Patients with cystic fibrosis (CF) whose lungs have never been colonized by the Pseudomonas aeruginosa bacterium have a milder form of the disease, a retrospective study based on registry data suggests.
The study, “Clinical and microbiological characteristics of cystic fibrosis adults never colonized by Pseudomonas aeruginosa: Analysis of the French CF registry,” was published in the journal Plos One.
P. aeruginosa infections in the airways can cause inflammation and subsequent pulmonary exacerbations that impair lung function over time.
Previous reports from national CF registries in the U.S., Canada, France, Germany, Ireland, and the U.K. all suggest that P. aeruginosa prevalence in CF patients increases with age up to 20-25 years old, and then stabilizes at 50-70 percent afterward. This means that 30-50% of CF patients do not have P. aeruginosa. These percentages also include patients who have been infected but cleared of the bacterium by antibiotic treatment.
To better understand predictive features associated with P. aeruginosa infection history, a research team in France evaluated differences between CF patients with no clinical history of P. aeruginosa and patients with reported P. aeruginosa colonization (the bacterium is established in the airways).
The study analyzed data from 2,130 patients, ages 20 and older, in the French CF patient registry between 2013 and 2014. Of these, 1,827 had been reported positive for P. aeruginosa at least once, and 303 had no documented history of P. aeruginosa colonization.
Researchers compared clinical features of CF patients, including age, CFTR mutations, pancreas-related implications, and lung function. They also analyzed associations between P. aeruginosa exposure history and the prevalence of other pathogenic bacteria.
They found six clinical features that were independently associated with CF patients without documented P. aeruginosa infection: older age at diagnosis, absence of diabetes, absence of aspergillosis (infection by fungi Aspergillus), pancreatic sufficiency, absence of F508del mutations in the CFTR gene (the main cause of CF), and forced expiratory volume in one second (a measure of lung function) equal or greater than 80%, which is considered a normal value, indicating preserved lung function.
In particular, analysis of CFTR mutation types showed that a lack of F508del — a common mutation in CF — in both alleles (maternal and paternal) was significantly associated with patients with no documented P. aeruginosa history. F508del is linked to about 70 percent of defective CFTR alleles, and has been shown to predispose CF patients to infections by opportunistic pathogens such as P. aeruginosa.
Negative correlations between four preventable or treatable comorbidities, or coexisting conditions, and the absence of P. aeruginosa infection were also found. Patients who had never been colonized by P. aeruginosa showed an absence of aspergillosis (which is common in CF patients), diabetes, and pancreatic insufficiency. Furthermore, compared with CF patients with previous P. aeruginosa colonization, these patients also had preserved lung function.
When researchers further analyzed the association between bacterial infections and the two patient groups, they found distinct microbiological profiles related to patients without reported P. aeruginosa histories. Specifically, this patient group was significantly associated with the presence of Haemophilus influenzae, and absence of Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Aspergillus spp.
“The fact that these organisms, just like P. aeruginosa, are essentially responsible for opportunistic infections reinforce the idea that patients in the [“Never colonized”] group have a better health status than those in the [“Previously colonized”] group,” the researchers wrote.
They note that retrospective studies, although valuable, cannot confirm any causal relationships in CF patients with or without P. aeruginosa.
“A prospective study would be necessary to assess these factors, especially in the pediatric population, as the primary colonization with P. aeruginosa occurs at a mean age of 8 years in [France],” they said.
“The lower prevalence of aspergillosis, diabetes, pancreatic insufficiency and F508del/F508del genotype in the [“Never colonized”] population together with older age at CF diagnosis are consistent with a milder form of the disease and better capacity of this minority of patients to resist colonization by P. aeruginosa and other environmental microbes,” the researchers concluded.