Interstitial lung abnormalities (ILAs) progress radiologically in many patients and may reflect early interstitial lung disease (ILD). Within idiopathic pulmonary fibrosis and other smoking-related ILDs, there is increasing evidence that aberrant airway biology plays a role in disease development and progression. In this study, we sought to investigate associations between radiologic features of airways disease and progressive ILAs that could provide valuable insights into the management of patients at risk for developing ILD.
Methods:
We performed a retrospective study of subjects undergoing low-dose computed tomography (LDCT) for lung cancer screening between January 2016 and August 2022. Adults aged 50–80 years with ≥2 LDCTs performed ≥24 months apart were included. Demographic data, medical history, and LDCTs were collected. LDCTs were qualitatively analyzed for ILAs and features of airways disease by a thoracic radiologist. Data were analyzed using a generalized estimating equation adjusted for age, sex, pack-years of tobacco, and a radiologic usual interstitial pneumonia pattern.
Results:
Of 482 subjects, 54% (259/482) were female, and 66% (316/482) were Black. Average age was 64 years. The majority of subjects were current smokers (n = 276, 57%). Thirty-one percent (n = 147) had COPD, and 11% had asthma (n = 56). Median time between LDCTs was 51 (39–61) months. There were 85 subjects with ILAs, and of those, 42 (49.4%) had progressive ILAs. Bronchial wall thickening and mosaic attenuation were associated with ILA progression in adjusted models (odds ratio [OR] = 2.61, 95% CI: 1.08–6.23 and OR = 2.51, 95% CI: 1.02–6.17, respectively).
Conclusions:
Radiologic features of airways disease, including bronchial wall thickening and mosaic attenuation, were associated with ILA progression in subjects undergoing lung cancer screening.
SverzellatiN, GuerciL, RandiG, et al.Interstitial lung diseases in a lung cancer screening trial. Eur Respir J, 2011; 38(2):392–400; doi: 10.1183/09031936.00201809
2.
JinGY, LynchD, ChawlaA, et al.Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiol, 2013; 268(2):563–571; doi: 10.1148/radiol.13120816
3.
PompeE, de JongPA, LynchDA, et al.Computed tomographic findings in subjects who died from respiratory disease in the National Lung Cancer Screening Trial. Eur Respir J, 2017; 49(4):1601814; doi: 10.1183/13993003.01814-2016
4.
HoyerN, WilleMMW, ThomsenLH, et al.Interstitial lung abnormalities are associated with increased mortality in smokers. Respir Med, 2018; 136:77–82; doi: 10.1016/j.rmed.2018.02.001
5.
KristAH, DavidsonKW, MangioneCM, et al.; US Preventative Services Task Force. Screening for lung cancer: US Preventative Services Task Force recommendation statement. JAMA, 2021; 325(10):962–970; doi: 10.1001/jama.2021.1117
6.
HatabuH, HunninghakeGM, RicheldiL, et al.Interstitial lung abnormalities detected incidentally on CT: a position paper from the Fleischner Society. Lancet Respir Med, 2020; 8(7):726–737; doi: 10.1016/S2213-2600(20)30168-5
7.
HataA, SchieblerML, LynchDA, et al.Interstitial lung abnormalities: State of the art. Radiology, 2021; 301(1):19–34; doi: 10.1148/radiol.2021204367
PatelAS, MillerE, RegisSM, et al.Interstitial lung abnormalities in a large clinical lung cancer screening cohort: association with mortality and ILD diagnosis. Respir Res, 2023; 24(1):49; doi: 10.1186/s12931-023-02359-9
10.
ArakiT, PutmanRK, HatabuH, et al.Development and progression of interstitial lung abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med, 2016; 194(12):1514–1522; doi: 10.1164/rccm.201512-2523OC
11.
PodolanczukAJ, HunninghakeGM, WilsonKC, et al.Approach to the evaluation and management of interstitial lung abnormalities: An official American Thoracic Society clinical statement. Am J Respir Crit Care Med, 2025; 211(7):1132–1155; doi: 10.1164/rccm.202505-1054ST
12.
PutmanRK, GudmundssonG, ArakiT, et al.The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes. Eur Respir J, 2017; 50(3):1700537; doi: 10.1183/13993003.00537-2017
13.
WashkoGR, HunninghakeGM, FernandezIE, et al.; COPDGene Investigators. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med, 2011; 364(10):897–906; doi: 10.1056/NEJMoa1007285
14.
KatzensteinAL, MukhopadhyayS, ZanardiC, et al.Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. Hum Pathol, 2010; 41(3):316–325; doi: 10.1016/j.humpath.2009.09.003
15.
KawabataY, HoshiE, MuraiK, et al.Smoking-related changes in the background of lung specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course. Histopathology, 2008; 53(6):707–714; doi: 10.1111/j.1365-2559.2008.03183.x
16.
EvansCM, FingerlinTE, SchwarzMI, et al.Idiopathic pulmonary fibrosis: a genetic disease that involves mucociliary dysfunction of the peripheral airways. Physiol Rev, 2016; 96(4):1567–1591; doi: 10.1152/physrev.00004.2016
17.
