Day-to-day variability of forced oscillatory mechanics for early detection of acute exacerbations in COPD.

BACKGROUND: Telemonitoring trials for early detection of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have provided mixed results. Day-to-day variations in lung function measured by the forced oscillation technique (FOT) may yield greater insight. We evaluated the clinical utility of home telemonitoring of variability in FOT measures in terms of 1) the relationship with symptoms and quality of life (QoL); and 2) the timing of variability of FOT measures and symptom changes prior to AECOPD. METHODS: Daily FOT parameters at 5 Hz (resistance (R) and reactance (X); Resmon Pro Diary, Restech Srl, Milan, Italy), daily symptoms (COPD Assessment Test (CAT)) and 4-weekly QoL data (St George's Respiratory Questionnaire (SGRQ)) were recorded over 8-9 months from chronic obstructive pulmonary disease (COPD) patients. Variability of R and X was calculated as the standard deviation (sd) over 7-day running windows and we also examined the effect of varying window size. The relationship of FOT versus CAT and SGRQ was assessed using linear mixed modelling, daily changes in FOT variability and CAT prior to AECOPD using one-way repeated measures ANOVA. RESULTS: Fifteen participants with a mean±sd age of 69±10 years and a % predicted forced expiratory volume in 1 s (FEV1) of 39±10% had a median (interquartile range (IQR)) adherence of 95.4% (79.0-98.8%). Variability of the inspiratory component of X (indicated by the standard deviation of inspiratory reactance (SDXinsp)) related to CAT and weakly to SGRQ (fixed effect estimates 1.57, 95% CI 0.65-2.49 (p=0.001) and 4.41, 95% CI -0.06 to 8.89 (p=0.05), respectively). SDXinsp changed significantly on the same day as CAT (1 day before AECOPD, both p=0.02) and earlier when using shorter running windows (3 days before AECOPD, p=0.01; accuracy=0.72 for 5-day windows). CONCLUSIONS: SDXinsp from FOT telemonitoring reflects COPD symptoms and may be a sensitive biomarker for early detection of AECOPD.

Reduced lung elastic recoil and fixed airflow obstruction in asthma.

BACKGROUND AND OBJECTIVE: Fixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma. METHODS: Non-smoking asthmatic subjects aged >40 years, treated with 2 months of high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs5 ) and respiratory system reactance at 5 Hz (Xrs5 ) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure-volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC), Rrs5 and Xrs5 were assessed. RESULTS: Eighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z-score) post-bronchodilator FEV1 : -2.2 ± 0.5, FVC: -0.7 ± 1.0, FEV1 /FVC: -2.6 ± 0.7) and by increased Rrs5 (median (IQR) z-score) 2.7 (1.9 to 3.2) and decreased Xrs5 : -4.1(-2.4 to -7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV1 /FVC correlated negatively with K (rs = -0.60, P = 0.008) and Rrs5 correlated negatively with B/A (rs = -0.52, P = 0.026), independent of age. Xrs5 did not correlate with lung elasticity indices. CONCLUSION: Increased lung compliance and loss of elastic recoil relate to airflow obstruction in older non-smoking asthmatic subjects, independent of ageing. Thus, structural lung tissue changes may contribute to persistent, steroid-resistant airflow obstruction. CLINICAL TRIAL REGISTRATION: ACTRN126150000985583 at anzctr.org.au (UTN: U1111-1156-2795).

Discrepancy between in vivo and in vitro comparisons of forced oscillation devices.

The forced oscillation technique (FOT) is an emerging clinical lung function test, with commercial devices becoming increasingly available. However comparability across existing devices has not been established. We evaluated in vivo and in vitro measurements made using three commercial devices against a custom-built device (WIMR): Resmon Pro Diary (Restech srl, Italy), tremoFlo C-100 (Thorasys Medical Systems, Canada), Jaeger Masterscope CT IOS (CareFusion, Hoechberg, Germany). Respiratory system resistance Rrs and reactance Xrs at 5 Hz were examined in twelve healthy subjects (mean age 33 ± 11 years, 7 males), and in two test standards of known resistance and reactance. Subjects performed three measurements during tidal breathing on the four devices in random order. Total, inspiratory and expiratory Rrs and Xrs were calculated and compared using one-way repeated measures ANOVA and Bonferroni post-hoc tests. Rrs did not differ between devices, with <10% deviation from predicted, except for the IOS device. With Xrs, similar values were seen between the WIMR and Resmon devices and between the tremoFlo and IOS devices. No differences were observed using test standards; deviation from theoretical value was <2% for resistance and <5% for reactance. The WIMR, tremoFlo and Resmon Pro but not IOS devices measure similar Rrs, whereas there was more disparity across devices in the estimation of Xrs parameters. The discrepancy between in vivo and in vitro measurements suggest that FOT validation procedures need to take into account the breathing pattern, either using biological controls or a breathing model.

Higher body mass index is associated with increased lung stiffness and less airway obstruction in individuals with asthma and fixed airflow obstruction.

Higher body mass index (BMI) is associated with less severe airway obstruction in older asthma patients with fixed airflow obstruction. This is potentially mediated through BMI-related mechanisms that increase lung stiffness (i.e. reduce lung compliance). https://bit.ly/3jBwCNy.

