Cystic Fibrosis in Primary Care An Essential Guide to a Complex, Multi-System Disease Douglas Lewis Editor 123 Cystic Fibrosis in Primary Care Douglas Lewis Editor Cystic Fibrosis in Primary Care An Essential Guide to a Complex, Multi-System Disease Editor Douglas Lewis, MD, FAAFP St Joseph Family Medicine Clinic Via Christi Regional Medical Center Wichita, KS USA ISBN 978-3-030-25908-2 ISBN 978-3-030-25909-9 (eBook) https://doi.org/10.1007/978-3-030-25909-9 © Springer Nature Switzerland AG 2020 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Foreword This book has grown out of the integration of the Adult Cystic Fibrosis Center with the Family Medicine Program in Wichita, Kansas As is often the case, Dr Doug Lewis entered the world of CF via a side door, by way of his interest in exercise- induced hyponatremia and the role of sweat electrolytes in this disorder From this point, he became more interested in cystic fibrosis generally and also recognized the local need for physician providers to care for the increasing number of adults with cystic fibrosis in the Wichita Center By working in the multidisciplinary clinic with many experienced providers, Dr Lewis was able to fill this need while gaining knowledge and increasing the depth of his own experience Through this connection, the Family Medicine Residency was able to develop inpatient services for adults with CF, contributing to a more defined transition to adult care and expanding the experiences of other Family Medicine faculty and their residents As a result, the great majority of the authors in this book are Family Medicine Residency faculty members Further, there are regional Family Medicine physicians who have participated in the care of adults with cystic fibrosis and have a working relationship with the Director of their local CF Center The world of cystic fibrosis is undergoing rapid change with the development and approval of CFTR modulator therapies Beginning with the approval of ivacaftor in 2012, patients with specific genotypes have experienced significant improvement in nutrition and lung function, followed by improved stability of respiratory health The next leap forward was the 2015 approval of a combination of a CFTR “corrector,” lumacaftor, with ivacaftor, a “potentiator,” extending benefits to patients homozygous for F508del, the most common genotype Benefits did not seem to be as great as had been seen in the cohort qualifying for ivacaftor alone; yet, significant nutritional gains and relative stabilization of respiratory health were seen (one parent described this as “freezing CF in place”); it was disappointing that the impact on F508del CFTR was not strong enough to benefit heterozygotes Now, there is great excitement about the “triple combo” of two correctors, tezacaftor and elexacaftor, each affecting the CFTR molecule by different mechanisms, with the workhorse potentiator, ivacaftor Results of clinical trials and cell culture studies place the impact of this combination on salt transport capacity within the range seen v vi Foreword with the ivacaftor-alone cohort, benefiting patients with either one or two copies of F508del (stronger effect in homozygous individuals) There is plausible expectation that this triple combo will be approved (age 12 and over) in late 2019 or early 2020 and will extend effective therapies to over 90% of individuals and families living with cystic fibrosis This will be a great success overall, yet a significant disappointment to those remaining outside of these treatable cohorts When the CF gene was identified in 1989, the vision of correcting the basic genetic defect naturally grew The hope was to restore normal gene expression by way of gene replacement; significant effort was directed to this end and there was promise of success with viral vectors inserting the normal gene into respiratory epithelial cells, thereby correcting the defect for the life cycle of those specific cells This would have required periodic delivery of new genetic material, likely every few weeks or months; this is where the concept failed, as immunity to the attenuated viral vectors developed rather rapidly Other techniques of gene delivery are still being sought Intervention in the process of gene expression is the current strategy, either by gene editing (repairing the defective gene to produce a normal gene) or using RNA in one of two ways, to bypass the translation step of gene expression by delivering mRNA with the normal gene to accomplish production of normal CFTR or using exogenous “suppressor” tRNA to promote bypassing the abnormal stop mutations of nonsense mutations The final strategy is stem cell therapy, by which means a cell line, such as respiratory epithelium, would be replaced by a donor line with normal CFTR genes The CFF (Cystic Fibrosis Foundation) is deeply committed to these strategies, which would function independent of specific mutations, with active engagement in the pursuit of the science and with significant funding These accomplishments are the direct result of a highly committed organization of families and other supporters working together to push forward with standards of care and research, implemented through a highly structured system of care and research centers It is essential that CF Care Centers remain as the core of cystic fibrosis medicine The net impact of the current medical breakthroughs will vary widely among individual