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The outbreak of the COVID-19 pandemic in late 2019 and in 2020 presented challenges to healthcare workers (HCW) around the world that were unexpected and dramatic. The relentless progress of infection, starting in China and rapidly spreading to Europe, North America and elsewhere gave more remote countries, like Australia, time to prepare but also time for unease. HCW everywhere had to readjust and change their work practices to cope. Further waves of infection and transmission with newer variants pose challenges to HCW and health systems, even after mass vaccination. Respiratory medicine HCW found themselves at the frontline, developing critical care services to support intensive care units and grappling with unanticipated concerns about safety, risk and the need to retrain. Several studies have addressed the need for rapid changes in the healthcare workforce for COVID-19 and the impact of this preparation on HCW themselves. In this paper, we present a scoping review of the literature on preparing HCW for the pandemic, explore the Australian experience of building the respiratory workforce and propose evidence-based recommendations to sustain this workforce in an unprecedented high-risk environment.

Aim: Single (SLTx) and double lung transplantation (DLTx) are therapeutic options for end-stage interstitial lung disease (ILD). The aim of this study is to describe oscillometry indices in stable SLTx compared to DLTx recipients. Methods: Oscillometry & spirometry were performed on all stable LTx recipients at 2 Australian centres from 2020-2021 using TremoFlo C-100 to obtain resistance (R5, R5-19), reactance (X5) and reactance area (Ax). Subjects with baseline, acute or chronic lung allograft dysfunction were excluded. SLTx for ILD (SLTx-ILD) recipients were compared with DLTx for ILD (DLTx-ILD) and were matched by age and gender. Results: 17 SLTx-ILD were included and compared with 10 matched stable DLTx-ILD. Baseline demographics of SLTx-ILD [88% males; mean age 64 (SD 5)] and DLTx-ILD [90% males; mean age 63 (SD 6)] were similar. Median X5 (-1.86 vs -1.14, p=0.02) and Ax (12.60 vs 5.57, p=0.04) differed significantly between SLTx-ILD and DLTx-ILD recipients, but resistance (R5, R5-19) measurements did not. Conclusion: SLTx for ILD is characterised by significantly worse X5 and Ax (increased elastance) as compared to DLTx for ILD. The abnormal reactance, in addition to insignificant differences in resistance measurements between SLTx and DLTx, may be due to the fibrotic contralateral native lung. However, contribution from other factors such as differences in lung size matching needs to be assessed. Longitudinal oscillometry studies are required to ascertain whether abnormal reactance – when assessed against patients9 baseline measurements – can be indicative of earlier progressive lung graft dysfunction and a worse prognosis in SLTx, as compared to using traditional methods.

Eosinophils are increasingly being recognised as an important characteristic feature of COPD. Patients with COPD and eosinophilic inflammation tend to respond to steroid therapy; however, many questions remain regarding the optimum measurement. Eosinophilic inflammation may be defined based on various sampling techniques, including eosinophil levels in blood, sputum, bronchoalveolar lavage or biopsy, which leads to inconsistencies in its definition. Blood eosinophils may increase in conjunction with sputum eosinophils during COPD exacerbations and therefore may be a good surrogate marker of airway eosinophilic inflammation. However, the timing of the blood eosinophil measurement, the stability of the eosinophil count and the threshold used in different studies are variable. The use of blood eosinophil count to direct biological therapies in COPD has also had variable outcomes. Eosinophilic inflammation has an important role in COPD management; however, its use as the optimum biomarker still needs further investigation. Key points Eosinophilia may play a significant role in the pathogenesis of COPD. Eosinophilic inflammation in COPD can be steroid responsive; however, eosinophilic inflammation is variable, and caution needs to be taken with measurements and the thresholds used. The long-term effects of reducing eosinophil levels in COPD is unclear. Educational aims To explore current knowledge of eosinophils in COPD. To explore the relationship between eosinophilia and corticosteroid use. To understand the limitations of assessing and using eosinophilia in COPD., Eosinophilia is common in COPD and has utility in predicting responses to inhaled or oral corticosteroids, but has limitations as a biomarker http://bit.ly/2lQcMpy

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.

Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge., Airway smooth muscle cells from severe asthma patients with FAO respond to β2-agonists and corticosteroids in vitro, and at a level similar to mild asthmatics. Intrinsic dysfunction of these signalling pathways is unlikely to contribute to FAO. https://bit.ly/3muvNsW

In asthma, abnormal mechanical properties of the airways and lung tissue leads to airway narrowing and changes in ventilation distribution [1]. Ventilation distribution is determined by the variation of time constants [2], a product of resistance×static compliance of individual lung units. Ventilation distribution is heterogeneous in healthy lungs, but even more so in airways diseases, including asthma [3]. This is because time constants are often even more heterogeneous in disease due to changes in resistances and compliances [3, 4]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Chapman has nothing to disclose. Conflict of interest: Dr. Tonga reports personal fees from GlaxoSmithKline, Roche, outside the submitted work. Conflict of interest: Dr. Rutting has nothing to disclose. Conflict of interest: Dr. Durack has nothing to disclose. Conflict of interest: Dr. Thamrin has a patent WO 2006130922 A1 issued which is broadly relevant to the work. In addition, Dr. Thamrin has intellectual property arrangements with Thorasys Medical Systems and Restech srl relating to research collaborations, but does not have any financial relationships with either company. Conflict of interest: Dr. King reports grants from University of Sydney Bridging Grant, during the conduct of the study; grants, personal fees and other from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini, MundiPharma, grants from National Health & Medical Research Council, Asthma Foundation, Philanthropic donations via Sydney University, other from ATS and ERS, non-financial support and other from Restech, outside the submitted work;.

