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Sample records for non-cystic fibrosis bronchiectasis

  1. Using Cystic Fibrosis Therapies for Non-Cystic Fibrosis Bronchiectasis.

    PubMed

    ElMaraachli, Wael; Conrad, Douglas J; Wang, Angela C C

    2016-03-01

    Non-cystic fibrosis bronchiectasis (NCFB) is an increasingly prevalent disease that places a significant burden on patients and health systems globally. Although many of the therapies used to treat NCFB were originally developed as cystic fibrosis (CF) therapies, not all of them have been demonstrated to be efficacious in NCFB and some may even be harmful. This article explores the evidence for which therapeutic strategies used to treat CF have been translated into the care of NCFB. The conclusion is that therapies for adult NCFB cannot be simply extrapolated from CF clinical trials, and in some instances, doing so may actually result in harm. PMID:26857775

  2. [Treatment of non-cystic fibrosis bronchiectasis].

    PubMed

    Martínez García, Miguel Ángel; Máiz Carro, Luis; Catalán Serra, Pablo

    2011-12-01

    Bronchiectasis is currently growing in importance due to both the increase in the number of diagnoses made as well as the negative impact that its presence has on the baseline disease that generates it. A fundamental aspect in these patients is the colonization and infection of the bronchial mucous by potentially pathogenic microorganisms (PPM), which are the cause in most cases of the start of the chronic inflammatory process that results in the destruction and dilatation of the bronchial tree that is characteristic in these patients. The treatment of the colonization and chronic bronchial infection in these patients should be based on prolonged antibiotic therapy in its different presentations. Lately, the inhaled form is becoming especially prominent due to its high efficacy and limited production of important adverse effects. However, one must not overlook the fact that the management of patients with bronchiectasis should be multidisciplinary and multidimensional. In addition to antibiotic treatment, the collaboration of different medical and surgical specialties is essential for the management of the exacerbations, nutritional aspects, respiratory physiotherapy, muscle rehabilitation, complications, inflammation and bronchial hyperreactivity and the hypersecretion that characterizes these patients. PMID:21798654

  3. Evidence of Inhaled Tobramycin in Non-Cystic Fibrosis Bronchiectasis

    PubMed Central

    Vendrell, Montserrat; Muñoz, Gerard; de Gracia, Javier

    2015-01-01

    There is currently less experience with inhaled tobramycin in non-cystic fibrosis bronchiectasis than in cystic fibrosis (CF). Intravenous formulation and solution for inhalation (TSI) have been studied in non-CF bronchiectasis patients with chronic P. aeruginosa bronchial infection. An improvement in clinical parameters and a reduction in bacterial density have been shown with both inhaled solutions in these patients. However, further trials are needed to determine the most effective dose and administration protocol in these patients. Based on the current evidence, recommendations cannot be made regarding the use of TSI to treat exacerbations. Although no systemic toxicity has been reported in studies specifically investigating this treatment, patients with known kidney disease or ear disorders should be treated with caution. Adverse respiratory effects are reported to be more common in non-CF patients than in CF patients, who tend to be non-smokers and younger. Research is being conducted into the possibility of combining tobramycin with other antibiotics to increase its antibacterial activity. In this review we will present and discuss the published evidence regarding the use of inhaled tobramycin in non–CF bronchiectasis. PMID:25893022

  4. Non-cystic fibrosis bronchiectasis: diagnosis and management in 21st century.

    PubMed

    Goeminne, Pieter; Dupont, Lieven

    2010-08-01

    Bronchiectasis is permanently dilated airways caused by chronic bronchial inflammation secondary to inappropriate clearance of various micro-organisms and recurrent infections in the airways. At diagnosis, one should search for the underlying disease process, most of the time excluding cystic fibrosis (CF). However, in a substantial number of patients no cause is found. Next, patients need individualised therapy and follow-up by monitoring of their symptoms. Useful tools are the Leicester Cough Questionnaire and the Sputum Colour Chart. Screening patients for bacterial colonisation on a regular basis seems to be equally important, as many patients become colonised by pathogenic micro-organisms. Treatment for non-cystic fibrosis bronchiectasis differs in certain aspects from cystic fibrosis bronchiectasis and often lacks evidence. Overall, bronchiectasis is an underestimated disease, not only in prevalence and incidence, but also in its ability to cause morbidity and mortality. Further research into the underlying pathophysiological mechanisms and trials evaluating new treatments are an absolute necessity. PMID:20709772

  5. A review of non-cystic fibrosis pediatric bronchiectasis.

    PubMed

    Boren, Eric J; Teuber, Suzanne S; Gershwin, M Eric

    2008-04-01

    With the implementation of vaccination programs and the use of antibiotics, developed countries have seen a decline in infection-related pediatric bronchiectasis. However, significant morbidity from bronchiectasis is still seen and both infectious and noninfectious causes of bronchiectasis in the pediatric population remain. A review of the literature will be presented including causes of pediatric bronchiectasis, clinical symptoms and signs, laboratory evaluation and imaging, as well as treatment options. This review stresses the importance of early evaluation and treatment in children with recurrent cough, sinusitis, potential foreign-body aspiration, or gastroesophageal reflux to prevent the complications of ongoing respiratory disease and bronchiectasis. PMID:18330730

  6. Defining severity in non-cystic fibrosis bronchiectasis.

    PubMed

    Poppelwell, Lucy; Chalmers, James D

    2014-04-01

    Bronchiectasis is a common disease with important impacts on patient's quality of life and on healthcare systems in terms of healthcare costs, hospitalisations and mortality. After decades of being regarded as an orphan disease there are an increasing numbers of treatments available, or in late-stage clinical trials. Assessment of disease severity is fundamental to clinical management. To date, however, there is no agreed definition of what constitutes mild, moderate or severe bronchiectasis. These terms are often applied to radiological appearances, but while important, computed tomography findings are not sufficiently precise to capture the complex impact of the disease. Studies are beginning to define the risk factors for mortality, hospital admissions, exacerbations and impaired quality of life in bronchiectasis, allowing us to propose new definitions of what constitutes severe bronchiectasis. An improved understanding of severity and prognosis in this disease will aid clinical decision making and the application of new therapies. PMID:24601664

  7. A randomised crossover trial of chest physiotherapy in non-cystic fibrosis bronchiectasis.

    PubMed

    Murray, M P; Pentland, J L; Hill, A T

    2009-11-01

    Regular chest physiotherapy is advocated in non-cystic fibrosis bronchiectasis despite little evidence supporting its routine use. This study aimed to establish the efficacy of regular chest physiotherapy in non-cystic fibrosis bronchiectasis compared with no regular chest physiotherapy. 20 patients not practising regular chest physiotherapy were enrolled in a randomised crossover trial of 3 months of twice daily chest physiotherapy using an oscillatory positive expiratory pressure device compared with 3 months of no chest physiotherapy. The primary end-point was the Leicester Cough Questionnaire (LCQ). Additional outcomes included 24-h sputum volume, forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF(25-75%)), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), exercise capacity, sputum microbiology and St George's Respiratory Questionnaire (SGRQ). The treatment effect was estimated using the differences of the pairs of observations from each patient. There was a significant improvement in all domains and total LCQ score with regular chest physiotherapy (median (interquartile range) total score improvement 1.3 (-0.17-3.25) units; p = 0.002). 24-h sputum volume increased significantly with regular chest physiotherapy (2 (0-6) mL; p = 0.02), as did exercise capacity (40 (15-80) m; p = 0.001) and SGRQ total score (7.77 (-0.99-14.5) unit improvement; p = 0.004). No significant differences were seen in sputum bacteriology, FEV(1), FVC, FEF(25-75%), MIP or MEP. Regular chest physiotherapy in non-cystic fibrosis bronchiectasis has small, but significant benefits. PMID:19541717

  8. Validation of the Leicester Cough Questionnaire in non-cystic fibrosis bronchiectasis.

    PubMed

    Murray, M P; Turnbull, K; MacQuarrie, S; Pentland, J L; Hill, A T

    2009-07-01

    Health-related quality of life is a potentially important marker for evaluating existing and new therapies in bronchiectasis. The Leicester Cough Questionnaire (LCQ) is a symptom specific questionnaire designed to assess the impact of cough severity, a major symptom of bronchiectasis. This study aimed to validate the LCQ in bronchiectasis. The validity, responsiveness and reliability of the LCQ were assessed as follows: ability to discriminate severe and mild disease; change in score following antibiotic treatment for exacerbations; repeatability over a 6-month period in stable disease; and comparison with the St George's Respiratory Questionnaire (SGRQ). In total, 120 patients (51 with severe disease, 29 with moderate disease and 40 with mild disease) completed the LCQ and SGRQ. The area under the receiver-operator curve was good for both severe and mild disease (0.84 and 0.80 respectively, p<0.0001). Following 2 weeks' antibiotic treatment, the median LCQ score (interquartile range) improved from 11.3 (9.3-13.7) to 17.8 (15-18.8) (p<0.0001). The LCQ score was repeatable over 6 months in stable disease (intraclass correlation coefficient of 0.96 (95%CI 0.93-0.97), p<0.0001). Correlation between the LCQ and SGRQ scores was -0.7 in both stable disease and exacerbations (p<0.0001). The LCQ can discriminate disease severity, is responsive to change and is reliable for use in non-cystic fibrosis bronchiectasis. PMID:19196812

  9. Lobar distribution in non-cystic fibrosis bronchiectasis predicts bacteriologic pathogen treatment.

    PubMed

    Izhakian, S; Wasser, W G; Fuks, L; Vainshelboim, B; Fox, B D; Fruchter, O; Kramer, M R

    2016-05-01

    Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity due to frequent infectious exacerbations. We analyzed the influence of patient age and bronchiectasis location on the bacterial profile of patients with NCFBr. This retrospective cohort study included 339 subjects diagnosed with an infectious exacerbation of NCFBr during the 9-year period between January 2006 and December 2014. Bronchoalveolar lavage (BAL) cultures and high-resolution computed tomography scans (HRCT) were utilized to characterize the location of the bronchiectasis and bacteriologic pathogenic profile. In univariate logistic regression, the frequency of Haemophilus influenzae was higher in patients aged ≤64 years (OR = 0.969, p < 0.0001, 95 % CI 0.954-0.983), whereas the frequency of Pseudomonas aeruginosa (OR = 1.027, p = 0.008, 95 % CI 1.007-1.048) and Enterobacteriaceae (OR = 1.039, p = 0.01, 95 % CI 1.009-1.069) were significantly higher in patients aged >64 years. The lobar distribution of bronchiectasis in the subjects was 25.9 % in the right middle lobe (RML), 20.7 % in the right lower lobe (RLL), 20.4 % in the left lower lobe (LLL), 13.8 % in the lingula, 13 % in the right upper lobe (RUL), and 6.2 % in the left upper lobe (LUL). In the lower lobes, H. influenzae was the dominant species isolated, whereas in the RUL it was P. aeruginosa and in the LUL it was non- tuberculous mycobacterium (NTM). H. influenzae was more prevalent in younger patients, whereas P. aeruginosa, Enterobacteriaceae and NTM predominated in older patients. Different pathogens were associated with different lobar distributions. The RML, RLL and LLL showed a greater tendency to develop bronchiectasis than other lobes. PMID:26873379

  10. Adult Non-Cystic Fibrosis Bronchiectasis Is Characterised by Airway Luminal Th17 Pathway Activation

    PubMed Central

    Chen, Alice C.-H.; Martin, Megan L.; Lourie, Rohan; Rogers, Geraint B.; Burr, Lucy D.; Hasnain, Sumaira Z.; Bowler, Simon D.; McGuckin, Michael A.; Serisier, David J.

    2015-01-01

    Background Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation. Methods Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined. Results BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α. Conclusions and Clinical Relevance Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity. PMID:25822228

  11. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis.

    PubMed

    Qi, Q; Li, T; Li, J C; Li, Y

    2015-08-01

    The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<25.0 kg/m2), overweight (25.0≤BMI<30.0 kg/m2), and obese (BMI≥30.0 kg/m2). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis. PMID:26176309

  12. Advantages and drawbacks of long-term macrolide use in the treatment of non-cystic fibrosis bronchiectasis

    PubMed Central

    Fan, Li-Chao

    2014-01-01

    Non-cystic fibrosis (non-CF) bronchiectasis is a respiratory disease characterized by persistent airway inflammation and dilation of bronchial wall driven by various causes. Patients with bronchiectasis suffer from excessive sputum production, recurrent exacerbations, and progressive airway destruction. Major therapy for bronchiectasis is focused on breaking the “vicious cycle” of mucus stasis, infection, inflammation, and airway destruction. Growing evidences have been shown that macrolides possess immunoregulatory and anti-inflammatory functions beyond their antimicrobial effects. Macrolide antibiotics have been effectively used in the treatment of diffuse panbronchiolitis, CF and bronchiolitis obliterans syndrome. Currently a number of clinical trials were performed to assess macrolide treatment in the management of non-CF bronchiectasis. The purpose of this paper is to review the efficacy and potential risks of these recent studies on the use of macrolides in non-CF bronchiectasis. PMID:25093082

  13. Airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis

    PubMed Central

    Bergin, David A; Hurley, Killian; Mehta, Adwait; Cox, Stephen; Ryan, Dorothy; O’Neill, Shane J; Reeves, Emer P; McElvaney, Noel G

    2013-01-01

    Bronchiectasis is an airway disease characterized by thickening of the bronchial wall, chronic inflammation , and destruction of affected bronchi. Underlying etiologies include severe pulmonary infection and cystic fibrosis (CF); however, in a substantial number of patients with non-CF-related bronchiectasis (NCFB), no cause is found. The increasing armamentarium of therapies now available to combat disease in CF is in stark contrast to the limited tools employed in NCFB. Our study aimed to evaluate similarities and differences in airway inflammatory markers in patients with NCFB and CF, and to suggest potential common treatment options. The results of this study show that NCFB bronchoalveolar lavage fluid samples possessed significantly increased NE activity and elevated levels of matrix metalloproteinases 2 (MMP-2) and MMP-9 compared to healthy controls (P < 0.01); however, the levels detected were lower than in CF (P < 0.01). Interleukin-8 (IL-8) concentrations were significantly elevated in NCFB and CF compared to controls (P < 0.05), but in contrast, negligible levels of IL-18 were detected in both NCFB and CF. Analogous concentrations of IL-10 and IL-4 measured in NCFB and CF were statistically elevated above the healthy control values (P < 0.05 and P < 0.01, respectively). These results indicate high levels of important proinflammatory markers in both NCFB and CF and support the use of appropriate anti-inflammatory therapies already employed in the treatment of CF bronchiectasis in NCFB. PMID:23426081

  14. Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin Free Base in Non-Cystic Fibrosis Bronchiectasis Patients

    PubMed Central

    Hagedoorn, Paul; Alffenaar, Jan-Willem C.; van der Werf, Tjip S.; Kerstjens, Huib A. M.; Frijlink, Henderik W.; de Boer, Anne H.

    2016-01-01

    Rationale Bronchiectasis is a condition characterised by dilated and thick-walled bronchi. The presence of Pseudomonas aeruginosa in bronchiectasis is associated with a higher hospitalisation frequency and a reduced quality of life, requiring frequent and adequate treatment with antibiotics. Objectives To assess local tolerability and the pharmacokinetic parameters of inhaled excipient free dry powder tobramycin as free base administered with the Cyclops dry powder inhaler to participants with non-cystic fibrosis bronchiectasis. The free base and absence of excipients reduces the inhaled powder dose. Methods Eight participants in the study were trained in handling the device and inhaling correctly. During drug administration the inspiratory flow curve was recorded. Local tolerability was assessed by spirometry and recording adverse events. Serum samples were collected before, and 15, 30, 45, 60, 75, 90, 105, 120 min; 4, 8 and 12 h after inhalation. Results and Discussion Dry powder tobramycin base was well tolerated and mild tobramycin-related cough was reported only once. A good drug dose-serum concentration correlation was obtained. Relatively small inhaled volumes were computed from the recorded flow curves, resulting in presumably substantial deposition in the central airways—i.e., at the site of infection. Conclusions In this first study of inhaled dry powder tobramycin free base in non-cystic fibrosis bronchiectasis patients, the free base of tobramycin and the administration with the Cyclops dry powder device were well tolerated. Our data support further clinical studies to evaluate safety and efficacy of this compound in this population. PMID:26959239

  15. Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis.

    PubMed

    Park, In Kwon; Olivier, Kenneth N

    2015-04-01

    Increasing numbers of cystic fibrosis (CF) and non-CF bronchiectasis patients are affected by pulmonary nontuberculous mycobacteria (NTM) infection worldwide. Two species of NTM account for up to 95% of the pulmonary NTM infections: Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC). Diagnosis of pulmonary NTM infection is based on criteria specified in the 2007 American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) guidelines. While many initial positive cultures do not progress to active NTM disease, even a single positive NTM sputum culture obtained from higher risk groups such as classic CF or older women with bronchiectasis and very low body mass index should be closely monitored for progressive disease. Macrolides remain the most effective agents available against MAC and MABSC. Infection with MABSC may be associated with worse clinical outcomes, as more than half of MABSC isolates have inducible macrolide resistance conferred by an active erm(41) gene. Of growing concern in CF is that MABSC is becoming more common than MAC, seems to target younger patients with classic CF, and is more difficult to manage, often requiring prolonged courses of intravenous antibiotics. Recurrence rates of NTM after initial successful treatment remain high, likely due to nonmodifiable risk factors raising the question of whether secondary prophylaxis is feasible. More rapid and readily available methods for detecting inducible macrolide resistance and better in vitro susceptibility testing methods for other drugs that correlate with clinical responses are needed. This is crucial to identify more effective regimens of existing drugs and for development of novel drugs for NTM infection. PMID:25826589

  16. A metagenomic approach to characterize temperate bacteriophage populations from Cystic Fibrosis and non-Cystic Fibrosis bronchiectasis patients

    PubMed Central

    Tariq, Mohammad A.; Everest, Francesca L. C.; Cowley, Lauren A.; De Soyza, Anthony; Holt, Giles S.; Bridge, Simon H.; Perry, Audrey; Perry, John D.; Bourke, Stephen J.; Cummings, Stephen P.; Lanyon, Clare V.; Barr, Jeremy J.; Smith, Darren L.

    2015-01-01

    Pseudomonas aeruginosa (Pa), normally a soil commensal, is an important opportunistic pathogen in Cystic Fibrosis (CF) and non-Cystic Fibrosis Bronchiectasis (nCFBR). Persistent infection correlates with accelerated decline in lung function and early mortality. The horizontal transfer of DNA by temperate bacteriophages can add gene function and selective advantages to their bacterial host within the constrained environment of the lower lung. In this study, we chemically induce temperate bacteriophages from clonal cultures of Pa and identify their mixed viral communities employing metagenomic approaches. We compared 92 temperate phage metagenomes stratified from these clinical backgrounds (47 CF and 45 nCFBR Pa isolates) using MG-RAST and GeneWise2. KEGG analysis shows the complexity of temperate phage accessory gene carriage increases with duration and severity of the disease. Furthermore, we identify the presence of Ig-like motifs within phage structural genes linked to bacterial adhesion and carbohydrate binding including Big_2, He_Pig, and Fn3. This study provides the first clinical support to the proposed bacteriophage adherence to mucus (BAM) model and the evolution of phages interacting at these mucosal surfaces over time. PMID:25741327

  17. A metagenomic approach to characterize temperate bacteriophage populations from Cystic Fibrosis and non-Cystic Fibrosis bronchiectasis patients.

    PubMed

    Tariq, Mohammad A; Everest, Francesca L C; Cowley, Lauren A; De Soyza, Anthony; Holt, Giles S; Bridge, Simon H; Perry, Audrey; Perry, John D; Bourke, Stephen J; Cummings, Stephen P; Lanyon, Clare V; Barr, Jeremy J; Smith, Darren L

    2015-01-01

    Pseudomonas aeruginosa (Pa), normally a soil commensal, is an important opportunistic pathogen in Cystic Fibrosis (CF) and non-Cystic Fibrosis Bronchiectasis (nCFBR). Persistent infection correlates with accelerated decline in lung function and early mortality. The horizontal transfer of DNA by temperate bacteriophages can add gene function and selective advantages to their bacterial host within the constrained environment of the lower lung. In this study, we chemically induce temperate bacteriophages from clonal cultures of Pa and identify their mixed viral communities employing metagenomic approaches. We compared 92 temperate phage metagenomes stratified from these clinical backgrounds (47 CF and 45 nCFBR Pa isolates) using MG-RAST and GeneWise2. KEGG analysis shows the complexity of temperate phage accessory gene carriage increases with duration and severity of the disease. Furthermore, we identify the presence of Ig-like motifs within phage structural genes linked to bacterial adhesion and carbohydrate binding including Big_2, He_Pig, and Fn3. This study provides the first clinical support to the proposed bacteriophage adherence to mucus (BAM) model and the evolution of phages interacting at these mucosal surfaces over time. PMID:25741327

  18. Efficiency and safety of surgical intervention to patients with Non-Cystic Fibrosis bronchiectasis: a meta-analysis

    PubMed Central

    Fan, Li-Chao; Liang, Shuo; Lu, Hai-Wen; Fei, Ke; Xu, Jin-Fu

    2015-01-01

    No quantitative systematic review was found to report the efficiency and safety of surgical resection in the management of non-cystic fibrosis (non-CF) bronchiectasis. We therefore conducted a meta-analysis to assess the effects of operative intervention to patients with non-CF bronchiectasis. PubMed, the Cochrane library and Web of Science databases were searched up to July 8th, 2015. The pooled mortality from 34 studies recruiting 4788 patients was 1.5% (95% CI, 0.9–2.5%). The pooled morbidity from 33 studies consisting of 4583 patients was 16.7% (95% CI, 14.8–18.6%). The pooled proportion of patients from 35 studies, consisting of 4614 patients who were free of symptoms was 66.5% (95% CI, 61.3–71.7%) after surgery. The summary proportion of patients from 35 articles including 4279 participants who were improved was 27.5% (95% CI, 22.5–32.5%), and 9.1% (95% CI, 7.3–11.5%) showed no clinical improvement. In conclusion, our analysis indicated that lung resection in the management of non-CF bronchiectasis is associated with significant improvements in symptoms, low risk of mortality and acceptable morbidity. PMID:26627202

  19. Risk factors for morbidity and death in non-cystic fibrosis bronchiectasis: a retrospective cross-sectional analysis of CT diagnosed bronchiectatic patients

    PubMed Central

    2012-01-01

    Introduction There is a relative lack of information about the death rate and morbidity of non-cystic fibrosis bronchiectasis and most studies are limited due to referral bias. We wanted to assess death rate and morbidity in those patients at our hospital. Methods Adult patients seen at our department between June 2006 and November 2009 were recruited if the key string "bronchiect-" was mentioned in electronic clinical records and if chest CT imaging was available. Clinical records of all patients with confirmed radiologic diagnosis of bronchiectasis were reviewed and clinical characteristics were analyzed. Results 539 patients with a radiographic diagnosis of non-cystic fibrosis bronchiectasis were identified in a retrospective cross-sectional analysis giving a prevalence of 2.6% in our hospital population. A wide range of etiologies was found with idiopathic bronchiectasis in 26%. In the 41 months interval, 57 patients (10.6%) died. We found a median exacerbation rate of 1.94 per year. Bacterial colonization status was associated with more deaths, exacerbation rate, symptoms and reduced pulmonary function. Pulmonary hypertension was found in 48% of our patients. Conclusions We evaluated a large non-cystic fibrosis bronchiectasis population, and provided new epidemiological data on associations between clinical characteristics and deaths and morbidity in these patients. PMID:22423975

  20. The effects of pulmonary rehabilitation in patients with non-cystic fibrosis bronchiectasis: protocol for a randomised controlled trial

    PubMed Central

    2010-01-01

    Background Non-cystic fibrosis bronchiectasis is characterised by sputum production, exercise limitation and recurrent infections. Although pulmonary rehabilitation is advocated for this patient group, its effects are unclear. The aims of this study are to determine the short and long term effects of pulmonary rehabilitation on exercise capacity, cough, quality of life and the incidence of acute pulmonary exacerbations. Methods/Design This randomised controlled trial aims to recruit 64 patients with bronchiectasis from three tertiary institutions. Participants will be randomly allocated to the intervention group (supervised, twice weekly exercise training with regular review of airway clearance therapy) or a control group (twice weekly telephone support). Measurements will be taken at baseline, immediately following the intervention and at six and 12 months following the intervention period by a blinded assessor. Exercise capacity will be measured using the incremental shuttle walk test and the six-minute walk test. Quality of life and health status will be measured using the Chronic Respiratory Questionnaire, Leicester Cough Questionnaire, Assessment of Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale. The rate of hospitalisation will be captured as well as the incidence of acute pulmonary exacerbations using a daily symptom diary. Discussion Results from this study will help to determine the efficacy of supervised twice-weekly pulmonary rehabilitation upon exercise capacity and quality of life in patients with bronchiectasis and will contribute to clinical practice guidelines for physiotherapists in the management of this population. Trial registration This study protocol is registered with ClinicalTrials.gov (NCT00885521). PMID:20122281

  1. Adrenal insufficiency in patients with stable non-cystic fibrosis bronchiectasis

    PubMed Central

    Rajagopala, Srinivas; Ramakrishnan, Anantharaman; Bantwal, Ganapathi; Devaraj, Uma; Swamy, Smrita; Ayyar, S V; D’Souza, George

    2014-01-01

    Background & objectives: Suppressed adrenal responses associated with inhaled steroid use have been reported in patients with bronchiectasis and have been shown to be associated with poor quality of life. This study was undertaken to examine the prevalence of suppressed cortisol responses in stable bronchiectasis and determine their correlation with the use of inhaled corticosteroids, radiologic severity of bronchiectasis and quality of life (QOL) scores. Methods: In this case-control study, cases were patients with bronchiectasis and suppressed cortisol responses and controls were healthy volunteers, and patients with bronchiectasis without suppressed cortisol responses. Symptoms, lung function test values, exercise capacity, HRCT severity scores for bronchiectasis, exacerbations, inhaled corticosteroid use and quality of life scores were compared between patients with and without suppressed cortisol values. Results: Forty consecutive patients with bronchiectasis and 40 matched controls underwent 1-μg cosyntropin testing. Baseline cortisol (mean difference -2.0 μg/dl, P=0.04) and 30-minute stimulated cortisol (mean difference -3.73 μg/dl, P=0.001) were significantly lower in patients with bronchiectasis. One patient had absolute adrenal insufficiency and 39.5 per cent (15/38) patients with bronchiectasis had impaired stimulated responses. Baseline and stimulated cortisol responses were unaffected by inhaled steroids (O.R 1.03, P=0.96). SGRQ scores were negatively correlated with body mass (r= -0.51, P=0.001) and bronchiectasis severity (r=0.37, P=0.019), but not related to baseline or stimulated cortisol responses. Interpretation & conclusions: Our results showed that the impaired adrenal responses to 1-μg cosyntropin were common in patients with bronchiectasis. This was not associated with the use of inhaled steroids or severity of bronchiectasis. Poor health status was associated with advanced disease and not with cortisol responses to the 1-μg cosyntropin

  2. The short and long term effects of exercise training in non-cystic fibrosis bronchiectasis – a randomised controlled trial

    PubMed Central

    2014-01-01

    Background Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis. Methods Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months. Results Eighty-five participants (mean FEV1 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1–3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1–3]) compared to the control group (2[1–3]) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p = 0.047). Conclusions Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and

  3. Observational study of sleep, respiratory mechanics and quality of life in patients with non-cystic fibrosis bronchiectasis: a protocol study

    PubMed Central

    Faria Júnior, Newton Santos; Oliveira, Luis Vicente Franco; Perez, Eduardo Araújo; de Oliveira, Ezequiel Fernandes; Apostolico, Nadua; Pereira, Nixon Alves; dos Santos, Israel dos Reis; Urbano, Jessica Julioti; Souza, Ismael Dias; Polonio, Igor Bastos; Romaldini, José Gustavo Barian; Pereira, Déborah Madeu; Alves, Vera Lúcia dos Santos; Souza, Ângela Honda; Nascimento, Oliver Augusto; Jardim, José Roberto; Stirbulov, Roberto

    2015-01-01

    Introduction Bronchiectasis is a chronic disorder characterised by permanent and irreversible abnormal dilation of the bronchi and bronchioles, primarily caused by repeated cycles of pulmonary infections and inflammation, which lead to reduced mucociliary clearance and to the excessive production of sputum. Patients with non-cystic fibrosis bronchiectasis may be predisposed to hypoxemia during sleep, or to symptoms that may lead to arousals and thereby reduce the quality of life, because of the irreversible dilation of the bronchi and the presence of secretions and airflow obstruction. Methods and analysis For this cross-sectional observational study, patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis will be recruited from the Bronchiectasis Clinic of the Pneumology Department of the Santa Casa de Misericordia Hospital and the Federal University of São Paulo (São Paulo, Brazil). Patients of either sex will be included if high-resolution CT of the thorax and classic sweat test confirms they have non-cystic fibrosis bronchiectasis, are between 18 and 80 years old, use long-acting bronchodilators, are clinically stable for a least 1 month, agree to participate in the study and they sign a statement of informed consent. The first part of the study will involve a clinical evaluation, maximal respiratory pressures, spirometry and the Saint George's Respiratory Questionnaire. The Sleep Laboratory of the Master's and Doctoral Postgraduate Program in Rehabilitation Sciences of the Nove de Julho University (São Paulo, Brazil) will perform the polysomnographic studies, Berlin Questionnaire, Epworth Sleepiness Scale, waist and neck circumferences, modified Mallampati classification and tonsil index. Ethics and dissemination This protocol has been approved by the Human Research Ethics Committees of Santa Casa de Misericordia Hospital (process number 178/2012) and Human Research Ethics Committee of Nove de Julho University (process number 370474

  4. Respiratory Exacerbations in Indigenous Children From Two Countries With Non-Cystic Fibrosis Chronic Suppurative Lung Disease/Bronchiectasis

    PubMed Central

    Singleton, Rosalyn J.; Valery, Patricia C.; Williams, Hayley; Grimwood, Keith; Morris, Peter S.; Torzillo, Paul J.; McCallum, Gabrielle B.; Chikoyak, Lori; Holman, Robert C.; Chang, Anne B.

    2014-01-01

    BACKGROUND: Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis. METHODS: Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter. RESULTS: Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators. CONCLUSIONS: AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care. PMID:24811693

  5. Macrolide Therapy in Adults and Children with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and Meta-Analysis

    PubMed Central

    Tang, Yan; Gao, Yang; Lin, Zhi-ya; Lin, Zhi-min; Zhong, Nan-shan; Chen, Rong-chang

    2014-01-01

    Background A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis. Methods We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events. Results Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75–0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, −6.56; 95% CI, −11.99 to −1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, −11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy. Conclusions Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in Qo

  6. Familial non-cystic fibrosis mucus inspissation of respiratory tract.

    PubMed Central

    Perlman, M; Williams, J; Hirsch, M; Bar-Ziv, J

    1975-01-01

    Perlman, M., Williams, J., Hirsch, M., and Bar-Ziv, J. (1975). Archives of Disease in Childhood, 50, 727. Familial non-cystic fibrosis mucus inspissation of respiratory tract. Two sibs, whose parents are first cousins, have had chronic obstructive airways disease from birth with recurrent otitis media, sinusitis, and mastoiditis. The disease, associated with clinically abnormal mucus, differs from other familial obstructive airways diseases and probably constitutes a new entity. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:1190822

  7. Imaging of Cystic Fibrosis and Pediatric Bronchiectasis.

    PubMed

    Murphy, Kevin P; Maher, Michael M; O'Connor, Owen J

    2016-03-01

    1. CT is superior to pulmonary function tests and chest radiography for the assessment and monitoring of cystic fibrosis (CF)-related lung disease and, also, of pediatric bronchiectasis not caused by CF (hereafter referred to as non-CF bronchiectasis). 2. Low-dose CT protocols that impart radiation doses similar to those used in chest radiography are feasible for the surveillance of patients with bronchiectasis. 3. Chest radiography is still most commonly used as the first-line imaging examination of choice for the assessment of acute complications related to bronchiectasis. 4. Pulmonary MRI, with or without the use of inhaled hyperpolarized gas, can be performed to obtain functional information, and, in dedicated centers, it may yield imaging results comparable to those obtained by CT. 5. Gastrointestinal and pancreaticobiliary manifestations of CF are observed with greater frequency in adults, because of increased life expectancy. PMID:26901001

  8. Bronchiectasis

    MedlinePlus

    ... severe lung infection or inhaling a foreign object . Cystic fibrosis causes about a third of all bronchiectasis cases ... count (CBC) Genetic testing, including sweat test for cystic fibrosis PPD skin test to check for a past ...

