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.

Silver nitrate therapy for persistent tracheocutaneous fistula following prolonged tracheostomy and invasive ventilation: A case report.

We report the case of a man with severe Guillain-Barré syndrome who developed a persistent tracheocutaneous fistula (TCF) following prolonged tracheostomy and mechanical ventilation. Following tracheostomy decannulation, the TCF had a deleterious effect on non-invasive positive pressure ventilation efficacy and ability to effectively clear airway secretions due to air leaking from the patent stoma. This case highlights a non-surgical approach to TCF management that is not well-described in the literature and presents an alternative management option for cohorts of patients in which the risk associated with surgical interventions may be undesirable.

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.

Nocturnal hypoxaemia in interstitial lung disease: a systematic review.

BACKGROUND: Patients with interstitial lung disease (ILD) are at risk of developing nocturnal hypoxaemia due to ventilatory restriction and impaired gas exchange that worsen with supine posture and reduced ventilatory drive during sleep. This systematic review synthesised literature on the diagnostic evaluation, epidemiology, associations, management and prognosis of nocturnal hypoxaemia in ILD. METHODS: Ovid MEDLINE, Embase and CENTRAL databases were searched for eligible studies. Meta-analyses with subgroup analyses were conducted, where possible. RESULTS: Fifty-three studies were included (total participant number=2590). The most common definition for clinically significant nocturnal hypoxaemia was ≥10% of total sleep time with oxyhaemoglobin saturation <90%, with pooled prevalence of 37%. There were no significant differences in pooled prevalence according to ILD subtype and comorbid obstructive sleep apnoea status. Study heterogeneity precluded meta-analysis of associations and prognosis. Diffusing capacity for carbon monoxide (DLCO) and echocardiographic features for pulmonary hypertension were consistently associated with nocturnal hypoxaemia. There were inconsistent associations between nocturnal hypoxaemia with ILD subtype and severity. Multivariable analyses in most studies demonstrated significant associations of nocturnal hypoxaemia with survival. Two small short-term intervention studies demonstrated that supplemental oxygen of 1-3 L/min corrected nocturnal hypoxaemia, with improved heart rate control during in-laboratory observation and increased serum antioxidant levels after 1 month of therapy. CONCLUSION: Nocturnal hypoxaemia is common, associated with DLCO impairment and markers suggestive of pulmonary hypertension, and a potential prognostic factor in patients in ILD. There is a need to establish a consensus definition of nocturnal hypoxaemia and evaluate long-term effects of nocturnal supplemental oxygen in ILD.

Poor initiation of smoking cessation therapies in hospitalised patients with chronic obstructive pulmonary disease is associated with low levels of formal training among hospital doctors and under-utilisation of nursing-led interventions.

BACKGROUND: Smoking cessation intervention is a key component in the management of chronic obstructive pulmonary disease (COPD). AIMS: To evaluate the prescribing of smoking cessation therapies (SCT) among hospital clinicians and identify factors that may hinder delivery of effective interventions. METHODS: A retrospective analysis of medical records of patients admitted to the Royal Hobart Hospital with an acute exacerbation of COPD was performed. A survey of hospital clinicians was also performed to ascertain levels of training and confidence in prescribing SCT. RESULTS: Nearly all medical and non-medical hospital clinicians self-reported confidence in offering SCT (91.1 vs 82.5%, respectively, P = 0.216). However, of the 122 eligible patients in our study population, the majority did not have any form of SCT initiated during their admission (n = 68, 55.7%) and only 21 patients (17.2%) were referred to the nurse-led smoking cessation service. Very few patients were initiated on efficacious regimes such as combination-nicotine replacement therapy (n = 8, 6.6%) or varenicline (n = 2, 1.6%). Only a small proportion of hospital doctors reported confidence in prescribing varenicline and bupropion (17.2 and 6.9%, respectively). Furthermore, very few hospital doctors reported ever receiving formal training in SCT compared to non-medical hospital staff (42.2 vs 84.5%, P < 0.001). CONCLUSION: Our study highlights the real-life challenges in tackling nicotine dependence in hospitals: under-utilisation of evidence-based pharmacotherapies, limited access to formal training for doctors and poor uptake of nurse-led smoking cessation services. Granting limited prescribing rights for specialised nurses may help hospital clinicians to alleviate gaps in current clinical practice.