Clinical and Functional Characteristics of Patients with Unclassifiable Interstitial Lung Disease (uILD): Long-Term Follow-Up Data from European IPF Registry (eurIPFreg)
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Collection
2.2. Quality of Data and Statistical Analysis
- Age (pts. younger and older than 60 years)
- Annual decline in FVC in % pred.
- Smoking history
- Gender–Age–Physiology Index (GAP) at baseline (GAP stages I, II, and III). GAP score is a clinical predictor model of disease progression and mortality in ILD based on sex, age, and pulmonary function [20].
- Diffusing capacity of the lung for carbon monoxide (DLco) in % pred. at baseline
- Six minutes walking distance (6MWD) in meters at baseline
- UIP pattern in HRCT at the timepoint of a diagnosis; additionally, the whole cohort was retrospectively evaluated, applying Fleischner Society criteria [21].
3. Results
3.1. Demographics and Descriptive Characteristic of uILD Cohort
3.2. Comorbidities in uILD
3.3. Diagnosis of uILD
3.4. Pulmonary Function Test (PFT) Data at Baseline
3.5. HRCT in uILD Patients
3.6. Bronchoscopy, Bronchoalveolar Lavage (BAL), and Lung Biopsy in uILD
3.7. Impairment of HRQoL in uILD Patients
3.8. Treatment for uILD
3.9. Risk Factors for PFT Decline and Outcome Analyses
4. Discussion
5. Study Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Availability of data and materials
Competing interests
Trial registration
Copyright and license agreement
References
- Antoniou, K.M.; Margaritopoulos, G.A.; Tomassetti, S.; Bonella, F.; Costabel, U.; Poletti, V. Interstitial lung disease. Eur. Respir. Rev. 2014, 23, 40–54. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cottin, V.; Hirani, N.A.; Hotchkin, D.L.; Nambiar, A.M.; Ogura, T.; Otaola, M.; Skowasch, D.; Park, J.S.; Poonyagariyagorn, H.K.; Wuyts, W.; et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur. Respir. Rev. 2018, 27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wong, A.W.; Ryerson, C.J.; Guler, S.A. Progression of fibrosing interstitial lung disease. Respir. Res. 2020, 21, 32. [Google Scholar] [CrossRef] [PubMed]
- Barratt, S.L.; Creamer, A.; Hayton, C.; Chaudhuri, N. Idiopathic Pulmonary Fibrosis (IPF): An Overview. J. Clin. Med. 2018, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guenther, A.; Krauss, E.; Tello, S.; Wagner, J.; Paul, B.; Kuhn, S.; Maurer, O.; Heinemann, S.; Costabel, U.; Barbero, M.A.N.; et al. The European IPF registry (eurIPFreg): baseline characteristics and survival of patients with idiopathic pulmonary fibrosis. Respir. Res. 2018, 19, 141. [Google Scholar] [CrossRef] [Green Version]
- Loeh, B.; Brylski, L.T.; von der Beck, D.; Seeger, W.; Krauss, E.; Bonniaud, P.; Crestani, B.; Vancheri, C.; Wells, A.U.; Markart, P.; et al. Lung CT Densitometry in Idiopathic Pulmonary Fibrosis for the Prediction of Natural Course, Severity, and Mortality. Chest 2019, 155, 972–981. [Google Scholar] [CrossRef]
- Witt, S.; Krauss, E.; Barbero, M.A.N.; Müller, V.; Bonniaud, P.; Vancheri, C.; Wells, A.U.; Vasakova, M.; Pesci, A.; Klepetko, W.; et al. Psychometric properties and minimal important differences of SF-36 in Idiopathic Pulmonary Fibrosis. Respir. Res. 2019, 20, 47. [Google Scholar] [CrossRef] [Green Version]
- Neurohr, C.; Behr, J. Changes in the current classification of IIP: A critical review. Respirology 2015, 20, 699–704. [Google Scholar] [CrossRef] [Green Version]
