Life Of Cystic Fibrosis Patients Research Articles

Psychometric Assessment and Health Related Quality of Life of Children and adolescents With Cystic Fibrosis

Abstract Background Cystic fibrosis (CF) is an exhausting and time-consuming disease that can interfere or impair typical daily life activities and social interactions. Aim and Objectives Evaluation of psychological aspects and Quality of life in cystic fibrosis patients. Subjects and Methods This was a cross sectional study, conducted at the Paediatric Chest Clinic, Children's Hospital, Ain Shams University on 31 patients with verified diagnosis of CF compared to 31 healthy children. Psychological assessment was done using Children depression Inventory (CDI) Scale, Spence Children’s Anxiety Scale, and The Pediatric Quality of Life (PedsQLTM) Scales. Result: CF patients experienced statistically significant higher levels of depression and anxiety than their healthy peers (p < 0.001; p = 0.001, respectively). There were no significant differences in PedsQLTM Scales between the CF patients and the healthy controls (p > 0.05). Conclusion This study is significantly important for revealing that psychiatric symptoms are prevalent among children with CF, which implies that annual symptom screening is justified.

Sinus Symptoms in Cystic Fibrosis Patients and the Role of Interdisciplinary Care

Chronic rhinosinusitis (CRS) is known to occur in most cystic fibrosis (CF) patients. This phenomenon occurs because the genetic mutations in CF cause impaired chloride ion transport, which affects water transport and thus leads to thick mucus that cannot be cleared easily in both the lower and upper airways. While improvements continue to be made in treatment modalities for CF patients in terms of modulator therapies, the effect on sinus disease symptoms and the role of the otolaryngologist (ENT) continues to evolve. This study investigates the sinus symptoms of CF patients with comparison to ENT involvement in their care, the histories of polyps and sinus surgeries of these CF patients, and how their initiation to modulator treatment has affected ENT involvement in their care. A retrospective health records review was conducted including patients from Augusta University Adult Cystic Fibrosis Center with stratification based on demographics, mutations, modulators, ENT clinic visits, history of polyps or nasal surgery, and reported symptoms of headaches, olfactory dysfunction, and sleep problems. 98 patients of the Augusta University Adult Cystic Fibrosis Center met the inclusion criteria of this study. Most of the patients with reported ENT visits in the past 10 years were white and between the ages of 20-29. The most common modulator therapy of the CF patients was elexacaftor-tezacaftor-ivacaftor at 72.22%. More than half of the patients had a history of sinonasal surgery, and almost half had a history of polyps. In comparing ENT visits to the initiation of modulator therapy, 24% of the patients with reported ENT visits saw an ENT after starting modulator therapy. CRS can contribute to morbidity in CF patients with most patients requiring surgical intervention in their lifetime. Additionally, persistent sinonasal symptoms can reduce the quality of life in CF patients. Despite treatment with modulator therapies, otolaryngologists continue to have a role in interdisciplinary CF management.CF- Cystic Fibrosis; CFTR- Cystic Fibrosis Transmembrane Regulator; CRS- Chronic Rhinosinusitis; EMR- Electronic Medical Record; ENT- Otolaryngologist

Breathing for a Living: A Memoir

Breathing for a Living: A Memoir

What is the role of Achromobacter species in patients with cystic fibrosis?

In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the past, the most important health problem that has significantly reduced the quality of life in CF patients is the progressive deterioration of lung structure and function. In recent years, Achromobacter species have emerged with increasing incidence in the respiratory secretions of CF subjects. The significance of this detection remains debated. In this review article, the characteristics of these pathogens, the importance of their presence in CF patients, and possible antibiotic treatment of treatments for colonization and infection are discussed. Literature analysis shows that Achromobacter species, mainly A. xylosoxidans, are pathogens with intrinsic characteristics that favour persistent lung colonization and several virulence factors and secretion systems that significantly interfere with respiratory cell survival. However, although it seems undebatable that Achromobacterspecies detection is a marker of CF severity, the role of these pathogens as a cause of lung structure and functional deterioration is not definitively established. Nonetheless, there is general agreement about the need for antibiotic therapy to eradicate these pathogens when they are detected in CF patients. Unfortunately, eradication is difficult, and no standard treatment is recommended by scientific societies. New possibilities are potentially offered by some recently developed drugs, such as cefiderocol, but further studies on the dosage, treatment duration and efficacy and safety of this new antibiotic in CF patients of different ages are urgently needed.

