125 results on '"Lena Hjelte"'
Search Results
2. MAIT cell counts are associated with the risk of hospitalization in COPD
- Author
-
Terezia Pincikova, Tiphaine Parrot, Lena Hjelte, Marieann Högman, Karin Lisspers, Björn Ställberg, Christer Janson, Andrei Malinovschi, and Johan K. Sandberg
- Subjects
Human ,COPD ,MAIT cells ,T cells ,Immune activation ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with chronic inflammation in the airways. Mucosal-associated invariant T (MAIT) cells are unconventional, innate-like T cells highly abundant in mucosal tissues including the lung. We hypothesized that the characteristics of MAIT cells in circulation may be prospectively associated with COPD morbidity. Methods COPD subjects (n = 61) from the Tools for Identifying Exacerbations (TIE) study were recruited when in stable condition. At study entry, forced expiratory volume in 1 s (FEV1) was measured and peripheral blood mononuclear cells were cryopreserved for later analysis by flow cytometry. Patients were followed for 3 years to record clinically meaningful outcomes. Results Patients who required hospitalization at one or more occasions during the 3-year follow-up (n = 21) had lower MAIT cell counts in peripheral blood at study inclusion, compared with patients who did not get hospitalized (p = 0.036). In contrast, hospitalized and never hospitalized patients did not differ in CD8 or CD4 T cell counts (p = 0.482 and p = 0.221, respectively). Moreover, MAIT cells in hospitalized subjects showed a more activated phenotype with higher CD38 expression (p = 0.014), and there was a trend towards higher LAG-3 expression (p = 0.052). Conventional CD4 and CD8 T cells were similar between the groups. Next we performed multi-variable logistic regression analysis with hospitalizations as dependent variable, and FEV1, GOLD 2017 group, and quantity or activation of MAIT and conventional T cells as independent variables. MAIT cell count, CD38 expression on MAIT cells, and LAG-3 expression on both MAIT and CD8 T cells were all independently associated with the risk of hospitalization. Conclusions These findings suggest that MAIT cells might reflect a novel, FEV1-independent immunological dimension in the complexity of COPD. The potential implication of MAIT cells in COPD pathogenesis and MAIT cells’ prognostic potential deserve further investigation.
- Published
- 2022
- Full Text
- View/download PDF
3. Coxsackievirus B infections are common in Cystic Fibrosis and experimental evidence supports protection by vaccination
- Author
-
Virginia M. Stone, Renata Utorova, Marta Butrym, Amir-Babak Sioofy-Khojine, Minna M. Hankaniemi, Emma E. Ringqvist, Marfa Blanter, Anirudra Parajuli, Terezia Pincikova, Björn Fischler, Ferenc Karpati, Vesa P. Hytönen, Heikki Hyöty, Lena Hjelte, and Malin Flodström-Tullberg
- Subjects
Virology ,Science - Abstract
Summary: Viral respiratory tract infections exacerbate airway disease and facilitate life-threatening bacterial colonization in cystic fibrosis (CF). Annual influenza vaccination is recommended and vaccines against other common respiratory viruses may further reduce pulmonary morbidity risk. Enteroviruses have been found in nasopharyngeal samples from CF patients experiencing pulmonary exacerbations. Using serology tests, we found that infections by a group of enteroviruses, Coxsackievirus Bs (CVBs), are prevalent in CF. We next showed that a CVB vaccine, currently undergoing clinical development, prevents infection and CVB-instigated lung damage in a murine model of CF. Finally, we demonstrate that individuals with CF have normal vaccine responses to a similar, commonly used enterovirus vaccine (inactivated poliovirus vaccine). Our study demonstrates that CVB infections are common in CF and provides experimental evidence indicating that CVB vaccines could be efficacious in the CF population. The role of CVB infections in contributing to pulmonary exacerbations in CF should be further studied.
- Published
- 2022
- Full Text
- View/download PDF
4. A 16-year retrospective study on fungal prevalence and diversity in patients with cystic fibrosis: Candida dubliniensis was associated with a decline in lung function
- Author
-
Mahasin Al Shakirchi, Lena Klingspor, Peter Bergman, Lena Hjelte, and Isabelle de Monestrol
- Subjects
Cystic fibrosis ,Molds ,Yeasts ,Candida albicans ,Candida dubliniensis ,Aspergillus fumigatus ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: To study the prevalence of fungal species in cystic fibrosis (CF) patients over a 16 years period. To examine the impact of Candida albicans (C. albicans), Candida dubliniensis (C. dubliniensis) and Aspergillus fumigatus (A. fumigatus) on lung function. Methods: Observational single-center cohort study (2000–2015) including 133 CF patients (ages 6–66 years). Linear mixed models with autoregressive covariance matrix were used. Results: The most common fungus was C. albicans (prevalence 62%) followed by A. fumigatus (22%) and C. dubliniensis (11%). In the initial year of detection, there was no impact of C. albicans, C. dubliniensis or A. fumigatus on lung function. However, one and two years after detection of C. dubliniensis a reduction in percent predicted forced expiratory volume in the first second (ppFEV1) was observed of 3.8% (p = 0.022) and 4.1% (p = 0.017), respectively, compared with CF patients without these findings. Furthermore, patients with positive cultures for any of these fungal species for three consecutive years exhibited a decline in lung function: C. dubliniensis, 7.6% reduction in ppFEV1 (p = 0.001); A. fumigatus, 4.9% (p = 0.007); C. albicans, 2.6% (p = 0.014). The results were adjusted for age, CFTR genotype, chronic and intermittent P. aeruginosa colonization, and numbers of intravenous antibiotic treatments per year. Persistence of C. dubliniensis for three consecutive years was positively correlated to age and erythrocyte sedimentation rate (ESR) (both p = 0.001). Conclusions: Cystic fibrosis patients who were cultured positive for C. dubliniensis, C. albicans or A. fumigatus in sputum exhibited a decline in ppFEV1 over time. The effect was most pronounced for C. dubliniensis.
- Published
- 2020
- Full Text
- View/download PDF
5. Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
- Author
-
Silke van Koningsbruggen-Rietschel, Jane C. Davies, Tacjana Pressler, Rainald Fischer, Gordon MacGregor, Scott H. Donaldson, Knut Smerud, Nils Meland, Jann Mortensen, Marie Ø. Fosbøl, Damian G. Downey, Astrid H. Myrset, Hugo Flaten, Philip D. Rye, The following investigators and their teams (in alphabetical order) conducted this study., Mary Carroll, Jane Davies, Carsten Schwarz, Nico Derichs, Damian Downey, Olaf Eickmeier, Pal Leyell Finstad, Marie Øbro Fossbøl, Marita Gilljam, Lena Hjelte, Alan Knox, Susanne Nährig, Joachim Riethmüller, Felix C. Ringshausen, AS AlgiPharma, Laura Gow, Joy Conway, and William Bennett
- Subjects
Medicine - Abstract
Background OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF. Methods A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV1) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation. Results In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV1 was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group. Conclusions Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV1 was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo. Post hoc exploratory analyses showed subgroup results that indicate that further studies of OligoG in this patient population are justified.
- Published
- 2020
- Full Text
- View/download PDF
6. The Effects of Aspergillus fumigatus Colonization on Lung Function in Patients with Cystic Fibrosis
- Author
-
Mahasin Al Shakirchi, Kimmo Sorjonen, Lena Klingspor, Peter Bergman, Lena Hjelte, and Isabelle de Monestrol
- Subjects
cystic fibrosis ,fungi ,Aspergillus fumigatus ,lung function ,Biology (General) ,QH301-705.5 - Abstract
Aspergillus fumigatus is commonly isolated from CF airways. However, the impact on CF lung progression is not completely understood. In this study, using a 16-year retrospective observational cohort study (2000–2015) that included 132 patients, we determined the annual lung function, measured as percent predicted forced expiratory volume in the first second (ppFEV1), decline before and after the first colonization with A. fumigatus. Further, in the same individual, the ratios of lung function when patients were colonized with A. fumigatus and when they were not were calculated. The impact of eradication, with antifungal treatment or spontaneously, was assessed. The annual ppFEV1 was significantly lower after the first colonization with A. fumigatus. Furthermore, within the same individual, colonization with A. fumigatus for two and three years in a row was associated with 4.3% and 7.9% lower ppFEV1, respectively, compared to when not colonized. Finally, patients who eradicated A. fumigatus the following two years after colonization exhibited 9.9% and 14.5% higher ppFEV1 compared to patients who continued to produce cultures with A. fumigatus for two and three years. Our study demonstrated that A. fumigatus colonization was associated with a negative impact on lung function in the long term and eradication, spontaneously or with treatment, was associated with a better pulmonary outcome.
- Published
- 2021
- Full Text
- View/download PDF
7. Psychometric evaluation of the Swedish translation of the revised Cystic Fibrosis Questionnaire in adults
- Author
-
Jacek Hochwälder, Agneta Bergsten Brucefors, and Lena Hjelte
- Subjects
Adults ,cystic fibrosis ,CFQ-R ,health-related quality of life ,psychometrics ,Medicine - Abstract
Aim: The CFQ-R is one of the most established disease-specific, health-related quality of life (HRQOL) measurements for patients with cystic fibrosis (CF). The aim was to evaluate the psychometric properties of the Swedish translation of CFQ-R in adults. Method: A total of 173 CF patients answered the CFQ-R. The CFQ-R was evaluated with regard to: (1) distributional properties; (2) reliability; and (3) construct validity. Results: The majority of scales were negatively skewed with ceiling effects. Eight of the 12 scales had satisfactory homogeneity; 10 of the 12 scales had satisfactory test–retest reliability. On many of the CFQ-R scales expected differences were observed when patients were divided regarding disease severity, nutritional status, age, and gender. Conclusion: Some weaknesses were detected, but overall the instrument has satisfactory psychometric properties.
