Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Apr 2015
ReviewGenotypes and phenotypes in cystic fibrosis and cystic fibrosis transmembrane regulator-related disorders.
Cystic fibrosis (CF) is characterized by remarkable variability in severity, rate of disease progression, and organ involvement. In spite of the considerable amount of data collected on the relationship between genotype and phenotype in CF, this is still a challenging matter of debate. Barriers to the interpretation of this connection are the large number of mutations in the CF transmembrane regulator (CFTR) gene, the difficulties in attributing several of them to a specific mode of dysfunction, and a limited number of the almost 2,000 mutations so far detected, which have been clinically annotated. ⋯ The phenotype variability extends to conditions, named CFTR-related disorders, which are connected with CFTR dysfunction, but do not satisfy diagnostic criteria for CF. The current level of knowledge does not allow use of the CFTR genotype to predict individual outcome and cannot be used as an indicator of CF prognosis. This might change with the development of treatments targeting specific mutations and possibly capable of changing the natural history of the disease.
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Semin Respir Crit Care Med · Apr 2015
ReviewImaging in cystic fibrosis and non-cystic fibrosis bronchiectasis.
Bronchiectasis is defined as a permanent and progressive dilation of the airways, typically as a result of inflammation, infection, and subsequent repair. It typically presents with chronic cough, suppurative sputum production, and airway dilation. High-resolution computed tomography (HRCT) is now well established as the primary imaging tool for its investigation. ⋯ This is particularly relevant in a pulmonary disease such as bronchiectasis, which often undergoes serial HRCT surveillance in contemporary practice. Several new CT clinical applications in bronchiectasis have been recently advanced, and CT is now being increasingly incorporated into investigative algorithms to assess bronchiectasis treatment effects. In this review, we assess the latest imaging features of CF and non-CF bronchiectasis, discuss radiation dose reducing methods and technology of the latest scanners, describe recent CT clinical applications, and explore the use of CT as a treatment surrogate in CF and non-CF bronchiectasis.
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Semin Respir Crit Care Med · Apr 2015
ReviewThe microbiome and emerging pathogens in cystic fibrosis and non-cystic fibrosis bronchiectasis.
Chronic pulmonary sepsis is the predominant cause of morbidity for patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously it was thought that respiratory infection in these patients was mostly limited to a very small number of typical pathogens; however, in recent years there have been increasing reports of infection with other emerging potential pathogens including Burkholderia, Stenotrophomonas, Achromobacter, Ralstonia, Pandoraea, nontuberculous mycobacteria, and fungal species. Furthermore, culture-independent methodologies have established that the lungs of patients with CF and non-CF bronchiectasis comprise mixed microbiological communities of aerobic and anaerobic bacteria, fungal and viral species, collectively referred to as the lung microbiome. This article addresses the clinical relevance of emerging pathogens and the lung microbiome in CF and non-CF bronchiectasis.
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Improved clinical care has led to a dramatic increase in life expectancy for people with cystic fibrosis (CF). As they live longer, people with CF are therefore developing secondary complications. Cystic fibrosis-related diabetes (CFRD) is the commonest extrapulmonary complication of CF. ⋯ Many centers are therefore using continuous glucose monitoring to refine the diagnosis and investigate real-life glycemic control. Future research will hopefully widen our understanding of the pathophysiology of CFRD and therefore the treatment options available. There are clearly some promising results suggesting the use of oral agents may prove beneficial in treating CFRD but insulin should remain the mainstay of treatment until these are further evaluated.
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Semin Respir Crit Care Med · Apr 2015
ReviewCystic fibrosis transmembrane conductance regulator modulators: the end of the beginning.
Cystic fibrosis (CF) represents one of the success stories of modern medicine with sustained incremental increases in the survival from one of childhood death to one of adult survival into the middle decades over the past 30 years. Improving survival has focused on multidisciplinary management centered on treating the consequences of this genetic disease. It has been firmly established for more than 20 years that mutations in the CF transmembrane conductance regulator (CFTR) gene result in a defective protein that normally functions as a chloride channel on epithelial cell surfaces. ⋯ This review highlights the evidence to date on efforts to modulate CFTR and restore robust functional protein to the cell surface. This approach has now led to the licensing of one CFTR potentiator, which has been shown to have significant clinical improvements in a subset of CF patients. This success represents the beginning for CFTR modulation and further research is ongoing which aims to broaden the applicability of these techniques.