A modified Delphi exercise in physician-perceived risk factors for drug-induced pneumotoxicity in patients with rheumatological disease
Authors: Cartlidge Manjit K. , Brown Kevin K. , Chaudhuri Nazia , Corte Tamera J. , Dieudé Phillipe , John Levin , Kelly Clive , Khanna Dinesh , McRorie Euan , Nicol Lisa , Stewart Gareth , Walsh Simon L. F. , Wijsenbeek Marlies , Hirani Nik ,   PASSWRD participants, Chalmers George W , Golla Janardhana , Hyldgaard Charlotte , Chaigne Benjamin , López Miguel Patricia , Bendstrup Elisabeth , Carbone Roberto G , Selva-O’Callaghan Albert , Chaudhury Nazia , Selvi Enrico , Russell Tonya , Ferreira Pedro , Mukherjee Suranjan , Kah-Lai Leong Carrie , Alfaro Tiago , Carreira Patricia E , Dhasmana Devesh J , Cameli Paolo , Wuyts Wim A , Bennett David , Novelli Luca , Patel Divya C , Fahim Ahmed , Wilsher Margaret L , Shifren Adrian , Padilla Maria L. , Muller Carolina , Avdeev Sergey , Dzhus Marta , Papanikolaou Ilias C , Tanino Yoshinori , Fretheim Harvard , Balbir-Gurman Alexandra , Vicens-Zygmunt Vanesa , Jones Mark G , Perch Michael , Brito de Araujo Daniel , Conticini Edoardo , Keshavan V , Izumi Shinyu , Kalluri Meena , Hajari Case Amy , Turner Alice M , Baresic Marko , Koduri Gouri M , Amaral Alexandre Franco , Eiger Glenn , Salinas Mauricio , Nunes Mario Sergio , Chai Gin Tsen , Scarlata Simone , Radzikowska Elżbieta , Maher Toby M , Benucci Maurizio , Myall Katherine J , Davidsen Jesper Rømhild , Launay David , Culver Dr Emma L , Castro Horacio Matias , Devi HJ Gayathri , Naclerio Caterina , Walker Ulrich A. , Chua Felix , Garcia Gonzalez Estrella , Montoya Sandra Fabiana , Carty Sara Madelaine , Judge Eoin P , O’Beirne Sarah L , Johannson Kerri A , Camus Philippe , Bilaceroglu Semra , Gardiner Philip V , Nicol Lisa M , Garcia Martos Álvaro , Castillo Diego , Lipchik Randolph J , Drakopanagiotakis Fotio , Vikse Jens , Ramirez Maria Teresa Rio , Antin-Ozerkis Danielle , Grainger Rebecca , Stewart Gareth A , Borie Raphael , Agrawal Aditya , Ceribelli Angela , Guillen Alfredo , Saiton Shigeki , Tomii Keisuke , Luckhardt Tracy , Highland Kristin B , Gheorghiu Ana Maria , Kolb Martin , Cobilinschi Claudia , Jones Richard Mathew , Campainha Sergio , Rosato Edoardo , Foti Rosario , Juge Pierre-Antoine , Patil Shital , Busaid Nasser Al , Rednic Simona , Garzanova Liudmila , Solomon Joshua J , Kalyoncu Ali Fuat , Ross Alessandra Della , Perkovic Dijana , Kabasakal Yasemin , Mogulkoc Nesrin , Low Su-Ying , Godoy  , Spencer Lisa G , Delobbe Alain , Toma Claudia Lucia , Hysa Elvis , Reza Beiga Davide Mohammed , Waseda Yuko , MdC Venero , Parfrey Helen , Derrett-Smith Emma , Grazzini Silvia , Ryerson Christopher J , Iudici Michele , Nossent E J , Campochiaro Corrado , Al-farttoosi Abdulla , Manfredi Andreina , Robles-Perez Alejandro , van der Lee Ivo , Hirani Nik , Sulli Alberto , Marovic Kristina Frketic , Saunders Peter , Bernardino Vera , Matsuda Toshiaki , Rivera-Ortega Pilar , Berlengiero Virginia , Morovic-Vergles Jadranka , Kiyan Esen , Balestro Elisabetta , Gabrielli Armando , Sebastiani Marco , Confalonieri Paola , Crestani Bruno , Blum HC , Gudmundsson Gunnar , Crawshaw Anjali , Robles-Perez Alejandro , Stebbings Simon M , Sehga Sameep , Assaya Deborah , Nunes Hilario 
Published: October 2024

Abstract
Background
Drugs used to treat rheumatic disease are associated with pneumotoxicity (drug-induced lung disease), but little is known about associated risk factors.

Aim
To determine expert physician-perceived risk factors for developing pneumotoxicity in patients with rheumatologic conditions.

Methods
A modified international 3-tier Delphi exercise was performed. Tier 1 determined patient and drug variables that physicians perceive to be risk factors. Tier 2 determined degree of risk associated with the Tier-1 derived variables. Tier 3 aimed to internally validate and stratify exemplar cases into risk categories.

Results
134 pulmonologists and 49 rheumatologists responded to Tier 1;157 physicians completed all tiers. Perceived risk factors included: drug type; history of previous pneumotoxicity; age; smoking; underlying rheumatic disease type and activity; renal function; pulmonary hypertension; left ventricular failure;presence, nature, severity and progression of pre-existing interstitial lung disease. Tier 2 data stratified these variables into risk profiles e.g. never versus current smoking was perceived as low and high risk respectively. An example of perceived high risk resulting from Tier 3 is a 75-year-old current smoker with high-activity rheumatoid arthritis (RA) with severe, progressive ILD being started on methotrexate. A perceived low risk is a 75-year-old currentsmoker with moderate-activity RA and emphysema with no cardiac or renal disease and no pre-existing ILD being started on rituximab. A risk prediction scoring tool is being developed to be used in validation studies.

Conclusion
This modified Delphi exercise defined and stratified the perceived risk factors for developing pneumotoxicity. Age, current smoking, high underlying rheumatological disease activity, HRCT definite UIP and honeycombing, severity and progression of pre-existing ILD were perceived to be the highest risk-factors.