Dyspnoea is a common subjective experience associated with decreased exercise tolerance and mortality. Although several studies have explored its prevalence in the general population, there has been limited synthesis over broad income settings, particularly low-income countries. This review and meta-analysis aims to address these gaps by reviewing the global prevalence of dyspnoea across low, middle, and high-income countries and associated factors. A systematic review and meta-analysis were completed evaluating the prevalence of dyspnoea in the general population and associated factors including age, BMI, smoking status, underlying conditions, lung function indices and country of residence. The protocol followed PRISMA guidelines and was prospectively registered with PROSPERO (CRD42022374929). Of 13,504 records screened, 56 studies were included with a total of 450,520 participants. Using the mMRC Dyspnoea Scale, (n = 43), the pooled prevalence of dyspnoea was 22.2

Background: Life-course lung function trajectories leading to airflow obstruction, as measured by impaired FEV1/FVC (forced vital capacity), precede the onset of chronic obstructive pulmonary disease (COPD). We aimed to investigate whether individuals on impaired FEV1/FVC trajectories have an increased burden of respiratory symptoms, including those who do not meet the spirometric criteria for COPD. Methods: We analysed serial life-course data from two population-based cohort studies separately, which included respiratory symptoms and spirometry: the Tasmanian Longitudinal Health Study (TAHS, Australia) cohort was recruited at age 6-7 years and followed up until middle age (mean age 53 years; range 51-55); and the Coronary Artery Risk Development in Young Adults (CARDIA, USA) cohort was recruited at a mean age of 25 years (range 18-30) and followed up to a mean age of 55 years (range 47-64). Participants' symptom profiles at ages 53 and 55 years were derived by latent class analysis. Symptom profiles were compared across pre-bronchodilator FEV1/FVC trajectories derived by group-based modelling, then restricted to those without COPD defined by post-bronchodilator airflow obstruction (FEV1/FVC <5th percentile) at ages 51-55 years and 47-64 years. Findings: Six FEV1/FVC trajectories previously derived for TAHS were replicated in CARDIA. Optimal models identified five symptom profiles in TAHS (n=2421) and six in CARDIA (n=3153). For both cohorts, the most impaired FEV1/FVC trajectory (early low, rapid decline in TAHS; low peak, rapid decline in CARDIA) was associated with predominant wheeze (multinomial odds ratio [mOR] 671 [95% CI 410-1090] in TAHS and 990 [452-2170] in CARDIA) and nearly all respiratory symptoms (495 [252-974] and 1480 [597-3660]) at age 51-55 years in TAHS and age 47-64 years in CARDIA, compared with the average trajectory. Among individuals belonging to the three most impaired trajectories, the associations with predominant wheeze increased with worsening FEV1/FVC impairment and persisted when considering only those without spirometry-defined COPD. Additionally, for those belonging to the two rapid decline trajectories, both wheezing and usual phlegm or bronchitis were reported by 54 (20%) of 265 participants younger than 14 years in TAHS and by 31 (25%) of 123 participants aged 30 years or younger in CARDIA. Interpretation: In two independent cohorts that collected similar data, people on impaired FEV1/FVC trajectories often had a longstanding history of both wheeze and phlegm or bronchitis, and wheeze was the predominant symptom in individuals aged 47-64 years among those who had not already progressed to COPD.

BACKGROUND:Return-to-work (RTW) following lung transplant has been associated with increased quality of life, but little is known regarding the rates of and barriers to this in the Australian population. AIMS:We aimed to describe, characterise and determine predictors of return to work and social participation in Australian lung transplant recipients. We also sought to explore the relationship between return to work and quality of life. METHODS:We conducted a cross-sectional questionnaire-based study at the Alfred Hospital, Melbourne between October 2018 and August 2019. The questionnaire evaluated demographics, transplant history, respiratory parameters, employment history and social integration prior to and after lung transplantation. RESULTS:A total of 172 lung transplant recipients were included for analysis. The population was mostly male (56.5%), median age 61 years (interquartile range (IQR) 49.8-67.0) and median time from transplant 4 years (IQR 2-7). A total of 19.2% of patients were working at time of transplant, with 35.5% working after transplant representing an increase in workforce engagement of 84.8% (P < 0.001). A total of 96% of those who returned to work reported an improvement in quality of life. Median time to RTW after transplant was 180 days (IQR 90-360). Multivariable analysis demonstrated an increased rate of RTW in younger recipients (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.89-0.99, adjusted P = 0.029), at greater length of time after transplant (OR 1.09, 95% CI 0.99-1.19, P = 0.084), among those working at the time of transplant (OR 9.55, 95% CI 2.70-33.75, P < 0.001) and with higher socioeconomic status (OR 1.02, 95% CI 1.01-1.04, P = 0.009). Recipients with cystic fibrosis were more likely to RTW (65.8%) than those with other underlying conditions. CONCLUSIONS:RTW should be encouraged in lung transplant recipients. Targeted supports and resources aimed at younger recipients may result in greater workforce engagement and overall outcomes after transplant.