- Published
- 2017
- Full Text
- View/download PDF
8. Dietary intake and nutritional status in a Scandinavian adult cystic fibrosis-population compared with recommendations
- Author
-
Inger E. Moen, Kristina Nilsson, Anna Andersson, Morten W. Fagerland, Gjermund Fluge, Annika Hollsing, Marita Gilljam, Lena Mared, Tacjana Pressler, Henriette Santi, Olav-Trond Storrøsten, and Lena Hjelte
- Subjects
cystic fibrosis ,adult ,body mass index ,energy intake ,nutritional requirement ,forced expiratory volume ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Malnutrition is a well-known complication in cystic fibrosis (CF). There is good evidence that maintaining a normal body-weight correlates well with improved survival in CF. Energy intake in excess of 120% of the estimated average requirement (EAR) has been advised since 1980s.To investigate the nutritional intake and status in the adult Scandinavian CF-population.A cross-sectional multi-centre study was used to investigate the nutritional status of 456 adult CF-patients (2003 2006). Height and weight were measured and body mass index (BMI) and z-scores were calculated. Pulmonary function was examined by dynamic spirometry. A 7-day pre-coded food record (FR) obtained energy and nutrient intake data in 180 patients.The mean energy intake was 114 (SD 30.0)% of EAR and thus significantly lower than the target of 120% EAR (p< 0.001) for patients with pancreatic insufficiency (PI) (n=136). Mean BMI was 22.0 (SD 2.9), the prevalence of BMI
- Published
- 2011
- Full Text
- View/download PDF
9. A 16-year retrospective study on fungal prevalence and diversity in patients with cystic fibrosis: Candida dubliniensis was associated with a decline in lung function
- Author
-
Isabelle de Monestrol, Lena Hjelte, Mahasin Al Shakirchi, Peter Bergman, and Lena Klingspor
- Subjects
Male ,0301 basic medicine ,Cystic fibrosis ,Gastroenterology ,Aspergillus fumigatus ,Molds ,0302 clinical medicine ,Forced Expiratory Volume ,Yeasts ,Genotype ,Candida albicans ,Prevalence ,Medicine ,030212 general & internal medicine ,Child ,Lung ,Candida ,Candida dubliniensis ,biology ,medicine.diagnostic_test ,Biodiversity ,General Medicine ,Middle Aged ,Corpus albicans ,Respiratory Function Tests ,Infectious Diseases ,Erythrocyte sedimentation rate ,Female ,medicine.symptom ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,030106 microbiology ,lcsh:Infectious and parasitic diseases ,Young Adult ,03 medical and health sciences ,Internal medicine ,Humans ,lcsh:RC109-216 ,Aged ,Retrospective Studies ,business.industry ,Fungi ,Sputum ,biology.organism_classification ,medicine.disease ,business - Abstract
Objectives To study the prevalence of fungal species in cystic fibrosis (CF) patients over a 16 years period. To examine the impact of Candida albicans (C. albicans), Candida dubliniensis (C. dubliniensis) and Aspergillus fumigatus (A. fumigatus) on lung function. Methods Observational single-center cohort study (2000–2015) including 133 CF patients (ages 6–66 years). Linear mixed models with autoregressive covariance matrix were used. Results The most common fungus was C. albicans (prevalence 62%) followed by A. fumigatus (22%) and C. dubliniensis (11%). In the initial year of detection, there was no impact of C. albicans, C. dubliniensis or A. fumigatus on lung function. However, one and two years after detection of C. dubliniensis a reduction in percent predicted forced expiratory volume in the first second (ppFEV1) was observed of 3.8% (p = 0.022) and 4.1% (p = 0.017), respectively, compared with CF patients without these findings. Furthermore, patients with positive cultures for any of these fungal species for three consecutive years exhibited a decline in lung function: C. dubliniensis, 7.6% reduction in ppFEV1 (p = 0.001); A. fumigatus, 4.9% (p = 0.007); C. albicans, 2.6% (p = 0.014). The results were adjusted for age, CFTR genotype, chronic and intermittent P. aeruginosa colonization, and numbers of intravenous antibiotic treatments per year. Persistence of C. dubliniensis for three consecutive years was positively correlated to age and erythrocyte sedimentation rate (ESR) (both p = 0.001). Conclusions Cystic fibrosis patients who were cultured positive for C. dubliniensis, C. albicans or A. fumigatus in sputum exhibited a decline in ppFEV1 over time. The effect was most pronounced for C. dubliniensis.
- Published
- 2020
10. The Effects of Aspergillus fumigatus Colonization on Lung Function in Patients with Cystic Fibrosis
- Author
-
Peter Bergman, Lena Klingspor, Kimmo Sorjonen, Mahasin Al Shakirchi, Isabelle de Monestrol, and Lena Hjelte
- Subjects
Microbiology (medical) ,Antifungal ,Lung Progression ,medicine.medical_specialty ,medicine.drug_class ,QH301-705.5 ,Plant Science ,Cystic fibrosis ,Gastroenterology ,Article ,Aspergillus fumigatus ,cystic fibrosis ,Internal medicine ,Medicine ,In patient ,Colonization ,Biology (General) ,skin and connective tissue diseases ,Ecology, Evolution, Behavior and Systematics ,Lung function ,biology ,business.industry ,lung function ,medicine.disease ,biology.organism_classification ,fungi ,business ,Cohort study - Abstract
Aspergillus fumigatus is commonly isolated from CF airways. However, the impact on CF lung progression is not completely understood. In this study, using a 16-year retrospective observational cohort study (2000–2015) that included 132 patients, we determined the annual lung function, measured as percent predicted forced expiratory volume in the first second (ppFEV1), decline before and after the first colonization with A. fumigatus. Further, in the same individual, the ratios of lung function when patients were colonized with A. fumigatus and when they were not were calculated. The impact of eradication, with antifungal treatment or spontaneously, was assessed. The annual ppFEV1 was significantly lower after the first colonization with A. fumigatus. Furthermore, within the same individual, colonization with A. fumigatus for two and three years in a row was associated with 4.3% and 7.9% lower ppFEV1, respectively, compared to when not colonized. Finally, patients who eradicated A. fumigatus the following two years after colonization exhibited 9.9% and 14.5% higher ppFEV1 compared to patients who continued to produce cultures with A. fumigatus for two and three years. Our study demonstrated that A. fumigatus colonization was associated with a negative impact on lung function in the long term and eradication, spontaneously or with treatment, was associated with a better pulmonary outcome.
- Published
- 2021
11. Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study
- Author
-
Patrick A Flume, Reta Fischer Biner, Damian G Downey, Cynthia Brown, Manu Jain, Rainald Fischer, Kris De Boeck, Gregory S Sawicki, Philip Chang, Hildegarde Paz-Diaz, Jaime L Rubin, Yoojung Yang, Xingdi Hu, David J Pasta, Stefanie J Millar, Daniel Campbell, Xin Wang, Neil Ahluwalia, Caroline A Owen, Claire E Wainwright, Ronald L. Gibson, Steven M. Rowe, Noah Lechtzin, Richard C. Ahrens, Karen S. McCoy, Moira Aitken, Scott H. Donaldson, Kimberly Ann McBennett, Joseph M. Pilewski, Joanne Billings, Carlos Milla, Ronald Rubenstein, Daniel Brian Rosenbluth, Rachel Linnemann, Michael R. Powers, Christopher Fortner, Carla Anne Frederick, Theodore G. Liou, Philip Black, Janice Wang, John L. Colombo, Maria Berdella, Maria Veronica Indihar, Cynthia D. Brown, Michael Anstead, Lara Bilodeau, Leonard Sicilian, James Jerome Tolle, Kathryn Moffett, Samya Nasr, Jennifer Taylor-Cousar, Tara Lynn Barto, Nicholas Antos, John S. Rogers, Bryon Quick, Henry R. Thompson, Gregory Sawicki, Bruce Barnett, Robert L. Zanni, Thomas C. Smith, Karen D. Schultz, Claire Keating, Patrick Flume, Gregory J. Omlor, Alix Ashare, Karen Voter, Nighat Mehdi, Maria Gabriela Tupayachi Ortiz, Tonia E. Gardner, Steven R. Boas, Barbara Messore, Edith Zemanick, Raksha Jain, Michael McCarthy, Dana G. Kissner, Kapilkumar Patel, John McNamara, Julie Philley, Ariel Berlinski, Francisco J. Calimano, Terry Chin, Douglas Conrad, Cori Daines, Hengameh H. Raissy, Thomas G. Keens, Jorge E. Lascano, Bennie McWilliams, Brian Morrissey, Santiago Reyes, Subramanyam Chittivelu, Sabiha Hussain, Arvey Stone, James Wallace, Ross Klingsberg, Julie A. Biller, Stephanie Bui, Olaf Sommerburg, Elisabetta Bignamini, Mirella Collura, Alexander Moller, Donatello Salvatore, Chantal Belleguic, Lea Bentur, Ori Efrati, Eitan Kerem, Dario Prais, Esther Quintana Gallego, Peter Barry, Galit Livnat-Levanon, Jose Ramon Villa Asensi, David Stuart Armstrong, Oscar Asensio de la Cruz, Francis Gilchrist, Diana Elizabeth Tullis, Bradley Quon, Larry C. Lands, Nancy Morrison, Annick Lavoie, Barry Linnane, Okan Elidemir, Felix Ringshausen, Matthias Kappler, Helge Hebestreit, Jochen Mainz, Alexander Kiefer, Cordula Koerner-Rettberg, Doris Staab, Wolfgang Gleiber, Tacjana Pressler, Florian Stehling, Andreas Hector, Sivagurunathan Sutharsan, Lutz Naehrlich, Damian Downey, Jane Carolyn Davies, Robert Ian Ketchell, Mary Patricia Carroll, Simon Doe, Gordon MacGregor, Edward Fairbairn Nash, Nicholas Withers, Daniel Gavin Peckham, Martin James Ledson, Sonal Kansra, Timothy William Rayner Lee, Bertrand Delaisi, Gilles Rault, Jean Le Bihan, Dominique Hubert, Isabelle Fajac, Isabelle Sermet-Gaudelus, Marleen Bakker, Bert Arets, Christiane De Boeck, Raphael Chiron, Philippe Reix, Catherine Mainguy, Eva van Braeckel, Anne Malfroot, Isabelle Durieu, Nadine Desmazes Dufeu, Anne Prevotat, Renske van der Meer, Petrus Merkus, E.J.M. Weersink, Isabel Barrio Gomez-Aguero, Silvia Gartner, Amparo Sole Jover, Antonio Alvarez Fernandez, Desmond William Cox, Edward F. McKone, Barry James Plant, Hiranjan Selvadurai, Simon David Bowler, Claire Elizabeth Wainwright, Daniel Smith, Peter Gordon Middleton, John William Wilson, Sonia Volpi, Carla Colombo, Benedetta Fabrizzi, Vincenzina Lucidi, Federico Cresta, Salvatore Cucchiara, Ernst Eber, Helmut Ellemunter, Isidor Huttegger, Lena Hjelte, Christina Krantz, Marita Gilljam, and Pulmonology
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Indoles ,Cystic Fibrosis ,Cystic Fibrosis Transmembrane Conductance Regulator ,Quinolones ,Aminophenols ,Cystic fibrosis ,Time ,Ivacaftor ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Benzodioxoles ,030212 general & internal medicine ,Israel ,biology ,business.industry ,Australia ,medicine.disease ,Cystic fibrosis transmembrane conductance regulator ,Discontinuation ,Europe ,Drug Combinations ,Treatment Outcome ,Clinical research ,030228 respiratory system ,Tolerability ,Mutation ,North America ,biology.protein ,Female ,business ,medicine.drug - Abstract
Summary Background Tezacaftor–ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8–24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor–ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor–ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor–ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor–ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov ( NCT02565914 ). Findings Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor–ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor–ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor–ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation Tezacaftor–ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor–ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor–ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding Vertex Pharmaceuticals Incorporated.
