Home spirometry in patients with idiopathic pulmonary fibrosis: data from the INMARK trial

Abstract

Background: Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF).

Methods: Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients.

Results: In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72-0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks).

Conclusion: Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.

Trial registration: ClinicalTrials.gov NCT02788474.

Conflict of interest statement

Conflict of interest: I. Noth reports personal fees for advisory board work from Boehringer Ingelheim and Genentech, personal fees for consultancy from ImmuneWorks, outside the submitted work. Conflict of interest: V. Cottin reports personal fees for advisory board work and lectures, and nonfinancial support for meeting attendance from Actelion, grants, personal fees for consultancy and lectures, and nonfinancial support for meeting attendance from Boehringer Ingelheim, personal fees for advisory board and data monitoring committee work from Bayer/MSD and Galapagos, personal fees for lectures and advisory board work from Novartis, personal fees for consultancy and lectures, and nonfinancial support for meeting attendance from Roche, personal fees for lectures from Sanofi, personal fees for data monitoring and steering committee work from Promedior, personal fees for data monitoring work from Celgene and Galecto, outside the submitted work. Conflict of interest: N. Chaudhuri reports grants, personal fees for advisory board work and educational support to attend conferences from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: T.J. Corte reports grants and personal fees for travel, lectures and advisory board work from Boehringer Ingelheim, grants and personal fees for travel, lectures, steering committee work and advisory board work from Roche, grants from Gilead, Bayer and Intermune, personal fees for advisory board work from AstraZeneca and Ad Alta, grants and personal fees for steering committee and advisory board work from Bristol-Myers Squibb, personal fees for steering committee work from Promedior, during the conduct of the study. Conflict of interest: K.A. Johannson reports personal fees for advisory board work, consultancy and lectures from Boehringer Ingelheim, personal fees for advisory board work and lectures from Hoffman La Roche Ltd, personal fees for advisory board work and consultancy from Theravance and Blade Therapeutics, grants from Chest Foundation, University of Calgary School of Medicine, Pulmonary Fibrosis Society of Calgary and UCB Biopharma SPRL, personal fees for consultancy from Three Lakes Foundation, outside the submitted work. Conflict of interest: M. Wijsenbeek reports grants and personal fees from Boehringer Ingelheim and Hoffman La Roche, personal fees from Galapagos and Respivant, outside the submitted work; this article was based on discussions held at a meeting supported by Boehringer Ingelheim in June 2017. Conflict of interest: S. Jouneau reports fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, research projects from Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Galecto, Gilead, GlaxoSmithKline, LVL, Mundipharma, Novartis, Pfizer, Roche and Savara-Serendex, outside the submitted work. Conflict of interest: A. Michael is a contractor to Boehringer Ingelheim. Conflict of interest: M. Quaresma is an employee of Boehringer Ingelheim International GmbH. Conflict of interest: K.B. Rohr is an employee of Boehringer Ingelheim International GmbH. Conflict of interest: A-M. Russell reports grants and personal fees for meeting attendance from Boehringer Ingelheim, grants from Imperial Health Charity, Pulmonary Fibrosis Trust UK and Action for Pulmonary Fibrosis, personal fees for lectures from the Irish Lung Fibrosis Association and Hoffman La Roche, outside the submitted work. Conflict of interest: S. Stowasser is an employee of Boehringer Ingelheim International GmbH. Conflict of interest: T.M. Maher reports personal fees for advisory board work, consultancy or clinical trial work from Apellis, Boehringer Ingelheim, Roche, Bayer, Biogen Idec, Galapagos, Indalo, Galecto, Blade, Bristol-Myers Squibb, Novartis, Respivent and Trevi, grants and personal fees from UCB, grants and personal fees from GlaxoSmithKline, outside the submitted work.

Copyright ©ERS 2021.

Figures

FIGURE 1

Mean number of home spirometry measurements per subject per week. Analysis based on the total number of home spirometry measurements collected and the number of subjects who were still followed in the trial within the time period.

FIGURE 2

a) Mean adherence to weekly home spirometry. Adherence to weekly home spirometry was calculated as the number of weeks that a subject provided at least one measurement divided by the number of weeks that they were followed in the trial. b) Proportion of subjects with 100% adherence to weekly home spirometry. 100% adherence was defined as provision of at least one measurement per week for all the weeks that the subject was in the trial. The total number of subjects who were still followed in the trial within the time period was used as the denominator.

FIGURE 3

“Heatmaps” depicting correlations between a) lung function variables measured at home and in clinic at different time-points (r≥0.5 for all correlations), b) changes from baseline in lung function variables measured at home and in clinic at different time-points, and c) rates of decline in lung function variables measured at home and in clinic at different time-points. FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s; FEV6: forced expiratory volume in 6 s. Darker shades of red or blue indicate stronger positive or negative associations, respectively.

FIGURE 4

Changes from baseline in forced vital capacity (FVC) based on a) home spirometry and b) clinic spirometry. Boxes indicate median and interquartile range (IQR); “plus” symbols (+) indicate mean. Whiskers indicate 1.5 IQR. Outliers are shown as squares.