Home spirometry monitoring to identify loss of asthma control in adolescents

To the Editor,

The COVID-19 pandemic imposed limitations on health care and clinical research that increased the need for remote monitoring of chronic pulmonary diseases. Mobile spirometers for home monitoring of lung function have been commercially available for years but have not been widely adopted in clinical practice in the U.S. Multiple published investigations demonstrate that home spirometry measurements are reproducible and show a high degree of correlation with clinic-based spirometers in adults with asthma or COPD ^{1, 2}. Home spirometry studies of children have focused on the cystic fibrosis (CF) population rather than asthma and have reported little data on use in adolescent populations ^{3, 4}. Adolescents tend to have low engagement in asthma self-management and represent a group at high risk of asthma-related morbidity and mortality. The objective of our study was to determine if unsupervised home monitoring of lung function in adolescents at risk for future asthma exacerbation could detect clinically significant changes in FEV₁ during mild loss-of-control events. Early and accurate detection of loss-of-control events would allow for earlier intervention to prevent progression to severe symptoms.

Inclusion criteria included age 12-21 years, use of ≥1 asthma controller therapies, and a history of ≥1 exacerbations treated with systemic corticosteroids in the prior 12 months. Volunteers were excluded for asthma requiring daily oral corticosteroid therapy, other pulmonary diseases affecting interpretation of spirometry or symptoms (e.g., vocal cord dysfunction), inability to perform acceptable spirometry, or a history of spirometry-induced bronchospasm. At baseline and 2, 4 and 6 month follow up visits, medical history was reviewed including asthma exacerbations requiring systemic corticosteroids since the prior study visit. Participants performed spirometry using a clinic-based spirometer (KoKo^® SX 1000, NSpire Health, Inc) and received coaching on use of the home spirometer (Spirobank Smart^®, MIR) and smartphone application (VitalFlo^®). The app displayed an indicator of whether each trial was acceptable, and the best of three acceptable trials was recorded. FEV₁ percent predicted (FEV₁pp) was calculated using race-specific Global Lung Initiative (GLI) reference equations. Lung function data were not displayed to the user, and volunteers were not asked to change their behavior based on spirometry results. Participants completed unsupervised spirometry and a brief symptom survey once in the morning and once in the evening over the 6-month study period (Table E1 in the article’s online supplement). Volunteers were also provided with a written asthma action plan providing guidance on treatment during green, yellow and red zone events. Mirroring the asthma action plan, mild loss-of-control events were labeled “Yellow Zone” (YZ) events and were identified through participant survey-reported daytime or nighttime cough, wheeze, shortness of breath or chest tightness with or without use of rescue albuterol. A linear mixed-effects model was used to test whether home FEV₁ measured the day of a YZ event differed from the participant’s baseline FEV₁ obtained at the first study visit. A reduction of 10 percentage points or more in mean FEV₁pp was considered a clinically significant change. FEV₁ values were regressed on a yellow zone indicator variable, while controlling for secondhand smoke exposure, history of environmental allergies, and BMI, with random effects for individual patients to control for the non-independence of the within-patient data. For participants with YZ events, we fit an analogous model with an indicator for measurements made within three days prior to a YZ event. An alpha of .05 was used to determine significance. We additionally recorded participant-reported prescriptions for systemic corticosteroids related to asthma as a measure of severe loss-of-control events. The study was approved by the UNC Institutional Review Board. All participants provided written informed consent/assent.

Forty-two adolescents were enrolled and provided data for the study (Table E2 in the article’s online supplement). The median age of participants was 15.4 (SD 2.5) years, 43% were female, 62% self-identified as non-Hispanic Black, 29% as non-Hispanic White, and 7% as Hispanic White. Two-thirds of participants were prescribed step 4 therapy or higher, consistent with moderate to severe persistent asthma, and 79% were prescribed combination inhaled corticosteroid and long-acting beta agonist (ICS-LABA) therapy. The mean (SD) FEV₁pp at the enrollment visit was 90.7% (15.4%). Counting through the last day of participation, the median participant was adherent to once daily spirometry on 40% [IQR 18%, 77%] of enrolled days and twice-daily spirometry on 20% [IQR 8%, 52%] of enrolled days.

Median [IQR] FEV₁pp values measured by home spirometry were lower than clinic spirometry measurements (74.9% [56.3, 91.1] and 89.9% [77.5, 99.9], respectively). Thirty participants (71%) documented at least one YZ event during the study period, with a median [IQR] of 9 [0, 22] events per participant. Only three courses of systemic steroid treatment for severe asthma exacerbation had corresponding FEV₁ data from the date of prescription.

