Top PDF Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis.

Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis.

Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis.

In this study, we examined several biologically plausible biomarkers of disease activity that could be measured in the systemic circulation. Blood is an attractive biological compartment for biomarker measurement in CF as it can be obtained non- invasively in most clinical laboratories and has the potential for clinical application in patients of all ages and with all stages of lung disease severity. First, we examined whether stable visit biomarker levels were different in patients who were prone to experiencing an exacerbation requiring IV antibiotics within 4 months, compared to those who did not. sCD14 levels were significantly higher in patients who experienced an exacerbation in short-term follow-up. In identifying patients who do vs. do not exacerbate within 4 months of a stable clinic visit, test performance accuracy was optimized using a sCD14 cut-off value of 1450 ng/mL, with an area under ROC curve of 0.91 (95% CI 0.83–0.99). sCD14 possesses other desirable characteristics as a disease activity biomarker as it does not relate to underlying lung disease severity (i.e. FEV1% predicted) and exhibits minimal measurement variability over time when a patient is deemed clinically stable. sCD14 is biologically plausible as a biomarker of disease activity as it is involved in the innate immune response to infection and can mediate phagocytosis by binding to bacterial ligands, such as lipopolyassacharide (LPS), on the surface of gram-negative bacteria [11,12]. It is secreted in a protease-independent manner by monocytes and is cleaved from membrane-bound forms of CD14 on the surface of monocytes and macrophages by proteases such as neutrophil elastase [13]. It is also released as class 2 acute phase proteins from the liver (in response to IL-6), possibly bridging the gap between innate and adaptive immunity [14]. sCD14 has showed promise as a biomarker of pneumonia in children and sepsis in adults [13,15,16].
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IP-10 is a potential biomarker of cystic fibrosis acute pulmonary exacerbations.

IP-10 is a potential biomarker of cystic fibrosis acute pulmonary exacerbations.

other markers of disease activity, such as CRP. Additional study may also show that rising IP-10 levels herald the onset of APE. Further, evaluating whether IP-10 can be detected in serum could provide an even more convenient fashion to monitor the onset and resolution of APE. Another important limitation of our study is the non-randomized fashion in which it was conducted. As a result, several important differences exist between the inpatient and outpatient CF populations studied. Of note, the CF outpatient population is older and harbors a lower incidence of Pseudomonas infection. This Is clinically relevant as patients who are more stable with reduced incidence of CF pulmonary exacerbation are more likely to be older and have reduced incidence of CF complications, including CF-related diabetes. Thereby, while representing a limitation in comparison of disease severity, these differences are clinically relevant and relatively expected given the nature of CF lung disease.
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Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease

Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Mutations in CFTR result in airway mucus buildup and chronic airway infections. CF patients experience intermittent pulmonary exacerbations (CFPE), events that are poorly defined clinically, but known to lead to lung function decline and accelerated disease progression (Goss & Burns, 2007). A CFPE is characterized as an acute increase in symptom severity, such as dyspnea, cough, sputum production, chest pain, fevers, acute and chronic sinusitis, and occasionally hemoptysis (Dakin et al., 2001; Goss & Burns, 2007; Bilton et al., 2011; Stenbit & Flume, 2011). Exacerbations require an increased use of antibiotic, anti-inflammatory, and lung clearance therapies. These events decrease the quality of life of CF patients and a higher CFPE frequency is correlated with poor outcomes in one and three-year probability of death studies (De Boer et al., 2011; Aaron et al., 2014; Habib et al., 2015). CFPEs are challenging to predict (Rogers et al., 2011). Clinicians rely on symptoms common across patients or those that a single patient has previously experienced to provide some indication that a CFPE is occurring. Biomarkers that predict pulmonary exacerbations are needed to supplement existing clinical and physiological assessments (Rogers et al., 2011; Stenbit & Flume, 2011).
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Sao Paulo Med. J.  vol.121 número5

Sao Paulo Med. J. vol.121 número5

choscopy with bronchoalveolar lavage is inva- sive, risky and costly. Serial bronchoalveolar lavages are particularly difficult to perform. Furthermore, lavage generally samples only one or two segments of the lung, thereby possibly limiting the detection of infection. Oropharyn- geal cultures, commonly used in young chil- dren with cystic fibrosis who are not capable of expectorating, do not reliably predict the pres- ence of lower airway pathogens, lack sensitiv- ity for identifying Pseudomonas aeruginosa and Staphylococcus aureus, and provide no informa- tion about inflammation. 21
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Survival in idiopathic pulmonary fibrosis - cytotoxic agents compared to corticosteroids

