scholarly journals Update on Respiratory Fungal Infections in Cystic Fibrosis Lung Disease and after Lung Transplantation

2020 ◽  
Vol 6 (4) ◽  
pp. 381
Author(s):  
Sabine Renner ◽  
Edith Nachbaur ◽  
Peter Jaksch ◽  
Eleonora Dehlink
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Chloride Transport ◽  
Lung Damage ◽  
Western World ◽  
Detection Rates ◽  
Airway Infections ◽  
The Impact

Cystic fibrosis is the most common autosomal-recessive metabolic disease in the Western world. Impaired trans-membrane chloride transport via the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes thickened body fluids. In the respiratory system, this leads to chronic suppurative cough and recurrent pulmonary infective exacerbations, resulting in progressive lung damage and respiratory failure. Whilst the impact of bacterial infections on CF lung disease has long been recognized, our understanding of pulmonary mycosis is less clear. The range and detection rates of fungal taxa isolated from CF airway samples are expanding, however, in the absence of consensus criteria and univocal treatment protocols for most respiratory fungal conditions, interpretation of laboratory reports and the decision to treat remain challenging. In this review, we give an overview on fungal airway infections in CF and CF-lung transplant recipients and focus on the most common fungal taxa detected in CF, Aspergillus fumigatus, Candida spp., Scedosporium apiospermum complex, Lomentospora species, and Exophiala dermatitidis, their clinical presentations, common treatments and prophylactic strategies, and clinical challenges from a physician’s point of view.

scholarly journals Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 716
Author(s):  
Claudia Lattanzi ◽  
Giulia Messina ◽  
Valentina Fainardi ◽  
Maria Candida Tripodi ◽  
Giovanna Pisi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Diagnostic Criteria ◽  
Respiratory Infections ◽  
Fungal Infections ◽  
Early Recognition ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Clinical Manifestations ◽  
Diagnostic Tools ◽  
The Impact

Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa, have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression. Clinical features, diagnostic criteria and treatment of ABPA are still a matter of debate. Given the consequences of a late ABPA diagnosis or the risk of ABPA overdiagnosis, it is imperative that the diagnostic criteria guidelines are reviewed and standardized. Along with traditional criteria, radiological features are emerging as tools for further classification as well as novel immunological tests. Corticosteroids, itraconazole and voriconazole continue to be the bedrock of ABPA therapy, but other molecules, such as posaconazole, vitamin D, recombinant INF-γ and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, have been showing positive results. However, few studies have been conducted recruiting CF patients, and more research is needed to improve the prevention and the classification of clinical manifestations as well as to personalize treatment. Early recognition and early treatment of fungal infections may be fundamental to prevent progression of CF disease. The aim of this narrative review is to give an update on ABPA in children with CF.

scholarly journals Impact of CFTR modulator use on outcomes in people with severe cystic fibrosis lung disease

2020 ◽  
Vol 29 (155) ◽  
pp. 190112 ◽  
Author(s):  
Michal Shteinberg ◽  
Jennifer L. Taylor-Cousar
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Case Series ◽  
Lung Damage ◽  
Cystic Fibrosis Lung Disease ◽  
Drug Compounds ◽  
The Impact ◽  
Cftr Modulators ◽  
Severe Lung Disease

Drug compounds that augment the production and activity of the cystic fibrosis (CF) transmembrane regulator (CFTR) have revolutionised CF care. Many adults and some children with CF suffer advanced and severe lung disease or await lung transplantation. While the hope is that these drug compounds will prevent lung damage when started early in life, there is an ongoing need to care for people with advanced lung disease. The focus of this review is the accumulating data from clinical trials and case series regarding the benefits of CFTR modulator therapy in people with advanced pulmonary disease. We address the impact of treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor on lung function, pulmonary exacerbations, nutrition and quality of life. Adverse events of the different CFTR modulators, as well as the potential for drug–drug interactions, are discussed.

ClC-5: ontogeny of an alternative chloride channel in respiratory epithelia

2002 ◽  
Vol 282 (3) ◽  
pp. L501-L507 ◽  
Author(s):  
Rebecca D. Edmonds ◽  
Ian V. Silva ◽  
William B. Guggino ◽  
Robert B. Butler ◽  
Pamela L. Zeitlin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Chloride Transport ◽  
Premature Death ◽  
Fetal Lung ◽  
Chloride Secretion ◽  
Normal Lung ◽  
Ribonuclease Protection Assay

Chloride transport is critical to many functions of the lung. Molecular defects in the best-known chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR), lead to impaired function of airway defensins, hydration of airway surface fluid, and mucociliary clearance leading to chronic lung disease, and premature death, but do not cause defects in lung development. We examined the expression of one member of the ClC family of volume- and voltage-regulated channels using the ribonuclease protection assay and Western blot analysis in rats. ClC-5 mRNA and protein are most strongly expressed in the fetal lung, and expression is maintained although downregulated postnatally. In addition, using immunocytochemistry, we find that ClC-5 is predominantly expressed along the luminal surface of the airway epithelium, suggesting that ClC-5 may participate in lung chloride secretion. Identifying candidate genes for critical ion transport functions is essential for understanding normal lung morphogenesis and the pathophysiology of several lung diseases. In addition, the manipulation of non-CFTR chloride channels may provide a viable approach for treating cystic fibrosis lung disease.

