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Book Details
Abstract
Dr. Jon Koff has assembled and expert team of authors of the topic of Cystic Fibrosis. Articles include: Epidemiology and Pathobiology, Genetics and genetic medicine in Cystic Fibrosis, Innate and Adaptive Immunity in Cystic Fibrosis, Microbiome in Cystic Fibrosis, Diagnostic Testing in Cystic Fibrosis, Treating Pseudomonas in Cystic Fibrosis, Diagnosis of Adult Patients with Cystic Fibrosis, Transition from Pediatrics to Adult Care, Lung Transplant in Cystic Fibrosis, and more!
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Cystic Fibrosis\r | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| EDITOR | iii | ||
| AUTHORS | iii | ||
| Contents | vii | ||
| Preface: Cystic Fibrosis\r | vii | ||
| Epidemiology of Cystic Fibrosis\r | vii | ||
| Genetics of Cystic Fibrosis: Clinical Implications\r | vii | ||
| Innate and Adaptive Immunity in Cystic Fibrosis\r | vii | ||
| Diagnostic Testing in Cystic Fibrosis\r | vii | ||
| Diagnosis of Adult Patients with Cystic Fibrosis\r | viii | ||
| The Microbiome in Cystic Fibrosis\r | viii | ||
| The Approach to Pseudomonas aeruginosa in Cystic Fibrosis\r | viii | ||
| Nontuberculous Mycobacterial Infections in Cystic Fibrosis\r | viii | ||
| Nutritional Issues in Cystic Fibrosis\r | ix | ||
| Gastrointestinal Disorders in Cystic Fibrosis\r | ix | ||
| Cystic Fibrosis Transitions of Care: Lessons Learned and Future Directions for Cystic Fibrosis\r | ix | ||
| Lung Transplantation for Cystic Fibrosis\r | ix | ||
| Using Cystic Fibrosis Therapies for Non–Cystic Fibrosis Bronchiectasis\r | x | ||
| Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in\rChronic Bronchitis and Other Diseases of Mucus Clearance\r | x | ||
| PROGRAM OBJECTIVE | xi | ||
| TARGET AUDIENCE | xi | ||
| LEARNING OBJECTIVES | xi | ||
| ACCREDITATION | xi | ||
| DISCLOSURE OF CONFLICTS OF INTEREST | xi | ||
| UNAPPROVED/OFF-LABEL USE DISCLOSURE | xi | ||
| TO ENROLL | xii | ||
| METHOD OF PARTICIPATION | xii | ||
| CME INQUIRIES/SPECIAL NEEDS | xii | ||
| CLINICS IN CHEST MEDICINE\r | xiii | ||
| FORTHCOMING ISSUES | xiii | ||
| June 2016 | xiii | ||
| September 2016 | xiii | ||
| December 2016 | xiii | ||
| RECENT ISSUES | xiii | ||
| December 2015 | xiii | ||
| September 2015 | xiii | ||
| June 2015 | xiii | ||
| Preface: Cystic Fibrosis | xv | ||
| Epidemiology of Cystic Fibrosis | 1 | ||
| Key points | 1 | ||
| CHANGES IN INCIDENCE AND PREVALENCE | 2 | ||
| CYSTIC FIBROSIS–RELATED CONDITIONS | 2 | ||
| DIAGNOSIS | 3 | ||
| CLASSIFICATION OF MUTANT FORMS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR AND THEIR IMPLICATIONS | 3 | ||
| TREATMENTS DIRECTED AT THE BASIC DEFECT | 3 | ||
| CLINICAL MANIFESTATIONS OF CYSTIC FIBROSIS | 4 | ||
| OUTCOMES IN CYSTIC FIBROSIS: IMPROVEMENTS AND CHALLENGES | 5 | ||
| INCREASING ADULT POPULATION OF CYSTIC FIBROSIS PATIENTS | 6 | ||
| CYSTIC FIBROSIS CENTERS: IMPACT ON OUTCOMES | 6 | ||
| REFERENCES | 6 | ||
| Genetics of Cystic Fibrosis | 9 | ||
| Key points | 9 | ||
| INTRODUCTION | 9 | ||
| CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN MUTATIONS AND THE DISEASE SPECTRUM | 9 | ||
| CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN MUTATIONS DIVIDED INTO FUNCTIONAL CLASSES | 10 | ||
| MODIFIERS | 11 | ||
| GENETICS AND DIAGNOSIS | 11 | ||
| GENETICS AND THERAPIES | 11 | ||
| Gene Therapy: Replacement or Edit | 11 | ||
| SMALL MOLECULES DIRECTED AT FIXING MUTANT CFTR | 12 | ||
| APPROVED AGENTS: (IVACAFTOR AND IVACAFTOR/LUMACAFTOR) | 13 | ||
| Ivacaftor | 13 | ||
| Individuals with the G551D CFTR mutation | 13 | ||
| Individuals with non-G551D gating mutations and class IV mutations | 13 | ||
| Ivacaftor and F508del Mutation | 13 | ||
| Safety of Ivacaftor | 14 | ||
| Lumacaftor Plus Ivacaftor: Challenges with Correcting F508del | 14 | ||
| ADVERSE EVENTS | 14 | ||
| EMERGING THERAPIES | 15 | ||
| EMERGING READ-THROUGH AGENTS: ATALUREN | 15 | ||
| SUMMARY | 15 | ||
| REFERENCES | 15 | ||
| Innate and Adaptive Immunity in Cystic Fibrosis | 17 | ||
| Key points | 17 | ||
| INNATE IMMUNITY | 17 | ||
| Altered Barrier Function Impairs Host Defense in Cystic Fibrosis | 17 | ||
| Reduced mucociliary clearance | 17 | ||
| Altered airway surface liquid composition | 18 | ||
| Airway surface liquid acidification | 18 | ||
| Increased protease activity | 18 | ||
| Oxidative environment | 19 | ||
| Decreased nitric oxide | 19 | ||
| Abnormal cell-cell connections | 19 | ||
| Altered Innate Immune Responses Contribute to a Proinflammatory Environment in Cystic Fibrosis | 19 | ||
| Pattern recognition receptor signaling | 19 | ||
| Dysregulated immune pathways | 20 | ||
| Altered Phagocyte Function Contributes to Dysregulated Host Defense in Cystic Fibrosis | 20 | ||
| Neutrophils | 21 | ||
| Macrophages/Monocytes | 21 | ||
| ADAPTIVE IMMUNITY | 22 | ||
| Communication Between the Innate and Adaptive Immune Systems | 22 | ||
| Lymphocytes, Cystic Fibrosis, and Immune Dysfunction | 22 | ||
| Regulating the Immune Response Preserves Lung Function in Cystic Fibrosis | 23 | ||
| SUMMARY | 24 | ||
| REFERENCES | 24 | ||
| Diagnostic Testing in Cystic Fibrosis | 31 | ||
| Key points | 31 | ||
| INTRODUCTION | 31 | ||
| SCREENING PROTOCOLS FOR CYSTIC FIBROSIS | 32 | ||
| Prenatal Screening | 32 | ||
| Newborn Screening | 32 | ||
| DIAGNOSTIC TESTING FOR CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN DEFECTS | 33 | ||
| Sweat Chloride Testing | 35 | ||
| Fecal Elastase | 35 | ||
| Nasal Potential Difference | 36 | ||
| Intestinal Current Measurement | 36 | ||
| DIAGNOSTIC CRITERIA FOR CYSTIC FIBROSIS | 37 | ||
| North American Cystic Fibrosis Foundation Guidelines for Diagnosis of Cystic Fibrosis | 38 | ||
| European Cystic Fibrosis Society Diagnostic Guidelines | 39 | ||
| CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN-RELATED METABOLIC SYNDROME | 39 | ||
| Diagnosis and Management of Cystic Fibrosis Transmembrane Conductance Regulator Protein-Related Metabolic Syndrome | 39 | ||
| Outcomes in Cystic Fibrosis Transmembrane Conductance Regulator Protein-Related Metabolic Syndrome | 40 | ||
| CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN-RELATED DISORDERS | 41 | ||
| Congenital Bilateral Absence of the Vas Deferens | 41 | ||
