STUDIES IN CYSTIC FIBROSIS

The present report is an analysis of 65 patients with cystic fibrosis who are 17 years of age as of January 1, 1964. The oldest patient in this series is 32 9/12, with a mean age of slightly over 20½ years for the entire group. It is unique to have the opportunity to follow a large group of patients from early life beyond adolescence in a pediatric center by the same group of physicians. The follow-up period varied from over 20 years in 2 patients to less than 3 years in 6 patients, with an average of over 11½ years for the whole group. The earliest diagnosis was made at 2 days in an infant with meconium ileus. This boy, now 17 years, is our oldest survivor of meconium ileus corrected surgically. The diagnosis was made in 8 patients in their first year of life and 34 of the 65 patients were diagnosed under 10 years of age. Fifty-one of the 65 patients were diagnosed by us and 14 were diagnosed prior to referral. Forty-two or 65% of patients are male, whereas the sex incidence is equal in infancy and childhood. Of interest are the 7 patients who are married. None have borne children. The present clinical status of these patients is excellent in 7, good in 19, mild in 29, and moderate in 10. The type of follow-up care was considered good in 43 cases, fair in 13, and poor in 9. Brief attention is given to changing concepts of the disease especially as it relates to diagnosis and therapy. Since 1954 when the sweat test was introduced by us as a practical method we have considered this the most reliable single diagnostic test. Prior to 1954 all patients were subjected to duodenal intubation. These patients with no pancreatic insufficiency but with typical pulmonary features considered to have cystic fibrosis were subsequently found to have a positive sweat test. The changes in therapy as it has evolved over the years are mentioned. The most important single advance noted was the introduction of broad spectrum antibiotics in 1948, followed in the last 10 years by a variety of measures designed to keep the bronchopulmonary tree "clean." We feel that the early detection of this disease, plus the application of our current modes of therapy, will not only prevent numerous complications but will provide a much better prognosis for life.

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Inflammation in children with cystic fibrosis: contribution of bacterial production of long-chain fatty acids

Pediatric Research ◽

10.1038/s41390-021-01419-4 ◽

2021 ◽

Author(s):

Erin Felton ◽

Aszia Burrell ◽

Hollis Chaney ◽

Iman Sami ◽

Anastassios C. Koumbourlis ◽

...

Keyword(s):

Cystic Fibrosis ◽

Fatty Acid ◽

Antibiotic Treatment ◽

Bacterial Production ◽

Clinical Status ◽

Achromobacter Xylosoxidans ◽

List Type ◽

Future Studies ◽

Long Chain

Abstract Background Cystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status. Methods Respiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status. Results The mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001). Conclusions LCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF. Impact Increased levels of LCFAs are found after IV antibiotic treatment in persons with CF. LCFAs have previously been associated with increased lung inflammation in asthma. This is the first report of LCFAs in the airway of persons with CF. This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF. Future studies should evaluate LCFAs as predictors of future PExs.

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Newborn Screening for Cystic Fibrosis

PEDIATRICS ◽

10.1542/peds.87.6.954 ◽

1991 ◽

Vol 87 (6) ◽

pp. 954-955

Author(s):

IAN C. T. LYON ◽

DIANNE R. WEBSTER

Keyword(s):

Cystic Fibrosis ◽

Newborn Screening ◽

Elevated Level ◽

Meconium Ileus ◽

Screening Tests ◽

Initial Screening ◽

False Negatives ◽

Immunoreactive Trypsinogen

To the Editor.— The report on newborn screening for cystic fibrosis1 illustrates the need for continued evaluation of such programs. The authors state that the identification of cases of cystic fibrosis (CF) by an elevated level of immunoreactive trypsinogen (IRT) in second (follow-up) samples from infants with positive initial screening tests could result in false negatives in 27% of cases of cystic fibrosis without meconium ileus (MI). We have screened 401 122 infants using the method originally reported.2

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Detection and follow up of exocrine pancreatic insufficiency in cystic fibrosis: a review