- Oliveira, D.S.; Araújo Filho, J.d.A.; Paiva, A.F.L.; Ikari, E.S.; Chate, R.C.; Nomura, C.H. Idiopathic interstitial pneumonias: review of the latest American Thoracic Society/European Respiratory Society classification. Radiol. Bras. 2018, 51, 321–327. [Google Scholar] [CrossRef]
- Aburto, M.; Herráez, I.; Iturbe, D.; Jiménez-Romero, A. Diagnosis of Idiopathic Pulmonary Fibrosis: Differential Diagnosis. Med. Sci. (Basel) 2018, 6. [Google Scholar] [CrossRef] [Green Version]
- Hyldgaard, C.; Bendstrup, E.; Wells, A.U.; Hilberg, O. Unclassifiable interstitial lung diseases: Clinical characteristics and survival. Respirology 2017, 22, 494–500. [Google Scholar] [CrossRef]
- Brown, A.W. Unclassifiable Interstitial Lung Disease: Time to Shrink the Black Box. Ann. Am. Thorac. Soc. 2018, 15, 806–807. [Google Scholar] [CrossRef] [PubMed]
- Guler, S.A.; Ryerson, C.J. Unclassifiable interstitial lung disease: from phenotyping to possible treatments. Curr. Opin. Pulm. Med. 2018, 24, 461–468. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leung, S.C.; Churg, A.M.; Leipsic, J.A.; Levy, R.D.; Wilcox, P.G.; Ryerson, C.J. Unclassifiable interstitial lung disease: an unresolved diagnostic dilemma. Respirol. Case Rep. 2015, 3, 85–88. [Google Scholar] [CrossRef] [PubMed]
- Jones, K.D. Unclassifiable interstitial lung disease: a pathologist’s perspective. Eur. Respir. Rev. 2018, 27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nakamura, Y.; Sugino, K.; Kitani, M.; Hebisawa, A.; Tochigi, N.; Homma, S. Clinico-radio-pathological characteristics of unclassifiable idiopathic interstitial pneumonias. Respir. Investig. 2018, 56, 40–47. [Google Scholar] [CrossRef] [PubMed]
- Luppi, F.; Wells, A.U. Interstitial pneumonitis with autoimmune features (IPAF): a work in progress. Eur. Respir. J. 2016, 47, 1622–1624. [Google Scholar] [CrossRef] [Green Version]
- Collins, B.F.; Spiekerman, C.F.; Shaw, M.A.; Ho, L.A.; Hayes, J.; Spada, C.A.; Stamato, C.M.; Raghu, G. Idiopathic Interstitial Pneumonia Associated With Autoantibodies: A Large Case Series Followed Over 1 Year. Chest 2017, 152, 103–112. [Google Scholar] [CrossRef]
- Fischer, A.; Antoniou, K.M.; Brown, K.K.; Cadranel, J.; Corte, T.J.; Du Bois, R.M.; Lee, J.S.; Leslie, K.O.; Lynch, D.A.; Matteson, E.L.; et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur. Respir. J. 2015, 46, 976–987. [Google Scholar] [CrossRef] [Green Version]
- Ryerson, C.J.; Vittinghoff, E.; Ley, B.; Lee, J.S.; Mooney, J.J.; Jones, K.D.; Elicker, B.M.; Wolters, P.J.; Koth, L.L.; King, T.E.; et al. Predicting survival across chronic interstitial lung disease: the ILD-GAP model. Chest 2014, 145, 723–728. [Google Scholar] [CrossRef]
- Raghu, G.; Rochwerg, B.; Zhang, Y.; Garcia, C.A.C.; Azuma, A.; Behr, J.; Brozek, J.L.; Collard, H.R.; Cunningham, W.; Homma, S.; et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am. J. Respir. Crit. Care Med. 2015, 192, e3-19. [Google Scholar] [CrossRef] [PubMed]
- Raghu, G.; Remy-Jardin, M.; Myers, J.L.; Richeldi, L.; Ryerson, C.J.; Lederer, D.J.; Behr, J.; Cottin, V.; Danoff, S.K.; Morell, F.; et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am. J. Respir. Crit. Care Med. 2018, 198, e44–e68. [Google Scholar] [CrossRef] [PubMed]
- Travis, W.D.; Costabel, U.; Hansell, D.M.; King, T.E.; Lynch, D.A.; Nicholson, A.G.; Ryerson, C.J.; Ryu, J.H.; Selman, M.; Wells, A.U.; et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 2013, 188, 733–748. [Google Scholar] [CrossRef] [PubMed]
