Exacerbations In Cystic Fibrosis Patients Research Articles

Clinical significance of BPI-ANCA in patients with cystic fibrosis: a single center prospective study

Recurrent pulmonary exacerbation due to infection and inflammation remain the major cause of mortality and morbidity in patients with cystic fibrosis (CF). Increased levels of BPI-ANCA have been linked to Pseudomonas colonization and pulmonary exacerbations in patients with CF. The majority of these studies were done in Europe, and it is unclear whether similar findings are true in CF patients who lives in United States. In our single center study of 47 patients with CF, the prevalence of BPI-ANCA was 19% at baseline and 15% at annual follow-up visit. Overall, there were no statistical differences noted in FEV1 and frequency of pulmonary exacerbations in CF patients who were positive for BPI-ANCA compared to those who were negative for BPI-ANCA. The role of BPI-ANCA in patients with CF still remains unclear.

Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis (2023)

Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis (2023)

Evaluating the efficacy of inhaled amikacin as an adjunct to intravenous combination therapy (ceftazidime and amikacin) in pediatric cystic fibrosis pulmonary exacerbation.

Background: Pseudomonas aeruginosa is the most common microorganism found in the sputum culture of Cystic fibrosis (CF) patients causing the pulmonary destruction. Aminoglycosides have a low diffuse rate from lipid membranes, and respiratory system secretions. Regarding the burden of pulmonary exacerbation caused by the pseudomonas aeruginosa in cystic fibrosis patients in the long term and the limited number of clinical trials focused on appropriate treatment strategies, the present study evaluated the concurrent inhaled and intravenous aminoglycoside antibiotics for pulmonary exacerbation caused by the pseudomonas aeruginosa as a safe and effective treatment in children. Method: This study was a blinded, randomized clinical trial phase conducted in a tertiary referral pediatric teaching hospital from May 2021 to May 2022. The patients were randomly allocated to receive intravenously administered ceftazidime and Amikacin alone or with inhaled Amikacin. Forced expiratory volume (FEV1), Amikacin via the level, kidney function tests, audiometry, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), hospital stay, and bacterial eradication rate were compared in two therapy groups. Results: the average FEV1 has increased by 47% in Neb + group compared to Neb- group following treatment. Hospital stay was lower in Neb + group. No renal toxicity or ototoxicity was observed in both therapy groups. Pseudomonas aeruginosa eradication rate Neb- and Neb + groups were 44% and 69%, respectively (p-value = 0.15). Conclusion: Concurrent inhaled and intravenous Amikacin is safe and effective to treat Pseudomonas aeruginosa exacerbation in CF patients. Moreover, co-delivery antibiotics' route treatment increased the eradication rate. Although not statistically significant, never the less, it is clinically relevant. The intervention reduced the length of hospitalization in this group. Clinical Trial Registration: clinicaltrials.gov, identifier [IRCT20120415009475N10].

The association of fecal calprotectin and respiratory exacerbation in cystic fibrosis patients

BackgroundCF patients experience several episodes of pulmonary exacerbations and reduction in their lung function progressively. Lung function is not the only diagnostic index by physicians to decide if CF patients require antibiotic therapy following pulmonary exacerbations. Non-invasive fecal indicators are increasingly being used to assess intestinal inflammation. Calprotectin is the most extensively utilized fecal biomarker in recent CF researches.MethodsIn this longitudinal study, 30 CF patients (1–18 years) without current infectious gastroenteritis were recruited from Mofid Children's Hospital and Masih Daneshvari Hospital, Tehran, Iran. Then, fecal calprotectin levels were evaluated before treatment, two weeks after systemic antibiotic administration, as well as recurrence of pulmonary exacerbation after first post-hospital discharge.ResultsThe initial fecal calprotectin level in CF patients receiving antibiotics was 651.13 ± 671.04, significantly decreasing two weeks after antibiotic therapy and following recurrence (171.81 ± 224.40, 607.93 ± 549.89, respectively; P < 0.01). Following systemic antibiotic treatment, the patient's respiratory and GI symptoms improved (P < 0.01).ConclusionOur findings revealed that fecal calprotectin modifications are associated with CF pulmonary exacerbations and antibiotic treatment could reduce calprotectin levels. Therefore, the fecal calprotectin level could be considered as a diagnostic tool and an index to follow the response to treatment in CF pulmonary exacerbations.