European Journal of Pediatrics ◽

10.1007/s004310000507 ◽

2000 ◽

Vol 159 (8) ◽

pp. 563-568 ◽

Cited By ~ 27

Author(s):

Jasmine Leus ◽

Stéphanie Van Biervliet ◽

Eddy Robberecht

Keyword(s):

Cystic Fibrosis ◽

Pancreatic Insufficiency ◽

Exocrine Pancreatic Insufficiency

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Cystic fibrosis newborn screening: outcome of infants with normal sweat tests

Archives of Disease in Childhood ◽

10.1136/archdischild-2017-313290 ◽

2017 ◽

Vol 103 (8) ◽

pp. 753-756 ◽

Cited By ~ 6

Author(s):

Claire Edmondson ◽

Christopher Grime ◽

Ammani Prasad ◽

Jacqui Cowlard ◽

Chinedu E C Nwokoro ◽

...

Keyword(s):

Cystic Fibrosis ◽

Newborn Screening ◽

Genome Sequencing ◽

Dna Analysis ◽

Gene Mutations ◽

High Serum ◽

Sweat Test ◽

Sweat Chloride ◽

South East England

Newborn babies positively screened for cystic fibrosis (CF) (high serum immunoreactive trypsin (IRT) with DNA analysis) are referred for a diagnostic sweat test, which may be normal (sweat chloride <30 mmol/L). Unless two gene mutations are identified during Newborn screening (NBS), the babies are discharged from follow-up. We wished to check that none had subsequently developed symptoms suggestive of CF. We retrospectively reviewed patient notes and contacted general practitioners of all babies with a negative sweat test, conducted in one of the four paediatric specialist CF centres in London, over the first 6 years of screening in South East England.Of 511 babies referred, 95 (19%) had a normal sweat test. Five (5%) had CF diagnosed genetically, two of them on extended genome sequencing after clinical suspicion. Eleven (12%) were designated as CF screen positive inconclusive diagnosis (CFSPID); one of the five CF children was originally designated as CFSPID. Seventy-nine (83%) were assumed to be false-positive cases and discharged; follow-up data were available for 51/79 (65%); 32/51 (63%) had no health issues, 19/51 (37%) had other significant non-CF pathology.These results are reassuring in that within the limitations of those lost to follow-up, CF symptoms have not emerged in the discharged children. The high non-CF morbidity in these children may relate to known causes of high IRT at birth. Clinicians need to be aware that a child can have CF despite a normal sweat test following NBS, and if symptoms suggest the diagnosis, further testing, including extended genome sequencing, is required.

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Cholelithiasis in Cystic Fibrosis Patients in a Tertiary Care Center in Saudi Arabia

10.36502/2020/asjpch.6155 ◽

2020 ◽

Vol 2 (2) ◽

pp. 37-43

Author(s):

Banjar H ◽

Al-Ghuneim L ◽

Al-Shammari A ◽

Al-Mulhim FA ◽

Al-Eid M ◽

...

Keyword(s):

