scholarly journals Disease severity associated with cystic fibrosis mutations delta F508 and S549R [T-G]

2001 ◽  
Vol 7 (06) ◽  
pp. 975-980
Author(s):  
K. P. Dawson ◽  
P. M. Frossard ◽  
B. Al Awar
Keyword(s):  
Cystic Fibrosis ◽  
Disease Severity ◽  
United Arab Emirates ◽  
Clinical Presentation ◽  
Clinical Severity ◽  
Biochemical Variables ◽  
Sweat Chloride ◽  
Severe Clinical Presentation ◽  
Age And Sex

We compared the clinical severity associated with the two cystic fibrosis [CF] mutations S549R [T [R] G] and deltaF508. Clinical and biochemical variables of CF were compared in two age- and sex-matched groups of CF children in the United Arab Emirates [UAE]. The clinical severity of mutations S549R [T [R] G] and delta F508 showed comparable patterns, with very low Shwachman scores and high sweat chloride levels. We conclude that patients homozygous for the CF mutations deltaF508 and S549R [T [R] G] have a severe clinical presentation and illness and are indistinguishable on clinical grounds.

ΔF508 Genotype Does Not Predict Disease Severity in an Ethnically Diverse Cystic Fibrosis Population

PEDIATRICS ◽  
1994 ◽  
Vol 93 (1) ◽  
pp. 114-118
Author(s):  
Lucille A. Lester ◽  
Jerome Kraut ◽  
John Lloyd-Still ◽  
Theodore Karrison ◽  
Carol Mott ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Disease Severity ◽  
Ethnically Diverse ◽  
Clinical Parameter ◽  
Population Based ◽  
Age At Diagnosis ◽  
Chest Roentgenogram ◽  
Sweat Chloride ◽  
Cystic Fibrosis Population ◽  
Cftr Mutations

Objective. As part of a study to determine population-based frequencies of CFTR mutations in an ethnically diverse, midwestern cystic fibrosis (CF) population, clinical histories were studied in 119 CF patients. Methodology. We sought to examine the association between genotype as characterized by the ΔF508 and 11 other commonly occurring mutations and clinical parameters including age at diagnosis, clinical presentation, sweat chloride level, chest roentgenogram score, clinical scores, pulmonary function test results, percent weight for height, and presence of associated CF complications. Results. Age at diagnosis of CF was significantly associated with homozygosity for ΔF508 (mean age at diagnosis ± SE: 1.7 ± 0.3 years for ΔF508/ΔF508 vs 3.9 ± 0.9 years for ΔF508/other and other/other; P = .03). No other age-adjusted clinical parameter was significantly associated with ΔF508 or any other genotype. Conclusion. These data suggest that in this sample of CF patients, ΔF508 genotype is not predictive of disease severity. The lack of association between disease severity and genotype in this ethnically diverse sample may reflect the presence of more severe undetected mutations in our sample, or the effects of modifying genes at other, non-CF loci.

scholarly journals The relation between ACEI/ARB use and COVID-19 severity in RT-PCR–confirmed cases: A retrospective case-control study

2020 ◽  
Author(s):  
Sabrina Amaouche ◽  
Ziad Letaief ◽  
Nico Buls ◽  
Sabine Allard ◽  
Johan de Mey
Keyword(s):  
Odds Ratio ◽  
Clinical Presentation ◽  
Enzyme Inhibitor ◽  
Clinical Severity ◽  
Rt Pcr ◽  
Retrospective Case ◽  
Severe Clinical Presentation ◽  
Mortality Outcome ◽  
Polymerase Chain ◽  
Control Study

Abstract One hypothesis suggests that patients undergoing Angiotensin Converting Enzyme inhibitor (ACEI) or Angitensin Receptor Blocker (ARB) treatment might be at greater risk for severe COVID-19 disease. This retrospective study aims to elucidate whether patients with reverse transcription-polymerase chain reaction (RT-PCR)–confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection undergoing ACEI or ARB treatment present with a more severe clinical presentation or more severe lung injury than other patients, as evaluated by CT thorax scans. Comorbidities related to ACEI or ARB use, including arterial hypertension (AHT), heart disease (HD), and diabetes mellitus (DM), were found to be more frequent (p < 0.05 ) in the ACEI or ARB users’ group. The odds ratio of ACEI or ARB users for having a more severe clinical presentation was 1.12 (95% [CI] 0.59–2.13, p = 0.741). For having a severe CT severity score (with a cut-off of 12.5 on a total score of 25), the odds ratio was 1.46 (95% [CI] 0.73–2.94, p = 0.287). Furthermore, the odds ratio of the mortality outcome was 1.1 (95% [CI] 0.49–2.48, p = 0.824). Although the group of ACEI or ARB users had more comorbidities, we found no significant association between CT severity, clinical severity, or mortality and the use of these drugs. These findings bolster the argument against ACEI or ARB withdrawal in COVID-19 patients.

