- An Estimate of the Burden of Fungal Disease in Norway. [Journal Article]
- JFJ Fungi (Basel) 2018 Feb 21; 4(1)
- The aim of this study was to examine the burden of fungal disease in Norway, contributing to a worldwide effort to improve awareness of the needs for better diagnosis and treatment of such infections...
The aim of this study was to examine the burden of fungal disease in Norway, contributing to a worldwide effort to improve awareness of the needs for better diagnosis and treatment of such infections. We used national registers and actual data from the Departments of Microbiology from 2015 and estimated the incidence and/or prevalence of superficial, allergic and invasive fungal disease using published reports on specific populations at risk. One in 6 Norwegians suffered from fungal disease: Superficial skin infections (14.3%: 745,600) and recurrent vulvovaginal candidiasis in fertile women (6%: 43,123) were estimated to be the most frequent infections. Allergic fungal lung disease was estimated in 17,755 patients (341/100,000). Pneumocystis jirovecii was diagnosed in 262 patients (5/100,000), invasive candidiasis in 400 patients (7.7/100,000), invasive aspergillosis in 278 patients (5.3/100,000) and mucormycosis in 7 patients (0.1/100,000). Particular fungal infections from certain geographic areas were not observed. Overall, 1.79% of the population was estimated to be affected by serious fungal infections in Norway in 2015. Even though estimates for invasive infections are small, the gravity of such infections combined with expected demographic changes in the future emphasizes the need for better epidemiological data.
- Correlation of aspergillus skin hypersensitivity with the duration and severity of asthma. [Journal Article]
- MAMonaldi Arch Chest Dis 2017 Sep 25; 87(3):826
- Asthma is a significant health problem worldwide and Allergic Bronchopulmonary aspergillosis (ABPA) complicates the course of 1-2% of patients of asthma. Aspergillus skin hypersensitivity (AH) is the...
Asthma is a significant health problem worldwide and Allergic Bronchopulmonary aspergillosis (ABPA) complicates the course of 1-2% of patients of asthma. Aspergillus skin hypersensitivity (AH) is the first step for diagnosis of ABPA. This study was conducted to know the correlation of AH with severity and duration of asthma. Patients, age >15 years, of asthma attending this hospital from January 2015 to December 2015 were included. Asthma was diagnosed clinically and confirmed with spirometry. Of 282 patients 206 patients were AH positive. The AST-positivity in patients having severe asthma (96.8%) was higher than that in patients having mild (36.8%) and moderate asthma (80.4%). The median (IQR) duration of asthma of AH positive patients was 5.0 yrs. This study emphasized the need of ABPA screening by intradermal skin test especially in patients having severe asthma and/or those having asthma for longer duration in order for early diagnosis of ABPA.
- Can Controlling Endoplasmic Reticulum Dysfunction Treat Allergic Inflammation in Severe Asthma With Fungal Sensitization? [Review]
- AAAllergy Asthma Immunol Res 2018; 10(2):106-120
- Severe asthma is a heterogeneous disease entity to which diverse cellular components and pathogenetic mechanisms contribute. Current asthma therapies, including new biologic agents, are mainly target...
Severe asthma is a heterogeneous disease entity to which diverse cellular components and pathogenetic mechanisms contribute. Current asthma therapies, including new biologic agents, are mainly targeting T helper type 2 cell-dominant inflammation, so that they are often unsatisfactory in the treatment of severe asthma. Respiratory fungal exposure has long been regarded as a precipitating factor for severe asthma phenotype. Moreover, as seen in clinical definitions of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS), fungal allergy-associated severe asthma phenotype is increasingly thought to have distinct pathobiologic mechanisms requiring different therapeutic approaches other than conventional treatment. However, there are still many unanswered questions on the direct causality of fungal sensitization in inducing severe allergic inflammation in SAFS. Recently, growing evidence suggests that stress response from the largest organelle, endoplasmic reticulum (ER), is closely interconnected to diverse cellular immune/inflammatory platforms, thereby being implicated in severe allergic lung inflammation. Interestingly, a recent study on this issue has suggested that ER stress responses and several associated molecular platforms, including phosphoinositide 3-kinase-δ and mitochondria, may be crucial players in the development of severe allergic inflammation in the SAFS. Defining emerging roles of ER and associated cellular platforms in SAFS may offer promising therapeutic options in the near future.