FEV₁ measured by home spirometry tended to be higher on YZ days than on survey-reported “good” asthma days (Figure 1). Examining home spirometry only, YZ events were associated with FEV₁pp that was 1.6 percentage points higher than on days without YZ events (β=1.6, SE=.57, η²=8.1, df=1, p=.004). As sensitivity analyses, we included self-reported albuterol use in our model to account for the effect of bronchodilator. Additionally, we refit the model after excluding data from a single participant whose FEV₁ measurements included extreme values in both directions (ranging from 21.9 to 136.1) concerning for poor technique. The association between YZ events and FEV₁pp was no longer significant (η²=.0, df=1, p=.99); there was insufficient evidence to detect a difference in FEV₁pp from baseline during YZ events. However, FEV₁pp values were a significant predictor of whether a day was ≤3 days prior to a YZ event (β=.017 SE=.004, p<.001); higher FEV₁pp measurements were associated with greater risk of a YZ event occurring within the next 3 days (Figure 2).

Figure 1.

The distribution of FEV₁pp values by day category (A), by frequency of self-reported rescue albuterol use (B), and by self-reported asthma status (C). YZE, yellow zone event; OCS, oral corticosteroid. *Categories are not necessarily mutually exclusive. Some days do not fall into any category so are not included.

Figure 2.

FEV₁pp values from pre-YZ days are shown in the spineplot. The higher the bar in each bin, the higher the probability of a YZ event occurring in the next 3 days. The spineplot demonstrates that the highest FEV₁pp values were associated with the greatest probability of a YZ event occurring within the next 3 days. YZE, yellow zone event.

In our racially diverse adolescent study population with asthma, we observed that uncoached home-based FEV₁ measurements did not significantly change during mild loss of asthma control events. We initially found that FEV₁pp measurements taken on YZ event days were 1.6 percentage points higher than on days without YZ events. However, this effect was lost during sensitivity analyses. Home FEV₁ measurements were lower and displayed greater variability than FEV₁ measured by a clinic spirometer. This finding aligns with a recently published study of home spirometry in children with CF; the authors concluded that unsupervised home spirometry was not equivalent to clinic spirometry, with lower and more variable FEV₁ measurements associated with home spirometry, though these were measured during periods of clinical stability ³.

Intriguingly, we observed that higher FEV₁ was more predictive of a YZ event occurring within the next 3 days than lower FEV₁pp values. There are several potential explanations for this result. Increased awareness of asthma symptoms may prompt improved adherence to controller therapies or greater effort during spirometry measurement. Consistent with clinical practice and published findings, when symptoms increase, adherence to controller therapies often increases ⁵. This is of particular interest with respect to ICS/LABA therapies, which 79% of participants in the study were prescribed. Better adherence to ICS/LABA may have resulted in greater bronchodilation, causing FEV₁pp measurements to be higher on days with more asthma symptoms. Undocumented rescue medication use is also possible. This study was conducted prior to the release of the 2020 updates to the asthma management guidelines report from the National Asthma Education and Prevention Program’s Expert Panel Working Group; as such, use of single maintenance and reliever therapy (SMART) was not a common practice at the time, and to our knowledge, none of the enrolled participants were using their ICS-LABA for rescue therapy. We were not able to account for the timing of bronchodilator use relative to spirometry measurement, which is a limitation of our study design. In future work, incorporating devices that track controller and rescue medication use may be helpful for determining whether this relationship between FEV₁ and risk of loss-of-control events is reproducible. Our data were insufficient to draw conclusions about severe exacerbations that required treatment with systemic corticosteroids.

Our study was also limited by lower than desired adherence to spirometry measurement and survey completion, which may have resulted in missed YZ events and lack of corresponding spirometry during events. The frequency of severe asthma exacerbations requiring systemic steroid treatment during the study period was lower than anticipated and was likely impacted by the COVID-19 pandemic stay-at-home orders that limited respiratory infections during the last 6 months of study. Some study visits were converted to virtual visits, which resulted in missing clinic spirometry data.

In conclusion, home-based spirometry monitoring did not detect clinically significant changes in FEV₁ during mild loss-of-control events in adolescents with persistent asthma. Additionally, we observed that higher FEV₁pp was more predictive of future YZ events than lower FEV₁pp values. FEV₁ is often preserved in children, even in those with severe asthma ⁶, and published evidence suggests that increased frequency of symptoms may influence adherence to controller medications such as ICS-LABA. These facts may limit the usefulness of monitoring lung function to detect early loss-of-control events. Further study is needed to determine whether home-based monitoring of FEV₁ can predict more severe loss-of-control events in adolescents.