Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are ...applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL
Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29-0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33-0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
Background The clinical relevance of increased ventilation heterogeneity, a marker of small-airways disease, in asthmatic patients is unclear. Ventilation heterogeneity is an independent determinant ...of airway hyperresponsiveness (AHR), improves with bronchodilators and inhaled corticosteroids (ICSs), and worsens during exacerbations, but its relationship to asthma control is unknown. Objective We sought to determine the association between ventilation heterogeneity and current asthma control before and after ICS treatment. Methods Adult subjects with asthma had lung function and asthma control (5-item Asthma Control Questionnaire ACQ-5 score ≥1.5 = poorly controlled, ACQ-5 score ≤0.75 = well controlled) measured at baseline. A subgroup with AHR had repeat measurements after 3 months of high-dose ICS treatment. The indices of ventilation heterogeneity in the regions of the lung where gas transport occurs predominantly through convection (ventilation heterogeneity in convection-dependent airways Scond) and through diffusion (ventilation heterogeneity in diffusion-dependent airways Sacin) were derived by using the multiple-breath nitrogen washout technique. Results At baseline (n = 105), subjects with poorly controlled asthma had worse FEV1 , fraction of exhaled nitric oxide measured at 200 mL/s (F eno ), Scond, and Sacin values. In the treatment group (n = 50) spirometric, F eno , residual volume (RV)/total lung capacity (TLC), AHR, and Scond values significantly improved. Asthma control also improved (mean ACQ-5 score, 1.3-0.7; P < .0001). The change in ACQ-5 score correlated with changes in F eno ( rs = 0.31, P = .03), Sacin ( rs = 0.32, P = .02), and Scond ( rs = 0.41, P = .003) values. The independent predictors of a change in asthma control were changes in Scond and Sacin values (model r2 = 0.20, P = .005). Conclusions Current asthma control is associated with markers of small-airways disease. Improvements in ventilation heterogeneity with anti-inflammatory therapy are associated with improvements in symptoms. Sensitive measures of small-airway function might be useful in monitoring the response to therapy in asthmatic subjects.
ABSTRACT
The obese asthma phenotype is an increasingly common encounter in our clinical practice. Epidemiological data indicate that obesity increases the prevalence and incidence of asthma, and ...evidence that obesity precedes the development of asthma raises the possibility of a causal association. Obese patients with asthma experience more symptoms and increased morbidity compared with non‐obese asthma patients. Despite more than a decade of research into this association, the exact mechanisms that underlie the interaction of obesity with asthma remain unclear. It is unlikely that the asthma–obesity association is simply due to comorbidities such as obstructive sleep apnoea or gastroesophageal reflux disease. Although inflammatory pathways are purported to play a role, there is scant direct evidence in humans that systemic inflammation modulates the behaviour of the asthmatic airway or the expression of symptoms in the obese. The role of non‐eosinophilic airway inflammation also requires further study. Obesity results in important changes to the mechanical properties of the respiratory system, and these obesity‐related factors appear to exert an additive effect to the asthma‐related changes seen in the airways. An understanding of the various physiological perturbations that might be contributing to symptoms in obese patients with asthma will allow for a more targeted and rational treatment approach for these patients.
Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment ...and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.
Persistent bronchodilator response (BDR) following diagnosis of asthma is an underrecognized treatable trait, associated with worse lung function and asthma control. The forced oscillation technique ...(FOT) measures respiratory system impedance, and BDR cutoffs have been proposed for healthy adults; however, the relevance in asthma is unknown. We compared BDR cutoffs, using FOT and spirometry, in asthma and the relationship with asthma control.
Data from patients with asthma who withheld bronchodilator medication for at least 8 h before a tertiary airway clinic visit were reviewed. All subjects performed FOT and spirometry before and after salbutamol administration, and completed the Asthma Control Test. FOT parameters examined included respiratory system resistance (R5) and reactance (X5) at 5 Hz, and area under the reactance curve (AX). BDR was defined by standard recommendations for spirometry and based on the 95th percentile of BDR in healthy adults for FOT.
Fifty-two subjects (18 men; mean age, 53 ± 18 years) were included. BDR was identified more frequently by FOT than spirometry (54% vs 27% of subjects). BDR assessed by X5 and AX, but not R5, was associated with spirometric BDR (χ2, P < .01) and correlated with asthma control (X5: rs = –0.36, P < .01; AX: rs = 0.34, P = .01). BDR measured by reactance parameters identified more subjects with poor asthma control than did spirometry (AX, 69% vs spirometry, 41%).
BDR assessed by FOT can identify poor asthma control. Reactance parameters were more sensitive in identifying poor asthma control than spirometry, supporting the use of FOT to complement spirometry in the clinical management of asthma.
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.
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
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.
Fifteen participants with a mean±sd age of 69±10 years and a % predicted forced expiratory volume in 1 s (FEV
) 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 (SDX
)) 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). SDX
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).
SDX
from FOT telemonitoring reflects COPD symptoms and may be a sensitive biomarker for early detection of AECOPD.
ABSTRACT
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)
We measured lung elastic recoil, spirometry and the forced oscillation technique in older non‐smoking asthmatic subjects with fixed airflow obstruction (FAO). In addition to airway remodelling, FAO can be attributed to reduced lung elastic recoil. Identification of the mechanisms leading to loss of lung elasticity may offer new targets for intervention.
See related Editorial
Treatment with mepolizumab in severe eosinophilic asthma (SEA) significantly reduces exacerbations with modest improvements in symptom control and spirometry. The time course of any changes in small ...airway function is unknown.
To describe changes in ventilation inhomogeneity, a marker of small airway function, after commencing mepolizumab.
Prospective cohort of 20 adults (12 male) with SEA commencing monthly mepolizumab. Measurements at baseline, Week 4 and Week 26 included the Asthma Control Questionnaire (ACQ-5), spirometry, fraction of exhaled nitric oxide (FeNO) and multiple breath nitrogen washout to measure global (Lung Clearance Index, LCI) and regional ventilation inhomogeneity in acinar (Sacin) and conducting (Scond) airways. Other asthma therapy remained unchanged between baseline and Week 4. Treatment related changes were assessed using RM-ANOVA and paired t-tests. Relationships between changes in lung function and symptoms were assessed by Pearson's correlation.
At Week 4, ACQ-5, spirometry, LCI and Sacin improved significantly (p < 0.04) and all were sustained at Week 26. The change in ACQ-5 correlated with the change in Sacin (r = 0.48, p = 0.03) and FRC (r = 0.46, p = 0.04), but not spirometry.
Improved symptom control improved rapidly after commencing mepolizumab in patients with SEA. The early improvement in small airway function was associated with asthma control and may be a significant contributor to the therapeutic response.
•Abnormal small airway function is important in severe eosinophilic asthma.•Mepolizumab improves small airway function after the first subcutaneous injection.•The change in acinar airway function following the commencement of mepolizumab relates to the improved symptom control.•Therapies that target small airway function can improve patient outcomes.
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