Cystic fibrosis [keywords]
- U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. [JOURNAL ARTICLE]
- MMWR Recomm Rep 2016; 65(3):1-103.
The 2016 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) comprises recommendations for the use of specific contraceptive methods by women and men who have certain characteristics or medical conditions. These recommendations for health care providers were updated by CDC after review of the scientific evidence and consultation with national experts who met in Atlanta, Georgia, during August 26-28, 2015. The information in this report updates the 2010 U.S. MEC (CDC. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR 2010:59 [No. RR-4]). Notable updates include the addition of recommendations for women with cystic fibrosis, women with multiple sclerosis, and women receiving certain psychotropic drugs or St. John's wort; revisions to the recommendations for emergency contraception, including the addition of ulipristal acetate; and revisions to the recommendations for postpartum women; women who are breastfeeding; women with known dyslipidemias, migraine headaches, superficial venous disease, gestational trophoblastic disease, sexually transmitted diseases, and human immunodeficiency virus; and women who are receiving antiretroviral therapy. The recommendations in this report are intended to assist health care providers when they counsel women, men, and couples about contraceptive method choice. Although these recommendations are meant to serve as a source of clinical guidance, health care providers should always consider the individual clinical circumstances of each person seeking family planning services. This report is not intended to be a substitute for professional medical advice for individual patients. Persons should seek advice from their health care providers when considering family planning options.
- Acquired Cystic Fibrosis Transmembrane Conductance Regulator Deficiency. [JOURNAL ARTICLE]
- Adv Otorhinolaryngol 2016.:78-85.
In the genetic airway disease cystic fibrosis (CF), deficiency or dysfunction of the cystic fibrosis membrane conductance regulator (CFTR) alters anion transport in respiratory epithelium and consequently disrupts mucociliary clearance. An enriched understanding of the role of CFTR in the maintenance of normal epithelial function has revealed that mild and variable CFTR mutations play a causative role in a number of diseases not classically associated with CF. Furthermore, recent evidence indicates that acquired defects in wild-type CFTR protein processing, endocytic recycling and function can contribute to the pathogenesis of airway diseases, such as chronic obstructive pulmonary disease. In this chapter, we discuss emerging findings implicating acquired CFTR dysfunction in the pathogenesis of chronic rhinosinusitis and propose a new and leading edge approach to future CRS therapy using CFTR potentiators.
- Cystic Fibrosis Sinusitis. [JOURNAL ARTICLE]
- Adv Otorhinolaryngol 2016.:29-37.
Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF transmembrane conductance regulator gene(CFTR) resulting in impaired ion transport. Nearly all people with CF will develop chronic rhino-sinusitis (CRS) and present with the characteristic viscous mucus, impaired mucociliary clearance and chronic inflammation/infection of the sinonasal cavity. While some individuals with CF can appear relatively asymptomatic in terms of their sinus disease, commonly reported symptoms include anosmia, headache, facial pain, nasal obstruction, chronic congestion and nasal discharge. Nasal endoscopy typically reveals mucosal edema, purulent discharge and nasal polyposis. Computed tomography (CT) imaging classically demonstrates the distinguishing findings of sinus hypoplasia or aplasia with generalized opacification, medial bulging of the lateral sinonasal sidewall and a demineralized uncinate process. Current treatment for CF sinusitis includes the use of hypertonic saline, topical and systemic steroids, antibiotics and endoscopic surgery. Research investigating novel therapies designed at targeting the primary defect of CF is showing promise for reversal of CF sinus disease, in addition to potential for disease prevention.
- Differential Diagnosis of Chronic Rhinosinusitis with Nasal Polyps. [JOURNAL ARTICLE]
- Adv Otorhinolaryngol 2016.:1-12.
Nasal polyps are semi-translucent mucosal outgrowths of the paranasal sinuses which typically arise in the setting of chronic rhinosinusitis (CRS). Nasal polyps are also associated with asthma, aspirin sensitivity, cystic fibrosis and allergic fungal rhinosinusitis (AFS). The majority of nasal polyps are bilateral and characterized by tissue edema and eosinophil infiltration. Patients with nasal polyps often present with complaints including nasal obstruction, congestion, rhinorrhea or altered sense of smell. The differential diagnosis ranges from benign masses such as schneiderian papilloma, antrochoanal polyp, angiofibroma and encephalocele to malignant neoplasms such as squamous cell carcinoma (SCC), esthesioneuroblastoma, nasal lymphoma and rhabdomyosarcoma. These lesions may have a similar appearance as nasal polyps and particular attention to an alternative diagnosis for nasal polyps should be entertained if the mass is unilateral or congenital in nature. Workup for patients with a unilateral mass should include radiographic imaging, possible biopsy and careful follow-up when appropriate. Here, we review the disease etiology of nasal polyps and describe the approach to the patient with nasal polyps with emphasis on differential diagnosis and workup.