- Raghu, G.; Collard, H.R.; Egan, J.J.; Martinez, F.J.; Behr, J.; Brown, K.K.; Colby, T.V.; Cordier, J.-F.; Flaherty, K.R.; Lasky, J.A.; 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, 788–824. [Google Scholar] [CrossRef] [PubMed]
- Mavroudi, M.; Papakosta, D.; Kontakiotis, T.; Domvri, K.; Kalamaras, G.; Zarogoulidou, V.; Zarogoulidis, P.; Latka, P.; Huang, H.; Hohenforst-Schmidt, W.; et al. Sleep disorders and health-related quality of life in patients with interstitial lung disease. Sleep Breath. 2018, 22, 393–400. [Google Scholar] [CrossRef] [PubMed]
- Traila, D.; Oancea, C.; Tudorache, E.; Mladinescu, O.F.; Timar, B.; Tudorache, V. Clinical profile of unclassifiable interstitial lung disease: Comparison with chronic fibrosing idiopathic interstitial pneumonias. J. Int. Med. Res. 2018, 46, 448–456. [Google Scholar] [CrossRef] [PubMed]
- Atienza-Mateo, B.; Remuzgo-Martínez, S.; Mora Cuesta, V.M.; Iturbe-Fernández, D.; Fernández-Rozas, S.; Prieto-Peña, D.; Calderón-Goercke, M.; Corrales, A.; Blanco Rodríguez, G.B.; Gómez-Román, J.J.; et al. The Spectrum of Interstitial Lung Disease Associated with Autoimmune Diseases: Data of a 3.6-Year Prospective Study from a Referral Center of Interstitial Lung Disease and Lung Transplantation. J. Clin. Med. 2020, 9. [Google Scholar] [CrossRef]
- Ryerson, C.J.; Urbania, T.H.; Richeldi, L.; Mooney, J.J.; Lee, J.S.; Jones, K.D.; Elicker, B.M.; Koth, L.L.; King, T.E.; Wolters, P.J.; et al. Prevalence and prognosis of unclassifiable interstitial lung disease. Eur. Respir. J. 2013, 42, 750–757. [Google Scholar] [CrossRef] [Green Version]
- Troy, L.K.; Hetzel, J. Lung cryobiopsy and interstitial lung disease: What is its role in the era of multidisciplinary meetings and antifibrotics? Respirology 2020. [Google Scholar] [CrossRef]
- Chaudhuri, N.; Spencer, L.; Greaves, M.; Bishop, P.; Chaturvedi, A.; Leonard, C. A Review of the Multidisciplinary Diagnosis of Interstitial Lung Diseases: A Retrospective Analysis in a Single UK Specialist Centre. J. Clin. Med. 2016, 5. [Google Scholar] [CrossRef] [Green Version]
- Skolnik, K.; Ryerson, C.J. Unclassifiable interstitial lung disease: A review. Respirology 2016, 21, 51–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ryerson, C.J.; Corte, T.J.; Lee, J.S.; Richeldi, L.; Walsh, S.L.F.; Myers, J.L.; Behr, J.; Cottin, V.; Danoff, S.K.; Flaherty, K.R.; et al. A Standardized Diagnostic Ontology for Fibrotic Interstitial Lung Disease. An International Working Group Perspective. Am. J. Respir. Crit. Care Med. 2017, 196, 1249–1254. [Google Scholar] [CrossRef] [PubMed]
- Behr, J.; Neuser, P.; Prasse, A.; Kreuter, M.; Rabe, K.; Schade-Brittinger, C.; Wagner, J.; Günther, A. Exploring efficacy and safety of oral Pirfenidone for progressive, non-IPF lung fibrosis (RELIEF) - a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial. BMC Pulm. Med. 2017, 17, 122. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guler, S.A.; Ellison, K.; Algamdi, M.; Collard, H.R.; Ryerson, C.J. Heterogeneity in Unclassifiable Interstitial Lung Disease. A Systematic Review and Meta-Analysis. Ann. Am. Thorac. Soc. 2018, 15, 854–863. [Google Scholar] [CrossRef] [PubMed]
- Lynch, D.A.; Sverzellati, N.; Travis, W.D.; Brown, K.K.; Colby, T.V.; Galvin, J.R.; Goldin, J.G.; Hansell, D.M.; Inoue, Y.; Johkoh, T.; et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir. Med. 2018, 6, 138–153. [Google Scholar] [CrossRef]
