Antifibrotic therapy in idiopathic pulmonary fibrosis candidates for lung transplantation undergoing pulmonary rehabilitation

Pereira, Monica Pruss; Branchini, Gisele; Nunes, Fernanda Bordignon; Altmayer, Stephan; Hetzel, Guilherme Moreira; Romero, Iveth; Rubin, Adalberto Sperb; Florian, Juliessa; Nascimento, Douglas Zaione; Watte, Guilherme

doi:10.36416/1806-3756/e20220250

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Jornal Brasileiro de Pneumologia

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ORIGINAL ARTICLE • J. bras. pneumol. 49 (01) • 2023 • https://doi.org/10.36416/1806-3756/e20220250 copy

Antifibrotic therapy in idiopathic pulmonary fibrosis candidates for lung transplantation undergoing pulmonary rehabilitation

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To investigate the impact of pulmonary rehabilitation (PR) on functional outcomes and health-related quality of life (HRQoL) in idiopathic pulmonary fibrosis (IPF) patients placed on a lung transplant waitlist and receiving antifibrotic therapy (AFT).

Methods:

This was a retrospective observational study of consecutive IPF patients receiving AFT with either pirfenidone or nintedanib (the AFT group) and undergoing PR between January of 2018 and March of 2020. The AFT group and the control group (i.e., IPF patients not receiving AFT) participated in a 12-week PR program consisting of 36 sessions. After having completed the program, the study participants were evaluated for the six-minute walk distance (6MWD) and HRQoL. Pre- and post-PR 6MWD and HRQoL were compared within groups and between groups.

Results:

There was no significant difference between the AFT and control groups regarding baseline characteristics, including age, airflow limitation, comorbidities, and oxygen requirement. The AFT group had a significant increase in the 6MWD after 12 weeks of PR (effect size, 0.77; p < 0.05), this increase being significant in the between-group comparison as well (effect size, 0.55; p < 0.05). The AFT group showed a significant improvement in the physical component of HRQoL at 12 weeks (effect size, 0.30; p < 0.05).

Conclusions:

Among IPF patients undergoing PR, those receiving AFT appear to have greater improvements in the 6MWD and the physical component of HRQoL than do those not receiving AFT.

Keywords:
Idiopathic pulmonary fibrosis; Lung transplantation; Rehabilitation

Variable	Group		p
	Control	AFT
	(n = 16)	(n = 16)
Male sex	13 (81.3)	12 (75.0)	1.000
Age, years	60 ± 9	63 ± 5	0.373
BMI, kg/m²	25.9 ± 1.42	27.8 ± 4.54	0.113
FEV₁, L	1.70 ± 0.46	1.68 ± 0.40	0.919
FEV₁, % predicted	55 ± 13	55 ± 14	0.953
FVC, L	1.98 ± 0.64	1.93 ± 0.54	0.818
FVC, % predicted	51 ± 14	49 ± 14	0.694
FEV₁/FVC ratio	0.87 ± 0.08	0.88 ± 0.08	0.785
DL_CO, % predicted	39 ± 11	37 ± 5	0.591
PASP, mmHg	45.5 ± 11.5	45.0 ± 14.9	0.919
6MWD, m	429 ± 104	358 ± 100	0.164
Hypertension	7 (43.8)	4 (25.0)	0.458
Diabetes mellitus	2 (12.5)	2 (12.5)	1.000
Osteopenia	4 (25.0)	1 (6.3)	0.333
Ischemic heart disease	5 (31.3)	3 (18.8)	0.685
Former smoker	11 (68.8)	8 (50.0)	0.473
Smoking, years	26 [18-31]	30 [5-37]	0.817
Long-term oxygen therapy	12 (85.7)	13 (81.3)	1.000
Oxygen flow rate, L/min	5.00 ± 1.96	4.81 ± 1.42	0.765