  9. Nontuberculous Mycobacteria in Noncystic Fibrosis Bronchiectasis

    PubMed Central

    Bonaiti, Giulia; Pesci, Alberto; Marruchella, Almerico; Lapadula, Giuseppe; Gori, Andrea

    2015-01-01

    During the past decades, a growing interest has been raised in evaluating nontuberculous mycobacteria (NTM) in patients with noncystic fibrosis bronchiectasis (NCFBE). This paper reviews several aspects of the correlations between NTM and NCFBE, including pathogenesis, radiological features, diagnosis, and management. Bronchiectasis and NTM lung disease are connected, but which one comes first is still an unresolved question. The rate of NTM lung disease in NCFBE varies through the studies, from 5% to 30%. The most frequent species isolated is MAC. NCFBE patients affected by NTM infection frequently present coinfections, including both other different NTM species and microorganisms, such as P. aeruginosa. Once a diagnosis of NTM disease has been reached, the initiation of therapy is not always mandatory. NTM species isolated, patients' conditions, and disease severity and its evolution should be considered. Risk factors for disease progression in NCFBE patients with NTM are low body mass index, cavitary disease, consolidations, and macrolide resistance at presentation. PMID:26106603

  10. A neglected problem of developing countries: Noncystic fibrosis bronchiectasis

    PubMed Central

    Babayigit, Arzu; Olmez, Duygu; Uzuner, Nevin; Cakmakci, Handan; Tuncel, Tuba; Karaman, Ozkan

    2009-01-01

    BACKGROUND: Bronchiectasis has been defined as the abnormal and permanent dilation of the bronchi. It is still an important problem in many developing countries. AIM: The aim of this study was to identify the chacteristics and underlying etiology of children followed with the diagnosis of noncystic fibrosis bronchiectasis. MATERIALS AND METHODS: Children with bronchiectasis confirmed with high-resolution computed tomography were enrolled into the study. The data of the patients, including symptoms of the disease, age at the onset of symptoms, findings of physical examination, labrotory investigations performed in order to identify the etiology of bronchiectasis, etiology of bronchiectasis if found, radiologic findings and treatment modalities were noted. RESULTS: Sixty-six children between 1 and 17 years were included in the study retrospectively. Forty-four of them were males (66.7%) and 22 (33.3%) were females. The most common presenting symptoms were cough (100%) and sputum expectoration (50%). An underlying etiology was identified in 44 (66.7%) of the study subjects. The four most common underlying causes were found as infections (21.2%), asthma (16.7%), aspiration syndromes and/or gastroesophageal reflux disease (9.1%) and immunodeficiency syndromes (7.6%), respectively. CONCLUSION: Identifying an underlying etiology will have a significant effect on the management of noncystic fibrosis bronchiectasis. Defining the cause of bronchiectasis may also decrease its incidence, progression and complications. PMID:19561918

  11. Bronchiectasis

    PubMed Central

    2011-01-01

    Introduction Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions. Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, beta2 agonists, bronchopulmonary hygiene physical therapy, corticosteroids (inhaled, oral), exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, and surgery. PMID:21846412

  12. Gastro-Oesophageal Reflux in Noncystic Fibrosis Bronchiectasis

    PubMed Central

    Lee, Annemarie L.; Button, Brenda M.; Denehy, Linda; Wilson, John W.

    2011-01-01

    The clinical presentation of noncystic fibrosis bronchiectasis may be complicated by concomitant conditions, including gastro-oesophageal reflux (GOR). Increased acidic GOR is principally caused by gastro-oesophageal junction incompetence and may arise from lower oesophageal sphincter hypotension, including transient relaxations, hiatus hernia, and oesophageal dysmotility. Specific pathophysiological features which are characteristic of respiratory diseases including coughing may further increase the risk of GOR in bronchiectasis. Reflux may impact on lung disease severity by two mechanisms, reflex bronchoconstriction and pulmonary microaspiration. Symptomatic and clinically silent reflux has been detected in bronchiectasis, with the prevalence of 26 to 75%. The cause and effect relationship has not been established, but preliminary reports suggest that GOR may influence the severity of bronchiectasis. Further studies examining the implications of GOR in this condition, including its effect across the disease spectrum using a combination of diagnostic tools, will clarify the clinical significance of this comorbidity. PMID:22135740

  13. [Bronchiectasis in pediatrics, diagnosis approach and management].

    PubMed

    Alvarez Caro, Francisco; Gómez Farpón, Angela; Ruiz del Árbol Sánchez, Paloma; de Miguel Mallén, Ma Ángeles; Alvarez Berciano, Francisco

    2012-01-01

    Bronchiectasis is still an important health problem in both, developed and developing countries. Cystic fibrosis is one of the most important causes, but a great variety of other causes makes non cystic fibrosis bronchiectasis a relatively frequent diagnosis. Early diagnosis based on medical history and radiological confirmation is only the starting point to determine the specific etiology, in order to establish a treatment focused on the underlying cause. For this purpose, an orderly and systematic diagnostic evaluation is required. A review article about bronchiectasis, particularly those not related to cystic fibrosis, is presented. PMID:22307423

  14. Pharmacologic agents for mucus clearance in bronchiectasis.

    PubMed

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. PMID:22640851

  15. British Thoracic Society guideline for non-CF bronchiectasis.

    PubMed

    Pasteur, M C; Bilton, D; Hill, A T

    2010-07-01

    The diagnosis, investigation and particularly management of bronchiectasis has been largely empirical and the subject of relatively few controlled clinical trials. There are no clear guidelines, although an Australian position statement has been published concerning bronchiectasis in children. The purposes of these guidelines were therefore threefold: (1) to identify relevant studies in non-cystic fibrosis (CF) bronchiectasis; (2) to provide guidelines on management based on published studies where possible or a consensus view; and (3) to identify gaps in our knowledge and identify areas for future study. PMID:20627931

  16. Bronchiectasis

    MedlinePlus

    ... Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Atelectasis Cough Cystic Fibrosis Primary Ciliary Dyskinesia Respiratory Failure Send a link ...

  17. Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis.

    PubMed

    Garratt, Luke W; Sutanto, Erika N; Ling, Kak-Ming; Looi, Kevin; Iosifidis, Thomas; Martinovich, Kelly M; Shaw, Nicole C; Kicic-Starcevich, Elizabeth; Knight, Darryl A; Ranganathan, Sarath; Stick, Stephen M; Kicic, Anthony

    2015-08-01

    Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix modelling and are activated by neutrophil elastase. The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young children with cystic fibrosis.Total MMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 levels were measured in bronchoalveolar lavage fluid collected from young children with cystic fibrosis during annual clinical assessment. Active/pro-enzyme ratio of MMP-9 was determined by gelatin zymography. Annual chest computed tomography imaging was scored for bronchiectasis.A higher MMP-9/TIMP-1 ratio was associated with free neutrophil elastase activity. In contrast, MMP-2/TIMP-2 ratio decreased and MMP-1 and MMP-7 were not detected in the majority of samples. Ratio of active/pro-enzyme MMP-9 was also higher in the presence of free neutrophil elastase activity, but not infection. Across the study cohort, both MMP-9/TIMP-1 and active MMP-9 were associated with progression of bronchiectasis.Both MMP-9/TIMP-1 and active MMP-9 increased with free neutrophil elastase and were associated with bronchiectasis, further demonstrating that free neutrophil elastase activity should be considered an important precursor to cystic fibrosis structural disease. PMID:25929954

  18. Molecular Characterization of Achromobacter Isolates from Cystic Fibrosis and Non-Cystic Fibrosis Patients in Madrid, Spain

    PubMed Central

    Barrado, Laura; Brañas, Patricia; Orellana, M. Ángeles; Martínez, M. Teresa; García, Gloria; Otero, Joaquín R.

    2013-01-01

    Multilocus sequence typing and nrdA sequence analysis identified 6 different species or genogroups and 13 sequence types (STs) among 15 Achromobacter isolates from cystic fibrosis (CF) patients and 7 species or genogroups and 11 STs among 11 isolates from non-CF patients. Achromobacter xylosoxidans was the most frequently isolated species among CF patients. PMID:23536401

  19. Pulmonary bacterial communities in surgically resected noncystic fibrosis bronchiectasis lungs are similar to those in cystic fibrosis.

    PubMed

    Maughan, Heather; Cunningham, Kristopher S; Wang, Pauline W; Zhang, Yu; Cypel, Marcelo; Chaparro, Cecilia; Tullis, D Elizabeth; Waddell, Thomas K; Keshavjee, Shaf; Liu, Mingyao; Guttman, David S; Hwang, David M

    2012-01-01

    Background. Recurrent bacterial infections play a key role in the pathogenesis of bronchiectasis, but conventional microbiologic methods may fail to identify pathogens in many cases. We characterized and compared the pulmonary bacterial communities of cystic fibrosis (CF) and non-CF bronchiectasis patients using a culture-independent molecular approach. Methods. Bacterial 16S rRNA gene libraries were constructed from lung tissue of 10 non-CF bronchiectasis and 21 CF patients, followed by DNA sequencing of isolates from each library. Community characteristics were analyzed and compared between the two groups. Results. A wide range of bacterial diversity was detected in both groups, with between 1 and 21 bacterial taxa found in each patient. Pseudomonas was the most common genus in both groups, comprising 49% of sequences detected and dominating numerically in 13 patients. Although Pseudomonas appeared to be dominant more often in CF patients than in non-CF patients, analysis of entire bacterial communities did not identify significant differences between these two groups. Conclusions. Our data indicate significant diversity in the pulmonary bacterial community of both CF and non-CF bronchiectasis patients and suggest that this community is similar in surgically resected lungs of CF and non-CF bronchiectasis patients. PMID:22448327

  20. Genome macrorestriction analysis of sequential Pseudomonas aeruginosa isolates from bronchiectasis patients without cystic fibrosis.

    PubMed Central

    Hla, S W; Hui, K P; Tan, W C; Ho, B

    1996-01-01

    The respiratory tracts of bronchiectasis patients may be persistently colonized with Pseudomonas aeruginosa, despite intensive chemotherapy. The organism may undergo phenotypic changes in these patients, providing misleading typing results by conventional methods. We prospectively studied eight bronchiectasis patients without cystic fibrosis over a period of 1 year. A high microbial load of P. aeruginosa was found in 70% of sputum samples collected. Of these, 55 sequential P. aeruginosa isolates were characterized by a genotyping method, pulsed-field gel electrophoresis, to overcome the problem of differentiating the P. aeruginosa strains during chemotherapy. Genome macrorestriction fingerprinting patterns were analyzed after digestion with XbaI restriction endonuclease. Of the eight patients, six harbored a single dominant strain of P. aeruginosa, with an intrapatient macrorestriction similarity pattern range of 96 to 100%. The other two patients were infected with mixed bacterial isolates including P. aeruginosa. However, diversity was observed in the P. aeruginosa isolates from all eight patients, with a relatedness of only 55 to 65%. The study further strengthens the fact that pulsed-field gel electrophoresis can be used efficiently and effectively to differentiate P. aeruginosa strains in bronchiectasis patients without cystic fibrosis. PMID:8904417

  1. Non-tuberculous mycobacteria in patients with bronchiectasis

    PubMed Central

    Wickremasinghe, M; Ozerovitch, L; Davies, G; Wodehouse, T; Chadwick, M; Abdallah, S; Shah, P; Wilson, R

    2005-01-01

    Background: Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Patients with pre-existing lung damage are susceptible to NTM, but their prevalence in bronchiectasis is unknown. Distinguishing between lung colonisation and disease can be difficult. Methods: A prospective study of 100 patients with bronchiectasis was undertaken to evaluate the prevalence of NTM in sputum, and a retrospective analysis of clinical, microbiological, lung function and radiology data of our clinic patients with NTM sputum isolates over 11 years was performed. Results: The prevalence of NTM in this population of patients with bronchiectasis was 2%. Patients in the retrospective study were divided into three groups: bronchiectasis + multiple NTM isolates (n = 25), bronchiectasis + single isolates (n = 23), and non-bronchiectasis + multiple isolates (n = 22). Mycobacterium avium complex (MAC) species predominated in patients with bronchiectasis compared with non-bronchiectasis lung disease (72% v 9%, p<0.0001). Single isolates were also frequently MAC (45.5%). Multiple isolates in bronchiectasis were more often smear positive on first sample than single isolates (p<0.0001). NTM were identified on routine screening samples or because of suggestive radiology. No particular bronchiectasis aetiology was associated with an NTM. Pseudomonas aeruginosa and Staphylococcus aureus were frequently co-cultured. Six (25%) of multiple NTM patients had cavities of which five were due to MAC. Half the patients with multiple isolates were treated, mostly due to progressive radiology. Conclusions: NTM are uncommon in non-cystic fibrosis bronchiectasis. Routine screening identifies otherwise unsuspected patients. MAC is the most frequent NTM isolated. PMID:16227333

  2. Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis.

    PubMed

    Dente, Federico L; Bilotta, Marta; Bartoli, Maria Laura; Bacci, Elena; Cianchetti, Silvana; Latorre, Manuela; Malagrinò, Laura; Nieri, Dario; Roggi, Maria Adelaide; Vagaggini, Barbara; Paggiaro, Pierluigi

    2015-01-01

    Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152 NFCB patients (62.6 years; females: 57.2%) underwent clinical and functional cross-sectional evaluation, including microbiologic and inflammatory cell profile in sputum, and exhaled breath condensate malondialdehyde (EBC-MDA). NFCB severity was assessed using BSI and FACED criteria. Results. Sputum neutrophil percentages inversely correlated with FEV1 (P < 0.0001; rho = -0.428), weakly with Leicester Cough Questionnaire score (P = 0.068; rho = -0.58), and directly with duration of the disease (P = 0.004; rho = 0.3) and BSI severity score (P = 0.005; rho = 0.37), but not with FACED. Sputum neutrophilia was higher in colonized subjects, P. aeruginosa colonized subjects showing greater sputum neutrophilia and lower FEV1. Patients with ≥3 exacerbations in the last year showed a significantly greater EBC-MDA than the remaining patients. Conclusions. Sputum neutrophilic inflammation and biomarkers of oxidative stress in EBC can be considered good biomarkers of disease severity in NCFB patients, as confirmed by pulmonary function, disease duration, bacterial colonization, BSI score, and exacerbation rate. PMID:26819500

  3. Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis

    PubMed Central

    Dente, Federico L.; Bilotta, Marta; Bartoli, Maria Laura; Bacci, Elena; Cianchetti, Silvana; Latorre, Manuela; Malagrinò, Laura; Nieri, Dario; Roggi, Maria Adelaide; Vagaggini, Barbara; Paggiaro, Pierluigi

    2015-01-01

    Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152 NFCB patients (62.6 years; females: 57.2%) underwent clinical and functional cross-sectional evaluation, including microbiologic and inflammatory cell profile in sputum, and exhaled breath condensate malondialdehyde (EBC-MDA). NFCB severity was assessed using BSI and FACED criteria. Results. Sputum neutrophil percentages inversely correlated with FEV1 (P < 0.0001; rho = −0.428), weakly with Leicester Cough Questionnaire score (P = 0.068; rho = −0.58), and directly with duration of the disease (P = 0.004; rho = 0.3) and BSI severity score (P = 0.005; rho = 0.37), but not with FACED. Sputum neutrophilia was higher in colonized subjects, P. aeruginosa colonized subjects showing greater sputum neutrophilia and lower FEV1. Patients with ≥3 exacerbations in the last year showed a significantly greater EBC-MDA than the remaining patients. Conclusions. Sputum neutrophilic inflammation and biomarkers of oxidative stress in EBC can be considered good biomarkers of disease severity in NCFB patients, as confirmed by pulmonary function, disease duration, bacterial colonization, BSI score, and exacerbation rate. PMID:26819500

  4. Efficacy of Halotherapy for Improvement of Pulmonary function Tests and Quality of Life of Non-Cystic Fibrosis Bronchiectatic Patients

    PubMed Central

    Rabbani, Bita; Najafizadeh, Katayoon; Vishteh, Hamid Reza Khodami; Shafaghi, Shadi; Karimi, Shirin; Mahmoodian, Saeid

    2013-01-01

    Background Halotherapy is a treatment modality suggested for patients with chronic pulmonary diseases. In this technique, inhalation of crystal salt stones extracted from mines improves patients’ pulmonary function tests and symptoms by facilitating the secretion or expulsion of phlegm and mucus and reducing the risk of bacterial infections. Bronchiectasis is chronic disease of the airways characterized by irreversible dilation of airways. It has a progressive course and despite the available treatments, many of these patients eventually enter the advanced phase of disease. The aim of this study was to evaluate the effect of halotherapy on pulmonary function tests and quality of life of non-CF bronchiectatic patients. Materials and Methods This clinical trial evaluated the results of spirometry and 6-minute walk test as well as the quality of life (according to SF-36 questionnaire) of stable non-CF bronchiectatic patients presenting to the pulmonary clinic before and after the use of salt spray for 2 months. Results Of 40 study patients, 20 were excluded due to various reasons and 20 were evaluated. The mean age of patients was 35±11 years and the underlying cause of disease was chronic pulmonary infection in 65% of cases. Comparison of the results of pulmonary function tests and 6-minute walk test and quality of life indices in SF-36 questionnaire before and after the intervention showed no significant difference (P > 0.05). However, 65% of patients were satisfied with halotherapy and requested to receive the medication again. Conclusion Our study results indicated that 2-month halotherapy with Salitair inhaler containing salt crystals extracted from the Klodawa mine in Poland could not improve the pulmonary function tests or quality of life of non-CF bronchiectatic patients. No significant side effects were noted in understudy patients. Future studies with larger sample size and longer duration of treatment are recommended to better determine the efficacy of

  5. Improvement in health status following bronchopulmonary hygiene physical therapy in patients with bronchiectasis.

    PubMed

    Mutalithas, Kugathasan; Watkin, Gillian; Willig, Briony; Wardlaw, Andrew; Pavord, Ian D; Birring, Surinder S

    2008-08-01

    Chronic productive cough is a common symptom in patients with bronchiectasis that is associated with a reduction in health-related quality of life (QOL). Bronchopulmonary hygiene physical therapy (BHPT) is widely prescribed for patients with bronchiectasis, although the evidence for its efficacy is limited. We set out to prospectively evaluate the impact of BHPT on health-related QOL in patients with non-cystic fibrosis bronchiectasis. We assessed cough symptoms (0-100mm visual analogue scale; VAS) and cough-related QOL in 53 patients with stable non-cystic fibrosis bronchiectasis at baseline and >4 weeks after outpatient-based BHPT. Cough specific health status was assessed with the Leicester Cough Questionnaire (LCQ; total score range 3-21, higher scores representing better QOL). All patients with bronchiectasis complained of cough as the major symptom and had mean (SEM) FEV(1) of 2.1 (0.1)L. Cough-related health status was reduced at baseline; mean (SEM) LCQ score 14.3 (0.6). There were significant improvements in cough symptoms (mean cough VAS before 43.3 (3.6) vs after 27.5 (3.1); mean difference 15.8; 95% CI of difference 9.6-22; p<0.0001) and cough-related health status after BHPT (mean LCQ total score before 14.2 vs after 17.3; mean difference 3.1; 95% confidence interval of difference 2.4-3.9; p<0.001). A significant improvement was seen in all LCQ health-related domains (physical, psychological and social; all p<0.001). Our findings suggest that bronchopulmonary hygiene physical therapy can lead to a significant improvement in cough-related quality of life. PMID:18585027

  6. Neutrophil Fates in Bronchiectasis and Alpha-1 Antitrypsin Deficiency.

    PubMed

    Russell, Derek W; Gaggar, Amit; Solomon, George M

    2016-04-01

    The neutrophil is a powerful cellular defender of the vulnerable interface between the environment and pulmonary tissues. This cell's potent weapons are carefully calibrated in the healthy state to maximize effectiveness in fighting pathogens while minimizing tissue damage and allowing for repair of what damage does occur. The three related chronic airway disorders of cystic fibrosis, non-cystic fibrosis bronchiectasis, and alpha-1 antitrypsin deficiency all demonstrate significant derangements of this homeostatic system that result in their respective pathologies. An important shared feature among them is the inefficient resolution of chronic inflammation that serves as a central means for neutrophil-driven lung damage resulting in disease progression. Examining the commonalities and divergences between these diseases in the light of their immunopathology is informative and may help guide us toward future therapeutics designed to modulate the neutrophil's interplay with the pulmonary environment. PMID:27115946

  7. Diagnostic challenges of bronchiectasis.

    PubMed

    Suarez-Cuartin, Guillermo; Chalmers, James D; Sibila, Oriol

    2016-07-01

    Bronchiectasis is a condition of increasing incidence and prevalence around the world. Many different diseases have been associated with bronchiectasis, and their treatment can differ widely. Recent guidelines have helped to approach aetiological diagnosis but it is still a complex process. Identifying the cause of the bronchiectasis may determine a change in the treatment of a large group of subjects. That is one of the main reasons why the aetiological diagnosis is crucial in the proper management of bronchiectasis patients. Postinfectious bronchiectasis is the most frequent entity among different studies, but a high percentage of cases still remain without a clear aetiology. Bronchiectasis related to allergic bronchopulmonary aspergillosis (ABPA), immunodeficiencies with antibody production deficiency, primary ciliary dyskinesia, cystic fibrosis and alpha-1-antitrypsin deficiency, among others, require a specific management that may improve quality of life and prognosis in a large group of individuals. Therefore, the aim of this article is to review the main bronchiectasis related diseases and to simplify the aetiological diagnosis, in order to improve the management of bronchiectasis patients, especially in those where a specific treatment is available. PMID:27296824

  8. Effect of Low-Dose, Long-Term Roxithromycin on Airway Inflammation and Remodeling of Stable Noncystic Fibrosis Bronchiectasis

    PubMed Central

    Zhong, Xiaoning; He, Zhiyi; Wei, Lianghong; Zheng, Xiaozhen; Zhang, Jianquan; Bai, Jing; Zhong, Wei; Zhong, Dengjun

    2014-01-01

    Background. Noncystic fibrosis bronchiectasis (NCFB) is characterized by airway expansion and recurrent acute exacerbations. Macrolide has been shown to exhibit anti-inflammatory effects in some chronic airway diseases. Objective. To assess the efficacy of roxithromycin on airway inflammation and remodeling in patients with NCFB under steady state. Methods. The study involved an open-label design in 52 eligible Chinese patients with NCFB, who were assigned to control (receiving no treatment) and roxithromycin (receiving 150 mg/day for 6 months) groups. At baseline and 6 months, the inflammatory markers such as interleukin- (IL-)8, neutrophil elastase (NE), matrix metalloproteinase- (MMP)9, hyaluronidase (HA), and type IV collagen in sputum were measured, along with the detection of dilated bronchus by throat computed tomography scan, and assessed the exacerbation. Results. Forty-three patients completed the study. The neutrophil in the sputum was decreased in roxithromycin group compared with control (P < 0.05). IL-8, NE, MMP-9, HA, and type IV collagen in sputum were also decreased in roxithromycin group compared with the control group (all P < 0.01). Airway thickness of dilated bronchus and exacerbation were reduced in roxithromycin group compared with the control (all P < 0.05). Conclusions. Roxithromycin can reduce airway inflammation and airway thickness of dilated bronchus in patients with NCFB. PMID:25580060

  9. SINUSITIS, BRONCHIECTASIS, AND FLATUS IN A SUMATRAN ORANGUTAN (PONGO ABELII): COULD THIS BE CYSTIC FIBROSIS?

    PubMed

    Stringer, Elizabeth; Cossaboon, Cindy; Han, Sushan; Taylor-Cousar, Jennifer L

    2016-03-01

    A 31-yr-old male Sumatran orangutan (Pongo abelii) presented with 14 yr of chronic purulent nasal drainage and cough with intermittent exacerbation of symptoms requiring systemic antibiotic treatment. He was diagnosed with a cystic fibrosis (CF)-like condition. Evaluation consisted of bronchoscopy with bronchoalveolar lavage, culture, and computed tomography scanning of the sinuses and chest. Although the presence of low fecal elastase activity increased the suspicion for a diagnosis of CF, pilocarpine iontophoresis with sweat collection and analysis ("sweat testing") was inconclusive. Medical management included twice-daily nebulization with bronchodilators and alternating month inhaled antibiotics, pancreatic enzyme replacement therapy, and simethicone as needed. Sinopulmonary and gastrointestinal symptoms improved substantially with treatment. Several years later, the animal died acutely of colonic volvulus. Necropsy and histopathology confirmed CF-like lung disease with chronic air sacculitis. PMID:27010300

  10. A prospective cohort study of the use of domiciliary intravenous antibiotics in bronchiectasis

    PubMed Central

    Bedi, Pallavi; Sidhu, Manjit K; Donaldson, Lucienne S; Chalmers, James D; Smith, Maeve P; Turnbull, Kim; Pentland, Joanna L; Scott, Jenny; Hill, Adam T

    2014-01-01

    Background: We introduced domiciliary intravenous (IV) antibiotic therapy in patients with bronchiectasis to promote patient-centred domiciliary treatment instead of hospital inpatient treatment. Aim: To assess the efficacy and safety of domiciliary IV antibiotic therapy in patients with non-cystic fibrosis bronchiectasis. Methods: In this prospective study conducted over 5 years, we assessed patients’ eligibility for receiving domiciliary treatment. All patients received 14 days of IV antibiotic therapy and were monitored at baseline/day 7/day 14. We assessed the treatment outcome, morbidity, mortality and 30-day readmission rates. Results: A total of 116 patients received 196 courses of IV antibiotics. Eighty courses were delivered as inpatient treatment, 32 as early supported discharge (ESD) and 84 as domiciliary therapy. There was significant clinical and quality of life improvement in all groups, with resolution of infection in 76% in the inpatient group, 80% in the ESD group and 80% in the domiciliary group. Morbidity was recorded in 13.8% in the inpatient group, 9.4% in the ESD group and 14.2% in the domiciliary IV group. No mortality was recorded in either group. Thirty-day readmission rates were 13.8% in the inpatient group, 12.5% in the ESD group and 14.2% in the domiciliary group. Total bed days saved was 1443. Conclusion: Domiciliary IV antibiotic therapy in bronchiectasis is clinically effective and was safe in our cohort of patients. PMID:25340361

  11. Bronchiectasis exacerbations: The role of atypical bacteria and respiratory syncytial virus

    PubMed Central

    Metaxas, Eugenios I; Balis, Evangelos; Papaparaskevas, Joseph; Spanakis, Nicholas E; Tatsis, Georgios; Tsakris, Athanasios

    2015-01-01

    BACKGROUND: Aside from the known role of common bacteria, there is a paucity of data regarding the possible role of atypical bacteria and viruses in exacerbations of non-cystic fibrosis bronchiectasis. OBJECTIVE: To explore the possible role of atypical bacteria (namely, Mycoplasma pneumoniae and Chlamydophila pneumoniae) and respiratory syncytial virus (RSV) as causative agents of bronchiectasis exacerbations. METHODS: A cohort of 33 patients was studied over a two-year period (one year follow-up for each patient). Polymerase chain reaction for the detection of M pneumoniae, C pneumoniae and RSV in bronchoalveolar lavage samples were performed during all visits. Antibody titres (immunoglobulin [Ig]M and IgG) against the aforementioned pathogens were also measured. In addition, cultures for common bacteria and mycobacteria were performed from the bronchoalveolar lavage samples. RESULTS: Fifteen patients experienced a total of 19 exacerbations during the study period. Although RSV was detected by polymerase chain reaction during stable visits in four patients, it was never detected during an exacerbation. M pneumoniae and C pneumoniae were never detected at stable visits or during exacerbations. IgM antibody titres for these three pathogens were negative in all patient visits. CONCLUSIONS: Atypical pathogens and RSV did not appear to be causative agents of bronchiectasis exacerbations. PMID:25874735

  12. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    PubMed Central

    2012-01-01

    people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886. PMID:22937736

  13. Cystic Fibrosis

    MedlinePlus

    ... for the Public » Health Topics » Cystic Fibrosis Explore Cystic Fibrosis What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Living With Clinical Trials Links Related Topics Bronchiectasis ...

  14. Comparison of susceptibility of cystic-fibrosis-related and non-cystic-fibrosis-related Pseudomonas aeruginosa to chlorine-based disinfecting solutions: implications for infection prevention and ward disinfection.

    PubMed

    Moore, John E; Rendall, Jacqueline C

    2014-09-01

    Multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from cystic fibrosis (CF) sputum was shown to be more tolerant to the most commonly used chlorine-based disinfecting agent in the UK, with approximately 7 out of 10 isolates surviving a residual free chlorine (RFC) concentration of 500 p.p.m., when compared with antibiotic-sensitive invasive P. aeruginosa from a non-CF blood culture source, where 8 out of 10 isolates were killed at a RFC concentration of 100 p.p.m. All CF isolates were killed at 1000 p.p.m. chlorine. Additional studies were performed to examine factors that influenced the concentration of RFC from chlorine-based (sodium dichloroisocyanurate) disinfecting agents in contact with CF sputum and their components (bacterial cells, glycocalyx) to assess the reduction of the bactericidal activity of such disinfecting agents. Pseudomonas glycocalyx had a greater inhibitory effect of chlorine deactivation than bacterial cells. Calibration curves demonstrated the relative deactivating capacity on RFC from clinical soils, in the order pus>CF sputum>wound discharge fluid/synovial fluid>ascites fluid>bile, where quantitatively each 1 % (w/v) CF sputum reduced the RFC by 43 p.p.m. Sublethal stressing of P. aeruginosa with chlorine resulted in lowered susceptibility to colistin (P = 0.0326) but not to meropenem, tobramycin or ciprofloxacin. In conclusion, heavy contamination of healthcare fomites with CF sputum containing MDR P. aeruginosa may result in exhaustion of RFC, and this, combined with an increased resistance to chlorine with such strains, may lead to their survival and increased antibiotic resistance in such environments. CF infection prevention strategies in such scenarios should therefore target interventions with increased concentrations of chlorine to ensure the eradication of MDR P. aeruginosa from the CF healthcare environment. PMID:24925907

  15. Use of aerosols in bronchiectasis patients.

    PubMed

    Dal Negro, R W; Micheletto, C; Tognella, S

    2011-09-01

    Bronchiectasis is a chronic respiratory disease which recognises different etiologies, and characterised by persistent cough, bronchial hypersecretion, airway colonisation with Gram-negative pathogens; frequent infectious exacerbations; progressive lung function decline, and poor quality of life. Several therapeutic strategies are used for managing bronchiectasis, and nebulised medications are regarded with great and ever increasing interest because they allow the direct medication of targets airway structures, higher concentrations of the drug employed, and much less systemic effects. In general terms, the available therapeutic strategies lead to different results depending of whether bronchiectasis are related to cystic fibrosis or not. The effects of the main classes of drugs for aerosol delivery in bronchiectasis patients have been reviewed and updated. Further research is needed in order to ameliorate therapeutic interventions in bronchiectasis, both in terms of new molecules and aerosol formulations to use, and of systems able to optimize drug delivery and drug effectiveness. PMID:22428222

  16. To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE). Methods/Design This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year. Discussion We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung

  17. Bronchiectasis revisited.

    PubMed Central

    Lindskog, G. E.