- Lichen secondary metabolite evernic acid as potential quorum sensing inhibitor against Pseudomonas aeruginosa. [Journal Article]
- World J Microbiol Biotechnol 2016 Sep; 32(9):150.
Cystic Fibrosis is a genetic disease and it affects the respiratory and digestive systems. Pseudomonas aeruginosa infections in Cystic Fibrosis are presented as the main cause for high mortality and morbidity rates. Pseudomonas aeruginosa populations can regulate their virulence gene expressions via the bacterial communication system: quorum sensing. Inhibition of quorum sensing by employing quorum sensing inhibitors can leave the bacteria vulnerable. Therefore, determining natural sources to obtain potential quorum sensing inhibitors is essential. Lichens have ethnobotanical value for their medicinal properties and it is possible that their secondary metabolites have quorum sensing inhibitor properties. This study aims to investigate an alternative treatment approach by utilizing lichen secondary metabolite evernic acid to reduce the expressions of Pseudomonas aeruginosa virulence factors by inhibiting quorum sensing. For this purpose, fluorescent monitor strains were utilized for quorum sensing inhibitor screens and quantitative reverse-transcriptase PCR analyses were conducted for comparison. Results indicate that evernic acid is capable of inhibiting Pseudomonas aeruginosa quorum sensing systems.
- Abnormal Glucose Tolerance in Infants and Young Children with Cystic Fibrosis. [JOURNAL ARTICLE]
- Am J Respir Crit Care Med 2016 Jul 22.
In cystic fibrosis, abnormal glucose tolerance is associated with decreased lung function and worsened outcomes. Translational evidence indicates that abnormal glucose tolerance may begin in early life.Determine whether very young children with cystic fibrosis have increased abnormal glucose tolerance prevalence compared to controls.Compare area under the curve for glucose and insulin in cystic fibrosis children to controls.Prospective multicenter study in children ages 3 months- 5 years with and without cystic fibrosis.Oral glucose tolerance testing with glucose, insulin, and C-peptide sampled at 0,10,30,60,90 and 120 min.Twenty-three children with cystic fibrosis and 9 controls had complete data. All controls had normal glucose tolerance. Nine of 23 cystic fibrosis subjects had abnormal glucose tolerance (39%) (p= 0.03). Of those, two met criteria for cystic fibrosis-related diabetes, two indeterminate glycemia, and six impaired glucose tolerance. Children with cystic fibrosis failed to exhibit the normal increase in area under the curve insulin with age observed in controls (p<0.01), despite increased area under the curve glucose (p=0.02).Abnormal glucose tolerance is notably prevalent among young children with cystic fibrosis. Children with cystic fibrosis lack the normal increase in insulin secretion that occurs in early childhood despite increased glucose. These findings demonstrate glycemic abnormalities begin very early in cystic fibrosis, possibly due to insufficient insulin secretion.
- Phenotypes of California CF Newborn Screen-Positive Children with CFTR 5T Allele by TG Repeat Length. [JOURNAL ARTICLE]
- Genet Test Mol Biomarkers 2016 Jul 22.
At the cystic fibrosis transmembrane conductance regulator (CFTR) gene (IVS8)-(TG)m(T)n locus, a lower number of thymidines (legacy names 9T vs. 7T vs. 5T) and a higher number of (TG) repeats (TG-11 vs. 12 vs. 13) are associated with decreasing translation of functional CFTR protein in vitro.Retrospective cohort study comparing phenotypes of California CF newborn screen-positive children (followed 2-8 years) who had two CF-causing mutations (diagnosed as CF) with those who had one mutation from a panel of 40 CF-causing mutations (CF40mut) and one (IVS8)-(TG)11, 12, or 13-5T mutation detected by sequencing (diagnosed as CFTR-related metabolic syndrome [cRMS]).The study included 428 children, of which 234 had two CF-causing mutations, and were used to compare with the other 194 children with one CF-causing mutation and one isolated 5T allele [CF40mut/(TG)13-5T = 21, CF40mut/(TG)12-5T = 85, and CF40mut/(TG)11-5T = 88]. Among children with CF40mut/(TG)13-5T, 38% were diagnosed with CF by 8 years, based on sweat chloride results and clinical presentation. Six percent of those with CF40mut/(TG)12-5T, and none with CF40mut/(TG)11-5T, reached diagnostic criteria.CFTR (IVS8)-(TG)m-5T allele (TG) tract length determination provides valuable information in predicting the risk of developing a CF phenotype. Of the three types of 5T alleles evaluated, screen-positive children with genotype CF40mut/(TG)13-5T progressed from CRMS to CF at a high rate, while there was little evidence of clinical disease in those with CF40mut/(TG)11-5T. Additional data from longer follow-up intervals are needed to fully understand the natural history of individuals with a CF40mut/(TG)m-5T genotype.
