Handbook of Cystic Fibrosis

110 Pages·2016·2.515 MB·English

by  Amy G. Filbrun, Thomas Lahiri, Clement L Ren (auth.)

Amy G. Filbrun
Thomas Lahiri
Clement L. Ren
Handbook of
Cystic Fibrosis
Handbook of Cystic Fibrosis

Amy G. Filbrun (cid:129) Thomas Lahiri
Clement L. Ren
Handbook of Cystic
Fibrosis
Amy G. Filbrun Clement L. Ren
Department of Pediatrics Indiana University School
C.S. Mott Children’s Hospital of Medicine
University of Michigan Riley Hospital for Children
Ann Arbor , MI Indianapolis , IN
USA USA
Thomas Lahiri
Department of Pediatrics
The University of Vermont
College of Medicine
Burlington , VT
USA
ISBN 978-3-319-32502-6 ISBN 978-3-319-32504-0 (eBook)
DOI 10.1007/978-3-319-32504-0
Library of Congress Control Number: 2016954157
© Springer International Publishing Switzerland 2016
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Contents
1 Introduction and Epidemiology of Cystic Fibrosis . . . . 1
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Pathophysiology of Cystic Fibrosis . . . . . . . . . . . . . . . 5
2.1 CFTR Structure and Function . . . . . . . . . . . . . . . 5
2.2 CFTR Mutation Classes . . . . . . . . . . . . . . . . . . . . 6
2.3 Relationship Between CFTR Mutations
and Clinical Phenotype . . . . . . . . . . . . . . . . . . . . . 7
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3 Clinical Features and Complications of Cystic
Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.1 Pulmonary Disease and Complications . . . . . . . 9
3.1.1 Pathophysiology of Cystic Fibrosis
Lung Disease . . . . . . . . . . . . . . . . . . . . . . . 9
3.1.2 Pulmonary Exacerbations . . . . . . . . . . . . 12
3.1.3 Hemoptysis . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.1.4 Pneumothorax . . . . . . . . . . . . . . . . . . . . . . 14
3.1.5 Respiratory Failure . . . . . . . . . . . . . . . . . . 15
3.1.6 Allergic Bronchopulmonary
Aspergillosis . . . . . . . . . . . . . . . . . . . . . . . . 15
3.1.7 Asthma in Patients with Cystic
Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.2 Upper Airway Disease . . . . . . . . . . . . . . . . . . . . . 17
3.3 Microbiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.3.1 Microbiology in Early Life . . . . . . . . . . . . 18
3.3.2 Staphylococcus aureus . . . . . . . . . . . . . . . 19
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3.3.3 Pseudomonas aeruginosa . . . . . . . . . . . . . 20
3.3.4 Burkholderia cepacia Complex . . . . . . . . 21
3.3.5 Other Cystic Fibrosis-Associated
Microorganisms . . . . . . . . . . . . . . . . . . . . . 22
3.3.6 Nontuberculous Mycobacteria . . . . . . . . 22
3.4 Gastrointestinal and Nutritional Disease . . . . . . 23
3.4.1 Pancreatic Insufficiency . . . . . . . . . . . . . . 23
3.4.2 Fat-Soluble Vitamin Deficiency . . . . . . . . 25
3.4.3 Meconium Ileus . . . . . . . . . . . . . . . . . . . . . 25
3.4.4 Distal Intestinal Obstruction Syndrome . . 26
3.4.5 Gastroesophageal Reflux Disease . . . . . 27
3.4.6 Recurrent Pancreatitis . . . . . . . . . . . . . . . 27
3.4.7 Rectal Prolapse . . . . . . . . . . . . . . . . . . . . . 28
3.4.8 Hepatobiliary Disease . . . . . . . . . . . . . . . 28
3.4.9 Other Gastrointestinal Complications
of Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . 29
3.5 Endocrine Disease . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.5.1 Cystic Fibrosis-Related Diabetes . . . . . . 29
3.5.2 Bone Disease . . . . . . . . . . . . . . . . . . . . . . . 30
3.6 Urogenital Tract Disease . . . . . . . . . . . . . . . . . . . 30
3.7 Psychiatric Complications . . . . . . . . . . . . . . . . . . 31
3.8 Other Conditions Associated with Cystic
Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
3.8.1 Hyponatremic Dehydration . . . . . . . . . . . 32
3.8.2 Drug Allergy . . . . . . . . . . . . . . . . . . . . . . . 32
3.8.3 Joint Disease . . . . . . . . . . . . . . . . . . . . . . . 32
3.8.4 Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.8.5 Dermatologic Manifestations . . . . . . . . . 33
3.8.6 Nephrolithiasis . . . . . . . . . . . . . . . . . . . . . . 34
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4 Diagnosis of Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . 43
4.1 Background and History . . . . . . . . . . . . . . . . . . . 43
4.2 The Sweat Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
4.3 Genetic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.4 Newborn Screening . . . . . . . . . . . . . . . . . . . . . . . . 47
4.4.1 Newborn Screening Algorithms . . . . . . . 47