Relationships Between Forced Oscillatory Impedance and 6-minute Walk Distance After Pulmonary Rehabilitation in COPD.

Rationale: Pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) reduces dyspnoea and improves exercise capacity and quality of life. The improvement in exercise capacity is variable and unpredictable, however. Respiratory system impedance obtained by forced oscillation technique (FOT) as a measure of ventilatory impairment in COPD may relate to improvement in exercise capacity with pulmonary rehabilitation. We aimed to determine if baseline FOT parameters relate to changes in exercise capacity following pulmonary rehabilitation. Methods: At the start of rehabilitation, 15 COPD subjects (mean(SD) 75.2(6.1) years, FEV1 z-score -2.61(0.84)) had measurements by FOT, spirometry, plethysmographic lung volumes and 6-minute walk distance (6MWD). Respiratory system resistance (Rrs) and reactance (Xrs) parameters as the mean over all breaths (Rmean, Xmean), during inspiration only (Rinsp, Xinsp), and expiratory flow limitation (DeltaXrs = Xinsp-Xexp), were calculated. FOT and 6MWD measurements were repeated at completion of rehabilitation and 3 months after completion. Results: At baseline, Xrs measures were unrelated to 6MWD. Xinsp improved significantly with rehabilitation (from mean(SD) -2.35(1.02) to -2.04(0.85) cmH2O.s.L-1, p=0.008), while other FOT parameters did not. No FOT parameters related to the change in 6MWD at program completion. Baseline Xmean, DeltaXrs, and FVC z-score correlated with the change in 6MWD between completion and 3 months after completion of rehabilitation (rs=0.62, p=0.03; rs=-0.65, p=0.02; and rs=0.62, p=0.03, respectively); with worse ventilatory impairment predicting loss of 6MWD. There were no relationships between Rrs parameters, FEV1 or FEV1/FVC z-scores and changes in 6MWD. Conclusion: Baseline reactance parameters may be helpful in predicting those patients with COPD at most risk of loss of exercise capacity following completion of pulmonary rehabilitation.

Dismantling airway disease with the use of new pulmonary function indices.

We are currently limited in our abilities to diagnose, monitor disease status and manage chronic airway disease like asthma and chronic obstructive pulmonary disease (COPD). Conventional lung function measures often poorly reflect patient symptoms or are insensitive to changes, particularly in the small airways where disease may originate or manifest. Novel pulmonary function tests are becoming available which help us better characterise and understand chronic airway disease, and their translation and adoption from the research arena would potentially enable individualised patient care.In this article, we aim to describe two emerging lung function tests yielding novel pulmonary function indices, the forced oscillation technique (FOT) and multiple breath nitrogen washout (MBNW). With a particular focus on asthma and COPD, this article demonstrates how chronic airway disease mechanisms have been dismantled with the use of the FOT and MBNW. We describe their ability to assess detailed pulmonary mechanics for diagnostic and management purposes including response to bronchodilation and other treatments, relationship with symptoms, evaluation of acute exacerbations and recovery, and telemonitoring. The current limitations of both tests, as well as open questions/directions for further research, are also discussed.

Time-based pulmonary features from electrical impedance tomography demonstrate ventilation heterogeneity in chronic obstructive pulmonary disease.

Pulmonary electrical impedance tomography (EIT) is a functional imaging technique that allows real-time monitoring of ventilation distribution. Ventilation heterogeneity (VH) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and has previously been quantified using features derived from tidal variations in the amplitude of the EIT signal. However, VH may be better described by time-based metrics, the measurement of which is made possible by the high temporal resolution of EIT. We aimed 1) to quantify VH using novel time-based EIT metrics and 2) to determine the physiological relevance of these metrics by exploring their relationships with complex lung mechanics measured by the forced oscillation technique (FOT). We performed FOT, spirometry, and tidal-breathing EIT measurements in 11 healthy controls and 9 volunteers with COPD. Through offline signal processing, we derived 3 features from the impedance-time (Z-t) curve for each image pixel: 1) tE, mean expiratory time; 2) PHASE, mean time difference between pixel and global Z-t curves; and 3) AMP, mean amplitude of Z-t curve tidal variation. Distribution was quantified by the coefficient of variation (CV) and the heterogeneity index (HI). Both CV and HI of the tE and PHASE features were significantly increased in COPD compared with controls, and both related to spirometry and FOT resistance and reactance measurements. In contrast, distribution of the AMP feature showed no relationships with lung mechanics. These novel time-based EIT metrics of VH reflect complex lung mechanics in COPD and have the potential to allow real-time visualization of pulmonary physiology in spontaneously breathing subjects.NEW & NOTEWORTHY Pulmonary electrical impedance tomography (EIT) is a real-time imaging technique capable of monitoring ventilation with exquisite temporal resolution. We report novel, time-based EIT measurements that not only demonstrate ventilation heterogeneity in chronic obstructive pulmonary disease (COPD), but also reflect oscillatory lung mechanics. These EIT measurements are noninvasive, radiation-free, easy to obtain, and provide real-time visualization of the complex pathophysiology of COPD.