Divergent dynamics of inflammatory mediators and multiplex PCRs during airway infection in cystic fibrosis patients and healthy controls: Serial upper airway sampling by nasal lavage.

In cystic fibrosis (CF), acute respiratory exacerbations critically enhance pulmonary destruction. Since these mainly occur outside regular appointments, they remain unexplored. We previously elaborated a protocol for home-based upper airway (UAW) sampling obtaining nasal-lavage fluid (NLF), which, in contrast to sputum, does not require immediate processing. The aim of this study was to compare UAW inflammation and pathogen colonization during stable phases and exacerbations in CF patients and healthy controls. Initially, we obtained NLF by rinsing 10 ml of isotonic saline/nostril during stable phases. During exacerbations, subjects regularly collected NLF at home. CF patients directly submitted one aliquot for microbiological cultures. The remaining samples were immediately frozen until transfer on ice to our clinic, where PCR analyses were performed and interleukin (IL)-1β/IL-6/IL-8, neutrophil elastase (NE), matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were assessed. Altogether, 49 CF patients and 38 healthy controls (HCs) completed the study, and 214 NLF samples were analyzed. Of the 49 CF patients, 20 were at least intermittently colonized with P. aeruginosa and received azithromycin and/or inhaled antibiotics as standard therapy. At baseline, IL-6 and IL-8 tended to be elevated in CF compared to controls. During infection, inflammatory mediators increased in both cohorts, reaching significance only for IL-6 in controls (p=0.047). Inflammatory responses tended to be higher in controls [1.6-fold (NE) to 4.4-fold (MMP-9)], while in CF, mediators increased only moderately [1.2-1.5-fold (IL-6/IL-8/NE/TIMP-1/MMP-9)]. Patients receiving inhalative antibiotics or azithromycin (n=20 and n=15, respectively) revealed lower levels of IL-1β/IL-6/IL-8 and NE during exacerbation compared to CF patients not receiving those antibiotics. In addition, CF patients receiving azithromycin showed MMP-9 levels significantly lower than CF patients not receiving azithromycin at stable phase and exacerbation. Altogether, rhinoviruses were the most frequently detected virus, detected at least once in n=24 (49.0%) of the 49 included pwCF and in n=26 (68.4%) of the 38 healthy controls over the 13-month duration of the study. Remarkably, during exacerbation, rhinovirus detection rates were significantly higher in the HC group compared to those in CF patients (65.8% vs. 22.4%; p<0.0001). Non-invasive and partially home-based UAW sampling opens new windows for the assessment of inflammation and pathogen colonization in the unified airway system.

Comparison of endoscopic sinus surgery timing in lung transplant patients with cystic fibrosis

No studies have investigated when endoscopic sinus surgery (ESS) is best performed in lung transplant patients with cystic fibrosis (CF). We sought to examine the effects of ESS timing on pulmonary health in this population. A retrospective review of all adult lung transplant patients with CF who underwent ESS at our academic medical center over a near 25-year period was performed. Patients were split into two groups based on median time from lung transplantation to ESS. Twenty-three patients were included (12 ESS early and 11 ESS delayed). Outcomes included changes in pulmonary function tests (PFTs) from baseline, preoperative to postoperative measurements, the number and duration of hospitalizations for pulmonary exacerbations, and the number of antibiotic courses used specifically to treat pulmonary exacerbations during the 12 months before and after ESS. Baseline demographics, operative history, and pulmonary function characteristics were similar between groups. While the ESS early group saw significant improvement from preoperative percent-predicted FEV1 (ppFEV1 ) at 12months postoperatively (confidence interval [CI]: 0.729-11.452, p=0.030), there were no significant postoperative PFT changes for the ESS delayed group. Postoperative improvement in FEV1 and ppFEV1 at 12months was significantly higher for the ESS early group relative to the ESS delayed group (CI: 0.010-0.583, p=0.043; CI: 1.240-16.692, p=0.025; respectively). The ESS early group had a significant reduction in the need for total antibiotic courses compared with the ESS delayed group (ESS early median: -1, interquartile range [IQR]: -1.5 to -0.5vs. ESS delayed median: 0, IQR: 0 to 0; p=0.027). Earlier ESS interventions following lung transplantation may improve pulmonary function and attenuate pulmonary exacerbations in CF patients.

Effect of endoscopic sinus surgery on clinical outcomes in DeltaF508 cystic fibrosis patients.

