Introduction: Interstitial lung diseases (ILDs) are associated with a high economic burden, yet prospective data of the German healthcare system are sparse. Objective: We assessed average ILD-related costs of pharmacological and non-pharmacological (hospitalizations, outpatient, rehabilitation, physiotherapy, and medical aids) interventions in ILD. Methods: We used data from the multicenter, observational, prospective Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases registry to evaluate adjusted per capita costs and cost drivers for ILD-related healthcare costs over 4 years, using generalized estimating equation regression models. Results: Idiopathic pulmonary fibrosis (IPF) had the highest annual pharmacological costs >EUR 21,000, followed by connective tissue disease-associated ILD (CTD-ILD) averaging EUR 6,000. Other idiopathic interstitial pneumonias and hypersensitivity pneumonitis averaged below EUR 2,400 and sarcoidosis below EUR 400. There were no significant differences in pharmacological costs over time. Trends in non-pharmacological costs were statistically significant. At year 1, CTD-ILD had the highest costs (EUR 7,700), while sarcoidosis had the lowest (EUR 2,547). By year 4, these declined to EUR 3,218 and EUR 232, respectively. Regarding cost drivers, the ILD subtype had the greatest impact with 75 times higher pharmacological costs in IPF and 4 times higher non-pharmacological costs in CTD-ILD, compared to the reference. Pulmonary hypertension (PH) and gastroesophageal reflux disease (GERD) triggered higher pharmacological costs, and higher values of forced vital capacity % predicted were associated with lower pharmacological and non-pharmacological costs. Conclusion: Stabilizing lung function and reducing the impact of PH and GERD are crucial in reducing the economic burden of ILD. There is an urgent need for effective treatment options, especially in CTD-ILD.

1.
Antoniou KM, Margaritopoulos GA, Tomassetti S, Bonella F, Costabel U, Poletti V. Interstitial lung disease.
Eur Respir Rev
. 2014 Mar;23(131):40–54.
2.
Caruana LB, Redwine GD, Rohde RE, Russian CJ. A prospective study of patients diagnosed with sarcoidosis: factors – environmental exposure, health assessment, and genetic outlooks. Sarcoidosis, Vasc Diffus lung.
Dis Off J WASOG
. 2019 Sep;36(3):228–42.
3.
Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M, et al. Diagnosis of hypersensitivity pneumonitis in adults: an official ATS/JRS/ALAT clinical practice guideline.
Am J Respir Crit Care Med
. 2020 Aug;202(3):E36–69.
4.
Meyer KC. Diagnosis and management of interstitial lung disease.
Transl Respir Med
. 2014 Dec;2(1):4.
5.
Ryerson CJ, Vittinghoff E, Ley B, Lee JS, Mooney JJ, Jones KD, et al. Predicting survival across chronic interstitial lung disease: the ILD-GAP model.
Chest
. 2014 Apr;145(4):723–8.
6.
Margaritopoulos GA, Antoniou KM, Wells AU. Comorbidities in interstitial lung diseases.
Eur Respir Rev
. 2017 Jan;26(143):160027.
7.
Schwarzkopf L, Witt S, Waelscher J, Polke M, Kreuter M. Associations between comorbidities, their treatment and survival in patients with interstitial lung diseases: a claims data analysis.
Respir Res
. 2018 Apr;19(1):73.
8.
King CS, Nathan SD. Pulmonary hypertension due to interstitial lung disease.
Curr Opin Pulm Med
. 2019;25(5):459–67.
9.
Kalchiem-Dekel O, Galvin JR, Burke AP, Atamas SP, Todd NW. Interstitial lung disease and pulmonary fibrosis: a practical approach for general medicine physicians with focus on the medical history.
J Clin Med
. 2018 Nov;7(12):476.
10.
Kreuter M, Herth FJF, Wacker M, Leidl R, Hellmann A, Pfeifer M, et al. Exploring clinical and epidemiological characteristics of interstitial lung diseases: rationale, aims, and design of a nationwide prospective registry-the EXCITING-ILD registry.
