Diurnal variation in forced vital capacity in patients with fibrotic interstitial lung disease using home spirometry

Abstract

Forced vital capacity (FVC) is used as the routine physiological measure to assess disease progression in fibrotic interstitial lung diseases (f-ILDs) [1]. New drugs are currently being investigated on top of "standard care" with antifibrotic drugs in idiopathic pulmonary fibrosis (IPF) and other f-ILD, resulting in small margins of change in FVC [2, 3]. Recently, the first trial of antifibrotic medication in patients with systemic sclerosis-associated interstitial lung disease has shown a numerically small but significant lower annualised rate of FVC decline (41 mL) in patients treated with nintedanib compared with placebo [3]. Data regarding a possible circadian rhythm in pulmonary function are contradictory [4-6]. Diurnal variation has never been investigated in f-ILD but could have implications for the interpretation and design of clinical trials, and for monitoring in daily practice. Taking advantage of new e-health technologies [7, 8], we aimed to assess whether there is a diurnal variation in FVC in patients with f-ILD using home spirometry. Furthermore, we evaluated whether there was a relationship between FVC and activity as we hypothesised that exercise just before the measurement may affect FVC values. Between December 2018 and May 2019, consecutive outpatients with f-ILD were invited to participate in this prospective, single-centre, observational study for 6 weeks. Medical ethical committee approval was obtained and all patients provided written informed consent. Our previously developed and validated home monitoring programme was used for home-based measurements [7]. Patients measured FVC twice daily with a handheld spirometer (Spirobank Smart; MIR, Rome, Italy), once in the morning and once in the afternoon. FVC measurements were excluded if only one measurement was available for that day, if the morning FVC measurement was before 06:00 h or if difference from baseline FVC was >20%. In addition, steps were continuously counted using an activity tracker (Flex 2; FitBit, San Francisco, CA, USA) in blocks of 15 min to assess activity during the hour before FVC measurement. At baseline and after 6 weeks, patients completed the King's Brief Interstitial Lung Disease (K-BILD) questionnaire online [9]. In-hospital spirometry was performed at the start of the study and patients received standardised instructions about the home monitoring programme. Linear mixed models were used to evaluate differences between morning and afternoon measurements. Pearson correlation coefficient was used to assess correlations between study parameters (R version 3.5.2; The R Foundation for Statistical Computing, Vienna, Austria). We estimated that between four and 50 patients would be needed to determine a significant difference between morning and afternoon FVC with a power of 90%, assuming a total variance of 0.026 L and between-patient standard deviation of 0.006-0.1 L, based on pilot data. Of 57 invited patients, 50 patients consented to participate. The median (range) age of patients was 68 (43-79) years and 68% were mal...

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

“…Within-subject variability in FVC measurements taken day-to-day or week-to-week has been observed in healthy individuals [ 17 ] as well as in subjects with IPF [ 4 , 6 ]. The literature is inconsistent with respect to diurnal variations in FVC; several studies have found FVC to be generally higher in the morning than in the afternoon [ 18 – 20 ], but this has not been observed in all studies [ 21 ]. In the INMARK trial, subjects were asked to perform spirometry in the morning, but fewer than a third of subjects adhered to this request.…”

Feasibility of online home spirometry in systemic sclerosis–associated interstitial lung disease: a pilot study

“…This high variability was probably caused by a lack of good instruction regarding home spirometry, adherence problems and technical problems with the hand-held spirometers [ 21 ]. The online home monitoring program used in the current study yielded similar results in IPF, sarcoidosis and other forms of pulmonary fibrosis, with a low variability in home-based FVC and a small number of technical issues and missing data [ 12–14 , 16 ]. Hence we believe that most issues raised in previous studies can be addressed by the use of an online system with direct data transmission to the hospital, low-threshold communication, e-mail reminders and feedback on the quality of the measurements.…”

“…Half of the patients started with weekly home spirometry and the other 50% of patients started with daily home spirometry. Patients were instructed to perform spirometry at approximately the same time every day to reduce variability [ 16 ]. Measurements were sent directly to the hospital via an encrypted connection.…”

Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study

“…A handheld spirometer (Spirobank Smart, MIR, Italy) will be handed out to all patients. Patients will be instructed to undertake spirometry (three consecutive measurements) once a week at the same day, at approximately the same time to enhance compliance and reduce variability [ 23 ]. The best result of the day will be transmitted real-time to the patients’ personal platform and will be directly accessible for both patients and the study team.…”