Cystic Fibrosis ◽

Clinical Laboratory ◽

Care Center ◽

Pancreatic Insufficiency ◽

Tertiary Care ◽

Age Groups ◽

Retrospective Chart Review ◽

Abdominal Ultrasound ◽

Abdominal Sonography

Introduction: Cholelithiasis has been reported in 12%-24% of Cystic Fibrosis (CF) patients, and is usually made up of cholesterol gallstones. These abnormalities are frequently asymptomatic and can include intra and extrahepatic ducts, gallbladder thickening and contraction, micro gallbladders, and cholelithiasis. Abdominal sonography is routinely used in order to detect these abnormalities. Objectives: To obtain the prevalence of gall stones (Cholelithasis) in CF patients and its relation to other clinical, laboratory, radiological, and genetic data. Methodology: A retrospective chart review as part of the CF registry data from the period 1st January 1984 – 1st June 2018. All confirmed CF the patients of all age groups that have US studies done were included in the study. Patients with positive gallstones or sludge were evaluated and discussed. Results: A total of 391 confirmed CF patients were involved. Out of them, 252 patients had an abdominal ultrasound, 7 patients (3%) had gallstones on the abdominal US, 8 patients (3%) were revealed to have sludge and 237 patients (94%) had normal gallbladders. Pancreatitis was found in 4 patients (2%). 191 patients (76%) had pancreatic insufficiency.77 patients had follow up abdominal ultrasounds and 5 patients (7%) were found to have persistent gallstones, 4 patients (5%) had persistent sludge and 68 patients (88%) remained negative for gallstones. 2 patients required cholecystectomy. Conclusion: Cholelithiasis is a common complication of CF disease; its incidence is more than the general population. Thus, we recommend that every CF patient get an ultrasonography study as part of liver disease screening to rule out any Gallbladder pathology.

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Functional insufficiency of the pancreas and the metabolic activity of the microbiota in cystic fibrosis adults patients

Terapevticheskii arkhiv ◽

10.26442/terarkh201890104-88 ◽

2018 ◽

Vol 90 (10) ◽

pp. 84-88

Author(s):

L V Vinokurova ◽

G E Baimakanova ◽

S A Krasovsky ◽

S Yu Silvestrova ◽

E A Dubtsova ◽

...

Keyword(s):

Cystic Fibrosis ◽

Fatty Acids ◽

Metabolic Activity ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Sweat Test ◽

Exocrine Insufficiency ◽

Elastase Level ◽

First Year Of Life ◽

Chain Fatty Acids

In order to optimize the therapy, the functional state of the pancreas (P) and the peculiarities of metabolic activity of intestinal microbiota in adults with cystic fibrosis (CF) were assessed. Materials and methods. 14 CF patients (20-34 years, 7 men, 7 women) were enrolled. In 8 patients, the diagnosis was confirmed in the first year of life on the basis of clinical data, positive sweat test, 5 had genetic confirmation. In 4 patients, the diagnosis was confirmed at the age of 8-13 years and 2 patients aged 18, 27 years. In this group, genetic confirmation was in 4 subjects. In addition to general clinical studies, the level of C-peptide in blood, elastase and the concentration of short chain fatty acids in feces was determined. Results and discussion. Of elastase feces in 9 patients was 5.5±4.7 icg/g, that is revealed severe exocrine insufficiency of the pancreas and in 5 patients the elastase level was normal and amounted to 402±124 icg/g. Deployed the clinical picture of diabetes mellitus was observed in 3 patients. Metabolic activity of the colon microflora as a whole was reduced, the sum of the concentration of short-chain fatty acids (ΣCn) was 6.03±4.11 mg/g at a rate of 10.61±5.11 (p

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Cystic fibrosis: a diagnosis in an adolescent

BMJ Case Reports ◽

10.1136/bcr-2021-245971 ◽

2021 ◽

Vol 14 (11) ◽

pp. e245971

Author(s):

Monica Bennett ◽

Andreia Filipa Nogueira ◽

Maria Manuel Flores ◽

Teresa Reis Silva

Keyword(s):

Cystic Fibrosis ◽

Inhaled Corticosteroids ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Sweat Test ◽

Oral Antibiotic ◽

Atypical Symptoms ◽

Oral Antibiotic Therapy ◽

Long Acting ◽

First Year Of Life

Most patients with cystic fibrosis (CF) develop multisystemic clinical manifestations, the minority having mild or atypical symptoms. We describe an adolescent with chronic cough and purulent rhinorrhoea since the first year of life, with diagnoses of asthma, allergic rhinitis and chronic rhinosinusitis. Under therapy with long-acting bronchodilators, antihistamines, inhaled corticosteroids, antileukotrienes and several courses of empirical oral antibiotic therapy, there was no clinical improvement. There was no reference to gastrointestinal symptoms. Due to clinical worsening, extended investigations were initiated, which revealed Pseudomonas aeruginosa in sputum culture, sweat test with a positive result and heterozygosity for F508del and R334W mutations in genetic study which allowed to confirm the diagnosis of CF. In this case, heterozygosity with a class IV mutation can explain the atypical clinical presentation. It is very important to consider this diagnosis when chronic symptoms persist, despite optimised therapy for other respiratory pathologies and in case of isolation of atypical bacterial agents.

