Joseph H. Tashjian

A combined pulmonary -radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation

Abstract The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. Methods: Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9–11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. Results: Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. Conclusions: Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.

Genome-wide association study of smoking behaviours in patients with COPD

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within cholinergic receptors, nicotinic, alpha 3/5 (CHRNA3/CHRNA5; eg, p=0.00011 for SNP rs1051730) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6; eg, p=2.78×10−5 for a non-synonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in DBH was significantly (p=0.015) associated with smoking cessation. Conclusion The authors identified two candidate regions associated with age at smoking initiation in patients with COPD. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviours of patients with COPD.

Pleural effusion complicates monitoring of respiratory mechanics

Objectives:Although pleural effusion reduces respiratory system compliance by restricting the lungs, the effusion volume is partially accommodated by chest wall expansion. The implications for these opposing volume changes on airway pressure monitoring in ventilated patients with pleural effusion are unreported. We investigated the interactions among pleural effusion, positive end-expiratory pressure, and indices of respiratory mechanics in a swine model. Design:Interventional animal model. Setting:Hospital animal research facility. Subjects:Nine deeply anesthetized swine. Interventions:The preparation included tracheostomy, arterial/venous catheter placement, and chest tube insertion. Animals were ventilated throughout the study at 9 mL/kg, and frequency was adjusted to maintain normocapnia (inspiratory:expiratory = 1:2, Fio2 = 0.5) and positive end-expiratory pressure of 1 cm H2O and 10 cm H2O. Fluid was instilled into the right pleural space to simulate effusions of 13 mL/kg (pleural effusion 1) and 26 mL/kg (pleural effusion 2). Measurements and Main Results:Quantitative computerized tomography studies (in five animals) and functional residual capacity volumes (wash-in/wash-out technique) were obtained for each pleural effusion/positive end-expiratory pressure combination. Mean functional residual capacity compared to baseline at positive end-expiratory pressure of 1 cm H2O was decreased by pleural effusion 1 and pleural effusion 2 (−42%, −64%) and restored by positive end-expiratory pressure of 10 cm H2O (moderate) to +23% of baseline for pleural effusion 1 and +1% for pleural effusion 2. Plateau pressure increased and compliance decreased in response to pleural effusion 1 and pleural effusion 2. Moderate positive end-expiratory pressure applied during both pleural effusion quantities restored plateau pressure and tidal compliance to prepleural effusion values. Computed tomography studies revealed lung compression and tidal derecruitment cycles occurring with pleural effusion at positive end-expiratory pressure of 1 cm H2O, whereas a moderate positive end-expiratory pressure restored prepleural effusion functional residual capacity and prevented lung and intratidal derecruitment. Conclusions:When pleural effusion is present, respiratory mechanics must be interpreted cautiously and sufficient positive end-expiratory pressure should be applied to prevent extensive collapse and intratidal cycles of recruitment/derecruitment.

Experimental intra-abdominal hypertension attenuates the benefit of positive end-expiratory pressure in ventilating effusion-compressed lungs*.

Objective:To test the ability of positive end-expiratory pressure to offset the reduction of resting lung volume caused by intra abdominal hypertension, unilateral pleural effusion, and their combination. Design:Controlled application of intrapleural fluid, raised abdominal pressure and their combination before and after positive end-expiratory pressure in an anesthetized porcine model of controlled ventilation. Setting:Large animal laboratory of a university-affiliated hospital. Subjects:Fourteen deeply anesthetized swine (weight 30–35 kg). Interventions:Unilateral pleural effusion instillation (13 mL/kg), intra-abdominal hypertension (15 mm Hg), and simultaneous pleural effusion/intra abdominal hypertension. Measurements:Tidal compliance, end-expiratory lung aeration by gas dilution functional residual capacity, and quantitative analyses of computerized tomograms of the lungs at the extremes of the tidal cycle. Main Results:Positive end-expiratory pressure of 10 cm H2O (positive end-expiratory pressure10) increased mean functional residual capacity by 368 mL when pleural effusion was present and by 184 mL when intra-abdominal hypertension was present. When pleural effusion and intra-abdominal hypertension were simultaneously applied, positive end-expiratory pressure 10 failed to improve tidal compliance and increased functional residual capacity by only 77 mL, whereastidal recruitment during ventilation remained substantial. Conclusions:The presence of intra-abdominal hypertension negates most of the positive end-expiratory pressure10 benefit in reversing pleural effusion–induced de-recruitment. Relief of intra-abdominal hypertension may be instrumental to the treatment of pleural effusion-associated lung restriction and cyclical tidal collapse and reopening.

Semi‐quantitative tracking of intra‐airway fluids by computed tomography

Background:  Airway secretions are a source of complications for patients with acute and chronic lung diseases, yet lack of techniques to quantitatively track secretions hampers research into clinical measures to reduce their pathologic consequences.