David Geoffrey Chapman

Background: Many individuals with chronic obstructive pulmonary disease (COPD) experience frequent hospitalization and readmissions, which is burdensome on the health system. This study aims to investigate factors associated with unplanned readmissions and mortality following a COPD-related hospitalization over a 12-month period in Australia, focusing on mental disorders and accounting for the acute phase of the COVID-19 pandemic. Methods: A retrospective cohort study using linked hospitalization and mortality records identified individuals aged ≥40 years who had at least one hospital admission with a principal diagnosis of COPD between 2014 and 2020 in New South Wales, Australia. A semi-competing risk analysis was conducted to examine factors associated with unplanned readmission and mortality. Results: Adults with a mental disorder diagnosis, specifically anxiety, had a higher risk of 12-month unplanned readmission. Individuals with anxiety and dementia also had a higher risk of mortality pre- and post-unplanned readmission. Individuals who were admitted during the acute phase of the COVID-19 pandemic period had lower risk of unplanned readmission, but higher risk of mortality without unplanned readmission. Conclusion: Interventions aimed at reducing admissions should consider adults living with mental disorders such as anxiety or dementia to improve healthcare delivery and health outcomes for individuals living with COPD.

The Thoracic Society of Australia and New Zealand (TSANZ) and the Australian and New Zealand Society of Respiratory Science (ANZSRS) commissioned a joint position paper on pulmonary function testing during coronavirus disease 2019 (COVID‐19) in July 2021. A working group was formed via an expression of interest to members of both organizations and commenced work in September 2021. A rapid review of the literature was undertaken, with a ‘best evidence synthesis’ approach taken to answer the research questions formed. This allowed the working group to accept findings of prior relevant reviews or societal document where appropriate. The advice provided is for providers of pulmonary function tests across all settings. The advice is intended to supplement local infection prevention and state, territory or national directives. The working group's key messages reflect a precautionary approach to protect the safety of both healthcare workers (HCWs) and patients in a rapidly changing environment. The decision on strategies employed may vary depending on local transmission and practice environment. The advice is likely to require review as evidence grows and the COVID‐19 pandemic evolves. While this position statement was contextualized specifically to the COVID‐19 pandemic, the working group strongly advocates that any changes to clinical/laboratory practice, made in the interest of optimizing the safety and well‐being of HCWs and patients involved in pulmonary function testing, are carefully considered in light of their potential for ongoing use to reduce transmission of other droplet and/or aerosol borne diseases.

Introduction: The multiple breath nitrogen washout (MBNW) test provides important clinical information in obstructive airways diseases. Recently, a significant cross-sensitivity error in the O₂and CO₂sensors of a widely used commercial MBNW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) was detected, which leads to overestimation of N₂concentrations. Significant errors in functional residual capacity (FRC) and lung clearance index (LCI) have been reported in infants and children. This study investigated the impact in adults, and on additional important indices reflecting conductive (S_cond) and acinar (S_acin) ventilation heterogeneity, in health and disease.Methods: Existing MBNW measurements of 27 healthy volunteers, 20 participants with asthma and 16 smokers were reanalysed using SPIROWARE V 3.3.1, which incorporates an error correction algorithm. Uncorrected and corrected indices were compared using paired t-tests and Bland–Altman plots.Results: Correction of the sensor error significantly lowered FRC (mean difference 9%) and LCI (8–10%) across all three groups.S_condwas higher following correction (11%, 14% and 36% in health, asthma and smokers, respectively) with significant proportional bias.S_acinwas significantly lower following correction in the asthma and smoker groups, but the effect was small (2–5%) and with no proportional bias.Discussion: The O₂and CO₂cross-sensitivity sensor error significantly overestimated FRC and LCI in adults, consistent with data in infants and children. There was a high degree of underestimation ofS_condbut minimal impact onS_acin. The presence of significant proportional bias indicates that previous studies will require reanalysis to confirm previous findings and to allow comparability with future studies.

Introduction: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function.Methods: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (Rrs₆) and reactance (Xrs₆) at 6 Hz, before and after inhalation of salbutamol 200 μg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease inRrs₆and 95th percentile increase inXrs₆in a healthy subgroup.Results: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔRrs₆was −1.38 cmH₂O·s·L⁻¹(−30.0% or −1.42 Z-scores) and upper threshold for ΔXrs₆was 0.57 cmH₂O·s·L⁻¹(1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔXrs₆was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score.Discussion: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry.

Asthma is characterized by heterogeneous ventilation as measured by three-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) treatment response is variable in asthma, and effects on regional ventilation are unknown. Our aims were to determine whether regional ventilation defects decrease after ICS/LABA treatment and whether small airways dysfunction predicts response in uncontrolled asthma. Twenty-two symptomatic participants with asthma underwent single-photon emission computed tomography (SPECT)/CT imaging with Technegas, before and after 8-wk fluticasone/formoterol (1,000/40 µg/day) treatment. Lung regions that were nonventilated, low ventilated, or well ventilated were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. Multiple-breath nitrogen washout (MBNW) was used to measure diffusion-dependent and convection-dependent small airways function (Sacin and Scond, respectively). Forced oscillation technique (FOT) was used to measure respiratory system resistance and reactance. At baseline and posttreatment, Scond z-score was related to percentage of nonventilated lung, whereas Sacin z-score was related to percentage of low-ventilated lung. Although symptoms, spirometry, FOT, and MBNW improved following treatment, there was no mean change in ventilation measured by SPECT. There was, however, a wide range of changes in SPECT ventilation such that greater percentage of nonventilated lung, older age, and higher Scond predicted a reduction in nonventilated lung after treatment. SPECT ventilation defects are overall unresponsive to ICS/LABA, but the response is variable, with improvement occurring when small airways dysfunction and ventilation defects are more severe. Persistent ventilation defects that correlate with Scond suggest that mechanisms such as non-ICS responsive inflammation or remodeling underlie these defects. NEW & NOTEWORTHY This study provides insights into the mechanisms of high-dose ICS treatment in uncontrolled asthma. Ventilation defects as measured by SPECT/CT imaging respond heterogeneously to increased ICS/LABA treatment, with improvement occurring when ventilation defects and impairment of convection-dependent small airways function are more severe. Persistent correlations between ventilation defects and measures of small airways function suggest the potential presence of ICS nonresponsive inflammation and/or remodeling.

Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM_2.5 (PM_2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM_2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM_2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM_2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM_2.5 exerted transgenerational impairment on lung health.

In older non-smokers with asthma and fixed airflow obstruction, X₅ measured by oscillometry reflects dynamic rather than static compliance. Distinguishing between dynamic and static compliance is important as they are due to different factors.https://bit.ly/3th0uEr

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

FOT parameters have good long-term repeatability in patients with stable obstructive airways disease, facilitating its ability to detect sensitive changes in airways disease. Novel cut-off values presented may help determine clinically significant change.https://bit.ly/3emL7FI