Bacterial Subversion of Autophagy in Cystic Fibrosis.

Cystic fibrosis (CF) is a genetic disease affecting more than 70,000 people worldwide. It is caused by a mutation in the cftr gene, a chloride ion transporter localized in the plasma membrane of lung epithelial cells and other organs. The loss of CFTR function alters chloride, bicarbonate, and water transport through the plasma membrane, promoting the production of a thick and sticky mucus in which bacteria including Pseudomonas aeruginosa and Burkholderia cenocepacia can produce chronic infections that eventually decrease the lung function and increase the risk of mortality. Autophagy is a well-conserved lysosomal degradation pathway that mediates pathogen clearance and plays an important role in the control of bacterial infections. In this mini-review, we describe the principal strategies used by P. aeruginosa and B. cenocepacia to survive and avoid microbicidal mechanisms within the autophagic pathway leading to the establishment of chronic inflammatory immune responses that gradually compromise the lung function and the life of CF patients.

The Correlation of Health-Related Quality of Life with Cystic Fibrosis Severity Markers in Chest CT Scan and 6-Minute Walk Test: A Cross-Sectional Study.

To investigatethe correlation between severity of lung disease determined by chest computed tomography (CT) and 6-min walk test (6MWT) with health-related quality of life (HRQoL) score in cystic fibrosis (CF) patients. This cross-sectional study evaluated 76 CF patients referred to CF Clinic, aged 7-14 y. Subjects were asked to complete Pediatric quality of life (PedsQL4.0) forms, during their outpatient visits to determine their HRQoL score. Patients' lung disease severity was quantified by Bhalla score determined by the child's chest CT and their 6MWT. These three variables were then analyzed to determine whether there is correlation between HRQoL with severity of lung disease. The mean distance of patients 6MWT score was 447.4 ± 81.4m. There was a positive correlation between distance and HRQoL score in total, social, school and emotional function (p < 0.05). However, in physical function the correlation lacked significance (p = 0.07). Patients with a Bhalla score of less than 15 were older than patients with a Bhalla score of more than 15 (p < 0.001). Physical, emotional, social, school, and total function scores were significantly lower in patients with Bhalla score less than 15, compared to those with Bhalla score greater than 15 (p < 0.05). The correlation among Bhalla score on CT scan, 6-min walk test, and HRQoL indicates that pulmonary disease has a clear impact on the quality of life of CF patients. HRQoL can be used in the care program of children with CF.

An In Vitro Cell Culture Model for Pyoverdine-Mediated Virulence.

Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that utilizes a wide-range of virulence factors to cause acute, life-threatening infections in immunocompromised patients, especially those in intensive care units. It also causes debilitating chronic infections that shorten lives and worsen the quality of life for cystic fibrosis patients. One of the key virulence factors in P. aeruginosa is the siderophore pyoverdine, which provides the pathogen with iron during infection, regulates the production of secreted toxins, and disrupts host iron and mitochondrial homeostasis. These roles have been characterized in model organisms such as Caenorhabditis elegans and mice. However, an intermediary system, using cell culture to investigate the activity of this siderophore has been absent. In this report, we describe such a system, using murine macrophages treated with pyoverdine. We demonstrate that pyoverdine-rich filtrates from P. aeruginosa exhibit substantial cytotoxicity, and that the inhibition of pyoverdine production (genetic or chemical) is sufficient to mitigate virulence. Furthermore, consistent with previous observations made in C. elegans, pyoverdine translocates into cells and disrupts host mitochondrial homeostasis. Most importantly, we observe a strong correlation between pyoverdine production and virulence in P. aeruginosa clinical isolates, confirming pyoverdine’s value as a promising target for therapeutic intervention. This in vitro cell culture model will allow rapid validation of pyoverdine antivirulents in a simple but physiologically relevant manner.