scholarly journals Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function

2018 ◽  
Vol 52 (3) ◽  
pp. 1702529 ◽  
Author(s):  
Karin M. de Winter-de Groot ◽  
Hettie M. Janssens ◽  
Rick T. van Uum ◽  
Johanna F. Dekkers ◽  
Gitte Berkers ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Disease Severity ◽  
Gastrointestinal Disease ◽  
Pancreatic Insufficiency ◽  
Chloride Concentration ◽  
Individual Level ◽  
Outcome Parameters ◽  
Sweat Chloride ◽  
Intestinal Organoids ◽  
Residual Capacity

Forskolin-induced swelling (FIS) of intestinal organoids from individuals with cystic fibrosis (CF) measures function of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein mutated in CF.We investigated whether FIS corresponds with clinical outcome parameters and biomarkers of CFTR function in 34 infants diagnosed with CF. Relationships with FIS were studied for indicators of pulmonary and gastrointestinal disease.Children with low FIS had higher levels of immunoreactive trypsinogen (p=0.030) and pancreatitis-associated protein (p=0.039), more often had pancreatic insufficiency (p<0.001), had more abnormalities on chest computed tomography (p=0.049), and had lower z-scores for maximal expiratory flow at functional residual capacity (p=0.033) when compared to children with high FIS values. FIS significantly correlated with sweat chloride concentration (SCC) and intestinal current measurement (ICM) (r= −0.82 and r=0.70, respectively; both p<0.001). Individual assessment of SCC, ICM and FIS suggested that FIS can help to classify individual disease severity.Thus, stratification by FIS identified subgroups that differed in pulmonary and gastrointestinal outcome parameters. FIS of intestinal organoids correlated well with established CFTR-dependent biomarkers such as SCC and ICM, and performed adequately at group and individual level in this proof-of-concept study.

scholarly journals Lung function and disease severity in cystic fibrosis patients heterozygous for p.Arg117His

2017 ◽  
Vol 3 (1) ◽  
pp. 00056-2016 ◽  
Author(s):  
Michal Shteinberg ◽  
Damian G. Downey ◽  
Diane Beattie ◽  
John McCaughan ◽  
Alastair Reid ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Disease Severity ◽  
Pancreatic Insufficiency ◽  
Forced Expiratory Volume ◽  
Class I ◽  
Lung Function Decline ◽  
Diagnostic Features ◽  
Sweat Chloride ◽  
In Trans

Expression of p.Arg117His cystic fibrosis (CF) transmembrane conductance regulator is influenced by a polythymidine (poly-T) tract and a thymidine–guanine (TG) repeat on intron 9, which vary in length and affect exon 10 skipping.We compared clinical characteristics and the rate of progression of lung disease of CF patients carrying the p.Arg117His mutation with different intron 9 varying sequences (poly-T) and mutation classes in trans.Data were collected from patients in Northern Ireland, UK, including diagnostic features, sweat chloride, nutritional status, sputum microbiology, CF-related complications and lung function. Poly-T and TG repeats were determined by PCR. Forced expiratory volume in 1 s (FEV1) decline was determined from linear regression of FEV1 measurements of patients over time.We identified 62 patients with p.Arg117His, 55 with a class I/II mutation in trans and six with p.Arg117His/p.Gly551Asp. 42 patients had 5T and 13 had 7T. All patients had 12 TG repeats. Patients with p.Arg117His-5T had greater lung function decline, sweat chloride concentrations, pancreatic insufficiency and prevalence of Pseudomonas aeruginosa infection compared with patients with p.Arg117His-7T.Lung function decline and disease severity in p.Arg117His is determined by the poly-T tract length and identity of the mutation in trans. Patients with p.Arg117His-5T and a second class I/II mutation have a severity similar to p.Phe508del homozygous patients, although lung function decline is delayed to an older age. There may be linkage disequilibrium between p.Arg117His and 12 TG repeats.

scholarly journals Prognosis and treatment of 46 Chinese pediatric cystic fibrosis patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qionghua Chen ◽  
Yuelin Shen ◽  
Hui Xu ◽  
Xiaolei Tang ◽  
Haiming Yang ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Respiratory Tract Infections ◽  
Adverse Reactions ◽  
Clinical Presentation ◽  
Public Awareness ◽  
Sputum Production ◽  
Tract Infections ◽  
Lost To Follow Up