This Thoracic Society of Australia and New Zealand Guideline on the provision of home oxygen therapy in adults updates a previous Guideline from 2015. The Guideline is based upon a systematic review and meta-analysis of literature to September 2022 and the strength of recommendations is based on GRADE methodology. Long-term oxygen therapy (LTOT) is recommended for its mortality benefit for patients with COPD and other chronic respiratory diseases who have consistent evidence of significant hypoxaemia at rest (PaO2 <= 55 mm Hg or PaO2 <= 59 mm Hg in the presence of hypoxaemic sequalae) while in a stable state. Evidence does not support the use of LTOT for patients with COPD who have moderate hypoxaemia or isolated nocturnal hypoxaemia. In the absence of hypoxaemia, there is no evidence that oxygen provides greater palliation of breathlessness than air. Evidence does not support the use of supplemental oxygen therapy during pulmonary rehabilitation in those with COPD and exertional desaturation but normal resting arterial blood gases. Both positive and negative effects of LTOT have been described, including on quality of life. Education about how and when to use oxygen therapy in order to maximize its benefits, including the use of different delivery devices, expectations and limitations of therapy and information about hazards and risks associated with its use are key when embarking upon this treatment.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the first-line treatment but recent reports suggest the efficacy of granulocyte–macrophage colony-stimulating factor (GM-CSF). We aimed to review the efficacy and safety of nebulised GM-CSF in aPAP. Methods: We conducted a systematic review and meta-analysis searching Embase, CINAHL, MEDLINE and Cochrane Collaborative databases (1946–1 April 2022). Studies included patients aged >18 years with aPAP receiving nebulised GM-CSF treatment and a comparator cohort. Exclusion criteria included secondary or congenital pulmonary alveolar proteinosis, GM–CSF allergy, active infection or other serious medical conditions. The protocol was prospectively registered with PROSPERO (CRD42021231328). Outcomes assessed were St George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), gas exchange (diffusing capacity of the lung for carbon monoxide (DLCO) % predicted) and arterial–alveolar oxygen gradient. Results: Six studies were identified for review and three for meta-analysis, revealing that SGRQ score (mean difference −8.09, 95% CI −11.88– −4.3, p<0.0001), functional capacity (6MWT) (mean difference 21.72 m, 95% CI −2.76–46.19 m, p=0.08), gas diffusion (DLCO % predicted) (mean difference 5.09%, 95% CI 2.05–8.13%, p=0.001) and arterial–alveolar oxygen gradient (mean difference −4.36 mmHg, 95% CI −7.19– −1.52 mmHg, p=0.003) all significantly improved in GM-CSF-treated patients with minor statistical heterogeneity (I2=0%). No serious trial-related adverse events were reported. Conclusions: Patients with aPAP treated with inhaled GM-CSF demonstrated significant improvements in symptoms, dyspnoea scores, lung function, gas exchange and radiology indices after treatment with nebulised GM-CSF of varying duration. There is an important need to review comparative effectiveness and patient choice in key clinical outcomes between the current standard of care, whole lung lavage, with the noninvasive treatment of nebulised GM-CSF in aPAP.

