Oisin O'Connell

Bacterial cis -2-unsaturated fatty acids found in the cystic fibrosis airway modulate virulence and persistence of Pseudomonas aeruginosa

There is an increasing appreciation of the polymicrobial nature of many bacterial infections such as those associated with cystic fibrosis (CF) and of the potentially important role for interspecies interactions in influencing both bacterial virulence and response to therapy. Patients with CF are often co-infected with Pseudomonas aeruginosa and other pathogens including Burkholderia cenocepacia and Stenotrophomonas maltophilia. These latter bacteria produce signal molecules of the diffusible signal factor (DSF) family, which are cis-2-unsaturated fatty acids. We have previously shown by in vitro studies that DSF from S. maltophilia leads to altered biofilm formation and increased resistance to antibiotics by P. aeruginosa; these responses of P. aeruginosa require the sensor kinase PA1396. Here we show that DSF signals are present in sputum taken from patients with CF. Presence of these DSF signals was correlated with patient colonization by S. maltophilia and/or B. cenocepacia. Analysis of 50 clinical isolates of P. aeruginosa showed that each responded to the presence of synthetic DSF by increased antibiotic resistance and these strains demonstrated little sequence variation in the PA1396 gene. In animal experiments using CF transmembrane conductance regulator knockout mice, the presence of DSF promoted P. aeruginosa persistence. Furthermore, antibiotic resistance of P. aeruginosa biofilms grown on human airway epithelial cells was enhanced in the presence of DSF. Taken together, these data provide substantial evidence that interspecies DSF-mediated bacterial interactions occur in the CF lung and may influence the efficacy of antibiotic treatment, particularly for chronic infections involving persistence of bacteria.

Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades.

OBJECTIVE With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period. METHODS Estimated cumulative effective dose (CED) from all thoracic and extrathoracic imaging modalities and interventional radiology procedures for both adult and pediatric patients with CF, exclusively attending a nationally designated CF center between 1992-2009 for > 1 year, was determined. The study period was divided into three equal tertiles, and estimated CED attributable to all radiologic procedures was estimated for each tertile. RESULTS Two hundred thirty patients met inclusion criteria (2,240 person-years of follow-up; 5,596 radiologic procedures). CED was > 75 mSv for one patient (0.43%), 36 patients (15.6%) had a CED between 20 and 75 mSv, 56 patients (24.3%) had a CED between 5 and 20 mSv, and in 138 patients (60%) the CED was estimated to be between 0 and 5 mSv over the study period. The mean annual CED per patient increased consecutively from 0.39 mSv/y to 0.47 mSv/y to 1.67 mSv/y over the tertiles one to three of the study period, respectively (P < .001). Thoracic imaging accounted for 46.9% of the total CED and abdominopelvic imaging accounted for 42.9% of the CED, respectively. There was an associated 5.9-fold increase in the use of all CT scanning per patient (P < .001). CONCLUSIONS This study highlights the increasing exposure to ionizing radiation to patients with CF as a result of diagnostic imaging, primarily attributable to CT scanning. Increased awareness of CED and strategies to reduce this exposure are needed.

Microbiota and Metabolite Profiling Reveal Specific Alterations in Bacterial Community Structure and Environment in the Cystic Fibrosis Airway during Exacerbation

Chronic polymicrobial infections of the lung are the foremost cause of morbidity and mortality in cystic fibrosis (CF) patients. The composition of the microbial flora of the airway alters considerably during infection, particularly during patient exacerbation. An understanding of which organisms are growing, their environment and their behaviour in the airway is of importance for designing antibiotic treatment regimes and for patient prognosis. To this end, we have analysed sputum samples taken from separate cohorts of CF and non-CF subjects for metabolites and in parallel, and we have examined both isolated DNA and RNA for the presence of 16S rRNA genes and transcripts by high-throughput sequencing of amplicon or cDNA libraries. This analysis revealed that although the population size of all dominant orders of bacteria as measured by DNA- and RNA- based methods are similar, greater discrepancies are seen with less prevalent organisms, some of which we associated with CF for the first time. Additionally, we identified a strong relationship between the abundance of specific anaerobes and fluctuations in several metabolites including lactate and putrescine during patient exacerbation. This study has hence identified organisms whose occurrence within the CF microbiome has been hitherto unreported and has revealed potential metabolic biomarkers for exacerbation.

Peri-Lung Transplant Renal Issues in Patients With Cystic Fibrosis

journal.publications.chestnet.org Financial/nonfi nancial disclosures: The authors have reported to CHEST that no potential confl icts of interest exist with any companies/organizations whose products or services may be discussed in this article . Correspondence to: Constantine A. Manthous, MD, FCCP, Department of Internal Medicine, The Hospital of Central Connecticut, 100 Grand St, New Britain, CT 06050; e-mail: cmanthous@ thocc.org

Adalimumab-induced lupus serositis

A 61-year-old man presented with a 1-month history of breathlessness, chest pain and lethargy. He had been taking adalimumab for ankylosing spondylitis for 2 years. Pleural and pericardial effusions were both found. A video-assisted thorascopic (VATS) pleural and lung biopsy were performed. The pleural pathology showed eosinophils, acute inflammatory cells and lymphoid aggregates. The patient was positive for antinuclear, antidouble-stranded and antihistone antibodies consistent with drug-induced lupus due to adalimumab. His serositis resolved on withdrawal of the drug. Drug-induced lupus can occur as a consequence of anti-TNF-α agents from induction of autoimmunity in a predisposed host.

Is Extended-Release Guaifenesin No Better Than a Placebo?

In this issue of Respiratory Care, Hoffer-Schaefer et al[1][1] report the results of a double-blind randomized placebo-controlled trial examining the effects of guaifenesin on both the volume and physical properties of sputum in patients with acute respiratory tract infections (RTIs). Guaifenesin