- Published
- 2021
- Full Text
- View/download PDF
12. Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods
- Author
-
Pressler, Tacjana, Karpati, Ferenc, Granström, Marta, Knudsen, Per Kristian, Anders, Lindblad, Lena, Hjelte, Olesen, Hanne V., Meyer, Peter, and Høiby, Niels
- Published
- 2009
- Full Text
- View/download PDF
13. Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells
- Author
-
T. Pincikova, Johan K. Sandberg, Markus Moll, Malin Flodström-Tullberg, Lena Hjelte, and Dominic Paquin-Proulx
- Subjects
Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Immune defense ,Cystic Fibrosis ,medicine.drug_class ,Cell ,Antibiotics ,Mucosal associated invariant T cell ,Critical Care and Intensive Care Medicine ,Peripheral blood mononuclear cell ,Cystic fibrosis ,Mucosal-Associated Invariant T Cells ,Young Adult ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,medicine ,Humans ,Respiratory system ,business.industry ,Bacterial Infections ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Impaired control ,Immunology ,Cardiology and Cardiovascular Medicine ,business ,030215 immunology - Abstract
Here we report a unique case of a patient with cystic fibrosis characterized by severely impaired control of bacterial respiratory infections. This patient's susceptibility to such infections was much worse than expected from a cystic fibrosis clinical perspective, and he died at age 22 years despite extensive efforts and massive use of antibiotics. We found that this severe condition was associated with a near-complete deficiency in circulating mucosal-associated invariant T (MAIT) cells as measured at several time points. MAIT cells are a large, recently described subset of T cells that recognize microbial riboflavin metabolites presented by the highly evolutionarily conserved MR1 molecules. The MAIT cell deficiency was specific; other T-cell subsets were intact. Even though this is only one unique case, the findings lend significant support to the emerging role of MAIT cells in mucosal immune defense and suggest that MAIT cells may significantly modify the clinical phenotype of respiratory diseases.
- Published
- 2018
- Full Text
- View/download PDF
14. P257 Assessing possible role of enterovirus infections in diabetes onset in a Swedish cohort of cystic fibrosis patients
- Author
-
H. Hyöty, R. Utorova, T. Pincikova, Malin Flodström-Tullberg, A. Sioofy Khojine, and Lena Hjelte
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Enterovirus Infections ,business.industry ,Diabetes mellitus ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Cohort ,medicine ,medicine.disease ,business ,Cystic fibrosis - Published
- 2020
- Full Text
- View/download PDF
15. P398 Most adult patients with cystic fibrosis at Stockholm Cystic Fibrosis Centre have a full-time or part-time occupation
- Author
-
Lena Hjelte, I. Durand De Monestrol D’Esquille, M. Al Shakirchi, L. Backström Eriksson, M. Moller, and A. Törnberg
- Subjects
Pulmonary and Respiratory Medicine ,Pediatrics ,medicine.medical_specialty ,Adult patients ,business.industry ,Pediatrics, Perinatology and Child Health ,Medicine ,business ,medicine.disease ,Cystic fibrosis - Published
- 2020
- Full Text
- View/download PDF
16. S13.2 The Swedish cystic fibrosis Registry facilitates the evaluation of Orkambi® treatment
- Author
-
C. Krantz, M. Gilljam, Lena Hjelte, P. Ericson, A. Hedborg, I. de Monestrol, C.R. Hansen, U. Lindberg, and Andreas Lindblad
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Medicine ,business ,medicine.disease ,Cystic fibrosis - Published
- 2020
- Full Text
- View/download PDF
17. WS19.5 Decrease of faecal calprotectin in adults after initiation of Orkambi®, a Registry-based study
- Author
-
M. Gilljam, A. Hedborg, C. Krantz, Lena Hjelte, I. de Monestrol, Andreas Lindblad, and U. Lindberg
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,medicine.disease ,business ,Gastroenterology ,Cystic fibrosis ,Faecal calprotectin - Published
- 2020
- Full Text
- View/download PDF
18. Cystic fibrosis bronchial epithelial cells have impaired ability to activate vitamin D
- Author
-
T. Pincikova, Lena Hjelte, Emma Svedin, Erna Domsgen, and Malin Flodström-Tullberg
- Subjects
0301 basic medicine ,Respiratory Mucosa ,Pathology ,medicine.medical_specialty ,Cystic Fibrosis ,business.industry ,Epithelial Cells ,General Medicine ,medicine.disease ,Cystic fibrosis ,Cell Line ,Activation, Metabolic ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Text mining ,Cell culture ,Pediatrics, Perinatology and Child Health ,medicine ,Vitamin D and neurology ,Humans ,Vitamin D ,business ,030217 neurology & neurosurgery - Published
- 2016
- Full Text
- View/download PDF
19. Vitamin D treatment modulates immune activation in cystic fibrosis
- Author
-
Johan K. Sandberg, Lena Hjelte, Malin Flodström-Tullberg, Dominic Paquin-Proulx, and T. Pincikova
- Subjects
0301 basic medicine ,Vitamin ,CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,Adolescent ,Cystic Fibrosis ,T cell ,Immunology ,Programmed Cell Death 1 Receptor ,Pilot Projects ,CD38 ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Cystic fibrosis ,Immunomodulation ,03 medical and health sciences ,chemistry.chemical_compound ,Internal medicine ,medicine ,Vitamin D and neurology ,Immunology and Allergy ,Humans ,Vitamin D ,Child ,Cholecalciferol ,CD86 ,Membrane Glycoproteins ,biology ,Haptoglobins ,Dendritic Cells ,HLA-DR Antigens ,Original Articles ,medicine.disease ,ADP-ribosyl Cyclase 1 ,3. Good health ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Dietary Supplements ,Ergocalciferols ,Pseudomonas aeruginosa ,biology.protein ,Female ,B7-2 Antigen ,Antibody ,CD8 - Abstract
Summary Persistent inflammatory response in cystic fibrosis (CF) airways is believed to play a central role in the progression of lung damage. Anti-inflammatory treatment may slow lung disease progression, but adverse side effects have limited its use. Vitamin D has immunoregulatory properties. We randomized 16 CF patients to receive vitamin D2, vitamin D3 or to serve as controls, and investigated the effect of vitamin D supplementation on soluble immunological parameters, myeloid dendritic cells (mDCs) and T cell activation. Three months of vitamin D treatment were followed by two washout months. Vitamin D status at baseline was correlated negatively with haptoglobin, erythrocyte sedimentation rate and immunoglobulin A concentration. Total vitamin D dose per kg bodyweight correlated with the down-modulation of the co-stimulatory receptor CD86 on mDCs. Vitamin D treatment was associated with reduced CD279 (PD-1) expression on CD4+ and CD8+ T cells, as well as decreased frequency of CD8+ T cells co-expressing the activation markers CD38 and human leucocyte antigen D-related (HLA-DR) in a dose-dependent manner. There was a trend towards decreased mucosal-associated invariant T cells (MAIT) cell frequency in patients receiving vitamin D and free serum 25-hydroxyvitamin D (free-s25OHD) correlated positively with CD38 expression by these cells. At the end of intervention, the change in free-s25OHD was correlated negatively with the change in CD279 (PD-1) expression on MAIT cells. Collectively, these data indicate that vitamin D has robust pleiotropic immunomodulatory effects in CF. Larger studies are needed to explore the immunomodulatory treatment potential of vitamin D in CF in more detail.
- Published
- 2017
20. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial
- Author
-
Laura A. Sass, Thomas Lahiri, Alicia Casey, Carlos Milla, James F. Chmiel, Fadi Asfour, Seth Walker, Alastair Reid, Jane C. Davies, Michael J. Rock, Xiaohong Huang, Barry Clements, Ronald C. Rubenstein, Tacjana Pressler, Philippe Reix, Anne Munck, Howard Schmidt, Timothy D. Starner, Doris Staab, Stephanie Bui, Christiane De Boeck, Melinda Solomon, Don S. Urquhart, Diana Quintero, Tim Lee, Gautham Marigowda, Fadel Ruiz, Margaret Rosenfeld, Floyd Livingston, Sanja Stanojevic, Matthias Griese, Anne Malfroot, Deborah Froh, Mark A. Chilvers, Isabelle Sermet Gaudelus, John McNamara, Sibylle Junge, Thomas G. Keens, Aaron Chidekel, Ian M. Balfour-Lynn, S. Tian, Claire E. Wainwright, Brian O'Sullivan, Susanna A. McColley, Christopher Hug, Philip Black, Lutz Naehrlich, Silke van Koningsburggen-Rietschel, Philip Robinson, John L. Colombo, Hiranjan Selvadurai, Felix Ratjen, George Z. Retsch-Bogart, Carlos E Milla, David M. Orenstein, David Schaeffer, Lena Hjelte, David Waltz, Alexandra G Cornell, Jodi Hilton, Larry C. Lands, Paul Robinson, Patrick A. Flume, Gary Mueller, Clinical sciences, and Growth and Development
- Subjects
Male ,Pediatrics ,Cystic Fibrosis ,Respiratory System ,Aminopyridines ,Cystic Fibrosis Transmembrane Conductance Regulator ,Quinolones ,Aminophenols ,Cystic fibrosis ,DISEASE ,law.invention ,Ivacaftor ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Forced Expiratory Volume ,Surveys and Questionnaires ,Clinical endpoint ,030212 general & internal medicine ,Child ,Chloride Channel Agonists ,Sweat ,Lung ,ABNORMALITIES ,Lumacaftor ,INERT-GAS WASHOUT ,Drug Combinations ,Mucociliary Clearance ,Female ,Life Sciences & Biomedicine ,CLINICAL-TRIALS ,medicine.drug ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,YOUNG-CHILDREN ,Placebo ,LUNG CLEARANCE INDEX ,1117 Public Health and Health Services ,03 medical and health sciences ,Critical Care Medicine ,Double-Blind Method ,General & Internal Medicine ,medicine ,Humans ,Benzodioxoles ,Adverse effect ,Science & Technology ,business.industry ,1103 Clinical Sciences ,IN-VITRO ,medicine.disease ,PHE508DEL CFTR ,CFTR POTENTIATOR ,Clinical trial ,030228 respiratory system ,chemistry ,Mutation ,VX14-809-109 investigator group ,business ,1199 Other Medical and Health Sciences - Abstract
Background Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR in an open-label study. We report efficacy and safety of lumacaftor and ivacaftor in patients with cystic fibrosis aged 6–11 years homozygous for F508del-CFTR. Methods In this phase 3, randomised, double-blind, placebo-controlled, multicentre study, patients were enrolled at 54 hospitals and medical centres in nine countries (the USA, Australia, Belgium, Canada, Denmark, France, Germany, Sweden, and the UK). Eligible patients weighed at least 15 kg, with a confirmed diagnosis of cystic fibrosis, percent predicted forced expiratory volume in 1 s (FEV 1) of 70 or more, and lung clearance index 2·5 (LCI 2·5) of 7·5 or more at screening (values less than these thresholds were permitted at day 1). All patients were tested for CFTR genotype at screening; eligible patients had to have the F508del-CFTR mutation on both alleles. Exclusion criteria included any comorbidity or laboratory abnormality that might confound the study results or pose additional risk to the patient. Patients were stratified by weight (
- Published
- 2017
21. Time Point to Perform Lung Function Tests Evaluating the Effects of an Airway Clearance Therapy Session in Cystic Fibrosis
- Author
-
Lena Hjelte and Maria Cecilia Rodriguez Hortal
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Spirometry ,Respiratory Therapy ,medicine.medical_specialty ,Adolescent ,Cystic Fibrosis ,Chest physiotherapy ,Critical Care and Intensive Care Medicine ,Cystic fibrosis ,Pulmonary function testing ,FEV1/FVC ratio ,Forced Expiratory Volume ,Humans ,Medicine ,Prospective Studies ,Session (computer science) ,Time point ,Prospective cohort study ,Physical Therapy Modalities ,Sweden ,medicine.diagnostic_test ,business.industry ,General Medicine ,respiratory system ,medicine.disease ,Treatment Outcome ,Anesthesia ,Physical therapy ,Female ,business - Abstract
BACKGROUND: Lung function parameters are used as end points in most clinical and therapeutic trials in cystic fibrosis (CF) and to evaluate the effects of airway clearance techniques. The aim of the study was to identify at what time point after a physiotherapy session spirometry (FEV1 and FVC) should be performed to obtain the highest result compared to baseline and to determine whether there are inter-individual and intra-individual differences in children and adults with CF. METHODS: This was a prospective study. Twenty-four subjects with CF and mean FVC 70 30% and FEV1 61 30% of predicted were included. Each subject performed spirometry before their airway clearance session and then immediately after, 30 min after, and 1, 2, and 3 h after their physiotherapy session for 2 consecutive days. RESULTS: In adult subjects, mean FEV1 improved 30 min (P < .001) ,1h( P < .002), an d2h( P < .006) after physiotherapy compared to baseline. In pediatric subjects, it improved immediately after the session but was not statistically significant for recommendation. There were no intra-individual variations, but there were inter-individual variations (not statistically significant). CONCLUSIONS: Performing spirometry 30 min (adults) and immediately (children) after a session might be optimal if individual peak time values cannot be
- Published
- 2014
- Full Text
- View/download PDF
22. Associations between genetics, medical status, physical exercise and psychological well-being in adults with cystic fibrosis
- Author
-
Kimmo Sorjonen, Agneta Bergsten-Brucefors, Lena Backström-Eriksson, Lena Hjelte, and Bo Melin
- Subjects
Pulmonary and Respiratory Medicine ,Genetics ,Hospital anxiety ,Cystic Fibrosis ,business.industry ,Working capacity ,Physical exercise ,Disease ,medicine.disease ,Cystic fibrosis ,Cftr gene ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Psychological well-being ,Medicine ,Psychology ,030212 general & internal medicine ,business ,Body mass index ,Exercise - Abstract
Background Cystic fibrosis (CF) is the most common autosomal recessive, life-shortening disease among people of European origin. Type of genetic mutation and regular physical exercise has an impact on clinical outcome. This cross-sectional study explores the associations between genetics, medical status, physical exercise and psychological well-being in adult patients with CF. Methods Adult patients with CF (N=68; mean age: 32.2; range 18–67 years; 46% women) completed the Cystic Fibrosis Questionnaire-Revised and Hospital Anxiety Depression Scale. Measures about lung function/forced expiratory volume in 1 s per cent predicted, body mass index, physical working capacity, immunoglobulin G, CF Transmembrane Conductance Regulator (CFTR) mutations, and physical exercise were obtained. structural equation modelling was used to fit models to data. Results A cftr gene mutation×age interaction effect indicates a psychological disadvantage increasing with age of having more severe CFTR mutations; >65% of the effect is mediated by medical status. Physical exercise has a positive effect on psychological well-being, but >75% of the effect is mediated by medical status. Conclusions Psychological well-being decreases with age in patients with more severe cftr mutations, to a large extent due to a parallel deterioration of medical status. Physical exercise has a positive effect on psychological well-being if resulting in better health only. To manage the complexity of these patients9 needs, the CF-care should emphasise a holistic approach and offer individualised exercise/treatment programmes and psychological competence.