Obesity is associated with reduced operating lung volumes that may contribute to increased airway closure during tidal breathing and abnormalities in ventilation distribution. We investigated the effect of obesity on the topographical distribution of ventilation before and after methacholine-induced bronchoconstriction using single-photon emission computed tomography (SPECT)-computed tomography (CT) in healthy subjects. Subjects with obesity ( n = 9) and subjects without obesity ( n = 10) underwent baseline and postbronchoprovocation SPECT-CT imaging, in which Technegas was inhaled upright and followed by supine scanning. Lung regions that were nonventilated (Ventnon), low ventilated (Ventlow), or well ventilated (Ventwell) were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. To determine regional ventilation, lungs were divided into upper, middle, and lower thirds of axial length, derived from CT. At baseline, Ventnon and Ventlow for the entire lung were similar in subjects with and without obesity. However, in the upper lung zone, Ventnon (17.5 ± 10.6% vs. 34.7 ± 7.8%, P < 0.001) and Ventlow (25.7 ± 6.3% vs. 33.6 ± 5.1%, P < 0.05) were decreased in subjects with obesity, with a consequent increase in Ventwell (56.8 ± 9.2% vs. 31.7 ± 10.1%, P < 0.001). The greater diversion of ventilation to the upper zone was correlated with body mass index ( rs = 0.74, P < 0.001), respiratory system resistance ( rs = 0.72, P < 0.001), and respiratory system reactance ( rs = −0.64, P = 0.003) but not with lung volumes or basal airway closure. Following bronchoprovocation, overall Ventnon increased similarly in both groups; however, in subjects without obesity, Ventnon only increased in the lower zone, whereas in subjects with obesity, Ventnon increased more evenly across all lung zones. In conclusion, obesity is associated with altered ventilation distribution during baseline and following bronchoprovocation, independent of reduced lung volumes. NEW & NOTEWORTHY Using ventilation SPECT-computed tomography imaging in healthy subjects, we demonstrate that ventilation in obesity is diverted to the upper lung zone and that this is strongly correlated with body mass index but is independent of operating lung volumes and of airway closure. Furthermore, methacholine-induced bronchoconstriction only occurred in the lower lung zone in individuals who were not obese, whereas in subjects who were obese, it occurred more evenly across all lung zones. These findings show that obesity-associated factors alter the topographical distribution of ventilation.

Background and objective Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple-breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high-dose ICS/LABA treatment. Methods A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs5Hz ) and reactance (Xrs5Hz ), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion-convection-dependent (Sacin) and convection-dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily. Results Treatment improved ACQ5 (P = 0.0002), FEV1 (P = 0.02), FVC (P = 0.04), FeNO (P = 0.0008), Xrs5Hz (P = 0.01), LCI (P = 0.0002), Sacin (P = 0.006) and Scond (P = 0.01). At baseline, ACQ5 correlated with Xrs5Hz (rs = 0.52, P = 0.03) and Rrs5Hz (rs = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI (P = 0.03), Scond (P = 0.02) and Rrs5Hz (P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC-AUC = 0.91, P = 0.007). Conclusion Step-up to high-dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs5Hz and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up-titration in uncontrolled asthmatic patients.

There is limited evidence linking airway inflammation and lung function impairment in older non-smoking asthmatics with fixed airflow obstruction (FAO), which can develop despite treatment with inhaled corticosteroids (ICS). We assessed lung function (spirometry, forced oscillation technique (FOT)), lung elastic recoil and airway inflammation using bronchoalveolar lavage (BAL) in non-smoking adult asthmatics with FAO, following 2 months treatment with high-dose ICS/long-acting beta-agonist. Subjects demonstrated moderate FAO, abnormal FOT indices and loss of lung elastic recoil. This cross-sectional study showed a lack of a relationship between BAL neutrophils, eosinophils, inflammatory cytokines and lung function impairment. Other inflammatory pathways or the effect of inflammation on lung function over time may explain FAO development.

Background and Aim: Multiple-breath nitrogen washout (MBNW) system validation is based on accurate functional residual capacity (FRC) measurement. Our aim was to perform in-vitro and in-vivo FRC comparisons between 2 commercial devices (EasyOne Pro® LAB, ndd Medical Technologies, analysed using both clinical (“nddClinical”) and updated research software (“nddWBreath” Version 3.41.4.1); Exhalyzer® D, Eco Medics AG, “EM”) and an in-house device (“WIMR”). Methods:In-vitro FRC (FRCin-vitro) was measured using an optimised syringe lung model (FRC 2.11 L, ATPD conditions). In-vivo FRC (FRCin-vivo) was measured in 18 healthy and 9 asthmatic subjects (10 male;mean±SD age 37±13 years). MBNW measurements were performed in triplicate on each device, in random order on the same day, followed by body plethysmography (Pleth). FRC differences between devices were examined by repeated measures ANOVA and posthoc tests. Results: FRCin-vitro measurements were within 10% of 2.11 L on all devices except on nddClinical. FRCin-vivo measurements on all devices were significantly different from each other (p Conclusion: FRC can be standardised across MBNW devices in-vitro but accuracy varies in-vivo. Better understanding of the reasons behind these differences is vital for MBNW standardisation efforts. A syringe lung model provides useful information as a MBNW development and calibration.

Loss of lung elastic recoil is associated with increased ventilation heterogeneity in diffusion-dependent airways in older nonsmokers with asthma and fixed airflow obstructionhttp://ow.ly/g2Sk30nbVXv