| Recurrent Pancreatitis | 41 | ||
| Idiopathic Bronchiectasis | 42 | ||
| SUMMARY | 42 | ||
| REFERENCES | 42 | ||
| Diagnosis of Adult Patients with Cystic Fibrosis | 47 | ||
| Key points | 47 | ||
| NATURE OF THE PROBLEM | 47 | ||
| DIAGNOSTIC CRITERIA | 48 | ||
| Sweat Chloride Testing | 48 | ||
| Cystic Fibrosis Transmembrane Receptor Genotype Analysis | 48 | ||
| Other Considerations | 50 | ||
| CLINICAL MANIFESTATIONS | 50 | ||
| Pulmonary Manifestations | 50 | ||
| Airway Infections | 50 | ||
| Chronic Sinusitis | 50 | ||
| Gastrointestinal Manifestations | 50 | ||
| Pancreatitis | 51 | ||
| Congenital Bilateral Absence of the Vas Deferens | 51 | ||
| Female Gender | 51 | ||
| CLINICAL FINDINGS | 51 | ||
| Physical Examination | 51 | ||
| Ancillary Testing | 52 | ||
| DIAGNOSTIC DILEMMAS | 54 | ||
| OUTCOMES FOR PATIENTS WITH CYSTIC FIBROSIS DIAGNOSED AS ADULTS | 54 | ||
| SUMMARY | 54 | ||
| REFERENCES | 55 | ||
| The Microbiome in Cystic Fibrosis | 59 | ||
| Key points | 59 | ||
| INTRODUCTION | 59 | ||
| OVERVIEW OF METHODS AND CONSIDERATIONS IN LUNG MICROBIOME INVESTIGATION | 60 | ||
| THE CYSTIC FIBROSIS RESPIRATORY MICROBIOME | 60 | ||
| Bacteria: Culture-based Investigations | 60 | ||
| Bacteria: Culture-independent Molecular Studies | 60 | ||
| Fungal Microbiota in Cystic Fibrosis | 62 | ||
| Viral Microbiota in Cystic Fibrosis Airways | 62 | ||
| FUNCTIONAL FEATURES OF THE CYSTIC FIBROSIS MICROBIOME | 63 | ||
| THE GASTROINTESTINAL MICROBIOME IN CYSTIC FIBROSIS | 63 | ||
| FUTURE DIRECTIONS IN CYSTIC FIBROSIS MICROBIOME RESEARCH | 64 | ||
| REFERENCES | 64 | ||
| The Approach to Pseudomonas aeruginosa in Cystic Fibrosis | 69 | ||
| Key points | 69 | ||
| INTRODUCTION | 69 | ||
| PREVENTION | 70 | ||
| Infection Control | 70 | ||
| Vaccination Against Pseudomonas aeruginosa | 70 | ||
| Prophylactic Antibiotics | 71 | ||
| EARLY ERADICATION THERAPY | 71 | ||
| MAINTENANCE THERAPY FOR CHRONIC INFECTION | 72 | ||
| Tobramycin | 73 | ||
| Aztreonam | 73 | ||
| Colistin | 73 | ||
| Fluoroquinolones | 74 | ||
| Amikacin | 74 | ||
| Continuous and Continuous Alternating Therapy | 74 | ||
| Chronic Oral Antibiotics | 75 | ||
| TREATMENT OF ACUTE PULMONARY EXACERBATIONS | 75 | ||
| The Use of Antimicrobial Susceptibility Testing to Guide Therapy | 75 | ||
| Route of Antibiotic Administration | 76 | ||
| Single Versus Double Coverage of Pseudomonas aeruginosa | 77 | ||
| Antibiotic Dosing Considerations | 77 | ||
| Duration of Treatment | 77 | ||
| Location of Treatment | 77 | ||
| SUMMARY | 78 | ||
| REFERENCES | 78 | ||
| Nontuberculous Mycobacterial Infections in Cystic Fibrosis | 83 | ||
| Key points | 83 | ||
| INTRODUCTION | 83 | ||
| EPIDEMIOLOGY | 83 | ||
| Individual Risk Factors for Nontuberculous Mycobacteria in Cystic Fibrosis | 84 | ||
| Environmental Risk Factors | 85 | ||
| DIAGNOSIS OF NONTUBERCULOUS MYCOBACTERIA LUNG DISEASE IN CYSTIC FIBROSIS | 85 | ||
| Laboratory Identification of Nontuberculous Mycobacteria in the Cystic Fibrosis Sputum | 86 | ||
| Drug Susceptibility Testing | 87 | ||
| SCREENING FOR NONTUBERCULOUS MYCOBACTERIA IN THE CYSTIC FIBROSIS POPULATION | 87 | ||
