Cystic Fibrosis and Sleep Circadian Rhythms.

Cystic fibrosis (CF) is due to a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which leads to unusual water and chloride secretion across epithelial surfaces. The lungs are responsible for most morbidity, though other organs are frequently affected. Sleep abnormalities have long been recognized in CF. Abnormal ventilation and oxygenation, sinus disease, deconditioning due to muscle weakness and recurrent infections, and inflammation have been thought to play a role in sleep disorders in CF. However, there is evidence that CFTR gene dysregulation can affect circadian rhythms in CF. Early recognition and treatment of circadian rhythms may improve outcomes in CF.

Airway Clearance Therapy in Cystic Fibrosis Patients Insights from a Clinician Providing Cystic Fibrosis Care.

Cystic fibrosis (CF) is a genetic disease characterized by an accumulation of thick layers of mucus, leading to airway obstruction and air trapping. Poorly cleared mucus leads to frequent respiratory infections that produce chronic cough and dyspnea. The presence of infected mucus induces progressive inflammation. The resulting damage anatomically distorts airways leading to development of bronchiectasis. Bronchiectasis is irreversible and results in progressive respiratory function decline over time. Impaired mucociliary clearance together with tenacious mucus makes expectoration with cough alone problematic. Clinicians providing effective care for CF patients must have knowledge of the wide variety of treatment options currently available. Knowledge of these techniques will enable clinicians to prescribe airway clearance therapy (ACT) where necessary and provide treating physicians the ability to adapt to changing patient treatments as necessary. Training programs frequently do not provide in-depth knowledge of ACT technologies in CF patients resulting in knowledge gaps once physicians are in practice. This paper reviews strategies for ACT. It is specifically targeted for clinicians who frequently provide care for patients with CF.

Managing Fungal Infections in Cystic Fibrosis Patients: Challenges in Clinical Practice.

Cystic Fibrosis (CF) is an autosomal recessive disease characterized by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Impairment of the CFTR protein in the respiratory tract results in the formation of thick mucus, development of inflammation, destruction of bronchial tissue, and development of bacterial or fungal infections over time. CF patients are commonly colonized and/or infected with fungal organisms, Candida albicans or Aspergillus fumigatus, with prevalence rates ranging from 5% to 78% in the literature. Risk factors for acquiring fungal organisms include older age, coinfection with Pseudomonas aeruginosa, prolonged use of oral and inhaled antibiotics, and lower forced expiratory volume (FEV1). There are limited data available to differentiate between contamination, colonization, and active infection. Furthermore, the pathogenicity of colonization is variable in the literature as some studies report a decline in lung function associated with fungal colonization whereas others showed no difference. Limited data are available for the eradication of fungal colonization and the treatment of active invasive aspergillosis in adult CF patients. In this review article, we discuss the challenges in clinical practice and current literature available for laboratory findings, clinical diagnosis, and treatment options for fungal infections in adult CF patients.

Emerging Alternatives to Conventional Clinic Visits in the Era of COVID-19: Adoption of Telehealth at VCU Adult Cystic Fibrosis Center.

Cystic fibrosis (CF) is a genetic disease in which consistent follow-up care is required to avoid a decline in pulmonary and nutritional health. It is believed that if a CF patient ceases treatment for 2 days, this can result in an exacerbation. One week of missed treatments can result in a hospitalization and 1 month of missed treatments can result in an earlier demise. With a global pandemic that has affected more than 9 million people, many CF clinics were required to take steps to avoid transmission of this dangerous virus. This may result in delays in delivery of timely CF care due to closure of clinics and pulmonary function testing (PFT) laboratories and limited staff allowed on site for conducting in-person visits. These measures, along with suggestions from the Cystic Fibrosis Foundation (CFF) to extend the social distancing longer than traditional CDC recommendations for the CF community, create an urgent need to explore novel ways to deliver safer care via new standards in chronic health conditions like CF. Especially, as these preventive strategies may be necessary for long-term maintenance, few objective alternatives exist to guide clinicians and allied health professionals in CF centers how to proceed in this new era. This also presents an opportunity for novel approaches that could improve delivery of CF care with remote monitoring and real-time delivery of care in patients' home environments. Such emerging approaches could benefit patient care, leading to reduced costs and readmissions and improved access to care, medication adherence, and patient communication. We summarize our own experience and discuss the emerging delivery of CF care which can be generalizable to other pulmonary illnesses.

The Lung Life of a Cystic Fibrosis Patient: A Patient and Physician Perspective.

This article is co-authored by a patient living with cystic fibrosis, and her treating physician. The first section of this commentary article is authored by a patient, who describes their experience of living with cystic fibrosis. The following section is authored by the patient's physician, who discusses the management of cystic fibrosis in the context of the patient's experiences.

The Use of Amikacin Liposome Inhalation Suspension (Arikayce) in the Treatment of Refractory Nontuberculous Mycobacterial Lung Disease in Adults.

