Signs of Gas Trapping in Normal Lung Density Regions in Smokers

COPDGene Investigators; Sandeep Bodduluri; Joseph M Reinhardt; Eric A Hoffman; John D Newell; Hrudaya Nath; Mark T Dransfield; Surya P Bhatt

doi:10.1164/rccm.201705-0855OC

Signs of Gas Trapping in Normal Lung Density Regions in Smokers

COPDGene Investigators, Sandeep Bodduluri, Joseph M Reinhardt, Eric A Hoffman, John D Newell, Hrudaya Nath, Mark T Dransfield, Surya P Bhatt

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

RATIONALE: A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known.

OBJECTIVES: To identify subthreshold structural disease in normal-appearing lung regions in smokers.

METHODS: We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity.

MEASUREMENTS AND MAIN RESULTS: The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted β = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted β = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV1 change at follow-up (adjusted β = -3.013; 95% CI, -4.478 to -1.548; P = 0.001).

CONCLUSIONS: Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Original language	English
Pages (from-to)	1404-1410
Number of pages	7
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	196
Issue number	11
Early online date	14 Jul 2017
DOIs	https://doi.org/10.1164/rccm.201705-0855OC
Publication status	Published - Dec 2017
Externally published	Yes

Keywords / Materials (for Non-textual outputs)

Female
Forced Expiratory Volume
Gases
Humans
Lung
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive
Severity of Illness Index
Smokers
Smoking
Surveys and Questionnaires
Tomography, X-Ray Computed
Walk Test
Clinical Trial, Phase I
Journal Article

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10.1164/rccm.201705-0855OC

Cite this

@article{b63f40a9bc494fb7b9584082e5054e36,

title = "Signs of Gas Trapping in Normal Lung Density Regions in Smokers",

abstract = "RATIONALE: A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known.OBJECTIVES: To identify subthreshold structural disease in normal-appearing lung regions in smokers.METHODS: We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity.MEASUREMENTS AND MAIN RESULTS: The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted β = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted β = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV1 change at follow-up (adjusted β = -3.013; 95% CI, -4.478 to -1.548; P = 0.001).CONCLUSIONS: Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).",

keywords = "Female, Forced Expiratory Volume, Gases, Humans, Lung, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Smokers, Smoking, Surveys and Questionnaires, Tomography, X-Ray Computed, Walk Test, Clinical Trial, Phase I, Journal Article",

author = "{COPDGene Investigators} and Sandeep Bodduluri and Reinhardt, {Joseph M} and Hoffman, {Eric A} and Newell, {John D} and Hrudaya Nath and Dransfield, {Mark T} and Bhatt, {Surya P}",

year = "2017",

month = dec,

doi = "10.1164/rccm.201705-0855OC",

language = "English",

volume = "196",

pages = "1404--1410",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "11",

}

TY - JOUR

T1 - Signs of Gas Trapping in Normal Lung Density Regions in Smokers

AU - COPDGene Investigators

AU - Bodduluri, Sandeep

AU - Reinhardt, Joseph M

AU - Hoffman, Eric A

AU - Newell, John D

AU - Nath, Hrudaya

AU - Dransfield, Mark T

AU - Bhatt, Surya P

PY - 2017/12

Y1 - 2017/12

N2 - RATIONALE: A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known.OBJECTIVES: To identify subthreshold structural disease in normal-appearing lung regions in smokers.METHODS: We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity.MEASUREMENTS AND MAIN RESULTS: The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted β = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted β = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV1 change at follow-up (adjusted β = -3.013; 95% CI, -4.478 to -1.548; P = 0.001).CONCLUSIONS: Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

AB - RATIONALE: A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known.OBJECTIVES: To identify subthreshold structural disease in normal-appearing lung regions in smokers.METHODS: We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity.MEASUREMENTS AND MAIN RESULTS: The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted β = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted β = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV1 change at follow-up (adjusted β = -3.013; 95% CI, -4.478 to -1.548; P = 0.001).CONCLUSIONS: Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

KW - Female

KW - Forced Expiratory Volume

KW - Gases

KW - Humans

KW - Lung

KW - Male

KW - Middle Aged

KW - Pulmonary Disease, Chronic Obstructive

KW - Severity of Illness Index

KW - Smokers

KW - Smoking

KW - Surveys and Questionnaires

KW - Tomography, X-Ray Computed

KW - Walk Test

KW - Clinical Trial, Phase I

KW - Journal Article

U2 - 10.1164/rccm.201705-0855OC

DO - 10.1164/rccm.201705-0855OC

M3 - Article

C2 - 28707983

SN - 1073-449X

VL - 196

SP - 1404

EP - 1410

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 11

ER -

Signs of Gas Trapping in Normal Lung Density Regions in Smokers

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Keywords / Materials (for Non-textual outputs)

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