma (P < 0.05). The mean (±SD) AT segment score in patients with a body mass index ⩾30 kg/m2 was lower than in patients with a body mass index <30 kg/m2 (3.5 ± 4.6 vs. 5.5 ± 6.3; P = 0.008), and the frequency of AT in lower lobe segments in obese patients was less than in upper and middle lobe segments (35% vs. 46%; P = 0.001). The AT segment score in patients with sputum eosinophils ⩾2% was higher than in patients without sputum eosinophilia (7.0 ± 6.1 vs. 3.3 ± 4.9; P < 0.0001). Lung segments with AT more frequently had airway mucus plugging than lung segments without AT (48% vs. 18%; P ⩽ 0.0001). Conclusions: In patients with asthma, air trapping is more severe in those with airway eosinophilia and mucus plugging, whereas those who are obese have less severe trapping because their lower lobe segments are spared.

MDCT and MRI in Bronchiectasis in Older Children and Young Adults - A Non-Inferiority Trial.

OBJECTIVES: To compare and evaluate the usefulness of magnetic resonance imaging (MRI) with computed tomography (CT) in bronchiectasis; to compare MRI and CT scores with pulmonary function tests (PFT) and to evaluate the role of Diffusion-weighted imaging (DWI) in bronchiectasis. METHODS: In this prospective study, 25 patients between 7-21 y of age with a clinical/radiological diagnosis of bronchiectasis underwent MDCT and MRI chest. MRI and CT scoring was performed using modified Bhalla-Helbich's score by two independent radiologists for all parameters. A final consensus score was recorded. The overall image quality of different MRI sequences to identify pathologies was also assessed. Appropriate statistical tests were used for inter-observer agreements, and correlation amongst CT and MRI; as well as CT, MRI and PFT. RESULTS: Strong agreement (ICC 0.80-0.95) between CT and MRI was seen for extent and severity of bronchiectasis, number of bullae, sacculation/abscess, emphysema, collapse/ consolidation, mucus plugging, and mosaic perfusion. Overall CT and MRI scores had perfect concordance (ICC 0.978). Statistically significant (p-value <0.01) intra-observer and inter-observer agreement for all CT and MRI score parameters were seen. A strong negative correlation was seen between total CT and MRI severity scores and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF) 25-75%. DWI MR, with an apparent diffusion coefficient (ADC) cut-off of 1.62 × 10-3 mm3/s had a sensitivity of 70% and specificity of 75% in detecting true mucus plugs. CONCLUSIONS: MRI with DWI can be considered as a radiation-free alternative in the diagnostic algorithm for assessment of lung changes in bronchiectasis, especially in follow-up.

Computer-assisted evaluation of small airway disease in CT scans of Iran-Iraq war victims of chemical warfare by a locally developed software: comparison between different quantitative methods.

OBJECTIVE: Diagnosis of small airway disease on computed tomography (CT) scans is challenging in patients with a history of chemical warfare exposure. We developed a software package based on different methodologies to identify and quantify small airway disease in CT images. The primary aim was to identify the best automatic methodology for detecting small airway disease in CT scans of Iran-Iraq War victims of chemical warfare. METHODS: This retrospective case-control study enrolled 46 patients with a history of chemical warfare exposure and 27 controls with inspiratory/expiratory (I/E) CT scans and spirometry tests. Image data were automatically segmented, and inspiratory images were registered into the expiratory images' frame using the locally developed software. Parametric response mapping (PRM) and air trapping index (ATI) mapping were performed on the CT images. Conventional QCT methods, including expiratory/inspiratory mean lung attenuation (E/I MLA) ratio, normal density E/I (ND E/I) MLA ratio, attenuation volume Index (AVI), %low attenuation areas (LAA) < -856 in exhale scans, and %LAA < -950 in inhale scans were also computed. QCT measurements were correlated with spirometry results and compared across the two study groups. RESULTS: The correlation analysis showed a significant negative relationship between three air trapping (AT) measurements (PRM, ATI, and %LAAExp < -856) and spirometry parameters (Fev1, Fvc, Fev1/Fvc, and MMEF). Moreover, %LAAExp < -856 had the highest significant negative correlation with Fev1/Fvc (r = -0.643, P-value < 0.001). Three AT measurements demonstrated a significant difference between the study groups. The E/I ratio was also significantly different between the two groups (P-value < 0.001). Binary logistic regression models showed PRMFsad, %LAAExp < -856, and ATI as significant and strong predictors of the study outcome. Optimal cut-points for PRMFsad = 19%, %LAAExp < -856 = 23%, and ATI = 27% were identified to classify the participants into two groups with high accuracy. CONCLUSION: QCT methods, including PRM, ATI, and %LAAExp < -856 can greatly advance the identification and quantification of SAD in chemical warfare victims. The results should be verified in well-designed prospective studies involving a large population.