JohkohT, MullerNL, IchikadoK, et al.Respiratory change in size of honeycombing: inspiratory and expiratory spiral volumetric CT analysis of 97 cases. J Comput Assist Tomogr, 1999; 23(2):174–180; doi: 10.1097/00004728-199903000-00003
18.
MartenK, MilneD, AntoniouKM, et al.Non-specific interstitial pneumonia in cigarette smokers: a CT study. Eur Radiol, 2009; 19(7):1679–1685; doi: 10.1007/s00330-009-1308-7
19.
CaminatiA, HarariS. Smoking-related interstitial pneumonias and pulmonary Langerhans cell histiocytosis. Proc Am Thorac Soc, 2006; 3(4):299–306; doi: 10.1513/pats.200512-135TK
20.
MargaritopoulosGA, VasarmidiE, JacobJ, et al.Smoking and interstitial lung diseases. Eur Respir Rev, 2015; 24(137):428–435; doi: 10.1183/16000617.0050-2015
21.
TsushimaK, SoneS, YoshikawaS, et al.The radiological patterns of interstitial change at an early phase: over a 4-year follow-up. Respir Med, 2010; 104(11):1712–1721; doi: 10.1016/j.rmed.2010.05.014
22.
KazerooniEA, AustinJHM, BlackWC, et al.; Society of Thoracic Radiology. ACR-STR practice parameter for the performance and reporting of lung cancer screening thoracic computed tomography (CT): 2014 (resolution 4). J Thorac Imaging, 2014; 29(5):310–316; doi: 10.1097/RTI.0000000000000097
23.
SilvaCIS, ColbyTV, MüllerNL. Asthma and associated conditions: high-resolution CT and pathologic findings. AJR Am J Roentgenol, 2004; 183(3):817–824; doi: 10.2214/ajr.183.3.1830817
24.
AdegunsoyeA, OldhamJM, BellamSK, et al.African-American race and mortality in interstitial lung disease: a multicenter propensity-matched analysis. Eur Respir J, 2018; 51(6):1800255; doi: 10.1183/13993003.00255-2018
25.
AdegunsoyeA, FreiheitE, WhiteEN, et al.Evaluation of pulmonary fibrosis outcomes by race and ethnicity in US adults. JAMA Netw Open, 2023; 6(3):e232427; doi: 10.1001/jamanetworkopen.2023.2427
26.
Kawano-DouradoL, GlassbergMK, Molina-MolinaM, et al.Gender equity in interstitial lung disease. Lancet Respir Med, 2020; 8(9):842–843; doi: 10.1016/S2213-2600(20)30310-6
27.
AllenRJ, Guillen-GuioB, OldhamJM, et al.Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2020; 201(5):564–574; doi: 10.1164/rccm.201905-1017OC
28.
PeljitoAL, BlumhagenRZ, WaltsAD, et al.Idiopathic pulmonary fibrosis is associated with common genetic variants and limited rare variants. Am J Respir Crit Care Med, 2023; 207(9):1194–1202; doi: 10.1164/rccm.202207-1331OC
29.
HunninghakeGM, HatabuH, OkajimaY, et al.MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med, 2013; 368(23):2192–2200; doi: 10.1056/NEJMoa1216076
30.
KimJS, ManichaikulAW, HoffmanEA, et al.MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study. Thorax, 2023; 78(6):566–573; doi: 10.1136/thorax-2021-218139
31.
MillerER, PutmanRK, DiazAA, et al.Increased airway wall thickness in interstitial lung abnormalities and idiopathic pulmonary fibrosis. Ann Am Thorac Soc, 2019; 16(4):447–454; doi: 10.1513/AnnalATS.201806-424OC
32.
RaghuG, Remy-JardinM, RicheldiL, et al.Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med, 2022; 205(9):e18–e47; doi: 10.1164/rccm.202202-0399ST
33.
BarnettJ, MolyneauxPL, RawalB, et al.Variable utility of mosaic attenuation to distinguish fibrotic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis. Eur Respir J, 2019; 54(1):1900531; doi: 10.1183/13993003.00531-2019
34.
SilvaCIS, MullerNL, LynchDA, et al.Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology, 2008; 246(1):288–297; doi: 10.1148/radiol.2453061881
35.
YagihashiK, HuckleberryJ, ColbyTV, et al.; Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet). Radiologic-pathologic discordance in biopsy-proven usual interstitial pneumonia. Eur Respir J, 2016; 47(4):1189–1197; doi: 10.1183/13993003.01680-2015
36.
MastoraI, Remy-JardinM, SobaszekA, et al.Thin-section CT finding in 250 volunteers: assessment of the relationship of CT findings with smoking history and pulmonary function test results. Radiology, 2001; 218(3):695–702; doi: 10.1148/radiology.218.3.r01mr08695
37.
OldhamJM, AdegunsoyeA, KheraS, et al.Underreporting of interstitial lung abnormalities on lung cancer screening computed tomography. Ann Am Thorac Soc, 2018; 15(6):764–766; doi: 10.1513/AnnalsATS.201901-053RL
38.
KlingermanSJ, HenryT, LinCT, et al.Mosaic attenuation: etiology, methods of differentiation, and pitfalls. Radiographics, 2015; 35(5):1360–1380; doi: 10.1148/rg.2015140308