patients, influenced by the age and state of health at the initiation of therapy, adherence to treatment (adolescents will continue to be invincible), comorbidities, and health-care financing (a likely contributor to the recognized higher life expectancy in Canada compared to the United States) And, as noted above, there are patients not eligible for these therapies (as noted above, the CFF has committed itself to continued support of research to find effective therapy or cure for all patients); the care of these patients, including access to other new therapies and the opportunity to participate in research to address their specific genotypes (such as nonsense mutations) or therapies that are independent of genotype, will not change in the near future Now, coming back to Dr Lewis’ book, if the expected benefits of the newest generation of CFTR modulation are found to be true and enduring, longevity and overall wellness will increase In parallel with this, more people with CF will be faced with conventional medical needs: hypertension, type diabetes, arthritis, pregnancies, menopause, and obesity In addition, there will undoubtedly arise some questioning of the need for the same intensity of treatment and the frequency Foreword vii of monitoring that has been aggressively practiced or pursued for decades This would be a dramatic attitude adjustment for care providers, medical and family, even were it to emerge only slowly Many patients, however, have always had some degree of resistance to the burdens of care they see as being pushed upon them; they are certainly not all wrong Family medicine providers, particularly outside of urban areas, have a more holistic approach to patient care than I think is found in specialty centers (I think general pediatricians are similar, yet with less awareness of family, particularly extended family, dynamics), and are generally eager to help lessen the burden of therapy provided that the burden of illness does not suffer I view this book, and future updated editions, as a support mechanism for increased participation of primary care providers (family medicine, pediatrics, general internal medicine, and med-peds practitioners) in the care of people with cystic fibrosis This will warrant caution and patience and has to include development of a working relationship between the primary care and CF Center providers The preponderance of CF care should remain with the CF Center; yet, this will evolve in its own way Guidelines for care of CF will change, as well, perhaps becoming more specific for differing severity of illness and differing ages, and adjusting to patients’ perceptions of needs for and benefits of specialty care Increased contributions from the primary care providers will certainly play a key role Via Christi Cystic Fibrosis Clinic Philip Black, MD Wichita, KS, USA Preface This book was developed and written with the primary care provider in mind Since the early 1950s in particular, the median age of survival for patients with cystic fibrosis (CF) has improved dramatically The reasons for this improvement are multifactorial, and the reader will be exposed to the entirety of CF care throughout this work Because of the increased survivability of those affected by CF, primary care providers are increasingly exposed to providing care in regular clinics, minor emergency centers, emergency departments, etc While there is abundant literature on the delivery of care to this population, there is a paucity of material written with a primary care audience in mind Furthermore, from concept to authorship to the editorial process, this work was produced by primary care physicians who regularly care for patients with CF I, Dr Lewis, have been involved in CF care and research for approaching 10 years and am presently the director of the Ascension Via Christi Cystic Fibrosis Clinic The family medicine residency program, where I am full-time faculty, manages our CF patients on the hospital medicine service, and many other faculty alongside residents have served as chapter authors I wish to thank the entire staff of the Ascension Via Christi Cystic Fibrosis Care Center for presenting their ideas to the team of authors, for allowing observation of clinic processes, and for enduring endless hours of writing and rewriting Wichita, KS, USA Douglas Lewis, MD, FAAFP ix Contents 1 Evolution of Cystic Fibrosis Care���������������������������������������������������������� 1 Douglas Lewis, Natalie Sollo, and Philip Black 2 CF Basics�������������������������������������������������������������������������������������������������� 9 Natalie Sollo and Mazahir Ali 3 CFTR Physiology ������������������������������������������������������������������������������������ 19 Apeksha Sathyaprasad 4 Spirometry in Cystic Fibrosis ���������������������������������������������������������������� 27 Donald Seery and Lary Hill 5 Exercise for CF���������������������������������������������������������������������������������������� 41 Maurice Duggins and Douglas Lewis 6 Inflammation in Cystic Fibrosis ������������������������������������������������������������ 47 Rex B Keith and Douglas Lewis 7 CF Airway Clearance������������������������������������������������������������������������������ 57 Dee Ann Bragg and Douglas Lewis 8 Acute and Chronic Infection Management in CF�������������������������������� 69 Patrick Allen, Joseph Borick, and Jamie Borick 9 