- Published
- 2016
23. Psychometric evaluation of the Swedish translation of the revised Cystic Fibrosis Questionnaire in adults
- Author
-
Jacek Hochwälder, Agneta Bergsten Brucefors, and Lena Hjelte
- Subjects
Gerontology ,Adult ,Male ,psychometrics ,medicine.medical_specialty ,Psychometrics ,Adolescent ,Cystic Fibrosis ,lcsh:Medicine ,Cystic fibrosis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Quality of life (healthcare) ,Surveys and Questionnaires ,CFQ-R ,medicine ,Humans ,Adults ,Translations ,Young adult ,Aged ,Language ,Health related quality of life ,Sweden ,business.industry ,030503 health policy & services ,lcsh:R ,Reproducibility of Results ,General Medicine ,Original Articles ,Middle Aged ,medicine.disease ,health-related quality of life ,030220 oncology & carcinogenesis ,Physical therapy ,Quality of Life ,Female ,0305 other medical science ,business ,Biomedical sciences - Abstract
Aim: The CFQ-R is one of the most established disease-specific, health-related quality of life (HRQOL) measurements for patients with cystic fibrosis (CF). The aim was to evaluate the psychometric properties of the Swedish translation of CFQ-R in adults. Method: A total of 173 CF patients answered the CFQ-R. The CFQ-R was evaluated with regard to: (1) distributional properties; (2) reliability; and (3) construct validity. Results: The majority of scales were negatively skewed with ceiling effects. Eight of the 12 scales had satisfactory homogeneity; 10 of the 12 scales had satisfactory test–retest reliability. On many of the CFQ-R scales expected differences were observed when patients were divided regarding disease severity, nutritional status, age, and gender. Conclusion: Some weaknesses were detected, but overall the instrument has satisfactory psychometric properties.
- Published
- 2016
24. Ataluren in nonsense mutation cystic fibrosis patients not receiving chronic inhaled tobramycin: Evaluation of exacerbations and lung function
- Author
-
Lena Hjelte, Harm A.W.M. Tiddens, Jane C. Davies, Christiane De Boeck, Yiping Sun, Anne Malfroot, Harry G.M. Heijerman, Eitan Kerem, Joseph McIntosh, and Isabelle Sermet-Gaudelus
- Subjects
medicine.medical_specialty ,Exacerbation ,business.industry ,Nonsense mutation ,Phases of clinical research ,Placebo ,medicine.disease ,Cystic fibrosis ,Gastroenterology ,Ataluren ,chemistry.chemical_compound ,Inhaled tobramycin ,chemistry ,Internal medicine ,medicine ,Tobramycin ,business ,Intensive care medicine ,medicine.drug - Abstract
Introduction Ataluren functions by interacting with ribosomes to promote read-through of nonsense mutations in CF. Ataluren9s activity was shown to be inhibited by certain aminoglycosides such as tobramycin that also bind to the ribosome. Aim To investigate the effect of ataluren on lung function (LF) and pulmonary exacerbations. Methods A post-hoc analysis was performed on a recent randomized, double-blind, placebo-controlled, phase 3 study to determine the efficacy and safety of ataluren in patients with nonsense mutation cystic fibrosis (nmCF) (Kerem E, et al. Lancet Respir Med. 2014;2:539-47) on %-predicted FEV 1 (ppFEV 1 ) and exacerbations by use of chronic inhaled tobramycin at baseline. Results Patients not receiving chronic inhaled tobramycin (non-TOBI; n=146), showed a 5.7% difference in relative ppFEV 1 between ataluren and placebo (−0.7% vs −6.4%; p=0.0082) and 40% fewer exacerbations (1.42 vs 2.18; p=0.0061). Non-TOBI patients ≥6 to 1 between ataluren and placebo (4.9% vs −3.3%; p=0.026) and a 60% lower exacerbation rate favoring ataluren (p=0.030). In all intent-to-treat patients (N=232) at week 48, including tobramycin patients, neither relative change from baseline in ppFEV 1 (−2.5% vs −5.5%; p=0.12), nor number of exacerbations (1.42 vs 1.78; p=0.099) significantly differed between ataluren and placebo. Conclusions Ataluren significantly reduced exacerbations and improved LF in nmCF patients not receiving chronic inhaled tobramycin, with markedly improved treatment effect in children and adolescents. Ataluren thus shows promise as a disease-modifying therapy in nmCF.
- Published
- 2016
- Full Text
- View/download PDF
25. Clinical impact of vitamin D treatment in cystic fibrosis: a pilot randomized, controlled trial
- Author
-
T. Pincikova, Lena Hjelte, Dominic Paquin-Proulx, Malin Flodström-Tullberg, Johan K. Sandberg, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, and University of Tampere
- Subjects
Vitamin ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cystic Fibrosis ,Biolääketieteet - Biomedicine ,Vital Capacity ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,Pilot Projects ,Cystic fibrosis ,Gastroenterology ,vitamin D deficiency ,law.invention ,03 medical and health sciences ,FEV1/FVC ratio ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Vitamin D and neurology ,Medicine ,Humans ,Vitamin D ,Child ,Lung ,Cholecalciferol ,Nutrition and Dietetics ,business.industry ,Sisätaudit - Internal medicine ,Vitamins ,medicine.disease ,Vitamin D Deficiency ,Näringslära ,Ergocalciferol ,Endocrinology ,Treatment Outcome ,030228 respiratory system ,chemistry ,Dietary Supplements ,Ergocalciferols ,Female ,business ,medicine.drug - Abstract
BACKGROUND/OBJECTIVES: Vitamin D insufficiency in cystic fibrosis is common. Vitamin D3 is currently preferred over D2. We aimed to study the efficacy of vitamin D2 and D3 at increasing serum 25-hydroxyvitamin D (s25OHD) concentrations and their effect on respiratory health in cystic fibrosis. SUBJECTS/METHODS: Sixteen CF patients were randomized to receive vitamin D2 or D3 or to serve as controls. The starting dose of 5000 IU (< 16 years old) or 7143 IU/day (>= 16 years old) was further individually adjusted. Three months of intervention were followed by two of washout (ClinicalTrials. gov NCT01321905). RESULTS: To increase s25OHD, the mean daily dose of vitamin D2 and D3 had to be increased up to 15650 and 8184 IU, respectively. The combined group of vitamin D2 and D3 treated patients decreased plasma IL-8 (P < 0.05). Patients provided vitamin D3 improved FVC at the end of the trial (P < 0.05). Change in s25OHD was positively correlated with changes in the adult Quality-of-Life respiratory score at the end of supplementation (P = 0.006, r = 0.90), and with changes in FEV1 (P = 0.042, r = 0.62) and FVC (P = 0.036, r = 0.63) at one month of washout. CONCLUSIONS: Vitamin D supplementation may contribute to reduced inflammation and improved lung function in CF.
- Published
- 2016
26. Association between genotype and pulmonary phenotype in cystic fibrosis patients with severe mutations
- Author
-
A. Geborek and Lena Hjelte
- Subjects
Spirometry ,Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,Cystic Fibrosis ,Genotype ,Vital Capacity ,Cystic Fibrosis Transmembrane Conductance Regulator ,medicine.disease_cause ,Gastroenterology ,Cystic fibrosis ,Severity of Illness Index ,Pulmonary function testing ,FEV1/FVC ratio ,Young Adult ,Mutation class ,Internal medicine ,Forced Expiratory Volume ,medicine ,Humans ,Genetic Predisposition to Disease ,Pediatrics, Perinatology, and Child Health ,CFTR ,Child ,Lung ,Mutation ,medicine.diagnostic_test ,biology ,business.industry ,medicine.disease ,Lung function ,Cystic fibrosis transmembrane conductance regulator ,medicine.anatomical_structure ,Cross-Sectional Studies ,Phenotype ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Exocrine Pancreatic Insufficiency ,Female ,business - Abstract
Background Despite numerous studies a clear relationship between genotype and pulmonary phenotype has not been established within the group pancreatic insufficient cystic fibrosis (CF) patients. We studied the relationship between class I and class II mutations and pulmonary function in Swedish patients with known CFTR functional classification. Methods 170 CF patients with two class II mutations, 18 with two class I mutations and 78 with a combination of class I and II mutations were included in the study. Spirometry was performed when patients were in an optimal clinical condition. Results Patients with two class I mutations had lower lung function (FEV 1 and FVC) compared to the group with either a combination of class I and II mutations or two class II mutations. Conclusion CF patients carrying two class I mutations risk developing more severe lung disease compared to patients with at least one class II mutation.