Survival in idiopathic pulmonary fibrosis - cytotoxic agents compared to corticosteroids

likely that these older agents will never be evaluated by large prospective multicenter studies. Several early studies of patients with IPF cited responses of 10 to 30% with CS, but these series failed to classify patients according to histologic entities or well-defined radiologic criteria. 7,23 In a study from Michigan, 2 29 patients with well-defined IPF were treated with CS only. The survival was less than 3 years. A recent study 12 found similar mortality rates among untreated patients with IPF, compared with those treated with a combina- tion of CS and immunosupressor agents, but it is difficult to accept the first group as an adequate control group, since treatment could be avoided due to stable disease, a finding observed in many cases, with resultant better prognosis. In our study, 10 patients not treated were excluded; the median survival exceeded 60 months in these cases. In Collard’s study, 12 lung biopsy was obtained in all treated patients, but in only 15% of the untreated patients. The median survival in untreated patients with lung biopsy showing UIP was around 23 months only, compared to 56 months of untreated patients without lung biopsy, suggesting that other diseases were included in the last group. Cyclophospha- mide, either given orally or by pulse therapy, has been used in a number of studies in patients with
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Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Although there is no indicator of human schisto- somiasis in liver biopsy, use of non-invasive biologi- cal markers to predict fibrosis severity is important for monitoring the transition to the severe forms of the dis- ease and prognosis of these patients. In the areas where access to health care services is limited, these markers are also essential to evaluate fibrosis regression after treatment (Burchard et al. 1998, Ricard-Blum et al. 1999, Köpke-Aguiar et al. 2002). Most of the studies regarding biological serum markers of fibrosis have focused on HC or schistosomiasis as an isolated disease. The main ob- jective of this study was to correlate levels of biological serum markers with the prediction of clinically signifi- cant fibrosis and necroinflammatory activity in HC and schistosomiasis, not only as isolated diseases, but also as co-infections.
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Hemoglobin oxygen affinity in patients with cystic fibrosis.

Hemoglobin oxygen affinity in patients with cystic fibrosis.

[Hb] and Hct were higher in males than females, but there were no significant differences between controls and patients (Table 3). In the male patients [Hb] was negatively correlated with FEV1 (r = 20.762, P,0.05). MCHC, however, was slightly but signif- icantly lowered in patients. They showed also slightly decreased [Cl 2 ] in plasma and red cells. [BPG] and [ATP] were significantly increased in the patients inspite of very low [BPG] (9.8 m mol/gHb) in the subject with the G551D mutation. Additionally there was a sex difference for [BPG] with higher concentrations in females. After equilibration [BPG] and [ATP] tended to slightly higher values (0.9 and 0.2 m mol/gHb on average, respectively, not significant) compared to native blood.
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J. bras. pneumol.  vol.37 número2 en v37n2a08

J. bras. pneumol. vol.37 número2 en v37n2a08

Objective: To assess the quality of life (QoL) of patients with cystic fibrosis (CF) followed at a university referral center for CF. Methods: A cross-sectional study involving application of the Cystic Fibrosis Questionnaire (CFQ) and Shwachman score in CF patients between April of 2008 and June of 2009. Results: The sample consisted of 75 patients. The mean age was 12.5 ± 5.1 years (range, 6.1-26.4 years). The patients were divided into three groups by age in years: group I (< 12), II (12-14), and III (≥ 14). The highest and lowest CFQ scores were for the nutrition domain in group III (89.3 ± 16.2) and the social domain in group II (59.5 ± 22.3), respectively. Groups I and III differed significantly regarding the treatment domain (p = 0.001). Regarding Shwachman scores, there were significant differences between patients scoring ≤ 70 and those scoring > 70 in the social (group I; p = 0.045), respiratory (group II; p = 0.053), and digestive (p = 0.042) domains. In group III, severity did not correlate with QoL. In groups I and II, patients with an FEV 1 < 80% of predicted did not differ from other patients for any CFQ domain. However, in group III, values for the following domains were significantly lower in patients with an FEV 1 < 80%: physical (p = 0.012); body image (p = 0.031); respiratory (p = 0.023), emotional (p = 0.041); and
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Vitamin K status in cystic fibrosis patients

