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Sharon R Davis,1 Biljana Cvetkovski,1 Gregory Peter Katsoulotos,2,* Joy W Lee,3,* Janet Rimmer,4,* Natasha Smallwood,3,* Katrina O Tonga,5,* Penelope Abbott,6 Sinthia Z Bosnic-Anticevich1,7 1Woolcock Institute of Medical Research, Macquarie Park, NSW, Australia; 2School of Medicine, Sydney Campus, The University of Notre Dame, Sydney, NSW, Australia; 3Department of Respiratory Medicine, Alfred Hospital, Melbourne, VIC, Australia; 4Department of Respiratory Medicine, St Vincent’s Hospital, Darlinghurst, NSW, Australia; 5Respiratory Department, Westmead Hospital, Westmead Clinical School, Faculty of Medicine & Health, University of Sydney, Sydney, NSW, Australia; 6School of Medicine, Western Sydney University, Penrith, NSW, Australia; 7Macquarie Medical School, Macquarie University, Macquarie Park, NSW, Australia*These authors contributed equally to this workCorrespondence: Biljana Cvetkovski, Email biljana.cvetkovski@woolcock.org.auPurpose: Severe asthma poses a significant health burden in those with the disease, therefore a timely diagnosis can ensure patients receive specialist care and appropriate medication management. This study qualitatively explored the patient experience of adult Australians with severe asthma regarding specialist referral, to identify potential opportunities to streamline the process of severe asthma diagnosis and treatment and optimise referral pathways.Patients and Methods: Adults currently being treated with medication for severe asthma were invited to participate in this study. Participants were interviewed and asked to describe initial diagnosis of their asthma or severe asthma, and how they came to be referred to secondary care. Interviews were transcribed verbatim, coded by two members of the research team and thematically analysed.Results: Thirty-two people completed the study; 72% were female. Mean interview length was 33 minutes. The major themes generated were patient-related factors contributing to seeking a severe asthma diagnosis; perceptions of health care provision; diagnosis of severe asthma and the referral journey. Key findings were that both patient and healthcare provider attitudes contributed to participants’ willingness to seek or receive a referral, and referral to respiratory specialists was often delayed. Contributing factors included a mismatch between patient expectations and general practice, lack of continuity of primary care, and a lack of patient understanding of the role of the respiratory specialist.Conclusion: Timely severe asthma diagnosis in Australia appears to be hampered by an absence of a clear referral process, lack of general practitioner (GP) knowledge of additional treatment options, underutilisation of pharmacists, and multiple specialists treating patient comorbidities. Directions for future research might include interviewing healthcare providers regarding how well the referral process works for severe asthma patients, and researching the time between referral and when a patient sees the respiratory specialist.Keywords: respiratory, patient, referral, diagnosis, comorbidities

Background: Descriptions of eosinophils in transbronchial biopsy (TBBx) pathology reports after lung transplantation (LTx) are associated with poor long-term outcomes. The absence of routine reporting and standardization precludes accurate assessment of this histologic predictor. A systematic reporting scheme for the presence of TBBx eosinophils after LTx was implemented. This report aims to assess this scheme by describing the presence, pattern, and gradation of TBBx eosinophils and clinical associations., Methods: A prospective cross-sectional study of all TBBx reports was performed including all patients presenting for a surveillance or diagnostic TBBx between January 2020 and June 2023. Each TBBx was systematically reported in a blinded manner. Mixed-effects logistic regression was performed to measure the association between concurrent clinical and histologic features, and the presence of TBBx eosinophils., Results: A total of 410 TBBx reports from 201 patients were systematically reported. In 43.8% recipients, any TBBx eosinophils were detected and in 17.1% recipients, higher-grade eosinophils (≥3 per high power field) were present. Adjusted analysis showed that retransplantation, A- and B-grade cellular rejection, positive bronchoalveolar lavage (BAL) bacterial microbiology, and elevated blood eosinophil count were independently associated with the presence of any TBBx eosinophils. Diagnostic "for-cause" procedures were independently associated with higher quantities of TBBx eosinophils., Conclusions: Systematic reporting demonstrates that TBBx eosinophils are a distinct inflammatory response associated with rejection, infection, and peripheral eosinophilia. Although these findings require multicenter external validation, standardized reporting for TBBx eosinophils may assist in identifying recipients at risk of poor outcomes and provides a platform for mechanistic research into their role after lung transplantation., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Peak spirometry after single lung transplantation (SLTx) for interstitial lung disease (ILD) is lower than after double lung transplantation (DLTx), however the pathophysiologic mechanisms are unclear. We aim to assess respiratory mechanics in SLTx and DLTx for ILD using oscillometry. Spirometry and oscillometry (tremoflo ® C-100) were performed in stable SLTx and DLTx recipients in a multi-center study. Resistance (R 5 , R 5-19 ) and reactance (X 5 ) were compared between LTx recipient groups, matched by age and gender. A model of respiratory impedance using ILD and DLTx data was performed. In total, 45 stable LTx recipients were recruited (SLTx n = 23, DLTx n = 22; males: 87.0% vs. 77.3%; median age 63.0 vs. 63.0 years). Spirometry was significantly lower after SLTx compared with DLTx: %-predicted mean (SD) FEV 1 [70.0 (14.5) vs. 93.5 (26.0)%]; FVC [70.5 (16.8) vs. 90.7 (12.8)%], p < 0.01 . R 5 and R 5-19 were similar between groups ( p = 0.94 and p = 0.11 , respectively) yet X 5 was significantly worse after SLTx: median (IQR) X 5 [-1.88 (-2.89 to -1.39) vs. -1.22 (-1.87 to -0.86)] cmH 2 O.s/L], p < 0.01 . R 5 and X 5 measurements from the model were congruent with measurements in SLTx recipients. The similarities in resistance, yet differences in spirometry and reactance between both transplant groups suggest the important contribution of elastic properties to the pathophysiology. Oscillometry may provide further insight into the physiological changes occurring post-LTx., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sim, Nilsen, Borg, Levvey, Vazirani, Ennis, Plit, Snell, Darley and Tonga.)