- Published
- 2011
- Full Text
- View/download PDF
27. Age at diagnosis and disease progression of cystic fibrosis in an area without newborn screening
- Author
-
Åsa Klint, Pär Sparén, Isabelle de Monestrol, and Lena Hjelte
- Subjects
Newborn screening ,Pediatrics ,medicine.medical_specialty ,Lung ,Epidemiology ,business.industry ,Disease progression ,Hazard ratio ,Age at diagnosis ,medicine.disease ,Cystic fibrosis ,Confidence interval ,Proportional hazards regression ,medicine.anatomical_structure ,mental disorders ,Pediatrics, Perinatology and Child Health ,medicine ,business - Abstract
We studied age at diagnosis and disease progression of cystic fibrosis (CF) patients with a new study design, using data of 119 patients extracted from Stockholm CF Centre registry. Risk factors for overall morbidity and for lung, liver and nutritional morbidity were investigated separately using time to event methodology (Kaplan-Meier curves, proportional hazards regression). The patients were followed from: (i) healthy at diagnosis to morbidity, (ii) diagnosis with symptoms of morbidity to being free of morbidity, and (iii) free of morbidity to relapse of morbidity. Median age at diagnosis was 5.0 months. Of the patients with overall morbidity at diagnosis 50% became free of morbidity after 4.8 years; however, the patients above the age of 24 months at diagnosis had a reduced chance of becoming free of morbidity (crude hazard ratio 0.14 [95 % confidence interval 0.04, 0.45]) compared with those with diagnosis between the ages of 2 and 12 months (P
- Published
- 2011
- Full Text
- View/download PDF
28. Mental health and sense of coherence among Swedish adults with cystic fibrosis
- Author
-
Lena Hjelte, Agneta Bergsten Brucefors, and Jacek Hochwälder
- Subjects
medicine.medical_specialty ,Vital capacity ,business.industry ,media_common.quotation_subject ,Public Health, Environmental and Occupational Health ,medicine.disease ,Cystic fibrosis ,Mental health ,Salutogenesis ,Medicine ,General Health Questionnaire ,business ,Psychiatry ,Body mass index ,Seriousness ,media_common ,Sense of coherence - Abstract
Scand J Caring Sci; 2011; 25; 365–372 Mental health and sense of coherence among Swedish adults with cystic fibrosis The purpose of this study was to describe mental health among adult Swedish patients with cystic fibrosis (CF) and to study if mental health and the salutogene factor sense of coherence (SOC) intercorrelate with good medical status. Women and men were compared. The patient group (n = 59) attended the Stockholm CF Center. Mental health was measured with the General Health Questionnaire (GHQ-28) and the salutogenesis by SOC-3. Medical status included forced vital capacity and forced expiratory volume in 1 second in per cent of predicted as well as Body Mass Index. The differences within and between groups were tested with t-tests and the relations between the variables were described by Spearman’s correlation coefficient. The patients had on the whole good mental health, but the group with a risk of mental ill-health (n = 19) experienced life as difficult to manage, meaningless and hard to understand compared to the group with a small risk of mental ill-health (n = 40). Women at risk of mental ill-health (n = 10) experienced difficulties in managing life to a greater extent than women with a small risk of mental ill-health (n = 16). Men at risk of mental ill-health (n = 9) found life hard to understand. Mental health and SOC did not correlate significantly with the medical status of the CF patients. The conclusion was that there were comparably few problems of mental health among the patients with CF. The problems that were found were not related to the seriousness of their CF. Women had a more complex pattern of problems in mental health and SOC than men had.
- Published
- 2010
- Full Text
- View/download PDF
29. Parental support for newborn screening for cystic fibrosis
- Author
-
Birgitta Sjöberg, Isabelle de Monestrol, Lena Hjelte, and Agneta Bergsten Brucefors
- Subjects
Response rate (survey) ,Newborn screening ,education.field_of_study ,Pediatrics ,medicine.medical_specialty ,Parental support ,business.industry ,Population ,General Medicine ,medicine.disease ,Cystic fibrosis ,Social support ,Diabetes mellitus ,Pediatrics, Perinatology and Child Health ,Carrier status ,Medicine ,business ,education - Abstract
Aim: To describe the attitudes among parents towards including cystic fibrosis (CF) in the newborn screening programme and towards the potential knowledge of their own carrier status. Methods: A questionnaire with three to five response categories and an information leaflet was posted to 143 CF parents, 3 matched diabetes and 3 matched population parents, the response rate being 85%, 74% and 70%, respectively. Comparisons between groups were made with statistical tests for independent groups. Results: Eighty-six percent of CF, 70% of diabetes and 77% of population parents were in favour of newborn screening for CF, 47%, 45% and 50%, respectively, wished to know their CF carrier status. The parental attitude was independent of the age of the child, as well as delay of diagnosis and well-being of the CF child at the time of diagnosis. Sixty percent of the CF parents experienced the diagnosis as delayed. Conclusion: Parents in Sweden support CF newborn screening. Half of the parents wanted to know their CF carrier status.
- Published
- 2010
- Full Text
- View/download PDF
30. Gender differences in the Scandinavian cystic fibrosis population
- Author
-
Tacjana Pressler, Per Kristian Knudsen, Marie Johannesson, Anders Lindblad, Lena Mared, Lena Hjelte, Hanne Vebert Olesen, and Birger Norderud Lærum
- Subjects
2. Zero hunger ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Population ,Prevalence ,medicine.disease ,Cystic fibrosis ,3. Good health ,Surgery ,03 medical and health sciences ,Chronic infection ,0302 clinical medicine ,030228 respiratory system ,Pseudomonas infection ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Cohort ,medicine ,030212 general & internal medicine ,education ,business ,Body mass index - Abstract
Aims: To explore whether gender differences in the Scandinavian Cystic Fibrosis (CF) patients exist in the areas of key clinical parameters, complications, and medication. Methods: Cross-sectional data on 890 (416 female) pancreatic insufficient CF patients were evaluated regarding chronic infection, body mass index, lung function, medication, and diabetes, as well as data of Pseudomonas infection status, antibiotic treatment and hospitalization from 1-year follow-up. Results: We found no differences in lung function, body mass index, or frequency of diabetes. The adult group consisted of more males than females (208:168). We found no significant difference in prevalence of chronic Pseudomonas aeruginosa infection, but during the follow-up the incidence of new chronic infection was higher in adult females (10/33 vs. 4/56). Females had higher prevalence of Burkholderia infection (21/416 vs. 11/474). Adult females had more days on intravenous antibiotics (median 39 vs. 26 days/year), and days in hospital (median 2 vs. 0 days/year). More adult females received inhaled and oral steroids. In the pediatric cohort, females were treated more often with macrolides as an anti-inflammatory agent. Conclusion: We found no gender difference in key clinical parameters in our CF population. However, our study showed a higher risk of Pseudomonas and Burkholderia infection among the female patients. Additionally, we found that female patients require more intensified treatment regarding antibiotics, macrolides, steroids and days of hospitalization, indicating a true female disadvantage even with modern aggressive treatment. The finding of more males than females in the adult population suggesting a male advantage, warrants a mortality study. Pediatr Pulmonol. 2010; 45:959-965. (C) 2010 Wiley-Liss, Inc.
- Published
- 2010
- Full Text
- View/download PDF
31. P068 Presence of Candida dubliniensis in the cystic fibrosis respiratory tract was associated with a significant decline in lung function – results from a 16-year retrospective study
- Author
-
Peter Bergman, M. Al Shakirchi, I. de Monestrol, Lena Klingspor, and Lena Hjelte
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,biology ,business.industry ,Retrospective cohort study ,medicine.disease ,biology.organism_classification ,Gastroenterology ,Cystic fibrosis ,medicine.anatomical_structure ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,business ,Lung function ,Candida dubliniensis ,Respiratory tract - Published
- 2018
- Full Text
- View/download PDF
32. Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease
- Author
-
Marianne Schwartz, Veronika Skalická, Miroslava Balascakova, Manfred Stuhrmann, Martine Jaspers, Frauke Stanke, Kris De Boeck, Burkhard Tümmler, Isabelle de Monestrol, Judit Korbmacher, Brigitte Boissier, Lena Hjelte, Yann Fichou, Harry Cuppens, L. Bassinet, Mireille Claustres, Abul Kalam Azad, Marie des Georges, Dragica Radojkovic, Christoph Korbmacher, Robert Rauh, Jean-Jacques Cassiman, Martin Schwarz, François Vermeulen, Emmanuelle Girodon, Lieven Dupont, Claude Férec, Carlo Castellani, and Patrick Lebecque
- Subjects
Epithelial sodium channel ,Heterozygote ,medicine.medical_specialty ,Cystic Fibrosis ,Population ,Cystic Fibrosis Transmembrane Conductance Regulator ,Biology ,medicine.disease_cause ,Cystic fibrosis ,Internal medicine ,Genetics ,medicine ,Humans ,Epithelial Sodium Channels ,education ,Genetics (clinical) ,Mutation ,education.field_of_study ,Polymorphism, Genetic ,Heterozygote advantage ,respiratory system ,medicine.disease ,Cystic fibrosis transmembrane conductance regulator ,Amiloride ,Endocrinology ,Case-Control Studies ,biology.protein ,ATP synthase alpha/beta subunits ,medicine.drug - Abstract
We investigated whether mutations in the genes that code for the different subunits of the amiloride-sensitive epithelial sodium channel (ENaC) might result in cystic fibrosis (CF)-like disease. In a small fraction of the patients, the disease could be potentially explained by an ENaC mutation by a Mendelian mechanism, such as p.V114I and p.F61L in SCNN1A. More importantly, a more than three-fold significant increase in incidence of several rare ENaC polymorphisms was found in the patient group (30% vs. 9% in controls), indicating an involvement of ENaC in some patients by a polygenetic mechanism. Specifically, a significantly higher number of patients carried c.-55+5G>C or p.W493R in SCNN1A in the heterozygous state, with odds ratios (ORs) of 13.5 and 2.7, respectively.The p.W493R-SCNN1A polymorphism was even found to result in a four-fold more active ENaC channel when heterologously expressed in Xenopus laevis oocytes. About 1 in 975 individuals in the general population will be heterozygous for the hyperactive p.W493R-SCNN1A mutation and a cystic fibrosis transmembrane conductance regulator (CFTR) gene that results in very low amounts (0-10%) functional CFTR. These ENaC/CFTR genotypes may play a hitherto unrecognized role in lung diseases.