Vitamin K status in cystic fibrosis patients

CF is the most common autosomal recessive genetic disease in the Caucasian popu- lation [Hecker and Aris 2004]. It is caused by a mutation in the CFTR gene (cystic fi- brosis transmembrane conductance regulator). The product of this gene – CFTR protein – is a chloride ion channel found in epithelial tissues in the lungs, pancreas, gastrointes- tinal tract and skin. CFTR modulates the transport of salt and water across these organs epithelia. CFTR mutations lead to alterations in host defense in the respiratory tract and can cause an increase in chronic, progressive infections with Pseudomonas aeruginosa, Staphylococcus aureus and other pathogens, pancreatic duct obstruction and pancreatic insufficiency, biliary obstruction, cirrhosis and distal intestinal obstruction syndrome [Aris et al. 2005]. The main possible causes of vitamin K deficiency in CF patients include: fat malabsorption due to pancreatic exocrine insufficiency, cholestatic or non- cholestatic liver disease, reduced production of vitamin K by colonic flora related to chronic antibiotic treatments, bowel resections and also via increased mucous accu- mulation in the bowel [Drury et al. 2008, Durie 1994].
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Medications used in pediatric cystic fibrosis population

Medications used in pediatric cystic fibrosis population

Objective: To describe the drug utilization profile used by pediatric cystic fibrosis patients. Methods: A transversal study comprising the analysis of records and interviews with caregivers of pediatric patient in a reference center of Southern Brazil. We collected information about patients’ clinical condition, medication used and household therapy. Results: Out of 78 patients participating in the study, prevailing characteristics were: female, self-declared white color, mutation F508del and countryside resident. Forty-three patients had health monitoring exclusively in the hospital’s outpatient division. We analyzed 509 prescribed medication (6.5 medication/patient). The caregiver acknowledged the correct indication in 83% of cases. Patients with pulmonary complications and diseases and/or comorbities related to the cystic fibrosis had an increased quantity of prescribed medication. Vitamins, pancreatic enzymes, hypertonic saline solution, dornase alpha, acid ursodesoxicolic and inhalation antibiotics were most commonly prescribed. Out of the sum of medication, 265 (52.1%) were registered in the Relação Nacional de Medicamentos Essenciais, 26.7% were registered in the basic component and 25.4% were registered in the specialized component of pharmaceutical assistance. Seventy-four interviewees informed difficulty in the acquisition of at least one prescribed medication. Most of the reports acknowledge the State Health Department as the place to find and receive medication for cystic fibrosis. Conclusion: This study allowed reaching a deeper understanding about therapy, caring needed with patients with cystic fibrosis, highlighting to implement strategies that might contribute to enhance life quality and to execute the patients’ therapy plan.
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Rev. Nutr.  vol.28 número4

Rev. Nutr. vol.28 número4

no families belonging to classes A, D, and E). The patient’s medical record variables were: use of pancreatic enzymes (yes/no); use of antibiotics and pulmonary bacterial colonization during the period of data collection (yes/no); and type of pulmonary bacterial colonization (Burkholderiacepacia, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus). The colonization-type test was performed by collecting material from the oropharynx. Bacteriological determination was performed using the quantitative method, and a count of >10 4 CFU/mL indicated presence of
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Cystic fibrosis, are we missing in India?

Cystic fibrosis, are we missing in India?

Material and methods: Tool used was a questionnaire (Annexure I ) which was prevalidated by the departmental faculty with 15 items which included experience regarding CF patients in relation to knowledge about diagnosis and prognosis of CF patients, availability about diagnostic and management services of CF was administered to the pediatricians who participated in the training workshop at Pune Regional centre, Aundh, Pune, Maharashtra, India. ( n = 40).