Sexual and Reproductive Health and Counseling�������������������������������� 89 Lisa Gilbert, Sara Johnson, and Sarah Stokes 10 Gastrointestinal Disease and Nutrition in Cystic Fibrosis ������������������ 105 Sheryl Beard and Margaret Pray 11 CF Related Diabetes�������������������������������������������������������������������������������� 117 Douglas Lewis, Melissa C Norton, and Lyndsey N Buzzard 12 Electrolyte Abnormalities in CF ������������������������������������������������������������ 127 Jennifer Wipperman and Jackie Anderson xi xii Contents 13 CFTR Carrier Status������������������������������������������������������������������������������ 141 Bonnie Tibbe and Craig Cunningham 14 CFTR Corrector Therapies/New Therapies������������������������������������������ 153 Douglas Lewis 15 Psychology and Psychotherapy in CF���������������������������������������������������� 161 Ruth Nutting and Stephen Amos Index������������������������������������������������������������������������������������������������������������������ 177 168 R Nutting and S Amos Adolescence Management and Development Patients and families experience significant adaptations in daily routines and social roles secondary to managing CF [28, 29], with increased adaptations during adolescence [28, 30] Adolescence is a period in which youth seek independence and spend increased amounts of time within their social networks [28–30] In turn, adolescents may desire less assistance from parents with treatment regimens When adolescent patients perceive family members as nagging, when parents disengage totally from the supervision of CF medical treatment, or when social obligations interfere with treatment regimens, adherence declines [28, 30] It is important that family members and friends remain mindful of patients’ treatment regimens and help protect treatment time in a supportive manner Parents may need to re-educate adolescents on knowledge and understanding of the importance of treatments, as they seek increased independence It is also imperative for parents to continually assess adherence, and may need to increase supervision for a period, before beginning to “fade,” as adolescents demonstrate greater responsibility [30] Patient Perspective I am 13 years old and in the eighth grade This is my typical day living with CF. To start, I wake at 5:45 to morning treatments, which consist of various kinds of medicines that are inhaled These treatments last for 45 minutes Before heading to school, I eat breakfast, count carbs for what I ate, and test my blood sugars—I test my sugars because I have CF-related diabetes I then take my 12 morning pills, primarily consisting of enzymes to help digest my food and keep me healthy Then it’s off to school At lunchtime I go to the school office to test my sugars again While I’m in the office, I pick up enzymes that I will take with my lunch Since I pack my own lunch, I know the amount of carbs I have for lunch and can tally that quickly I keep a book where I write all my numbers to track By the time I get home, I have worked up an appetite and eat a snack Before I eat the snack, I test my sugars again and another carb count I take more enzymes and then homework as I snack Then comes dinner and the whole routine repeats Test sugars, count carbs, and take enzymes This time it’s 14 pills I hate taking them, but I want to be as healthy as I can, so I it anyway At about 8:00 pm, my parents start reminding me about doing my breathing treatments I’m now tired and just want to hang out with family and friends but I know I can’t I start my vest for a long 20 minutes, while my Mom will try to find something for me to watch on TV. I also one of my inhalers while doing my vest Once I’m done with my vest, I will start on my nebulizer, hypertonic saline, Pulmozyme, amikacin, and my last inhaler I’m finally done! The last thing I is have a snack before bedtime So again, the routine of checking sugars, counting carbs, and taking enzymes Then I go to sleep When I wake up, it’s the same thing, day after day and month after month Hopefully, year after year too Intervention Parents and adolescents need anticipatory guidance on how and when to best transition responsibility for daily treatment regimens This guidance 15 Psychology and Psychotherapy in CF 169 should teach parents how to prompt adolescents in gaining responsibility in treatment adherence and how family systems can continue to adapt to developmental changes for all family members [30] It is critical that practitioners remain mindful to assess family functioning and communication to suggest appropriate family interventions targeted at improving adolescent adherence See Table 15.1 for specific CF milestone tools that can be shared with families to assist with the transitional demands of adolescents Young Adulthood Management and Development With the survival rate of patients with CF continually rising, there is a growing population of adults living with CF [3] As adolescents mature to young adults, they experience transitions such as beginning work, beginning/finishing postsecondary education and graduate programs, beginning careers, supporting oneself, and forming deep relationships [18, 31] This is also a time in which patients may experience increased social stigma, as their sense of identity is developed, greater independence is negotiated from parents, and social comparisons increasingly influence social