Association of quantitative CT lung density measurements and lung function decline in World Trade Center workers

Abstract

Background Occupational exposures at the WTC site after 11 September 2001 have been associated with presumably inflammatory chronic lower airway diseases. Aims In this study, we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of those trajectories with quantitative computed tomography (QCT) imaging measurement of increased and decreased lung density. Methods We examined the trajectories of expiratory air flow decline in a group of 1,321 former WTC workers and volunteers with at least three periodic spirometries, and using QCT‐measured low (LAV%, −950 HU) and high (HAV%, from −600 to −250 HU) attenuation volume percent. We calculated the individual regression line slopes for first‐second forced expiratory volume (FEV1slope), identified subjects with rapidly declining (“accelerated decliners”) and increasing (“improved”), and compared them to subjects with “intermediate” (0 to −66.5 mL/year) FEV1slope. We then used multinomial logistic regression to model those three trajectories, and the two lung attenuation metrics. Results The mean longitudinal FEV1 slopes for the entire study population, and its intermediate, decliner, and improved subgroups were, respectively, −40.4, −34.3, −106.5, and 37.6 mL/year. In unadjusted and adjusted analyses, LAV% and HAV% were both associated with “accelerated decliner” status (ORadj, 95% CI 2.37, 1.41–3.97, and 1.77, 1.08–2.89, respectively), compared to the intermediate decline. Conclusions Longitudinal FEV1 decline in this cohort, known to be associated with QCT proximal airway inflammation metric, is also associated with QCT indicators of increased and decreased lung density. The improved FEV1 trajectory did not seem to be associated with lung density metrics.

Quantitative CT lung densitometry for the diagnosis of bronchiolitis obliterans in children

“…LAA from both -850 and -900 HU thresholds showed a statistically significant correlation with specific airway resistance sRaw in multivariate analysis, indicating high OR and high AUC values for BO diagnosis. In previous studies in adult patients, the attenuation threshold range from -856 to -950 HU has been shown to be the most applicable for identifying pathologic air trapping 10,[18][19][20][21][22] .…”

Cluster Analysis of World Trade Center Related Lower Airway Diseases

“…and A.P.R.). 4,8,[10][11][12] We selected spirometries that met our quality selection requirement, namely, forced exhalatory time >6 seconds and overall spirometry (reproducibility) grades A, B, or (if at least five trials were available) C. 2,8,23 As previously reported, 23 our spirometry program quality assurance included both daily inspiratory and expiratory volume calibration checks and weekly expiratory linearity checks.…”

“…For the cluster analysis, we examined 21 characteristics, including those in the following groups 1 : self-reported demographic information such as age on September 11, 2001, sex, and ethnicity/race (grouped into Latino of any race, non-Latino White, and all other races) 2 ; smoking status (never, former, and current) and intensity of smoking (in pack-years), as previously defined 2,243 ; self-reported indicators of occupational exposures at the WTC site, such as early arrival (within 48 hours) at the site 25 and cumulative exposure duration. 2,6 From the periodic surveillance visit closest to the chest CT scan, we included the following 4 : clinically significant dyspnea (defined as a modified Medical Research Council score ≥2 ["I walk slower than people of my same age on the level because of breathlessness, or have to stop for breath when walking at my own pace on the level"] 26 ) 5 ; spirometric pattern, classified as normal, low forced vital capacity (FVC < lower limit of normal, with normal ratio of first-second forced expiratory volume [FEV 1 ] to FVC, FEV 1 /FVC), or obstructive (FEV 1 / FVC < lower limit of normal). 2,27 We also considered 6 bronchodilator response (BDR) at any visit, most often the baseline, defined as an increase in either FEV 1 or FVC of at least 12% and 200 mL in response to inhaled albuterol administration 7,10 ; body mass index (BMI) in kilograms per square meter measured at the baseline visit 8 ; weight gain (as indicated by longitudinal measured BMI trajectory (BMIslope) in kilograms per square meter per year 10 ).…”

“…2,27 We also considered 6 bronchodilator response (BDR) at any visit, most often the baseline, defined as an increase in either FEV 1 or FVC of at least 12% and 200 mL in response to inhaled albuterol administration 7,10 ; body mass index (BMI) in kilograms per square meter measured at the baseline visit 8 ; weight gain (as indicated by longitudinal measured BMI trajectory (BMIslope) in kilograms per square meter per year 10 ). Lastly, from the QCT data, 9 total lung volume (TLV CT ), with calculated predicted values 28 and assessed by z scores, 10 lung attenuation volume percent, either high (HAV% from −600 to −250 Hounsfield units [HU], with >10% as cut point) and low (LAV% less than −950 HU, low attenuation volume percent, with >2.5% as cut point), 4,29 indirect distal airway measurements such as 11 end-expiratory air trapping at −856 HU (AT EXP 856), 8,29 and 12 mean expiratory:inspiratory lung density ratio (MLD EI ), 8 and proximal airway metrics such as 13 wall area percent (WAP) directly measured on the third generation of the right upper lobe, 8,10,29 and 14 Pi10, the average wall thickness of a hypothetical airway with a 10-mm luminal perimeter on CT. 29,30 As in previous studies of longitudinal lung function trajectories among participants in the Mount Sinai WTC GRC cohort, 4,10 we conducted a secondary analysis of the FEV 1 trajectories for the resulting clusters. As in previous work, 4 we estimated the longitudinal FEV 1 slopes for each subject with at least 3 good quality (as defined previously) spirometries performed between July 2002 and December 2018, and used them to define the following three trajectories as follows: rapid FEV 1 decline ("rapid decliner") by an FEV 1 slope < −66.5 mL/y (ie, less than the group mean-0.5 SD), FEV 1 gain ("gainer") by an FEV 1 slope > 0 mL/y, and intermediate FEV 1 decline ("intermediate decliner") by an FEV 1 slope between 0 and −66.5 mL/y (ie, between 0 and the group mean-0.5 SD).…”

“…Among workers engaged in rescue and recovery efforts, occupational exposures to dust and fumes at the World Trade Center (WTC) disaster site have been associated with lower respiratory symptoms, 1 worse lung function 2 and accelerated longitudinal lung function decline trajectories, 3,4 asthma 5 and other chronic airway diseases, 6–8 and both qualitative 9 and quantitative 4,8,10–12 abnormalities on computed tomography (CT) of the chest. Common co-existing morbidities, such as obesity, are linked to greater severity of WTC-related respiratory symptoms, airway disorders, and morbidity 13–19 …”