Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2020

01-12-2020 | Lung Cancer | Research article

Increased respiratory morbidity in individuals with interstitial lung abnormalities

Authors: Nils Hoyer, Laura H. Thomsen, Mathilde M. W. Wille, Torgny Wilcke, Asger Dirksen, Jesper H. Pedersen, Zaigham Saghir, Haseem Ashraf, Saher B. Shaker

Published in: BMC Pulmonary Medicine | Issue 1/2020

Login to get access

Abstract

Background

Interstitial lung abnormalities (ILA) are common in participants of lung cancer screening trials and broad population-based cohorts. They are associated with increased mortality, but less is known about disease specific morbidity and healthcare utilisation in individuals with ILA.

Methods

We included all participants from the screening arm of the Danish Lung Cancer Screening Trial with available baseline CT scan data (n = 1990) in this cohort study. The baseline scan was scored for the presence of ILA and patients were followed for up to 12 years. Data about all hospital admissions, primary healthcare visits and medicine prescriptions were collected from the Danish National Health Registries and used to determine the participants’ disease specific morbidity and healthcare utilisation using Cox proportional hazards models.

Results

The 332 (16.7%) participants with ILA were more likely to be diagnosed with one of several respiratory diseases, including interstitial lung disease (HR: 4.9, 95% CI: 1.8–13.3, p = 0.008), COPD (HR: 1.7, 95% CI: 1.2–2.3, p = 0.01), pneumonia (HR: 2.0, 95% CI: 1.4–2.7, p <  0.001), lung cancer (HR: 2.7, 95% CI: 1.8–4.0, p <  0.001) and respiratory failure (HR: 1.8, 95% CI: 1.1–3.0, p = 0.03) compared with participants without ILA. These findings were confirmed by increased hospital admission rates with these diagnoses and more frequent prescriptions for inhalation medicine and antibiotics in participants with ILA.