Obstructive sleep apnea (OSA) is a significant healthcare burden affecting approximately one billion people worldwide. The prevalence of OSA is rising with the ongoing obesity epidemic, a key risk factor for its development. While in-laboratory polysomnography (PSG) is the gold standard for diagnosing OSA, it has significant drawbacks that prevent widespread use. Portable devices with different levels of monitoring are available to allow remote assessment for OSA. To better inform clinical practice and research, this comprehensive systematic review evaluated diagnostic performances, study cost and patients’ experience of different levels of portable sleep studies (type 2, 3, and 4), as well as wearable devices and non-contact systems, in adults. Despite varying study designs and devices used, portable diagnostic tests are found to be sufficient for initial screening of patients at risk of OSA. Future studies are needed to evaluate cost effectiveness with the incorporation of portable diagnostic tests into the diagnostic pathway for OSA, as well as their application in patients with chronic respiratory diseases and other comorbidities that may affect test performance.

Background: There has been a rapid growth in wearables marketed to measure sleep. Fitbit trackers collect data through an internal accelerometer and use heart rate variability to estimate the sleep-wake state. There is a paucity of “real-world” data in patients who are being evaluated for sleep disorders. Aim: To evaluate the agreement between Fitbit Charge3TM & in-lab polysomnography (PSG) in patients who require a PSG for assessment. Methods: A prospective study of patients attending a PSG through Epworth Camberwell Sleep Lab between 2020-2021 was conducted. Fitbit Charge3TM was worn on the dominant wrist with concurrent PSG monitoring. Parameters measured included total sleep time; TST (min), Sleep onset latency; SOL (min), sleep efficiency; SE (%), wake after sleep onset; WASO (min) and time spent in N1, N2, N3 and REM sleep (min). 30 second epoch-by-epoch analyses were conducted. Results: Seventy patients (male=52), median age of 55 years; IQR(45,67) completed the study. On average, the Fitbit significantly overestimated light sleep by 62.99 min, TST by 29.50 min, and SE by 3.33% and underestimated deep sleep by 40.55 min WASO by 28 min. Fitbit and PSG did not significantly differ on REM or SOL measurements. Conclusion: Our findings may support the use of Fitbit Charge3TM as an initial screening device to assess sleep duration and architecture in select patients attending sleep clinics Table 1: Comparison of sleep variables between PSG and Fitbit Charge 3TM

Oxygen is a life-saving therapy but, when given inappropriately, may also be hazardous. Therefore, in the acute medical setting, oxygen should only be given as treatment for hypoxaemia and requires appropriate prescription, monitoring and review. This update to the Thoracic Society of Australia and New Zealand (TSANZ) guidance on acute oxygen therapy is a brief and practical resource for all healthcare workers involved with administering oxygen therapy to adults in the acute medical setting. It does not apply to intubated or paediatric patients. Recommendations are made in the following six clinical areas: assessment of hypoxaemia (including use of arterial blood gases); prescription of oxygen; peripheral oxygen saturation targets; delivery, including non-invasive ventilation and humidified high-flow nasal cannulae; the significance of high oxygen requirements; and acute hypercapnic respiratory failure. There are three sections which provide (1) a brief summary, (2) recommendations in detail with practice points and (3) a detailed explanation of the reasoning and evidence behind the recommendations. It is anticipated that these recommendations will be disseminated widely in structured programmes across Australia and New Zealand.

Qaseem A, Etxeandia-Ikobaltzeta I, Fitterman N, et al. Ann Intern Med. 2021;174:977-84. 33900796.

Abstract Background There has been a rapid growth in wearable devices marketed for sleep. Trackers such as the Fitbit collect data through an accelerometer and use heart rate variability to estimate the sleep-wake state. Currently, Fitbit validation studies have only been with “healthy” adults and Insomnia Disorder. Aims The purpose of this study is to evaluate the accuracy of Fitbit Charge3TM compared to in-lab polysomnography (PSG) in patients with sleep disorders. Our hypothesis is that Fitbit Charge 3TM will perform with less sensitivity and specificity relative to PSG in the presence of sleep disorders. Methods A prospective study of patients attending a PSG through Epworth Camberwell Sleep Lab between 2019–2021 will be conducted. Fitbit Charge3TM will be worn on the wrist with concurrent PSG monitoring. Parameters measured with both PSG and Fitbit Charge3TM will include total sleep time, Sleep onset latency, wake after sleep onset and time spent in N1, N2, N3 and REM sleep (min). Standard PSG data will be evaluated to diagnose sleep-disordered breathing. Progress to date:Ethics approval has been obtained, and 110 participants have been recruited. 30-second epoch-by-epoch analysis will now be conducted. Bland-Altman analyses will be performed to assess agreement between the Fitbit and PSG. Intended outcome and impact: Our novel study findings will provide evidence to address queries regarding the accuracy of the Fitbit trackers to evaluate sleep and may support the use of Fitbit Charge3TM as an initial screening device to assess sleep duration and sleep architecture in select patients.