- Published
- 2009
- Full Text
- View/download PDF
33. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients
- Author
-
Peter Meyer, Ferenc Karpati, Gjermund Fluge, Hanne Vebert Olesen, O. T. Storrosten, Lena Hjelte, Marita Gilljam, and Tania Pressler
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Abdominal pain ,Malabsorption ,Adolescent ,Cystic Fibrosis ,Cross-sectional study ,Population ,Prevalence ,Co-morbidity ,Comorbidity ,Scandinavian and Nordic Countries ,Gastroenterology ,Cystic fibrosis ,Young Adult ,Internal medicine ,medicine ,Celiac disease ,Humans ,Pediatrics, Perinatology, and Child Health ,Child ,education ,education.field_of_study ,business.industry ,Infant ,Middle Aged ,medicine.disease ,Immunoglobulin A ,Celiac Disease ,Cross-Sectional Studies ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,Scandinavia ,medicine.symptom ,business - Abstract
Background The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. Methods Transglutaminase-IgA (TGA), endomysium-IgA (EMA) and total IgA in serum were measured in 790 CF patients (48% females, 86% with pancreatic insufficiency). Six patients were diagnosed with CD prior to the study, all receiving a gluten-free diet. Patients with elevated TGA (>50 Units/mL) and a positive EMA test were offered a gastroscopy obtaining mucosal biopsies from the duodenum. Results Four new cases of CD were diagnosed. Two additional patients had positive serological tests, but normal biopsies. In total, 10 cases of CD (1.2%, 1:83) indicate a prevalence rate about three times higher than the general prevalence of CD in Norway and Sweden. No CD patients were detected in the Danish CF cohort. Patients diagnosed with untreated CD reported symptoms typical of both CF and CD (poor weight gain, loose and/or fatty stools, fatigue, irritability, abdominal pain). They improved after introduction of a gluten-free diet. Conclusions Systematic screening for CD in a Scandinavian cohort of CF patients revealed a higher prevalence of CD than in the general population. Clinical signs of CD are difficult to differentiate from CF with malabsorption, and patients may go undiagnosed for a long time. In a population where CD is common we recommend screening for CD in patients with CF.
- Published
- 2009
- Full Text
- View/download PDF
34. Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods
- Author
-
Tacjana, Pressler, Ferenc, Karpati, Marta, Granström, Per Kristian, Knudsen, Anders, Lindblad, Lena, Hjelte, Hanne V, Olesen, Peter, Meyer, Niels, Høiby, and Birger N, Laerum
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Adolescent ,Comorbidity ,medicine.disease_cause ,Cystic fibrosis ,Immunoglobulin G ,Serology ,Young Adult ,Predictive Value of Tests ,Risk Factors ,medicine ,Humans ,Pseudomonas Infections ,Serologic Tests ,Prospective Studies ,Anti-Pseudomonas antibodies ,Pediatrics, Perinatology, and Child Health ,Risk factor ,Child ,Aged ,biology ,Pseudomonas aeruginosa ,business.industry ,Infant ,Middle Aged ,medicine.disease ,Chronic infection ,Child, Preschool ,Predictive value of tests ,Chronic Disease ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Female ,Antibody ,business ,Serological assays - Abstract
The aim of the study was to evaluate three serological methods for their ability to identify CF patients in different infection status especially those at risk of developing chronic Pseudomonas aeruginosa (Pa) infection. Methods: Two ELISA methods: exotoxin A (ExoA) and CF-IgG-ELISA (CF-IgG) and Crossed Immunoelectrophoresis (CIE) were used for measurement of Pa-antibodies in sera from 791 Scandinavian CF patients. Results: 381 patients were cultured negative for Pa in the year before study start, 129 patients were intermittently colonized and 281 patients were chronically infected. The sensitivity of the investigated assays was 96%, 93% and 97%, specificity 89%, 89% and 83% for CIE, ExoA and CF-IgG respectively. The negative predictive value was for CIE 97%, for ExoA 95% and for CF-IgG 98% and positive predictive values 87%, 86% and 80%. Out of the 381 patients cultured negative for Pa, 11 changed status to chronically infected. Twenty-four out of the 129 patients intermittently colonized became chronically infected. The antibody levels in this latter group of patients were significantly higher already at the study start and increased significantly during the study period (p < 0.05). Elevated levels of specific anti-Pseudomonal antibodies showed to be the risk factor for developing chronic P. aeruginosa infection (OR 4.9 and OR 2.7, p < 0.05 for CF-IgG and ExoA). Conclusion: All three serological assays were equally informative. The very high sensitivity of the assays made it possible to characterize patients with different infection status. Elevated levels of specific anti-Pseudomonas antibodies showed to be the risk factor for developing chronic Pa infection. Due to the specificity of the tests, antibiotic treatment based on serology might be considered in selected cases. There is a window of opportunity for suppression and eradication of initial P aeruginosa infection making measurement of specific anti-Pseudomonas antibodies helpful. (c) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. (Less)
- Published
- 2009
- Full Text
- View/download PDF
35. Expression of Intestinal and Lung Alkaline Sphingomyelinase and Neutral Ceramidase in Cystic Fibrosis F508del Transgenic Mice
- Author
-
Bob J. Scholte, Malin Flodström-Tullberg, Lena Hjelte, Lena Ohlsson, Martina Wilke, Michael Huhn, Åke Nilsson, Cell biology, and Biochemistry
- Subjects
Male ,medicine.medical_specialty ,Brush border ,Cystic Fibrosis ,Colon ,Cystic Fibrosis Transmembrane Conductance Regulator ,Mice, Transgenic ,Biology ,Cystic fibrosis ,Mice ,Internal medicine ,Neutral Ceramidase ,Intestine, Small ,Weight Loss ,medicine ,Animals ,Humans ,Lung ,DNA Primers ,Sequence Deletion ,Microvilli ,Body Weight ,Gastroenterology ,Organ Size ,Ceramidase ,medicine.disease ,Sphingolipid ,Small intestine ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,Sphingomyelin Phosphodiesterase ,Pediatrics, Perinatology and Child Health ,Mutation ,Female ,Acid sphingomyelinase ,Sphingomyelin ,medicine.drug - Abstract
Objectives: The intestinal brush border enzymes alkaline sphingomyelinase (alk-SMase) and neutral ceramidase (CDase) digest milk sphingomyelin in suckling neonates. In addition alk-Smase, CDase, and acid sphingomyelinase (acid-SMase) have been implicated in sphingolipid signaling, which exhibits abnormalities in cystic fibrosis (CF). In this study, we tested the hypothesis that the expression of these enzymes is different in CF. Materials and Methods: We used mice with F508del (Cftr(tmlEur)) mutation. a CF mouse model with well-characterized intestinal pathology, Enzyme activities were measured using radiolabeled sphingolipid substrates incubated with tissue homogenates from different organs and intersinal contents of wild-type mice. homozygous, and heterozygous F508del mice. Results: No difference was found in levels of CDase and alk-SMase in the small intestinal mucosa or in their longitudinal distribution. Acid-SMase activity was significantly lower in the mucosa of the distal half of the small intestine of F508del compared with wild-type mice. Despite a lower body weight of F508del mice, length and weight of the small intestine and weight per centimeter of colon were larger than in wild-type Neutral CDase and alk-SMase activities in lungs were lower than in the gut, whereas acid-SMase activity was comparable in both organs. CDase activity in the spleen was significantly higher in F508del than in wild-type mice. Conclusions: Alk-SMase and neutral CDase are normally expressed in F508del CF mice. whereas activity of acid-SMase in the distal small intestine is decreased. We found no differences in activity of these enzymes in lungs in this mouse model. JPGN 47:547-554, 2008.
- Published
- 2008
- Full Text
- View/download PDF
36. Anxiety and depression in adults with cystic fibrosis: a comparison between patients and the general population in Sweden and three other European countries
- Author
-
Lena Backström-Eriksson, Lena Hjelte, Kimmo Sorjonen, Bo Melin, and Agneta Bergsten-Brucefors
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cystic Fibrosis ,Population ,Anxiety ,Logistic regression ,Hospital Anxiety and Depression Scale ,Severity of Illness Index ,Young Adult ,Belgium ,Germany ,Surveys and Questionnaires ,Severity of illness ,medicine ,Prevalence ,Psychology ,Humans ,Young adult ,Psychiatry ,education ,Depression (differential diagnoses) ,Aged ,Aged, 80 and over ,Sweden ,education.field_of_study ,Depressive Disorder ,HADS ,business.industry ,Depression ,Case-control study ,CF ,Middle Aged ,Anxiety Disorders ,United Kingdom ,Case-Control Studies ,Female ,medicine.symptom ,business ,Research Article - Abstract
Background Cystic fibrosis (CF) is the most common autosomal recessive life-shortening disease among Caucasians. Studies exploring the prevalence of anxiety and depression in adult CF patients are few, show inconsistent findings and rarely include comparisons with general populations. Prevalence and degree of anxiety and depression were investigated in adult CF patients in Sweden, Belgium, Germany and the UK, and compared to corresponding general population data. Methods Adult non-transplanted CF patients from the three largest CF-centres (out of four) in Sweden (N = 129; Age range 18–70 years; 50 % women) completed the Hospital Anxiety and Depression Scale (HADS). Studies using HADS in adult CF populations in the UK, Germany, and Belgium were included, as well as HADS normative data from the corresponding general populations. Results No elevated risk for anxiety and depression was found among the CF patients. However, a Country x Group interaction effect emerged; CF patients experienced a higher degree of anxiety than the general population in Sweden, but not in the other countries, though this finding did not remain significant in a logistic regression analysis. In Sweden the effect was limited to women. A Country x Group interaction effect was also found for Depression; CF patients experienced lower degree of depression than the general population in Sweden, Germany and the UK, but not in Belgium/Netherlands. Conclusions Contrary to earlier outcomes, the present results do not indicate any general elevated risk for anxiety and depression among CF patients. Anxiety was slightly higher in the Swedish CF population, compared to the general population; this finding was not seen in the other countries. Depression among CF patients was lower than or similar to that in the general populations in the studied countries.