scholarly journals Cystic Fibrosis-AssociatedStenotrophomonas maltophiliaStrain-Specific Adaptations and Responses to pH

2019 ◽  
Vol 201 (7) ◽  
Author(s):  
Tara Gallagher ◽  
Joann Phan ◽  
Andrew Oliver ◽  
Alexander B. Chase ◽  
Whitney E. England ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Infections ◽  
Expression Profiles ◽  
Bacterial Colonization ◽  
Low Ph ◽  
Lung Damage ◽  
Ph Gradients ◽  
Content Type ◽  
The Impact

ABSTRACTThe airway fluids of cystic fibrosis (CF) patients contain local pH gradients and are more acidic than those of healthy individuals. pH is a critical factor that is often overlooked in studies seeking to recapitulate the infection microenvironment. We sought to determine the impact of pH on the physiology of a ubiqituous yet understudied microbe,Stenotrophomonas maltophilia. Phylogenomics was first used to reconstruct evolutionary relationships between 74 strains ofS. maltophilia(59 from CF patients). Neither the core genome (2,158 genes) nor the accessory genome (11,978 genes) distinguish the CF and non-CF isolates; however, strains from similar isolation sources grouped into the same subclades. We grew two human and six CFS. maltophiliaisolates from different subclades at a range of pH values and observed impaired growth and altered antibiotic tolerances at pH 5. Transcriptomes revealed increased expression of both antibiotic resistance and DNA repair genes in acidic conditions. Although the gene expression profiles ofS. maltophiliain lab cultures and CF sputum were distinct, we found that the same genes associated with low pH were also expressed during infection, and the higher pH cultures were more similar to sputum metatranscriptomes. Our findings suggest thatS. maltophiliais not well adapted to acidity and may cope with low pH by expressing stress response genes and colonizing less acidic microenvironments. As a whole, our study underlines the impact of microenvironments on bacterial colonization and adaptation in CF infections.IMPORTANCEUnderstanding bacterial responses to physiological conditions is an important priority for combating opportunistic infections. The majority of CF patients succumb to inflammation and necrosis in the airways, arising from chronic infection due to ineffective mucociliary clearance. Steep pH gradients characterize the CF airways but are not often incorporated in standard microbiology culture conditions.Stenotrophomonas maltophiliais a prevalent CF opportunistic pathogen also found in many disparate environments, yet this bacterium’s contribution to CF lung damage and its response to changing environmental factors remain largely understudied. Here, we show that pH impacts the physiology and antibiotic susceptibility ofS. maltophilia, with implications for the development of relevantin vitromodels and assessment of antibiotic sensitivity.

scholarly journals A Prospective Real-World Study of the Impact of an Antifungal Stewardship Program in a Tertiary Respiratory-Medicine Setting

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Lisa Nwankwo ◽  
Jimstan Periselneris ◽  
Jamie Cheong ◽  
Keith Thompson ◽  
Peter Darby ◽  
...  
Keyword(s):  
Lung Disease ◽  
Fungal Infections ◽  
Health Care Systems ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Defined Daily Dose ◽  
Antifungal Stewardship ◽  
Team Meetings ◽  
Stewardship Program ◽  
Care Systems ◽  
The Impact

ABSTRACT 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 health care 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 18 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 the 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 program can significantly reduce expenditure in a specialist respiratory service.

scholarly journals The CFTR and ENaC debate: how important is ENaC in CF lung disease?

2012 ◽  
Vol 302 (11) ◽  
pp. L1141-L1146 ◽  
Author(s):  
James F. Collawn ◽  
Ahmed Lazrak ◽  
Zsuzsa Bebok ◽  
Sadis Matalon
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Bacterial Infections ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Ongoing Debate ◽  
The Subject ◽  
Cystic Fibrosis Transmembrane ◽  
Epithelial Sodium Channel Enac

Cystic fibrosis (CF) is caused by the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) function and results in a respiratory phenotype that is characterized by dehydrated mucus and bacterial infections that affect CF patients throughout their lives. Much of the morbidity and mortality in CF results from a failure to clear bacteria from the lungs. What causes the defect in the bacterial clearance in the CF lung has been the subject of an ongoing debate. Here we discuss the arguments for and against the role of the epithelial sodium channel, ENaC, in the development of CF lung disease.

scholarly journals Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections

2015 ◽  
Vol 53 (7) ◽  
pp. 2262-2270 ◽  
Author(s):  
Tyler E. Warkentien ◽  
Faraz Shaikh ◽  
Amy C. Weintrob ◽  
Carlos J. Rodriguez ◽  
Clinton K. Murray ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Bacterial Infections ◽  
Wound Closure ◽  
Fungal Infections ◽  
Combat Trauma ◽  
Content Type ◽  
Transfusion Requirements ◽  
Severity Of Injury ◽  
Significant Difference ◽  
The Impact

Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively;P< 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds withMucoralesgrowth than for wounds with non-Mucoralesgrowth (median, 17 days versus 13 days;P< 0.01). When wounds withMucoralesandAspergillusspp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: orderMucorales,Aspergillusspp., andFusariumspp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds withMucoralesgrowth.

scholarly journals Study of the post tuberculosis lung diseases and the impact of various patient and disease related factors on its occurrence

2019 ◽  
Vol 6 (4) ◽  
pp. 1241
Author(s):  
Jayasri Helen Gali ◽  
Harsha Vardhana Varma ◽  
Aruna Kumari Badam
Keyword(s):  
Lung Disease ◽  
Urban Areas ◽  
Lung Diseases ◽  
Lung Damage ◽  
Common Symptom ◽  
Related Factors ◽  
Cross Sectional ◽  
Restrictive Lung Disease ◽  
Co Morbidity ◽  
The Impact

Background: More than fifty percent of the cured cases of pulmonary tuberculosis develop some form of chronic pulmonary dysfunction. It can present with varying degrees of lung damage, ranging from minimum functional abnormalities to severe forms of dysfunction that can be an important cause of death. Objective of the study to identify the various Post Tuberculosis Lung Diseases (PTBLDs) and to study impact of the patient and disease related factors on its occurrence.Methods: Cross-sectional, observational study was conducted in 134 adult, post tuberculosis patients, aged between 18-65 years, who have completed at least one year after the end of anti-tubercular treatment. All symptomatic post TB lung disease patients coming to the pulmonology out-patient clinic at the Apollo Institute of Medical sciences and Research were included in the study.Results: Majority were more than 50 years (35.3%) and males (59.4%). Majority were from urban areas (70.7%), low social class (72.2%), and unskilled workers (56.4%). Most common symptom was cough in 74.4% cases. Majority of the cases had symptoms from one week to one month i.e. 47.4%. Only eight cases were found out to be very prompt in reporting their symptoms. 39 cases had some or the other co-morbidity. Current chest X-ray status was normal in only three cases. Mean FEV1 was 1.38 which increased to 1.52; mean FVC was 1.23 which increased to 1.58; mean FEV1/FVC was 67.37 which increased to 72.76 after giving the bronchodilator. 78(58.6%) cases had obstructive and 27(20.3%) had restrictive lung disease. In 30 cases the disease was reversible. Majority of the cases were of pulmonary fibrosis followed by bronchiectasis.Conclusion: Further studies are needed to develop approaches for the prevention, care and treatment of patients with post TBLD.

scholarly journals Aspergillus-related lung disease in people with cystic fibrosis: can imaging help us to diagnose disease?

2021 ◽  
Vol 30 (162) ◽  
pp. 210103
Author(s):  
Qianting Lv ◽  
Bernadette B.L.J. Elders ◽  
Adilia Warris ◽  
Daan Caudri ◽  
Pierluigi Ciet ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Computed Tomography ◽  
Cystic Fibrosis ◽  
Lung Disease ◽  
Lung Damage ◽  
Current Evidence ◽  
Resonance Imaging ◽  
Chronic Infections ◽  
Chest Computed Tomography ◽  
Different Types

In people with cystic fibrosis (PwCF), viscous sputum and dysfunction of the mucociliary escalator leads to early and chronic infections. The prevalence of Aspergillus fumigatus in sputum is high in PwCF and the contribution of A. fumigatus to the progression of structural lung disease has been reported. However, overall, relatively little is known about the contribution of A. fumigatus to CF lung disease. More knowledge is needed to aid clinical decisions on whether to start antifungal treatment. In this review, we give an overview of A. fumigatus colonisation and infection in PwCF and the different types of pulmonary disease caused by it. Furthermore, we discuss the current evidence for structural lung damage associated with A. fumigatus in PwCF on chest computed tomography and magnetic resonance imaging. We conclude that radiological outcomes to identify disease caused by A. fumigatus can be important for clinical studies and management.

scholarly journals Genomic and Phenotypic Evolution of Achromobacter xylosoxidans during Chronic Airway Infections of Patients with Cystic Fibrosis

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
S. M. Hossein Khademi ◽  
Migle Gabrielaite ◽  
Magnus Paulsson ◽  
Mattis Knulst ◽  
Eleni Touriki ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bacterial Infections ◽  
Bacterial Genome ◽  
Bacterial Pathogen ◽  
Achromobacter Xylosoxidans ◽  
Phenotypic Evolution ◽  
Unique Challenge ◽  
Human Host ◽  
Airway Infections ◽  
Chronic Airway

A thorough understanding of bacterial pathogen adaptation is essential for the treatment of chronic bacterial infections. One unique challenge in the analysis and interpretation of genomics data is identifying the function impact of mutations accumulated in the bacterial genome during colonization in the human host.

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