Purpose of review Nasal high flow therapy (NHF) is increasingly used in acute care settings. In this review, we consider recent advances in the utilization of NHF in chronic obstructive pulmonary disease (COPD), terminal cancer and symptom management. Considerations around NHF use during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are also discussed. Recent findings NHF enables humidification and high flows to be provided together with titrated, supplemental oxygen therapy. Compared to conventional oxygen therapy, NHF improves respiratory physiology by reducing workload, enhancing muco-ciliary clearance and improving dead space washout. Some studies suggest that early use of NHF in people being cared for in the emergency department leads to lower rates of invasive ventilation and noninvasive ventilation. There is also emerging evidence for NHF use in people with COPD and chronic respiratory failure, and in palliative care. NHF is comfortable, well-tolerated and safe for use in the management of breathlessness in people with cancer. NHF can be delivered by face mask to patients with SARS-CoV-2 infection, to ease the burden on critical care resources. Summary The evidence base for NHF is rapidly growing and offers promise in relieving troublesome symptoms and for people receiving palliative care.

Pulmonary alveolar proteinosis (PAP) is a rare respiratory syndrome, which can be challenging to diagnose given its non-specific presentation and imaging findings. While most primary cases of PAP have an autoimmune basis, the triggers for the disease are uncertain with occupational factors increasingly thought to be important. We report the unusual complication of pneumomediastinum and bilateral pneumothoraces following endobronchial ultrasound-guided transbronchial needle aspirate in the setting of PAP. We discuss the possible physiological mechanisms of this complication, which appears to be more common in conditions with reduced lung compliance.

SOURCE CITATION Qaseem A, Etxeandia-Ikobaltzeta I, Fitterman N, et al. Appropriate use of high-flow nasal oxygen in hospitalized patients for initial or postextubation management of acute respiratory failure: a clinical guideline from the American College of Physicians. Ann Intern Med. 2021;174:977-84. 33900796.

Introduction: Bronchiolitis obliterans syndrome (BOS) after allogeneic haemopoietic stem cell transplant (HSCT) is an under-recognised and difficult to treat disease. This occurs in the context of limited clinical research and inconsistent diagnostic criteria. Method: Retrospective data was collected on 275 patients who underwent allogeneic HSCT at an Australian tertiary hospital between 2007 and 2017. The prevalence of BOS, defined by 2014 National Institute of Health criteria, as well as predictors for BOS and mortality were determined. Treatment outcomes, using serial spimmetry, were compared between patients who received early versus late immunosuppression for BOS. Results: The prevalence of BOS was 9.1%. Myeloablative conditioning (OR: 2.7, 95%CI: 1.13-6.50, p = 0.03) and extra-pulmonary chronic graft-versus-host disease (OR 2.62, 95% CI: 1.04-6.60, p = 0.04) were associated with BOS. There was reduced median survival in the BOS group compared with the non-BOS group, but this was not statistically significant (4.lyears (IQR: 2.8, 6.8) versus 4.6years (IQR: 2.4, 7.8), respectively, p = 0.33). The vast majority (87.5%) of BOS patients failed to attain improvement in FEV1 at 12 months, regardless of treatment strategy. Patients who underwent a late immunosuppression strategy had worse mean FEV1 decline compared to those who received early immunosuppression (-36.3% versus -1.6%, respectively, p = 0.03). Conclusion: BOS is a common and progressive disease following HSCT and is largely refractory to current treatment strategies. Compared to late immunosuppression, early augmentation of immunosuppression may slow lung function deterioration in the short term. However, further research is urgently needed to identify effective prevention and treatment strategies for BOS.