Chronic rhinosinusitis (CRS) is prevalent in the Cystic Fibrosis (CF) population. CRS exacerbations in CF are thought to contribute to pulmonary exacerbations. Literature regarding the impact of endoscopic sinus surgery (ESS) is inconclusive. This study examines rates of lung function decline and pulmonary exacerbation in CF patients who have undergone ESS. Retrospective review of medical records. Academic Hospital. 40 adult CF patients. Rate of lung function decline (% predicted Forced Expiratory Volume in 1second [ppFEV1 ]), number of pulmonary exacerbations (IV/oral antibiotic therapy±hospital admission) and total number days hospitalised 2-year postoperatively was collected. CRS patients undergoing ESS were matched to those without ESS by gender, age, and F508del genotype. Forty patients (mean age 37.4, 60% male) were reviewed. No significant difference was found between the surgical group and controls in baseline ppFEV1 (72.5% vs. 72.7%, P=.98), 2-year preoperative number of pulmonary exacerbations (3.05 vs. 1.65, P=.10), or Lund-Mackay scores (12.25 vs. 11.55, P=.71). No significant difference was found in 1-year (70.5% vs. 72.8%, P=.84) or 2-year (70.4% vs. 72.6% P=.80) postoperative ppFEV1 and 2-year postoperative pulmonary exacerbations (1.7 vs. 1.45, P=.87). A significant increase was identified in total number days hospitalised postoperatively (4.85, P=.02). In the surgical group, no significant difference was identified between preoperative and postoperative ppFEV1 , 1year (-2.51%, P=.32) and 2years after ESS (-3.10%, P=.51), postoperative rate of pulmonary exacerbations (-1.28, P=.11), or in total number days hospitalised (3.74, P=.14). In this study, ESS does not appear to significantly improve ppFEV1 or decrease the number of pulmonary exacerbations postoperatively.

Azithromycin potentiates avian IgY effect against Pseudomonas aeruginosa in a murine pulmonary infection model

Cystic fibrosis (CF) patients are at risk of acquiring chronic Pseudomonas aeruginosa lung infections. The biofilm mode of growth of P. aeruginosa induces tolerance to antibiotics and the host response; accordingly, treatment failure occurs. Supplemental azithromycin has proven beneficial in CF owing to potential immunomodulatory mechanisms. Clinical studies have demonstrated a reduction in exacerbations in CF patients by avian IgY anti-Pseudomonas immunotherapy. We hypothesise that azithromycin pre-treatment could potentiate the observed anti-Pseudomonas effect of IgY opsonisation in vivo. Evaluation of phagocytic cell capacity was performed using in vitro exposure of azithromycin pre-treated human polymorphonuclear neutrophils to IgY opsonised P. aeruginosa PAO3. A murine lung infection model using nasal planktonic P. aeruginosa inoculation and successive evaluation 24 h post-infection was used to determine lung bacteriology and subsequent pulmonary inflammation. Combined azithromycin treatment and IgY opsonisation significantly increased bacterial killing compared with the two single-treated groups and controls. In vivo, significantly increased bacterial pulmonary elimination was revealed by combining azithromycin and IgY. A reduction in the inflammatory markers mobiliser granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 2 (MIP-2) and interleukin 1 beta (IL-1β) paralleled this effect. Combination of azithromycin and anti-Pseudomonas IgY potentiated the killing and pulmonary elimination of P. aeruginosa in vitro and in vivo. The augmented effect of combinatory treatment with azithromycin and IgY constitutes a potential clinical application for improving anti-Pseudomonas strategies.

The Effects of Respiratory Viruses on the Acute Pulmonary Exacerbations in Cystic Fibrosis Patients

The Effects of Respiratory Viruses on the Acute Pulmonary Exacerbations in Cystic Fibrosis Patients

Stenotrophomonas maltophilia Encodes a VirB/VirD4 Type IV Secretion System That Modulates Apoptosis in Human Cells and Promotes Competition against Heterologous Bacteria, Including Pseudomonas aeruginosa.