- A Multifaceted Role of Tryptophan Metabolism and Indoleamine 2,3-Dioxygenase Activity in Aspergillus fumigatus-Host Interactions. [Review]
- FIFront Immunol 2017; 8:1996
- Aspergillus fumigatus is the most prevalent filamentous fungal pathogen of humans, causing either severe allergic bronchopulmonary aspergillosis or often fatal invasive pulmonary aspergillosis (IPA) ...
Aspergillus fumigatus is the most prevalent filamentous fungal pathogen of humans, causing either severe allergic bronchopulmonary aspergillosis or often fatal invasive pulmonary aspergillosis (IPA) in individuals with hyper- or hypo-immune deficiencies, respectively. Disease is primarily initiated upon the inhalation of the ubiquitous airborne conidia-the initial inoculum produced by A. fumigatus-which are complete developmental units with an ability to exploit diverse environments, ranging from agricultural composts to animal lungs. Upon infection, conidia initially rely on their own metabolic processes for survival in the host's lungs, a nutritionally limiting environment. One such nutritional limitation is the availability of aromatic amino acids (AAAs) as animals lack the enzymes to synthesize tryptophan (Trp) and phenylalanine and only produce tyrosine from dietary phenylalanine. However, A. fumigatus produces all three AAAs through the shikimate-chorismate pathway, where they play a critical role in fungal growth and development and in yielding many downstream metabolites. The downstream metabolites of Trp in A. fumigatus include the immunomodulatory kynurenine derived from indoleamine 2,3-dioxygenase (IDO) and toxins such as fumiquinazolines, gliotoxin, and fumitremorgins. Host IDO activity and/or host/microbe-derived kynurenines are increasingly correlated with many Aspergillus diseases including IPA and infections of chronic granulomatous disease patients. In this review, we will describe the potential metabolic cross talk between the host and the pathogen, specifically focusing on Trp metabolism, the implications for therapeutics, and the recent studies on the coevolution of host and microbe IDO activation in regulating inflammation, while controlling infection.
- Differential susceptibility of Dectin-1 isoforms to functional inactivation by neutrophil and fungal proteases. [Journal Article]
- FJFASEB J 2018 Jan 22; :fj201701145R
- Patients with cystic fibrosis (CF) experience chronic or recurrent bacterial and fungal lung infections. Many patients with CF cannot effectively clear Aspergillus from their lungs. This may result i...
Patients with cystic fibrosis (CF) experience chronic or recurrent bacterial and fungal lung infections. Many patients with CF cannot effectively clear Aspergillus from their lungs. This may result in IgE sensitization and the development of allergic bronchopulmonary aspergillosis, or invasive infections, such as Aspergillus bronchitis. Lung disease in patients with CF is associated with neutrophil-dominated inflammation and elevated levels of the serine protease, neutrophil elastase (NE). Various C-type lectin-like receptors (CLRs), including Dectin-1 and Dectin-2, are involved in the immune response to Aspergillus. Here, we show that purified NE cleaves Dectin-1 in an isoform-specific manner. Bronchoalveolar lavage fluid from patients with CF, which contains high NE activity, induces Dectin-1 cleavage. Similarly, filtrate from a protease-producing strain of Aspergillus fumigatus induces isoform-specific cleavage of Dectin-1. Dectin-1 knockout (KO) cells and NE-treated cells demonstrated reduced phagocytosis of zymosan, a fungal cell wall preparation. In addition, NE cleaves 2 other CLRs, Dectin-2 and Mincle, and fungal-induced cytokine production was reduced in Dectin-1 KO cells, Dectin-2 KO cells, and NE-treated cells. Thus, Dectin-1 and Dectin-2 cleavage by NE and/or A. fumigatus-derived proteases results in an aberrant antifungal immune response that likely contributes to disease pathology in patients with CF.-Griffiths, J. S., Thompson, A., Stott, M., Benny, A., Lewis, N. A., Taylor, P. R., Forton, J., Herrick, S., Orr, S. J., McGreal, E. P. Differential susceptibility of Dectin-1 isoforms to functional inactivation by neutrophil and fungal proteases.