Conclusions

Individuals with ILA are more likely to receive a diagnosis and treatment for several respiratory diseases, including interstitial lung disease, COPD, pneumonia, lung cancer and respiratory failure during long-term follow-up.
Appendix
Available only for authorised users
Literature
1.
go back to reference Doyle TJ, Hunninghake GM, Rosas IO. Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med. 2012 Jun 1;185(11):1147–53.CrossRef Doyle TJ, Hunninghake GM, Rosas IO. Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med. 2012 Jun 1;185(11):1147–53.CrossRef
2.
go back to reference Sverzellati N, Guerci L, Randi G, Calabrò E, La Vecchia C, Marchianò A, et al. Interstitial lung diseases in a lung cancer screening trial. Eur Respir J. 2011 Aug;38(2):392–400.CrossRef Sverzellati N, Guerci L, Randi G, Calabrò E, La Vecchia C, Marchianò A, et al. Interstitial lung diseases in a lung cancer screening trial. Eur Respir J. 2011 Aug;38(2):392–400.CrossRef
3.
go back to reference Mackintosh JA, Marshall HM, Slaughter R, Reddy T, Yang IA, Bowman RV, et al. Interstitial lung abnormalities in the queensland lung cancer screening study: prevalence and progression over two years of surveillance. Intern Med J. 2018;1:843–9. Mackintosh JA, Marshall HM, Slaughter R, Reddy T, Yang IA, Bowman RV, et al. Interstitial lung abnormalities in the queensland lung cancer screening study: prevalence and progression over two years of surveillance. Intern Med J. 2018;1:843–9.
4.
go back to reference Tsushima K, Sone S, Yoshikawa S, Yokoyama T, Suzuki T, Kubo K. The radiological patterns of interstitial change at an early phase: over a 4-year follow-up. Respir Med. 2010;104(11):1712–21.CrossRef Tsushima K, Sone S, Yoshikawa S, Yokoyama T, Suzuki T, Kubo K. The radiological patterns of interstitial change at an early phase: over a 4-year follow-up. Respir Med. 2010;104(11):1712–21.CrossRef
5.
go back to reference Lederer DJ, Enright PL, Kawut SM, Hoffman EA, Hunninghake G, Van Beek EJR, et al. Cigarette smoking is associated with subclinical parenchymal lung disease: the multi-ethnic study of atherosclerosis (MESA)-lung study. Am J Respir Crit Care Med. 2009 Sep 1;180(5):407–14.CrossRef Lederer DJ, Enright PL, Kawut SM, Hoffman EA, Hunninghake G, Van Beek EJR, et al. Cigarette smoking is associated with subclinical parenchymal lung disease: the multi-ethnic study of atherosclerosis (MESA)-lung study. Am J Respir Crit Care Med. 2009 Sep 1;180(5):407–14.CrossRef
6.
go back to reference Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011 Mar 10;364(10):897–906.CrossRef Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011 Mar 10;364(10):897–906.CrossRef
7.
go back to reference Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA. 2016;315(7):672–81.CrossRef Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA. 2016;315(7):672–81.CrossRef
8.
go back to reference Jin GY, Lynch D, Chawla A, Garg K, Tammemagi MC, Sahin H, et al. Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology. 2013;268(2):563–71.CrossRef Jin GY, Lynch D, Chawla A, Garg K, Tammemagi MC, Sahin H, et al. Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology. 2013;268(2):563–71.CrossRef
9.
go back to reference Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.CrossRef Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.CrossRef
10.
go back to reference Rosas IO, Ren P, Avila NA, Chow CK, Franks TJ, Travis WD, et al. Early interstitial lung disease in familial pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176(7):698–705.CrossRef Rosas IO, Ren P, Avila NA, Chow CK, Franks TJ, Travis WD, et al. Early interstitial lung disease in familial pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176(7):698–705.CrossRef
11.
go back to reference Doyle TJ, Washko GR, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med. 2012;185(7):756–62.CrossRef Doyle TJ, Washko GR, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med. 2012;185(7):756–62.CrossRef
12.
go back to reference Araki T, Putman RK, Hatabu H, Gao W, Dupuis J, Latourelle JC, et al. Development and progression of interstitial lung abnormalities in the Framingham heart study. Am J Respir Crit Care Med. 2016;194(12):1514–22.CrossRef Araki T, Putman RK, Hatabu H, Gao W, Dupuis J, Latourelle JC, et al. Development and progression of interstitial lung abnormalities in the Framingham heart study. Am J Respir Crit Care Med. 2016;194(12):1514–22.CrossRef
13.
go back to reference Hoyer N, Wille MMW, Thomsen LH, Wilcke T, Dirksen A, Pedersen JH, et al. Interstitial lung abnormalities are associated with increased mortality in smokers. Respir Med. 2018;136:77–82.CrossRef Hoyer N, Wille MMW, Thomsen LH, Wilcke T, Dirksen A, Pedersen JH, et al. Interstitial lung abnormalities are associated with increased mortality in smokers. Respir Med. 2018;136:77–82.CrossRef