relationships [32] Cystic fibrosis may be stigmatizing due to visible symptoms, shortened life expectancy, and the potential for treatment regimens to disrupt activities [32] This stigma is associated with increased psychological distress, lower quality of life, poor body image, lowered self-esteem, and lower sense of personal control [33] Consequently, patients may experience increased social anxiety and decreased adherence to conceal their diagnosis from others by minimizing symptoms or hiding medication usage, to feel more like peers [32, 34] Patient Perspective The thing about CF is that you don’t just get better It is not like a normal sickness where you take medicine and in a week you feel back to yourself You must choose every day to remain compliant and give yourself the best chance at life For me that means waking up at least 2 hours before I need to go anywhere to have enough time to complete the multiple breathing treatments and therapies I must in the morning Then, throughout the day, it is remembering to take the dozens of pills you need, clean all your neb cups, and get some exercise in On top of that, it is staying up even later at night to even more breathing treatments The hard thing is that we are still expected to normal adult things like cook dinner, keep up with laundry, clean, and work I always thought that as I would get older, managing CF would get easier; however I learned that is not the case, especially as I transitioned from high school into college Learning how to manage being a full-time student, having a job, maintaining a social life, and everything dealing with CF was extremely hard Doctors can try their best to prepare us for what to expect while living a life with CF. However, there are just some things that no one can prepare you for 170 R Nutting and S Amos It is the frustrating things that we all must process for ourselves: the looks that strangers give you while you are having a coughing attack in public; living your whole life being told you have a life expectancy, and even though you spend every day doing all you can to stay healthy, there is no guarantee that it will work; having to take time off of work because you are too sick; and the guilt you might have from always feeling like you are a burden to your family and friends While it can be easy to focus on the negative things that come with having CF, it is important that you not let your mind go there, because it is easy to get swallowed up into a black hole of feeling sorry for yourself That will only lead to you filling more stressed which takes a toll on your health CF can take a toll on your mental health, but I always try to remember that there is so much more to who I am than just having cystic fibrosis Intervention Research continues to identify that optimistic and hopeful outlooks are protective factors for optimal emotional and physical functioning [20, 32, 35] specifically among those experiencing increased rates of stigma [32] Patients experiencing higher rates of stigma may be at a higher risk of psychological distress and low quality of life Specifically, patients with lower optimism and higher reported stigma may be more likely to experience distress and may benefit from further psychosocial assessment or intervention [32] It is important for practitioners to overtly attend to patients’ affect and mood as emotions are discussed and practitioners support patients in finding meaning and hope through adversity [20] See Table 15.1 for mindfulness interventions targeted at decreasing negative psychological symptoms such as anxiety and depression Parent Management and Development Cystic fibrosis requires adjustment from both patients and parents Some children and parents adjust well to CF, while others struggle [36] Positive parent coping, which includes optimism and hope for future outcomes, is considered an important factor in adjustment to CF for both parents and patients [36], as these coping constructs have been shown to positively influence health and well-being [37], while negative coping constructs, such as despair, challenge positive adjustment [36] In addition, parents who blame themselves for their children’s illness or disengage from pursuing goals for their children are at an increased risk of experiencing emotional distress, such as anxiety and depression [36], while parents who have hopeful outlooks for their children and provide emotional support experience lower levels of emotional distress [20, 36] Therefore, it is important for parents to perceive their children as having the potential to live a normal life, regardless of having CF 15 Psychology and Psychotherapy in CF 171 Parent Perspective As a parent of a now “adult” CF patient, the landscape of CF and the way our family navigates this disease have changed My wife and I prepared our daughter to move into the adult phase of life as much as possible The transition into adulthood with CF comes with a lot of concern and a lot of faith in the path that we set on preparing for this time in life The truth is that our daughter is a normal kid who happens to have CF. When she was a child, we encouraged her to get involved with all the activities and sports that interested her We didn’t want CF to slow her down at all, and we didn’t want to be too overprotective Of course, we were always careful with her, but we wanted her to live her life to the fullest It was easy to monitor how she seemed