Longitudinal assessment of cystic fibrosis pulmonary diseaseusing clinical, biochemical and emerging microbiological techniques

Abstract

Cystic Fibrosis (CF) causes chronic lower respiratory tract infection leading to morbidity and mortality. CF Pulmonary Exacerbations (CFPEs) cause accentuated symptoms and increase mortality. The definition and aetiology of CFPEs has however proved elusive. Recently, culture independent techniques have shown that there is much greater diversity of bacteria than previously detected by culture dependent methods. Building on this, in the work presented here, the bacteria in respiratory samples from adults with CF were studied over a 12 month period. Each subject provided thrice weekly sputum samples for analysis by culture and culture independent microbiological methods. Concurrently an in-depth assessment of their subjective and objective health using Visual Analogue Scales (VAS) and spirometry (FEV1) was undertaken. Inflammation markers were also measured.

A total of 2061 samples from fourteen adults (mean age 30.2; mean FEV1% predicted 53.3%; 6 females; 8 ?F508 homozygotes) were collected. Subjective VAS measures correlated with objective spirometric measures. However, previously unsuspected complexity of subjective symptomatology was found. Ribosomal clone sequence analysis identified 90 different species, including 15 not previously reported in CF lung disease. Notably 44% of species detected were obligate anaerobes, and 72% were species previously associated with the human oro-pharynx. During the study period, subjects experienced 42 CFPEs requiring treatment. New species were not seen to enter the bacterial community as aetiological agents for CFPEs. However, whilst treatment for CFPEs caused a large fall in the proportion of anaerobic species, no significant change in the proportion of Pseudomonas aeruginosa was detected.

Significant and potentially important differences in bacterial community composition, structure and stability between subjects separated by gender, genotype and lung function were observed. Moreover, the presence of certain species correlated with subjects suffering frequent CFPEs.

The results presented here give new insights in to the complexity of symptoms and bacterial diversity in CF pulmonary disease

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