    1986-01-01

    The writer of this retrospective essay witnessed his first open chest operation during the academic year 1928-29 while an intern in general surgery at Lakeside Hospital, Cleveland, Ohio. The operative procedure was probably the first of its kind to be performed at that teaching hospital, and it involved the excision of a mediastinal tumefaction through a median sternotomy. Now, more than fifty-five years and several thousand thoracic operations later, the author recounts the evolution of pulmonary resection, particularly in relation to the therapy of bronchiectasis. The technical obstacles which delayed too long the achievement of reasonably safe and anatomically complete resections of lung are discussed, and the circuitous route trod by pioneering surgeons in their struggle toward that desired goal is described. In addition, some contributions made along the way by members of the faculty at the Yale University School of Medicine to our present knowledge of bronchiectasis--its pathologic anatomy, pathophysiology, and surgical therapy--are summarized briefly. PMID:3515779

  18. Bronchiectasis in China.

    PubMed

    Lin, Jie-Lu; Xu, Jin-Fu; Qu, Jie-Ming

    2016-05-01

    Bronchiectasis is a common but long-neglected disease in China, causing a substantial disease burden both to patients and to society. The overall prevalence of physician-diagnosed bronchiectasis in people aged 40 years or older is estimated at 1.2% and is trending upward with aging of the population. The etiology of bronchiectasis has not been identified heretofore in more than 70% of patients in China, although pneumonia and tuberculosis still appear to be the most common causes of acquired bronchiectasis. Etiologies, comorbidities, and infecting organisms vary greatly across previously published epidemiological studies, resulting in considerable uncertainty. Little is known about the spectrum of severity of bronchiectasis in China. Presently, engagement of pulmonologists is largely limited to acute treatment of exacerbations of severe bronchiectasis. Based on limited available data and expert consensus, the first comprehensive guidelines for the diagnosis and treatment of bronchiectasis in China were published in 2012. Research to advance medical care for patients with this disease in China should focus on several priorities, including: standardization of diagnostic criteria with appropriate application of computed tomographic imaging; use of validated multidimensional grading systems to assess the severity of bronchiectasis; and epidemiological studies that are designed to measure mild to moderate as well as severe disease, and to represent the population beyond large urban centers. Better estimates of the true burden of bronchiectasis are needed to guide allocation of national medical resources and to implement public health strategies for prevention of the disease. Treatment should be expanded to include expert maintenance care of ambulatory patients in addition to treatment of exacerbations. PMID:26882271

  19. Humoral immunity in bronchiectasis.

    PubMed

    Barker, A F; Craig, S; Bardana, E J

    1987-09-01

    Bronchiectasis occurs in patients with immunodeficiency and fungal hypersensitivity disorders. To assess the prevalence of abnormal humoral immune parameters in bronchiectasis, a retrospective study was carried out on sera from 30 patients. Studies included immunoglobulin quantitation and specific antibody to fungal species. Eleven patients were found to have immunodeficiency (nine with panhypoglobulinemia and two with selective IgM deficiency). Six patients had elevations of serum IgA and four patients had elevations of serum IgE. Six patients had elevated total antibody to Aspergillus or Candida species and six had precipitin bands to one or more fungal antigens. This study indicates that immunodeficiency is prevalent and plays a causative role in some patients with bronchiectasis. Hypersensitivity reactions to Aspergillus, Candida, and other ubiquitous environmental fungi may also play an etiopathogenic role in this disease (bronchiectasis, humoral immunity, immunodeficiency). PMID:3631652

  20. Bacterial colonization and associated factors in patients with bronchiectasis

    PubMed Central

    Borekci, Sermin; Halis, Ayse Nigar; Aygun, Gokhan; Musellim, Benan

    2016-01-01

    OBJECTIVES: To evaluate the bacterial colonization and associated risk factors in patients with bronchiectasis. METHODS: A total of 121 patients followed at the Bronchiectasis Unit, between 1996 and 2013 and diagnosed as having noncystic fibrosis bronchiectasis with high resolution computed tomography or multi-slice computed tomography were included in this retrospective study. The following definition of colonization was used for study purposes: Detection of at least two isolates of an organism separated by at least 3 months in a year. RESULTS: Of these 121 patients, 65 (54%) were female and 56 (46%) were male. Mean age was 50.6 ± 16.1 years. Mean duration of illness was 20.3 ± 15.5 years. 43 (35.5%) cases had colonization. The major pathogens responsible for colonization were Pseudomonas aeruginosa (n = 25; 20.6%) and Haemophilus influenzae (n = 14, 11.5%). The stepwise logistic regression analysis showed a significant association between colonization and a low percentage of forced vital capacity (FVC%) and the presence of cystic bronchiectasis (P < 0.05). CONCLUSION: The following factors have been found to be associated with colonization in patients with bronchiectasis: Low FVC% and the presence of cystic bronchiectasis. PMID:26933458

  1. Pediatric bronchiectasis: No longer an orphan disease.

    PubMed

    Goyal, Vikas; Grimwood, Keith; Marchant, Julie; Masters, I Brent; Chang, Anne B

    2016-05-01

    Bronchiectasis is described classically as a chronic pulmonary disorder characterized by a persistent productive cough and irreversible dilatation of one or more bronchi. However, in children unable to expectorate, cough may instead be wet and intermittent and bronchial dilatation reversible in the early stages. Although still considered an orphan disease, it is being recognized increasingly as causing significant morbidity and mortality in children and adults in both affluent and developing countries. While bronchiectasis has multiple etiologies, the final common pathway involves a complex interplay between the host, respiratory pathogens and environmental factors. These interactions lead to a vicious cycle of repeated infections, airway inflammation and tissue remodelling resulting in impaired airway clearance, destruction of structural elements within the bronchial wall causing them to become dilated and small airway obstruction. In this review, the current knowledge of the epidemiology, pathobiology, clinical features, and management of bronchiectasis in children are summarized. Recent evidence has emerged to improve our understanding of this heterogeneous disease including the role of viruses, and how antibiotics, novel drugs, antiviral agents, and vaccines might be used. Importantly, the management is no longer dependent upon extrapolating from the cystic fibrosis experience. Nevertheless, substantial information gaps remain in determining the underlying disease mechanisms that initiate and sustain the pathophysiological pathways leading to bronchiectasis. National and international collaborations, standardizing definitions of clinical and research end points, and exploring novel primary prevention strategies are needed if further progress is to be made in understanding, treating and even preventing this often life-limiting disease. Pediatr Pulmonol. 2016;51:450-469. © 2016 Wiley Periodicals, Inc. PMID:26840008

  2. Bronchiectasis: a bacteriological profile

    PubMed Central

    Bopaka, Régis Gothard; El Khattabi, Wiam; Janah, Hind; Jabri, Hasna; Afif, Hicham

    2015-01-01

    The occurrence of bronchiectasis can involve a combination of many environmental factors, including infection. The aim of our work is to determine the bacteriological profile of bronchiectasis. This is a retrospective study of 100 patients hospitalized in between January 2010 and July 2013. The average age was 48 years with a 58% female predominance. Symptomatology was by a bronchial syndrome in 90% of cases. Bacteriological examination was able to isolate the microbe in 35% of cases. In our study it was through the examination of sputum cytology in 27% of cases, through the examination of liquid bronchial aspiration in 5% of cases, and through direct examination of sputum in search of Mycobacterium tuberculosis in 3% of cases. Microbes isolated were: Streptococcus pneumonia in 11 cases; Pseudomonas aeruginosa in 10 cases, Klebsiella pneumonia and Mycobacterium tuberculosis in 3 cases each; Moraxella catarrhalis, Haemophilus influenzae, Escherichia coli, Citrobacter spp, Serratia marcescens, Mycoplasma pneumoniae, Acinetobacter baumannii and Staphylococcus aureus in one case each. Through this work, the authors highlight that Streptococcus pneumoniae and Pseudomonas aeruginosa are the most commonly- identified microbes in their patients. It is necessary to have a full bacterial examination and to repeat it regularly over the course of the bronchiectasis. PMID:27047618

  3. Bronchiectasis following pulmonary ammonia burn

    SciTech Connect

    Hoeffler, H.B.; Schweppe, H.I.; Greenberg, S.D.

    1982-12-01

    Long-term follow-up of the pulmonary lesions of severe exposure to ammonia in humans has seldom been documented, and development of bronchiectasis continues to be of concern. We studied a previously healthy 30-year-old woman whose lungs at time of necropsy, three years after massive exposure to ammonia fumes, had extensive cylindrical and saccular bronchiectasis. We concluded that massive exposure to ammonia can lead to bronchiectasis. It is not known, however, whether the bronchiectasis resulted from chemical injury by ammonia or from a superimposed bacterial bronchitis.

  4. Impact of Different Etiologies of Bronchiectasis on the Pulmonary Function Tests

    PubMed Central

    Lopes, Agnaldo José; Camilo, Gustavo Bittencourt; de Menezes, Sara Lucia Silveira; Guimarães, Fernando Silva

    2015-01-01

    Background Bronchiectasis develops along the natural course of several respiratory and systemic conditions and induces significant changes in the morphofunctional structure of airways. Our objective was to assess the impact of various causes of bronchiectasis on clinical data, pulmonary function tests, and high-resolution computed tomography (HRCT). Methods The present report was a cross-sectional study that was conducted with 112 consecutive patients with bronchiectasis, who were allocated to five groups, as follows: sequelae of tuberculosis, history of non-tuberculosis infection, cystic fibrosis (CF), primary ciliary dyskinesia (PCD), and rheumatoid arthritis. All of the participants underwent spirometry, whole-body plethysmography, measurement of the diffusing capacity for carbon monoxide (DLco), and HRCT. Results The highest HRCT score was exhibited in patients with CF (6.03±1.03). The values of forced expiratory volume in 1 second (FEV1) (52.2±17.7%) and DLco (74.1±15.2%) were lower in patients with sequelae of tuberculosis. The increase in the residual volume was more accentuated in the patients with CF (193.5 ± 39.5%) and PCD (189 ± 36.4%). By the multivariate analysis, the cause of FEV1 and bronchiectasis, HRCT score, and degree of dyspnea behaved as independent predictors of DLco. Conclusion In individuals with bronchiectasis, the pulmonary function abnormalities are associated with the etiology of the underlying disease. PMID:25380609

  5. Measurement of intracellular mediators in enterocytes isolated from jejunal biopsy specimens of control and cystic fibrosis patients.

    PubMed Central

    Hitchin, B W; Dobson, P R; Brown, B L; Hardcastle, J; Hardcastle, P T; Taylor, C J

    1991-01-01

    A method that maximises the yield of viable enterocytes has been developed for the isolation of enterocytes from human jejunal biopsy specimens. These enterocytes have been used to study the values of intracellular free calcium and the rises in adenosine 3'5'-cyclic monophosphate (cAMP) induced by secretagogues in normal and cystic fibrosis cells. Basal intracellular free calcium of cystic fibrosis enterocytes, measured fluorimetrically with fura-2, was within the range of the basal intracellular free calcium of non-cystic fibrosis enterocytes (cystic fibrosis 263 nmol/l; non-cystic fibrosis 287 nmol/l). Changes in intracellular free calcium were observed after exposure to ionomycin: a 100 nmol/l solution induced a 2.5 fold increase in intracellular free calcium in the cystic fibrosis enterocytes and a 2.2 fold increase in the intracellular free calcium concentration of the non-cystic fibrosis enterocytes. Basal cAMP values were not significantly different between cystic fibrosis and non-cystic fibrosis enterocytes (cystic fibrosis 575 fmol/100,000 cells; non-cystic fibrosis 716 fmol/100,000 cells, p greater than 0.05) and the enterocyte cAMP value increased in response to stimulation with prostaglandin E2 (7 mumol/l) (cystic fibrosis 2.2 fold increase over basal, p less than 0.05; non-cystic fibrosis 1.9 fold stimulation over basal, p less than 0.05) and vasoactive intestinal polypeptide (100 nmol/l) (cystic fibrosis 7.1 fold increase over basal, p less than 0.05; non-cystic fibrosis 5.8 fold increase over basal, p less than 0.05). There was no significant difference in the magnitude of the response between cystic fibrosis and non-cystic fibrosis enterocytes (p greater than 0.05). These results indicate that the cystic fibrosis defect in the small intestine, as in other affected epithelia, seems to be distal to the production of second messengers. The small intestine is therefore an appropriate model in which to study the biochemical defect in cystic fibrosis

  6. Humoral Immunity in Bronchiectasis: Finding Good's Syndrome

    PubMed Central

    Pu, C.; Sukhal, S.; Fakhran, S.

    2015-01-01

    We present a case of a 37-year-old man with a past history of a surgically removed thymoma, who presented with recurrent pulmonary infections and bronchiectasis. On further testing, he was found to have low total immunoglobulin levels, a constellation of findings known as Good's syndrome. He responded well to immunoglobulin replacement, in addition to the usual treatments for bronchiectasis. We present this case to emphasize the association of bronchiectasis, low immunoglobulins, and thymomas and the role of immunoglobulin replacement as a treatment option. PMID:26839727

  7. CFTR gene variant IVS8-5T in disseminated bronchiectasis

    SciTech Connect

    Pignatti, P.F.; Bombieri, C.; Benetazzo, M.; Casartelli, A.

    1996-04-01

    Obstructive pulmonary disease includes asthma, chronic obstructive pulmonary disease (COPD; i.e., pulmonary emphysema and chronic bronchitis), bronchiectasis, and cystic fibrosis (CF). It represents a leading cause of death in developed countries. Both familial clustering of non-CF obstructive pulmonary disease and familial aggregation of impaired lung function have been described. This suggests that genetic factors contribute to non-CF obstructive pulmonary disease, even if it is difficult to determine the relative contribution of environmental factors. 11 refs., 1 tab.

  8. Bronchiectasis

    MedlinePlus

    ABOUT US OUR INITIATIVES LUNG HEALTH & DISEASES SUPPORT & COMMUNITY STOP SMOKING GET INVOLVED DONATE - ABOUT US Mission, Impact & History Local Associations Our Leadership Scientific Advisors Financial Statements Media ...

  9. Bronchiectasis

    MedlinePlus

    When listening to the chest with a stethoscope, the doctor may hear small clicking, bubbling, wheezing, rattling, or other sounds, usually in the lower lungs. Tests may include: Aspergillosis precipitin test ( ...

  10. [New and Current Concepts of Therapy in Non-CF Bronchiectasis].

    PubMed

    Allewelt, Markus; de Roux, Andrés

    2016-05-01

    Non-CF (NCF)-bronchiectasis is a syndrome of chronic inflammation leading to dilatation of airways and structural lung damage. Improvements of diagnostic procedures increase its perceived frequency. In Germany, recent data suggest a prevalence of 67/100 000.The outcome of therapeutic interventions is critically related to thorough diagnostic procedures. Genetical or immunological disorders (cystic fibrosis, alpha-1-AT deficiency, immune deficiency syndromes) require treatment options different from idiopathic NCF-bronchiectasis.Therapy is aimed at suppression of chronic inflammation and includes continuous mobilisation of secretions, immunomodulatory strategies and antibiotic therapy, whenever required. Surgical procedures are limited to specific complications (e. g. destroyed lung after airway obstruction, uncontrolled hemorrhage)Macrolides show a variety of immunological properties with favourable results in reduction of symptoms and frequency of exacerbations. Longtime tolerance is good, if individual risk factors are excluded.Antibiotics are given according to resistance patterns in acute exacerbations and in first-time detection of Pseudomonas aeruginosa and MRSA. Inhaled antibiotics for NCF-bronchiectasis will gain importance, depending on future studies. Currently, they are only used in individualized concepts of therapy. PMID:27176062

  11. Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial

    PubMed Central

    2012-01-01

    Background The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. Methods/design We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12–24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4

  12. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    PubMed

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. PMID:25929952

  13. Resolution of extensive severe bronchiectasis in an infant.

    PubMed

    Crowley, Suzanne; Matthews, Iren

    2010-07-01

    Bronchiectasis is, by definition, an irreversible condition. Following recent reports of reversible bronchiectasis in children, it has been suggested that the definition be broadened to include pre-bronchiectasis and transitional reversible states. We describe the case of a young infant who had extensive, severe bronchiectasis of unknown etiology that resolved following prolonged treatment with antibiotics and a tapering course of oral steroids. We suggest that the prolonged treatment may have played a role, perhaps by eradicating infection and thus enabling regeneration of bronchial anatomy. PMID:20575086

  14. miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production.

    PubMed

    Oglesby, Irene K; Vencken, Sebastian F; Agrawal, Raman; Gaughan, Kevin; Molloy, Kevin; Higgins, Gerard; McNally, Paul; McElvaney, Noel G; Mall, Marcus A; Greene, Catherine M

    2015-11-01

    Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis. IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in βENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/- and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis versus non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide, Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured. miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, βENaC-transgenic mice and bronchial epithelial cells chronically stimulated with Pseudomonas-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o(-) tracheal, CFBE41o(-) and/or IB3 bronchial epithelial cells. These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases. PMID:26160865

  15. [Pancreatic cystic fibrosis in Mexicans over 15 years of age].

    PubMed

    Quezada, R; Hernandez, N; Sada, E

    1990-01-01

    A better knowledge of cystic fibrosis of the pancreas has contributed to raise the detection of cystic fibrosis in adults. We describe nine Mexican patients older than 15 years with cystic fibrosis. Respiratory symptoms were predominant and they were secondary to bronchiectasis. All patients were infected by mucoid Pseudomona aeruginosa and in some cases, the finding of this microorganism in sputum suggested the diagnosis. In Mexican population the cystyc fibrosis of the pancreas can be found in adult patients, and it should be considered in the differential diagnosis of chronic respiratory diseases in adults. PMID:2125356

  16. Colloid (mucinous non-cystic) carcinoma of the pancreas: A case report

    PubMed Central

    GAO, YANG; ZHU, YA-YUN; YUAN, ZHOU

    2015-01-01

    Colloid carcinoma (CC) of the pancreas, also known as mucinous non-cystic carcinoma, is a rare histological variant of pancreatic cancer. The present study reports the case of a 65-year-old male with a pancreatic head tumor 4.6×3.1 cm in size. The tumor had not invaded the superior mesenteric or celiac arteries. Laboratory data showed elevated alkaline phosphatase, γ-gluytamyl transpeptidase and cancer antigen 19-9 (CA19-9) levels. The patient underwent a pancreaticoduodenectomy (PD), and the pathology revealed CC extending to the submucosa of the duodenum, with mild atypical hyperplasia of the pancreatic duct. The patient was negative for circulating tumor cells, indicating a good prognosis. The CA19-9 concentration decreased to within the normal range following surgery. The present study reports a rare case of CC of the pancreas presenting with obstructive jaundice, in which a PD procedure was performed. Primary surgical treatment with curative intent is the optimal management and this subtype of pancreatic cancer is associated with a better prognosis compared with pancreatic ductal adenocarcinoma. PMID:26722311

  17. Does airway colonization cause systemic inflammation in bronchiectasis?

    PubMed

    Ergan Arsava, Begüm; Cöplü, Lütfi

    2011-01-01

    Recent evidence suggests the presence of accompanying systemic inflammation in chronic inflammatory airway diseases such as chronic obstructive pulmonary disease and asthma; however little is known regarding the presence of systemic inflammation in bronchiectasis. Although bronchiectasis was initially considered a stationary process, chronic bacterial colonization causes airway inflammation and progressive airway damage. The aim of this study was to determine the level of systemic inflammation in bronchiectasis patients and identify its relationship with colonization. White blood cell (WBC) count, erythrocyte sedimentation rate, serum C-reactive protein (CRP), plasma fibrinogen, interleukin-8, tumor necrosis factor-α and leptin levels were determined in clinically stable bronchiectasis patients (n= 50), and age- and sex-matched controls. Bronchiectasis patients were also analyzed according to colonization in sputum samples. There was no significant difference between bronchiectasis and control groups with respect to inflammatory markers but median (interquartile range-IQR) WBC count, CRP and fibrinogen levels were significantly higher in colonized patients (n= 14) when compared to non-colonized patients [8.2 (6.4-9.5) vs. 6.4 (5.8-7.7) x 103/mm3, 0.91 (0.45-1.29) vs. 0.42 (0.30-0.77) mg/dL, 433.5 (390.3-490.3) vs. 392.0 (327.0-416.0) mg/dL, respectively; p< 0.05]. There was no evidence supporting the presence of systemic inflammation in the overall bronchiectasis group when compared to controls. However, elevated WBC count, CRP and fibrinogen levels in patients with colonization suggest the presence of a systemic inflammatory response in clinically stable bronchiectasis patients with colonization. PMID:22233303

  18. Cystic Fibrosis

    MedlinePlus

    ... and Diseases > Lung Disease Lookup > Cystic Fibrosis Cystic Fibrosis Cystic Fibrosis (CF) is an inherited disease that ... quality of life has improved. Learn About Cystic Fibrosis Cystic fibrosis is a genetic (inherited) condition that ...

  19. Diagnosis of Adult Patients with Cystic Fibrosis.

    PubMed

    Nick, Jerry A; Nichols, David P

    2016-03-01

    The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. PMID:26857767

  20. Pulmonary ventilation and gas exchange in bronchiectasis

    PubMed Central

    Pande, J. N.; Jain, B. P.; Gupta, R. G.; Guleria, J. S.

    1971-01-01

    The subdivisions of the lung volume, pulmonary mechanics, and resting steady state pulmonary transfer factor were measured in 31 patients with bronchographically proven bronchiectasis. In seven patients the process of gas exchange was further investigated by fractionating the total alveolar-arterial oxygen tension gradient into diffusion, distribution, and true shunt components. A restrictive type of ventilatory defect with varying degrees of airway obstruction was observed in a majority of the patients; the airway obstruction was partially reversed by a bronchodilator. Dynamic compliance was usually decreased and the pulmonary resistance increased. Pulmonary transfer factor was decreased in proportion to the number of segments involved. Vital capacity, maximum breathing capacity, and dynamic compliance bore a less significant correlation with the extent of disease. The degree of airway obstruction, as judged by pulmonary resistance, was independent of the extent of disease. All the patients were hypoxaemic and some had hypercapnia as well. The alveolar-arterial oxygen tension gradient was widened primarily because of distributional abnormalities and, to some extent, by the presence of true right-to-left shunts. The latter amounted to 13·6% of the total cardiac output. Surgical resection of the affected lobe or segments resulted in a further deterioration of all the parameters of pulmonary function tested. PMID:5144652

  1. Localised pulmonary resection for bronchiectasis in hypogammaglobulinaemic patients.

    PubMed Central

    Cohen, A. J.; Roifman, C.; Brendan, J.; Mullen, M.; Reid, B.; Weisbrod, G.; Downey, G. P.

    1994-01-01

    BACKGROUND--Bronchiectasis and pulmonary infections are common in patients with hypogammaglobulinaemia. Despite intravenous gammaglobulin treatment and appropriate antibiotics, a subgroup of patients remains with persistent localised pulmonary infection in segments where bronchiectasis had developed before appropriate treatment. As such localised pulmonary suppuration (segmental or lobar) may serve as a focus for progression of bronchiectasis, surgical resection of the involved segments may be considered. The outcome of pulmonary resection in four such patients is reported. RESULTS--Surgery was well tolerated except for one postoperative empyema. Information on follow up is available from 3.5 to 5 years. All patients experienced considerable reduction of symptoms including cough, sputum production, antibiotic use, and hospital admissions. CONCLUSIONS--Surgical resection of localised bronchiectatic segments should be considered in patients with hypogammaglobulinaemia with persistent localised suppuration and symptoms refractory to medical treatment. PMID:8016776

  2. Effects of pulmonary rehabilitation in bronchiectasis: A retrospective study.

    PubMed

    Ong, H K; Lee, A L; Hill, C J; Holland, A E; Denehy, L

    2011-01-01

    There is limited information about the benefits of pulmonary rehabilitation (PR) in patients with bronchiectasis. This study aimed to evaluate the effects of an out-patient PR program in patients with a primary diagnosis of bronchiectasis and to compare them with a matched COPD group who completed the same PR program. A retrospective review was conducted of patients with bronchiectasis or COPD who completed 6 to 8 weeks of PR at two tertiary institutions. The outcome measures were the 6-minute walk distance (6MWD) and Chronic Respiratory Disease Questionnaire (CRQ). Ninety-five patients with bronchiectasis completed the PR (48 male; FEV(1) 63 [24] % predicted; age 67 [10] years). Significant improvements in 6MWD (mean change 53.4 m, 95% CI 45.0 to 61.7) and CRQ total score (mean change 14.0 units, 95% CI 11.3 to 16.7) were observed immediately following PR. In patients with complete follow-up (n = 37), these improvements remained significantly higher than baseline at 12 months (20.5 m, 95% CI 1.4 to 39.5 for 6MWD; 12.1 points, 95% CI 5.7 to 18.4 for CRQ total score). The time trend and changes in the 6MWD and CRQ scores were not significantly different between the bronchiectasis and the COPD groups (all p > 0.05). This study supports the inclusion of patients with bronchiectasis in existing PR programs. Further prospective RCTs are warranted to substantiate these findings. PMID:21339371

  3. Co-existence of Bronchiectasis and Chronic Obstructive Pulmonary Disease.

    PubMed

    Goel, Nitin; Gupta, Pawan; Singh, Abhijeet; Prasad, Rajendra

    2015-01-01

    We present the case of a 56-year-old male who presented with cough and breathlessness. Chest radiograph (postero-anterior view) showed bulla and signs of hyperinflation in the right upper zone with cystic shadows in the left lower zone. Spirometry showed severe irreversible airflow obstruction with restriction and decreased diffusion capacity for carbon monoxide. On high resolution computed tomography (HRCT), right upper lobe bulla with emphysematous changes and left lower lobe cystic bronchiectasis were seen. Considering its rarity of occurrence and paucity of data in literature regarding co-existence of bronchiectasis with emphysema, this case is being reported. PMID:26591975

  4. Bronchiectasis and sino-nasal disease: a review.

    PubMed

    Philpott, C M; McKiernan, D C

    2008-01-01

    The 'one airway' model for upper and lower respiratory tract disease is a concept gaining increasing momentum in both respiratory medicine and otorhinolaryngology. The specific common aetiology and pathophysiology of concomitant bronchiectasis and sino-nasal disease, such as chronic rhinosinusitis, are discussed here, as well as the clinical manifestations, along with a review of all the relevant literature in the field. PMID:17592654

  5. Chloride and potassium channels in cystic fibrosis airway epithelia

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.; Liedtke, Carole M.

    1986-07-01

    Cystic fibrosis, the most common lethal genetic disease in Caucasians, is characterized by a decreased permeability in sweat gland duct and airway epithelia. In sweat duct epithelium, a decreased Cl- permeability accounts for the abnormally increased salt content of sweat1. In airway epithelia a decreased Cl- permeability, and possibly increased sodium absorption, may account for the abnormal respiratory tract fluid2,3. The Cl- impermeability has been localized to the apical membrane of cystic fibrosis airway epithelial cells4. The finding that hormonally regulated Cl- channels make the apical membrane Cl- permeable in normal airway epithelial cells5 suggested abnormal Cl- channel function in cystic fibrosis. Here we report that excised, cell-free patches of membrane from cystic fibrosis epithelial cells contain Cl- channels that have the same conductive properties as Cl- channels from normal cells. However, Cl- channels from cystic fibrosis cells did not open when they were attached to the cell. These findings suggest defective regulation of Cl- channels in cystic fibrosis epithelia; to begin to address this issue, we performed two studies. First, we found that isoprenaline, which stimulates Cl- secretion, increases cellular levels of cyclic AMP in a similar manner in cystic fibrosis and non-cystic fibrosis epithelial cells. Second, we show that adrenergic agonists open calcium-activated potassium channels, indirectly suggesting that calcium-dependent stimulus-response coupling is intact in cystic fibrosis. These data suggest defective regulation of Cl- channels at a site distal to cAMP accumulation.

  6. Characterization of Lung Function Impairment in Adults with Bronchiectasis

    PubMed Central

    Lin, Zhi-ya; Tang, Yan; Li, Hui-min; Lin, Zhi-min; Zheng, Jin-ping; Chen, Rong-chang; Zhong, Nan-shan

    2014-01-01

    Background Characteristics of lung function impairment in bronchiectasis is not fully understood. Objectives To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy). Methods We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence. Results In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV1 being 50%pred or less; and the only variable associated with reduced DLCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV1 during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV1 and DLCO reduction at baseline. Conclusion Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV1. Changes of other spirometric parameters were less significant during exacerbations. Trial Registration ClinicalTrials.gov NCT01761214 PMID:25405614

  7. Pulmonary fibrosis and emphysema: Is the emphysema type associated with the pattern of fibrosis?

    PubMed Central

    Oikonomou, Anastasia; Mintzopoulou, Paraskevi; Tzouvelekis, Argyris; Zezos, Petros; Zacharis, George; Koutsopoulos, Anastasios; Bouros, Demosthenes; Prassopoulos, Panos

    2015-01-01

    AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography (HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema (CPFE). METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on - HRCT - were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular (CLE), paraseptal (PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia (UIP), probable UIP and nonspecific interstitial pneumonia (NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis (Coarseness), extent of emphysema (emphysema), extent of interstitial lung disease (TotExtILD), extent of reticular pattern not otherwise specified (RetNOS), extent of ground glass opacity with traction bronchiectasis (extGGOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity (DLCO) and systolic pulmonary arterial pressure were compared among the groups. RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema (P < 0.001) and a lower extent of interstitial lung disease (P < 0.002), reticular pattern not otherwise specified (P < 0.023), extent of ground glass opacity with traction bronchiectasis (P < 0.002), extent of honeycombing (P < 0.001) and coarseness of fibrosis (P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema (P < 0.05), total lung capacity (P < 0.01) and diffusion capacity (DLCO) (P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise

  8. Identification of a novel SERPINA-1 mutation causing alpha-1 antitrypsin deficiency in a patient with severe bronchiectasis and pulmonary embolism.

