Cyanide in bronchoalveolar lavage is not diagnostic forPseudomonas aeruginosain children with cystic fibrosis

Abstract

Early detection of the cyanobacterium Pseudomonas aeruginosa in the lungs of young children with cystic fibrosis (CF) is considered the key to delaying chronic pulmonary disease. We investigated whether cyanide in bronchoalveolar lavage (BAL) fluid could be used as an early diagnostic biomarker of infection.Cyanide was measured in 226 BAL samples (36 P. aeruginosa infected) obtained from 96 infants and young children with CF participating in an early surveillance programme involving annual BAL.Cyanide was detected in 97.2% of P. aeruginosa infected and 60.5% of uninfected samples. Cyanide concentrations were significantly higher in BALs infected with P. aeruginosa (median (25th-75th percentile) 27.3 (22.1-33.3) mM) than those which were not (17.2 (7.85-23.0) mM, p,0.001). The best sensitivity, specificity, positive and negative predictive values were obtained with a cut-off concentration of 20.6 mM, and were 83%, 66%, 32% and 96%, respectively. Neutrophil number in BAL was a significant predictor of cyanide concentration (p,0.001).Cyanide concentration can distinguish between P. aeruginosa infected and uninfected BALs as a group, but not individually; therefore, cyanide is a poor diagnostic biomarker of P. aeruginosa infection. Cyanide levels in BAL are related to the level of neutrophilic inflammation.

Variation in hydrogen cyanide production between different strains ofPseudomonas aeruginosa

“…Regarding phenotype, previous studies have reported higher cyanide production by mucoid P. aeruginosa cultures [20,27]. Our data suggest the opposite, with nonmucoid cultures having higher HCN concentrations.…”

“…This is supported in vitro by reports of leukocytes challenged with Staphylococcus epidermidis producing HCN [25,26] and a recent study from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) team who found the neutrophil number in bronchoalveolar lavage (BAL) samples to be a predictor of cyanide concentration [27]. However, BAL neutrophil count is significantly higher in patients infected with P. aeruginosa compared with those with no infection or infection with other organisms [28] and previous studies have not identified cyanide in patients infected with organisms other than P. aeruginosa [13][14][15].…”

“…However, BAL neutrophil count is significantly higher in patients infected with P. aeruginosa compared with those with no infection or infection with other organisms [28] and previous studies have not identified cyanide in patients infected with organisms other than P. aeruginosa [13][14][15]. The high percentage of P. aeruginosa negative patients in whom cyanide was identified in the AREST CF study [27] is in contrast to previous papers and this is likely to be the reason why the authors were unable to use cyanide to differentiate between the patients who had P. aeruginosa infection and those they believed to be free from P. aeruginosa.…”

Pseudomonas aeruginosaand cyanide production

“…In the current issue of the European Respiratory Journal, STUTZ et al [24] have once again shown that cyanide is increased in relation to P. aeruginosa infection in children with CF. However, they also found increased levels of cyanide in children apparently uninfected with the organism and their results suggest that the differences between the two groups of patients were too small to be of value in the individual patient to use cyanide as a marker for the early detection/presence of P. aeruginosa.…”

Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function

“…HCN is volatile and its usefulness as a surrogate marker for the diagnosis of P. aeruginosa infection in children who cannot expectorate sputum is currently being investigated [21][22][23].…”