- Published
- 2015
37. Multicentre chest computed tomography standardisation in children and adolescents with cystic fibrosis: the way forward
- Author
-
Rosaria Casciaro, Philippe Reix, Adria Perez-Rovira, M. H. Smet, Desmond Cox, Anne Mehl, Pilar Garcia Peña, Torkel B. Brismar, Annmarie Jeanes, G Lucigrai, Silvia Gartner, Veronika Skalická, Marleen de Bruijne, Jacqueline Payen De La Garanderie, Marco Di Maurizio, Lena Hjelte, Marianne Nuijsink, I. Sermet, Kris De Boeck, David Rea, Mariëtte van de Corput, Herma C. Holscher, Cesare Braggion, Marcel van Straten, Harm A.W.M. Tiddens, Laureline Berteloot, Wieying Kuo, Jane C. Davies, David M. Hansell, C. Kors van der Ent, Pim A. de Jong, Nanko de Graaf, Ahmed Kheniche, Anne Munck, Isabelle Fajac, Tim W.R. Lee, Hana Vitouskova, and Florian Streitparth
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Cystic Fibrosis ,Computed tomography ,Cystic fibrosis ,030218 nuclear medicine & medical imaging ,Pattern Recognition, Automated ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Surveys and Questionnaires ,medicine ,Journal Article ,Image Processing, Computer-Assisted ,Humans ,Respiratory function ,Young adult ,Child ,Lung ,Clinical Trials as Topic ,medicine.diagnostic_test ,business.industry ,Phantoms, Imaging ,Respiration ,Infant, Newborn ,Infant ,Reproducibility of Results ,medicine.disease ,Clinical trial ,Europe ,medicine.anatomical_structure ,Treatment Outcome ,030228 respiratory system ,Lung disease ,Child, Preschool ,Disease Progression ,Radiography, Thoracic ,Radiology ,business ,Tomography, X-Ray Computed ,Cohort study - Abstract
Progressive cystic fibrosis (CF) lung disease is the main cause of mortality in CF patients. CF lung disease starts in early childhood. With current standards of care, respiratory function remains largely normal in children and more sensitive outcome measures are needed to monitor early CF lung disease. Chest CT is currently the most sensitive imaging modality to monitor pulmonary structural changes in children and adolescents with CF. To quantify structural lung disease reliably among multiple centres, standardisation of chest CT protocols is needed. SCIFI CF (Standardised Chest Imaging Framework for Interventions and Personalised Medicine in CF) was founded to characterise chest CT image quality and radiation doses among 16 participating European CF centres in 10 different countries. We aimed to optimise CT protocols in children and adolescents among several CF centres. A large variety was found in CT protocols, image quality and radiation dose usage among the centres. However, the performance of all CT scanners was found to be very similar, when taking spatial resolution and radiation dose into account. We conclude that multicentre standardisation of chest CT in children and adolescents with CF can be achieved for future clinical trials.
- Published
- 2015
38. Curcumin does not stimulate cAMP-mediated chloride transport in cystic fibrosis airway epithelial cells
- Author
-
Johan Björstad, Anca Dragomir, Godfried M. Roomans, and Lena Hjelte
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Curcumin ,Cystic Fibrosis ,Biophysics ,Cystic Fibrosis Transmembrane Conductance Regulator ,Fluorescent Antibody Technique ,Respiratory Mucosa ,Biology ,Biochemistry ,Cystic fibrosis ,chemistry.chemical_compound ,Chlorides ,Cricetinae ,Cyclic AMP ,Baby hamster kidney cell ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,ΔF508 ,Molecular Biology ,Endoplasmic reticulum ,Cell Biology ,Transfection ,respiratory system ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Epithelium ,respiratory tract diseases ,medicine.anatomical_structure ,chemistry ,Respiratory epithelium - Abstract
It has been suggested that curcumin and other sarcoplasmic/endoplasmic reticulum Ca(2+)-pump inhibitors could correct the defect in the most common mutation (DeltaF508) in cystic fibrosis (CF), and restore normal chloride transport. In the present study, the effect of curcumin was tested on baby hamster kidney (BHK) cells transfected with DeltaF508-CFTR, a CF airway epithelial cell line (CFBE), and cells isolated from the nasal epithelium of CF-patient homozygous for the DeltaF508-mutation. Curcumin had a small effect on basal (non-CFTR-mediated) chloride efflux in CFBE and CF nasal epithelial cells, but did not increase the net cAMP-activated (CFTR-mediated) chloride efflux. Curcumin caused a small increase in net cAMP-activated chloride efflux from DeltaF508-CFTR BHK cells. Immunocytochemical analysis failed to show significant movement of DeltaF508-CFTR to the plasma membrane in DeltaF508-CFTR BHK cells or CFBE cells. It is concluded that it is unlikely that curcumin has a significant positive effect on CFTR-mediated chloride transport in airway epithelial cells.
- Published
- 2004
- Full Text
- View/download PDF
39. Heparin can improve the viability of transfected cystic fibrosis cell lines in vitro
- Author
-
Anca Dragomir, Godfried M. Roomans, Lena Hjelte, and Lars Hagenfeldt
- Subjects
Cystic Fibrosis ,Cell Survival ,viruses ,Green Fluorescent Proteins ,Cystic Fibrosis Transmembrane Conductance Regulator ,Biology ,Transfection ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Flow cytometry ,Cricetinae ,medicine ,Baby hamster kidney cell ,Animals ,Humans ,Polyethyleneimine ,Cationic liposome ,Viability assay ,General Pharmacology, Toxicology and Pharmaceutics ,Fibroblast ,Phospholipids ,medicine.diagnostic_test ,Fatty Acids ,Anticoagulants ,General Medicine ,Heparin, Low-Molecular-Weight ,Flow Cytometry ,Molecular biology ,In vitro ,Luminescent Proteins ,Microscopy, Electron ,medicine.anatomical_structure ,Cell culture - Abstract
Cationic liposomes are widely used as gene transfer agents in in vitro and in vivo studies of cystic fibrosis. In this study we report comparative results of cationic mediated transfection in several cell lines. We have tested epithelial cell lines expressing the wild-type cystic fibrosis transmembrane protein CFTR (bronchial epithelium-16HBE14o-, submucosal gland-Calu3) and their cystic fibrosis counterparts (CFBE41o-, CFSMEo-), as well as baby hamster kidney fibroblast cell lines (BHK) heterologously expressing human CFTR. The cells were transfected with a green fluorescent protein plasmid complexed with commercial cationic liposome (Geneporter2, GP) and 25 kDa polyethylenimine (PEI). At the end of the incubation (2 hours), low molecular weight heparin was added in order to reduce the toxicity of the lipoplexes. Transfection efficiency and cell viability were measured by flow cytometry. Determination of fatty acid composition of cellular phospholipids was performed by capillary gas chromatography. The short incubation time was sufficient to obtain satisfactory transfection in all cell lines studied. Cells treated with PEI-complexes had lower transfection efficiency and viability compared to GP in all tested cell lines. DeltaF508 CFTR carrying airway epithelial cells were easier to transfect but had lower viability compared to their healthy counterparts. This was, however not the case for the BHK cells. The fatty acid analysis showed characteristic polyunsaturated fatty acid patterns, which correlated with the viability of the transfected cells. Low molecular mass heparin added at the end of the lipoplex incubation time could help to maintain the viability of the cells, without interfering with the transfection efficiency.
- Published
- 2004
- Full Text
- View/download PDF
40. Measurement of halide efflux from cultured and primary airway epithelial cells using fluorescence indicators
- Author
-
Charlotte Andersson, Aleksander Edelman, Ray Farley, Lena Hjelte, Godfried M. Roomans, Felix M. Munkonge, Gerry McLachlan, Anca Dragomir, M Stern, Eric W.F.W. Alton, and Heather Davidson
- Subjects
Pulmonary and Respiratory Medicine ,Cystic Fibrosis Transmembrane Conductance Regulator ,Halide ,Respiratory Mucosa ,SPQ ,chemistry.chemical_compound ,Chlorides ,Bromide ,Airway epithelial cell ,Fluorescence microscope ,Humans ,Medicine ,Pediatrics, Perinatology, and Child Health ,CFTR ,Cells, Cultured ,Fluorescent Dyes ,Fluorescence microscopy ,Chloride transport ,Ion Transport ,Efflux rate ,business.industry ,Quinolinium Compounds ,FLUORESCENCE MICROSCOPY ,MQAE ,Human airway ,Iodides ,Fluorescence ,Microscopy, Fluorescence ,chemistry ,Biochemistry ,Pediatrics, Perinatology and Child Health ,Biophysics ,Efflux ,business ,Quantitative analysis (chemistry) - Abstract
The use of the halide-sensitive fluorescent probes (6-methoxy-N-(−sulphopropyl)quinolinium (SPQ) and N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE)) to measure chloride transport in cells has now been established as an alternative to the halide-selective electrode technique, radioisotope efflux assays and patch-clamp electrophysiology. We report here procedures for the assessment of halide efflux, using SPQ/MQAE halide-sensitive fluorescent indicators, from both adherent cultured epithelial cells and freshly obtained primary human airway epithelial cells. The procedure describes the calculation of efflux rate constants using experimentally derived SPQ/MQAE fluorescence intensities and empirically derived Stern–Volmer calibration constants. These fluorescence methods permit the quantitative analysis of CFTR function.
- Published
- 2004
- Full Text
- View/download PDF
41. 264 Natural history of patients with cystic fibrosis carrying nonsense mutations: an analysis of placebo-treated patients from the 009 study
- Author
-
Lena Hjelte, K. De Boeck, Eitan Kerem, and Isabelle Sermet-Gaudelus
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Nonsense mutation ,medicine.disease ,Placebo ,Cystic fibrosis ,Gastroenterology ,Natural history ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Medicine ,030212 general & internal medicine ,business ,030217 neurology & neurosurgery - Published
- 2016
- Full Text
- View/download PDF
42. WS13.1 Ataluren significantly reduces exacerbations in nonsense mutation cystic fibrosis patients not receiving tobramycin
- Author
-
Harm A.W.M. Tiddens, Jane C. Davies, Anne Malfroot, K. De Boeck, Isabelle Sermet-Gaudelus, Lena Hjelte, J. Sun, Eitan Kerem, H.G.M. Heijerman, and J. Mcintosh
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Nonsense mutation ,medicine.disease ,Cystic fibrosis ,Gastroenterology ,Ataluren ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Tobramycin ,Medicine ,030212 general & internal medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Published
- 2016
- Full Text
- View/download PDF
43. Predictors of deterioration of lung function in cystic fibrosis*
- Author
-
Marie Johannesson, Andreas Lindblad, I de Monestrol, Birgitta Strandvik, Lena Hjelte, Lars Wahlgren, Lars Holmberg, Charlotta Schaedel, and Ragnhild Kornfält
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,education.field_of_study ,Pathology ,Pancreatic disease ,biology ,business.industry ,medicine.medical_treatment ,Respiratory disease ,Population ,medicine.disease ,Cystic fibrosis ,Gastroenterology ,Cystic fibrosis transmembrane conductance regulator ,Pulmonary function testing ,Internal medicine ,Diabetes mellitus ,Pediatrics, Perinatology and Child Health ,medicine ,biology.protein ,Lung transplantation ,education ,business - Abstract
The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.The severity of pulmonary disease was to some extent predicted by CFTR genotype. Furthermore, the present investigation is the first long-term study showing a significantly more rapid deterioration of lung function in patients with concomitant diabetes mellitus. Besides diabetes mellitus, pancreatic insufficiency and chronic Pseudomonas colonization were found to be negative predictors of pulmonary function. In contrast to several other reports, we found no significant differences in lung function between genders. Patients with pancreatic sufficiency have no or only a slight decline of lung function with age once treatment is started, but an early diagnosis in this group is desirable.