    PubMed

    Milger, Katrin; Holdt, Lesca Miriam; Teupser, Daniel; Huber, Rudolf Maria; Behr, Jürgen; Kneidinger, Nikolaus

    2015-01-01

    Deficiency in the serine protease inhibitor, alpha-1 antitrypsin (AAT), is known to cause emphysema and liver disease. Other manifestations, including airway disease or skin disorders, have also been described. A 44-year-old woman presented to our emergency department with dyspnea and respiratory insufficiency. She had never smoked, and had been diagnosed with COPD 9 years earlier. Three months previously, she had suffered a pulmonary embolism. Chest computed tomography scan revealed severe cystic bronchiectasis with destruction of the lung parenchyma. The sweat test was normal and there was no evidence of the cystic fibrosis transmembrane conductance regulator (CFTR) mutation. Capillary zone electrophoresis showed a decrease of alpha-1 globin band and AAT levels were below the quantification limit (<25 mg/dL). No S or Z mutation was identified, but sequencing analysis found a homozygous cytosine and adenine (CA) insertion in exon 2 of the SERPINA-1 gene, probably leading to a dysfunctional protein (PI Null/Null). This mutation has not been previously identified. The atypical presentation of the patient, with severe cystic bronchiectasis, highlights AAT deficiency as a differential diagnosis in bronchiectasis. Further, awareness should be raised regarding a possible increased risk of thromboembolism associated with AAT deficiency. PMID:26005342

  9. Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data

  10. Pregnancy outcomes in cystic fibrosis: a 10-year experience from a UK centre

    PubMed Central

    Priestley, L; Bennett, L; Mackillop, L; Chapman, SJ

    2015-01-01

    Background Cystic fibrosis manifests as a multisystem disease, despite this female fertility is relatively preserved with levels approaching that of the non-cystic fibrosis population. We reviewed pregnancies in cystic fibrosis patients over a 10-year period from a UK adult cystic fibrosis centre by considering maternal and fetal outcomes. Methods We conducted a retrospective case-note review of pregnancies during 2003–2013 using respiratory and obstetric records. Results We observed moderate falls in lung function immediately after delivery, which persisted at 12 months postpartum. We found that a decline in lung function at delivery was a marker for further decline in function during the subsequent postpartum period. We found baseline lung function was predictive of gestational age at delivery. We observed a high incidence of haemoptysis. Conclusion Consistent with current guidance we found pregnancy is feasible and well tolerated in the majority of patients with cystic fibrosis. There was a high incidence of haemoptysis, which warrants further study.

  11. Bronchiectasis: Current Concepts in Pathogenesis, Immunology, and Microbiology.

    PubMed

    Boyton, Rosemary J; Altmann, Daniel M

    2016-05-23

    Bronchiectasis is a disorder of persistent lung inflammation and recurrent infection, defined by a common pathological end point: irreversible bronchial dilatation arrived at through diverse etiologies. This suggests an interplay between immunogenetic susceptibility, immune dysregulation, bacterial infection, and lung damage. The damaged epithelium impairs mucus removal and facilitates bacterial infection with increased cough, sputum production, and airflow obstruction. Lung infection is caused by respiratory bacterial and fungal pathogens, including Pseudomonas aeruginosa, Haemophilus, Aspergillus fumigatus, and nontuberculous mycobacteria. Recent studies have highlighted the relationship between the lung microbiota and microbial-pathogen niches. Disease may result from environments favoring interleukin-17-driven neutrophilia. Bronchiectasis may present in autoimmune disease, as well as conditions of immune dysregulation, such as combined variable immune deficiency, transporter associated with antigen processing-deficiency syndrome, and hyperimmunoglobulin E syndrome. Differences in prevalence across geography and ethnicity implicate an etiological mix of genetics and environment underpinning susceptibility. PMID:26980162

  12. Mycobacteria as a cause of infective exacerbation in bronchiectasis.

    PubMed Central

    Chan, C. H.; Ho, A. K.; Chan, R. C.; Cheung, H.; Cheng, A. F.

    1992-01-01

    In 91 patients with bronchiectasis seen over 6 years, a positive mycobacterial culture was obtained in 12 cases (13%). The organisms isolated were Mycobacterium tuberculosis in nine cases, Mycobacterium avium in two cases and Mycobacterium tuberculosis and chelonei were obtained on separate occasions in one case. Computed tomography and/or bronchography showed that the bronchiectatic changes commonly involved the lower lobes and to a lesser extent, the middle and lingula lobes. In none of these 12 cases was tuberculosis strongly suspected on clinical or radiological grounds. We conclude that mycobacterial infections are common in patients with bronchiectasis and sputum should be cultured for mycobacteria periodically in these patients. In doubtful cases, bronchoscopy may be helpful to obtain a positive mycobacterial culture. PMID:1494510

  13. Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration.

    PubMed

    Aliberti, Stefano; Masefield, Sarah; Polverino, Eva; De Soyza, Anthony; Loebinger, Michael R; Menendez, Rosario; Ringshausen, Felix C; Vendrell, Montserrat; Powell, Pippa; Chalmers, James D

    2016-09-01

    Bronchiectasis is a disease of renewed interest in light of an increase in prevalence and increasing burden on international healthcare systems. There are no licensed therapies, and large gaps in knowledge in terms of epidemiology, pathophysiology and therapy. The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) is a European Respiratory Society (ERS) Clinical Research Collaboration, funded by ERS to promote high-quality research in bronchiectasis. The objective of this consensus statement was to define research priorities in bronchiectasis. From 2014 to 2015, EMBARC used a modified Delphi process among European bronchiectasis experts to reach a consensus on 55 key research priorities in this field. During the same period, the European Lung Foundation collected 711 questionnaires from adult patients with bronchiectasis and their carers from 22 European countries reporting important research priorities from their perspective. This consensus statement reports recommendations for bronchiectasis research after integrating both physicians and patients priorities, as well as those uniquely identified by the two groups. Priorities identified in this consensus statement provide the clearest possible roadmap towards improving our understanding of the disease and the quality of care for patients with bronchiectasis. PMID:27288031

  14. Inflammation and its genesis in cystic fibrosis.

    PubMed

    Nichols, David P; Chmiel, James F

    2015-10-01

    The host inflammatory response in cystic fibrosis (CF) lung disease has long been recognized as a central pathological feature and an important therapeutic target. Indeed, many believe that bronchiectasis results largely from the oxidative and proteolytic damage comprised within an exuberant airway inflammatory response that is dominated by neutrophils. In this review, we address the longstanding argument of whether or not the inflammatory response is directly attributable to impairment of the cystic fibrosis transmembrane conductance regulator or only secondary to airway obstruction and chronic bacterial infection and challenge the importance of this distinction in the context of therapy. We also review the centrality of neutrophils in CF lung pathophysiology and highlight more recent data that suggest the importance of other cell types and signaling beyond NF-κB activation. We discuss how protease and redox imbalance are critical factors in CF airway inflammation and end by reviewing some of the more promising therapeutic approaches now under development. PMID:26335954

  15. Cystic fibrosis

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000107.htm Cystic fibrosis To use the sharing features on this page, please enable JavaScript. Cystic fibrosis is a disease that causes thick, sticky mucus ...

  16. Pulmonary Fibrosis

    MedlinePlus

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue ... may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  17. Airway disease: similarities and differences between asthma, COPD and bronchiectasis

    PubMed Central

    Athanazio, Rodrigo

    2012-01-01

    Airway diseases are highly prevalent worldwide; however, the prevalence of these diseases is underestimated. Although these diseases present several common characteristics, they have different clinical outcomes. The differentiation between asthma, chronic obstructive pulmonary disease and bronchiectasis in the early stage of disease is extremely important for the adoption of appropriate therapeutic measures. However, because of the high prevalence of these diseases and the common pathophysiological pathways, some patients with different diseases may present with similar symptoms. The objective of this review is to highlight the similarities and differences between these diseases in terms of the risk factors, pathophysiology, symptoms, diagnosis and treatment. PMID:23184213

  18. A retrospective study of the relationship between tracheal collapse and bronchiectasis in dogs.

    PubMed

    Marolf, Angela; Blaik, Margaret; Specht, Andrew

    2007-01-01

    Tracheal collapse is common in middle age toy and miniature breed dogs. Cartilaginous defects have been identified histologically and are considered a form of chondromalacia. In addition to tracheal cartilaginous changes, concurrent lower airway histologic changes indicative of inflammation have been noted in dogs with tracheal collapse and these changes may lead t o concurrent bronchiectasis. The purpose of this study was to investigate the prevalence of bronchiectasis in dogs with a previous radiographic diagnosis of tracheal collapse. The thoracic radiographs of 60 dogs with tracheal collapse were evaluated for evidence of concurrent bronchiectasis. Eighteen of 60 (30%) dogs had evidence of bronchiectasis, and all were cylindrical in morphology. The signalment of affected dogs was similar to that previously reported. The occurrence of bronchiectasis in this group of dogs with tracheal collapse (18 dogs) was six times higher (P < 0.05) than the expected prevalence within a random sample population (three dogs). The results of this study provide evidence of a link between tracheal collapse and bronchiectasis. A finding of bronchiectasis with tracheal collapse should encourage further evaluation for chronic lower airway disease in these patients. PMID:17508504

  19. Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis

    PubMed Central

    Guan, Wei-jie; Yuan, Jing-jing; Gao, Yong-hua; Li, Hui-min; Zheng, Jin-ping; Chen, Rong-chang; Zhong, Nan-shan

    2016-01-01

    Little is known about the comparative diagnostic value of lung clearance index (LCI) and maximal mid-expiratory flow (MMEF) in bronchiectasis. We compared the diagnostic performance, correlation and concordance with clinical variables, and changes of LCI and MMEF% predicted during bronchiectasis exacerbations (BEs). Patients with stable bronchiectasis underwent history inquiry, chest high-resolution computed tomography (HRCT), multiple-breath nitrogen wash-out test, spirometry and sputum culture. Patients who experienced BEs underwent these measurements during onset of BEs and 1 week following antibiotics therapy. Sensitivity analyses were performed in mild, moderate and severe bronchiectasis. We recruited 110 bronchiectasis patients between March 2014 and September 2015. LCI demonstrated similar diagnostic value with MMEF% predicted in discriminating moderate-to-severe from mild bronchiectasis. LCI negatively correlated with MMEF% predicted. Both parameters had similar concordance in reflecting clinical characteristics of bronchiectasis and correlated significantly with forced expiratory flow in one second, age, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, ventilation heterogeneity and bilateral bronchiectasis. In exacerbation cohort (n = 22), changes in LCI and MMEF% predicted were equally minimal during BEs and following antibiotics therapy. In sensitivity analyses, both parameters had similar diagnostic value and correlation with clinical variables. MMEF% predicted is a surrogate of LCI for assessing bronchiectasis severity. PMID:27339787

  20. Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis.

    PubMed

    Guan, Wei-Jie; Yuan, Jing-Jing; Gao, Yong-Hua; Li, Hui-Min; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

    2016-01-01

    Little is known about the comparative diagnostic value of lung clearance index (LCI) and maximal mid-expiratory flow (MMEF) in bronchiectasis. We compared the diagnostic performance, correlation and concordance with clinical variables, and changes of LCI and MMEF% predicted during bronchiectasis exacerbations (BEs). Patients with stable bronchiectasis underwent history inquiry, chest high-resolution computed tomography (HRCT), multiple-breath nitrogen wash-out test, spirometry and sputum culture. Patients who experienced BEs underwent these measurements during onset of BEs and 1 week following antibiotics therapy. Sensitivity analyses were performed in mild, moderate and severe bronchiectasis. We recruited 110 bronchiectasis patients between March 2014 and September 2015. LCI demonstrated similar diagnostic value with MMEF% predicted in discriminating moderate-to-severe from mild bronchiectasis. LCI negatively correlated with MMEF% predicted. Both parameters had similar concordance in reflecting clinical characteristics of bronchiectasis and correlated significantly with forced expiratory flow in one second, age, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, ventilation heterogeneity and bilateral bronchiectasis. In exacerbation cohort (n = 22), changes in LCI and MMEF% predicted were equally minimal during BEs and following antibiotics therapy. In sensitivity analyses, both parameters had similar diagnostic value and correlation with clinical variables. MMEF% predicted is a surrogate of LCI for assessing bronchiectasis severity. PMID:27339787

  1. Severe tracheobronchial stenosis and bronchiectasis complicating ulcerative colitis.

    PubMed

    Suzuki, Toshio; Tsushima, Kenji; Sakairi, Yuichi; Yoshida, Shigetoshi; Yoshino, Ichiro; Tatsumi, Koichiro

    2014-03-01

    A 37-year-old woman with a 20-year history of ulcerative colitis (UC) was admitted with complaints of cough and increasing sputum production. Chest computed tomography showed severe stenosis of the left main bronchus and bronchiectasis of the left lower lobe. Biopsy specimens from the area of bronchial stenosis showed chronic inflammation with lymphocyte infiltration, and we diagnosed respiratory involvement of UC. The bronchial stenosis was successfully treated with yttrium aluminum garnet (YAG) laser. UC is a systemic illness with occasional extraintestinal manifestations, but upper airway involvement is rare, and to our knowledge, this is the first published report of UC complicated with bronchopulmonary lesions with successful YAG laser treatment of the main bronchial stenosis. PMID:25473563

  2. The Role of Computed Tomography in Monitoring Patients with Cystic Fibrosis.

    PubMed

    Rybacka, Anna; Karmelita-Katulska, Katarzyna

    2016-01-01

    Cystic fibrosis is the most common lethal autosomal recessive disorder in the Caucasian population. Although the survival rate in patients constantly improves, lung damage is still the major cause of morbidity and mortality in patients with cystic fibrosis. In clinical practice, evaluation of patients' pulmonary state is made by combination of monitoring of lung function and more directly by assessing the lung structure in imaging studies. Studies showed that computed tomography findings are more sensitive as compared to the pulmonary function tests. Computed tomography can identify a wide range of morphological abnormalities in patients with cystic fibrosis, such as bronchiectasis (which is progressive, irreversible and probably the most relevant structural change in cystic fibrosis) peribronchial thickening, mucous plugging and many other disorders that occur in the course of the disease. Computed tomography has a crucial role in the assessment of pulmonary damage over time, detecting complications and monitoring treatment effects in patients with cystic fibrosis. PMID:27103945

  3. The Role of Computed Tomography in Monitoring Patients with Cystic Fibrosis

    PubMed Central

    Rybacka, Anna; Karmelita-Katulska, Katarzyna

    2016-01-01

    Summary Cystic fibrosis is the most common lethal autosomal recessive disorder in the Caucasian population. Although the survival rate in patients constantly improves, lung damage is still the major cause of morbidity and mortality in patients with cystic fibrosis. In clinical practice, evaluation of patients’ pulmonary state is made by combination of monitoring of lung function and more directly by assessing the lung structure in imaging studies. Studies showed that computed tomography findings are more sensitive as compared to the pulmonary function tests. Computed tomography can identify a wide range of morphological abnormalities in patients with cystic fibrosis, such as bronchiectasis (which is progressive, irreversible and probably the most relevant structural change in cystic fibrosis) peribronchial thickening, mucous plugging and many other disorders that occur in the course of the disease. Computed tomography has a crucial role in the assessment of pulmonary damage over time, detecting complications and monitoring treatment effects in patients with cystic fibrosis. PMID:27103945

  4. Effect of airway Pseudomonas aeruginosa isolation and infection on steady-state bronchiectasis in Guangzhou, China

    PubMed Central

    Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Lin, Zhi-Ya; Tang, Yan; Li, Hui-Min; Li, Zhi-Min; Zheng, Jin-Ping

    2015-01-01

    Background Current status of Pseudomonas aeruginosa (PA) infection in clinically stable bronchiectasis in mainland China remains unclear. Objective To compare the inflammation and lung function impairment in bronchiectasis patients isolated or infected with PA, potentially pathogenic microorganisms (PPMs) and commensals, and to identify factors associated with PA isolation and infection. Methods Patients with steady-state bronchiectasis and healthy subjects were recruited. Peripheral blood and sputum were sampled to determine inflammatory markers and bacterial loads in steady-state bronchiectasis and health. Spirometry and diffusing capacity were also measured. Results We enrolled 144 bronchiectasis patients and 23 healthy subjects. PA isolation and infection accounted for 44 and 39 patients, who demonstrated significant inflammatory responses and markedly impaired spirometry, but not diffusing capacity, compared with healthy subjects and patients isolated with other PPMs and commensals (all P<0.05). Except for heightened sputum inflammatory responses, there were no notable differences in serum inflammation and lung function as with the increased density of PA. Female gender [odds ratio (OR): 3.10 for PA isolation; OR: 3.74 for PA infection], 4 or more exacerbations within 2 years (OR: 3.74 for PA isolation, OR: 2.95 for PA infection) and cystic bronchiectasis (OR: 3.63 for PA isolation, OR: 4.47 for PA infection) were the factors consistently associated with PA isolation and infection. Conclusions PA elicits intense inflammation and lung function impairment in steady-state bronchiectasis. The density of PA does not correlate with most clinical indices. PA infection is associated with females, frequent exacerbations and cystic bronchiectasis. PMID:25973228

  5. Radiologic and Clinical Bronchiectasis Associated with Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Moua, Teng; Zand, Ladan; Hartman, Robert P.; Hartman, Thomas E.; Qin, Dingxin; Peikert, Tobias; Qian, Qi

    2014-01-01

    Background Polycystin 1 and 2, the protein abnormalities associated with autosomal dominant polycystic kidney disease (ADPKD), are also found in airway cilia and smooth muscle cells. There is evidence of increased radiologic bronchiectasis associated with ADPKD, though the clinical and functional implications of this association are unknown. We hypothesized an increased prevalence of both radiologic and clinical bronchiectasis is associated with APDKD as compared to non-ADPKD chronic kidney disease (CKD) controls. Materials and Methods A retrospective case-control study was performed at our institution involving consecutive ADPKD and non-ADPKD chronic kidney disease (CKD) patients seen over a 13 year period with both chest CT and PFT. CTs were independently reviewed by two blinded thoracic radiologists. Manually collected clinical data included symptoms, smoker status, transplant history, and PFT findings. Results Ninety-two ADPKD and 95 non-ADPKD CKD control patients were compared. Increased prevalence of radiologic bronchiectasis, predominantly mild lower lobe disease, was found in ADPKD patients compared to CKD control (19 vs. 9%, P = 0.032, OR 2.49 (CI 1.1–5.8)). After adjustment for covariates, ADPKD was associated with increased risk of radiologic bronchiectasis (OR 2.78 (CI 1.16–7.12)). Symptomatic bronchiectasis occurred in approximately a third of ADPKD patients with radiologic disease. Smoking was associated with increased radiologic bronchiectasis in ADPKD patients (OR 3.59, CI 1.23–12.1). Conclusions Radiological bronchiectasis is increased in patients with ADPKD particularly those with smoking history as compared to non-ADPKD CKD controls. A third of such patients have symptomatic disease. Bronchiectasis should be considered in the differential in ADPKD patients with respiratory symptoms and smoking history. PMID:24747723

  6. Bronchiectasis as a Comorbidity of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Du, Qingxia; Jin, Jianmin; Liu, Xiaofang; Sun, Yongchang

    2016-01-01

    Background Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies. Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression. Methods Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts. A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients. Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. Odds ratios (ORs) were pooled by random effects models. Results Fourteen observational studies were eligible for the study. Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29–3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16–7.82), severe airway obstruction (1.31, 95% CI, 1.09–1.58) and mortality (1.96, 95% CI, 1.04–3.70). Conclusions The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. PMID:26978269

  7. Cystic fibrosis

    MedlinePlus

    ... or three times each week. Swimming, jogging, and cycling are good options. Clearing or bringing up mucus ... cannot be prevented. Screening those with a family history of the disease may detect the cystic fibrosis ...

  8. Disseminated bronchiectasis in an adult with common variable immunodeficiency.

    PubMed

    Zea-Vera, Andrés Felipe; Agudelo-Rojas, Olga Lucia

    2015-01-01

    Primary immunodeficiencies (PID) are traditionally considered childhood diseases; however, adults account for 35% of all patients with PID. Antibody deficiencies, especially Common Variable Immunodeficiency (CVID), which have their peak incidence in adulthood, require a high suspicion index. Even though the estimated frequency of CVID is not high (1:25,000), high rates of under diagnosis and under reporting are very likely. The delay in diagnosis increases the morbidity and mortality; therefore, adult physicians should be able to suspect, identify and initiate management of individuals with PID. Here we report the case of a 37 year-old man presenting to the emergency room with dyspnea, fever and cough; he developed respiratory failure requiring mechanical ventilation. He complained of recurring pneumonia associated with widespread bronchiectasis since he was 18 years old. Serum immunoglobulins quantification showed severe hypogammaglobulinemia (total IgG <140 mg/dL; total IgA, 2.9 mg/dL; and total IgM <5 mg/dL). Treatment with Human Intravenous Immunoglobulin (IVIG) 10% was started, and with antibiotic treatment for severe pneumonia (during 14 days) was also prescribed. His clinical evolution has been favorable after one year follow-up. Common Variable Immunodeficiency (CVID) diagnosis was made. PMID:26019385

  9. Sensory functions of motile cilia and implication for bronchiectasis

    PubMed Central

    Jain, Raksha; Javidan-Nejad, Cylen; Alexander-Brett, Jennifer; Horani, Amjad; Cabellon, Michelle C.; Walter, Michael J.; Brody, Steven L.

    2013-01-01

    Cilia are specialized organelles that extend from the surface of cells into the local environment. Airway epithelial cell cilia are motile to provide mucociliary clearance for host defense. On other cells, solitary cilia are specialized to detect chemical or mechanosensory signals. Sensory proteins in motile cilia have recently been identified that detect shear stress, osmotic force, fluid flow, bitter taste and sex hormones. The relationship of sensory function in human motile cilia to disease is now being revealed. One example is polycystin-1 and polycystin-2. As a complex, these proteins function as a flow sensor in cilia and are mutated in autosomal dominant polycystic kidney disease (ADPKD). The polycystins are also expressed in motile cilia of the airways, potentially operating as sensors in the lung. Computed tomography studies from patients with ADPKD revealed radiographic evidence for bronchiectasis, suggesting that polycystin-1 and -2 are important in lung function. The expression of this complex and sensory channel TRPV4, and bitter taste and sex hormones receptors in motile cilia indicate that the cell is wired to interpret environmental cues to regulate cilia beat frequency and other functions. Defective signaling of sensory proteins may result in a ciliopathy that includes lung disease. PMID:22202111

  10. Idiopathic Pulmonary Fibrosis

    MedlinePlus

    ... the NHLBI on Twitter. What Is Idiopathic Pulmonary Fibrosis? Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a ... time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, your lungs can' ...

  11. Cystic fibrosis - resources

    MedlinePlus

    Resources - cystic fibrosis ... The following organizations are good resources for information on cystic fibrosis : Cystic Fibrosis Foundation -- www.cff.org March of Dimes -- www.marchofdimes.org/baby/cystic-fibrosis-and- ...

  12. Capsaicin Cough Sensitivity and the Association with Clinical Parameters in Bronchiectasis

    PubMed Central

    Lin, Zhi-ya; Tang, Yan; Li, Hui-min; Lin, Zhi-min; Zheng, Jin-ping; Chen, Rong-chang; Zhong, Nan-shan

    2014-01-01

    Background Cough hypersensitivity has been common among respiratory diseases. Objective To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis. Methods We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5). Results Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P<0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35–7.83, P<0.01), HRCT total score between 7–12 (OR: 2.57, 95%CI: 1.07–6.173, P = 0.04), BSI between 5–8 (OR: 4.05, 95%CI: 1.48–11.06, P<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48–12.93, P<0.01). Conclusion Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials. PMID:25409316

  13. Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications

    PubMed Central

    Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Li, Hui-Min; Yuan, Jing-Jing; Zheng, Jin-Ping

    2016-01-01

    Background Bronchial dilation testing is an important tool to assess airway reversibility in adults with bronchiectasis. This study aims to investigate the association of bronchodilator response (BDR) and clinical parameters in bronchiectasis, and the utility of BDR to indicate lung function decline and risks of bronchiectasis exacerbations (BEs). Methods We recruited 129 patients with clinically stable bronchiectasis. Baseline measurements included assessment of sputum inflammation and matrix metalloproteinase-8 and -9, sputum bacterial culture, spirometry, bronchial dilation test (for baseline FEV1 less than 80% predicted only) and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed-up for 1 year to determine the incidence of BEs and lung function trajectories. Significant BDR was defined as FEV1 improvement from pre-dose value by at least 200 mL and 12%. Clinical trial registry No.: NCT01761214; URL: www.clinicaltrials.gov. Results BDR was negatively correlated with baseline FEV1 percentage predicted, but not blood or sputum eosinophil count. Significant BDR was not associated with greater proportion of never-smokers, poorer past history, greater HRCT scores, poorer diffusing capacity or increased sputum matrix metalloproteinases (all P>0.05). There was a trend towards higher bronchiectasis severity index (BSI) and greater proportion of patients with Pseudomonas aeruginosa isolation or infection. Significant BDR at baseline was linked to poorer spirometry, but not more rapid lung function decline, throughout follow-up. Patients with significant BDR demonstrated non-significantly lower risks of experiencing the first BEs than those without (P=0.09 for log-rank test). Conclusions Significant BDR is associated with poorer lung function compared with non-significant BDR. Whether BDR predicts future risks of BEs needs to be tested in a larger cohort. PMID:26904207

  14. Extrapulmonary features of bronchiectasis: muscle function, exercise capacity, fatigue, and health status

    PubMed Central

    2012-01-01

    Background There are limited number of studies investigating extrapulmonary manifestations of bronchiectasis. The purpose of this study was to compare peripheral muscle function, exercise capacity, fatigue, and health status between patients with bronchiectasis and healthy subjects in order to provide documented differences in these characteristics for individuals with and without bronchiectasis. Methods Twenty patients with bronchiectasis (43.5 ± 14.1 years) and 20 healthy subjects (43.0 ± 10.9 years) participated in the study. Pulmonary function, respiratory muscle strength (maximal expiratory pressure – MIP - and maximal expiratory pressure - MEP), and dyspnea perception using the Modified Medical Research Council Dyspnea Scale (MMRC) were determined. A six-minute walk test (6MWT) was performed. Quadriceps muscle, shoulder abductor, and hand grip strength (QMS, SAS, and HGS, respectively) using a hand held dynamometer and peripheral muscle endurance by a squat test were measured. Fatigue perception and health status were determined using the Fatigue Severity Scale (FSS) and the Leicester Cough Questionnaire (LCQ), respectively. Results Number of squats, 6MWT distance, and LCQ scores as well as lung function testing values and respiratory muscle strength were significantly lower and MMRC and FSS scores were significantly higher in patients with bronchiectasis than those of healthy subjects (p < 0.05). In bronchiectasis patients, QMS was significantly associated with HGS, MIP and MEP (p < 0.05). The 6MWT distance was significantly correlated to LCQ psychological score (p < 0.05). The FSS score was significantly associated with LCQ physical and total and MMRC scores (p < 0.05). The LCQ psychological score was significantly associated with MEP and 6MWT distance (p < 0.05). Conclusions Peripheral muscle endurance, exercise capacity, fatigue and health status were adversely affected by the presence of bronchiectasis. Fatigue was associated

  15. Cystic Fibrosis

    MedlinePlus

    Cystic fibrosis (CF) is an inherited disease of the mucus and sweat glands. It affects mostly your lungs, pancreas, liver, intestines, sinuses, and sex organs. CF causes your mucus to be thick and sticky. The mucus clogs the lungs, causing breathing problems ...

  16. The reproducibility and responsiveness of the lung clearance index in bronchiectasis.

    PubMed

    Grillo, Lizzie; Irving, Samantha; Hansell, David M; Nair, Arjun; Annan, Bertrand; Ward, Simon; Bilton, Diana; Main, Eleanor; Davies, Jane; Bush, Andrew; Wilson, Robert; Loebinger, Michael R

    2015-12-01

    Lung clearance index (LCI) is a potential clinical outcome marker in bronchiectasis. Its responsiveness to therapeutic intervention has not been determined. This study evaluates its responsiveness to a session of physiotherapy and intravenous antibiotic treatment of an exacerbation.32 stable and 32 exacerbating bronchiectasis patients and 26 healthy controls were recruited. Patients had LCI and lung function performed before and after physiotherapy on two separate occasions in the stable patients and at the beginning and end of an intravenous antibiotic course in the exacerbating patients.LCI was reproducible between visits in 25 stable patients, with an intraclass correlation of 0.978 (0.948, 0.991; p<0.001). There was no significant difference in LCI (mean±sd) between stable 11.91±3.39 and exacerbating patients 12.76±3.47, but LCI was significantly higher in both bronchiectasis groups compared with healthy controls (7.36±0.99) (p<0.001). Forced expiratory volume in 1 s improved after physiotherapy, as did alveolar volume after intravenous antibiotics, but LCI did not change significantly.LCI is reproducible in stable bronchiectasis but unlike conventional lung function tests, is unresponsive to two short-term interventions and hence is unlikely to be a useful clinical tool for short-term acute assessment in these patients. Further evaluation is required to establish its role in milder disease and in the evaluation of long-term interventions. PMID:26341989

  17. Tuberculosis, bronchiectasis, and infertility: what ailed George Orwell?

    PubMed

    Ross, John J

    2005-12-01

    In the last and most productive years of his life, George Orwell struggled with pulmonary tuberculosis, dying at the dawn of the era of chemotherapy. His case history illustrates clinical aspects of tuberculosis with contemporary relevance: the role of poverty in its spread, the limited efficacy of monotherapy, the potential toxicity of treatment, and the prominence of cachexia as a terminal symptom. Orwell's ordeals with collapse therapy may have influenced the portrayal of the tortures of Winston Smith in the novel 1984. I discuss unifying diagnoses for Orwell's respiratory problems and apparent infertility, including tuberculous epididymitis, Young syndrome, immotile cilia syndrome, and cystic fibrosis. PMID:16267732

  18. [Retroperitoneal fibrosis].

    PubMed

    Babski, Paweł; Wojtuń, Stanisław; Gil, Jerzy

    2007-05-01

    Retroperitoneal fibrosis is a rare clinical entity characterised by the presence of patologic collagen tissue in a retroperitoneal space. The fibrous mass covers abdominal organs causing their disfunctions. RPF was described at the begining of XX century but its etiology is not clear yet. Usually it causes an ureter obstuction and hydronephrosis, that is why most commonly is diagnosed by urologists and nephrologists. However, retroperitoneal fibrosis can be multifacial disease. In some patients localisation of fibrosis is atypical and manifestationns can be varied. Gastrological symptoms like jaundice, bowel obstuction, ascites can occure. Besides, some early signs of RPF are nonspecific and can imitate alarming symptoms of neoplasma, e.g.: weight loss, anemia, malaise, anorexia, fever. This force us to initiate gastrological investigation. The awareness of this disease is important. The early diagnosis and treatment improves prognosis and alows to avoid heavy complications. In typical cases radiology is often enough for diagnosis. However, histological examination is needed in many cases, especialy when patological mass is located atypical. A treatment is made up of farmacology and surgery. The first one is based on steroids, immunossuppressant and tamoxifen. Surgery is needed to eliminate organs obstruction. PMID:17679405

  19. Cystic Fibrosis Research

    MedlinePlus

    ... turn Javascript on. Feature: Steady Advances Against Cystic Fibrosis Cystic Fibrosis Research Past Issues / Fall 2012 Table of Contents "Remarkable strides in cystic fibrosis research over the past two decades have culminated ...