| TREATMENT OF NONTUBERCULOUS MYCOBACTERIA LUNG DISEASE | 88 | ||
| Treatment of Mycobacterium avium Complex Lung Disease | 88 | ||
| Treatment of Mycobacterium abscessus Complex Lung Disease | 88 | ||
| Monitoring of Drug Toxicity and Clinical Response | 89 | ||
| Therapeutic Drug Monitoring | 89 | ||
| NONPHARMACOLOGIC TREATMENT OPTIONS | 90 | ||
| SURGICAL TREATMENT OPTIONS | 90 | ||
| TREATMENT OUTCOMES AND IMPACT OF NONTUBERCULOUS MYCOBACTERIA LUNG DISEASE | 91 | ||
| RECOMMENDATIONS FOR FOLLOW-UP | 91 | ||
| LUNG TRANSPLANTATION IN CYSTIC FIBROSIS AND NONTUBERCULOUS MYCOBACTERIA | 91 | ||
| INFECTION PREVENTION | 92 | ||
| SUMMARY/DISCUSSION | 92 | ||
| REFERENCES | 92 | ||
| Nutritional Issues in Cystic Fibrosis | 97 | ||
| Key points | 97 | ||
| INTRODUCTION | 97 | ||
| EFFECT OF NUTRITIONAL STATUS ON CYSTIC FIBROSIS LUNG DISEASE AND SURVIVAL | 97 | ||
| LUNG TRANSPLANTATION AND NUTRITIONAL STATUS | 98 | ||
| PATHOGENESIS OF DISORDERED NUTRITION IN CYSTIC FIBROSIS | 98 | ||
| Undernutrition | 98 | ||
| Increased demand | 98 | ||
| Reduced intake | 99 | ||
| Increased loss | 99 | ||
| Overnutrition | 99 | ||
| Body Composition in Cystic Fibrosis | 100 | ||
| NUTRITIONAL ASSESSMENT | 100 | ||
| ENERGY INTAKE, VITAMIN AND MINERAL SUPPLEMENTATION | 101 | ||
| Pancreatic Enzyme Replacement Therapy | 101 | ||
| Fat-Soluble Vitamins | 101 | ||
| Essential Fatty Acids | 102 | ||
| Sodium | 102 | ||
| Zinc | 102 | ||
| BEHAVIORAL CONSIDERATION | 102 | ||
| ORAL SUPPLEMENTATION | 102 | ||
| APPETITE STIMULATION | 102 | ||
| ENTERAL SUPPLEMENTATION | 104 | ||
| COMPLICATIONS OF CYSTIC FIBROSIS | 104 | ||
| Cystic Fibrosis–Related Diabetes | 104 | ||
| Bone Health | 104 | ||
| Cystic Fibrosis–Related Liver Disease | 105 | ||
| SUMMARY | 105 | ||
| REFERENCES | 105 | ||
| Gastrointestinal Disorders in Cystic Fibrosis | 109 | ||
| Key points | 109 | ||
| INTRODUCTION | 109 | ||
| GASTROESOPHAGEAL REFLUX DISEASE | 110 | ||
| PANCREATIC INSUFFICIENCY AND PANCREATITIS | 110 | ||
| DYSMOTILITY AND SMALL INTESTINAL BACTERIAL OVERGROWTH | 112 | ||
| DISTAL INTESTINAL OBSTRUCTION SYNDROME AND CONSTIPATION | 113 | ||
| GASTROINTESTINAL MALIGNANCY | 115 | ||
| SUMMARY AND FUTURE CONSIDERATIONS | 115 | ||
| REFERENCES | 116 | ||
| Cystic Fibrosis Transitions of Care | 119 | ||
| Key points | 119 | ||
| DEVELOPMENT AND IMPLEMENTATION OF A CYSTIC FIBROSIS CARE CENTER NETWORK TRANSITION POLICY | 119 | ||
| What Has Transition From Pediatric to Adult Cystic Fibrosis Care Looked Like? | 120 | ||
| IMPROVING CYSTIC FIBROSIS TRANSITIONS | 120 | ||
| The Patient | 120 | ||
| Assessing patient readiness | 120 | ||
| Improving patient readiness | 121 | ||
| Mental health in young adults with cystic fibrosis | 121 | ||
| Adherence and burnout | 121 | ||
| Special populations: developmental disability | 121 | ||
| The Family, Friends, and Significant Others | 122 | ||
| Cultural competency | 122 | ||
| The Provider | 122 | ||
| CLINICAL OUTCOMES: MEASURING SUCCESS IN TRANSITIONS | 122 | ||
| TRANSITION AS A QUALITY IMPROVEMENT PROCESS | 122 | ||
| FUTURE NEEDS AND CURRENT CAPACITY FOR MEASURING QUALITY IMPROVEMENT ACTIVITIES | 123 | ||