14.
go back to reference Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med. 1994;150(4):967–72.CrossRef Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med. 1994;150(4):967–72.CrossRef
15.
go back to reference Ley B, Collard HR. Epidemiology of idiopathic pulmonary fibrosis. Clin Epidemiol. 2013;5:483–92.CrossRef Ley B, Collard HR. Epidemiology of idiopathic pulmonary fibrosis. Clin Epidemiol. 2013;5:483–92.CrossRef
16.
go back to reference Hunninghake GM. Interstitial lung abnormalities: erecting fences in the path towards advanced pulmonary fibrosis. Thorax. 2019;74:506–11 thoraxjnl-2018-212446.CrossRef Hunninghake GM. Interstitial lung abnormalities: erecting fences in the path towards advanced pulmonary fibrosis. Thorax. 2019;74:506–11 thoraxjnl-2018-212446.CrossRef
17.
go back to reference Vaidya S, Hibbert CL, Kinter E, Boes S. Identification of key cost generating events for idiopathic pulmonary fibrosis: a systematic review. Lung. 2016;195:1–8.CrossRef Vaidya S, Hibbert CL, Kinter E, Boes S. Identification of key cost generating events for idiopathic pulmonary fibrosis: a systematic review. Lung. 2016;195:1–8.CrossRef
18.
go back to reference Raimundo K, Chang E, Broder MS, Alexander K, Zazzali J, Swigris JJ. Clinical and economic burden of idiopathic pulmonary fibrosis: a retrospective cohort study. BMC Pulm Med. 2016;16:2.CrossRef Raimundo K, Chang E, Broder MS, Alexander K, Zazzali J, Swigris JJ. Clinical and economic burden of idiopathic pulmonary fibrosis: a retrospective cohort study. BMC Pulm Med. 2016;16:2.CrossRef
19.
go back to reference Wu N, Yu YF, Chuang C-C, Wang R, Benjamin NN, Coultas DB. Healthcare resource utilization among patients diagnosed with idiopathic pulmonary fibrosis in the United States. J Med Econ. 2014;6998(April 2016):1–26. Wu N, Yu YF, Chuang C-C, Wang R, Benjamin NN, Coultas DB. Healthcare resource utilization among patients diagnosed with idiopathic pulmonary fibrosis in the United States. J Med Econ. 2014;6998(April 2016):1–26.
20.
go back to reference Wille MMW, Dirksen A, Ashraf H, Saghir Z, Bach KS, Brodersen J, et al. Results of the randomized Danish lung Cancer screening trial with focus on high-risk profiling. Am J Respir Crit Care Med. 2016;193(5):542–51.CrossRef Wille MMW, Dirksen A, Ashraf H, Saghir Z, Bach KS, Brodersen J, et al. Results of the randomized Danish lung Cancer screening trial with focus on high-risk profiling. Am J Respir Crit Care Med. 2016;193(5):542–51.CrossRef
21.
go back to reference Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948–68.CrossRef Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948–68.CrossRef
22.
go back to reference Wille MMW, Thomsen LH, Dirksen A, Petersen J, Pedersen JH, Shaker SB. Emphysema progression is visually detectable in low-dose CT in continuous but not in former smokers. Eur Radiol. 2014;24(11):2692–9.CrossRef Wille MMW, Thomsen LH, Dirksen A, Petersen J, Pedersen JH, Shaker SB. Emphysema progression is visually detectable in low-dose CT in continuous but not in former smokers. Eur Radiol. 2014;24(11):2692–9.CrossRef
23.
go back to reference Ghosh D, Lin DY. Marginal regression models for recurrent and terminal events. Stat Sin. 2002;12:663–88. Ghosh D, Lin DY. Marginal regression models for recurrent and terminal events. Stat Sin. 2002;12:663–88.
24.
go back to reference Podolanczuk AJ, Oelsner EC, Barr RG, Bernstein EJ, Hoffman EA, Easthausen IJ, et al. High-attenuation areas on chest computed tomography and clinical respiratory outcomes in community-dwelling adults. Am J Respir Crit Care Med. 2017;196(11):1434–42.CrossRef Podolanczuk AJ, Oelsner EC, Barr RG, Bernstein EJ, Hoffman EA, Easthausen IJ, et al. High-attenuation areas on chest computed tomography and clinical respiratory outcomes in community-dwelling adults. Am J Respir Crit Care Med. 2017;196(11):1434–42.CrossRef
25.
go back to reference Cottin V, Richeldi L. Neglected evidence in idiopathic pulmonary fibrosis and the importance of early diagnosis and treatment. Eur Respir Rev. 2014;23(131):106–10.CrossRef Cottin V, Richeldi L. Neglected evidence in idiopathic pulmonary fibrosis and the importance of early diagnosis and treatment. Eur Respir Rev. 2014;23(131):106–10.CrossRef
26.
go back to reference Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;27(1):136–42.CrossRef Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;27(1):136–42.CrossRef
27.
go back to reference Bozzetti F, Paladini I, Rabaiotti E, Franceschini A, Alfieri V, Chetta A, et al. Are interstitial lung abnormalities associated with COPD? A nested case-control study. Int J Chron Obstruct Pulmon Dis. 2016;11:1087–96.CrossRef Bozzetti F, Paladini I, Rabaiotti E, Franceschini A, Alfieri V, Chetta A, et al. Are interstitial lung abnormalities associated with COPD? A nested case-control study. Int J Chron Obstruct Pulmon Dis. 2016;11:1087–96.CrossRef