- Telehealth clinics increase access to care for adults with cystic fibrosis living in rural and remote Western Australia. [JOURNAL ARTICLE]
- J Telemed Telecare 2016 Jul 20.
A significant proportion (15%, n = 28) of the adults with cystic fibrosis (CF) in Western Australia (WA) live in rural and remote areas and have difficulty accessing specialist care at the state adult CF centre, located in Perth. We aimed to increase access by offering telehealth clinics, and evaluate the impact on health outcomes.Telehealth clinics were offered via videoconference over a 12-month period, with uptake and satisfaction measured at the end of the intervention. Participants could still attend in person clinics at the CF centre if requested. Other outcomes comprised healthcare utilisation (HCU), spirometry, weight and health-related quality of life.In 21 participants, total clinic visits increased from 46 (median (range) per participant 2 (0-6)) in the 12-month period preceding the study to 100 (5 (2-8), p < 0.001) during the intervention. Of the 100 clinics in total, 66 were delivered via telehealth. Satisfaction with telehealth was high and most (94%) participants agreed that telehealth is a good way to deliver CF care. An increase in intravenous antibiotic days (incident rate ratio (IRR) 2.3, p = 0.03) and hospital admission days (IRR 3.7, p = 0.01) was observed. There was an improvement in the vitality domain of the Cystic Fibrosis Questionnaire - Revised (p < 0.05).Telehealth had good uptake and increased clinic attendance in adults with CF living in rural and remote WA, and had high satisfaction amongst participants. The increase in HCU, resulting from increased detection and treatment of exacerbations, may improve long-term outcomes in this population.
- Primary Ciliary Dyskinesia: First Health-related Quality of Life Measures for Pediatric Patients. [JOURNAL ARTICLE]
- Ann Am Thorac Soc 2016 Jul 27.
Primary ciliary dyskinesia (PCD) is a rare disease. There are no available data on disease-specific pediatric patient-reported outcomes.Our objective was to create developmentally-appropriate, health-related quality of life questionnaires (QOL-PCD) for children (6-12 years) and adolescents (13-17 years) with PCD and a parent proxy measure.QOL-PCD was developed using a cross-cultural protocol-driven approach satisfying both North American and European drug regulatory agency guidelines. A conceptual framework was generated by literature review, focus groups (expert clinicians and patients/parents) and open-ended interviews with children, adolescents and parents of PCD patients. We recruited participants from international research consortiums, PCD clinics and patient advocacy groups, aiming for representation of a wide spectrum of disease severity, sociodemographic status and ethnicity. Qualitative interviews were conducted by trained and experienced research assistants and psychologists. Transcripts were content-analyzed with Atlas.ti/Nvivo to assess saturation of content. A self-completed item relevance survey was administered to European Union participants. Qualitative and quantitative data were used to construct draft instruments. Questionnaires were further refined following cognitive interviews.Focus groups (n=62 experts; n=20 patients/parents) and open-ended interviews with patients/parents (n=69; 34 males; age of diagnosis 0-15 years; forced expiratory volume in one second (FEV1) 58-118% predicted) revealed a wide spectrum of issues unique to this population. Content analysis of transcripts identified the following domains, depending on age: Respiratory Symptoms, Physical Functioning, Emotional Functioning, Treatment Burden, Ears & Hearing, Sinus Symptoms, Social Functioning, Role Functioning, Vitality, Health Perceptions, School Functioning, and Eating & Weight. Different items were retained in questionnaires based on age and role of respondent: 37, 43 and 41 items for children, adolescents, and parent proxy respectively. The item relevance survey (n=57) yielded similar results to open-ended interviews. Cognitive testing (n=47; 20 males; age of diagnosis 0-11 years; FEV 49-124% predicted) confirmed that items and response choices were clear, understood by respondents and that all relevant items were included.QOL-PCD measures developed using rigorous, protocol-driven methods and international collaborations have demonstrated content validity and cross-cultural equivalence for implementation in English-speaking populations. Psychometric testing is underway to determine their measurement properties for evaluating clinical interventions and informing quality of care.