Outcome	PR	Mean ± SD		Within-group comparison between pre- and post-PR values	Between-group comparison between pre- and post-PR values
Outcome	PR	Pre-PR	Post-PR	Mean difference (95% CI); Effect size¹⁸18 McGraw K, Wong S. A Common Language Effect Size Statistic. Psychol Bull. 1992;111:361-365. https://doi.org/10.1037/0033-2909.111.2.361 https://doi.org/10.1037/0033-2909.111.2.... *	Mean difference (95% CI); Effect size¹⁹19 Carlson KD, Schmidt FL. Impact of experimental design on effect size: Findings from the research literature on training. J Appl Psychol 1999;84(6):851-862. https://doi.org/10.1037/0021-9010.84.6.851 https://doi.org/10.1037/0021-9010.84.6.8... ^,²⁰20 Morris SB. Estimating Effect Sizes From Pretest-Posttest-Control Group Designs. Organ Res Methods. 2008;11(2):364-386. https://doi.org/10.1177/1094428106291059 https://doi.org/10.1177/1094428106291059... *
Six-minute walk test
6MWD, m	CG	429 ± 104	448 ± 107	18 (−17 to 55); 0.18	59 (11 to 105); 0.554**
	AFT	358 ± 100	435 ± 99	77 (43 to 111); 0.77**	59 (11 to 105); 0.554**
Post-PR HR, bpm	CG	120 ± 26	132 ± 22	12 (1 to 24); 0.49	2 (−16 to 18); 0.087
	AFT	115 ± 18	129 ± 21	14 (1 to 27); 0.71	2 (−16 to 18); 0.087
Post-PR SpO₂, %	CG	76 ± 6	76 ± 8	0 (−2.0 to 0.4); 0.00	−1.0 (−7.3 to 5.6); 0.110
	AFT	81 ± 11	80 ± 7	−1.0 (−2.7 to 1.1); 0.10	−1.0 (−7.3 to 5.6); 0.110
Post-PR dyspnea, modified Borg scale score	CG	5 ± 3	4 ± 2	−1.0 (−2.0 to 2.8); 0.32	0.0 (−2.0 to 2.5); 0.000
	AFT	5 ± 3	4 ± 1	-1.0 (−2.7 to 1.0); 0.44	0.0 (−2.0 to 2.5); 0.000
Post-PR leg discomfort, modified Borg scale score	CG	2 ± 2	2 ± 2	0.0 (0.0 to 0.0); 0.00	0.0 (0.0 to 0.0); 0.000
	AFT	2 ± 2	2 ± 2	0.0 (0.0 to 0.0); 0.00	0.0 (0.0 to 0.0); 0.000

Outcome	PR	Mean ± SD		Within-group comparison between pre- and post-PR values	Between-group comparison between pre- and post-PR values
Outcome	PR	Pre-PR	Post-PR	Mean difference (95% CI); Effect size¹⁸18 McGraw K, Wong S. A Common Language Effect Size Statistic. Psychol Bull. 1992;111:361-365. https://doi.org/10.1037/0033-2909.111.2.361 https://doi.org/10.1037/0033-2909.111.2.... *	Mean difference (95% CI); Effect size¹⁹19 Carlson KD, Schmidt FL. Impact of experimental design on effect size: Findings from the research literature on training. J Appl Psychol 1999;84(6):851-862. https://doi.org/10.1037/0021-9010.84.6.851 https://doi.org/10.1037/0021-9010.84.6.8... ^,²⁰20 Morris SB. Estimating Effect Sizes From Pretest-Posttest-Control Group Designs. Organ Res Methods. 2008;11(2):364-386. https://doi.org/10.1177/1094428106291059 https://doi.org/10.1177/1094428106291059... *
SF-36
Physical component summary	CG	33 ± 14	36 ± 17	3 (−5 to 10); 0.19	3 (−6 to 12); 0.134
	AFT	36 ± 15	41 ± 18	6 (0 to 12); 0.30**	3 (−6 to 12); 0.134
Mental component summary	CG	54 ± 18	61 ± 19	7(−3 to 18); 0.37	−4 (−19 to 10); 0.154
	AFT	56 ± 20	60 ± 27	3 (−8 to 15); 0.16	−4 (−19 to 10); 0.154

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[1] Correspondence to: Guilherme Watte. Serviço de Pneumologia, Pavilhão Pereira Filho, Irmandade Santa Casa de Misericórdia de Porto Alegre, Avenida Independência, 75, CEP 90020-160, Porto Alegre, RS, Brasil. Tel.: 55 51 3228-2789. E-mail: g.watte@gmail.com