Stenotrophomonas maltophilia is an emerging opportunistic and nosocomial pathogen. S. maltophilia is also a risk factor for lung exacerbations in cystic fibrosis patients. S. maltophilia attaches to various mammalian cells, and we recently documented that the bacterium encodes a type II secretion system which triggers detachment-induced apoptosis in lung epithelial cells. We have now confirmed that S. maltophilia also encodes a type IVA secretion system (VirB/VirD4 [VirB/D4] T4SS) that is highly conserved among S. maltophilia strains and, looking beyond the Stenotrophomonas genus, is most similar to the T4SS of Xanthomonas To define the role(s) of this T4SS, we constructed a mutant of strain K279a that is devoid of secretion activity due to loss of the VirB10 component. The mutant induced a higher level of apoptosis upon infection of human lung epithelial cells, indicating that a T4SS effector(s) has antiapoptotic activity. However, when we infected human macrophages, the mutant triggered a lower level of apoptosis, implying that the T4SS also elaborates a proapoptotic factor(s). Moreover, when we cocultured K279a with strains of Pseudomonas aeruginosa, the T4SS promoted the growth of S. maltophilia and reduced the numbers of heterologous bacteria, signaling that another effector(s) has antibacterial activity. In all cases, the effect of the T4SS required S. maltophilia contact with its target. Thus, S. maltophilia VirB/D4 T4SS appears to secrete multiple effectors capable of modulating death pathways. That a T4SS can have anti- and prokilling effects on different targets, including both human and bacterial cells, has, to our knowledge, not been seen before.

Tobramycin reduces key virulence determinants in the proteome of Pseudomonas aeruginosa outer membrane vesicles

Tobramycin is commonly used to treat Pseudomonas aeruginosa lung infections in patients with Cystic Fibrosis (CF). Tobramycin treatment leads to increased lung function and fewer clinical exacerbations in CF patients, and modestly reduces the density of P. aeruginosa in the lungs. P. aeruginosa resides primarily in the mucus overlying lung epithelial cells and secretes outer membrane vesicles (OMVs) that diffuse through the mucus and fuse with airway epithelial cells, thus delivering virulence factors into the cytoplasm that modify the innate immune response. The goal of this study was to test the hypothesis that Tobramycin reduces the abundance of virulence factors in OMVs secreted by P. aeruginosa. Characterization of the proteome of OMVs isolated from control or Tobramycin-exposed P. aeruginosa strain PAO1 revealed that Tobramycin reduced several OMV-associated virulence determinants, including AprA, an alkaline protease that enhances P. aeruginosa survival in the lung, and is predicted to contribute to the inhibitory effect of P. aeruginosa on Phe508del-CFTR Cl- secretion by primary human bronchial epithelial cells. Deletion of the gene encoding AprA reduced the inhibitory effect of P. aeruginosa on Phe508del-CFTR Cl- secretion. Moreover, as predicted by our proteomic analysis, OMVs isolated from Tobramycin treated P. aeruginosa had a diminished inhibitory effect on Phe508del-CFTR Cl- secretion compared to OMVs isolated from control P. aeruginosa. Taken together, our proteomic analysis of OMVs and biological validation suggest that Tobramycin may improve lung function in CF patients infected with P. aeruginosa by reducing several key virulence factors in OMVs that reduce CFTR Cl- secretion, which is essential for bacterial clearance from the lungs.

The expression of Mirc1/Mir17–92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients

IntroductionCystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment. MethodsMirc1/Mir17–92 cluster expression was measured in human CF and non-CF plasma, blood-derived neutrophils, and sputum samples. Values were correlated with pulmonary function, exacerbations and use of CFTR modulators. ResultsMirc1/Mir17–92 cluster expression was not significantly elevated in CF neutrophils nor plasma when compared to the non-CF cohort. Cluster expression in CF sputum was significantly higher than its expression in plasma. Elevated CF sputum Mirc1/Mir17–92 cluster expression positively correlated with pulmonary exacerbations and negatively correlated with lung function. Patients with CF undergoing treatment with the CFTR modulator Ivacaftor/Lumacaftor did not demonstrate significant change in the expression Mirc1/Mir17–92 cluster after six months of treatment. ConclusionsMirc1/Mir17–92 cluster expression is a promising biomarker of respiratory status in patients with CF including pulmonary exacerbation.

Proton Pump Inhibitor Use Is Associated With an Increased Frequency of Hospitalization in Patients With Cystic Fibrosis.