Acute Hypercapnic Respiratory Failure in COPD.

COPD is a progressive inflammatory process affecting both the airways and alveolar structures of the lungs. Exacerbations of COPD are episodes of acute worsening of this inflammatory process, often triggered by infections. The most severe exacerbations are characterized by substantial air trapping and inspiratory muscle overload, which leads to hypercapnic respiratory failure. Pharmacologic therapies focus on intense bronchodilator administration (usually by aerosol), corticosteroids, and antibiotics. Respiratory life support technologies are often needed for severe exacerbations and range from carefully titrated supplemental O2 administration to positive-pressure ventilation (both invasive and noninvasive). Future life support strategies will likely involve extracorporeal life support technologies.

Air trapping in small airway diseases: A review of imaging technique and findings with an overview of small airway diseases.

Air trapping is a common finding radiologists encounter on CT imaging of the thorax. This term is used when there are geographic areas of differing attenuation within the lung parenchyma. Most commonly, this is the result of abnormal retention of air due to complete or partial airway obstruction from small airway pathologies. Perfusional differences due to underlying vascular diseases could also result in these appearances, and hence, inspiratory and full expiratory phase CT studies are required to accurately diagnose air trapping. It is important to note that this can occasionally be present in healthy patients. Multiple diseases are associated with air trapping. Determining the aetiology relies on accurate patient history and concomitant findings on CT. There is currently no consensus on accurate assessment of the severity of air trapping. The ratio of mean lung density between expiration and inspiration on CT and the change in lung volume have demonstrated a positive correlation with the presence of small airway disease. Treatment and resultant patient outcome depend on the underlying aetiology, and hence, radiologists need to be familiar with the common causes of air trapping. This paper outlines the most common disease processes leading to air trapping, including Constrictive bronchiolitis, Hypersensitivity pneumonitis, DIPNECH, and Post-infectious (Swyer-James/Macleod). Various diseases result in the air trapping pattern seen on the expiratory phase CT scan of the thorax. Combining patient history with other concomitant imaging findings is essential for accurate diagnosis and to further guide management.

Changes in Lung Volumes with Spirometric Disease Progression in COPD.

Background: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear. Methods: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.S. Department of Veterans Affairs electronic health records (n=71,356) and lung volumes measured by computed tomography (supine posture) available from the COPD Genetic Epidemiology (COPDGene®) study (n=7969) and the SubPopulations and InterMediate Outcome Measures In COPD Study (SPIROMICS) (n=2552) cohorts, and studied their cross-sectional distributions and longitudinal changes across the airflow obstruction spectrum. Patients with preserved ratio-impaired spirometry (PRISm) were excluded from this analysis. Results: Lung volumes from all 3 cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction. The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases. When stratified by airflow obstruction using Global initiative for chronic Obstructive Lung Disease (GOLD) stages, patients with GOLD 1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD 0 (smokers with preserved spirometry) or GOLD 2 (moderate) disease. In longitudinal follow-up of baseline GOLD 0 patients who progressed to spirometric COPD, those with an initially higher TLC and VC developed mild obstruction (GOLD 1) while those with an initially lower TLC and VC developed moderate obstruction (GOLD 2). Conclusions: In COPD, TLC, and VC have biphasic distributions, change in nonlinear fashions as obstruction worsens, and could differentiate those GOLD 0 patients at risk for more rapid spirometric disease progression.