to be feeling, and it was also easy to make sure she would get all her treatments and meds taken every single day Compliance came easy to us as parents If we were told to something for her and schedule her treatments to so, we would it Now we can no longer know for sure if she is getting all her treatments done and meds taken at the appropriate time throughout her day We are certain she isn’t 100 percent executing her care to the best of her ability She is finding her way, and that’s important In her freshman year of college, she went through a period where she tried to figure out how much of her treatments she could skip and still maintain a certain degree of health Predictably her lung function dropped Her doctor had a very frank conversation with her, and that really helped get her back on the right track As parents, it’s hard to stand back and watch your child “fail” for lack of a better term We were anticipating a bit of a crash but were hoping to avoid a crash and burn Fortunately, she was able to turn her health around and got herself feeling much better CF never goes away and dealing with it in one way or another never stops Our daughter is a very strong independent woman, and that will serve her well as she navigates the waters of adult life My wife is a tremendous help with the ongoing coordination in dealing with this disease: doctors’ appointments, drug studies, refilling prescriptions, and dealing with health insurance on so many levels With all these my daughter is trying to be a full-time student and holding down a part- time job It is easy to look at our daughter with pride and admiration for the young woman she is She has dealt with CF head-on from day Our role now is different than the first 18 years of her life; however our goal for her is still the same We want to the best we can for her and help her to have the best life she can Intervention It is important, for healthcare teams, to support parents in reducing self-blame and increasing focus on supporting their children in attaining important life transitions [20, 36] to increase positive illness-related adjustment This can be supported through interventions directed toward enhancing parents’ hope and addressing patterns of self-blame while also taking into consideration parenting needs Review Table 15.1 for resources on parent guidance 172 R Nutting and S Amos End of Life Preparation Coming to terms with death and loss is the most difficult challenge a family will face [38] With a disease like CF, loss may begin tentatively, with hopes for a life-extending lung transplant, to greater probability, and then certainty of loss during the terminal phase [38] Through these stages, patients and family members confront death in their own ways With chronic illnesses, such as CF, healthcare teams often form lifelong relationships with CF patients and their families These practitioners are uniquely positioned to support families through the terminal phase by assisting families in adapting through active coping of struggling well and meeting challenges [38] Supporting families through this phase is an honor as well as a challenge With lifetime relationships forged with these patients and families, practitioners have their own emotionally charged responses to end-of-life tasks Professional Perspective I entered my office to find her sitting, breathing in a labored fashion even with oxygen being dispensed and her parents at her side As I sat down, she looked at me through hollow eyes and asked, “Am I dying?” It was exactly at that moment that I realized I was ill prepared to answer that question I had done my fair share of counseling people through their own grief processes after a death of a loved one had occurred, but had little experience giving that kind of news to someone who clearly was dying In retrospect, I suppose we all knew the answer, but she needed to hear it too So, I was left, in that moment, hearing myself say “yes, you are,” and that is when the real conversation began We talked about hopes and dreams, about friends and family, about God and faith, and about endings and beginnings In the end she wanted to tell her story, and I wanted to listen Intervention It is beyond the scope of this chapter to delineate the complex and often heart-wrenching end-of-life journey Embracing a systemic perspective that attends to the past, present, and future as well as the meaning of death for families within social context and developmental passage is critical in helping families build resilience Effectively working with patients and families during this phase involves shared acknowledgement of the reality of death and encouraging patients and family members to share their personal feelings of loss with one another [38] Family communication, over the course of the loss process, is crucial Open communication will allow for family systems to recognize their hopes and desires for now and the future It will also assist in the reorganization and reinvestment in other relationships and life pursuits as time passes [38] Practitioners often feel ill-equipped in fully supporting families during this phase It is important to recognize the importance of the alliance between practitioners, patients, and families and that this alliance is composed of trust, compassion, and involvement—interpersonal factors that develop and strengthen over time [39] These skills are a necessity as practitioners learn to