BackgroundProton pump inhibitors (PPIs) are among the most commonly prescribed medications in clinical practice. PPI use has been associated with the development of community-acquired pneumonia. With a reported prevalence of gastroesophageal reflux disease (GERD) and PPI use that is higher than the general population, patients with cystic fibrosis (CF) are particularly vulnerable to PPI adverse effects. We sought to explore whether PPI use was associated with a higher number of hospitalizations for CF pulmonary exacerbation.MethodsWe conducted a longitudinal retrospective review in an academic outpatient setting. Patients > 18 years of age with a diagnosis of CF and at least 1 year of follow-up were eligible for inclusion. Baseline characteristics, PPI use, and details of hospitalization through 1 year of follow-up were collected.ResultsOne hundred fourteen patients met inclusion criteria. Fifty-nine patients (51.7%) were hospitalized at least once in the follow-up year, mean number of hospitalizations was 2.17 (± 1.9). At least 6 months of PPI use was observed in 59 patients (51.7%). In univariate analysis, PPI use was associated with a significantly higher mean number of hospitalizations (0.9 vs. 1.4, P = 0.009). In a multi-variable regression model, PPI use remained significantly associated with a higher number of hospitalizations (P = 0.03), while controlling for risk factors traditionally associated with increased pulmonary exacerbations.ConclusionPPI use is highly prevalent in CF patients. Exposure to PPI therapy is independently associated with a higher number of hospitalizations for pulmonary exacerbation in CF patients.

Evaluation of children with cystic fibrosis by impulse oscillometry when stable and at exacerbation.

Pulmonary function tests are important in the diagnosis and follow-up of airway disease in cystic fibrosis (CF). Conventional spirometry for which repeated forced expiration maneuver are needed is considered as the main method. Impulse oscillometry (IOS) is a non-invasive method, which needs minimal cooperation. We performed a prospective cross-sectional study to determine the pulmonary function in CF children with IOS, and evaluate the IOS measurements during acute exacerbation. We hypothesized that IOS can detect lung function impairment in CF patients and detect changes during acute exacerbations. CF patients aged 3-18 years were included as the study group and healthy children of the same age formed the control group. The patients were evaluated three times at 3-month intervals. Patients aged >6 years performed both spirometry and IOS while patients aged ≤6 years performed only IOS. In patients with acute exacerbation, spirometry and IOS were performed both at and after the exacerbation. Forty-nine CF patients and 45 healthy children were enrolled to the study. Sixteen patients were admitted with acute exacerbation during the study. The resistance values (R5-10-15-20 Hz) as well as Z5, Fres, and AX values of the patients were higher than those of the control group, while reactance values (X5-10-15-20 Hz) were lower. R values as well as Z5, Fres, and AX values increased during exacerbation and decreased after treatment; X (10-15 Hz) values decreased during exacerbation and increased after recovery (P < 0.05). IOS may be useful to evaluate pulmonary functions and detect acute exacerbations in CF patients. Pediatr Pulmonol. 2016;51:1151-1158. © 2016 Wiley Periodicals, Inc.

Cystic Fibrosis Frequently Asked Questions: Question 4: What is the appropriate duration of therapy for respiratory exacerbations in Cystic Fibrosis patients infected with Pseudomonas aeruginosa?

Cystic Fibrosis Frequently Asked Questions: Question 4: What is the appropriate duration of therapy for respiratory exacerbations in Cystic Fibrosis patients infected with Pseudomonas aeruginosa?

Factors associated with response to treatment of pulmonary exacerbations in cystic fibrosis patients

BackgroundPulmonary exacerbations are associated with significant lung function decline from baseline in cystic fibrosis (CF) and it is not well understood why some patients do not respond to antibiotic therapy. The objective of this study was to identify factors associated with lung function response to antibiotic treatment of pulmonary exacerbations. MethodsAs a secondary analysis of a randomized, controlled trial of intravenous antibiotic treatment for pulmonary exacerbations in CF patients, we investigated whether baseline factors and changes in sputum bacterial density, serum or sputum inflammatory markers were associated with recovery of lung function and risk of subsequent exacerbation. ResultsIn 36 of the 70 exacerbations (51%), patients’ lung function returned to >100% of their baseline at day 14 of antibiotic treatment; 34 exacerbations were classified as non-responders. Baseline characteristics were not significantly different between responders and non-responders. Less of a drop in FEV1 from baseline to exacerbation (OR 1.09, 95% CI 1.0, 1.18, p=0.04) as well as a greater decrease in sputum neutrophil elastase (OR 2.94, 95% CI 1.07, 8.06, p=0.04) were associated with response to antibiotic treatment at day 14. In addition, higher CRP (HR 1.35 (95% CI: 1.01, 1.78), p=0.04) and sputum neutrophil elastase (HR 1.71 (95% CI: 1.02, 2.88), p=0.04) at day 14 of antibiotic therapy were associated with an increased risk of subsequent exacerbation. ConclusionsInadequate reduction of inflammation during an exacerbation is associated with failure to recover lung function and increased risk of subsequent re-exacerbation in CF patients.