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PDF EN Jornal Brasileiro de Pneumologia 2 8 english

PDF EN Jornal Brasileiro de Pneumologia 2 8 english

Objective: To assess the quality of life (QoL) of patients with cystic fibrosis (CF) followed at a university referral center for CF. Methods: A cross-sectional study involving application of the Cystic Fibrosis Questionnaire (CFQ) and Shwachman score in CF patients between April of 2008 and June of 2009. Results: The sample consisted of 75 patients. The mean age was 12.5 ± 5.1 years (range, 6.1-26.4 years). The patients were divided into three groups by age in years: group I (< 12), II (12-14), and III (≥ 14). The highest and lowest CFQ scores were for the nutrition domain in group III (89.3 ± 16.2) and the social domain in group II (59.5 ± 22.3), respectively. Groups I and III differed significantly regarding the treatment domain (p = 0.001). Regarding Shwachman scores, there were significant differences between patients scoring ≤ 70 and those scoring > 70 in the social (group I; p = 0.045), respiratory (group II; p = 0.053), and digestive (p = 0.042) domains. In group III, severity did not correlate with QoL. In groups I and II, patients with an FEV 1 < 80% of predicted did not differ from other patients for any CFQ domain. However, in group III, values for the following domains were significantly lower in patients with an FEV 1 < 80%: physical (p = 0.012); body image (p = 0.031); respiratory (p = 0.023), emotional (p = 0.041); and
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J. bras. pneumol.  vol.33 número2

J. bras. pneumol. vol.33 número2

Female patients, homozygous for ∆F508, and patients with severe pancreatic insufficiency present a higher risk of developing this complication. The decline in pulmonary function is more accelerated in glucose intolerant patients than in those with normal glycemic metabolism. The decreased survival and increased morbidity associated with CFRD make early diagnosis fundamental. Since the onset of the disease is often insidious, it is important that symptoms suggestive of CFRD, such as worsening of pulmonary function, significant weight loss, and worsening of overall health status, be noted. Microvascular complications are associated with the duration of the disease and glycemic control. The risk of macrovascular complications is low. Triage, using the OGTT, should be performed annually for patients from 6 to 10 years of age. Through this test, patients are classified as presenting normal glucose tolerance, being glucose intolerant, having CFRD with fasting hyperglycemia, or having CFRD without fasting hyperglycemia. Insulin therapy is the pharmacological approach of choice for CFRD with fasting hyperglycemia. Oral hypoglycemic agents are not indicated. Hypoglycemia and ketoacidosis are rarely observed. In these patients, multidiscipli- nary follow-up evaluations play a fundamental role in treatment compliance and clinical improvement.
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Nutritional Assesment in Cystic Fibrosis Patients( Iran and Newzeland)

Nutritional Assesment in Cystic Fibrosis Patients( Iran and Newzeland)

Under-nutrition was more frequent in Iranian than NZ patients (39% versus 0%, p=0.0001), whereas over-nutrition was more prevalent in NZ children (9% versus 17%, p=0.05). At the first visit, MacDonald and Australasian guidelines were able to recognize 77% and 61% of under-nourished Iranian patients, respectively. The mean sensitivity and specificity for all visits for the MacDonald tool were 83% & 73% (Iran) and 65% & 86% (NZ). Sensitivity and specificity for the Australasian guidelines were 79% & 79% (Iran) and 70% & 90% (NZ).
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Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention.

Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention.

To determine whether the P3-CHA bacteriophage could be used to prevent an infection by the CHA strain, we prepared an endotoxin-free bacteriophage solution (see Materials and Methods). This reduced the possibility of stimulating an immune response in the host, which could mask the effects of bacteriophage treatment. We first determined the rate of elimination of the P3-CHA bacteriophage from the lungs of uninfected mice and found that its concentration decreased by slightly more than half-log/day (over 500 fold decrease between day 0 and day 4, Figure 6). Only 20% of animals given 3610 7 bacteriophages four days prior to infection with 3610 6 bacteria were protected whereas 100% of the animals given 3610 8 bacteriophages were protected (Figure 1B). 100% of the animals pre-treated 4 days before infection with the equivalent of 3610 8 pfu of heat-killed P3-CHA solution died within 2 days (Figure 1B), showing that an active bacteriophage is required. Twenty hours after infection of a group of mice pre-treated with P3- CHA bacteriophage (3610 8 pfu) four days earlier, animals were euthanized to perform histological analyses and to quantify bacteria, bacteriophages, cytokines, and LDH. Bacterial counts were lower in P3-CHA pre-treated mice than in heat-killed P3-CHA pre-treated mice (Figure 1C). Bacteriophage counts were higher in P3-CHA pre-treated mice than in non-infected P3-CHA pre-treated mice (Figure 1D). Cytokine concentrations were also significantly lower for P3-CHA pre-treated mice, whereas LDH concentrations were similar in both groups (Figure 2). Furthermore the level of both active and heat-inactivated solutions of bacteriophage gave rise to identically low levels of pro-inflammatory markers (Figure 2). Histological analyses showed that lung damage was markedly less severe in P3-CHA pre-treated mice than the controls, with histological lesions being scored at 7 out of 25 (Figure 3C and M). Immuno-histochemistry of lungs from mice that were pre-treated with P3-CHA bacteriophages showed a pattern that was similar to curative treatment. Bacterial antigens were detected only in the cytoplasm of alveolar macrophages (Figure 3G and K). These data confirmed the efficacy of the preventive bacteriophage treatment.
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The Cystic Fibrosis Transmembrane Regulator (CFTR) in the Kidney