understand families’ cultural and spiritual belief systems as they make meaning of death, to assist them in engaging 15 Psychology and Psychotherapy in CF 173 Table 15.1 Cystic fibrosis resources for healthcare practitioners and families Cystic Fibrosis Foundation www.cff.org Children’s Hospital-London Health Sciences Centre https://www.lhsc.on.ca/childrens-cystic-fibrosis Cystic Fibrosis R.I.S.E www.cfrise.com Body Scan Meditation https://youtu.be/ZM3eYRODNbc Progressive Muscle Relaxation https://www.youtube.com/watch?v=86HUcX8ZtAk Guided Imagery https://www.youtube.com/watch?v=ar_W4jSzOlM&t=44s Wellbeing and Spirituality https://newharbinger.com SPIKES https://www.youtube.com/watch?v=JtkgTzCSzqk Families Talking about Death: A Dialogue between Parent and Child By: Earl A. Grollman There Are No Alligators in Heaven: A Family’s Perspectives on Surviving the Unrelenting Savagery of Cystic Fibrosis By: Donna Codell, Evan Michael Codell, & Jennifer Hale Good Grief: A Companion for Every Loss By: Granger E. Westberg Grief: The Mourning After By: Catherine M. Sanders Parents Helping Children Cope with Grief By: Alan Wolfelt The Unspeakable Loss: How Do You Live After a Child Dies? By: Nisha Zenoff Partners Grief Day by Day: Simple Practices and Daily Guidance for Living with Loss By: Jan Warner How to Survive the Loss of a Love By: Melba Colgrove, Harold H. Bloomfield, & Peter McWilliams Practitioners When Practitioners Weep: Emotional Countertransference Responses in Palliative and End-of-Life Care Edited by: Renee S. Kats & Therese A. Johnson Educational resources for patients and families on diagnosis, treatment, transitions, and daily living with CF A series of CF knowledge and skills assessments on various topics to help identify areas where care teams can partner with patients and families to provide additional support and education Mindfulness coping skills and materials related to decreasing negative psychological symptoms of CF for patients and families A video clip that encapsulates how to provide a compassionate diagnosis and prognosis by utilizing the SPIKES approach Books for families, parents, partners, and practitioners on death, grief, and living on 174 R Nutting and S Amos with one another in the dying and mourning process [38] It is important to note that there is no essential commonality nor a complete conception of what is a “normal” grief process nor a clear consensus about how long one can or should grieve the loss of a loved one Even with practitioners becoming well versed in end-of-life issues, our patients tend to be our best teachers Conclusion CF is a complex disease that encompasses the life cycle In addition to the numerous physical complexities patients experience, psychological implications are posed for them and their family members Healthcare teams are uniquely positioned, as longitudinal relationships allow for practitioners to provide systemic interventions at each phase of life The aim of these interventions is to allow families to make meaning out of adversity, foster positive outlooks, increase communication, and reorganize family functioning—ensuring coping and resilience References Cystic Fibrosis Foundation of America [Internet] Life with CF 2017 [Cited 2019 Feb 25] Available from: https://www.cff.org/ Quittner AL, Abbott J, Georgiopoulos AM, Goldbeck L, Smith B, Hempstead SE, et al International committee on mental health in cystic fibrosis: Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus statements for screening and treating depression and anxiety Thorax 2016;71(1):26–34 Sawicki GS, Sellers DE, Robinson WM. 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Strengthening the systemic ties that bind: integrating common factors into marriage and family therapy curricula J Marital Fam Ther 2015;41(2):136–49 Index A Achromobacter xylosoxidans, 74 Active cycle of breathing technique (ACBT), 62 Airway clearance ACTs ACBT, 62 autogenic drainage, 62, 63 compliance importance, 64 CPT, 61, 62 guidelines, 60, 61 HFCWO, 63, 64 novel ACT devices, 64 PEP and oscillating PEP, 63 mucolytic agents hypertonic saline, 59 NAC, 59, 60 principles, 57, 58 recombinant human DNAse, 58, 59 Airway clearance techniques (ACTs) ACBT, 62 autogenic drainage, 62, 63 compliance importance, 64 CPT, 61, 62 guidelines, 60, 61 HFCWO, 63, 64 novel ACT devices, 64 PEP and oscillating PEP, 63 Airway surface layer (ASL), 59 Airway surface liquid, 154 Airway surface liquid and mucus layer (ASLM), 49, 50 Albuterol, 31 Allergic bronchopulmonary aspergillosis (ABPA), 146 Antenatal carrier testing, 148, 149 © Springer Nature Switzerland AG 2020 D Lewis (ed.), Cystic Fibrosis in Primary Care, https://doi.org/10.1007/978-3-030-25909-9 Anxiety, 15 Aquagenic wrinkling of palms, 145 Ascites, 112 Aspergillus sp., 75 A.fumigatus, 74 Assisted reproductive techniques (ART), 144 Autogenic drainage (AD), 62, 63 Azoospermia, 93 Aztreonam, 80 B Baseline pulmonary function, 97 Behavioral modification, 108 Beta-lactams, 100 Biofilms, 72, 76, 78 Bone health, 114, 115 Breastfeeding, 101 Bronchial asthma, 146, 147 Bronchiectasis, 21 Burkholderia spp., 98 Burkholderia cepacia complex (BCC), 72, 73, 79 C Candida, 75 C albicans, 74 Carrier status, ABPA, 146 antenatal carrier testing, 148, 149 aquagenic wrinkling of palms, 145 bronchial asthma, 146, 147 CBAVD, 143, 144 CFTR function, repression of, 148 chronic rhinosinusitis, 147 177 178 Carrier status (cont.) CRMS, 142, 143 