- Burden of Serious Fungal Infections in Jordan. [Journal Article]
- JFJ Fungi (Basel) 2018 Jan 18; 4(1)
- CONCLUSIONS: Based on local data and literature estimates of the frequency of mycoses in susceptible populations, at least 1.9% of Jordanians have some form of serious fungal disease.
- A Randomized Trial of Itraconazole vs Prednisolone in Acute-Stage Allergic Bronchopulmonary Aspergillosis Complicating Asthma. [Journal Article]
- ChestChest 2018 Jan 11
- CONCLUSIONS: Prednisolone was more effective in inducing response than itraconazole in acute-stage ABPA. However, itraconazole was also effective in a considerable number and, with fewer side effects compared with prednisolone, remains an attractive alternative in the initial treatment of ABPA.
- Vitamin D levels in asthmatic patients with and without allergic bronchopulmonary aspergillosis. [Journal Article]
- MMycoses 2018 Jan 04
- Vitamin D deficiency is believed to a pathogenetic factor in patients with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. Whether vitamin D deficiency is also prevalent in ABPA c...
Vitamin D deficiency is believed to a pathogenetic factor in patients with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. Whether vitamin D deficiency is also prevalent in ABPA complicating asthma, remains unknown. Herein, we evaluate vitamin D levels in asthmatic patients with and without ABPA. In a prospective study, plasma vitamin D (25[OH]D) levels were measured in consecutive subjects with asthma (n=75), ABPA (n=158) and healthy volunteers (n=50). Vitamin D levels <20 ng/mL were considered as vitamin D deficiency. There was no difference in mean (95% CI) vitamin D levels between healthy controls (15.3 [12.7-17.9]), asthmatics (19.2 [16.3-22.1]) and subjects with ABPA (18.9 [16.9-20.8]) (p=0.22). Vitamin D deficiency was encountered in 70%, 64% and 65% of the healthy controls, asthmatics and ABPA subjects, respectively, and was not different between the groups (p=0.79). There was no difference in the asthma control, pulmonary function, immunological findings and the severity of bronchiectasis, in patients with ABPA, with and without vitamin D deficiency. Vitamin D deficiency is equally prevalent in asthmatic patients with or without ABPA in the Indian subcontinent, and does not appear to play a major role in the pathogenesis of ABPA complicating asthma. This article is protected by copyright. All rights reserved.
- Bronchiectasis. [Journal Article]
- JAJ Allergy Clin Immunol Pract 2018 Jan - Feb; 6(1):315-316
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- Fungi in Bronchiectasis: A Concise Review. [Review]
- IJInt J Mol Sci 2018 Jan 04; 19(1)
- Although the spectrum of fungal pathology has been studied extensively in immunosuppressed patients, little is known about the epidemiology, risk factors, and management of fungal infections in chron...
Although the spectrum of fungal pathology has been studied extensively in immunosuppressed patients, little is known about the epidemiology, risk factors, and management of fungal infections in chronic pulmonary diseases like bronchiectasis. In bronchiectasis patients, deteriorated mucociliary clearance-generally due to prior colonization by bacterial pathogens-and thick mucosity propitiate, the persistence of fungal spores in the respiratory tract. The most prevalent fungi in these patients areCandida albicansandAspergillus fumigatus; these are almost always isolated with bacterial pathogens likeHaemophillus influenzaeandPseudomonas aeruginosa, making very difficult to define their clinical significance. Analysis of the mycobiome enables us to detect a greater diversity of microorganisms than with conventional cultures. The results have shown a reduced fungal diversity in most chronic respiratory diseases, and that this finding correlates with poorer lung function. Increased knowledge of both the mycobiome and the complex interactions between the fungal, viral, and bacterial microbiota, including mycobacteria, will further our understanding of the mycobiome's relationship with the pathogeny of bronchiectasis and the development of innovative therapies to combat it.