- Estimated burden of serious human fungal diseases in Turkey. [Journal Article]
- MMycoses 2018 Aug 14
- The current number of fungal infections occurring each year in Turkey is unknown. We estimated the burden of serious human fungal diseases based on the population at risk, existing epidemiological da...
The current number of fungal infections occurring each year in Turkey is unknown. We estimated the burden of serious human fungal diseases based on the population at risk, existing epidemiological data from 1920 to 2017, and modelling previously described by the LIFE program Among the population of Turkey (80.8 million in 2017), approximately 1,785,811 (2.21%) people are estimated to suffer from a serious fungal infection each year. The model used predicts high prevalences of allergic fungal rhinosinusitis episodes (312,994 cases) (392/100,000), of severe asthma with fungal sensitization (42,989 cases) (53.20 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (32,594 cases) (40.33/100,000), of fungal keratitis (26,671 cases) (33/100,000), and of chronic pulmonary aspergillosis (5,890 cases) (7.29/100,000). The estimated annual incidence for invasive aspergillosis is lower (3,991 cases) (4.94/100,000 annually). Amongst about 22.5 million women aged 15-50 years, recurrent vulvovaginal candidiasis (RVVC) is estimated to occur in 1,350,371 (3,342/100,000) females. The burden of three superficial fungal infections was also estimated: tinea pedis (1.79 million), tinea capitis (43,900), and onychomycosis (1.73 million). Given that the modeling estimates reported in the current study might be substantially under- or over-estimated, formal epidemiological and comprehensive surveillance studies are required to validate or modify these estimates. This article is protected by copyright. All rights reserved.
- A Case of Allergic Broncopulmonary Aspergillosis Associated With Hematopoietic Stem Cell Transplantation Due to Chronic Granulomatous Disease. [Journal Article]
- JPJ Pediatr Hematol Oncol 2018 Aug 08
- Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. This disorder is most commonly seen in patients with poorly controlle...
Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. This disorder is most commonly seen in patients with poorly controlled asthma and cystic fibrosis. It is rarely reported in chronic granulomatous disease patients; however, there are no cases reported with hematopoietic stem cell transplantation in the English literature. Herein, we report a patient with chronic granulomatous disease who had hematopoietic stem cell transplantation and subsequently developed allergic bronchopulmonary aspergillosis.
- [Real-world effectiveness of ivacaftor in children with cystic fibrosis and the G551D mutation]. [Journal Article]
- APAn Pediatr (Barc) 2018 Aug 06
- CONCLUSIONS: Children with cystic fibrosis and the F508del/G551D genotype receiving treatment with ivacaftor experienced a real-world improvement in lung function, nutritional status, respiratory exacerbations, isolation of P. aeruginosa, and dose of pancreatic enzymes.
- Allergic fungal rhinosinusitis. [Review]
- JAJ Allergy Clin Immunol 2018; 142(2):341-351
- Allergic fungal rhinosinusitis (AFRS) is a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by antifungal IgE sensitivity, eosinophil-rich mucus (ie, allergic mucin), and cha...
Allergic fungal rhinosinusitis (AFRS) is a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by antifungal IgE sensitivity, eosinophil-rich mucus (ie, allergic mucin), and characteristic computed tomographic and magnetic resonance imaging findings in paranasal sinuses. AFRS develops in immunocompetent patients, with occurrence influenced by climate, geography, and several identified host factors. Molecular pathways and immune responses driving AFRS are still being delineated, but prominent adaptive and more recently recognized innate type 2 immune responses are important, many similar to those established in patients with other forms of CRSwNP. It is unclear whether AFRS represents merely a more extreme expression of pathways important in patients with CRSwNP or whether there are other disordered immune responses that would define a distinct endotype or endotypes. Although AFRS and allergic bronchopulmonary aspergillosis share some analogous immune mechanisms, the 2 conditions do not occur commonly in the same patient. Treatment of AFRS almost always requires surgical debridement of the involved sinuses. Oral corticosteroids decrease recurrence after surgery, but other adjunctive pharmacologic agents, including topical and oral antifungal agents, do not have a firm evidence basis for use. There is good rationale for use of biologic agents that target eosinophilic inflammation or other type 2 responses, but studies in patients with AFRS are required.
