Teck Boon Low

IMMUNOLOGICAL COROLLARY OF THE PULMONARY MYCOBIOME IN BRONCHIECTASIS: THE CAMEB STUDY

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis. Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes. The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations. The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients. The airway mycobiome in bronchiectasis is associated with clinically significant disease http://ow.ly/MCKj30knVrn

Disseminated Cryptococcus gattii infection preceding onset of pulmonary alveolar proteinosis: Cryptococcosis preceding PAP onset

A 50‐year‐old immunocompetent man presented with intracranial space‐occupying lesions and a right lung mass. This was found to be disseminated Cryptococcus gattii infection. Following 15 months of anti‐fungal therapy, imaging showed reduction in the size of the pulmonary cryptococcoma and new multi‐lobar ground‐glass opacities interspersed with a crazy‐paving pattern. Surgical lung biopsy was performed after bronchoscopic evaluation was non‐yielding. Histology showed intra‐alveolar accumulation of foamy macrophages and airspaces containing periodic acid Schiff‐positive amorphous eosinophilic material with strong immune positivity for surfactant A, consistent with a diagnosis of pulmonary alveolar proteinosis (PAP). The majority of adult‐onset PAP is due to the presence of anti‐granulocyte macrophage colony‐stimulating factor antibodies. Opportunistic fungal and mycobacterial infections are known to occur in these patients due to alveolar macrophage and neutrophilic dysfunction. The onset of PAP may occur concurrently with, or be temporally distinct from, opportunistic infections. For patients with respiratory failure, whole lung lavage is a therapeutic strategy.

A new therapeutic avenue for bronchiectasis: Dry powder inhaler of ciprofloxacin nanoplex exhibits superior ex vivo mucus permeability and antibacterial efficacy to its native ciprofloxacin counterpart

Graphical abstract Figure. No caption available. ABSTRACT Non‐cystic fibrosis bronchiectasis (NCFB) characterized by permanent bronchial dilatation and recurrent infections has been clinically managed by long‐term intermittent inhaled antibiotic therapy among other treatments. Herein we investigated dry powder inhaler (DPI) formulation of ciprofloxacin (CIP) nanoplex with mannitol/lactose as the excipient for NCFB therapy. The DPI of CIP nanoplex was evaluated against DPI of native CIP in terms of their (1) dissolution characteristics in artificial sputum medium, (2) ex vivo mucus permeability in sputum from NCFB and healthy individuals, (3) antibacterial efficacy in the presence of sputum against clinical Pseudomonas aeruginosa strains (planktonic and biofilm), and (4) cytotoxicity towards human lung epithelial cells. Despite their similarly fast dissolution rates in sputum, the DPI of CIP nanoplex exhibited superior mucus permeability to the native CIP (5–7 times higher) attributed to its built‐in ability to generate highly supersaturated CIP concentration in the sputum. The superior mucus permeability led to the CIP nanoplexs higher antibacterial efficacy (>3 log10 CFU/mL). The DPI of CIP nanoplex exhibited similar cytotoxicity towards the lung epithelial cells as the native CIP indicating its low risk of toxicity. These results established the promising potential of DPI of CIP nanoplex as a new therapeutic avenue for NCFB.