| SUMMARY | 124 | ||
| ACKNOWLEDGMENTS | 124 | ||
| REFERENCES | 124 | ||
| Lung Transplantation for Cystic Fibrosis | 127 | ||
| Key points | 127 | ||
| BACKGROUND | 127 | ||
| GUIDELINES FOR REFERRAL AND EVALUATION | 128 | ||
| SELECTION OF CANDIDATES FOR LUNG TRANSPLANTATION | 128 | ||
| TYPE OF TRANSPLANTATION | 129 | ||
| COMORBIDITIES IN CYSTIC FIBROSIS AND IMPACT ON TRANSPLANT CANDIDACY AND OUTCOMES | 129 | ||
| Prior Thoracic Procedures | 129 | ||
| CF Bacterial Pathogens | 130 | ||
| Fungal Pathogens | 131 | ||
| Nontuberculous Mycobacteria | 131 | ||
| Gastrointestinal Comorbidities | 132 | ||
| Sinus Disease | 133 | ||
| Osteoporosis | 133 | ||
| Diabetes | 133 | ||
| MECHANICAL SUPPORT AS A BRIDGE TO LUNG TRANSPLANTATION | 134 | ||
| SURVIVAL AND QUALITY OF LIFE CONCERNS | 134 | ||
| OPPORTUNITIES FOR IMPROVED TRANSPLANT OUTCOMES | 135 | ||
| SUMMARY | 135 | ||
| REFERENCES | 135 | ||
| Using Cystic Fibrosis Therapies for Non–Cystic Fibrosis Bronchiectasis | 139 | ||
| Key points | 139 | ||
| INTRODUCTION | 139 | ||
| PATHOPHYSIOLOGY | 139 | ||
| PATIENT EVALUATION | 140 | ||
| PHARMACOLOGIC TREATMENT OPTIONS | 140 | ||
| Bronchodilators | 140 | ||
| Anti-inflammatory Therapy | 140 | ||
| Corticosteroids | 140 | ||
| Nonsteroidal anti-inflammatory therapy | 141 | ||
| Macrolides | 141 | ||
| Antibiotics | 141 | ||
| Systemic antibiotics | 141 | ||
| Inhaled antibiotics | 142 | ||
| Hyperosmolar and Mucolytic Therapy | 142 | ||
| Nebulized hypertonic saline | 142 | ||
| Inhaled mannitol | 143 | ||
| Inhaled DNase | 143 | ||
| NONPHARMACOLOGIC TREATMENT OPTIONS | 143 | ||
| Exercise | 143 | ||
| Airway Clearance Therapy | 143 | ||
| SURGICAL TREATMENT OPTIONS | 143 | ||
| EXPERIMENTAL THERAPIES | 143 | ||
| SUMMARY/DISCUSSION | 143 | ||
| REFERENCES | 143 | ||
| Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus ... | 147 | ||
| Key points | 147 | ||
| INTRODUCTION | 148 | ||
| Disease States Associated with CFTR Dysfunction | 148 | ||
| Pathologic Resemblance of Cystic Fibrosis and Chronic Bronchitis | 148 | ||
| Clinical Subphenotype in Chronic Obstructive Pulmonary Disease | 149 | ||
| EXPERIMENTAL DATA SHOWING ACQUIRED CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR DYSFUNCTION FROM SMOKING | 149 | ||
| Cigarette Smoke Blockade of Cystic Fibrosis Transmembrane Conductance Regulator Function | 149 | ||
| ACQUIRED CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR DYSFUNCTION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 150 | ||
| Patients with Chronic Obstructive Pulmonary Disease Show Reduced Cystic Fibrosis Transmembrane Conductance Regulator Activi ... | 150 | ||
| Sustained and Systemic Cystic Fibrosis Transmembrane Receptor Defects in Chronic Obstructive Pulmonary Disease | 150 | ||
| MEDIATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR DYSFUNCTION IN CIGARETTE SMOKE | 151 | ||
| SECONDHAND SMOKING | 151 | ||
| ACQUIRED CYSTIC FIBROSIS TRANSMEMBRANE RECEPTOR DYSFUNCTION AND ASTHMA | 152 | ||
| THERAPEUTIC APPROACHES | 154 | ||
| SUMMARY | 154 | ||
| FUNDING | 154 | ||
| CONFLICTS OF INTEREST | 154 | ||
| REFERENCES | 154 | ||
| Index | 159 |