disease and CFTR function, 141, 142 disseminated bronchiectasis, 145, 146 nasal polyposis, 147, 148 pancreatitis and pancreatic insufficiency, 144, 145 Cepacia syndrome, 73, 79 Chest physiotherapy (CPT), 108 Chloride, 130 Cholelithiasis, 111 Cholestasis, 112 Chronic airway infection, 21 Chronic infections, 80, 81 infection prevention and control, 82, 83 lung transplantation, 82 pharmacokinetic considerations, 81, 82 Chronic rhinosinusitis (CRS), 147 Chronic/acute infection management cystic fibrosis, clinical microbiology in Achromobacter xylosoxidans, 74 BCC, 72, 73 fungi, 74, 75 NTM, 73 Pseudomonas aeruginosa, 71, 72 respiratory viruses, 75, 76 Staphylococcus aureus, 71 Stenotrophomonas maltophilia, 73, 74 epidemiology, 70 infection, pathophysiological for, 69 pulmonary exacerbations diagnosis and etiology, 77 treatment, 77–80 Ciprofloxacin, 78, 100 Cirrhosis, 112 Colorectal cancer, 15 Congenital bilateral absence of vas deferens (CBAVD), 23, 93, 143, 144 Constipation, 109 Continuous positive expiratory pressure (CPEP), 64 Contraception, 91, 92 Conventional chest physiotherapy (CPT), 61, 62 Coping, 162, 163 Corpulmonale, 98 Cystic fibrosis (CF), 19 adolescence intervention, 168 management and development, 168 patient approach, 168 CFRD, 14, 15 Index CFTR-RD, 13 childhood family approach, 166, 167 intervention, 167 management and development, 166 clinical manifestations liver disease, 14 lung disease, 13, 14 pancreatic insufficiency and malabsorption, 14 colorectal cancer, 15 CRMS/ CFSPID, 13 Cystic Fibrosis Foundation and CF Care Centers Care Centers, 3–5 depression and anxiety, 15 diagnosis, 11, 12 discovery of, 1–3 end of life intervention, 172, 174 preparation, 172 professional approach, 172 genetic testing, 13 genetics, 9, 10 incidence, 10 infancy, 164, 165 inflammation in (see Inflammation) intervention, 165 management, 161, 162 newborn screening, 12 parent intervention, 171 management and development, 170 parent approach, 171 psychological implications, 162 reproductive challenges, 15 resources for health care practitioners and families, 173 survival, 11 sweat testing, 12 systemic treatment coping, 162, 163 resilience, 163 treatment paradigm shift, 15, 16 young adulthood intervention, 170 management and development, 169 patient approach, 169, 170 Cystic fibrosis Foundation (CFF), 3–5, 153 Cystic fibrosis lung disease, neutrophils and neutrophil products in, 48, 49 Cystic fibrosis screen positive inconclusive diagnosis (CFSPID), 13 Index CFTR corrector therapies epithelial sodium channel, 159 gene therapy, 154 restoring CFTR function, 154–158 CFTR defect, to inflammation, 49–51 CFTR modulator therapy, 158 CFTR-RD, 13 CFTR-related metabolic syndrome (CRMS), 13, 142, 143 Cystic Fibrosis Care Center network, 3–5 Cystic fibrosis related diabetes (CFRD), 6, 14, 15, 117 clinical presentation, 119 complications, 124 acute, 124 chronic, 124, 125 diagnosis, 121 management, 121 glycemic control with insulin, 122, 123 glycemic targets and self-monitored blood glucose, 123 pulmonary function status and infection risk, 123, 124 weight management with insulin, 123 pathophysiology, 118 insulin function and utilization, 118 insulin release, effect on, 118, 119 screening, 120 Cystic fibrosis transmembrane conductance regulator (CFTR), 7, molecular mechanism, 19, 20 mutation classes, 20 pathophysiology gastrointestinal tract, 22 hepatobiliary system, 23 lung disease, 21, 22 pancreas, 22, 23 reproductive tract, 23 sweat glands, 20 D Dehydration, 132 Delayed puberty, 90 Delivery, preconception care, 101 Depo-Provera, 91 Depression, 15 Diabetic ketoacidosis, 124 Disseminated bronchiectasis (DB), 145, 146 Distal intestinal obstruction, 108 Distal intestinal obstruction syndrome (DIOS), 14, 108, 109 179 DNase I, 58 Dornase alfa, 58 Doxycycline, 78 Dyspnea, 44 E Elastase, 106 Electrolyte, 136 Electrolyte abnormalities, 127–131 clinical presentation, 131 pathophysiology, 130 Electrolyte metabolism, 44 Endoplasmic reticulum associated degradation (ERAD), 155 Endoscopic retrograde cholangiopancreatography (ERCP), 111 Epithelial sodium channel, 159 Euvolemia, 134 Euvolemic hyponatremia, 133 Excessive inflammation, 21 Exercise, 135, 136 in general population, 41–43 to patient, 43, 44 risk to avoid, 44, 45 Exercise-associated hyponatremia (EAH), 132 Exophiala dermatitidis, 75 F F508del, 9, 157 Family diagnosis, 166 Fertile window, 95 Fertility, 92 FEV1/FVC ratio, 30 Fibrosis, 112 Flow-volume loops, 31, 32 Follicle-stimulating hormone (FSH), 94 Forced expiratory flow, spirometry, 30 Forced Expiratory volume in one second (FEV1), 29 Forced vital capacity (FVC), 29, 30 G G551D mutation, 157 Gastroesophageal reflux disease, 107 Gastrointestinal (GI) diseases, 107–109 Gastrointestinal system, Gastrointestinal tract, CFTR, 22 Gastropathy, 112 Index 180 Gene therapy, 154 Genetic counseling, 96, 149 Genetic testing, 13 Glycemic targets, 123 H Health and Human Services, 42 Heat exhaustion, 127 Hepatic congestion, 112 Hepatic steatosis, 112 Hepatobiliary disease, 110–113 Hepatobiliary system, CFTR, 23 High-frequency chest wall oscillation (HFCWO), 63, 64 Human sweat glands, 129 Hydration, 44 Hypertension, 125 Hypertonic saline, 59 Hyponatremia clinical presentation, 131 EAH, 132 epidemiology, 128, 129 evaluation, 132, 133 pathophysiology, 129–131 presentation of, 137 prevention, 135, 136 treatment, 134, 135 Hypoosmolality, 133 Hypovolemia, 133 Hypovolemic hyponatremia, 133 Hypoxia, 44 I