Managing the Steps in Cystic Fibrosis Pulmonary Flare-ups

A new study entitled “Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention,” published in The International Society for Microbial Ecology Journal, investigated how bacterial communities in the lung change over time in relation to the disease state and progression of cystic fibrosis. The study’s researchers believe that the findings are highly relevant to improving standard management strategies for pulmonary exacerbations.

Cystic fibrosis (CF) is a recessive genetic disorder affecting an estimated 100,000 individuals worldwide. Although the disease affects several organs, the main cause of morbidity and mortality is chronic lung infections and concomitant airway inflammation. Until recently, there has been no approved treatment available that addresses the underlying cause of the disease, and the best alternative for treating CF has been to improve upon therapies that address chronic polymicrobial lung infections.

In cystic fibrosis patients, there is gradual decline of pulmonary function interlaced with periods of severe deterioration of respiratory symptoms, known as CF pulmonary exacerbations (CFPEs). These cumulative pulmonary exacerbations are associated with a rapid disease progression and lower survival as well as a reduction in quality of life and an increase in healthcare costs. Presently, there is no agreement among clinicians for a common definition of CFPE symptoms.

CFPEs are treated with high-dose intravenous antibiotics that affect a wide group of pathogens, but are used frequently in CF patients to target Pseudomonas aeruginosa, the most prevalent disease pathogen. It is widely accepted that urgent management of CFPE leads to a better prognosis and increased probability of patient recovery, stressing the importance of CFPE diagnosis. As a result, identifying and developing more consistent biomarkers of disease state change is crucial. Due to a lack of studies, moreover, there is an essential knowledge gap in relation to how CF microbiota behaves and responds to CFPE, and in subsequent antibiotic interventions.

In this study, several sputum samples were collected from 10 CF adult patients during a CFPE. The results were divided into five clinical periods: (B₀) baseline pre-CFPE; (E) CFPE, 30 days prior to treatment; (T) treatment for CFPE; (R) recovery, 30 days post-CFPE; and (B₁) baseline post-CFPE.  Additionally, several sputum samples were collected from two adult CF patients who were clinically stable during the same time period (B₀ only). During periods B₀, E, R, and B₁, patients were receiving their standard doses of maintenance antibiotics. For the treatment phase, patients were hospitalized and received intravenous antibiotics. The study allowed for a full examination of how changes in CF microbiota are associated with the appearance of CFPEs, the effect of antibiotic therapy during CFPE on the CF microbiota, and the identification of potential biomarkers of disease state alteration.

The research team found, consistent with previous studies, that the whole microbiota did not significantly change in composition during the five clinical periods analyzed, suggesting resistance to disturbances by antibiotics therapy within the lung. They also found that P. aeruginosa‘s proportional abundance remained high in all clinical periods, even showing a considerable increase in the recovery state. This could be explained by the antibiotic therapy leading to a decrease in other less abundant pathogens, thereby allowing P. aeruginosa to grow and take advantage of newly available physical niche space. However, P. aeruginosa returned to baseline levels after the 30-day post-treatment recovery period, probably to the resilience of the less abundant species. These findings are of particular interest to clinicians, since the antibiotic treatment seems to not impact positively on P. aeruginosa.

The researchers in the study also identified Veillonella species related to V. parvula/rogosae and Prevotella species related to P. melaninogenica/veroralis/histicola as potential biomarkers of disease state, since there were significant alterations in their abundance from baseline before starting antibiotic treatment. However, the authors emphasize the need to develop new analytic tools to target the Veillonella and Prevotella species to test the efficacy of these less abundant species as molecular diagnostic tools for the onset of CFPE.

Acknowledging the relatively small sample size of the study, the authors stress the relevance of their findings to current management strategies for CFPEs. They also highlight that this type of study may help disclose the essential cause or causes of CFPE.

The authors concluded by stating, “this study strongly highlights the merits of continual reassessment of existing antimicrobial treatment regimens and antibiotic delivery strategies.”