- de Sadeleer, L.J.; Goos, T.; Yserbyt, J.; Wuyts, W.A. Towards the Essence of Progressiveness: Bringing Progressive Fibrosing Interstitial Lung Disease (PF-ILD) to the Next Stage. J. Clin. Med. 2020, 9. [Google Scholar] [CrossRef]
Demographic Parameters | Values |
---|---|
Male (n, %) | 81, 57.9% |
BMI (mean value + SD (kg-m²)), | 24.2 ± 4.8 |
range (minimum- maximum, kg-m²) | 16–32 |
Age at enrollment into the registry mean value + SD (years) | 68.2 ± 11.0 |
Time between onset of symptoms and inclusion into eurIPFreg (mean value ± SD (months)) | 6.7 ± 12.6 |
Smokers (yes, no, missing data in %) | 71%, 54%, 15% |
Kind of smoker (current, former, never smoked, missing data, %) | 7.1%, 43.6%, 38.6%, 10.7% |
Number of pack-years (mean value ± SD) | 28.5 ± 20.2 |
GAP Stage I /II /III (n, %) | 43, 30.1%/45, 31.5%/18, 12.6% |
Velcro rales at auscultation (n, %) | 103, 73.6% |
Parameters | Mean Value ± SD |
---|---|
VC (% pred.) | 69.3 ± 21.3 |
FVC (% pred.) | 67.8 ± 22.1 |
FEV 1 (% pred.) | 76.3 ± 55.6 |
FEV 1% FVC (% pred.) | 106.0 ± 16.8 |
RV (% pred.) | 94.3 ± 60.8 |
TLC (% pred.) | 74.6 ± 22.7 |
DLco (% pred.) | 43.8 ± 26.3 |
pO2 (mm Hg) at rest | 70.7 ± 12.6 |
pCO2 (mm Hg) at rest | 38.5 ± 4.6 |
6 MWD (m) | 367.8 ± 121.9 |
Patients receiving LTOT (n;%) | 41; 29.3 |
Oxygen flow at rest (l/min) | 3.0 ± 1.8 |
Oxygen flow at exertion (l/min) | 4.2 ± 2.5 |
HRQoL Variables | Mean Value | Min | Maximum | SD |
---|---|---|---|---|
Physical functioning % | 39.5 | 0 | 100 | 29.1 |
Role limitations due to physical health % | 33.5 | 0 | 100 | 42.0 |
Role limitations due to emotional problems % | 62.0 | 0 | 100 | 46.4 |
Energy/fatigue | 40.6 | 0 | 87.0 | 21.6 |
Emotional well-being % | 61.9 | 0 | 100 | 21.2 |
Social functioning % | 60.1 | 0 | 100 | 30.9 |
Pain % | 62.9 | 0 | 100 | 33.1 |
General health % | 40.2 | 0 | 85 | 18.7 |
Health change % | 30.3 | 0 | 100 | 23.5 |
SF 36 mean value | 48.0 | 2.78 | 88.2 | 21.1 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Krauss, E.; El-Guelai, M.; Pons-Kuehnemann, J.; Dartsch, R.C.; Tello, S.; Korfei, M.; Mahavadi, P.; Breithecker, A.; Fink, L.; Stoehr, M.; et al. Clinical and Functional Characteristics of Patients with Unclassifiable Interstitial Lung Disease (uILD): Long-Term Follow-Up Data from European IPF Registry (eurIPFreg). J. Clin. Med. 2020, 9, 2499. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082499
Krauss E, El-Guelai M, Pons-Kuehnemann J, Dartsch RC, Tello S, Korfei M, Mahavadi P, Breithecker A, Fink L, Stoehr M, et al. Clinical and Functional Characteristics of Patients with Unclassifiable Interstitial Lung Disease (uILD): Long-Term Follow-Up Data from European IPF Registry (eurIPFreg). Journal of Clinical Medicine. 2020; 9(8):2499. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082499
Chicago/Turabian StyleKrauss, Ekaterina, Mustapha El-Guelai, Joern Pons-Kuehnemann, Ruth C. Dartsch, Silke Tello, Martina Korfei, Poornima Mahavadi, Andreas Breithecker, Ludger Fink, Mark Stoehr, and et al. 2020. "Clinical and Functional Characteristics of Patients with Unclassifiable Interstitial Lung Disease (uILD): Long-Term Follow-Up Data from European IPF Registry (eurIPFreg)" Journal of Clinical Medicine 9, no. 8: 2499. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082499