Immunoreactive trypsinogen level (IRT), 12 Impaired fertilization, 94 Infertility among men with CF, 93, 94 among patients with CF, 95, 96 among women with CF, 94, 95 Inflammation, 47, 48 bacteria and, 51 CF inflammatory response, 48 CF lung disease, neutrophils and neutrophil products in, 48, 49 CFTR defect to, 49–51 Inhaled antibiotics, 75 Insulin function and utilization, 118 glycemic control with, 122, 123 weight management with, 123 Insulin release, effect on, 118, 119 Intrapulmonary percussive ventilation (IPV) device, 64 Intravenous aminoglycosides, 82 Intussusception, 109 Ischemia-reperfusion injury, 112 Islet cell damage, collateral damage mechanism of, 118 Ivacaftor, 80, 156 K Kalydeco, 158 L Life-cycle process, 162 Liver disease, 14, 110 Liver failure, 113 Lumacaftor, 158 Lung clearance index (LCI), spirometry, 30 Lung disease, 13, 14 CFTR, 21, 22 Lung inflammation, bacteria and, 51 Lung transplantation, chronic infections, 82 Luteinizing hormone (LH), 94, 95 M Mycobacterium spp M abscessus, 79 M avium, 80 Macrovascular atherosclerotic disease, 125 Malabsorption, 14 Male infertility, 93 Marquette method, 95 Mechanical airway clearance, Medroxyprogesterone acetate injection, 91 Metabolic disruption, 44 MetaNeb®, 64 Methicillin-sensitive Staphylococcus aureus, 78 Microcolonies, 69 Mucolytic agents hypertonic saline, 59 NAC, 59, 60 recombinant human DNAse, 58, 59 Multi-system autosomal recessive disease, Muscle damage, 44 N Nasal polyposis, 147, 148 National Lung Health education program, 28 Index Neonatal cholestasis, 111 Neutrophil extracellular traps (NETs), 49 Newborn screening, 12 Nexplanon, 91 NFκB-dependent transcription, 50 Nontuberculous mycobacteria (NTM), 73, 79 Nutrition bone health and, 114, 115 issues, 113, 114 vitamin deficiencies, 114 O Oral glucose tolerance test (OGTT), 90, 98, 120 Oscillating PEP, 63 Osmosis, 59 Osmotic demyelination syndrome (ODS), 134, 135 P Pancreas, CFTR, 22, 23 Pancreatic enzyme replacement therapy (PERT), 14, 106 Pancreatic insufficiency (PI), 14, 105–107, 144, 145 Pancreatitis, 144, 145 Polycystic ovarian syndrome (PCOS), 94 Portal hypertension, 112 Positive expiratory pressure (PEP) devices, 63 Post-bronchodilator testing, spirometry, 31 Potentiator, 158 Preconception care, 96 breastfeeding, 101 delivery, 101 intrapartum management, 100 pregnancy, 99, 100 genetic and ethical implications of, 96, 97 medical optimization, 97, 98 Pregnancy, preconception care, 99, 100 Preimplantation genetic diagnosis (PGD), 96 Proton pump inhibitors (PPIs), 107 Pseudohyponatremia, 132, 133 Pseudomonas aeruginosa, 71, 72, 79 Pubertal development, 90, 91 Pulmonary exacerbation (PEx), 37, 38 Pulmonary exacerbations chronic/acute infection diagnosis and etiology, 77 treatment, 77–80 Pulmonary function testing (PFT), 27 181 long-term care, 36 pulmonary exacerbation, 37, 38 spirometry and, 28 R Recombinant human DNAse, 58 Rectal prolapse, 109 Rehydration fluids, 44 Reproductive tract, CFTR, 23 Resilience, 163 Respiratory syncytial virus (RSV), 75, 76 S Salt, 136 Scedosporium, 75 S apiospermum, 74 Self-monitored blood glucose, 123 Serum osmolality, 132 Sexual and reproductive health (SRH), 89 contraception, 91, 92 infertility amongmen with CF, 93, 94 amongpatients with CF, 95, 96 amongwomen with CF, 94, 95 preconception care, 96 breastfeeding, 101 delivery, 101 intrapartum management, 100 pregnancy, 99, 100 pregnancy, genetic and ethical implications of, 96, 97 pregnancy, medical optimization, 97, 98 pregnancy,medical optimization, 97 principles, 89 pubertal development, 90, 91 sexual function, 92 sexually transmitted infections, 92, 93 Sexual function, 92 Sexually transmitted infections, 92, 93 Slow vital capacity (SVC), spirometry, 30 Small intestine bacterial overgrowth (SIBO), 108 Socosahexaenoic acid, 50 Sodium, 129, 131, 133, 135 Spirometry, 27, 28 children 1-3 years of age, 35 3-6 years of age, 35 years and up, 35 Clinical Practice Guidelines for Cystic Fibrosis, 34, 35 Index 182 Spirometry (cont.) cross-contamination, 33 diffusing capacity, 31 FEV1, 29 flow-volume loops, 31, 32 Forced Expiratory Flow, 30 FVC, 29, 30 LCI, 30 long-term care, pulmonary function testing in, 36 majority of, 28, 29 post-bronchodilator testing, 31 procedure, 34 pulmonary exacerbation, 37, 38 and pulmonary function testing, 28 quality control, 32, 33 SVC, 30 Staphylococcus aureus, 71 Stenotrophomonas maltophilia, 73, 74 Sweat chloride, 143 Sweat gland, 129 CFTR, 20 physiology, 130 Sweat testing, 12 Symdeko, 158 Syndrome of inappropriate antidiuretic hormone (SIADH), 130 T Teicoplanin, 78 Therapeutic Development Network (TDN), Tobramycin, 100 U Urinary incontinence, 93 V Venture Philanthropy Model, 153, 155 Vest®, 64 VibraLung®, 64 Viruses, chronic/acute infection management, 75, 76 Vitamin A, 99 Vitamin D, 99 Vitamin deficiencies, 114 ... 40 36 32 28 13 16 -1 -1 11 12 -1 -1 10 09 -1 -1 08 -1 07 -0 06 -0 05 -0 04 -0 02 03 -0 -0 01 -0 00 -0 99 -0 98 -0 97 -9 96 -9 95 -9 94 -9 93 -9 92 -9 91 -9 90 -9 89 -9 88 87 86 -9 24 Year Fig 2.2 ... Pulmonologist, Via Christi Cystic Fibrosis Clinic, Wichita, KS, USA © Springer Nature Switzerland AG 2020 D Lewis (ed. ), Cystic Fibrosis in Primary Care, https://doi.org/10.1007/97 8-3 -0 3 0-2 590 9-9 _1 D... au/journal/2012/196/1/lessons-learned-20-years-newborn-screening -cystic- fibrosis Accessed 15 Feb 2019 19 Ren CL, Borowitz DS, Gonska T, Howenstine MS, Levy H, Massie J, et al Cystic fibrosis transmembrane