- The spectrum of pulmonary aspergillosis. [Review]
- RMRespir Med 2018; 141:121-131
- Notable progress has been made in the past years in the classification, diagnosis and treatment of pulmonary aspergillosis. New criteria were proposed by the Working Group of the International Societ...
Notable progress has been made in the past years in the classification, diagnosis and treatment of pulmonary aspergillosis. New criteria were proposed by the Working Group of the International Society for Human and Animal Mycology (ISHAM) for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). The latest classification of chronic pulmonary aspergillosis (CPA) suggested by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) has become widely accepted among clinicians. Subacute invasive pulmonary aspergillosis is now considered a type of CPA, yet it is still diagnosed and treated similarly to invasive pulmonary aspergillosis (IPA). Isavuconazole, an extended-spectrum triazole, has recently been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of IPA. The most recent Infectious Diseases Society of America (IDSA) guidelines strongly recommend reducing mold exposure to patients at high risk for pulmonary aspergillosis. The excessive relapse rate following discontinuation of therapy remains a common reality to all forms of this semi-continuous spectrum of diseases. This highlights the need to continuously reassess patients and individualize therapy accordingly. Thus far, the duration of therapy and the frequency of follow-up have to be well characterized.
- Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice. [Journal Article]
- JVJ Vis Exp 2018 07 04; (137)
- The nasal potential difference test has been used for almost three decades to assist in the diagnosis of cystic fibrosis (CF). It has proven to be helpful in cases of attenuated, oligo- or mono-sympt...
The nasal potential difference test has been used for almost three decades to assist in the diagnosis of cystic fibrosis (CF). It has proven to be helpful in cases of attenuated, oligo- or mono-symptomatic forms of CF usually diagnosed later in life, and of CF-related disorders such as congenital bilateral absence of vas deferens, idiopathic chronic pancreatitis, allergic bronchopulmonary aspergillosis, and bronchiectasis. In both clinical and preclinical settings, the test has been used as a biomarker to quantify responses to targeted therapeutic strategies for CF. Adapting the test to a mouse is challenging and can entail an associated mortality. This paper describes the adequate depth of anesthesia required to maintain a nasal catheter in situ for continuous perfusion. It lists measures to avoid broncho-aspiration of solutions perfused in the nose. It also describes the animal care at the end of the test, including administration of a combination of antidotes of the anesthetic drugs, leading to rapidly reversing the anesthesia with full recovery of the animals. Representative data obtained from a CF and a wild-type mouse show that the test discriminates between CF and non-CF. Altogether, the protocol described here allows reliable measurements of the functional status of trans-epithelial chloride and sodium transporters in spontaneously breathing mice, as well as multiple tests in the same animal while reducing test-related mortality.
- A novel microRNA miR-1165-3p as a potential diagnostic biomarker for allergic asthma. [Journal Article]
- BBiomarkers 2018 Jul 17; :1-31
- CONCLUSIONS: This study showed that serum miR-1165-3p can potentially be utilized as a noninvasive biomarker that is able to aid in the diagnosis and characterization of allergic asthma.
- Impact of an antifungal stewardship programme in a tertiary respiratory medicine setting: A prospective real-world study. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Jul 16
- There has been an increase in fungal infections in patients with chronic lung disease over the past decades, which is associated with rapidly increasing costs to healthcare systems.An antifungal stew...