Nontuberculous mycobacteria (NTM) can cause and perpetuate chronic inflammation and lung infection. Despite having the diagnostic criteria, as defined by the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA), clinicians find it challenging to diagnose and treat NTM-induced lung disease. Inhaled antibiotics are suitable for patients with lung infection caused by Pseudomonas aeruginosa and other organisms, but until recently, their utility in NTM-induced infection was not established. The most common NTM pathogens identified are the slow-growing Mycobacterium avium complex (MAC) and the rapid-growing M. abscessus complex (MABSC), both of which include several subspecies. Other less commonly isolated species include M. kansasii, M. simiae, and M. fortuitum. NTM strains are frequently more resistant than what is found in bacterial sputum cultures. Until recently, there was no approved inhaled antibiotic therapy for patients who were culture positive for pulmonary NTM infection. Of late, inhaled amikacin has been under investigation for the treatment of NTM-induced pulmonary infection. The FDA approved Arikayce (amikacin liposome inhalation suspension or ALIS) based on results from the ongoing Phase 3 CONVERT trial. In this study, the use of Arikayce met its primary endpoint of sputum culture conversion by the sixth month of treatment. The addition of Arikayce to guideline-based therapy led to negative sputum cultures for NTM by month 6 in 29% of patients compared to 8.9% of patients treated with guideline-based therapy alone. The effectiveness of Arikayce holds promise. However, due to limited data on Arikayce's safety, it is currently useful only for a specific population, particularly patients with refractory NTM-induced lung disease. Future trials must verify the target group and endorse the clinical benefits of Arikayce.

Triplet CFTR modulators: future prospects for treatment of cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive genetic disease characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a chloride channel responsible for ion flow across epithelial surfaces of lung, sinuses, pancreas, intestine, and liver. Researchers have grouped CFTR genetic mutations into various protein defects: reduced protein synthesis (class 1 mutations), abnormal protein folding and maturation (class 2 mutation), and abnormal gating (class 3 mutation). These mutations usually present as severe forms of CF due to complete absence of CFTR at cell surfaces. Milder forms (eg, protein maturation and conductance defects, classes 4-6) present as less severe forms of CF related to the presence of CFTR at the cell surface. Differences in severity are directly due to CFTR function which is based on the severity of CFTR mutation. This knowledge has proven useful for designing therapy for individual mutations and mutation classes. The discovery and US Food and Drug Administration approval of Kalydeco® (ivacaftor) in early 2011 marked the beginning of a new era of therapies that are focused on improving defective CFTR protein function. However, due to its specificity for the G551D mutation, ivacaftor only benefits5% of CF patients. Approximately 50% of CF patients have two copies of the F508Del mutation, while other CF patients carry only one copy of this gene. More recently, Orkambi®, a two compound medication composed of lumacaftor and ivacaftor, has provided the foundation necessary to further build on molecular concepts of: correction of trafficking, potentiation, and amplification of defective CFTR. These new concepts will form the basis of future CF therapies and extend CFTR treatment to almost 50% of CF patients. Evolving knowledge of the molecular mechanisms responsible for defective CFTR has prompted new research focused on "repair" of each phase of CFTR expression and function, thus creating a new class of combination "CFTR correctors" referred to as "triplet CFTR compounds." This article will review how patients can be selected and treated with these newer agents that are based on specific mutations. In the future, many CF practitioners have expectations that initiation of treatment for CF patients will occur simply by use of biomarkers of CFTR expression (eg, sweat chloride, nasal potential difference, rectal organoids) rather than testing for specific mutations. As continued research identifies biomarkers with greater specificity and which predict clinical response, therapies can potentially be tailored to individual responses.

Prognostic value of cardiac-specific troponins in chronic obstructive pulmonary disease exacerbations: a systematic review.

UNLABELLED: fer useful prognostic information in this population and might identify a group of patients to target for more intensive thera- peutic interventions. BACKGROUND: Cardiac troponins are specific and sensitive biomarkers used for diagnosis and prognosis in myocardial infarction. Troponin elevations can also occur in other disorders and may be useful to predict mortality. This systematic review is intended to determine whether or not elevated troponins are predictive of mortality (in-hospital, short term, and longer-term) among patients admitted with COPD exacerbation. METHODS: PubMed/Medline was searched to identify relevant English language articles that measured troponin T or troponin I in patients hospitalized for COPD exacerbation and assessed mortality, with or without other clinical outcomes. Only studies of significant size that presented original data were included. RESULTS: Nine research reports (4 prospective, 5 retrospective) qualified for review. Mortality was consistently increased in seven of these studies among COPD patients who had elevated troponin levels during an exacerbation. One retrospective study found no effect on (in-hospital) mortality but reported increased morbidity (greater oxygen requirements and more ventilatory failure) and increased length of hospital stay in patients with elevated troponin whereas discharge troponin T in one prospective study predicted hospitalizations. CONCLUSIONS: The review shows a strong direct association between cardiac troponin and mortality in patients hospitalized for COPD exacerbations. Troponin monitoring could offer useful prognostic information in this population and might identify a group of patients to target for more intensive therapeutics interventions.

Outpatient treatment of adults with cystic fibrosis by primary care physicians.

Primary care physicians now see adult patients with Cystic Fibrosis (CF) who have multi organ consequences of the disease that present a complex management dilemma. Early diagnosis and treatment of these problems is important to limit morbidity. In this article we will review common problems experienced by these patients and present approaches to their management.