Abstract Background Since public awareness of cystic fibrosis (CF) has increased, more children have been diagnosed with CF in China. This study aimed to investigate medical and other challenges faced by pediatric CF patients in China. Method Treatments and treatment outcomes were retrospectively analyzed for 46 pediatric CF patients diagnosed from August 2009 to June 2019. Pre- and post-treatment results were compared using independent samples t-test. Results Of 46 pediatric CF study patients, four died and five were lost to follow-up. Thirty-seven patients were monitored for 0.03 to 9.21 years; patients exhibited fewer attacks of respiratory tract infections after diagnosis (4.49 ± 2.13 episodes/year before diagnosis vs 1.97 ± 1.87 times/year after 1-year treatment, p < 0.05), significantly reduced sputum production and experienced 1.62 ± 1.71 exacerbations/year. Patient mean body mass index was 16.87 ± 3.53 and pancreatic malfunction persisted in 15 patients. For 17 children, no significant differences in lung function were found at follow-up as compared to lung function at diagnosis (FEV1: 82.45% ± 16.56% vs 75.26% ± 22.34%, FVC: 87.18% ± 13.64% vs 86.99% ± 19.95%, FEF75%: 46.51% ± 28.78% vs 36.63% ± 24.30%, P = 0.27, 0.97, 0.20, respectively). Pseudomonas aeruginosa (17/27) and bronchiectasis (22/22) were found during follow-up evaluation. Twenty-four patients (64.8%) maintained good adherence to therapies. Overall, azithromycin and tobramycin treatments were administered for 0.5–62 months and 0.5–48 months, respectively, and triggered no obvious adverse reactions. Conclusion No obvious declines in clinical presentation or lung function were found in Chinese pediatric CF patients after receiving standard therapeutic and active treatments, although malnutrition and low compliance were persistent challenges.

scholarly journals The Epidemiology of Cystic Fibrosis in Arab Countries: A Systematic Review

2021 ◽  
Vol 3 (2) ◽  
pp. 490-498
Author(s):  
Samer Hammoudeh ◽  
Wessam Gadelhaq ◽  
Yahya Hani ◽  
Nadia Omar ◽  
Darine El Dimassi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
United Arab Emirates ◽  
Autosomal Recessive ◽  
Arab World ◽  
Life Quality ◽  
Epidemiological Data ◽  
Arab Countries ◽  
Inclusion Criteria ◽  
Multiple Systems ◽  
Endocrine Symptoms

AbstractCystic fibrosis (CF) is a genetic autosomal recessive disease that involves multiple systems. Both life quality and expectation are affected by the debilitating multi-system involvement of the disease which includes pulmonary, gastrointestinal, reproductive, and endocrine symptoms. Very few studies have covered the epidemiological aspects of the disease among Arab countries. To systematically review the available epidemiological literature on cystic fibrosis in order to describe the epidemiological state of this disease in the Arab world, this review used PubMed to search for relevant articles related to patients with cystic fibrosis, with no restriction on gender or age. Google scholar and the snowballing technique were used to locate further articles. A total of 17 articles met the inclusion criteria for this review. These articles were from Bahrain, Egypt, Jordan, Kuwait, Morocco, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates. The articles scored 1.5–6.5 out of 8 on the quality assessment. The epidemiological data reported varied based on country and type of study. The establishment of CF registries is definitely a priority in the region, as well as the need for more research involving CF patients particularly those involving the epidemiological and clinical characteristics of these patients.

EDA-ID: a Severe Clinical Presentation Associated with a New IKBKG Mutation

2021 ◽  
Author(s):  
Coline Bret Puvilland ◽  
Bertrand Boisson ◽  
Mathieu Fusaro ◽  
Jacinta Bustamante ◽  
Yves Bertrand ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Severe Clinical Presentation

scholarly journals HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease Screening

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2556
Author(s):  
Mary C. Bedard ◽  
Alessandro de Alarcon ◽  
Yann-Fuu Kou ◽  
David Lee ◽  
Alexandra Sestito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Disease Severity ◽  
Disease Onset ◽  
Tissue Bank ◽  
Benign Neoplasm ◽  
Recurrent Respiratory Papillomatosis ◽  
Clinical Severity ◽  
Viral Gene ◽  
Juvenile Onset ◽  
Severity Scores

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common benign neoplasm of the larynx in children, presenting with significant variation in clinical course and potential for progression to malignancy. Since JoRRP is driven by human papillomavirus (HPV), we evaluated viral factors in a prospective cohort to identify predictive factors of disease severity. Twenty children with JoRRP undergoing routine debridement of papillomas were recruited and followed for ≥1 year. Demographical features, clinical severity scores, and surgeries over time were tabulated. Biopsies were used to establish a tissue bank and primary cell cultures for HPV6 vs. HPV11 genotyping and evaluation of viral gene expression. We found that patients with HPV11+ disease had an earlier age at disease onset, higher frequency of surgeries, increased number of lifetime surgeries, and were more likely to progress to malignancy. However, the amplitude of viral E6/E7 gene expression did not account for increased disease severity in HPV11+ patients. Determination of HPV strain is not routinely performed in the standard of care for JoRRP patients; we demonstrate the utility and feasibility of HPV genotyping using RNA-ISH for screening of HPV11+ disease as a biomarker for disease severity and progression in JoRRP patients.

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