Effects of Curcumin Supplementation on Quality of Life of Cystic Fibrosis Patients

Background: Cystic fibrosis (CF) is one of the most common genetic disorders in children. CF patients are susceptible to chronic lung infections and malabsorption. Although patient longevity is increased by multidisciplinary care, patients still suffer from respiratory failure and low quality of life. In this situation, CF patients tend to use complementary treatments. To the best of our knowledge there is no research about curcumin supplementation in CF patients; thus, we decided to investigate the effects of curcumin supplementation on anthropometric indices, and quality of life in children with cystic fibrosis. Materials and Methods This randomized control-controlled clinical study was conducted in Tabriz University of Medical Sciences, Iran. Forty CF patients were randomly sorted into intervention (n=20), and control (n=20) groups. Patients received 3 curcumin nanoparticles (80 mg; total dose 240 mg/d) for six consecutive months. Before and after intervention, height and weight were measured and quality of life of patients was evaluated by the Pediatric Quality of Life Inventory (PedsQL) 4.0 (CITE). Results: After intervention, the percentage of weight changes showed a significant increase in the curcumin group compared to the control group (7.48±4.68 vs. 4.15±4.68 kg, p=0.03). Following the intervention, only the percentage of change in emotional functioning scores was significant (p=0.01). Subjects in the curcumin group showed a trend towards more improvement in terms of percentage change in physical functioning (19.28±31.65 vs. 15.24±47.14), and school functioning scores (40.96±42.93 vs 23.90±14.82) compared with the control group. Conclusion Our findings suggest that curcumin may be a useful, inexpensive, and safe supplement in combination with conventional therapy to improve body weight in CF children.

Coping with Cystic Fibrosis in the Republic of Macedonia-Parent Perspective.

Cystic fibrosis (CF) is a progressive, life-threatening, genetic disease which mainly damages the lungs and the digestive system. It's a complex medical condition, with several individual forms and variation in the symptoms severity. Few factors such as age of establishing the diagnosis, the number and the type of infections and their management, best treatment options, comorbid conditions etc. can influence the patient's overall health, disease progression and quality of life. Many CF patients will reach adulthood, so coping with the chronic disease is very important for the overall health and everyday living. To screen the quality of life in CF patients in the Republic of Macedonia, from the parent perspective. In the study we have included 55 parents of CF patients. We have created a questionnaire, specially designed for this survey, with questions related to their everyday coping with CF and quality of life. The majority of the parents refer to the overall typical social and emotional life of their children, addressing some difficulties concerning the financial aspect of the disease and still significantly having fear from the stigma in the society. CF patients and their families in the Republic of Macedonia must overcome many obstacles on daily basis. Despite that, they can still have full and meaningful lives.

Features of changes in the quality of life in cystic fibrosis patients against the background of its effective treatment