  20. Cystic fibrosis in Sudanese children: First report of 35 cases

    PubMed Central

    Ibrahim, Salah A; Fadl Elmola, Munadhil A; Karrar, Zain A; Arabi, Ali M E; Abdullah, Mohamed A; Ali, Sulafa K; Elawad, Fathelrahman; Ali, Tag Elsir A; Abdulrahman, Mashair B; Ahmed, Salma O; Gundi, Abelrazzag S

    2014-01-01

    Cystic fibrosis is the most common severe genetic disorder among children of European descent. It is much less common in Africans and Asians. It affects most critically the lungs causing chronic lung disease, failure to thrive and social deprivation. This is a retrospective review of 35 Sudanese patients with confirmed cystic fibrosis. About 60% of cases presented before the age of 5 years and male to female ratio was 1.7:1.0. Consanguinity was reported in 25 of the families. The main presenting features were productive cough, wheeze and clubbing. The chest X-ray showed variable degrees of hyperinflation, collapse, cystic, fibrotic changes and bronchiectasis involving both upper and lower lobes with blurring of cardiac border and hilar vasculature in the majority of cases. The sweat chloride was between 70 and 140 mmol/l in 83% of the patients (positive > 60 mmol/l). Three patients underwent DNA study and confirmed to have cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. Gene study was not available for the rest of the patients. To our knowledge this is the first report of confirmed cases of cystic fibrosis in Sudanese patients. PMID:27493388

  1. Impacts of Co-Existing Chronic Rhinosinusitis on Disease Severity and Risks of Exacerbations in Chinese Adults with Bronchiectasis

    PubMed Central

    Guan, Wei-jie; Gao, Yong-hua; Li, Hui-min; Yuan, Jing-jing; Chen, Rong-chang; Zhong, Nan-shan

    2015-01-01

    Background Mounting evidence supports the notion of “one airway, one disease.” Objective To determine whether chronic rhinosinusitis (CRS) poses adverse impacts on Chinese adults with bronchiectasis. Methods We enrolled 148 consecutive adults with clinically stable bronchiectasis. CRS diagnosed based on the 2012 EP3OS criteria. We systematically evaluated the bronchiectasis etiology, radiology, lung function, sputum bacteriology, airway inflammatory biomarkers, Bronchiectasis Severity Index, cough sensitivity and healthcare resource utilization. All patients were prospectively followed-up for 1 year to examine the frequency of bronchiectasis exacerbations (BEs). Results Forty-seven patients (31.8%) were diagnosed as having CRS. Bronchiectasis etiologies did not vary statistically between CRS and no-CRS group. There was a trend towards non-statistically higher Bronchiectasis Severity Index [6.4±3.4 vs. 5.0(6.0), P = 0.19], a higher proportion of patients with BEs needing hospitalization before enrollment (48.9% vs. 29.7%, P = 0.13), poorer FVC [78.2±19.8% vs. 82.2(16.8)%, P = 0.54] and FEV1 [68.2±24.8% vs. 74.8(21.2)%, P = 0.29], a higher prevalence of Pseudomonas aeruginosa isolated (36.2% vs. 26.7%, P = 0.27) or colonized in sputum (36.2% vs. 21.8%, P = 0.12) and greater capsaicin cough sensitivity [C2: 3.9(123.0) μmol/L vs. 11.7(123.0) μmol/L, P = 0.81; C5: 62.5(996.0) μmol/L vs. 250.0(973.0) μmol/L, P = 0.32]. Patients with CRS had significantly greater risks of experiencing BEs during follow-up (P = 0.02 for negative binominal regression test). Conclusion Chinese adults with bronchiectasis appear to have a lower prevalence of CRS than that in western countries. There was a trend towards greater adverse impacts on bronchiectasis in patients with CRS. Studies with greater sample sizes might help to resolve this issue. In future clinical practice, physicians should be vigilant to the screening of concomitant CRS in bronchiectasis so as to better improve

  2. Renal Fibrosis

    PubMed Central

    Zeisberg, Michael; Maeshima, Yohei; Mosterman, Barbara; Kalluri, Raghu

    2002-01-01

    During progression of chronic renal disease, qualitative and quantitative changes in the composition of tubular basement membranes (TBMs) and interstitial matrix occur. Transforming growth factor (TGF)-β1-mediated activation of tubular epithelial cells (TECs) is speculated to be a key contributor to the progression of tubulointerstitial fibrosis. To further understand the pathogenesis associated with renal fibrosis, we developed an in vitro Boyden chamber system using renal basement membranes that partially mimics in vivo conditions of TECs during health and disease. Direct stimulation of TECs with TGF-β1/epithelial growth factor results in an increased migratory capacity across bovine TBM preparations. This is associated with increased matrix metalloproteinase (MMP) production, namely MMP-2 and MMP-9. Indirect chemotactic stimulation by TGF-β1/EGF or collagen type I was insufficient in inducing migration of untreated TECs across bovine TBM preparation, suggesting that basement membrane integrity and composition play an important role in protecting TECs from interstitial fibrotic stimuli. Additionally, neutralization of MMPs by COL-3 inhibitor dramatically decreases the capacity of TGF-β1-stimulated TECs to migrate through bovine TBM preparation. Collectively, these results demonstrate that basement membrane structure, integrity, and composition play an important role in determining interstitial influences on TECs and subsequent impact on potential aberrant cell-matrix interactions. PMID:12057905

  3. Culture and PCR Detection of Haemophilus influenzae and Haemophilus haemolyticus in Australian Indigenous Children with Bronchiectasis

    PubMed Central

    Binks, M. J.; Grimwood, K.; Chang, A. B.; Leach, A. J.; Smith-Vaughan, H.

    2012-01-01

    A PCR for protein D (hpd#3) was used to differentiate nontypeable Haemophilus influenzae (NTHI) from Haemophilus haemolyticus. While 90% of nasopharyngeal specimens and 100% of lower-airway specimens from 84 Indigenous Australian children with bronchiectasis had phenotypic NTHI isolates confirmed as H. influenzae, only 39% of oropharyngeal specimens with phenotypic NTHI had H. influenzae. The nasopharynx is therefore the preferred site for NTHI colonization studies, and NTHI is confirmed as an important lower-airway pathogen. PMID:22553240

  4. Biomarkers for liver fibrosis

    SciTech Connect

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  5. A case of bronchiectasis needing lung isolation for cerebello pontine angle tumor excision: Anesthetic challenges.

    PubMed

    Srinivasan, C; Kurian, G P; Mariappan, R

    2016-01-01

    The main goals of neuroanesthesia are the maintenance of adequate cerebral perfusion pressure, avoidance of hypercarbia, hypoxemia, and to provide better brain relaxation. Providing anesthesia for a patient with bronchiectasis needing lung isolation for craniotomy can be challenging. A 56-year-old male patient, case of right lung bronchiectasis with a right cerebello pontine angle tumor underwent excision in the left lateral position. Since he had severe bronchiectasis of the right lung, we had isolated the right lung using right-sided double lumen tube to avoid spillage. Intraoperative split lung test was performed to assess the right lung contribution on carbon dioxide (CO2) elimination and found that there was a significant contribution from the right lung. Hence, both lungs were ventilated to control CO2. The importance of lung isolation to prevent spillage and avoidance of one lung ventilation to control the arterial CO2 are highlighted in this case report. By providing a balanced anesthetic keeping both, the neurosurgical and thoracic concerns are important for better postoperative outcome. PMID:27375400

  6. A case of bronchiectasis needing lung isolation for cerebello pontine angle tumor excision: Anesthetic challenges

    PubMed Central

    Srinivasan, C; Kurian, GP; Mariappan, R

    2016-01-01

    The main goals of neuroanesthesia are the maintenance of adequate cerebral perfusion pressure, avoidance of hypercarbia, hypoxemia, and to provide better brain relaxation. Providing anesthesia for a patient with bronchiectasis needing lung isolation for craniotomy can be challenging. A 56-year-old male patient, case of right lung bronchiectasis with a right cerebello pontine angle tumor underwent excision in the left lateral position. Since he had severe bronchiectasis of the right lung, we had isolated the right lung using right-sided double lumen tube to avoid spillage. Intraoperative split lung test was performed to assess the right lung contribution on carbon dioxide (CO2) elimination and found that there was a significant contribution from the right lung. Hence, both lungs were ventilated to control CO2. The importance of lung isolation to prevent spillage and avoidance of one lung ventilation to control the arterial CO2 are highlighted in this case report. By providing a balanced anesthetic keeping both, the neurosurgical and thoracic concerns are important for better postoperative outcome. PMID:27375400

  7. Assessing idiopathic pulmonary fibrosis (IPF) with bronchoscopic OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hariri, Lida P.; Adams, David C.; Colby, Thomas V.; Tager, Andrew M.; Suter, Melissa J.

    2016-03-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal form of fibrotic lung disease, with a significantly worse prognosis than other forms of pulmonary fibrosis (3-year survival rate of 50%). Distinguishing IPF from other fibrotic diseases is essential to patient care because it stratifies prognosis and therapeutic decision-making. However, making the diagnosis often requires invasive, high-risk surgical procedures to look for microscopic features not seen on chest CT, such as characteristic cystic honeycombing in the peripheral lung. Optical coherence tomography (OCT) provides rapid 3D visualization of large tissue volumes with microscopic resolutions well beyond the capabilities of CT. We aim to determine whether bronchoscopic OCT can provide a low-risk, non-surgical method for IPF diagnosis. We have developed bronchoscopic OCT catheters that access the peripheral lung and conducted in vivo peripheral lung imaging in patients, including those with pulmonary fibrosis. We also conducted bronchoscopic OCT in ex vivo lung from pulmonary fibrosis patients, including IPF, to determine if OCT could successfully visualize features of IPF through the peripheral airways. Our results demonstrate that OCT is able to visualize characteristic features of IPF through the airway, including microscopic honeycombing (< 1 mm diameter) not visible by CT, dense peripheral fibrosis, and spatial disease heterogeneity. We also found that OCT has potential to distinguish mimickers of IPF honeycombing, such as traction bronchiectasis and emphysema, from true honeycombing. These findings support the potential of bronchoscopic OCT as a minimally-invasive method for in vivo IPF diagnosis. However, future clinical studies are needed to validate these findings.

  8. Chest CT abnormalities and quality of life: relationship in adult cystic fibrosis

    PubMed Central

    Kilcoyne, Aoife; Lavelle, Lisa P.; McCarthy, Colin J.; McEvoy, Sinead H.; Fleming, Hannah; Gallagher, Annika; Loeve, Martine; Tiddens, Harm; McKone, Edward; Gallagher, Charles C.

    2016-01-01

    Background To evaluate the relationship between lung parenchymal abnormalities on chest CT and health-related quality of life in adult cystic fibrosis (CF). Methods The chest CT scans of 101 consecutive CF adults (mean age 27.8±7.9, 64 males) were prospectively scored by two blinded radiologists in consensus using a modified Bhalla score. Health-related quality of life was assessed using the revised Quittner Cystic Fibrosis Questionnaire (CFQ-R). Multiple regressions were performed with each of the CFQ-R domains and all clinical and imaging findings to assess independent correlations. Results There were 18 inpatients and 83 outpatients. For the cohort of inpatients, CT abnormalities were significantly (P<0.005 for all) associated with Respiratory Symptoms (Air Trapping), and also with Social Functioning (Consolidation) and Role Functioning (Consolidation). For outpatients, CT abnormalities were significantly (P<0.005 for all) associated with Respiratory Symptoms (Consolidation) and also with Physical Functioning (Consolidation), Vitality (Consolidation, Severity of Bronchiectasis), Eating Problems (airway wall thickening), Treatment Burden (Total CT Score), Body Image (Severity of Bronchiectasis) and Role Functioning (Tree-in-bud nodules). Consolidation was the commonest independent CT predictor for both inpatients (predictor for 2 domains) and outpatients (predictor in 3 domains). Several chest CT abnormalities excluded traditional measures such as FEV1 and BMI from the majority of CFQ-R domains. Conclusions Chest CT abnormalities are significantly associated with quality of life measures in adult CF, independent of clinical or spirometric measurements. PMID:27047946

  9. Familial Pulmonary Fibrosis

    MedlinePlus

    ... are here: Health Information > Condition Information Familial Pulmonary Fibrosis: Overview When two or more members within the ... Associate Professor View full profile More Familial Pulmonary Fibrosis Information Forms Causes Genetic Counseling Print Page Email ...

  10. What Causes Cystic Fibrosis?

    MedlinePlus

    ... What Causes Cystic Fibrosis? A defect in the CFTR gene causes cystic fibrosis (CF). This gene makes ... and very salty sweat. Research suggests that the CFTR protein also affects the body in other ways. ...

  11. Bilateral Bronchiectasis as a Presentation Form of Pulmonary Marginal Zone B-Cell Lymphoma of Bronchus Associated Lymphoid Tissue

    PubMed Central

    Ernst, Glenda; Torres, Carla; Borsini, Eduardo; Vigovich, Félix; Downey, Daniel; Salvado, Alajandro; Bosio, Martín

    2015-01-01

    The pulmonary marginal zone B-cell lymphoma of bronchus associated lymphoid tissue of the lung (BALT) is a rare illness that can remain without symptoms. Radiological findings of pulmonary lymphoma are heterogeneous. In literature, bronchiectasis is only described in one patient who also had besides adenomegalies. We reported on a 48-year-old female patient. She showed symptoms consistent with dyspnea with productive cough; there were crepitant sounds in the auscultation. Pulmonary functional test has shown a severe restrictive pattern with a low FVC and DLCO. CT scan showed bronchiectasis in the medium lobule without adenomegalies. Echocardiogram was normal, and the laboratory findings only showed leukocytosis. There were no findings in the bronchoscopy, but the lung biopsy showed a B-cell pulmonary lymphoma (positive to CD20 and CD79a in immunostaining). A wide variety of radiological manifestations has been previously described; however, we have presented this rare case, with bronchiectasis, as unique radiological finding. PMID:26839723

  12. Living with Cystic Fibrosis

    MedlinePlus

    ... from the NHLBI on Twitter. Living With Cystic Fibrosis If you or your child has cystic fibrosis (CF), you should learn as much as you ... about CF Care Centers, go to the Cystic Fibrosis Foundation's Care Center Network Web page. It's standard ...

  13. Pulmonary function abnormalities in adult patients with acute exacerbation of bronchiectasis: A retrospective risk factor analysis.

    PubMed

    Ma, Yanliang; Niu, Yuqian; Tian, Guizhen; Wei, Jingan; Gao, Zhancheng

    2015-08-01

    Lung function impairments, especially airflow obstruction, are important features during acute exacerbation in patients with bronchiectasis. Recognition of the risk factors associated with airflow obstruction is important in the management of these exacerbations. The medical records of adult patients admitted to the Peking University People's Hospital, Beijing, China, from 2004 to 2011 with a diagnosis of bronchiectasis were reviewed retrospectively. Univariate and multivariate analyses were used to evaluate the risk factors associated with airflow obstruction. Airflow obstruction was found in 55.6% of 156 patients hospitalized with acute exacerbation of bronchiectasis, and the risk factors associated with airflow obstruction included young age (≤14 years old) at diagnosis (odds ratio (OR) = 3.454, 95% confidence interval (CI) 1.709-6.982, p = 0.001) as well as the presence of chronic obstructive pulmonary disease (COPD; OR = 14.677, 95% CI 5.696-37.819, p = 0.001), asthma (OR = 3.063, 95% CI 1.403-6.690, p = 0.005), and wheezing on auscultation (OR = 3.279, 95% CI 1.495-7.194, p = 0.003). The C-reactive protein (13.9 mg/dl vs. 6.89 mg/dl, p = 0.005), partial pressure of arterial oxygen (66.7 ± 8.57 mmHg vs. 89.56 ± 12.80 mmHg, p < 0.001), and partial pressure of arterial carbon dioxide (40.52 ± 2.77 mmHg vs. 42.87 ± 5.39 mmHg, p = 0.02) profiles were different between patients with or without airflow obstruction. In addition, patients colonized with potential pathogenic microorganisms had a decreased diffusing capacity (56.0% vs. 64.7%, p = 0.04). Abnormal pulmonary function was common in hospitalized patients with bronchiectasis exacerbations. Airflow obstruction was correlated with the patient's age at diagnosis, as well as the presence of combined COPD and asthma, and wheezing on auscultation, which also resulted in more severe systemic inflammation and hypoxemia. PMID:25882894

  14. Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis

    PubMed Central

    Hodge, G.; Upham, J. W.; Chang, A. B.; Baines, K. J.; Yerkovich, S. T.; Pizzutto, S. J.; Hodge, S.

    2015-01-01

    Objective Bronchiectasis (BE) in children is common in some communities including Indigenous children in Australia. Relatively little is known about the nature of systemic inflammation in these children, especially the contribution of specific pro-inflammatory and cytotoxic lymphocyte subsets: T-cells, natural killer (NK) cells and NKT-like cells. We have shown that these cells produce increased cytotoxic (granzyme b and perforin) and inflammatory (IFNγ and TNFα) mediators in several adult chronic lung diseases and hypothesised that similar changes would be evident in children with BE. Methods Intracellular cytotoxic mediators perforin and granzyme b and pro-inflammatory cytokines were measured in T cell subsets, NKT-like and NK cells from blood and bronchoalveolar samples from 12 children with BE and 10 aged-matched control children using flow cytometry. Results There was a significant increase in the percentage of CD8+ T cells and T and NKT-like subsets expressing perforin/granzyme and IFNγ and TNFα in blood in BE compared with controls. There was a further increase in the percentage of pro-inflammatory cytotoxic T cells in Indigenous compared with non-Indigenous children. There was no change in any of these mediators in BAL. Conclusions Childhood bronchiectasis is associated with increased systemic pro-inflammatory/cytotoxic lymphocytes in the peripheral blood. Future studies need to examine the extent to which elevated levels of pro-inflammatory cytotoxic cells predict future co-morbidities. PMID:26258716

  15. Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy.

    PubMed

    Cantin, André M; Hartl, Dominik; Konstan, Michael W; Chmiel, James F

    2015-07-01

    Lung disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Although CF lung disease is primarily an infectious disorder, the associated inflammation is both intense and ineffective at clearing pathogens. Persistent high-intensity inflammation leads to permanent structural damage of the CF airways and impaired lung function that eventually results in respiratory failure and death. Several defective inflammatory responses have been linked to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency including innate and acquired immunity dysregulation, cell membrane lipid abnormalities, various transcription factor signaling defects, as well as altered kinase and toll-like receptor responses. The inflammation of the CF lung is dominated by neutrophils that release oxidants and proteases, particularly elastase. Neutrophil elastase in the CF airway secretions precedes the appearance of bronchiectasis, and correlates with lung function deterioration and respiratory exacerbations. Anti-inflammatory therapies are therefore of particular interest for CF lung disease but must be carefully studied to avoid suppressing critical elements of the inflammatory response and thus worsening infection. This review examines the role of inflammation in the pathogenesis of CF lung disease, summarizes the results of past clinical trials and explores promising new anti-inflammatory options. PMID:25814049

  16. A long-term study assessing the factors influencing survival and morbidity in the surgical management of bronchiectasis

    PubMed Central

    2011-01-01

    Background Although the prevalence of bronchiectasis decreased significantly in developed countries, in less developed and in developing countries, it still represents a significant cause of morbidity and mortality. The aim of this retrospective study is to present our surgical experiences, the morbidity and mortality rates and outcome of surgical treatment for bronchiectasis. Methods We reviewed the medical records of 129 patients who underwent surgical resection for bronchiectasis between April 2002 and April 2010, at Van Training and Research Hospital, Thoracic Surgery Department. Variables of age, sex, symptoms, etiology, and surgical procedures, mortality, morbidity and the result of surgical therapy were analyzed retrospectively. Results Mean age was 21.8 year (the eldest was 67 year, the youngest was 4 years-old). Male/female ratio was 1.86 and 75% of all patients were young population under the age of 40. Bilateral involvement was 14.7%, left/right side ratio according to localization was 2.1/1. The most common reason for bronchiectasis was recurrent infection. Surgical indications were as follows: recurrent infection (54%), hemoptysis (35%), empyema (6%), and lung abscess (5%). There was no operative mortality. Complications occurred in 29 patients and the morbidity rate was 22.4%. Complete resection was achieved in 110 (85.2%) patients. Follow-up data were obtained for 123 (95%) of the patients. One patient died during follow-up. The mean follow-up of this patient was 9 months. Mean postoperative hospitalization time was 9.15 ± 6.25 days. Significantly better results were obtained in patients who had undergone a complete resection. Conclusions Surgical treatment of bronchiectasis can be performed with acceptable morbidity and mortality at any age. The involved bronchiectatic sites should be resected completely for the optimum control of symptoms. PMID:22152759

  17. Genetics Home Reference: retroperitoneal fibrosis

    MedlinePlus

    ... Understand Genetics Home Health Conditions retroperitoneal fibrosis retroperitoneal fibrosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Retroperitoneal fibrosis is a disorder in which inflammation and extensive ...

  18. How Is Cystic Fibrosis Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Cystic Fibrosis Diagnosed? Doctors diagnose cystic fibrosis (CF) based on ... to see whether the baby has CF. Cystic Fibrosis Carrier Testing People who have one normal CFTR ...

  19. An evaluation of automated broncho-arterial ratios for reliable assessment of bronchiectasis

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Lerallut, Jean-Francois

    2008-03-01

    Bronchiectasis, the permanent dilatation of the airways, is frequently evaluated by computed tomography (CT) in order to determine disease progression and response to treatment. Normal airways have diameters of approximately the same size as their accompanying artery, and most scoring systems for quantifying bronchiectasis severity ask physicians to estimate the broncho-arterial ratio. However, the lack of standardization coupled with inter-observer variability limits diagnostic sensitivity and the ability to make reliable comparisons with follow-up CT studies. We have developed a Computer Aided Diagnosis method to detect airway disease by locating abnormal broncho-arterial ratios. Our approach is based on computing a tree model of the airways followed by automated measurements of broncho-arterial ratios at peripheral airway locations. The artery accompanying a given bronchus is automatically determined by correlation of its orientation and proximity to the airway, while the diameter measurements are based on the full-width half maximum method. This method was previously evaluated subjectively; in this work we quantitatively evaluate the airway and vessel measurements on 9 CT studies and compare the results with three independent readers. The automatically selected artery location was in agreement with the readers in 75.3% of the cases compared with 65.6% agreement of the readers with each other. The reader-computer variability in lumen diameters (7%) was slightly lower than that of the readers with respect to each other (9%), whereas the reader-computer variability in artery diameter (18%) was twice that of the readers (8%), but still acceptable for detecting disease. We conclude that the automatic system has comparable accuracy to that of readers, while providing greater speed and consistency.

  20. Practical management of Idiopathic Pulmonary Fibrosis.

    PubMed

    Kishaba, Tomoo

    2015-01-01

    Idiopathic Pulmonary Fibrosis (IPF) is relentless progressive interstitial lung disease (ILD) of unknown etiology. Main pathogenesis is aberrant recovery of epithelial injury and collagen deposition. Majority of IPF patients have been elderly men with smokers. However, there are important differential diagnosis such as fibrotic non-specific interstitial pneumonia (NSIP), Connective Tissue Disease (CTD) associated ILD, chronic hypersensitivity pneumonia (CHP). Clinical point of view, non-productive cough and progressive exertional dyspnea are main symptoms. In addition, scalene muscle hypertrophy, fine crackles and finger clubbing are key findings. Serum marker such as lactate deydrogenase (LDH), Krebs von den Lungeng-6 (KL-6) are sensitive for ILD detection and activity. Pulmonary function test and 6 minute walk test (6MWT) are quite meaningful physiological examination. Serial change of forced vital capacity 6MWT distance predict mortality of IPF. International IPF guideline published recently and highlighted on the importance of high resolution computed tomography (HRCT) findings. Key findings of IPF are honeycombing, traction bronchiectasis and subpleural reticular opacity. IPF is chronic progressive disease. Therefore, tracing disease behavior is crucial and unifying clinical, physiological, imaging information over time provide useful information for physicians.In management, many candidate agent failed to have positive result. Pirfenidone which is anti-fibrotic agent showed to slow the decline of vital capacity and prevent of acute exacerbation. Molecular agent such as nintedanib is promising agent for prevention of progression of IPF. In this review, we review the clinical information of IPF and IPF guideline. Lastly, we show the clinical algorithm of this devastated disease. PMID:26278687

  1. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004-2013: a population based cohort study

    PubMed Central

    Quint, Jennifer K.; Millett, Elizabeth R. C.; Joshi, Miland; Navaratnam, Vidya; Thomas, Sara L.; Hurst, John R.; Smeeth, Liam; Brown, Jeremy S.

    2016-01-01

    Background There is a paucity of data on incidence, prevalence and mortality associated with non-CF bronchiectasis. Methods Using Clinical Practice Research Datalink (CPRD) for participants registered between 1st January 2004 and 31st December 2013, we determined incidence, prevalence and mortality associated with bronchiectasis in the UK and investigated changes over time. Results The incidence and point prevalence of bronchiectasis increased yearly during the study period. Across all age groups, the incidence in women increased from 21.2/100,000 person-years in 2004 to 35.2/100,000 person-years in 2013, and in men from 18.2/100,000 person-years in 2004 to 26.9/100,000 person-years in 2013. The point prevalence in women increased from 350.5/100,000 in 2004 to 566.1/100,000 in 2013 and in men from 301.2/100,000 to 485.5/100,000 in 2013. Comparing morality rates in women and men with bronchiectasis in England and Wales (n=11,862) to mortality rates in the general population from ONS data, showed that in women the age adjusted mortality rate for the bronchiectasis population was 1437.7/100,000 and for the general population 635.9/100,000; (comparative mortality figure of 2.26). In men, the age adjusted mortality rate for the bronchiectasis population was 1914.6/100,000 and for the general population 895.2/100,000; (comparative mortality figure of 2.14). Conclusion Bronchiectasis is surprisingly common and is increasing in incidence and prevalence in the UK, particularly in older age groups. Bronchiectasis is associated with a markedly increased mortality. PMID:26541539

  2. Angiogenesis and liver fibrosis

    PubMed Central

    Elpek, Gülsüm Özlem

    2015-01-01

    Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases (CLDs) that are characterized by inflammation and progressive fibrosis. Because anti-angiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical and experimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis. PMID:25848465

  3. Learning about Cystic Fibrosis

    MedlinePlus

    ... order to digest food. Cystic Fibrosis: A Single Gene Disease Mutations in a single gene - the Cystic ... the defective gene, or correcting the defective protein. Gene Therapy Research Offers Promise of a Cure for ...

  4. Idiopathic Pulmonary Fibrosis (IPF)

    MedlinePlus

    ... cough, shortness of breath, fatigue and low blood oxygen levels. Pulmonary fibrosis can be caused by an ... breath. Your health care provider may notice the oxygen levels in your blood drop when you walk. ...

  5. Fibrosis and Simple Cysts

    MedlinePlus

    ... lobular) Lobular carcinoma in situ (LCIS) Adenosis Fibroadenomas Phyllodes tumors Intraductal papillomas Granular cell tumors Fat necrosis ... caused by fibrosis and/or cysts, which are benign changes in breast tissue that happen in many ...

  6. Familial pulmonary fibrosis.

    PubMed

    Borie, R; Kannengiesser, C; Nathan, N; Tabèze, L; Pradère, P; Crestani, B

    2015-04-01

    The occurrence of pulmonary fibrosis in numerous individuals from the same family suggests a genetic cause for the disease. During the last 10 years, mutations involving proteins from the telomerase complex and from the surfactant system have been identified in association with pulmonary fibrosis. Mutations of TERT, the coding gene for the telomerase reverse transcriptase, are the most frequently identified mutations and are present in 15% of cases of familial pulmonary fibrosis. Other mutations (TERC, surfactant proteins genes) are only rarely evidenced in adults. Patients with mutations involving the telomerase complex may present with pulmonary fibrosis, hematologic, cutaneous or liver diseases. Other genetic variations associated with pulmonary fibrosis such as a polymorphism in the promoter of MUC5B or a polymorphism in TERT have been recently described, and could be considered to be part of a polygenic transmission. Evidence for mutations associated with the development of pulmonary fibrosis raises numerous clinical questions from establishing a diagnosis, providing counselling to deciding on therapy, and requires specific studies. From a pathophysiological point of view, the function of the genes highlights the central role of alveolar epithelium and aging in fibrogenesis. PMID:25596800

  7. DNA methylation in fibrosis.

    PubMed

    Dowson, Christopher; O'Reilly, Steven

    2016-09-01

    Fibrosis is characterised by an exuberant wound healing response and the major cell type responsible is the myofibroblast. The myofibroblast is typified by excessive ECM production and contractile activity and is demarcated by alpha-smooth muscle actin expression. What has recently come to light is that the activation of the fibroblast to myofibroblast may be under epigenetic control, specifically methylation. Methylation of DNA is a conserved mechanism to precisely regulate gene expression in a specific context. Hypermethylation leads to gene repression and hypomethylation results in gene induction. Methylation abnormalities have recently been uncovered in fibrosis, both organ specific and widespread fibrosis. The fact that these methylation changes are rapid and reversible lends themselves amenable to therapeutic intervention. This review considers the role of methylation in fibrosis and the activation of the myofibroblasts and how this could be targeted for fibrosis. Fibrosis is of course currently intractable to therapeutics and is a leading cause of morbidity and mortality and is an urgent unmet clinical need. PMID:27346523

  8. Magnetomotive optical coherence elastography for relating lung structure and function in cystic fibrosis

    NASA Astrophysics Data System (ADS)

    Chhetri, Raghav K.; Carpenter, Jerome; Superfine, Richard; Randell, Scott H.; Oldenburg, Amy L.

    2010-02-01

    Cystic fibrosis (CF) is a genetic defect in the cystic fibrosis transmembrane conductance regulator protein and is the most common life-limiting genetic condition affecting the Caucasian population. It is an autosomal recessive, monogenic inherited disorder characterized by failure of airway host defense against bacterial infection, which results in bronchiectasis, the breakdown of airway wall extracellular matrix (ECM). In this study, we show that the in vitro models consisting of human tracheo-bronchial-epithelial (hBE) cells grown on porous supports with embedded magnetic nanoparticles (MNPs) at an air-liquid interface are suitable for long term, non-invasive assessment of ECM remodeling using magnetomotive optical coherence elastography (MMOCE). The morphology of ex vivo CF and normal lung tissues using OCT and correlative study with histology is also examined. We also demonstrate a quantitative measure of normal and CF airway elasticity using MMOCE. The improved understanding of pathologic changes in CF lung structure and function and the novel method of longitudinal in vitro ECM assessment demonstrated in this study may lead to new in vivo imaging and elastography methods to monitor disease progression and treatment in cystic fibrosis.

  9. Multi-breath dry powder inhaler for delivery of cohesive powders in the treatment of bronchiectasis.

    PubMed

    Young, Paul M; Salama, Rania O; Zhu, Bing; Phillips, Gary; Crapper, John; Chan, Hak-Kim; Traini, Daniela

    2015-05-01

    A series of co-engineered macrolide-mannitol particles were successfully prepared using azithromycin (AZ) as a model drug. The formulation was designed to target local inflammation and bacterial colonization, via the macrolide component, while the mannitol acted as mucolytic and taste-masking agent. The engineered particles were evaluated in terms of their physico-chemical properties and aerosol performance when delivered via a novel high-payload dry powder Orbital(™) inhaler device that operates via multiple inhalation manoeuvres. All formulations prepared were of suitable size for inhalation drug delivery and contained a mixture of amorphous AZ with crystalline mannitol. A co-spray dried formulation containing 200 mg of 50:50 w/w AZ: mannitol had 57.6% ± 7.6% delivery efficiency with a fine particle fraction (≤6.8 µm) of the emitted aerosol cloud being 80.4% ± 1.1%, with minimal throat deposition (5.3 ± 0.9%). Subsequently, it can be concluded that the use of this device in combination with the co-engineered macrolide-mannitol therapy may provide a means of treating bronchiectasis. PMID:24811055

  10. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    MedlinePlus

    ... Cystic Fibrosis (CF) Chloride Sweat Test Lungs and Respiratory System Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition Lungs and Respiratory System Contact Us Print Resources Send to a friend ...

