Nebulised granulocyte-macrophage colony-stimulating factor (GM-CSF) in autoimmune pulmonary alveolar proteinosis: a systematic review and meta-analysis.

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 (D LCO) % 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 (D LCO % 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.

Portable evaluation of obstructive sleep apnea in adults: A systematic review.

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.

Thoracic Society of Australia and New Zealand Position Statement on Acute Oxygen Use in Adults: 'Swimming between the flags'.

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.

Pulmonary alveolar proteinosis with an unusual bronchoscopic complication.

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.

ACP provided 2 conditional recommendations on use of high-flow nasal oxygen in acute respiratory failure.

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.

Nasal high flow oxygen therapy during acute admissions or periods of worsening symptoms.

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.

Updated prevalence, predictors and treatment outcomes for bronchiolitis obliterans syndrome after allogeneic stem cell transplantation.

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 spirometry, 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 (4.1years (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.

Antimicrobial anaphylaxis: the changing face of severe antimicrobial allergy.

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, aminopenicillins (62/336, 18.5%) and aminocephalosporins (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 100 000 DDDs and the rate of hospital-acquired anaphylaxis was 1.9 (95% CI=2.1-3.3) per 100 000 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.

Hypotensive episodes associated with azithromycin infusion: a potentially fatal adverse drug reaction.

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.

Risk of anastomotic dehiscence in patients with pulmonary fibrosis transplanted while receiving anti-fibrotics: Experience of the Australian Lung Transplant Collaborative.

BACKGROUND: The new anti-fibrotics pirfenidone and nintedanib are now in widespread use for idiopathic pulmonary fibrosis (IPF), but they may have an adverse impact on pathways involved in wound-healing. This study aimed to establish the safety of anti-fibrotic therapy in the peri-transplant period, particularly with regard to healing of the bronchial anastomosis. METHODS: In this work we assessed a retrospective cohort of patients who had undergone lung transplantation with a diagnosis of pulmonary fibrosis between January 2012 and December 2017. Pre-transplant use of pirfenidone and nintedanib was identified. Anastomotic dehiscence of any extent was determined at bronchoscopy. Known risk factors for anastomotic dehiscence were evaluated in both anti-fibrotic and control groups. RESULTS: Two hundred twenty-six patients (160 males; mean age 59.7 ± 7.8 years) underwent transplantation in Australia for pulmonary fibrosis during the study period. Forty (17.7%) were receiving anti-fibrotics at the time of transplantation (29 with pirfenidone and 11 with nintedanib). There were 7 anastomotic dehiscence events, with overall incidence rates of 7.5% and 2.2% in the anti-fibrotic and control groups, respectively (p = 0.08). All episodes of dehiscence in the anti-fibrotic group and 2 of 4 in the comparator group occurred <6 weeks post-transplant. Survival at 30days was 100% and 96% (p = 0.21) and at 1 year was 93% and 88% (p = 0.01) in the anti-fibrotic and comparator groups, respectively. Two patients with dehiscence died. The other 5 anastomotic defects resolved, with 1 requiring stent insertion. CONCLUSIONS: The incidence of bronchial dehiscence after transplantation for IPF is low and is not significantly higher in patients receiving anti-fibrotic therapy at the time of transplantation.