For the determination of characteristics of LQ ofpatients with cystic fibrosis (CF) and evaluation of the efficacy of the management there was used Health Utilities Index (HUI) questionnaire. The study involved 99 CF patients at the age of from 5 to 18 years. The comparison group - 102 conditionally healthy peers of the same age. All children underwent to a comprehensive medical examination and treatment. LQ assessment was carried with the aid of the HUI questionnaire. CF patients were found to have a significant decline in overall LQ in 84,8% of cases in comparison with their healthy peers. Analysis of the «way of life cohort» showed the fall in multiattribute utility indices in children at the age of 6.12 and 16 years. There was also noted a pronounced decline of indices on attributes: «pain» in 55,6%, «emotions» - in 65,6% and the «self-care» - in 20,2% of cases. Factors significantly affecting on LQ of CF patients were established to be: the presence of homozygous or heterozygous delta F508 mutation, disturbances of the respiratory function and malnutrition, which contributed to a decrease as in the overall index as well in specific aspects of LQ. Against the background of the management during the one hospitalization there was noted the positive dynamics due to the gain in the index of the emotional background. A similar situation was revealed after 6 months in re-hospitalization. Pronounced positive dynamics was noted after the management of patients with severe course of the disease, the worst values of radiological indices and a decline in FEV1 indices. The authors believe the study of LQ of CF patients to be important not only for the evaluation of the impact of the disease on the patient’s LQ, but also for the determination of the efficacy of the management.

Cystic fibrosis transmembrane conductance regulator modulators: Present and future in cystic fibrosis treatment. A review.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are the present and future of drug management for patients with cystic fibrosis. The objective of this article is to review this therapeutic option. Scientific articles were reviewed by searching the MedLine database, which is available through the Cystic Fibrosis Foundation's official website, from 2009 to 2018, in English. Twelve articles about the current status of research in CFTR modulators were selected without restrictions regarding the type of study. To date, the United States Food and Drug Administration has approved three modulators: ivacaftor, lumacaftor + ivacaftor, and tezacaftor + ivacaftor, while other 11 drugs are being studied in different investigation phases. CFTR modulator therapy is a developing reality aimed at the highest goal of personalized medicine and promises to improve the quality of life of cystic fibrosis patients.

Decreased Antibiotic Utilization After Sinus Surgery in Cystic Fibrosis Patients With Lung Transplantation.

Background Patients with cystic fibrosis (CF) who have undergone lung transplantation frequently require hospitalizations and antibiotic treatments for respiratory tract infections. Although endoscopic sinus surgery (ESS) improves sinonasal quality of life in CF patients, it is unclear if ESS offers additional benefit in terms of antibiotics for pulmonary infection, hospitalization, and pulmonary function. Objective To determine whether ESS impacts antibiotic use or hospitalizations for pulmonary indications or pulmonary function in CF patients after lung transplantation. Methods This is a single-institution retrospective study of all patients who underwent lung transplantation for CF from 2005 to 2017. Patients who underwent ESS at least 1 year after transplant were included. Paired bivariate analyses were performed to determine whether there was a difference in the frequency and length of hospitalizations for pulmonary indications, number of antibiotic courses (intravenous and oral) for pulmonary exacerbations, and forced expiratory volume in 1 second (FEV1) slope in the 6 months before versus after ESS. Perioperative antibiotics and hospitalizations were not included in the analyses. Least squares regression was utilized to analyze FEV1 trends. Results A total of 20 patients underwent 36 ESS during the study period. There was significantly higher antibiotic utilization in the 6 months before ESS (0.89 ± 1.03) compared to the 6 months after ESS (0.33 ± 0.53) ( P = .002). The frequency and length of hospitalizations, FEV1 slope, and FEV1 trend before and after ESS were not significantly different. Conclusion Our results suggest that ESS is associated with a reduction in the frequency of antibiotic utilization for respiratory tract infections in lung transplant recipients with CF. A prospective study is needed to investigate these relationships further.

Evaluation of selected insomnia predictors in adolescents and young adults with cystic fibrosis.

