Granulocyte macrophage colony stimulating factor (GM-CSF) is a key participant in, and a clinical target for, the treatment of inflammatory diseases including rheumatoid arthritis (RA). Therapeutic inhibition of GM-CSF signalling using monoclonal antibodies to the α-subunit of the GM-CSF receptor (GMCSFRα) has shown clear benefit in patients with RA, giant cell arteritis (GCAs) and some efficacy in severe SARS-CoV-2 infection. However, GM-CSF autoantibodies are associated with the development of pulmonary alveolar proteinosis (PAP), a rare lung disease characterised by alveolar macrophage (AM) dysfunction and the accumulation of surfactant lipids. We assessed how the anti-GMCSFRα approach might impact surfactant turnover in the airway. Female C57BL/6J mice received a mouse-GMCSFRα blocking antibody (CAM-3003) twice per week for up to 24 weeks. A parallel, comparator cohort of the mouse PAP model, GM-CSF receptor β subunit (GMCSFRβ) knock-out (KO), was maintained up to 16 weeks. We assessed lung tissue histopathology alongside lung phosphatidylcholine (PC) metabolism using stable isotope lipidomics. GMCSFRβ KO mice reproduced the histopathological and biochemical features of PAP, accumulating surfactant PC in both broncho-alveolar lavage fluid (BALF) and lavaged lung tissue. The incorporation pattern of methyl-D9-choline showed impaired catabolism and not enhanced synthesis. In contrast, chronic supra-pharmacological CAM-3003 exposure (100 mg/kg) over 24 weeks did not elicit a histopathological PAP phenotype despite some changes in lung PC catabolism. Lack of significant impairment of AM catabolic function supports clinical observations that therapeutic antibodies to this pathway have not been associated with PAP in clinical trials.

(1959) found that an angulated catheter entered the left main bronchus through a tracheostomy tube far more readily than a straight catheter. Straight plastic catheters seldom entered the left bronchus regardless of the patient's head position (Kirimli et al., 1970). Even in infants, in whom the left and right main bronchi diverge from the trachea at almost equal angles, Bush (1963) observed that a straight catheter entered the right main bronchus far more commonly than the left. Haberman et al. (1973) have developed some practical guidelines that maximise the change of aspirating the left main bronchus. They recommended the use of angletipped catheters that had been packed straight rather than coiled, and that orotracheal rather than nasotracheal tubes be used. They also suggested that the patient's head should be turned to the right during catheter insertion. In 24 patients they had a 46% success rate in entering the left main bronchus, their successes increasing to over 60% in those patients with tracheostomies.We have used many of the guidelines suggested by Haberman et al. (1973) for catheterising the left main bronchus in a large number of patients. Our success rate was similar to that in previous studies and our experience has encouraged us to propose a further recommendation related to the length of catheters. Material and methodsForty-one patients in the Respiratory Intensive Care Unit were studied, 15 with tracheostomies and 26 with orotracheal tubes. The catheters were washed through with a radio-opaque solution, Lipiodol-Lafay (Denver Laboratories (Canada Limited)) for visualisation on the chest film. A total of 40 insertions was made on each group of patients, 20 with straight catheters and 20 with angled catheters.Intensive care unit nurses performed the aspirations. Specific attempts were made to place the catheter in the left main bronchus using catheter manipulation. In view of the minimal improvement reported by Haberman when turning the head to the contralateral side, this procedure was not followed. Initially the catheter was advanced until a resistance was met. A chest radiograph was then taken to determine the position of the catheter. All patients tolerated the procedure well.

Vascular rings can present with non-specific respiratory and/or oesophageal symptoms. Early diagnosis requires a high index of suspicion. This case report describes an uncommon acute presentation of a vascular ring. We report a thriving 14-month-old child with a long history of recurrent wheeze and ‘noisy breathing’. He presented acutely with food bolus impaction in the oesophagus which led to a respiratory arrest. Oesophagoscopy and bronchoscopy suggested vascular ring anomaly. A contrast-enhanced CT scan demonstrated a right-sided aortic arch with left ligamentum arteriosum encircling the oesophagus and airway. The ligament was ligated and divided. At follow-up 6 months later, the infant had mild persistent stridor but was otherwise well.