Fungal contamination of valved holding chambers (VHCS): potential to prevent, and effect on drug delivery


MJ Sanders 1, R Bruin 1, CH Tran 2

Author address:

1. Clement Clarke International Ltd, Harlow, UK;
2. i2c Pharmaceutical Services, Cardiff, UK

Full conference title:

British Thoracic Society Winter Meeting 2016


Introduction and objectives Able Spacerâ−2 VHC (AS2) is one of many accessory devices available to improve pressurised metered dose inhaler (pMDI) drug delivery, but uniquely includes a ∼ 1wt% body polymer silver ion additive ( ∼ 1%Ag+) to combat microbial growth and reduce static. Drug-specific bacterial growth on VHC polymers1 and the bacterial growth-reducing effects of the Ag+ polymer are known.2 The fungal pathogen Aspergillus fumigatus causes serious pulmonary disease. We assessed the effect of 4%Ag+ on fungal activity and, subsequently, drug delivery characteristics.

Methods Determination of fungal sporicidal activity was via modified ISO22196:2011 using flat body polymer discs (n = 3) of AS2 ∼ 1% Ag+ and AS2 4%Ag+, and sterile Control (same polymer minus Ag+, n = 6). 100mL A. fumigatus (5.0 x 105 spores/mL distilled water) was pipetted onto disc surfaces. Samples were incubated for 24 h at 35°C/ ≥ 95% relative humidity, with silver ions neutralised thereafter. Colony forming units (CFU) were enumerated by spiral dilution and converted to CFU/cm2. Aerosol performance of salbutamol (as salbutamol sulphate) pMDI (Ventolinâ Evohaler, GSK) through AS2 VHC ( ∼ 1% Ag+ as standard) and a newly-developed AS2 4% Ag+ VHC was assessed through a Next Generation Impactor (NGI) at 30 L/min. pMDIs and NGI were operated, and drug determinations made, using standard procedures.

Results 24 h geometric mean Log10 A. fumigatus CFU/cm2 were 4.2 × 103 (Control), 2.8 × 103 ( ∼ 1% Ag+), and 4.5 × 102 (4% Ag+), representing Log10 and% reductions from Control of 0.2 (34%) and 1.0 (89%) for ∼1% Ag+ and 4% Ag+. Key salbutamol aerosol performance data were emitted dose (mg) 95.9 ± 11.0 and 94.9 ± 9.1; fine particle fraction (% < 5.0 mm) 54.0 ± 4.3 and 53.6 ± 1.9; and fine particle dose (mg < 5.0 mm) 52.0 ± 8.7 and 50.7 ± 3.8 for AS2 ∼ 1% Ag+ and AS2 4% Ag+ respectively. NGI recovery (Figure 1) profiles were very similar, including the VHC component: 38.9 ± 4.2 (AS2 ∼ 1% Ag+) and 40.2 ± 5.3 (AS2 4% Ag+).

Conclusions Use of 4%Ag+ additive did not affect salbutamol aerosol performance and showed greater effect on A. fumigatus spored activity in vitro. VHC fungal Candida spp. and nebuliser Aspergillus spp. have been identified. The moist, anti-static setting of the Chamber may support and, of more concern, promote aerosolisation into the lungs of fungal material. Further research and understanding are necessary.


  1. Sanders. PCRM 2016;26(16022):16.

  2. Sanders MJ, et al. P87 Klebsiella Pneumoniae Survival On Plastic Valved Holding Chamber Bodies. Thorax 2014;69(Suppl 2):A114.

Abstract Number: P129

Conference Year: 2016

Link Conference abstract: 

BTS WM 2016

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