The Cystic Fibrosis Transmembrane Regulator (CFTR) in the Kidney

The cystic fibrosis transmembrane regulator (CFTR) is a Cl − channel. Mutations of this transporter lead to a defect of chloride secretion by epithelial cells causing the Cystic Fibrosis disease (CF). In spite of the high expression of CFTR in the kidney, patients with CF do not show major renal dysfunction, but it is known that both the urinary excretion of drugs and the renal capacity to concentrate and dilute urine is deficient. CFTR mRNA is expressed in all nephron segments and its protein is involved with chloride secretion in the distal tubule, and the principal cells of the cortical (CCD) and medullary (IMCD) collecting ducts. Several studies have demonstrated that CFTR does not only transport Cl − but also secretes ATP and, thus, controls other conductances such as Na + (ENaC) and K + (ROMK2) channels, especially in CCD. In the polycystic kidney the secretion of chloride through CFTR contributes to the cyst enlargement.
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Heterogeneity of Pseudomonas aeruginosa in Brazilian cystic fibrosis patients

Heterogeneity of Pseudomonas aeruginosa in Brazilian cystic fibrosis patients

The aim of this study was to assess the diversity and genomic variability of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients being treated at a university hospital in Brazil. Ninety-seven isolates of P. aeruginosa from 43 CF patients were characterized by macrorestriction analysis of chromosomal DNA by pulsed-field gel electrophoresis (PFGE) and tested for susceptibility to 20 antimicrobial agents by broth microdilution. It was possible to evaluate single isolates from 20 patients and multiple isolates (two to seven) from 23 patients collected during a 22-month period. Among all of the unrelated patients, we detected only one pair of patients sharing a common strain. Among the 77 isolates from 23 patients who had multiple isolates analyzed, we identified 37 major types by PFGE, and five different colonization patterns were recognized. The isolates were susceptible to several antimicrobial agents, although consecutive isolates from the same patient may display differences in their susceptibilities. Mucoid isolates were more resistant (P < 0.001) than nonmucoid isolates to five antibiotics. Our results indicate that CF patients remain colonized by more than one strain of P. aeruginosa for long periods of time. In addition, the finding of several different genotypes in the same patient suggests that the colonizing strain may occasionally be replaced.
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J. bras. pneumol.  vol.35 número2

J. bras. pneumol. vol.35 número2

contraindication to future lung transplantation. Although chemical pleurodesis and surgery have a high success rate in the prevention of recur- rent pneumothorax in the non-cystic fibrosis population, there is little evidence in the liter- ature regarding their efficacy in cystic fibrosis patients. Here, we describe a rare presentation of spontaneous pneumothorax in an adult patient with cystic fibrosis. In addition, we discuss the etiology and management of pneumothorax in cystic fibrosis patients, the prevalence of which is likely to increase, since the expected life span of these patients continues to increase.
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Evaluation of nutritional status in patiEnts with cystic fibrosis according to agE group

Evaluation of nutritional status in patiEnts with cystic fibrosis according to agE group

Objective: To evaluate the nutritional profile of the population assisted at a reference center for cystic fibrosis treatment. Methods: Cross‑sectional study including patients with cystic fibrosis assisted at a pediatric reference center in São Paulo, Brazil, in 2014. All patients attending regular visits who agreed to participate in the study were included. A questionnaire on dietary habits (24‑ hour diet recall) and socioeconomic characteristics was applied. Anthropometric data (compared with the reference from the World Health Organization, 2006 and 2007) and pulmonary function data were collected from medical records. Patients were stratified into age groups for statistical analysis.
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