  11. Novel human bronchial epithelial cell lines for cystic fibrosis research

    PubMed Central

    Fulcher, M. L.; Gabriel, S. E.; Olsen, J. C.; Tatreau, J. R.; Gentzsch, M.; Livanos, E.; Saavedra, M. T.; Salmon, P.; Randell, S. H.

    2009-01-01

    Immortalization of human bronchial epithelial (hBE) cells often entails loss of differentiation. Bmi-1 is a protooncogene that maintains stem cells, and its expression creates cell lines that recapitulate normal cell structure and function. We introduced Bmi-1 and the catalytic subunit of telomerase (hTERT) into three non-cystic fibrosis (CF) and three ΔF508 homozygous CF primary bronchial cell preparations. This treatment extended cell life span, although not as profoundly as viral oncogenes, and at passages 14 and 15, the new cell lines had a diploid karyotype. Ussing chamber analysis revealed variable transepithelial resistances, ranging from 200 to 1,200 Ω·cm2. In the non-CF cell lines, short-circuit currents were stimulated by forskolin and inhibited by CFTR(inh)-172 at levels mostly comparable to early passage primary cells. CF cell lines exhibited no forskolin-stimulated current and minimal CFTR(inh)-172 response. Amiloride-inhibitable and UTP-stimulated currents were present, but at lower and higher amplitudes than in primary cells, respectively. The cells exhibited a pseudostratified morphology, with prominent apical membrane polarization, few apoptotic bodies, numerous mucous secretory cells, and occasional ciliated cells. CF and non-CF cell lines produced similar levels of IL-8 at baseline and equally increased IL-8 secretion in response to IL-1β, TNF-α, and the Toll-like receptor 2 agonist Pam3Cys. Although they have lower growth potential and more fastidious growth requirements than viral oncogene transformed cells, Bmi-1/hTERT airway epithelial cell lines will be useful for several avenues of investigation and will help fill gaps currently hindering CF research and therapeutic development. PMID:18978040

  12. Mechanotransduction and fibrosis

    PubMed Central

    Duscher, Dominik; Maan, Zeshaan N.; Wong, Victor W.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Hu, Michael; Whitmore, Arnetha J.; Whittam, Alexander J.; Longaker, Michael T.; Gurtner, Geoffrey C.

    2015-01-01

    Scarring and tissue fibrosis represent a significant source of morbidity in the United States. Despite considerable research focused on elucidating the mechanisms underlying cutaneous scar formation, effective clinical therapies are still in the early stages of development. A thorough understanding of the various signaling pathways involved is essential to formulate strategies to combat fibrosis and scarring. While initial efforts focused primarily on the biochemical mechanisms involved in scar formation, more recent research has revealed a central role for mechanical forces in modulating these pathways. Mechanotransduction, which refers to the mechanisms by which mechanical forces are converted to biochemical stimuli, has been closely linked to inflammation and fibrosis and is believed to play a critical role in scarring. This review provides an overview of our current understanding of the mechanisms underlying scar formation, with an emphasis on the relationship between mechanotransduction pathways and their therapeutic implications. PMID:24709567

  13. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

    PubMed

    Hare, K M; Grimwood, K; Chang, A B; Chatfield, M D; Valery, P C; Leach, A J; Smith-Vaughan, H C; Morris, P S; Byrnes, C A; Torzillo, P J; Cheng, A C

    2015-11-01

    Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage. PMID

  14. Analysis of the Sputum and Inflammatory Alterations of the Airways in Patients with Common Variable Immunodeficiency and Bronchiectasis

    PubMed Central

    Pereira, Andrea Cristina; Kokron, Cristina M.; Romagnolo, Beatriz Mangueira Saraiva; Yagi, Claudia Simeire Albertini; Saldiva, Paulo Hilário Nascimento; Filho, Geraldo Lorenzi; Negri, Elnara Marcia

    2009-01-01

    INTRODUCTION: Common variable immunodeficiency is characterized by defective antibody production and recurrent pulmonary infections. Intravenous immunoglobulin is the treatment of choice, but the effects of Intravenous immunoglobulin on pulmonary defense mechanisms are poorly understood. OBJECTIVE: The aim of this study was to verify the impact of intravenous immunoglobulin on the physical properties of the sputum and on inflammatory alterations in the airways of patients with Common variable immunodeficiency associated with bronchiectasis. METHOD: The present study analyzed sputum physical properties, exhaled NO, inflammatory cells in the sputum, and IG titers in 7 patients with Common variable immunodeficiency and bronchiectasis with secretion, immediately before and 15 days after Intravenous immunoglobulin. A group of 6 patients with Common variable immunodeficiency and bronchiectasis but no sputum was also studied for comparison of the basal IgG level and blood count. The 13 patients were young (age=36±17 years) and comprised predominantly of females (n=11). RESULTS: Patients with secretion presented significantly decreased IgG and IgM levels. Intravenous immunoglobulin was associated with a significant decrease in exhaled NO (54.7 vs. 40.1 ppb, p<0.05), sputum inflammatory cell counts (28.7 vs. 14.6 cells/mm3, p<0.05), and a significant increase in respiratory mucus transportability by cough (42.5 vs. 65.0 mm, p < 0.05). CONCLUSION: We concluded that immunoglobulin administration in Common variable immunodeficiency patients results in significant improvement in indexes of inflammation of the airways with improvement in the transportability of the respiratory mucus by cough. PMID:20037702

  15. Importance of fractional exhaled nitric oxide in diagnosis of bronchiectasis accompanied with bronchial asthma

    PubMed Central

    Chen, Feng-Jia; Liao, Huai; Huang, Xin-Yan

    2016-01-01

    Background Fractional exhaled nitric oxide (FeNO) measurement is a simple, rapid, highly reproducible, and noninvasive method of airway inflammation assessment. Therefore, FeNO is extensively used for the diagnosis and management of asthma. The feasibility of using FeNO as an alternative to conventional pulmonary function test to differentiate patients with bronchiectasis (BE) and bronchial asthma from those with BE only remains unclear. Methods From February 2013 to February 2015, 99 patients diagnosed with BE through high-resolution computed tomography (HRCT) were subjected to FeNO measurement, bronchial challenge test (BCT), or bronchodilator test. Bronchial hyperreactivity and/or reversible airway obstruction was used to define asthma. The receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in the diagnosis of asthmatic patients with BE, and the optimal operating point was also determined. Results Of 99 patients with BE, 20 patients presented asthma, and 12 of these patients received regular treatment, which were given with budesonide (200 µg, bid) for 12 weeks to evaluate changes in the concentration and assess the role of FeNO in the treatment. The area under the ROC curve was estimated as 0.832 for FeNO. Results also revealed a cut off value of >22.5 part per billion (ppb) FeNO for differentiating asthmatic from non-asthmatic (sensitivity, 90.0%; specificity, 62.5%) patients with BE. FeNO and forced expiratory volume for 1 second significantly improved after the treatment. Conclusions Clinical FeNO measurement is a simple, noninvasive, and rapid method used to differentiate asthmatic from nonasthmatic patients with BE. This technique exhibits potential for asthma management. PMID:27162676

  16. Longitudinal Nasopharyngeal Carriage and Antibiotic Resistance of Respiratory Bacteria in Indigenous Australian and Alaska Native Children with Bronchiectasis

    PubMed Central

    Hare, Kim M.; Singleton, Rosalyn J.; Grimwood, Keith; Valery, Patricia C.; Cheng, Allen C.; Morris, Peter S.; Leach, Amanda J.; Smith-Vaughan, Heidi C.; Chatfield, Mark; Redding, Greg; Reasonover, Alisa L.; McCallum, Gabrielle B.; Chikoyak, Lori; McDonald, Malcolm I.; Brown, Ngiare; Torzillo, Paul J.; Chang, Anne B.

    2013-01-01

    Background Indigenous children in Australia and Alaska have very high rates of chronic suppurative lung disease (CSLD)/bronchiectasis. Antibiotics, including frequent or long-term azithromycin in Australia and short-term beta-lactam therapy in both countries, are often prescribed to treat these patients. In the Bronchiectasis Observational Study we examined over several years the nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in these two PCV7-vaccinated populations. Methods Indigenous children aged 0.5–8.9 years with CSLD/bronchiectasis from remote Australia (n = 79) and Alaska (n = 41) were enrolled in a prospective cohort study during 2004–8. At scheduled study visits until 2010 antibiotic use in the preceding 2-weeks was recorded and nasopharyngeal swabs collected for culture and antimicrobial susceptibility testing. Analysis of respiratory bacterial carriage and antibiotic resistance was by baseline and final swabs, and total swabs by year. Results Streptococcus pneumoniae carriage changed little over time. In contrast, carriage of Haemophilus influenzae declined and Staphylococcus aureus increased (from 0% in 2005–6 to 23% in 2010 in Alaskan children); these changes were associated with increasing age. Moraxella catarrhalis carriage declined significantly in Australian, but not Alaskan, children (from 64% in 2004–6 to 11% in 2010). While beta-lactam antibiotic use was similar in the two cohorts, Australian children received more azithromycin. Macrolide resistance was significantly higher in Australian compared to Alaskan children, while H. influenzae beta-lactam resistance was higher in Alaskan children. Azithromycin use coincided significantly with reduced carriage of S. pneumoniae, H. influenzae and M. catarrhalis, but increased carriage of S. aureus and macrolide-resistant strains of S. pneumoniae and S. aureus (proportion of carriers and all swabs), in a ‘cumulative dose-response’ relationship. Conclusions

  17. Video-assisted thoracoscopic segmentectomy of lingual segment of the left upper pulmonary lobe for chronic focal bronchiectasis

    PubMed Central

    Pan, Xue; Li, Xiangnan; Ding, Zheng; Zhu, Dengyan; Zhang, Chunyang; Zhao, Jia

    2016-01-01

    A 46-year-old male patient was admitted into the hospital due to repeated hemoptysis for more than seven months. Bronchiectasis of the left upper lobe was considered based on the symptoms, signs, and imaging findings. Thoracoscopic resection of lingual segment of the left upper pulmonary lobe was finally performed in the order of the lingual segmental vein, the lingual segmental bronchus, the lingual segmental artery, and the pulmonary tissues of the lingual segment. Total surgery time was 60 min and blood loss was 40 mL. The chest tube was removed on the 4th postoperative day. The patient was discharged home on the 8th postoperative day. PMID:27076962

  18. Adipose tissue fibrosis

    PubMed Central

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-01-01

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues. Stressed adipocytes and hypoxia contribute to immune cell immigration and activation which further aggravates adipose tissue fibrosis. There is substantial evidence that adipose tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in the clinical setting. Peroxisome proliferator activated receptor gamma agonists and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin resistance. Current knowledge suggests that antifibrotic drugs, increasing adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue function and thereby ameliorate metabolic diseases. PMID:25987952

  19. [News in cystic fibrosis].

    PubMed

    Delaisi, B

    2013-08-01

    The improvement over the last two decades in the treatment of cystic fibrosis led to an increase in life expectancy approaching 40 years at birth. Logically, the population of adult patients has been increasing and is currently 50% of patients followed in France. These therapeutic advances have justified the establishment in 2003 of a generalized neonatal screening for cystic fibrosis. The latest data of this screening show an incidence of CF of 1/5359 live births, far below the incidence of 1/2500 which was widely accepted twenty years ago. The performance of this screening is currently based on the dosage of trypsin immuno reactive, followed in case of exceeding the threshold of a search of the 30 most common mutations, can detect around 96% of 150 to 200 CF cases every year. Therefore, the possibility of a false negative of the screening cannot be excluded and evocative symptoms of cystic fibrosis, even for children born after 2003, will lead to prescribe a sweat test. While treatments available so far goal consequences of cystic fibrosis, a new therapeutic class to correct the functional defect of the mutated protein, called CFTR modulators, is emerging. Ivacaftor, leader of this new class, belonging to the category of "CFTR potentiator" got its access on the market in September 2012 for patients carrying the G551D mutation. New other molecules, named "CFTR correctors" which can have synergistic effect with ivacaftor and concern patients carrying the most common mutation--DF 508--are under development. PMID:23856023

  20. Pulmonary Fibrosis Foundation

    MedlinePlus

    ... 844.825.5733) to speak with a representative today. LEARN MORE It's Global PF Awareness Month! Download the toolkit to learn ... 19 NEW SITES The Pulmonary Fibrosis Foundation (PFF) today announced the expansion of the PFF Care Center Network with the selection of 19 additional sites, bringing the total number to 40 in 27 states. More Announcements ... SEP 12 ...

  1. Assessment of the quantity of microorganisms associated with bronchiectasis in saliva, sputum and nasal lavage after periodontal treatment: a study protocol of a randomised controlled trial

    PubMed Central

    Pinto, Erika Horácio; Longo, Priscila Larcher; de Camargo, Caroline Cristina Batista; Dal Corso, Simone; Lanza, Fernanda De Cordoba; Stelmach, Rafael; Athanazio, Rodrigo; Fernandes, Kristianne Porta Santos; Mayer, Marcia Pinto Alves; Bussadori, Sandra Kalil; Mesquita Ferrari, Raquel Agnelli; Horliana, Anna Carolina Ratto Tempestini

    2016-01-01

    Introduction The association between periodontal disease (PD) and chronic obstructive pulmonary disease (COPD) has been widely studied, with aspiration of periodontal pathogens being one of the most accepted causal mechanisms for pulmonary exacerbation. Periodontal treatment (PT) was associated with a decrease in these exacerbations. Bronchiectasis is a pulmonary disease that has many similarities to COPD; however, there are no studies correlating this condition to PD thus far. This study will evaluate if PT reduces proinflammatory cytokines in serum and saliva, as well as halitosis and the amount of microorganisms associated with exacerbation of bronchiectasis in saliva, sputum and nasal lavage 3 months after PT. Methods and analysis A total of 182 patients with PD and bronchiectasis will be randomly allocated to group 1 (positive control; scaling and root planing (SRP)+oral hygiene (OH)) or group 2 (experimental; SRP+photodynamic therapy+OH). After 3 months, samples of saliva, nasal lavage and sputum will be collected to determine the level of Pseudomonas aeruginosa, Staphylococcus aureus and Porphyromonas gingivalis by quantitative PCR. This protocol will determine the efficacy of PT in reducing the most likely niches of bronchiectasis exacerbation by comparing pre- and post-treatment microbiology samples. Furthermore, there will be assessment of oral halitosis and verification of inflammatory cytokines in serum and saliva. Ethics and dissemination This protocol has been approved by the Research Ethics Committee of Universidade Nove de Julho. Data will be published in a peer-reviewed journal. Trial registration number NCT02514226. PMID:27084279

  2. Recurrent Infections and Chronic Colonization by an Escherichia coli Clone in the Respiratory Tract of a Patient with Severe Cystic Bronchiectasis

    PubMed Central

    Wang, Jann-Yuan; Hsueh, Po-Ren; Wang, Jann-Tay; Lee, Li-Na; Yang, Pan-Chyr; Luh, Kwen-Tay

    2000-01-01

    A 39-year-old woman with cystic bronchiectasis had repeated pulmonary infections from 1996 to 1999, and 6 of a total of 28 isolates of Escherichia coli from sputum specimens were studied. Their identical antibiotype and randomly amplified polymorphic DNA patterns indicated a single clone of E. coli, which persistently colonized the respiratory tract, causing recurrent infections. PMID:10878083

  3. Pulmonary Physiology of Chronic Obstructive Pulmonary Disease, Cystic Fibrosis, and Alpha-1 Antitrypsin Deficiency.

    PubMed

    Stockley, James A; Stockley, Robert A

    2016-04-01

    Cystic fibrosis is predominantly an airway disease with marked bronchiectatic changes associated with inflammation, chronic colonization, and progressive airflow obstruction. The condition can be identified in childhood and monitored with detectable airway changes early in life while conventional spirometry remains in the normal range. Alpha-1 antitrypsin deficiency can also be detected early in life through blood spot and genetic testing and leads (in some) to the development of airflow obstruction and a predominant emphysema phenotype with bronchiectatic changes in about 30%. Early detection also allows the natural history of the pulmonary physiological changes to be determined. Chronic obstructive pulmonary disease is usually detected late in the disease process when significant damage has occurred. The condition consists of varying combinations of airway disease, bronchiectasis, colonization, and emphysema. Lessons learned from the physiological evolution of airway disease in cystic fibrosis and the emphysema of alpha-1 antitrypsin deficiency provide strategies to enable early detection of chronic obstructive pulmonary disease in general and its phenotypes. PMID:27115945

  4. The Cystic Fibrosis Intestine

    PubMed Central

    De Lisle, Robert C.; Borowitz, Drucy

    2013-01-01

    The clinical manifestations of cystic fibrosis (CF) result from dysfunction of the cystic fibrosis transmembrane regulator protein (CFTR). The majority of people with CF have a limited life span as a consequence of CFTR dysfunction in the respiratory tract. However, CFTR dysfunction in the gastrointestinal (GI) tract occurs earlier in ontogeny and is present in all patients, regardless of genotype. The same pathophysiologic triad of obstruction, infection, and inflammation that causes disease in the airways also causes disease in the intestines. This article describes the effects of CFTR dysfunction on the intestinal tissues and the intraluminal environment. Mouse models of CF have greatly advanced our understanding of the GI manifestations of CF, which can be directly applied to understanding CF disease in humans. PMID:23788646

  5. Gadolinium-Induced Fibrosis.

    PubMed

    Todd, Derrick J; Kay, Jonathan

    2016-01-01

    Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF. PMID:26768242

  6. Higher Human T-Lymphotropic Virus Type 1 Subtype C Proviral Loads Are Associated With Bronchiectasis in Indigenous Australians: Results of a Case-Control Study

    PubMed Central

    Einsiedel, Lloyd; Cassar, Olivier; Goeman, Emma; Spelman, Tim; Au, Virginia; Hatami, Saba; Joseph, Sheela; Gessain, Antoine

    2014-01-01

    Background.  We previously suggested that infection with the human T-lymphotropic virus type 1 (HTLV-1) subtype C is associated with bronchiectasis among Indigenous Australians. Bronchiectasis might therefore result from an HTLV-1-mediated inflammatory process that is typically associated with a high HTLV-1 proviral load (PVL). Human T-lymphotropic virus type 1 PVL have not been reported for Indigenous Australians. Methods.  Thirty-six Indigenous adults admitted with bronchiectasis from June 1, 2008, to December 31, 2009 were prospectively recruited and matched by age, sex, and ethno-geographic origin to 36 controls. Case notes and chest high-resolution computed tomographs were reviewed, and pulmonary injury scores were calculated. A PVL assay for the HTLV-1c subtype that infects Indigenous Australians was developed and applied to this study. Clinical, radiological, and virological parameters were compared between groups and according to HTLV-1 serostatus. Results.  Human T-lymphotropic virus type 1 infection was the main predictor of bronchiectasis in a multivariable model (adjusted risk ratio [aRR], 1.84; 95% confidence interval [CI], 1.19–2.84; P = .006). Moreover, the median HTLV-1c PVL (interquartile range) for cases was >100-fold that of controls (cases, 0.319 [0.007, 0.749]; controls, 0.003 [0.000, 0.051] per 100 peripheral blood lymphocytes; P = .007), and HTLV-1c PVL were closely correlated with radiologically determined pulmonary injury scores (Spearman's rho = 0.7457; P = .0000). Other predictors of bronchiectasis were positive Strongyloides serology (aRR, 1.69; 95% CI, 1.13–2.53) and childhood skin infections (aRR, 1.62; 95% CI, 1.07–2.44). Bronchiectasis was the major predictor of death (aRR, 2.71; 95% CI, 1.36–5.39; P = .004). Conclusions.  These data strongly support an etiological association between HTLV-1 infection and bronchiectasis in a socially disadvantaged population at risk of recurrent lower respiratory tract infections

  7. Aging and Cardiac Fibrosis

    PubMed Central

    Biernacka, Anna; Frangogiannis, Nikolaos G

    2011-01-01

    The aging heart is characterized by morphological and structural changes that lead to its functional decline and are associated with diminished ability to meet increased demand. Extensive evidence, derived from both clinical and experimental studies suggests that the aging heart undergoes fibrotic remodeling. Age-dependent accumulation of collagen in the heart leads to progressive increase in ventricular stiffness and impaired diastolic function. Increased mechanical load, due to reduced arterial compliance, and direct senescence-associated fibrogenic actions appear to be implicated in the pathogenesis of cardiac fibrosis in the elderly. Evolving evidence suggests that activation of several distinct molecular pathways may contribute to age-related fibrotic cardiac remodeling. Reactive oxygen species, chemokine-mediated recruitment of mononuclear cells and fibroblast progenitors, transforming growth factor (TGF)-β activation, endothelin-1 and angiotensin II signaling mediate interstitial and perivascular fibrosis in the senescent heart. Reduced collagen degradation may be more important than increased de novo synthesis in the pathogenesis of aging-associated fibrosis. In contrast to the baseline activation of fibrogenic pathways in the senescent heart, aging is associated with an impaired reparative response to cardiac injury and defective activation of reparative fibroblasts in response to growth factors. Because these reparative defects result in defective scar formation, senescent hearts are prone to adverse dilative remodeling following myocardial infarction. Understanding the pathogenesis of interstitial fibrosis in the aging heart and dissecting the mechanisms responsible for age-associated healing defects following cardiac injury are critical in order to design new strategies for prevention of adverse remodeling and heart failure in elderly patients. PMID:21837283

  8. Epidemiology of Cystic Fibrosis.

    PubMed

    Spoonhower, Kimberly A; Davis, Pamela B

    2016-03-01

    Improved quality of care and rapidly emerging therapeutic strategies to restore chloride transport profoundly impact the epidemiology and pathobiology of cystic fibrosis (CF) in the twenty-first century. CF now serves as a model for chronic illness management, continuous quality improvement via registry data, and a seamless link between basic science research, translational studies, clinical trials, and outcomes research to enable rapid expansion of treatment options. PMID:26857763

  9. Experimental models of liver fibrosis.

    PubMed

    Crespo Yanguas, Sara; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research. PMID:26047667

  10. Experimental models of liver fibrosis

    PubMed Central

    Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2015-01-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research. PMID:26047667

  11. Genetics Home Reference: congenital hepatic fibrosis

    MedlinePlus

    ... Home Health Conditions congenital hepatic fibrosis congenital hepatic fibrosis Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Congenital hepatic fibrosis is a disease of the liver that is ...

  12. Cystic Fibrosis Therapeutics

    PubMed Central

    Ramsey, Bonnie W.

    2013-01-01

    A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco. PMID:23276843

  13. [Idiopathic Pulmonary Fibrosis].

    PubMed

    Prasse, A

    2015-10-01

    Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and a disease of the elderly. Cigarette smoking and longterm exposure to substances harming alveolar epithelial cells are risk factors for the development of IPF. There is also evidence for a genetic susceptibility. IPF is defined as the idiopathic variant of Usual Interstitial Pneumonitis (UIP). Diagnosis of IPF is complex and based on the exclusion of other diseases associated with an UIP pattern. The only cure is lung transplantation. In the last years there was a breakthrough in the treatment of IPF. With pirfenidone and nintedanib there are now two compounds approved for the treatment of IPF. PMID:26444136

  14. Adenosine in fibrosis

    PubMed Central

    Chan, Edwin S. L.

    2011-01-01

    Adenosine is an endogenous autocoid that regulates a multitude of bodily functions. Its anti-inflammatory actions are well known to rheumatologists since it mediates many of the anti-inflammatory effects of a number of antirheumatic drugs such as methotrexate. However, inflammatory and tissue regenerative responses are intricately linked, with wound healing being a prime example. It has only recently been appreciated that adenosine has a key role in tissue regenerative and fibrotic processes. An understanding of these processes may shed new light on potential therapeutic options in diseases such as scleroderma where tissue fibrosis features prominently. PMID:19949965

  15. [Polymethoxylated flavonoids activate cystic fibrosis transmembrane conductance regulator chloride channel].

    PubMed

    Cao, Huan-Huan; Fang, Fang; Yu, Bo; Luan, Jian; Jiang, Yu; Yang, Hong

    2015-04-25

    Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (HTF) which could potentiate CFTR chloride channel activities. The present study was aimed to investigate the potentiation effects of HMF and HTF on CFTR Cl(-) channel activities by using a cell-based fluorescence assay and the short circuit Ussing chamber assay. The results of cell-based fluorescence assay showed that both HMF and HTF could dose-dependently potentiate CFTR Cl(-) channel activities in rapid and reversible ways, and the activations could be reversed by the CFTR blocker CFTRinh-172. Notably, HMF showed the highest affinity (EC50 = 2 μmol/L) to CFTR protein among the flavonoid CFTR activators identified so far. The activation of CFTR by HMF or HTF was forskolin (FSK) dependent. Both compounds showed additive effect with FSK and 3-Isobutyl-1-methylx (IBMX) in the activation of CFTR, while had no additive effect with genistein (GEN). In ex vivo studies, HMF and HTF could stimulate transepithelial Cl(-) secretion in rat colonic mucosa and enhance fluid secretion in mouse trachea submucosal glands. These results suggest that HMF and HTF may potentiate CFTR Cl(-) channel activities through both elevation of cAMP level and binding to CFTR protein pathways. The results provide new clues in elucidating structure and activity relationship of flavonoid CFTR activators. HMF might be developed as a new drug in the therapy of CFTR-related diseases such as bronchiectasis and habitual constipation. PMID:25896054

  16. Evolving therapies for liver fibrosis

    PubMed Central

    Schuppan, Detlef; Kim, Yong Ook

    2013-01-01

    Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for liver that address specific cell types and functional units that orchestrate fibrotic wound healing responses and have a sound preclinical database or antifibrotic activity in early clinical trials. We also touch upon relevant clinical study endpoints, optimal study design, and developments in fibrosis imaging and biomarkers. PMID:23635787

  17. Phenotypic expression of the p.Leu1077Pro CFTR mutation in Sicilian cystic fibrosis patients

    PubMed Central

    2013-01-01

    Background The p.Leu1077Pro CFTR mutation was firstly described in 1992 as a mild allele that confers a pancreatic sufficiency phenotype but the information collected in database CFTR2 lead to consider p.Leu1077Pro as a severe CF mutation. Although it is typical of Southern Italy, p.Leu1077Pro is not included in the mutation panel firstly tested in individuals originated from this area. The aim of our study was to describe prevalence and clinical features in patients bearing this mutation followed in our Cystic Fibrosis Centre to demonstrate that this mutation should be included in the mutation panel firstly tested in patients originated from Southern Italy. Findings We reviewed data from a cohort of 111 cystic fibrosis patients. 4 patients who were heterozygous for the p.Leu1077Pro mutation were included in the study. In our Cystic Fibrosis Centre, the prevalence of p.Leu1077Pro is 3.6% among all mutations. All patients had positive sweat test values, pancreatic insufficiency and pulmonary exacerbations. One out of four patients even showed both FEV1 and FVC values significantly below the normal range, the presence of bronchiectasis and chronic Pseudomonas aeruginosa colonization. Conclusions We found that the p.Leu1077Pro CFTR mutation is associated with a classic CF phenotype confirming what is reported in CFTR2 database. The relatively high prevalence of p.Leu1077Pro associated with the severe clinical course of the disease in patients bearing this mutation is of interest for genetic counselling purposes, as it should be part of mutation panel to be tested in individuals originated from Southern Italy. PMID:24225052

  18. Chloride impermeability in cystic fibrosis

    NASA Astrophysics Data System (ADS)

    Quinton, Paul M.

    1983-02-01

    Cystic fibrosis is the most common fatal genetic disease affecting Caucasians and is perhaps best characterized as an exocrinopathy involving a disturbance in fluid and electrolyte transport1. A high NaCl concentration in the sweat is characteristic of patients with this disease; the basic physiological reason for this abnormality is unknown. We have microperfused isolated sweat ducts from control subjects and cystic fibrosis patients, and report here results which suggest that abnormally low Cl- permeability in cystic fibrosis leads to poor reabsorption of NaCl in the sweat duct, and hence to a high concentration of NaCl in the sweat.

  19. Epigenetic regulation in cardiac fibrosis

    PubMed Central

    Yu, Li-Ming; Xu, Yong

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this mini-review, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs. PMID:26635926

  20. Gastrointestinal Manifestations of Cystic Fibrosis

    PubMed Central

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  1. Neutrophils in cystic fibrosis.

    PubMed

    Laval, Julie; Ralhan, Anjali; Hartl, Dominik

    2016-06-01

    Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. Among inflammatory cells, neutrophils represent the major cell population accumulating in the airways of CF patients. While neutrophils provide the first defensive cellular shield against bacterial and fungal pathogens, in chronic disease conditions such as CF these short-lived immune cells release their toxic granule contents that cause tissue remodeling and irreversible structural damage to the host. A variety of human and murine studies have analyzed neutrophils and their products in the context of CF, yet their precise functional role and therapeutic potential remain controversial and incompletely understood. Here, we summarize the current evidence in this field to shed light on the complex and multi-faceted role of neutrophils in CF lung disease. PMID:26854289

  2. Idiopathic Pulmonary Fibrosis.

    PubMed

    Martin, Maria D; Chung, Jonathan H; Kanne, Jeffrey P

    2016-05-01

    Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease and is associated with a very poor prognosis. IPF manifests histopathologically as usual interstitial pneumonia (UIP) and as subpleural and basal predominant reticulation with honeycombing on high-resolution computed tomography (HRCT) of the chest. When a high-confidence radiologic diagnosis of UIP is made on HRCT, surgical biopsy is rarely required. Therefore, radiologists should recognize a UIP pattern on HRCT as well as recognize other patterns of fibrosing lung disease such as nonspecific interstitial pneumonia or chronic hypersensitivity pneumonitis, both of which can be mistaken for UIP. This article reviews the clinical, CT, and histopathologic features of IPF, discusses the impact of CT findings on prognosis, and describes complications associated with IPF. PMID:27043425

  3. [Rhinosinusitis in cystic fibrosis].