MDCT-based longitudinal automated airway and air trapping analysis in school-age children with mild cystic fibrosis lung disease.

Objectives: Quantitative computed tomography (QCT) offers some promising markers to quantify cystic fibrosis (CF)-lung disease. Air trapping may precede irreversible bronchiectasis; therefore, the temporal interdependencies of functional and structural lung disease need to be further investigated. We aim to quantify airway dimensions and air trapping on chest CT of school-age children with mild CF-lung disease over two years. Methods: Fully-automatic software analyzed 144 serial spirometer-controlled chest CT scans of 36 children (median 12.1 (10.2-13.8) years) with mild CF-lung disease (median ppFEV1 98.5 (90.8-103.3) %) at baseline, 3, 12 and 24 months. The airway wall percentage (WP5-10), bronchiectasis index (BEI), as well as severe air trapping (A3) were calculated for the total lung and separately for all lobes. Mixed linear models were calculated, considering the lobar distribution of WP5-10, BEI and A3 cross-sectionally and longitudinally. Results: WP5-10 remained stable (P = 0.248), and BEI changed from 0.41 (0.28-0.7) to 0.54 (0.36-0.88) (P = 0.156) and A3 from 2.26% to 4.35% (P = 0.086) showing variability over two years. ppFEV1 was also stable (P = 0.276). A robust mixed linear model showed a cross-sectional, regional association between WP5-10 and A3 at each timepoint (P < 0.001). Further, BEI showed no cross-sectional, but another mixed model showed short-term longitudinal interdependencies with air trapping (P = 0.003). Conclusions: Robust linear/beta mixed models can still reveal interdependencies in medical data with high variability that remain hidden with simpler statistical methods. We could demonstrate cross-sectional, regional interdependencies between wall thickening and air trapping. Further, we show short-term regional interdependencies between air trapping and an increase in bronchiectasis. The data indicate that regional air trapping may precede the development of bronchiectasis. Quantitative CT may capture subtle disease progression and identify regional and temporal interdependencies of distinct manifestations of CF-lung disease.

Aerated Lobar Collapse.

Teaching Point: Air trapping is a useful sign for early detection of worsening lobar collapse in the follow-up of obstructive atelectasis.

Indoor environmental exposures and obstructive lung disease phenotypes among children with asthma living in poor urban neighborhoods.

BACKGROUND: Air trapping is an obstructive phenotype that has been associated with more severe and unstable asthma in children. Air trapping has been defined using pre- and postbronchodilator spirometry. The causes of air trapping are not completely understood. It is possible that environmental exposures could be implicated in air trapping in children with asthma. OBJECTIVE: We investigated the association between indoor exposures and air trapping in urban children with asthma. METHODS: Children with asthma aged 5 to 17 years living in Baltimore and enrolled onto the Environmental Control as Add-on Therapy for Childhood Asthma study were evaluated for air trapping using spirometry. Aeroallergen sensitization was assessed at baseline, and spirometry was performed at 0, 3, and 6 months. Air trapping was defined as an FVC z score of less than -1.64 or a change in FVC with bronchodilation of ≥10% predicted. Logistic normal random effects models were used to evaluate associations of air trapping and indoor exposures. RESULTS: Airborne and bedroom floor mouse allergen concentrations were associated with air trapping but not airflow limitation (odds ratio 1.19, 95% confidence interval 1.02-1.37, P = .02 per 2-fold increase in airborne mouse allergen; odds ratio 1.23, 95% confidence interval 1.07-1.41, P = .003 per 2-fold increase in bedroom floor mouse allergen). Other indoor exposures (cockroach, cat, dog, dust mite, particulate matter, and nicotine) were not associated with air trapping or airflow limitation. CONCLUSION: Mouse allergen exposure, but not other indoor exposure, was associated with air trapping in urban children with asthma.