Sleep disordered breathing (SDB) in heart failure (HF) is a common co-morbidity with an estimated prevalence of 50%. The high prevalence of mood disorders (anxiety and depression) in individuals with obstructive sleep apnoea (OSA) is well described. Little is known about the prevalence of mood disorders in central sleep apnoea (CSA). Aim: In patients with HF who had a polysomnography, our aim was to, (i) characterise the prevalence of SDB (OSA vs CSA) & (ii) assess anxiety & depression scores (14 question Hospital Anxiety and Depression Scale (HADS)) with a significant HADS A & D score of 8 & 11 respectively. Method: A retrospective record analysis of patients coded with a diagnosis of heart failure who underwent a polysomnography & transthoracic echocardiogram at a tertiary hospital between 2013-2019 were included. Results: 200 patients (68% males, median age 58 years) were included. 49% of patients had at least moderate OSA (AHI >15) & 5% had moderate CSA (AHI > 15). 24% of patients with OSA (AHI > 15) had an elevated HADS D score, however this was not statistically significant when compared to CSA (AHI >15) p=0.88. Similarly, 11% of patients reported a high HADS A score in the OSA group however was not significant compared to CSA (p=0.33). There was a trend towards higher HADS D scores for patients with SDB vs no SDB, however this was not statistically significant (25% vs 14%). Conclusion: HF patients with SDB report higher HADS D scores & lower HADS A scores compared to patients with no SDB. There was no significant difference in depression or anxiety scores between OSA & CSA patients. Further studies are needed to understand the strong interplay of mood disorders with HF & SDB.

Objectives: The epidemiology, clinical characteristics and outcomes of antimicrobial-associated anaphylaxis remain ill-defined. We sought to examine antimicrobial anaphylaxis with regard to: (i) the frequency of implicated antimicrobials; (ii) attributable mortality; and (iii) referral for definitive allergy assessment. Methods: This was conducted through a national retrospective multicentre cohort study at five Australian tertiary hospitals (January 2010 to December 2015). Cases of antimicrobial anaphylaxis were identified from ICD-10 coding and adverse drug reaction committee databases. Results: There were 293 participants meeting the case definition of antimicrobial anaphylaxis and 310 antimicrobial anaphylaxis episodes. Of 336 implicated antimicrobials, a minopenicillins (62/336, 18.5%) and a minocephalosporins (57/336, 17%) were implicated most frequently. ICU admission occurred in 43/310 (13.9%) episodes; however, attributable mortality was low (3/310, 1%). The rate of anaphylaxis to IV antibiotics was 3.5 (95% CI=2.9-4.3) per 100000 DDDs and the rate of hospital-acquired anaphylaxis was 1.9 (95% CI=2.1-3.3) per 100000 occupied bed-days. We observed overall low rates of hospital discharge documentation (222/310, 71.6%) and follow-up by specialist allergy services (73/310, 23.5%), which may compromise medication safety and antimicrobial prescribing in future. Conclusions: This study demonstrated that a high proportion of severe immediate hypersensitivity reactions presenting or acquired in Australian hospitals are secondary to aminopenicillins and aminocephalosporins. Overall rates of hospital-acquired anaphylaxis, predominantly secondary to cephalosporins, are low, and also associated with low inpatient mortality.

Medical Journal of AustraliaVolume 213, Issue 3 p. 109-110.e1 Perspectives E-cigarette or vaping product use-associated lung injury (EVALI): a cautionary tale Maitri Munsif, orcid.org/0000-0003-2755-4137 Alfred Health, Melbourne, VICSearch for more papers by this authorMark Hew, Alfred Health, Melbourne, VICSearch for more papers by this authorEli Dabscheck, Corresponding Author e.dabscheck@alfred.org.au Alfred Health, Melbourne, VICSearch for more papers by this author Maitri Munsif, orcid.org/0000-0003-2755-4137 Alfred Health, Melbourne, VICSearch for more papers by this authorMark Hew, Alfred Health, Melbourne, VICSearch for more papers by this authorEli Dabscheck, Corresponding Author e.dabscheck@alfred.org.au Alfred Health, Melbourne, VICSearch for more papers by this author First published: 29 June 2020 https://doi.org/10.5694/mja2.50691 Podcast with Eli Dabscheck available at mja.com.au/podcasts Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume213, Issue3August 2020Pages 109-110.e1 RelatedInformation

We report the first case of hypotensive episodes associated with intravenous (IV) azithromycin. This is a potentially fatal adverse drug reaction (ADR), with the risk of irreversible end‐organ damage, and therefore must be recognized and treated immediately. In our case, the reaction was successfully managed by immediate cessation of the azithromycin infusion. It is important for clinicians to be aware of this ADR as azithromycin is a commonly prescribed medication worldwide.