Seminars in respiratory and critical care medicine
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In the past decade, the medical management of people with cystic fibrosis (pwCF) has changed with the development of small molecules that partially restore the function of the defective CF transmembrane conductance regulator (CFTR) protein and are called CFTR modulators. Ivacaftor (IVA), a CFTR potentiator with a large effect on epithelial ion transport, was the first modulator approved in pwCF carrying gating mutations. Because IVA was unable to restore sufficient CFTR function in pwCF with other mutations, two CFTR correctors (lumacaftor and tezacaftor) were developed and used in combination with IVA in pwCF homozygous for F508del, the most common CFTR variant. ⋯ Recent clinical trials and real-world studies suggest that benefits of HEMT could even prove greater when used earlier in life (i.e., in younger children and infants). This article shortly reviews the past 10 years of development and use of CFTR modulators. Effects of HEMT on extrapulmonary manifestations and on CF demographics are also discussed.
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Semin Respir Crit Care Med · Apr 2023
Beyond the Lungs-Emerging Challenges in Adult Cystic Fibrosis Care.
Cystic fibrosis (CF) is a multisystem disease. This article provides an up-to-date review of many of the nonrespiratory complications of CF, including mental health issues, nutritional and gastrointestinal problems, fertility issues, diabetes mellitus, bone health and musculoskeletal problems, liver disease, renal problems, and risk of malignancy. It highlights the recent impact of new therapies, including CF transmembrane conductance regulator modulators, on the nonrespiratory complications of CF and provides insights into the potential challenges faced by an aging population of adults with CF and their caregivers, including the potential future risk for cardiovascular disease.
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In cystic fibrosis, a new era has started with the approval and use of highly effective cystic fibrosis transport regulator (CFTR) modulator therapy. As pulmonary function is increasing and exacerbation rate significantly decreases, the current meaning of fungal pulmonary diseases is questioned. During the past couple of decades, several studies have been conducted regarding fungal colonization and infection of the airways in people with cystic fibrosis. ⋯ Whether the percentage will decrease or not will be the task of future evaluations in studies and registry analysis. Using the established definition for different categories of fungal diseases is recommended and should be taken into account if patients are deteriorating without responding to antibiotic treatment. Drug-drug interactions, in particular when using azoles, should be recognized and therapies need to be adjusted accordingly.
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Semin Respir Crit Care Med · Apr 2023
ReviewMicrobial Epidemiology of the Cystic Fibrosis Airways: Past, Present, and Future.
Progressive obstructive lung disease secondary to chronic airway infection, coupled with impaired host immunity, is the leading cause of morbidity and mortality in cystic fibrosis (CF). Classical pathogens found in the airways of persons with CF (pwCF) include Pseudomonas aeruginosa, Staphylococcus aureus, the Burkholderia cepacia complex, Achromobacter species, and Haemophilus influenzae. While traditional respiratory-tract surveillance culturing has focused on this limited range of pathogens, the use of both comprehensive culture and culture-independent molecular approaches have demonstrated complex highly personalized microbial communities. ⋯ Recently, CF transmembrane conductance regulator (CFTR) modulators, small molecules designed to potentiate or restore diminished protein levels/function, have been successfully developed and have profoundly influenced disease course. Despite the multitude of clinical benefits, structural lung damage and consequent chronic airway infection persist in pwCF. In this article, we review the microbial epidemiology of pwCF, focus on our evolving understanding of these infections in the era of modulators, and identify future challenges in infection surveillance and clinical management.