There has been an increase in fungal infections in patients with chronic lung disease over the past decades, which is associated with rapidly increasing costs to healthcare systems.An antifungal stewardship team was introduced to a tertiary cardiopulmonary hospital, consisting of a medical mycologist and pharmacy support providing weekly stewardship ward rounds, twice monthly multidisciplinary team meetings and a dedicated weekly outpatient clinic. A database was set up to record the activity of the stewardship team.During the first eighteen months of implementation the antifungal stewardship team had reviewed 178 patients, with 285 recommendations made to inpatients, and 287 outpatient visits. The commonest diagnoses treated were allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Cystic fibrosis was the largest patient group treated followed by asthma and interstitial lung disease. There was a significant, sustained reduction in monthly antifungal expenditure (p=0.005) by £130,000 per month. There was also a significant reduction in antifungal use measured as Defined Daily Dose/100 bed days (p=0.017). There were no significant changes in expenditure on diagnostic tests. There has been a trend toward more patients having therapeutic levels of voriconazole (p=0.086) and a significant increase in therapeutic levels of posaconazole (p<0.0001).This study shows that an effective antifungal stewardship programme can significantly reduce expenditure in a specialist respiratory service.
- TGF-β/SMAD4 mediated UCP2 downregulation contributes to Aspergillus protease-induced inflammation in primary bronchial epithelial cells. [Journal Article]
- RBRedox Biol 2018 Jul 05; 18:104-113
- Elevated levels of mitochondrial reactive oxygen species (ROS) can lead to the development of airway inflammation. In this study, we investigated the role of Aspergillus proteases-which contribute to...
Elevated levels of mitochondrial reactive oxygen species (ROS) can lead to the development of airway inflammation. In this study, we investigated the role of Aspergillus proteases-which contribute to the pathogenesis of Aspergillus-induced diseases such as allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and atopic asthma-and their mechanisms of action in airway inflammation using primary human bronchial epithelial cells, and evaluated the inflammatory responses mediated by mitochondrial ROS. We found that Aspergillus proteases regulated the expression of multifunctional inflammatory cytokines such as interleukin (IL)- 1β, - 6, and - 8, and transforming growth factor (TGF)-β, which stimulated cytokine production and chemokines involved in leukocyte migration and activated an inflammatory cascade. Expression of these factors and activator protein (AP)- 1 were decreased by treatment with the mitochondrial ROS scavenger Mito-TEMPO, suggesting that mitochondria are important sources of ROS in the context of inflammatory response by Aspergillus protease. The regulation of mitochondrial ROS influenced the production of proinflammatory mediators by preventing mitochondrial ROS-induced AP-1 activation in airway epithelial cells. In addition, Aspergillus protease-mediated mitochondrial ROS production was associated with downregulation of uncoupling protein (UCP)- 2 expression by TGF-β-SMAD4 signaling, which may play a regulatory role in mitochondrial ROS formation during fungal protease-mediated epithelial inflammation. This improved understanding of the allergenic fungal protease-induced inflammatory mechanism in the bronchial epithelium will help in developing intervention strategies for the regulation of inflammatory response in allergic airway diseases.
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- Bronchiectasis: a case-based approach to investigation and management. [Review]
- EREur Respir Rev 2018 Sep 30; 27(149)
- Bronchiectasis is a chronic respiratory disease characterised by a syndrome of productive cough and recurrent respiratory infections due to permanent dilatation of the bronchi. Bronchiectasis represe...
Bronchiectasis is a chronic respiratory disease characterised by a syndrome of productive cough and recurrent respiratory infections due to permanent dilatation of the bronchi. Bronchiectasis represents the final common pathway of different disorders, some of which may require specific treatment. Therefore, promptly identifying the aetiology of bronchiectasis is recommended by the European Respiratory Society guidelines. The clinical history and high-resolution computed tomography (HRCT) features can be useful to detect the underlying causes. Despite a strong focus on this aspect of treatment a high proportion of patients remain classified as "idiopathic". Important underlying conditions that are treatable are frequently not identified for prolonged periods of time.The European Respiratory Society guidelines for bronchiectasis recommend a minimal bundle of tests for diagnosing the cause of bronchiectasis, consisting of immunoglobulins, testing for allergic bronchopulmonary aspergillosis and full blood count. Other testing is recommended to be conducted based on the clinical history, radiological features and severity of disease. Therefore it is essential to teach clinicians how to recognise the "clinical phenotypes" of bronchiectasis that require specific testing.This article will present the initial investigation and management of bronchiectasis focussing particularly on the HRCT features and clinical features that allow recognition of specific causes.