Quantifying variation in home spirometry in people with cystic fibrosis during baseline health, and associations with clinical outcomes

Abstract

Background: Home spirometry is increasingly used to monitor lung function in people with cystic fibrosis (pwCF). Although decreases in lung function in the setting of increased respiratory symptoms are consistent with a pulmonary exacerbation (PEx), the interpretation of home spirometry during asymptomatic periods of baseline health is unclear. The aims of this study were to determine the variation in home spirometry in pwCF during asymptomatic periods of baseline health and to identify associations between this variation and PEx.

Methods: Near-daily home spirometry measurements were obtained from a cohort of pwCF enrolled in a long-term study of the airway microbiome. Associations between the degree of variation in home spirometry and the time to next PEx were evaluated.

Results: Thirteen subjects (mean age of 29 years and mean percent predicted forced expiratory volume in one second [ppFEV₁] of 60) provided a median of 204 spirometry readings taken during 40 periods of baseline health. The mean week-to-week within-subject level of variation in ppFEV₁ was 15.2 ± 6.2%. The degree of variation in ppFEV₁ during baseline health was not associated with time to PEx.

Conclusions: Variation in ppFEV₁ measured with near-daily home spirometry in pwCF during periods of baseline health exceeded the variation in ppFEV₁ expected in clinic spirometry (based on ATS guidelines). The degree of variation in ppFEV₁ during baseline health was not associated with time to PEx. These data are relevant for guiding interpretation of home spirometry.

Keywords: Baseline health; Cystic fibrosis; Exacerbation; Home spirometry; Lung function.

Figure 1:. Baseline periods by subject.

The 13 subjects are grouped by disease stage: early, intermediate, and advanced. The baseline health periods (grey shade) for each subject are depicted. Dots represent the coefficient of variation (CoV) of home spirometry ppFEV₁ measures across each baseline period. Dotted horizontal lines represent the minimum and maximum CoV for each subject across all baseline periods. For subjects with a single baseline period, the CoV is shown across that period. Numbers above each bar represent the number of days with at least one home spirometry reading for the baseline period. Red arrows indicate PEx (periods of pulmonary exacerbation and antibiotic treatment).

Figure 2:. Home spirometry grading and mean ppFEV₁ and ppFEV₁ CoV for each subject.

Vertical dashed lines group subjects by disease stage. Shown for each subject is (A) the proportion of reproducible (grades A or B) spirometry measures; (B) the weekly mean ppFEV₁ calculated across all weeks during baseline periods; and (C) the weekly mean CoV of near daily ppFEV₁ calculated across all weeks during baseline periods. Boxes shown median and interquartile range (IQR), and whiskers show the range. Red asterisks (in panel B) show ppFEV₁ from clinic-measured spirometry prior to study initiation.

Figure 3:. Cox proportional hazard models.

Clinically relevant a priori-selected covariates are incorporated to evaluate the relationship of CoV across each baseline period in near-daily measures of ppFEV₁ to next exacerbation (panel A), to all exacerbations (panel B), and to all exacerbations by one-week time intervals (panel C). Results are represented by hazard ratio and 95% confidence intervals in parentheses. Clinic ppFEV₁ refers to the best clinic ppFEV₁ value obtained within six months of study initiation and at three-month intervals during study duration. Modulator refers to those subjects on CFTR modulator therapy at the start of the study period.