4.4.2 Benefits of Newborn Screening . . . . . . . . 49
4.4.3 CFTR-Related Metabolic Syndrome/
Cystic Fibrosis Screen Positive,
Inconclusive Diagnosis . . . . . . . . . . . . . . . 50
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4.5 CFTR-Related Disorder . . . . . . . . . . . . . . . . . . . . 55
4.6 Other Diagnostic Tests of CFTR Function . . . . 55
4.7 Patients with Clinical Features Suggestive
of Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . 58
4.8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
5 Monitoring and Evaluation of Patients with Cystic
Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
5.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
5.2 Nutritional Status . . . . . . . . . . . . . . . . . . . . . . . . . 65
5.3 Gastrointestinal Disease . . . . . . . . . . . . . . . . . . . . 66
5.4 Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
5.4.1 Chest Imaging . . . . . . . . . . . . . . . . . . . . . . 68
5.4.2 Physiologic Assessments . . . . . . . . . . . . . . 69
5.4.3 Assessment of Early Lung
Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
5.5 Microbiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
5.6 Endocrine Disease . . . . . . . . . . . . . . . . . . . . . . . . . 72
5.6.1 Cystic Fibrosis-Related Diabetes . . . . . . 72
5.6.2 Osteopenia . . . . . . . . . . . . . . . . . . . . . . . . . 73
5.7 Sinus Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
5.8 Reproductive and Sexual Health . . . . . . . . . . . . 74
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
6 Treatment of Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . 77
6.1 Gastrointestinal Disease and Nutrition . . . . . . . 77
6.1.1 Pancreatic Enzyme Replacement
Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
6.1.2 Caloric Supplementation . . . . . . . . . . . . . 78
6.1.3 Other Supplemental Therapy . . . . . . . . . 79
6.1.4 Hepatobiliary Disease . . . . . . . . . . . . . . . 79
6.1.5 Intestinal Obstruction . . . . . . . . . . . . . . . . 80
6.2 Pulmonary Disease . . . . . . . . . . . . . . . . . . . . . . . . 80
6.2.1 Airway Clearance Therapies . . . . . . . . . . 82
6.2.2 Bronchodilators . . . . . . . . . . . . . . . . . . . . . 83
6.2.3 Dornase Alfa . . . . . . . . . . . . . . . . . . . . . . . 83
6.2.4 Hypertonic Saline . . . . . . . . . . . . . . . . . . . 84
6.2.5 Anti-inflammatory Therapies . . . . . . . . . 84
6.2.6 Anti-Infective Therapy . . . . . . . . . . . . . . . 86
6.2.7 Pulmonary Exacerbations . . . . . . . . . . . . 87
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6.2.8 Other Pulmonary Complications . . . . . . 89
6.2.9 Lung Transplantation . . . . . . . . . . . . . . . . 90
6.3 Cystic Fibrosis-Related Diabetes . . . . . . . . . . . . 90
6.4 Sinusitis and Nasal Polyposis . . . . . . . . . . . . . . . . 91
6.5 Other Cystic Fibrosis Therapies. . . . . . . . . . . . . . 91
6.6 CFTR Modulators . . . . . . . . . . . . . . . . . . . . . . . . . 92
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Author Biographies
Amy G. Filbrun , MD, MS i s Clinical Associate Professor of
Pediatrics at University of Michigan and C.S. Mott Children’s
Hospital, in Ann Arbor, MI, USA. She received her BS in
Speech from Northwestern University and her MD from
Ohio State University. She completed her pediatric residency
at the Cleveland Clinic, in Cleveland, OH, and fellowship in
pediatric pulmonology at Columbus Children’s Hospital
(now Nationwide Children’s Hospital) in Columbus, OH,
USA. She received her MS in Clinical Research Design and
Statistical Analysis from University of Michigan. Her research
interests include the evaluation of early childhood lung dis-
eases, particularly measures of lung function in infants and
young children with chronic respiratory diseases. In addition,
Dr. Filbrun participates in numerous clinical trials in patients
with cystic fibrosis.
Thomas Lahiri , MD i s Professor of Pediatrics at the
University of Vermont College of Medicine and the Director
of Pediatric Pulmonology at the University of Vermont
Children’s Hospital in Burlington, USA. He received his BS
in Biology at McGill University and his MD from the
University of Connecticut School of Medicine. He completed
his pediatric residency training at the University of Vermont
and a fellowship in pediatric pulmonology at Boston
Children’s Hospital. His clinical interests include airway dis-
orders and cystic fibrosis. He recently co-chaired the Cystic
Fibrosis Preschool Guidelines Committee.
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