Biomed Res Int
. 2015;2015:123876.
11.
Kreuter M, Herth F, Wacker M, Witt S, Kabitz H, Hagmeyer L, et al. Diagnostik und Therapie von Patienten mit interstitiellen Lungenerkrankungen in Deutschland – das EXCITING ILD Register.
Pneumologie
. 2018 Mar;72(S 01):S28–28.
12.
Orbell S, Schneider H, Esbitt S, Gonzalez JS, Gonzalez JS, Shreck E, et al.
Health care utilization. Encyclopedia of behavioral medicine
. New York, NY: Springer New York; 2013. p. 909–10.
13.
Janssen LMM, Drost RMWA, Paulus ATG, Garfield K, Hollingworth W, Noble S, et al. Aspects and challenges of resource use measurement in health economics: towards a comprehensive measurement framework.
Pharmacoeconomics
. 2021 Sep;39(9):983–93.
14.
Bock JO, Brettschneider C, Seidl H, Bowles D, Holle R, Greiner W, et al. Ermittlung standardisierter Bewertungssätze aus gesellschaftlicher Perspektive für die gesundheitsökonomische Evaluation.
Das Gesundheitswes
. 2014 Jul;77(01):53–61.
15.
Wong AW, Ryerson CJ, Guler SA. Progression of fibrosing interstitial lung disease.
Respir Res
. 2020 Jan;21(1):32.
16.
Laird NM, Ware JH. Random-effects models for longitudinal data.
Biometrics
. 1982 Dec;38(4):963.
17.
Buntin MB, Zaslavsky AM. Too much ado about two-part models and transformation? Comparing methods of modeling Medicare expenditures.
J Health Econ
. 2004 May;23(3):525–42.
18.
Afifi AA, Kotlerman JB, Ettner SL, Cowan M. Methods for improving regression analysis for skewed continuous or counted responses.
Annul Rev Public Health
. 2007;28:95–111.
19.
Albera C, Costabel U, Fagan EA, Glassberg MK, Gorina E, Lancaster L, et al. Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function.
Eur Respir J
. 2016 Sep;48(3):843–51.
20.
Richeldi L, Cottin V, du Bois RM, Selman M, Kimura T, Bailes Z, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: combined evidence from the TOMORROW and INPULSIS® trials.
Respir Med
. 2016 Apr;113:74–9.
21.
Maqhuzu PN, Kreuter M, Bahmer T, Kahn N, Claussen M, Holle R, et al. Cost drivers in the pharmacological treatment of interstitial lung disease.
Respir Res
. 2021 Dec;22(1):218.
22.
Vaidya S, Hibbert CL, Kinter E, Boes S. Identification of key cost generating events for idiopathic pulmonary fibrosis: a systematic review.
Lung
. 2017 Feb;195(1):1–8.
23.
Corral M, Chang E, Broder MS, Gokhale S, Reddy SR. Healthcare use and costs among Medicare enrollees on pirfenidone versus nintedanib for idiopathic pulmonary fibrosis.
J Comp Eff Res
. 2020 Sep;9(13):933–43.
24.
Frank AL, Kreuter M, Schwarzkopf L. Economic burden of incident interstitial lung disease (ILD) and the impact of comorbidity on costs of care.
Respir Med
. 2019 Jun;152:25–31.
25.
Yamazaki R, Nishiyama O, Saeki S, Sano H, Iwanaga T, Tohda Y. Characteristics of patients with chronic idiopathic interstitial pneumonia undergoing repeated respiratory-related hospitalizations: a retrospective cohort study.
PLoS One
. 2020;15(4):e0232212.
26.
Wells AU, Flaherty KR, Brown KK, Inoue Y, Devaraj A, Richeldi L, et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases–subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial.
Lancet Respir Med
. 2020 May;8(5):453–60.
27.