28.
go back to reference Ash SY, Harmouche R, Putman RK, Ross JC, Diaz AA, Hunninghake GM, et al. Clinical and genetic associations of objectively identified interstitial changes in smokers. Chest. 2017;152(4):780–91.CrossRef Ash SY, Harmouche R, Putman RK, Ross JC, Diaz AA, Hunninghake GM, et al. Clinical and genetic associations of objectively identified interstitial changes in smokers. Chest. 2017;152(4):780–91.CrossRef
29.
go back to reference Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532–55.CrossRef Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532–55.CrossRef
30.
go back to reference Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax. 2013;68(11):1057–65.CrossRef Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax. 2013;68(11):1057–65.CrossRef
31.
go back to reference Putman RK, Hunninghake GM, Dieffenbach PB, Barragan-Bradford D, Serhan K, Adams U, et al. Interstitial lung abnormalities are associated with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195(1):138–41.CrossRef Putman RK, Hunninghake GM, Dieffenbach PB, Barragan-Bradford D, Serhan K, Adams U, et al. Interstitial lung abnormalities are associated with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195(1):138–41.CrossRef
32.
go back to reference Nathan SD, Meyer KC. IPF clinical trial design and endpoints. Curr Opin Pulm Med. 2014;20(5):463–71.CrossRef Nathan SD, Meyer KC. IPF clinical trial design and endpoints. Curr Opin Pulm Med. 2014;20(5):463–71.CrossRef
33.
go back to reference Raghu G, Collard HR, Anstrom KJ, Flaherty KR, Fleming TR, King TE, et al. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Respir Crit Care Med. 2012;185(10):1044–8.CrossRef Raghu G, Collard HR, Anstrom KJ, Flaherty KR, Fleming TR, King TE, et al. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Respir Crit Care Med. 2012;185(10):1044–8.CrossRef
34.
go back to reference Sprunger DB, Olson AL, Huie TJ, Fernandez-Perez ER, Fischer A, Solomon JJ, et al. Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J. 2012;39(1):125–32.CrossRef Sprunger DB, Olson AL, Huie TJ, Fernandez-Perez ER, Fischer A, Solomon JJ, et al. Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J. 2012;39(1):125–32.CrossRef
35.
go back to reference Ungprasert P, Crowson CS, Matteson EL. Association of Sarcoidosis with Increased Risk of VTE: a population-based study, 1976 to 2013. Chest. 2017;151(2):425–30.CrossRef Ungprasert P, Crowson CS, Matteson EL. Association of Sarcoidosis with Increased Risk of VTE: a population-based study, 1976 to 2013. Chest. 2017;151(2):425–30.CrossRef
36.
go back to reference Sode BF, Dahl M, Nielsen SF, Nordestgaard BG. Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med. 2010;181(10):1085–92.CrossRef Sode BF, Dahl M, Nielsen SF, Nordestgaard BG. Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med. 2010;181(10):1085–92.CrossRef
37.
go back to reference Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med. 2008;178(12):1257–61.CrossRef Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med. 2008;178(12):1257–61.CrossRef
38.
go back to reference Wells AU, Kokosi MA. Subclinical interstitial lung abnormalities: toward the early detection of idiopathic pulmonary fibrosis? Am J Respir Crit Care Med. 2016;194(12):1445–6.CrossRef Wells AU, Kokosi MA. Subclinical interstitial lung abnormalities: toward the early detection of idiopathic pulmonary fibrosis? Am J Respir Crit Care Med. 2016;194(12):1445–6.CrossRef
39.
go back to reference Podolanczuk AJ, Oelsner EC, Barr RG, Hoffman EA, Armstrong HF, Austin JHM, et al. High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study. Eur Respir J. 2016;48(5):1442–52.CrossRef Podolanczuk AJ, Oelsner EC, Barr RG, Hoffman EA, Armstrong HF, Austin JHM, et al. High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study. Eur Respir J. 2016;48(5):1442–52.CrossRef
40.
go back to reference Walsh SLF, Wells AU, Desai SR, Poletti V, Piciucchi S, Dubini A, et al. Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study. Lancet Respir Med. 2016;2600(16):1–9. Walsh SLF, Wells AU, Desai SR, Poletti V, Piciucchi S, Dubini A, et al. Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study. Lancet Respir Med. 2016;2600(16):1–9.
Metadata
Title
Increased respiratory morbidity in individuals with interstitial lung abnormalities
Authors
Nils Hoyer
Laura H. Thomsen
Mathilde M. W. Wille
Torgny Wilcke
Asger Dirksen
Jesper H. Pedersen
Zaigham Saghir
Haseem Ashraf
Saher B. Shaker
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-1107-0

Other articles of this Issue 1/2020

BMC Pulmonary Medicine 1/2020 Go to the issue