    PubMed

    Mainz, J G; Gerber, A; Arnold, C; Baumann, J; Baumann, I; Koitschev, A

    2015-11-01

    In cystic fibrosis (CF) mucociliary clearance of the entire respiratory system is impaired. This allows pathogens, such as Pseudomonas aeruginosa to persist and proliferate, which by progressive pulmonary destruction causes 90 % of premature deaths due to this inherited disease. The dramatic improvement in life expectation of patients due to intensive therapy has resulted in the inevitable but variably expressed sinonasal involvement coming into the clinical and scientific focus. Thereby, almost all CF patients reveal sinonasal pathology and many suffer from chronic rhinosinusitis. Recently, the sinonasal niche has been recognized as a site of initial and persistent colonization by pathogens. This article presents the pathophysiological background of this multiorgan disease as well as general diagnostic and therapeutic standards. The focus of this article is on sinonasal involvement and conservative and surgical options for treatment. Prevention of pathogen acquisition is an essential issue in the otorhinolaryngological treatment of CF patients. PMID:26495450

  4. Cystic fibrosis in pregnancy.

    PubMed Central

    Kent, N E; Farquharson, D F

    1993-01-01

    OBJECTIVE: To review the outcomes of pregnancies in women with cystic fibrosis (CF) and to address issues pertinent to the obstetric care of such women. DATA SOURCES: English-language case reports and case series published from 1960 to 1991 identified through a search of MEDLINE and Index Medicus. The terms of reference were "cystic fibrosis" and "pregnancy". Not all the reports reviewed addressed all the outcomes under consideration. STUDY SELECTION: A total of 20 reports citing cases of pregnancy in women with CF. DATA EXTRACTION: Outcomes included the number of spontaneous abortions, pregnancies continued beyond 20 weeks, preterm deliveries, maternal deaths at 6 months and 2 years after delivery and perinatal deaths. Breast-feeding was addressed. Measures to assess the severity of maternal disease included the mean age at diagnosis of CF, weight gain during pregnancy, pulmonary function studies if available and the need for pancreatic enzyme replacement therapy. DATA SYNTHESIS: Of 217 pregnancies in 162 women spontaneous abortion occurred in 10 (4.6%). Pregnancy progressed beyond 20 weeks in 81.6% of cases; 24.3% of the deliveries were preterm. The maternal death rate did not exceed that among age-related women with CF who were not pregnant. The rate of perinatal death was 7.9%. Breast milk was not hypernatremic. Poor outcomes were associated with a weight gain of less than 4.5 kg and a forced vital capacity of less than 50% of the predicted value. CONCLUSIONS: Premature labour and delivery remain a significant risk for pregnant women with CF, contributing to a high rate of perinatal death. Maternal illness and death result from deteriorating pulmonary function. Breast-feeding is not contraindicated. Attention to energy intake and pulmonary function is important. PMID:8374843

  5. Mechanisms of Lung Fibrosis Resolution.

    PubMed

    Glasser, Stephan W; Hagood, James S; Wong, Simon; Taype, Carmen A; Madala, Satish K; Hardie, William D

    2016-05-01

    Fibrogenesis involves a dynamic interplay between factors that promote the biosynthesis and deposition of extracellular matrix along with pathways that degrade the extracellular matrix and eliminate the primary effector cells. Opposing the often held perception that fibrotic tissue is permanent, animal studies and clinical data now demonstrate the highly plastic nature of organ fibrosis that can, under certain circumstances, regress. This review describes the current understanding of the mechanisms whereby the lung is known to resolve fibrosis focusing on degradation of the extracellular matrix, removal of myofibroblasts, and the role of inflammatory cells. Although there are significant gaps in understanding lung fibrosis resolution, accelerated improvements in biotechnology and bioinformatics are expected to improve the understanding of these mechanisms and have high potential to lead to novel and effective restorative therapies in the treatment not only of pulmonary fibrosis, but also of a wide-ranging spectrum of chronic disorders. PMID:27021937

  6. Steady Advances Against Cystic Fibrosis

    MedlinePlus

    ... age 2, he grew up playing everything from football and lacrosse to ice hockey and golf. And ... Who's at Risk? Cystic fibrosis affects males and females from all racial and ethnic groups. It is ...

  7. Genetics Home Reference: cystic fibrosis

    MedlinePlus

    ... protects the linings of the airways, digestive system, reproductive system, and other organs and tissues. In people with ... experience health problems affecting the respiratory, digestive, and reproductive systems. Most men with cystic fibrosis have congenital bilateral ...

  8. De novo deletion of HOXB gene cluster in a patient with failure to thrive, developmental delay, gastroesophageal reflux and bronchiectasis.

    PubMed

    Pajusalu, Sander; Reimand, Tiia; Uibo, Oivi; Vasar, Maire; Talvik, Inga; Zilina, Olga; Tammur, Pille; Õunap, Katrin

    2015-01-01

    We report a female patient with a complex phenotype consisting of failure to thrive, developmental delay, congenital bronchiectasis, gastroesophageal reflux and bilateral inguinal hernias. Chromosomal microarray analysis revealed a 230 kilobase deletion in chromosomal region 17q21.32 (arr[hg19] 17q21.32(46 550 362-46 784 039)×1) encompassing only 9 genes - HOXB1 to HOXB9. The deletion was not found in her mother or father. This is the first report of a patient with a HOXB gene cluster deletion involving only HOXB1 to HOXB9 genes. By comparing our case to previously reported five patients with larger chromosomal aberrations involving the HOXB gene cluster, we can suppose that HOXB gene cluster deletions are responsible for growth retardation, developmental delay, and specific facial dysmorphic features. Also, we suppose that bilateral inguinal hernias, tracheo-esophageal abnormalities, and lung malformations represent features with incomplete penetrance. Interestingly, previously published knock-out mice with targeted heterozygous deletion comparable to our patient did not show phenotypic alterations. PMID:25907420

  9. Cystic Fibrosis Sinusitis.

    PubMed

    Le, Christopher; McCrary, Hilary C; Chang, Eugene

    2016-01-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF transmembrane conductance regulator gene(CFTR) resulting in impaired ion transport. Nearly all people with CF will develop chronic rhino-sinusitis (CRS) and present with the characteristic viscous mucus, impaired mucociliary clearance and chronic inflammation/infection of the sinonasal cavity. While some individuals with CF can appear relatively asymptomatic in terms of their sinus disease, commonly reported symptoms include anosmia, headache, facial pain, nasal obstruction, chronic congestion and nasal discharge. Nasal endoscopy typically reveals mucosal edema, purulent discharge and nasal polyposis. Computed tomography (CT) imaging classically demonstrates the distinguishing findings of sinus hypoplasia or aplasia with generalized opacification, medial bulging of the lateral sinonasal sidewall and a demineralized uncinate process. Current treatment for CF sinusitis includes the use of hypertonic saline, topical and systemic steroids, antibiotics and endoscopic surgery. Research investigating novel therapies designed at targeting the primary defect of CF is showing promise for reversal of CF sinus disease, in addition to potential for disease prevention. PMID:27466844

  10. Mucolytics in cystic fibrosis.

    PubMed

    Henke, Markus O; Ratjen, Felix

    2007-03-01

    Mucus accumulation in the lower airways is a key feature of cystic fibrosis (CF) lung disease. The major component of mucus in CF is not mucin derived from mucus producing cells but rather pus that includes viscous material such as polymerized DNA derived from degraded neutrophils. This has important implications for mucolytic therapy aiming to improve mucus clearance from the airways, since degradation of mucin may not be a suitable treatment strategy. In addition, thinning of secretions may not always be beneficial, since it may negatively affect certain aspects of mucus transport such as cough clearance. While inhaled N-acetylcysteine has been used as a mucolytic drug in CF for decades, there is little evidence that it has any beneficial effect. Dornase alfa has been shown to reduce pulmonary exacerbations and improve lung function and is currently the only mucolytic agent with proven efficacy in CF. Newer agents targeting other components of CF mucus, such as filamentous actin, are currently in development. Ultimately, drugs that are mucokinetic, which preserve viscoelasticity, rather than mucolytic may prove to be beneficial for CF lung disease in the future. PMID:17419975

  11. Idiopathic Retroperitoneal Fibrosis.

    PubMed

    Vaglio, Augusto; Maritati, Federica

    2016-07-01

    Idiopathic retroperitoneal fibrosis (RPF), reviewed herein, is a rare fibro-inflammatory disease that develops around the abdominal aorta and the iliac arteries, and spreads into the adjacent retroperitoneum, where it frequently causes ureteral obstruction and renal failure. The clinical phenotype of RPF is complex, because it can be associated with fibro-inflammatory disorders involving other organs, is considered part of the spectrum of IgG4-related disease, and often arises in patients with other autoimmune conditions. Obstructive uropathy is the most common complication, although other types of renal involvement may occur, including stenosis of the renal arteries and veins, renal atrophy, and different types of associated GN. Environmental and genetic factors contribute to disease susceptibility, whereas the immunopathogenesis of RPF is mediated by different immune cell types that eventually promote fibroblast activation. The diagnosis is made on the basis of computed tomography or magnetic resonance imaging, and positron emission tomography is a useful tool in disease staging and follow-up. Treatment of idiopathic RPF aims at relieving ureteral obstruction and inducing disease regression, and includes the use of glucocorticoids, combined or not with other traditional immunosuppressants. However, biologic therapies such as the B cell-depleting agent rituximab are emerging as potentially efficacious agents in difficult-to-treat cases. PMID:26860343

  12. Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis

    PubMed Central

    O’Reilly, Ruth; Elphick, Heather E

    2013-01-01

    Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ∆F508) would allow 90% of the CF population to benefit from disease-modifying treatment. PMID:24039402

  13. The activin A antagonist follistatin inhibits cystic fibrosis-like lung inflammation and pathology

    PubMed Central

    Hardy, Charles L; King, Susannah J; Mifsud, Nicole A; Hedger, Mark P; Phillips, David J; Mackay, Fabienne; de Kretser, David M; Wilson, John W; Rolland, Jennifer M; O'Hehir, Robyn E

    2015-01-01

    Cystic fibrosis (CF) is the most common life-limiting genetically acquired respiratory disorder. Patients with CF have thick mucus obstructing the airways leading to recurrent infections, bronchiectasis and neutrophilic airway inflammation culminating in deteriorating lung function. Current management targets airway infection and mucus clearance, but despite recent advances in care, life expectancy is still only 40 years. We investigated whether activin A is elevated in CF lung disease and whether inhibiting activin A with its natural antagonist follistatin retards lung disease progression. We measured serum activin A levels, lung function and nutritional status in CF patients. We studied the effect of activin A on CF lung pathogenesis by treating newborn CF transgenic mice (β-ENaC) intranasally with the natural activin A antagonist follistatin. Activin A levels were elevated in the serum of adult CF patients, and correlated inversely with lung function and body mass index. Follistatin treatment of newborn β-ENaC mice, noted for respiratory pathology mimicking human CF, decreased the airway activin A levels and key features of CF lung disease including mucus hypersecretion, airway neutrophilia and levels of mediators that regulate inflammation and chemotaxis. Follistatin treatment also increased body weight and survival of β-ENaC mice, with no evidence of local or systemic toxicity. Our findings demonstrate that activin A levels are elevated in CF and provide proof-of-concept for the use of the activin A antagonist, follistatin, as a therapeutic in the long-term management of lung disease in CF patients. PMID:25753271

  14. Angiogenesis and experimental hepatic fibrosis.

    PubMed

    Lemos, Queli Teixeira; Andrade, Zilton A

    2010-08-01

    Angiogenesis is a basic change occurring during repair by granulation tissue. This process seems to precede fibrosis formation in most types of chronic liver disease. To examine its presence and significance in different types of hepatic insults, this paper sought to identify the presence, evolution and peculiarities of angiogenesis in the most common experimental models of hepatic fibrosis. The characterization of cells, vessels and extracellular matrix and the identification of factors associated with endothelium (factor VIII RA), vascular basement membrane, other components of the vascular walls (actin, elastin) and the presence of the vascular-endothelial growth factor were investigated. The models examined included Capillaria hepatica septal fibrosis, whole pig serum injections, carbon tetrachloride administration, main bile duct ligation and Schistosoma mansoni infection. The first four models were performed in rats, while the last used mice. All models studied exhibited prominent angiogenesis. The most evident relationship between angiogenesis and fibrosis occurred with the C. hepatica model due to circumstances to be discussed. Special attention was paid to the presence of pericytes and to their tendency to become detached from the vascular wall and be transformed into myofibroblasts, which is a sequence of events that explains the decisive role angiogenesis plays in fibrosis. PMID:20835605

  15. How Is Idiopathic Pulmonary Fibrosis Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Idiopathic Pulmonary Fibrosis Treated? Doctors may prescribe medicines, oxygen therapy , pulmonary ... PR), and lung transplant to treat idiopathic pulmonary fibrosis (IPF). Medicines Currently, no medicines are proven to ...

  16. Quantification of portal-bridging fibrosis area more accurately reflects fibrosis stage and liver stiffness than whole fibrosis or perisinusoidal fibrosis areas in chronic hepatitis C.

    PubMed

    Sandrini, Jérémy; Boursier, Jérôme; Chaigneau, Julien; Sturm, Nathalie; Zarski, Jean-Pierre; Le Bail, Brigitte; de Ledinghen, Victor; Calès, Paul; Rousselet, Marie-Christine

    2014-07-01

    Morphometry provides an objective evaluation of fibrosis in liver diseases. We developed an image analysis algorithm using automated thresholding and segmentation to separately quantify the areas and the fractal dimensions of portal-bridging fibrosis and perisinusoidal fibrosis in chronic hepatitis C liver biopsies. We studied 427 digitized liver biopsies and compared the automated measures of the different fibrosis compartments with (1) the Metavir F (fibrosis) and A (activity) histological scores, (2) the digitally assessed area of steatosis, and (3) the liver stiffness measured by elastography (Fibroscan). The perisinusoidal fibrosis area was higher than that of portal fibrosis in stages ≤F2; it reached its highest value in F2 stage and stabilized thereafter. The F3 stage was characterized by equal proportions of portal-bridging and perisinusoidal fibrosis, whereas portal-bridging area was predominant in cirrhosis. Measurement of portal-bridging fibrosis showed highly significantly different values between contiguous F stages; the ratio of portal-bridging fibrosis/perisinusoidal fibrosis displayed less overlap between Metavir stages than did the whole fibrosis area values. Fractal dimension showed that portal-bridging fibrosis tended to display a homogeneous surface-like spatial organization, whereas perisinusoidal fibrosis appeared more heterogeneous according to stage and curvilinear. The portal-bridging fibrosis area was low in cases with low Metavir activity and little steatosis, and became predominant with increasing activity and steatosis. Using stepwise multiple linear regression analysis, the liver stiffness was independently correlated to the portal-bridging fibrosis area (first step, P<0.001), the steatosis area (second step, P<0.001), and the Metavir A grade (third step, P=0.001), but not to the perisinusoidal fibrosis area. Automated quantification in a large cohort of chronic hepatitis C showed that perisinusoidal fibrosis progressively grew in

  17. Mediastinal fibrosis presenting as asthma.

    PubMed

    Chantaphakul, H; Rock, M J; Steiner, D S; Gern, J E

    1998-01-01

    Asthma is one of the most common chronic medical conditions affecting children. The usual presenting symptoms of asthma include wheezing, shortness of breath, and dyspnea on exertion. Occasionally, children who present with one of these respiratory complaints have a less common disorder. Mediastinal fibrosis is a rare and incurable condition in which an excessive fibrotic reaction in the mediastinum causes progressive cardiopulmonary compromise. The presentation is variable: many patients present with respiratory symptoms such as cough, wheezing, dyspnea, and/or hemoptysis, while others are asymptomatic and present with a mediastinal mass discovered incidentally on a radiograph. With such a broad array of presenting complaints, and a clinical course characterized by slow progression of symptoms, the early stages of mediastinal fibrosis can mimic other diseases such as asthma, chronic bronchitis, or the superior vena cava syndrome. In this report we describe two patients with mediastinal fibrosis who were initially thought to have asthma. PMID:9642434

  18. PAI-1 in Tissue Fibrosis

    PubMed Central

    Ghosh, Asish K.; Vaughan, Douglas E.

    2011-01-01

    1. Summary Fibrosis is defined as a fibroproliferative or abnormal fibroblast activation–related disease., Deregulation of wound healing leads to hyperactivation of fibroblasts and excessive accumulation of extracellular matrix (ECM) proteins in the wound area, the pathological manifestation of fibrosis. The accumulation of excessive levels of collagen in the extracellular matrix depends on two factors: an increased rate of collagen synthesis and or decreased rate of collagen degradation by cellular proteolytic activities. The urokinase-type/tissue-type plasminogen activator (uPA/tPA) and plasmin play significant roles in the cellular proteolytic degradation of ECM proteins and the maintenance of tissue homeostasis. The activities of uPA/tPA/plasmin and plasmin-dependent MMPs rely mostly on the activity of a potent inhibitor of uPA/tPA, plasminogen activator inhibitor-1 (PAI-1). Under normal physiologic conditions, PAI-1 controls the activities of uPA/tPA/plasmin/MMP proteolytic activities and thus maintains the tissue homeostasis. During wound healing, elevated levels of PAI-1 inhibit uPA/tPA/plasmin and plasmin-dependent MMP activities and thus help expedite wound healing. In contrast to this scenario, under pathologic conditions, excessive PAI-1 contributes to excessive accumulation of collagen and other ECM protein in the wound area and thus preserves scarring. While the level of PAI-1 is significantly elevated in fibrotic tissues, lack of PAI-1 protects different organs from fibrosis in response to injury-related profibrotic signals. Thus PAI-1 is implicated in the pathology of fibrosis in different organs including the heart, lung, kidney, liver and skin. Paradoxically, PAI-1 deficiency promotes spontaneous cardiac-selective fibrosis. In this review we discuss the significance of PAI-1 in the pathogenesis of fibrosis in multiple organs. PMID:21465481

  19. [Historical compilation of cystic fibrosis].

    PubMed

    Navarro, Salvador

    2016-01-01

    Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. PMID:26070393

  20. Fibrosis and Adipose Tissue Dysfunction

    PubMed Central

    Sun, Kai; Tordjman, Joan; Clément, Karine; Scherer, Philipp E.

    2013-01-01

    Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent pro-fibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart and kidney. Here, we discuss recent advances in our understanding of the genesis, modulation and systemic impact of excessive extracellular matrix (ECM) accumulation in adipose tissue of both rodents and humans and the ensuing impact on metabolic dysfunction. PMID:23954640

  1. Diagnostic Testing in Cystic Fibrosis.

    PubMed

    Brewington, John; Clancy, J P

    2016-03-01

    Cystic Fibrosis (CF) is a rare, multisystem disease leading to significant morbidity and mortality. CF is caused by defects in the cystic fibrosis transmembrane conductance regulator protein (CFTR), a chloride and bicarbonate transporter. Early diagnosis and access to therapies provides benefits in nutrition, pulmonary health, and cognitive ability. Several screening and diagnostic tests are available to support a diagnosis. We discuss the characteristics of screening and diagnostic tests for CF and guideline-based algorithms using these tools to establish a diagnosis. We discuss classification and management of common "diagnostic dilemmas," including the CFTR-related metabolic syndrome and other CFTR-associated diseases. PMID:26857766

  2. A randomised controlled crossover trial of nurse practitioner versus doctor led outpatient care in a bronchiectasis clinic

    PubMed Central

    Sharples, L; Edmunds, J; Bilton, D; Hollingworth, W; Caine, N; Keogan, M; Exley, A

    2002-01-01

    Background: With the decrease in junior doctor hours, the advent of specialist registrars, and the availability of highly trained and experienced nursing personnel, the service needs of patients with chronic respiratory diseases attending routine outpatient clinics may be better provided by appropriately trained nurse practitioners. Methods: A randomised controlled crossover trial was used to compare nurse practitioner led care with doctor led care in a bronchiectasis outpatient clinic. Eighty patients were recruited and randomised to receive 1 year of nurse led care and 1 year of doctor led care in random order. Patients were followed up for 2 years to ensure patient safety and acceptability and to assess differences in lung function. Outcome measures were forced expiratory volume in 1 second (FEV1), 12 minute walk test, health related quality of life, and resource use. Results: The mean difference in FEV1 was 0.2% predicted (95% confidence interval –1.6 to 2.0%, p=0.83). There were no significant differences in the other clinical or health related quality of life measures. Nurse led care resulted in significantly increased resource use compared with doctor led care (mean difference £1497, 95% confidence interval £688 to £2674, p<0.001), a large part of which resulted from the number and duration of hospital admissions. The mean difference in resource use was greater in the first year (£2625) than in the second year (£411). Conclusions: Nurse practitioner led care for stable patients within a chronic chest clinic is safe and is as effective as doctor led care, but may use more resources. PMID:12149523

  3. [Fibrosis of the pelvic floor].

    PubMed

    Beernaerts, A; Hirsch, F

    1984-01-01

    A pelvic pain is sometimes extremely difficult to define and to treat. The origin of this pain was said to be due to either neurological, psychosomatic, urological or orthopaedic factors. It was in fact an unilateral fibrosis of the perineal transverse muscle. A surgical section has definitively cured the patient. PMID:6539549

  4. Cutaneous manifestations of cystic fibrosis.

    PubMed

    Bernstein, Megan L; McCusker, Meagen M; Grant-Kels, Jane M

    2008-01-01

    Cystic fibrosis is an autosomal recessive disease reported in 1 in 2500 live births in Northern American and Northern European Caucasian populations. Classic disease findings include chronic bacterial infection of airways and sinuses, malabsorption of fat, infertility in men, and elevated concentrations of chloride in sweat. Less well-recognized findings associated with cystic fibrosis include cutaneous findings, which can be primary or secondary manifestations of the disease process. Patients demonstrate more atopic and drug hypersensitivity reactions than the general population, but have similar rates of urticaria compared with the general population. In atypical presentations of cystic fibrosis, the nutrient deficiency dermatitis of the disease may aid with diagnosis, and notably can be the presenting sign. Other dermatologic manifestations of cystic fibrosis include early aquagenic skin wrinkling and cutaneous vasculitis, which can be associated with arthralgias. Familiarity with the nutrient deficiency dermatitis of this entity may play a role in the timely diagnosis of the disease, and the other cutaneous findings add to our understanding of the protean nature of its manifestations. PMID:18429769

  5. [Therapeutic update in cystic fibrosis].

    PubMed

    Durupt, S; Nove Josserand, R; Durieu, I

    2014-06-01

    We present the recent therapeutic advances in the cystic fibrosis care. It concerns improvements in symptomatic treatment with the development of dry powder inhaled antibiotics that improved quality of life, and innovative treatments namely the modulators of the cystic fibrosis transmembrane protein conductance regulator (CFTR), molecules which act specifically at the level of the defective mechanisms implied in the disease. The life expectancy of cystic fibrosis patients born after 2000, is estimated now to be about 50 years. This improvement of survival was obtained with the organization of the care within the specialized centers for cystic fibrosis (Centre de ressource et de compétences de la mucoviscidose) and remains still based on heavy symptomatic treatments. Dry powder inhaled antibiotics constitute a significant time saving for patients to whom all the care can achieve two hours daily. Since 2012, the modulators of CFTR, molecules allowing a pharmacological approach targeted according to the type of the mutations, allows a more specific approach of the disease. Ivacaftor (Kalydeco(®)) which potentialises the function of the CFTR protein expressed on the cellular surface is now available for patients with the G551D mutation. Lumacaftor is going to be tested in association with ivacaftor in patients with the F508del mutation, that is present in at least 75% of the patients. The ataluren which allows the production of a functional protein CFTR in patients with a no sense mutation is the third representing of this new therapeutic class. We presently have numerous symptomatic treatments for the cystic fibrosis care. The development of CFTR modulators, today available to a restricted number of patients treated with ivacaftor represents a very promising therapeutic avenue. It will represent probably the first step to a personalized treatment according to CFTR genotype. PMID:24309546

  6. [Mechanism of and Therapy for Kidney Fibrosis].

    PubMed

    Kuma, Akihiro; Tamura, Masahito; Otsuji, Yutaka

    2016-03-01

    Fibrosis occurs in systemic tissues other than the brain and finally induces dysfunction of the fibrotic organ. Kidney fibrosis is related to scarring after acute kidney injury and the progression of chronic kidney disease. Kidney function decreases with the progression of kidney fibrosis. As fibrotic tissue cannot return to its original status, advanced kidney fibrosis requires the administration of dialysis or kidney transplantation. Thus, elucidation the mechanism of kidney fibrosis is an important research theme. The proliferation and activation of (myo) fibroblasts and the excessive production of an extracellular matrix are common mechanisms in fibrosis in many organs, but it seems that kidney fibrosis has specific pathways. Tubular epithelial, mesangial cells, and erythropoietin producing cells, which exist only in the kidney, participate in forming kidney fibrosis. This review highlights an understanding of the cells and their underlying mechanisms, which are specific to kidney fibrosis process: transforming growth factor-β (TGF-β), epithelial-mesenchymal transition, wingless/int-1 (WNT) signaling, renal anemia, and uremia. Finally, we describe potential therapies that focus on the mechanisms of kidney fibrosis: anti-TGF-β antibody and mammalian target of rapamycin (mTOR). PMID:26972942

  7. Oesophageal subepithelial fibrosis: an extension of oral submucosal fibrosis.

    PubMed

    Misra, S P; Misra, V; Dwivedi, M; Gupta, S C

    1998-12-01

    Fifty-five patients with oral submucosal fibrosis and an equal number of patients with no evidence of the disease were studied. All patients underwent upper gastrointestinal endoscopy and any abnormality was noted. Multiple oesophageal biopsies were obtained from the upper end of the oesophagus and from any endoscopically observed abnormality. The histological changes in the two groups were assessed blindly by an experienced histopathologist. Histological abnormalities were noted in the oesophageal mucosa in 2% of controls and 66% of patients with oral submucosal fibrosis (p < 0.0001). In the control group, acanthosis was seen in one patient, while in the patient group atrophy of the squamous epithelium was evident in 52%, hyperkeratosis in 52%, parakeratosis in 30%, dyskeratosis in 14%, acanthosis in 14%, and papillomatosis and mild dysplasia in 2% patients. Subepithelial collagenization was seen in 32 (64%) patients. The oesophageal abnormalities were seen more frequently in patients who had consumed Pan masala, Gutka, betel nut, tobacco or a combination of some or all of these, with or without betel leaf, for > or = 5 years compared to those consuming them for a shorter period of time (91% vs 46%, p < 0.001). It is concluded that oral submucosal fibrosis is not a disease confined to the oral cavity; the oesophagus may also be involved in about two-thirds of patients. PMID:10320888

  8. [Morbus Ormond (idiopatic retroperitoneal fibrosis)].

    PubMed

    Michaligová, A; Plank, L; Jezíková, A; Manka, V; Makovický, P; Mokán, M

    2011-05-01

    Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of fibrotic tissue around the abdominal aorta and iliac arteries and often involves structures as ureters and the inferior vena cava. The age at onset of signs and symptoms is between 40-60 years, males predominane over females. In most cases the clinical manifestation is presented as compressive syndrom of ureters, therefore the first known cases were described by urologists. In this report we present the case of 37-years old male examinated for persistent fever about 38 degrees C and high inflammatory activity in spite of empiric antibiotic therapy. Positron emission tomography (PET) showed locality of high metabolic activity of fluorodeoxyglucose with maximum paraaortal left. Microscopic examination of extracted mass showed presence of fibrous and inflammatory components. With clinical presentation, imaging and histological findings we made out the diagnosis of idiopathic retroperitoneal fibrosis--morbus Ormond. PMID:21695934

  9. Pharmacogenetics of cystic fibrosis treatment.

    PubMed

    Carter, Suzanne C; McKone, Edward F

    2016-08-01

    Cystic fibrosis (CF) is genetic autosomal recessive disease caused by reduced or absent function of CFTR protein. Treatments for patients with CF have primarily focused on the downstream end-organ consequences of defective CFTR. Since the discovery of the CFTR gene that causes CF in 1989 there have been tremendous advances in our understanding of the genetics and pathophysiology of CF. This has recently led to the development of new CFTR mutation-specific targeted therapies for select patients with CF. This review will discuss the characteristics of the CFTR gene, the CFTR mutations that cause CF and the new mutation specific pharmacological treatments including gene therapy that are contributing to the dawning of a new era in cystic fibrosis care. PMID:27490265

  10. [Cystic fibrosis and associated complications].

    PubMed

    Schwarz, C; Staab, D

    2015-03-01

    Cystic fibrosis (CF) is an autosomal recessive inherited metabolic disease. The mutation is located on the long arm of chromosome 7. Due to a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, chloride ion transport is reduced across the cell membrane. As a result, the disease can be described as an exocrinopathy. In all organs with exocrine glands, disorders occur in association with the defective chloride transport. The main impact of this defect is manifested in the lungs. Therefore, the most common cause of death is pulmonary disease with respiratory insufficiency due to recurrent infections. Unfortunately, a cure for the disease is still not available. However, new therapies that may affect the CFTR mutation more specifically give new hope for better therapeutic options in the future. The long-term goal of therapy is to develop a causal therapy for all six different mutation classes and thus for about 2000 mutations. PMID:25693903

  11. Hepatic fibrosis in Kabuki syndrome.

    PubMed

    Nobili, Valerio; Marcellini, Matilde; Devito, Rita; Capolino, Rossella; Viola, Laura; Digilio, M Cristina

    2004-01-15

    Kabuki (Niikawa-Kuroki) syndrome (KS) is characterized by a distinctive face, mental retardation, growth deficiency, skeletal anomalies, dermatoglyphic abnormalities, palatal anomalies, congenital heart defects, and urogenital malformations. Congenital hepatic abnormalities have been sporadically described in patients with KS from the literature, consisting of extrahepatic biliary atresia, neonatal sclerosing cholangitis, and severe neonatal jaundice. We report here on an additional patient with a congenital abnormality of the liver consisting of hepatic fibrosis. To our knowledge, idiopathic congenital hepatic fibrosis has not been reported in KS. Thus, our observation expands the spectrum of liver malformations found in KS with the inclusion of hepatic fibrosis and supports the evidence that hepatic abnormalities may not be uncommon in KS. Clinician should be advised to search for the specific facial anomalies of KS in patients with syndromic congenital hepatic diseases, and KS should be added to the list of previously recognized multiple congenital anomaly syndromes with hepatic involvement. Due to the frequent association with congenital heart malformations, KS should be considered in the evaluation of patients with neonatal liver disease and cardiac malformation. Due to the expression patterns of Notch genes, involvement of the Notch signaling pathway in the development of heart and liver anomalies in KS should be considered. PMID:14699623

  12. Liver fibrosis markers in alcoholic liver disease

    PubMed Central

    Chrostek, Lech; Panasiuk, Anatol

    2014-01-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  13. Swine flu fibrosis: Regressive or progressive?

    PubMed

    Singh, Nishtha; Singh, Sheetu; Sharma, Bharat Bhushan; Singh, Virendra

    2016-01-01

    Swine flu influenza had spread the world over in 2009. The main pathology was bilateral pneumonia. Majority of these cases recovered from pneumonia fully. Though in some cases, pulmonary fibrosis was reported as a sequel. However, long-term progression of such pulmonary fibrosis is uncertain. We are hereby reporting two cases of swine flu that showed residual pulmonary fibrosis. The clinical and laboratory parameters were also recorded. In both the cases, radiological shadows and spirometric values did not show deterioration. We conclude that swine flu pulmonary fibrosis is not a progressive condition. PMID:27051116

  14. Novel biomarkers of fibrosis in Crohn's disease.

    PubMed

    Pellino, Gianluca; Pallante, Pierlorenzo; Selvaggi, Francesco

    2016-08-15

    Fibrosis represents a major challenge in Crohn's disease (CD), and many CD patients will develop fibrotic strictures requiring treatment throughout their lifetime. There is no drug that can reverse intestinal fibrosis, and so endoscopic balloon dilatation and surgery are the only effective treatments. Since patients may need repeated treatments, it is important to obtain the diagnosis at an early stage before strictures become symptomatic with extensive fibrosis. Several markers of fibrosis have been proposed, but most need further validation. Biomarkers can be measured either in biological samples obtained from the serum or bowel of CD patients, or using imaging tools and tests. The ideal tool should be easily obtained, cost-effective, and reliable. Even more challenging is fibrosis occurring in ulcerative colitis. Despite the important burden of intestinal fibrosis, including its detrimental effect on outcomes and quality of life in CD patients, it has received less attention than fibrosis occurring in other organs. A common mechanism that acts via a specific signaling pathway could underlie both intestinal fibrosis and cancer. A comprehensive overview of recently introduced biomarkers of fibrosis in CD is presented, along with a discussion of the controversial areas remaining in this field. PMID:27574564

  15. Interaction and Localization of Synthetic Nanoparticles in Healthy and Cystic Fibrosis Airway Epithelial Cells: Effect of Ozone Exposure

    PubMed Central

    Raemy, David O.; Loader, Joan E.; Kailey, Jenai M; Neeves, Keith B.; White, Carl W.; Ahmad, Aftab; Gehr, Peter; Rothen-Rutishauser, Barbara M.