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EVALUATION OF A PROPHYLACTIC AND THERAPEUTIC PROGRAM FOR PATIENTS WITH CYSTIC FIBROSIS

PEDIATRICS ◽

10.1542/peds.36.5.675 ◽

1965 ◽

Vol 36 (5) ◽

pp. 675-688

Author(s):

Carl F. Doershuk ◽

LeRoy W. Matthews ◽

Arthur S. Tucker ◽

Samuel Spector

Keyword(s):

Cystic Fibrosis ◽

Pulmonary Function ◽

Treated Group ◽

Entire Group ◽

Weight Changes ◽

Clinical Evaluations ◽

Therapeutic Program ◽

Pulmonary Damage ◽

Chest X Ray

Data has been presented in support of the prophylactic utilization of a comprehensive therapeutic program for patients with cystic fibrosis. Ninety-eight consecutive patients have been followed for 3 to 7 years (average 4½ years). The course of the disease as shown by the clinical evaluations of General Activity, Physical Examination of the Chest, Nutrition, and Chest X-ray for the 49 of these patients considered to be on prophylactic therapy has been significantly different from the accepted natural course of the disease and from that of the 49 patients who had irreversible pulmonary damage when first seen. Objective data collected on these patients including growth and weight changes, morbidity and mortality experience, and pulmonary function studies showed good correlation with the clinical evaluations. No evidence of significant progression in the pulmonary lesion was observed by any criteria for the prophylactically treated group. Indeed, mean pulmonary function test results for these patients were well within the range of normal values even at the end of the average 4½-year follow-up period at an average age of 7 years. No deaths occurred in this group. The mortality rate of only 2% per year of follow-up, with no deaths under 6 years of age, for the entire group of 98 patients indicates the over-all effectiveness of the therapeutic program. This study supports the need for early diagnosis and the prophylactic approach to treatment.

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The 3849+10 kB C—>T Mutation in a 21-Year-Old Patient with Cystic Fibrosis

Ear Nose & Throat Journal ◽

10.1177/014556139607501212 ◽

1996 ◽

Vol 75 (12) ◽

pp. 793-795 ◽

Cited By ~ 2

Author(s):

D.M. Kaplan ◽

A. Niv ◽

M. Aviram ◽

R. Parvari ◽

A. Leiberman ◽

...

Keyword(s):

Cystic Fibrosis ◽

Dna Analysis ◽

Pancreatic Insufficiency ◽

Clinical Status ◽

Chloride Concentration ◽

Inherited Disease ◽

Normal Limits ◽

The Relationship ◽

Sinonasal Symptoms ◽

Sweat Tests

Cystic fibrosis (CF) is the most common lethal inherited disease in the white population. It is characterized by exocrine gland epithelia dysfunction, which leads to pulmonary and pancreatic insufficiency. Since the cloning of the CF gene in 1989 and the identification of the most common CF mutation (ΔF508), more than 400 different mutations have been described. These mutations appear to contribute to the heterogeneity of the CF phenotype and several reports have speculated on the relationship between the most common CF mutations and the patient's clinical status. We report the case of a 21-year-old woman with longstanding chronic pansinusitis, nasal polyposis, chronic cough and severe nasal crusting. During a period of five years she had been followed by her otolaryngologist and pediatric pulmonologist. Sweat tests performed at the age of 17 and 18 were within normal limits and she underwent repeated conventional sinonasal procedures, with no improvement in her clinical status. On her present admission, sweat tests showed a 70 meq/l chloride concentration. The diagnosis of CF was then confirmed by DNA analysis and the patient was found to carry the 3849+10 kB C—>T mutation. The early detection of this newly recognized form of CF in adults as well as in children presenting with sinonasal symptoms is critical for life expectancy and quality.

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