The purpose of the study was to assess the incidence of insomnia in adolescents and young adults with cystic fibrosis and its impact on the quality of life, and to examine whether demographic and clinical factors and negative emotional states are predictors of insomnia in these patients. The study was conducted among 95 cystic fibrosis patients aged 14-25 years. The study used a personal questionnaire survey, the Athens Insomnia Scale, the Cystic Fibrosis Quality of Life Questionnaire, the Hospital Anxiety and Depression Scale, and the Numeric Rating Scale. Insomnia was diagnosed in 38% of cystic fibrosis patients. In patients with insomnia, the level of anxiety (Me: 10 vs. 4; P=0.000) and depression (Me: 6.5 vs. 2; P=0.000) was significantly higher than in the good sleep quality group. The risk of insomnia increases as anxiety (OR: 4.31; 95% CI: 2.20 to 8.41) and depressive symptoms exacerbate (OR: 4.98; 95% CI: 1.84 to 13.43). Insomnia significantly worsens the quality of life in cystic fibrosis patients (ß=-0.5, P=0.000). Insomnia affects a large percentage of cystic fibrosis patients, and anxiety and depression are factors that increase the risk of insomnia. Insomnia decreases the quality of life in cystic fibrosis patients.

124 Influence of pulmonary exacerbations on quality of life of cystic fibrosis patients. Health UTIlities and Quality Of Life study (HUTIQOL)

124 Influence of pulmonary exacerbations on quality of life of cystic fibrosis patients. Health UTIlities and Quality Of Life study (HUTIQOL)

Impact de l’exercice physique chez les patients atteints de mucoviscidose : revue systématique

Beneficial effects of physical exercise have been previously demonstrated in patients with chronic obstructive pulmonary disease. The aim of this systematic review was to summarize the evidence supporting physical exercise to improve on lung function, exercise capacity and quality of life in cystic fibrosis patients. Medline database was used to search clinical studies from 2000to 2015. We also analyzed the bibliographic section of the included studies, in order to identify additional references. A total of 17studies were identified. A great disparity was found in the results of the different studies. No systematic benefit was found on lung function, exercise capacity or quality of life. No relationship between the type of program and the benefits achieved was observed. Evidence that physical exercise benefits lung function, exercise capacity and quality of life in cystic fibrosis patient is inconsistent and evidence does not support a particular standardized program for all patients.

Stimulation of nuclear receptor peroxisome proliferator-activated receptor-γ limits NF-κB-dependent inflammation in mouse cystic fibrosis biliary epithelium.

Cystic fibrosis-associated liver disease is a chronic cholangiopathy that negatively affects the quality of life of cystic fibrosis patients. In addition to reducing biliary chloride and bicarbonate secretion, up-regulation of toll-like receptor 4/nuclear factor kappa light-chain-enhancer of activated B cells (NF-κB)-dependent immune mechanisms plays a major role in the pathogenesis of cystic fibrosis-associated liver disease and may represent a therapeutic target. Nuclear receptors are transcription factors that regulate several intracellular functions. Some nuclear receptors, including peroxisome proliferator-activated receptor-γ (PPAR-γ), may counterregulate inflammation in a tissue-specific manner. In this study, we explored the anti-inflammatory effect of PPAR-γ stimulation in vivo in cystic fibrosis transmembrane conductance regulator (Cftr) knockout mice exposed to dextran sodium sulfate and in vitro in primary cholangiocytes isolated from wild-type and from Cftr-knockout mice exposed to lipopolysaccharide. We found that in CFTR-defective biliary epithelium expression of PPAR-γ is increased but that this does not result in increased receptor activity because the availability of bioactive ligands is reduced. Exogenous administration of synthetic agonists of PPAR-γ (pioglitazone and rosiglitazone) up-regulates PPAR-γ-dependent genes, while inhibiting the activation of NF-κB and the secretion of proinflammatory cytokines (lipopolysaccharide-induced CXC chemokine, monocyte chemotactic protein-1, macrophage inflammatory protein-2, granulocyte colony-stimulating factor, keratinocyte chemoattractant) in response to lipopolysaccharide. PPAR-γ agonists modulate NF-κB-dependent inflammation by up-regulating nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha, a negative regulator of NF-κB. Stimulation of PPAR-γ in vivo (rosiglitazone) significantly attenuates biliary damage and inflammation in Cftr-knockout mice exposed to a dextran sodium sulfate-induced portal endotoxemia. These studies unravel a novel function of PPAR-γ in controlling biliary epithelium inflammation and suggest that impaired activation of PPAR-γ contributes to the chronic inflammatory state of CFTR-defective cholangiocytes.