- Published
- 2002
- Full Text
- View/download PDF
44. Nasal Polyps in Cystic Fibrosis
- Author
-
Ann-Charlotte Wikström, Gert Henriksson, Karl Magnus Westrin, Lena Hjelte, Pontus Stierna, and Ferenc Karpati
- Subjects
Pulmonary and Respiratory Medicine ,Nasal cavity ,medicine.medical_specialty ,Pathology ,rhinorrhea ,business.industry ,Critical Care and Intensive Care Medicine ,medicine.disease ,Gastroenterology ,medicine.anatomical_structure ,Hyposmia ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Sputum ,Nasal Lavage ,Nasal polyps ,Nasal Lavage Fluid ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Nose - Abstract
Study objectives Nasal polyps frequently appear in patients with cystic fibrosis (CF). The aims of this study were to focus on what problems (symptoms, endoscopic findings, and laboratory correlates) nasal polyps cause the CF patient, and how these correlate to the total health situation of this patient group. Patients and study design The clinical histories, endoscopic investigations of the nasal cavity, and analyses of nasal lavage fluid of 44 patients with CF complicated with nasal polyposis have been compared with those of 67 CF control subjects. The patients were examined at annual control examinations (with pulmonary tests, working capacity, liver tests, and bacterial and blood tests) from 1995 to 1996 at Stockholm Cystic Fibrosis Center, Huddinge University Hospital. All patients were > 2 years of age. The endoscopic findings were related to the actual pulmonary function, inflammatory blood parameters, colonizing pathogens, antibodies (Staphylococcus aureus and Pseudomonas aeruginosa), and genotype. Results The patients with nasal polyps differed with respect to chronic colonization of P aeruginosa in sputum samples and had a higher occurrence of serum antibodies against the same species. The two groups did not differ in pulmonary functions, inflammatory parameters, or genotype. The polyps found were mainly small (within the meatus media) and gave no significant increase in ongoing clinical symptoms such as rhinorrhea, nasal obstruction, or hyposmia. Neither was any significantly marked finding concerning the nose (mucosal swellings, secretion, etc.) made in the polyp patients. The patients with CF scored slightly lower in a smell identification test in comparison with the healthy control group. The nasal lavage fluid was analyzed (in 93 of the 111 patients) for the occurrence of P aeruginosa (by polymerase-chain reaction [PCR]), interleukin [IL]-5, IL-8, and lysozyme. The lysozyme and IL-8 content was equal in the two CF groups but increased in comparison with the healthy control group. P aeruginosa was not detected with PCR in any nasal lavage fluid. No measurable levels of IL-5 in the nasal lavage were found. Conclusions There was a higher frequency of chronic colonization of P aeruginosa in the lower respiratory tract in patients with nasal polyps. Otherwise, nonsevere nasal polyposis was not an indicator of lower respiratory tract morbidity in CF patients.
- Published
- 2002
- Full Text
- View/download PDF
45. 84 Unexpectedly severe infection susceptibility in a CF patient defective in MAIT cells
- Author
-
Dominic Paquin-Proulx, Johan K. Sandberg, Malin Flodström-Tullberg, T. Pincikova, Lena Hjelte, and M. Moll
- Subjects
Pulmonary and Respiratory Medicine ,business.industry ,Pediatrics, Perinatology and Child Health ,Immunology ,MAIT Cells ,medicine ,medicine.disease ,business ,Cystic fibrosis - Published
- 2017
- Full Text
- View/download PDF
46. 393 Anxiety and depression can predict the development in lung function in adults with cystic fibrosis
- Author
-
Bo Melin, L. Backström Eriksson, Kimmo Sorjonen, Lena Hjelte, and A. Bergsten Brucefors
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,medicine.disease ,Cystic fibrosis ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Physical therapy ,Anxiety ,medicine.symptom ,business ,Depression (differential diagnoses) ,Lung function - Published
- 2017
- Full Text
- View/download PDF
47. Non-invasive Ventilation as Airway Clearance Technique in Cystic Fibrosis
- Author
-
Maria Cecilia, Rodriguez Hortal, Malin, Nygren-Bonnier, and Lena, Hjelte
- Subjects
Adult ,Male ,Respiratory Therapy ,Noninvasive Ventilation ,Adolescent ,Cystic Fibrosis ,Walk Test ,Respiratory Function Tests ,Positive-Pressure Respiration ,Young Adult ,Humans ,Female ,Prospective Studies ,Physical Therapy Modalities - Abstract
For patients with cystic fibrosis, chest physiotherapy is crucial for evacuating airway secretions. Because chest physiotherapy increases energy expenditure, fatigue and dyspnoea, non-invasive ventilation (NIV) could be beneficial for severely ill patients during airway clearance. The aim of the study is to evaluate and compare the effects between NIV and positive expiratory pressure (PEP) on airway clearance.Prospective, randomized trial compares PEP to NIV. Thirty-two subjects, mean age 31 years, mean forced expiratory volume in 1 second 47% (±14) and mean forced vital capacity 69% (±13), completed a 3-month randomized trial comparing NIV with standard PEP treatment as airway clearance technique. Lung functions testing, 6-minute walk test, blood gases, sputum culture and inflammatory parameters were measured before and after the treatment period.There was a significant reduction in lung clearance index (LCI) following NIV compared with PEP (p = 0.01). LCI is performed within the lung function testing.Non-invasive ventilation was shown to be a good alternative to PEP in chest physiotherapy for patients with cystic fibrosis who are severely ill.
- Published
- 2014
48. TNF-A and IL-8 in Consecutive Sputum Samples from Cystic Fibrosis Patients During Antibiotic Treatment
- Author
-
Bengt Wretlind, Ferenc Karpati, and Lena Hjelte
- Subjects
Adult ,Male ,Microbiology (medical) ,Staphylococcus aureus ,medicine.medical_specialty ,Pancreatic disease ,Adolescent ,Cystic Fibrosis ,Exacerbation ,Bacterial Toxins ,Enzyme-Linked Immunosorbent Assay ,Cystic fibrosis ,Gastroenterology ,Statistics, Nonparametric ,Proinflammatory cytokine ,Antibody Specificity ,Fibrosis ,Internal medicine ,medicine ,Humans ,Child ,Respiratory Tract Infections ,Lung ,General Immunology and Microbiology ,Tumor Necrosis Factor-alpha ,business.industry ,Interleukin-8 ,Respiratory disease ,Sputum ,General Medicine ,medicine.disease ,Antibodies, Bacterial ,Anti-Bacterial Agents ,Radiography ,Infectious Diseases ,medicine.anatomical_structure ,Acute Disease ,Pseudomonas aeruginosa ,Immunology ,Disease Progression ,Female ,medicine.symptom ,business ,Biomarkers ,Follow-Up Studies - Abstract
Proinflammatory cytokines in sputum are useful markers of the activity of lung disease in cystic fibrosis (CF). Tumour necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) concentrations in sputum of 10 CF patients were determined during exacerbation and IL-8 in sputum of 48 patients at a yearly follow-up when patients were in optimal clinical condition. In 9 patients of the former group, TNF-alpha levels were increased during exacerbation. In 4 patients, the peak occurred within 2 d (median value > 1500 ng/l), whereas the remaining 5 had peak values on days 3-6 (median value 720 ng/l). IL-8 levels were > 800 microg/l in all 10 patients, and in 9 cases there was a positive correlation between IL-8 and TNF-alpha. Baseline IL-8 levels of 48 patients showed considerable variation (median 207 microg/l, range 1.5-392). There was a significant correlation between IL-8 concentrations and current colonization with either Pseudomonas aeruginosa or Staphylococcus aureus in the lower airways (p = 0.002), immunoglobulin G levels (p = 0.02) and the severity of the pathological findings shown by chest X-ray (p = 0.008). High IL-8 and TNF-alpha values correlated with symptoms of deterioration. IL-8 levels seemed to be markers of both current bacterial colonization and the degree of lung damage.
- Published
- 2000
- Full Text
- View/download PDF
49. Three common CFTR mutations should be included in a neonatal screening programme for cystic fibrosis in Sweden
- Author
-
H Kollberg, Ragnhild Kornfält, Lars Holmberg, Charlotta Schaedel, Lena Hjelte, Marie Johannesson, and I de Monestrol
- Subjects
medicine.medical_specialty ,Mutation ,education.field_of_study ,Pancreatic disease ,biology ,medicine.diagnostic_test ,business.industry ,Population ,medicine.disease ,medicine.disease_cause ,Cystic fibrosis ,Cystic fibrosis transmembrane conductance regulator ,Endocrinology ,Internal medicine ,Genetics ,medicine ,biology.protein ,Immunoreactive trypsinogen ,Allele ,education ,business ,Allele frequency ,Genetics (clinical) - Abstract
Children with cystic fibrosis (CF) diagnosed by neonatal screening have a better nutritional development and other advantages compared with those in a nonscreened group. The two-tier immunoreactive trypsinogen (IRT)/DNA screening protocol has been found superior to the single-tier IRT approach, improving the positive predictive value and thus reducing the false-positive rate. However, variations of the DNA test are required for different populations. In this study we examined CFTR (cystic fibrosis transmembrane conductance regulator) mutations in 331 CF patients attending the centres in Stockholm, Lund and Uppsala, comprising about 75% of the CF population in Sweden. The frequency of deltaF508 among CF alleles was 68.3%. There were two other mutations, 394delTT and 3659delC, found to be fairly frequent, amounting to 8.5 and 7.9%, respectively. Other mutations were comparatively rare. A simple and effective method of analysing the three mutations from Guthrie cards has been developed. Assuming Hardy-Weinberg equilibrium, 90% of our CF patients will be expected to carry at least one deltaF508 allele and 97.6% to carry at least one deltaF508, 394delTT or 3659delC copy. Including the latter two in a screening programme would thus substantially reduce the risk of a false-negative outcome.
- Published
- 1999
- Full Text
- View/download PDF
50. Polymorphic Expression of Multidrug Resistance mRNA in Lung Parenchyma of Nonpregnant and Pregnant Rats: A Comparison to Cystic Fibrosis mRNA Expression
- Author
-
Nenad Bogdanovic, Martin Schalling, Marie Johannesson, Ann-Christin Sandberg Nordqvist, and Lena Hjelte
- Subjects
medicine.medical_specialty ,Cystic Fibrosis ,Biophysics ,Cystic Fibrosis Transmembrane Conductance Regulator ,ATP-binding cassette transporter ,Biochemistry ,Cystic fibrosis ,Rats, Sprague-Dawley ,Pregnancy ,Internal medicine ,Parenchyma ,Image Processing, Computer-Assisted ,medicine ,Animals ,Humans ,Secretion ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,RNA, Messenger ,Lung ,Molecular Biology ,Messenger RNA ,Polymorphism, Genetic ,biology ,Nucleic Acid Hybridization ,Cell Biology ,respiratory system ,medicine.disease ,Drug Resistance, Multiple ,Cystic fibrosis transmembrane conductance regulator ,Rats ,respiratory tract diseases ,medicine.anatomical_structure ,Endocrinology ,Immunology ,Chloride channel ,biology.protein ,Autoradiography ,Pregnancy, Animal ,Female - Abstract
Multidrug resistance (MDR1b) and cystic fibrosis transmembrane conductance regulator (CFTR) proteins are members of the "ATP-binding cassette" superfamily of transporters. They are associated with chloride channel activities and ATP secretion and have complementary patterns of expression in several organs. In the rat uterus, CFTR expression is replaced by MDR1b expression during pregnancy. We have studied whether expression of MDR1b and CFTR also vary in the lung during pregnancy. No variations in MDR1b or CFTR mRNA levels during pregnancy were detected. However, there was an unusual degree of variation in MDR1b mRNA expression in lung parenchyma between animals in both the control group and the pregnant group. If present among humans, polymorphic expression of MDR1 in lung parenchyma may explain part of the differences in lung symptomatology observed in the CF patients carrying the same mutation.
- Published
- 1997
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.