Olson AL, Brown KK, Fischer A. Connective tissue disease-associated lung disease.
Immunol Allergy Clin North Am
. 2012 Nov;32(4):513–36.
28.
Schulte JJ, Husain AN. Connective tissue disease related interstitial lung disease.
Surg Pathol Clin
. 2020 Mar;13(1):165–88.
29.
Antin-Ozerkis D, Hinchcliff M. Connective tissue disease-associated interstitial lung disease: evaluation and management.
Clin Chest Med
. 2019;40(3):617–36.
30.
Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update.
Ann Rheum Dis
. 2020 Jun;79(6):S685–99.
31.
Atzeni F, Gerardi MC, Barilaro G, Masala IF, Benucci M, Sarzi-Puttini P. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review.
Expert Rev Clin Immunol
. 2018 Jan;14(1):69–82.
32.
Šterclová M. Extrinsic allergic alveolitis: minimum for clinical practice.
Vnitr Lek
. 2017;63(11):802–6.
33.
Baughman RP, Field S, Costabel U, Crystal RG, Culver DA, Drent M, et al. Sarcoidosis in America: analysis based on health care use.
Ann Am Thorac Soc
. 2016;13(8):1244–52.
34.
Gade Sikjær M, Hilberg O, Ibsen R, Bock K, Løkke A. Direct and indirect economic and health consequences related to sarcoidosis in Denmark: a national register-based study.
Respir Med
. 2019;152:7–13.
35.
Ungprasert P, Ryu JH, Matteson EL. Clinical manifestations, diagnosis, and treatment of sarcoidosis.
Mayo Clin Proc Innov Qual Outcomes
. 2019 Sep;3(3):358–75.
36.
Pleasants R, Tighe RM. Management of idiopathic pulmonary fibrosis.
Ann Pharmacother
. 2019 Dec;53(12):1238–48.
37.
Sekine A, Wasamoto S, Hagiwara E, Yamakawa H, Ikeda S, Okabayashi H, et al. Beneficial impact of weight loss on respiratory function in interstitial lung disease patients with obesity.
Respir Investig
. 2021 Mar;59(2):247–51.
38.
Jouneau S, Crestani B, Thibault R, Lederlin M, Vernhet L, Valenzuela C, et al. Analysis of body mass index, weight loss and progression of idiopathic pulmonary fibrosis.
Respir Res
. 2020 Dec;21(1):312.
39.
Sangani RG, Ghio AJ, Mujahid H, Patel Z, Catherman K, Wen S, et al. Outcomes of idiopathic pulmonary fibrosis improve with obesity: a rural appalachian experience.
South Med J
. 2021 Jul;114(7):424–31.
40.
Kronzer VL, Huang W, Dellaripa PF, Huang S, Feathers V, Lu B, et al. Lifestyle and clinical risk factors for incident rheumatoid arthritis-associated interstitial lung disease.
J Rheumatol
. 2021;48(5):656–63.
41.
Kondoh Y, Taniguchi H, Ebina M, Azuma A, Ogura T, Taguchi Y, et al. Risk factors for acute exacerbation of idiopathic pulmonary fibrosis-extended analysis of pirfenidone trial in Japan.
Respir Investig
. 2015;53(6):271–8.
42.
Ley B, Collard HR, King TE. Clinical course and prediction of survival in idiopathic pulmonary fibrosis.
Am J Respir Crit Care Med
. 2011 Feb;183(4):431–40.
43.
Greiner GG, Schwettmann L, Goebel J, Maier W. Primary care in Germany: access and utilisation–A cross-sectional study with data from the German Socio-Economic Panel (SOEP).
BMJ Open
. 2018 Oct;8(10):e021036.
44.
Demedts M, Wells AU, Antó JM, Costabel U, Hubbard R, Cullinan P, et al. Interstitial lung diseases: an epidemiological overview.
Eur Respir Journal, Suppl.
. 2001;32(32):2–16.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.