Chronic obstructive pulmonary disease (COPD) is a complex and serious disease that is characterized by dyspnea, fatigue, decreased exercise tolerance, peripheral muscle dysfunction, and mood disorders. These manifestations are successfully treated with pulmonary rehabilitation, a comprehensive intervention and holistic approach designed to improve the physical and psychological condition of people with COPD. Exercise is a big component of pulmonary rehabilitation programs, but the efficacy of non-traditional forms of exercise as used in alternative medicine is poorly understood. Here, we aim to address this gap in knowledge and summarize the clinical evidence for the use of traditional exercise regimens in the pulmonary rehabilitation of COPD patients.

Background: Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry measures respiratory system mechanics and may provide insight into understanding the mechanisms of BLAD., Objectives: This study aims to describe and measure the association between airway oscillometry parameters [Reactance (X rs5 , Ax), Resistance (R rs5 , R rs5-19 )] (1) stable LTx recipients, comparing those with normal spirometry and those with BLAD; and (2) in recipients with chronic lung allograft dysfunction (CLAD), comparing those with normal baseline spirometry and those with BLAD., Methods: A multi-center cross-sectional study was performed including bilateral LTx between January 2020 and June 2021. Participants performed concurrent airway oscillometry and spirometry. Multivariable logistic regression was performed to measure the association between oscillometry parameters and BLAD., Results: A total of 404 LTx recipients performed oscillometry and 253 were included for analysis. Stable allograft function was confirmed in 149 (50.2%) recipients (92 (61.7%) achieving normal spirometry and 57 (38.3%) with BLAD). Among stable LTx recipients, lower X rs5 Z-Score (aOR 0.50 95% CI 0.37-0.76, p = 0.001) was independently associated with BLAD. CLAD was present in 104 (35.0%) recipients. Among recipients with CLAD, lower X rs5 Z-Score (aOR 0.73 95% CI 0.56-0.95, p = 0.02) was associated with BLAD., Conclusions: Oscillometry provides novel physiologic insights into mechanisms of BLAD. The independent association between X rs5 and BLAD, in both stable recipients and those with CLAD suggests that respiratory mechanics, in particular abnormal elastance, is an important physiologic feature. Further longitudinal studies are needed to understand the trajectory of oscillometry parameters in relation to allograft outcomes., Competing Interests: Financial conflict of interest statement Funding for this study was provided by in-kind support by the Lung Transplant St Vincent's Hospital Sydney and the Lung Transplant Service, The Alfred Hospital Melbourne., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., (© 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Asthma with irreversible or fixed airflow obstruction (FAO) is a severe clinical phenotype that is difficult to treat and is associated with an accelerated decline in lung function and excess morbidity. There are no current treatments to reverse or prevent this excessive decline in lung function in these patients, due to a lack of understanding of the underlying pathophysiology. The current paradigm is that FAO in asthma is due to airway remodeling driven by chronic inflammation. However, emerging evidence indicates significant and critical structural and functional changes to the lung parenchyma and its lung elastic properties in asthma with FAO, suggesting that FAO is a 'whole lung' problem and not just of the airways. In this Perspective we draw upon what is known thus far on the pathophysiological mechanisms contributing to FAO in asthma, and focus on recent advances and future directions. We propose the view that structural and functional changes in parenchymal tissue, are just as (if not more) important than airway remodeling in causing persistent lung function decline in asthma. We believe this paradigm of FAO should be considered when developing novel treatments., Competing Interests: GK reports that during the last 5 years and conduct of the study; grants, personal fees and other from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini, MundiPharma, Chiesi, Cipla, 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. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rutting, Thamrin, Cross, King and Tonga.)