    2012-01-01

    Abstract Background Nanoparticles (NPs) produced by nanotechnology processes have taken the field of medicine by storm. Concerns about safety of these NPs in humans, however, have recently been raised. Although studies of NP toxicity have focused on lung disease the mechanistic link between NP exposure and lung injury remained unclear. This is primarily due to a lack of availability of appropriate airway disease models and sophisticated microscopic techniques to study nano-sized particulate delivery and resulting responses. Methods Air–liquid interface (ALI) cultures of non-cystic fibrosis (CF) and CF airway epithelial cells were exposed to the FITC-labeled NPs using a PennCentury microsprayer™. Uptake of NPs was assessed by FACS. Laser scanning microscopy (LSM) was performed and the images were analyzed by an advanced imaging software to study particle deposition and uptake. Results Flow cytometry data revealed that CF cells accumulated increased amounts of NPs. The increased NP uptake could be attributed to the reduced CF transmembrane conductance regulator (CFTR) function as a similar increased retention/uptake was observed in cells whose CFTR expression was downregulated by antisense oligonucleotide. NPs alone did not induce pro-inflammatory cytokine release or cell death. The cell culture system was sensitive to ozone but exposure to the uncoated synthetic NPs used in this study, did not cause any synergistic or suppressive effects. LSM imaging and subsequent image restoration further indicated particle uptake and intracellular localization. Exposure to ozone increased nuclear uptake in both non-CF and CF cells. Conclusion Our findings demonstrate the uptake of NPs using ALI cultures of non-CF and CF airway epithelial cells. The NPs used here were useful in demonstrating uptake by airway epithelial cells without causing adverse effects in presence or absence of ozone. However, to totally exclude toxic effects, chronic studies under in vivo conditions using

  16. How Is Bronchiectasis Treated?

    MedlinePlus

    ... Remove mucus (a slimy substance) from your lungs. Maintaining good hydration helps with mucus removal. Prevent complications. ... home, in a hospital, or in another health facility. (For more information, go to the Health Topics ...

  17. Biliary complications of cystic fibrosis.

    PubMed Central

    O'Brien, S; Keogan, M; Casey, M; Duffy, G; McErlean, D; Fitzgerald, M X; Hegarty, J E

    1992-01-01

    One hundred and four adult patients with cystic fibrosis were evaluated for the presence of liver disease as defined by abnormal liver function tests of six months' duration, histological evidence of fibrosis or cirrhosis, or the presence of portal hypertension, or both. Twenty patients fulfilled these criteria and were evaluated further for the presence of biliary tract abnormalities with biliary scintigraphy using 99Tc diisopropylphenyl-carboxymethyl iminodiacetic acid (DISIDA) and endoscopic retrograde cholangiography. Clearance of 99Tc DISIDA from the liver and biliary tree was diminished at 45 (E45) and 60 (E60) minutes in the patients with liver disease compared with those without liver disease; E45 = 37.8% and 65.8%, p less than 0.01; E60 = 48.2% and 77.5%, p less than 0.01 respectively. Serial analogue images of the extrahepatic biliary tree were consistent with common bile duct obstruction with retention of DISIDA and tapering of the common bile duct in seven of 18 patients with and two of 10 patients without liver disease. Endoscopic retrograde cholangiography showed changes consistent with sclerosing cholangitis, with beading and stricturing of the intrahepatic ducts in 12 of the 14 patients. In all 14 patients, including those in whom biliary scintigraphy had suggested obstruction, no abnormality of the common bile duct was identified. These results indicate that abnormalities of the bile ducts in patients with cystic fibrosis related liver disease are confined to the intrahepatic biliary tree and that common bile duct strictures do not contribute to either the progression or development of liver disease in these patients. Images Figure 2 PMID:1568661

  18. Development of cystic fibrosis and noncystic fibrosis airway cell lines.

    PubMed

    Zabner, Joseph; Karp, Phil; Seiler, Michael; Phillips, Stacia L; Mitchell, Calista J; Saavedra, Mimi; Welsh, Michael; Klingelhutz, Aloysius J

    2003-05-01

    In this study, we utilized the reverse transcriptase component of telomerase, hTERT, and human papillomavirus type 16 (HPV-16) E6 and E7 genes to transform normal and cystic fibrosis (CF) human airway epithelial (HAE) cells. One cell line, designated NuLi-1 (normal lung, University of Iowa), was derived from HAE of normal genotype; three cell lines, designated CuFi (cystic fibrosis, University of Iowa)-1, CuFi-3, and CuFi-4, were derived from HAE of various CF genotypes. When grown at the air-liquid interface, the cell lines were capable of forming polarized differentiated epithelia that exhibited transepithelial resistance and maintained the ion channel physiology expected for the genotypes. The CF transmembrane conductance regulator defect in the CuFi cell lines could be corrected by infecting from the basolateral surface using adenoviral vectors. Using nuclear factor-kappaB promoter reporter constructs, we also demonstrated that the NuLi and CuFi cell lines retained nuclear factor-kappaB responses to lipopolysaccharide. These cell lines should therefore be useful as models for studying ion physiology, therapeutic intervention for CF, and innate immunity. PMID:12676769

  19. Endocrine Disorders in Cystic Fibrosis.

    PubMed

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. PMID:27469183

  20. Pancreatic pathophysiology in cystic fibrosis.

    PubMed

    Gibson-Corley, Katherine N; Meyerholz, David K; Engelhardt, John F

    2016-01-01

    The pancreas is one of the earliest, and most commonly affected, organs in patients with cystic fibrosis (CF). Studying the pathogenesis of pancreatic disease is limited in CF patients, due to its early clinical onset, co-morbidities and lack of tissue samples from the early phases of disease. In recent years, several new CF animal models have been developed that have advanced our understanding of both CF exocrine and endocrine pancreatic disease. Additionally, these models have helped us to better define the influence of pancreatic lesions on CF disease progression in other organs, such as the gastrointestinal tract and lung. PMID:26365583

  1. Pulmonary complications of cystic fibrosis.

    PubMed

    Ng, M Y; Flight, W; Smith, E

    2014-03-01

    The life expectancy of patients with cystic fibrosis (CF) has steadily increased over recent decades with a corresponding increase in the frequency of complications of the disease. Radiologists are increasingly involved with managing and identifying the pulmonary complications of CF. This article reviews the common manifestations of CF lung disease as well as updating radiologists with a number of less well-known complications of the condition. Early and accurate detection of the pulmonary effects of CF are increasingly important to prevent irreversible lung damage and give patients the greatest possibility of benefiting from the new therapies becoming available, which correct the underlying defect causing CF. PMID:24361142

  2. Nintedanib in idiopathic pulmonary fibrosis.

    PubMed

    Woodcock, H V; Maher, T M

    2015-06-01

    Idiopathic pulmonary fibrosis (IPF) conveys a median survival of 3 years and until recently has lacked effective therapies. Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. This monograph explores the preclinical rationale for the antifibrotic role of nintedanib and provides an overview of the available data on pharmacokinetics, efficacy and safety. PMID:26261848

  3. Cystic fibrosis presenting with bilateral facial palsy.

    PubMed

    Basu, Anna P; Kumar, Prashant; Devlin, Anita M; O'Brien, Christopher J

    2007-07-01

    A 15-week old male infant presented with bilateral lower motor neuron facial palsy of unknown cause. Subsequently his growth deteriorated and he developed progressively worsening cough and wheeze. A diagnosis of cystic fibrosis was confirmed and hypovitaminosis A detected. Improvement of the facial palsy was noted following standard management of cystic fibrosis including vitamin A supplementation. PMID:17287135

  4. A combination therapy for cystic fibrosis.

    PubMed

    Brodsky, Jeffrey L; Frizzell, Raymond A

    2015-09-24

    The most prevalent form of cystic fibrosis arises from an amino acid deletion in the cystic fibrosis transmembrane conductance regulator, CFTR. A recently approved treatment for individuals homozygous for this mutation combines a chemical corrector, which helps CFTR fold, and a potentiator that increases CFTR channel activity. PMID:26406363

  5. [Non-invasive assessment of liver fibrosis].

    PubMed

    Cohen-Ezra, Oranit; Ben-Ari, Ziv

    2015-03-01

    Chronic liver diseases represent a major public health problem, accounting for significant morbidity and mortality worldwide. Prognosis and management of chronic liver diseases depend on the amount of liver fibrosis. Liver biopsy has long remained the gold standard for assessment of liver fibrosis. Liver biopsy is an invasive procedure with associated morbidity, it is rarely the cause for mortality, and has a few limitations. During the past two decades, in an attempt to overcome the limitations of liver biopsy, non-invasive methods for the evaluation of liver fibrosis have been developed, mainly in the field of viral hepatitis. This review will focus on different methods available for non-invasive evaluation of liver fibrosis including a biological approach which quantifies serum levels of biomarkers of fibrosis and physical techniques which measure liver stiffness by transient elastography, ultrasound or magnetic resonance based elastography, their accuracy, advantages and disadvantages. PMID:25962254

  6. Minerals, fibrosis, and the lung.

    PubMed Central

    Heppleston, A G

    1991-01-01

    Determinants of pulmonary fibrosis induced by inhaled mineral dusts include quantity retained, particle size, and surface area, together with their physical form and the reactive surface groups presented to alveolar cells. The outstanding problem is to ascertain how these factors exert their deleterious effects. Both compact and fibrous minerals inflict membrane damage, for which chemical mechanisms still leave uncertainty. A major weakness of cytotoxicity studies, even when lipid peroxidation and reactive oxygen species are considered, lies in tacitly assuming that membrane damage suffices to account for fibrogenesis, whereas the parallel occurrence of such manifestations does not necessarily imply causation. The two-phase procedure established that particles, both compact and fibrous, induce release of a macrophage factor that provokes fibroblasts into collagen synthesis. The amino acid composition of the macrophage fibrogenic factor was characterized and its intracellular action explained. Fibrous particles introduce complexities respecting type, durability, and dimensions. Asbestotic fibrosis is believed to depend on long fibers, but scrutiny of the evidence from experimental and human sources reveals that a role for short fibers needs to be entertained. Using the two-phase system, short fibers proved fibrogenic. Other mechanisms, agonistic and antagonistic, may participate. Growth factors may affect the fibroblast population and collagen production, with cytokines such as interleukin-1 and tumor necrosis factor exerting control. Immune involvement is best regarded as an epiphenomenon. Downregulation of fibrogenesis may follow collagenase release from macrophages and fibroblasts, while augmented type II cell secretion of lipid can interfere with the macrophage-particle reaction. PMID:1954926

  7. Cystic Fibrosis: Brazilian ENT Experience

    PubMed Central

    Sih, Tania; Godinho, Ricardo; Franco, Leticia Paiva; Piltcher, Otávio

    2012-01-01

    Most published studies about Cystic Fibrosis (CF) are European or North American. There are still few publications about the characteristics of fibrocystic populations in developing countries. The incidence of cystic fibrosis (CF) in Brazil varies among different regions (1 : 10,000 in Minas Gerais, 1 : 9,500 in Paraná, 1 : 8,700 in Santa Catarina, and 1 : 1600 in Rio Grande do Sul). The prevalence of the DF508 mutation also varies according to population: 33% in Sao Paulo, 49% in Rio Grande do Sul, 27% in Santa Catarina, and 52% in Minas Gerais. Cough and nasal obstruction are the most common symptoms. The variation in nasal polyposis prevalence may be explained by population genotypic characteristics in a country that spans a continent. Findings on nasal endoscopy and computed tomography (CT) have better correlation than do this information compared with surgical and clinical history. Microbiologic studies suggest a high level of early contamination of the airways. Sensorineural hearing loss (SNHL) occurs in these patients as a result of ototoxic antibiotics. The data compiled in this paper is useful, but also lead to the general agreement that more research would be welcome due to the unique characteristics of this country. PMID:22611403

  8. Autophagy mediates oral submucous fibrosis

    PubMed Central

    LI, JIANG; ZHAO, TING-TING; ZHANG, PENG; XU, CHAO-JIN; RONG, ZHUO-XIANG; YAN, ZI-YI; FANG, CHANG-YUN

    2016-01-01

    Oral submucous fibrosis (OSF) is a chronic insidious disease of the oral mucosa, well-recognized as a premalignant condition and commonly found in Southern China. It is primarily caused by the habit of areca nut or gutkha chewing. OSF is believed to be a homeostatic disorder of the extracellular matrix and fibroblast proliferation. The present study demonstrated a novel link between autophagy and OSF. Tissue samples from human OSF showed an overexpression of the autophagy marker microtubule-associated protein 1 light chain 3 using immunohistochemistry and quantitative polymerase chain reaction. With regard to the crucial role of transforming growth factor (TGF)-β in OSF disease, western blot analysis demonstrated that TGF-β signaling was shown to contribute to the activation of autophagy in fibroblasts in vitro; however, a cell apoptosis and MTS assay demonstrated that the suppression of autophagy ameliorated the fibrosis induced by active TGF-β receptor type I signaling, as well as promoted fibroblast apoptosis and suppressed proliferation. Therefore, the present results suggest that autophagy serves a crucial function in OSF. PMID:27168817

  9. Aspergillus infections in cystic fibrosis.

    PubMed

    King, Jill; Brunel, Shan F; Warris, Adilia

    2016-07-01

    Patients with cystic fibrosis (CF) suffer from chronic lung infection and airway inflammation. Respiratory failure secondary to chronic or recurrent infection remains the commonest cause of death and accounts for over 90% of mortality. Bacteria as Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex have been regarded the main CF pathogens and their role in progressive lung decline has been studied extensively. Little attention has been paid to the role of Aspergillus spp. and other filamentous fungi in the pathogenesis of non-ABPA (allergic bronchopulmonary aspergillosis) respiratory disease in CF, despite their frequent recovery in respiratory samples. It has become more apparent however, that Aspergillus spp. may play an important role in chronic lung disease in CF. Research delineating the underlying mechanisms of Aspergillus persistence and infection in the CF lung and its link to lung deterioration is lacking. This review summarizes the Aspergillus disease phenotypes observed in CF, discusses the role of CFTR (cystic fibrosis transmembrane conductance regulator)-protein in innate immune responses and new treatment modalities. PMID:27177733

  10. Postinjection Muscle Fibrosis from Lupron

    PubMed Central

    Tsilianidis, Laurie A.; Ballock, Tracy; Haider, Anzar; Rogers, Douglas G.; Schweiger, B. Michelle

    2015-01-01

    We describe the case of a 6.5-year-old girl with central precocious puberty (CPP), which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate) Depot-Ped (3 months) intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection. PMID:26101682

  11. Managing diabetes in cystic fibrosis.

    PubMed

    Laguna, T A; Nathan, B M; Moran, A

    2010-10-01

    Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in persons with cystic fibrosis (CF). As the life expectancy of persons with CF continues to increase, the need to proactively diagnose and aggressively treat CFRD and its potential complications has become more apparent. CFRD negatively impacts lung function, growth and mortality, making its diagnosis and management crucial in a population already at high risk for early mortality. Compared to type 1 and type 2 diabetes, CFRD is a unique entity, requiring a thorough understanding of its unique pathophysiology to facilitate the creation and utilization of an effective medical treatment plan. The physiology of CFRD is complex, likely consisting of a combination of insulin deficiency, insulin resistance and a genetic predisposition towards the development of diabetes. However, the hallmark of CFRD is insulin deficiency, necessitating the use of exogenous insulin as the mainstay of therapy. Insulin administration, in combination with a multidisciplinary team of health professionals with expertise in the care of patients with CF and CFRD, is the cornerstone of the care for these patients. The goals of treatment of the CFRD population are to reverse protein catabolism, maintain a healthy weight, and reduce acute and chronic diabetes complications. Creating a partnership between the treatment team and the patient is the ideal way to accomplish these goals and is essential for successful diabetes care. PMID:20920037

  12. Postinjection Muscle Fibrosis from Lupron.

    PubMed

    Everest, Erica; Tsilianidis, Laurie A; Raissouni, Nouhad; Ballock, Tracy; Blatnik, Terra; Haider, Anzar; Rogers, Douglas G; Schweiger, B Michelle

    2015-01-01

    We describe the case of a 6.5-year-old girl with central precocious puberty (CPP), which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate) Depot-Ped (3 months) intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection. PMID:26101682

  13. Oral submucous fibrosis: an update

    PubMed Central

    Wollina, Uwe; Verma, Shyam B; Ali, Fareedi Mukram; Patil, Kishor

    2015-01-01

    Oral submucous fibrosis (OSF) is a premalignant condition caused by betel chewing. It is very common in Southeast Asia but has started to spread to Europe and North America. OSF can lead to squamous cell carcinoma, a risk that is further increased by concomitant tobacco consumption. OSF is a diagnosis based on clinical symptoms and confirmation by histopathology. Hypovascularity leading to blanching of the oral mucosa, staining of teeth and gingiva, and trismus are major symptoms. Major constituents of betel quid are arecoline from betel nuts and copper, which are responsible for fibroblast dysfunction and fibrosis. A variety of extracellular and intracellular signaling pathways might be involved. Treatment of OSF is difficult, as not many large, randomized controlled trials have been conducted. The principal actions of drug therapy include antifibrotic, anti-inflammatory, and antioxygen radical mechanisms. Potential new drugs are on the horizon. Surgery may be necessary in advanced cases of trismus. Prevention is most important, as no healing can be achieved with available treatments. PMID:25914554

  14. Heart involvement in cystic fibrosis: A specific cystic fibrosis-related myocardial changes?

    PubMed

    Labombarda, Fabien; Saloux, Eric; Brouard, Jacques; Bergot, Emmanuel; Milliez, Paul

    2016-09-01

    Cystic fibrosis is a complex multi-systemic chronic disease characterized by progressive organ dysfunction with development of fibrosis, possibly affecting the heart. Over the last four decades pathological, experimental, and clinical evidence points towards the existence of a specific myocardial involvement in cystic fibrosis. Multi-modality cardiac imaging, especially recent echocardiographic techniques, evidenced diastolic and/or systolic ventricular dysfunction in cystic fibrosis leading to the concept of a cystic fibrosis-related cardiomyopathy. Hypoxemia and inflammation are among the most important factors for heart involvement in cystic fibrosis. Cystic Fibrosis Transmembrane Regulator was found to be involved in the regulation of cardiomyocyte contraction and may also account for cystic fibrosis-related myocardial dysfunction. This review, mainly focused on echocardiographic studies, seeks to synthesize the existing literature for and against the existence of heart involvement in cystic fibrosis, its mechanisms and prognostic implications. Careful investigation of the heart function may be helpful for risk stratification and therapeutic decisions in patients with cystic fibrosis. PMID:27578468

  15. Smoking-associated fibrosis and pulmonary asbestosis.

    PubMed

    Bledsoe, Jacob R; Christiani, David C; Kradin, Richard L

    2015-01-01

    The diagnosis of pulmonary asbestosis is most often established based on clinical criteria and has both clinical and legal implications. Unfortunately, one of the confounding features in the diagnosis may be a history of cigarette abuse, which can produce interstitial opacities on chest imaging as well as diffusion defects on pulmonary function testing, criteria that are used in the diagnosis of pulmonary asbestosis. The objective of the present study was to evaluate the correlation of radiographically detected pulmonary fibrosis with fibrosis established histopathologically as attributable to asbestos, in a cohort referred for diagnosis of an asbestos-related malignancy in the context of litigation. We examined the slides of 186 cases with reported asbestos exposure, referred in consultation for asbestos-related malignancy and the presence of pulmonary fibrosis. Sixty-five cases had what was judged to be adequate tissue sampling for histopathologic evaluation of asbestosis as well as an existing radiologic assessment of pulmonary fibrosis by B-reader report. Of 24 cases judged to have asbestosis radiographically, which had sufficient tissue for pathologic examination, six showed asbestosis histopathologically. The remaining 18 cases (mean smoking history of 53 pack-years) showed interstitial fibrosis that was judged to be most consistent with smoking-associated pulmonary fibrosis. We conclude that the clinical diagnosis of mild asbestosis cannot be reliably distinguished from interstitial fibrosis in heavy smokers. PMID:25565798

  16. Aspergillus bronchitis in cystic fibrosis.

    PubMed

    Shoseyov, David; Brownlee, Keith G; Conway, Steven P; Kerem, Eitan

    2006-07-01

    Aspergillus fumigatus, a widely distributed spore-bearing fungus, is commonly grown in sputum cultures of patients with cystic fibrosis (CF). A fumigatus may cause allergic bronchopulmonary aspergillosis (ABPA), a complex condition that leads to worsening of airway inflammation and progressive damage and is diagnosed by specific criteria. In this report, we present six CF patients with respiratory deterioration that did not respond to appropriate antibiotic treatment. All had had A fumigatus in sputum cultures but did not fulfill the criteria of ABPA. Treatment with antifungal agents was followed by improvement in clinical condition. We suggest that in patients with CF, A fumigatus should be considered as a pathogen that may directly cause respiratory exacerbations. Antifungal therapy should be considered when deteriorating respiratory function is not responding to antibacterial therapy and A fumigatus is growing in sputum cultures. PMID:16840406

  17. [Fractal analysis of liver fibrosis].

    PubMed

    Soda, G; Nardoni, S; Bosco, D; Grizzi, F; Dioguardi, N; Melis, M

    2003-04-01

    This study realized by two different study groups use of Fractal geometry to quantify the complex collagen deposition during chronic liver disease. Thirty standard needle liver biopsy specimens were obtained from patients with chronic HCV-related disease. Three mu-thick sections were cut and stained by means of Picrosirius stain, in order to visualise collagen matrix. The degree of fibrosis was measured using a quantitative scoring system based on the computer-assisted evaluation of the fractal dimension of the deposited collagen surface. The obtained results by both study groups, show that the proposed method is reproducible, rapid and inexpensive. The complex distribution of its collagenous components can be quantified using a single numerical score. This study demonstrated that it is possible to quantify the collagen's irregularity in an objective manner, and that the study of the fractal properties of the collagen shapes is likely to reveal more about its structure and the complex behaviour of its development. PMID:12768879

  18. Cough in idiopathic pulmonary fibrosis.

    PubMed

    van Manen, Mirjam J G; Birring, Surinder S; Vancheri, Carlo; Cottin, Vincent; Renzoni, Elisabetta A; Russell, Anne-Marie; Wijsenbeek, Marlies S

    2016-09-01

    Many patients with idiopathic pulmonary fibrosis (IPF) complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF, which is most probably "multifactorial" and influenced by mechanical, biochemical and neurosensory changes, with an important role for comorbidities as well. Clinical trials of cough treatment in IPF are emerging, and cough is increasingly included as a secondary end-point in trials assessing new compounds for IPF. It is important that such studies include adequate end-points to assess cough both objectively and subjectively. This article summarises the latest insights into chronic cough in IPF. It describes the different theories regarding the pathophysiology of cough, reviews the different methods to assess cough and deals with recent and future developments in the treatment of cough in IPF. PMID:27581827

  19. Epidemiology of idiopathic pulmonary fibrosis

    PubMed Central

    Ley, Brett; Collard, Harold R

    2013-01-01

    Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause that occurs in adults and has a poor prognosis. Its epidemiology has been difficult to study because of its rarity and evolution in diagnostic and coding practices. Though uncommon, it is likely underappreciated both in terms of its occurrence (ie, incidence, prevalence) and public health impact (ie, health care costs and resource utilization). Incidence and mortality appear to be on the rise, and prevalence is expected to increase with the aging population. Potential risk factors include occupational and environmental exposures, tobacco smoking, gastroesophageal reflux, and genetic factors. An accurate understanding of its epidemiology is important, especially as novel therapies are emerging. PMID:24348069

  20. Epigenomics of idiopathic pulmonary fibrosis

    PubMed Central

    Yang, Ivana V

    2012-01-01

    Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Gene-expression profiling studies have taught us quite a bit about the biology of this fatal disease, but epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptome changes associated with the development of IPF. This review will begin with an introduction to the disease, followed by brief summaries of studies of gene expression in IPF and epigenetic marks associated with exposures relevant to IPF. The majority of the discussion will focus on epigenetic studies conducted so far in IPF, the limitations, challenges and future directions in this field. PMID:22449190

  1. Chronic pancreatitis and cystic fibrosis

    PubMed Central

    Witt, H

    2003-01-01

    Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. PMID:12651880

  2. Molecular and cellular mechanisms of pulmonary fibrosis

    PubMed Central

    2012-01-01

    Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

  3. Genetics Home Reference: idiopathic pulmonary fibrosis

    MedlinePlus

    ... However, the course of the disease is highly variable; some affected people become seriously ill within a ... idiopathic pulmonary fibrosis: an observational cohort study with independent validation. Lancet Respir Med. 2014 Jul;2(7): ...

  4. Noninvasive Markers to Assess Liver Fibrosis.

    PubMed

    Czul, Frank; Bhamidimarri, Kalyan R

    2016-07-01

    Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. Their prognosis and management greatly depends on the amount and progression of liver fibrosis with time and the risk of development of cirrhosis. Historically, liver biopsy was considered to be the gold standard for the detection of fibrosis. Nevertheless, liver biopsy is an invasive procedure that has limitations in terms of patient acceptance, risk-benefit ratio, cost-effectiveness, and its availability in various geographic regions. Moreover, it is a questionable gold standard due to significant sampling error and intraobserver and interobserver variability. These limitations have led to the development of noninvasive techniques for assessing the presence and the degree of liver fibrosis. This review aims to revise the most recent data from the literature about noninvasive methods useful in the evaluation of liver fibrosis. PMID:27105176

  5. "End-stage" pulmonary fibrosis in sarcoidosis.

    PubMed

    Teirstein, Alvin T; Morgenthau, Adam S

    2009-02-01

    Pulmonary fibrosis is an unusual "end stage" in patients with sarcoidosis. Fibrosis occurs in a minority of patients, and presents with a unique physiologic combination of airways dysfunction (obstruction) superimposed on the more common restrictive dysfunction. Imagin techniques are essential to the diagnosis, assessment and treatment of pulmonary fibrosis. Standard chest radiographs and CT scans may reveal streaks, bullae, cephalad retraction of the hilar areas, deviation of the trachea and tented diaphragm. Positive gallium and PET scans indicate residual reversible granulomatous disease and are important guides to therapy decisions. Treatment, usually with corticosteroids, is effective in those patients with positive scans, but fibrosis does not improve with any treatment. With severe functional impariment and patient disability, pulmonary hypertension and right heart failure may supervene for which the patient will require treatment. Oxygen, careful diuresis, sildenafil and bosentan may be salutary. These patients are candidates for lung transplantation. PMID:19170216

  6. Increased volume of conducting airways in idiopathic pulmonary fibrosis is independent of disease severity: a volumetric capnography study.

    PubMed

    Plantier, Laurent; Debray, Marie-Pierre; Estellat, Candice; Flamant, Martin; Roy, Carine; Bancal, Catherine; Borie, Raphaël; Israël-Biet, Dominique; Mal, Hervé; Crestani, Bruno; Delclaux, Christophe

    2016-03-01

    Bronchiectasis, bronchiolectasis, and bronchiolisation of alveolar regions are salient features of idiopathic pulmonary fibrosis (IPF). We asked whether IPF was associated with physiological changes consistent with increases in the volume of conducting airways, and whether airway volume was related to the severity of lung fibrosis. Patients with IPF (N  =  57, vital capacity-VC: 73  ±  20%), patients with non-IPF interstitial lung disease (non-IPF ILD, N  =  24, VC  =  78  ±  18%) and controls without lung disease (N  =  51, VC  =  112  ±  21%) underwent volumetric capnography for the determination of conducting airway volume using Fletcher's equal area method, reported to predicted total lung capacity to control for the effect of lung size (VDaw/TLCp, mL/L). VDaw/TLCp was higher in patients with IPF (45.3  ±  12.8 ml L(-1)) in comparison with controls (34.2  ±  11.0 ml L(-1), p  <  0.0001) and patients with non-IPF ILD (39.5  ±  9.2 ml L(-1), p  =  0.0496). The same differences were observed when analysis was restricted to subjects with moderate IPF (VC  ⩾  80% predicted). Among IPF patients, VDaw/TLCp was correlated with neither the mMRC dyspnea scale, nor VC, nor carbon monoxide transfer factor, nor computed tomography fibrosis scores. Volumetric capnography showed higher conducting airway volume in IPF patients in comparison with controls and non-IPF ILDs, independent of disease severity. This result is consistent with either anatomical predisposition or dilation/longitudinal growth of conducting airways in IPF. PMID:26828240

  7. Endomyocardial fibrosis in Egypt: an illustrated review.

    PubMed Central

    Rashwan, M. A.; Ayman, M.; Ashour, S.; Hassanin, M. M.; Zeina, A. A.

    1995-01-01

    The detailed features of right sided endomyocardial fibrosis are described in 15 out of 10,000 consecutive patients who all had infection with Schistosoma mansoni and came from rural Egypt. Laboratory investigations, 12 lead electrocardiography, chest radiography, and Doppler echocardiography were performed in all patients. Cardiac catheterisation and angiography were performed in eight. Endomyocardial biopsy specimens were obtained from the right ventricles of two patients and pericardial biopsy specimens from two. Pericardiocentesis was performed in all patients. All patients were infected with S mansoni and had schistosomal hepatic fibrosis and ascites. Eleven had splenomegaly. All patients had raised cervical venous pressure with prominent Y descent and atrial fibrillation. Eosinophilia was notably absent. Echocardiography showed apical fibrosis in the right ventricle, obliteration of the ventricle, and moderate to massive exudative pericardial effusion in all patients. Calcification and fibrosis extended into the right ventricular outflow tracts in two patients. Huge right atrial thrombi occurred in five patients. Tricuspid regurgitation (grades I-II) was detected in 11 patients by Doppler ultrasonography. Haemodynamic and angiographic data confirmed the pure right sided restrictive pathophysiology. Pericardial biopsy specimens showed perivascular inflammatory infiltrates in two patients and a schistosomal granuloma in one. Endocardial biopsy specimens showed dense fibrosis with many fibroblasts. Endomyocardial fibrosis in Egypt is unique in several aspects. It always affected only the right side of the heart. Calcification and fibrosis extended to the right ventricular outflow tract. Pericardial inflammatory reaction was present. The relation to schistosomiasis and the link to periportal hepatic fibrosis in these patients is intriguing. Images PMID:7727191

  8. Inhibition of SIRT2 suppresses hepatic fibrosis.

    PubMed

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis. PMID:27125275

  9. Cystic fibrosis from the gastroenterologist's perspective.

    PubMed

    Ooi, Chee Y; Durie, Peter R

    2016-03-01

    Cystic fibrosis is a life-limiting, recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Increased survival outcomes and the multisystem nature of the disease, including the involvement of hepatobiliary and gastrointestinal tracts, now require the need for more extensive knowledge and expertise in cystic fibrosis among gastroenterologists. Manifestations are either a direct consequence of the primary defect in cystic fibrosis or a secondary complication of the disease or therapy. Adult patients with cystic fibrosis also have an increased risk of malignancy in the gastrointestinal and pancreatico-biliary tracts compared with the general population. Novel treatments that target the basic defects in the CFTR protein have emerged, but to date not much is known about their effects on the gastrointestinal and hepatobiliary systems. The introduction of such therapies has provided new opportunities for the application of intestinal endpoints in clinical trials and the understanding of underlying disease mechanisms that affect the gut in cystic fibrosis. PMID:26790364

  10. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

    Knowles, M. R.; Stutts, M. J.; Spock, A.; Fischer, N.; Gatzy, J. T.; Boucher, R. C.

    1983-09-01

    The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.