Cystic fibrosis

Burkholderia cepacia complex ( Bcc ) is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic fibrosis (CF), Bcc can cause severe lung infections that lead to accelerated lung damage, which can be complicated by necrotizing pneumonia accompanied by high fevers, leucocytosis, and bacteraemia, which commonly causes fatal outcomes. Specifically, infection by Burkholderia cenocepacia is considered an exclusion criterion for lung transplantation...

In the last decade, fungal respiratory diseases have been increasingly investigated for their impact on the clinical course of people with cystic fibrosis (CF), with a particular focus on infections caused by Aspergillus spp. The most common organisms from this genus detected from respiratory cultures are Aspergillus fumigatus and Aspergillus terreus , followed by Aspergillus flavus , Aspergillus niger , and Aspergillus nidulans . These species have been identified to be both chronic colonizers and sources of active infection and may negatively impact lung function in people with CF...

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed...

BACKGROUND: Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR variant F508del is the commonest CF-causing variant (found in up to 90% of people with CF (pwCF)). The F508del variant lacks meaningful CFTR function - faulty protein is degraded before reaching the cell membrane, where it needs to be to effect transepithelial salt transport. Corrective therapy could benefit many pwCF...

New England Journal of Medicine, Volume 389, Issue 18, Page 1693-1707, November 2023.

With the 2019 breakthrough in the development of highly effective modulator therapy providing unprecedented clinical benefits for over 90% of patients with cystic fibrosis who are genetically eligible for treatment, this rare disease has become a front runner of transformative molecular therapy. This success is based on fundamental research, which led to the identification of the disease-causing CFTR gene and our subsequent understanding of the disease mechanisms underlying the pathogenesis of cystic fibrosis, working together with a continuously evolving clinical research and drug development pipeline...

Following discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 and subsequent elucidation of the varied CFTR protein abnormalities that result, a new era of cystic fibrosis management has emerged-one in which scientific principles translated from the bench to the bedside have enabled us to potentially treat the basic defect in the majority of children and adults with cystic fibrosis, with a resultant burgeoning adult cystic fibrosis population. However, the long-term effects of these therapies on the multiple manifestations of cystic fibrosis are still under investigation...

PURPOSE OF REVIEW: The nutritional landscape in cystic fibrosis has shifted dramatically in the era of CFTR modulator therapy. In this review, we will critically examine the literature on overweight and obesity in CF, current nutritional care unknowns and opportunities for further investigation or adaptation in clinical care. RECENT FINDINGS: Results of clinical trial and real-world data reflect marked improvement in nutritional status and quality of life. Clinical outcomes including CF related diabetes and CF related liver disease appear positively impacted...

PURPOSE OF REVIEW: Advances in cystic fibrosis (CF) therapies over the past decade pivotally changed the morbidity and mortality of CF with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators that rescue dysfunctional CFTR protein in individuals with eligible genotypes. However, a significant proportion of the CF population is in need of alternative treatment strategies to address CFTR variants that are ineligible for therapeutic protein correction and/or potentiation...

IMPORTANCE: Cystic fibrosis, a genetic disorder defined by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, affects more than 30 000 individuals in the US and approximately 89 000 worldwide. Absent or decreased function of the CFTR protein is associated with multiorgan dysfunction and shortened life expectancy. OBSERVATIONS: CFTR is an anion channel in the apical membrane of epithelial cells. Loss of function leads to obstructed exocrine glands...

With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is acute pulmonary exacerbation (PEx). Clinical and microbial epidemiology studies of CF PEx continue to provide important insight into the disease course, prognosis, and complications...

Recurrent and chronic bacterial infections are common in people with cystic fibrosis (CF) and contribute to lung function decline. Antibiotics are the mainstay in the treatment of exacerbations and chronic bacterial infection in CF. Inhaled antibiotics are effective in treating chronic respiratory bacterial infections and eradicating Pseudomonas aeruginosa from the respiratory tract, with limited systemic adverse effects. In the past decade, highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators have become a new therapy that partially corrects/opens chloride transport in patients with selected CFTR mutations, restoring mucus hydration and improving mucociliary clearance...

Diagnosing cystic fibrosis (CF) in adulthood is not a rare occurrence for CF centers despite the popular belief that the diagnosis is achieved almost universally in childhood by means of newborn screening or early clinical presentation. The purpose of this review article is to highlight specific considerations of adult diagnosis of CF. Obtaining a diagnosis of CF at any age is exceptionally important to ensure optimal treatment, monitoring, and support. In the new era of more personalized treatment with the advent of transformative therapies targeting the underlying protein defect, accurate diagnosis is of increasing importance...

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...

The threat of respiratory virus infection to human health and well-being has been clearly highlighted by the coronavirus disease 2019 (COVID-19) pandemic. For people with cystic fibrosis (CF), the clinical significance of viral infections long predated the emergence of severe acute respiratory syndrome coronavirus 2. This article reviews the epidemiology, diagnosis, and treatment of respiratory virus infection in the context of CF as well as the current understanding of interactions between viruses and other microorganisms in the CF lung...

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...

Lung infection is the leading cause of death in cystic fibrosis (CF), and antimicrobial therapies are the backbone of infection management. While many different strategies may be applied, rigorous microbiological surveillance, intensive eradication therapy, and long-term maintenance therapy based on inhaled antibiotics may be considered the main strategy for infection control in individuals with CF. While most of the existing evidence is based on infection with Pseudomonas aeruginosa , other important pathogens causing lung inflammation and deterioration exist and should be treated despite the evidence gap...

The coronavirus disease 2019 pandemic accelerated the implementation of digital technologies, which have now become embedded as essential tools for the management of chronic disease, including cystic fibrosis (CF). Despite subsequent easing of restrictions and because of improved clinical stability resulting from the introduction of highly effective modulator therapy, digital technologies including video and telephone consultations and remote monitoring are likely to remain integral to the future delivery of CF health care...

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...

Exercise and airway clearance techniques (ACTs) have been a cornerstone of treatment for people with cystic fibrosis (pwCF) for many decades. Exercise may confer both respiratory and nonrespiratory benefits for pwCF, with greater exercise capacity associated with improved survival. A wide variety of exercise interventions for pwCF have been investigated. ACTs may assist in reducing respiratory symptoms for pwCF and are currently recommended to be performed daily, with the types of ACTs used varying globally...