Candidate Markers Associated with the Probability of Future Pulmonary Exacerbations in Cystic Fibrosis Patients

IntroductionPulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.MethodsWe prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.ResultsOut of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.ConclusionOur results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.

The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients – clinical analysis of Trichosporonpositive patients in a Munich cohort

BackgroundThe relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated.MethodsThe clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 – 52.4 years; mean FEV1 2010 81.4% pred) were investigated.ResultsIn 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition.ConclusionsThis study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients.

206 Clinical and paraclinical profile and risk of exacerbations in patients with cystic fibrosis attending a national reference center in Latin America

Cystic fibrosis (CF) is characterized by chronic airway and systemic inflammation complicated by intermittent episodes of acute exacerbations that contribute to significant morbidity. Objectives: To characterize and identify possible risk factors related to exacerbations in CF patients attending the National Reference Center in Uruguay. Methods: We analyzed data from all patients at the database of our center for the period 2011–2012. One patient who died and two patients, who underwent double lung transplantation, were excluded. Exacerbations were defined as acute/ sub-acute worsening of respiratory symptoms severe enough to warrant intravenous (IV) antibiotics and hospitalization. Results: 54 patients were included, 57.4% male, mean age 26±9, BMI 22±4. At least one of the most common mutation delta F508, was present in 35%, pancreatic insufficiency in 44%, diabetes in 9% and hemoptysis in 62%. Up to 70% were colonized with: Pseudomonas aeruginosa (PA) 52%, St. aureus 26.3%, Alcaligenes 13%, Stenotrophomonas 2.6%. Mean FVC 90.1±23%, mean FEV1 80.6±27.8; 18.5% FEV1 <60%. Patients received treatment with: inhaled tobramycin 44%, pulmozyme 51.8%, Hypertonic Saline solution 61%. 35% of patients had at least one exacerbation or hospitalization/year. Using a linear regression model no correlation was found between exacerbations and: sex, age, age at diagnosis, colonization with PA, or hemoptysis. Exacerbations were strongly associated with poor lung function (R: 0.51, p = 0.0001). Conclusions: Data from a well characterized CF population suggest that acknowledging trends in lung function may contribute to identify patients at risk of exacerbation and increased morbidity.

207 Non-invasive ventilation in cystic fibrosis

Cystic fibrosis (CF) is characterized by chronic airway and systemic inflammation complicated by intermittent episodes of acute exacerbations that contribute to significant morbidity. Objectives: To characterize and identify possible risk factors related to exacerbations in CF patients attending the National Reference Center in Uruguay. Methods: We analyzed data from all patients at the database of our center for the period 2011–2012. One patient who died and two patients, who underwent double lung transplantation, were excluded. Exacerbations were defined as acute/ sub-acute worsening of respiratory symptoms severe enough to warrant intravenous (IV) antibiotics and hospitalization. Results: 54 patients were included, 57.4% male, mean age 26±9, BMI 22±4. At least one of the most common mutation delta F508, was present in 35%, pancreatic insufficiency in 44%, diabetes in 9% and hemoptysis in 62%. Up to 70% were colonized with: Pseudomonas aeruginosa (PA) 52%, St. aureus 26.3%, Alcaligenes 13%, Stenotrophomonas 2.6%. Mean FVC 90.1±23%, mean FEV1 80.6±27.8; 18.5% FEV1 <60%. Patients received treatment with: inhaled tobramycin 44%, pulmozyme 51.8%, Hypertonic Saline solution 61%. 35% of patients had at least one exacerbation or hospitalization/year. Using a linear regression model no correlation was found between exacerbations and: sex, age, age at diagnosis, colonization with PA, or hemoptysis. Exacerbations were strongly associated with poor lung function (R: 0.51, p = 0.0001). Conclusions: Data from a well characterized CF population suggest that acknowledging trends in lung function may contribute to identify patients at risk of exacerbation and increased morbidity.