Halotherapy in Patients with Cystic Fibrosis: A Pilot Study

Objectives: Cystic fibrosis (CF) is a complex genetic disorder involving the lower and upper respiratory tract. The purpose of this study is to evaluate the effect of Halotherapy on sinusitis symptoms, dyspnea, pulmonary function tests, and quality of life in CF patients. Study design: This was a pilot open-label before-and-after-study. Settings: The study was performed at the Salt Room® Orlando. Participants were from a single CF care center, and were enrolled in the study between January and June, 2012. Subjects and methods: Patients with clinically stable CF were included in the study. Participants received 9 sessions of HT, 45 minutes each, completed over a 3-week period. Study endpoints include: FEV1 and FVC, Borg dyspnea index test, Cystic Fibrosis Questionnaire-Revised (CFQ-R), and the Sino-Nasal Outcome Test (SNOT-20). Results: Twelve patients completed the study protocol. FEV1 and FVC did not change significantly (p= 0.49 and 0.87, respectively). SNOT-20 score improved by 0.62 points (95% CI -1.03 to -0.2, P = 0.007). There was a trend for improvement in Borg Dyspnea index; the mean score decreased by 0.79 (95% CI -1.64 to 0.05, P=0.065). There was significant improvement in the physical domain, the health perception domain, and the digestive domain.

Prática fisioterapêutica no tratamento da fibrose cística

A fibrose cística (FC), denominada também de mucoviscidose, é uma doença genética do tipo autossômica recessiva que acomete principalmente crianças e indivíduos de raça branca. O objetivo deste estudo foi propiciar uma visão sobre a FC, assim como as possíveis formas de tratamento fisioterapêutico. A pesquisa da literatura foi realizada nas bases de dados SciELO e PubMed, no período de abril de 2002 a março de 2013, através da seleção de artigos científicos referentes à FC, utilizando como palavras-chave: “fibrose cística”, “fisioterapia em fibrose cística” e “fisioterapia respiratória”. Por meio desta revisão, pôde-se observar que, apesar da complexidade da doença, a prática fisioterapêutica, com o uso das técnicas: tapotagem, vibração, drenagem postural (DP), huffing, oscilação oral de alta frequência (OOAF), drenagem autógena (DA) e o ciclo ativo da respiração (CAR), apresenta eficácia tanto no tratamento como na manutenção da qualidade de vida dos pacientes com FC.

The role of neutrophils in cystic fibrosis

Neutrophils are known to dominate the pulmonary inflammatory process observed in cystic fibrosis (CF). An enduring paradox is how these large numbers of neutrophils fail to eradicate colonizing bacteria. Major advances in our understanding of neutrophil dysfunction in CF and its effect on the innate immune system are leading to advances in our understanding of the pathophysiology and leading directly to new therapies. New mechanisms of neutrophil dysfunction have been described in CF including disabled cystic fibrosis transmembrane conductance regulator recruitment to phagosomes and novel mechanisms of protease-induced neutrophil dysfunction. Neutrophil elastase has been shown to be present in the airway very early in life in CF patients, and appears a biomarker of disease progression, predicting lung function decline and bronchiectasis. Elastase has also been shown to induce a pro-inflammatory state of senescence in bronchial epithelial cells in vitro and potentially in vivo. Inhibitors of neutrophil elastase are now entering clinical trials with promising results. New avenues of CF therapeutics are being explored including novel macrolides, CXCR2 antagonists and exogenous opsonins. This article reviews the past 12 months of research that contributes to our understanding of the role of neutrophils and immune dysfunction in CF.

Liver disease in cystic fibrosis: an update.

ContextCystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF.Evidence AcquisitionA literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library.ResultsCF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease.ConclusionsLiver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its progression prior to development its related complications.