Airway smooth muscle cells from severe asthma patients with FAO respond to β 2 -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., Competing Interests: Conflict of interest: S. Rutting has nothing to disclose. Conflict of interest: D. Xenaki has nothing to disclose. Conflict of interest: K.D. Reddy has nothing to disclose. Conflict of interest: M. Baraket has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: G.G. King reports grants, personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, MundiPharma and Novartis; and unrestricted research grants from the NHMRC, Boehringer Ingelheim, CycloPharma, GlaxoSmithKline, Menarini, MundiPharma, philanthropic individuals and societies; and nonfinancial and other support from Restech, Italy, during the conduct of the study. Conflict of interest: B.G. Oliver has nothing to disclose. Conflict of interest: K.O. Tonga reports a Lung Foundation Australia Ludwig Engel grant-in-aid during the conduct of the study., (Copyright ©The authors 2021.)

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., Competing Interests: Conflict of interest: S. Rutting has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: T. Badal has nothing to disclose. Conflict of interest: F. Sanai has nothing to disclose. Conflict of interest: S.C. Zimmermann reports nonfinancial support for travel and accommodation for educational respiratory symposia attendance from GlaxoSmithKline, Boehringer Ingelheim, Menarini, AstraZeneca and Novartis, outside the submitted work. Conflict of interest: C. Thamrin has nothing to disclose. Conflict of interest: G.G. King reports unrestricted research grants to support research projects, fees for consultancy services (which include lectures and advisory board services) and conference attendance support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants from the National Health & Medical Research Council, professional societies, The University of Sydney, and philanthropic individuals and societies, outside the submitted work. Conflict of interest: K.O. Tonga has nothing to disclose., (Copyright ©ERS 2021.)

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 (Rrs 5 ) and respiratory system reactance at 5 Hz (Xrs 5 ) 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 (FEV 1 /FVC), Rrs 5 and Xrs 5 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 FEV 1 : -2.2 ± 0.5, FVC: -0.7 ± 1.0, FEV 1 /FVC: -2.6 ± 0.7) and by increased Rrs 5 (median (IQR) z-score) 2.7 (1.9 to 3.2) and decreased Xrs 5 : -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. FEV 1 /FVC correlated negatively with K (r s = -0.60, P = 0.008) and Rrs 5 correlated negatively with B/A (r s = -0.52, P = 0.026), independent of age. Xrs 5 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)., (© 2019 Asian Pacific Society of Respirology.)

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 (Vent non ), low ventilated (Vent low ), or well ventilated (Vent well ) 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, Vent non and Vent low for the entire lung were similar in subjects with and without obesity. However, in the upper lung zone, Vent non (17.5 ± 10.6% vs. 34.7 ± 7.8%, P < 0.001) and Vent low (25.7 ± 6.3% vs. 33.6 ± 5.1%, P < 0.05) were decreased in subjects with obesity, with a consequent increase in Vent well (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 ( r s  = 0.74, P < 0.001), respiratory system resistance ( r s  = 0.72, P < 0.001), and respiratory system reactance ( r s  = -0.64, P = 0.003) but not with lung volumes or basal airway closure. Following bronchoprovocation, overall Vent non increased similarly in both groups; however, in subjects without obesity, Vent non only increased in the lower zone, whereas in subjects with obesity, Vent non 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.

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 ) t E , 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 t E 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.

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., Competing Interests: Conflict of interest: S.C. Zimmermann has nothing to disclose. Conflict of interest: K.O. Tonga has nothing to disclose. Conflict of interest: C. Thamrin has a patent (WO 2006130922 A1) issued and intellectual property arrangements with two FOT device companies, Thorasys Medical Systems and Restech srl relating to scientific collaborations, but does not have any financial relationships with either company., (Copyright ©ERS 2019.)

Functional residual capacity (FRC) accuracy is essential for deriving multiple-breath nitrogen washout (MBNW) indices, and is the basis for device validation. Few studies have compared existing MBNW devices. We evaluated in vitro and in vivo FRC using two commercial MBNW devices, the Exhalyzer D (EM) and the EasyOne Pro LAB (ndd), and an in-house device (Woolcock in-house device, WIMR). FRC measurements were performed using a novel syringe-based lung model and in adults (20 healthy and nine with asthma), followed by plethysmography (FRC pleth ). The data were analysed using device-specific software. Following the results seen with ndd, we also compared its standard clinical software (ndd v.2.00) with a recent upgrade (ndd v.2.01). WIMR and EM fulfilled formal in vitro FRC validation recommendations (>95% of FRC within 5% of known volume). Ndd v.2.00 underestimated in vitro FRC by >20%. Reanalysis using ndd v.2.01 reduced this to 11%, with 36% of measurements ≤5%. In vivo differences from FRC pleth (mean±sd) were 4.4±13.1%, 3.3±11.8%, -20.6±11% (p<0.0001) and -10.5±10.9% (p=0.005) using WIMR, EM, ndd v.2.00 and ndd v.2.01, respectively. Direct device comparison highlighted important differences in measurement accuracy. FRC discrepancies between devices were larger in vivo , compared to in vitro results; however, the pattern of difference was similar. These results represent progress in ongoing standardisation efforts., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.com