1 INTRODUCTION

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the CFTR gene is ubiquitious, persons with CF (pwCF) often experience a variety of complications throughout the pulmonary, gastrointestinal, and endocrine systems. A comprehensive approach to care of pwCF is strongly needed. It is well-recognized that many pwCF see their CF center as their primary care home; therefore, as CF centers see increased rates of obesity it is important to consider implementing adapted general population guidelines for obesity and the related comorbidities, especially obstructive sleep apnea (OSA).

One of the major reasons for the increased rate of overweight and obesity being seen is CFTR modulator therapy. Ivacaftor, an oral CFTR potentiator initially first available in 2011, was shown to increase the opening of the CFTR channel in pwCF with the most common gating mutation, G551D.¹ This medication caused an increase in weight in both children and adults.² The postulated reasons for increased weight included improved mucociliary clearance and improved lung function with decreased resting energy expenditure.² In addition, improved biliary flow was noted resulting in improved fat and nutrient absorption and improved insulin secretion.² Mechanisms for weight gain with the use of ivacaftor were further investigated by Stallings and colleagues and reported to be related to decreased resting energy expenditure (REE), increased dietary fat intake due to instructions about medication, and decreased gut inflammation.³ The combination of these changes was found to result in overall positive energy balance and weight gain.³ Both pancreatic insufficient and pancreatic sufficient patients were found to have increased weight, although the response was more robust in those with pancreatic insufficiency (PI).³

The CF community has a long history of advocating for optimal nutrition as crucial for preserving lung function in pwCF. A higher body-mass index (BMI) correlates with a higher forced expiratory volume in the first second (FEV1), an important measure of pulmonary function.⁴ PwCF often have higher metabolic rates compared to the general population and a higher risk of malnutrition.⁵ CF teams are routinely monitoring growth and weight throughout the lifespan, and avoiding undernutrition has been the focus for many decades.⁶ This focus was cemented by a landmark study by Corey and colleagues in 1988, which determined the reason for the higher survival seen in adult CF participants in Toronto CF center compared to Boston CF center.⁷ Both centers were similar, with the main difference being Toronto clinicians advocated for a high fat and high calorie diet as opposed to the low fat, high calorie diet recommended by Boston clinicians.⁷ Corey and colleagues demonstrated that better outcomes in the Toronto cohort was secondary to improved growth and nutrition from early childhood.⁷ Subsequently, the “Consensus report on nutrition for pediatric patients with CF” recommended a high fat, high calorie diet in guidelines published in 2002.⁶ These guidelines did not change substantially over the next two decades and were adopted by most CF centers for pwCF without modification until recently, when interim guidance was published.⁸

In 2023, Leonard and colleagues publication “Nutritional considerations for a new era: A CF foundation position paper” provided guidance and considerations for overnutrition in pwCF.⁸ The recommendations in this paper were decided upon by a multidisciplinary committee with four working groups: weight management, eating behavior/food insecurity, salt homeostasis, and pancreatic enzyme use.⁸ The weight management working group recommendations are highly pertinent to our review paper given the relationship between weight and obstructive sleep apnea. In 2019, before the widespread use of highly effective modulator therapy, up to 23% of pwCF in the US had a BMI that qualified as overweight or obese.⁸ By 2021 up to 40% of this population was in these categories. Using the CF Patient Registry, Szentpetery and colleagues identified a decrease in underweight status by about 40% over the last two decades.⁹ There was a >3-fold and >4-fold increase in pwCF classified as overweight or obese, respectively, between 2000 and 2019.⁹ Milder CFTR mutations, pancreatic sufficiency, and CFTR modulator use were all identified as variables leading to overweight status or obesity.⁹ These studies demonstrate that the prevalence of overweight and obesity in pwCF has increased during the time span where CFTR modulators became available. In the same time period, more knowledge has been gained about the imperfect nature of BMI as a surrogate for nutritional status and potential metabolic risk. Therefore, the CF foundation position paper suggests that nutrition recommendations should now be personalized to the individual using the available clinical data and goals.⁸ It is no longer advisable to suggest a high fat high calorie diet universally for pwCF, particularly those on highly effective modulator therapies. In particular, given the increased cardiometabolic risk in the aging population, it is encouraged to recommend intake of food such as fruits, vegetables, lean proteins, low fat dairy, whole grains, and legumes.⁸ The unique structure of the CF clinical multidisciplinary team at each center is well-poised to implement these personalized guidelines. The position paper acknowledges that there is limited data on cardiovascular outcomes in pwCF; however, given the high prevalence of obesity, rates of insulin resistance and the longer lifespan it is reasonable to recommend a personalized approach that considers cardiometabolic risk factors.⁸ Leonard and colleagues also highlight the need for weight neutral approaches, approaches that focus on optimizing health outcomes rather than promoting weight loss, when CF teams counsel patients.⁸

Being overweight or obese are associated with several comorbidities in the general population including metabolic and cardiovascular diseases. As may be expected, in pwCF, overweight status or obesity is associated with insulin resistance, dyslipidemia, obstructive sleep apnea, and hypertension.^{8, 10} In this review, we discuss how general population guidelines for screening and management of obesity and obstructive sleep apnea can be adapted for use in pwCF.

2 OBSTRUCTIVE SLEEP APNEA (OSA)

Sleep-disordered breathing (SDB) encompasses OSA which is due to intermittent collapse of the upper airway during sleep, central sleep apnea (CSA) which is due to the intermittent absence of respiratory effort during sleep, as well as hypoventilation, which may occur in persons with CF from various mechanisms.^{11, 12} Early studies often reported on SDB without differentiating between SDB patterns and since OSA is the most common SDB pattern, the term OSA will be used in describing these studies.^{13, 14} The intermittent collapse of the upper airway during sleep in OSA leads to breathing pauses and may cause oxygen desaturation and sleep fragmentation. OSA is prevalent in the United States and worldwide.¹⁵ It is associated with substantial morbidity including hypertension,¹⁶ diabetes,¹⁷ cardiovascular disease,¹⁸ and cerebrovascular disease,¹⁹ as well as increased mortality.^{20, 21} Therefore, assessment for OSA is an important part of a medical evaluation.

OSA is a disease with identified modifiable and nonmodifiable risk factors.¹⁵ The most important modifiable risk factor is obesity. In an early study looking at the prevalence of OSA in a US population, various measures of body habitus including weight, BMI, neck girth, and skin fold thickness were associated with an increased likelihood of OSA.²² Another observational study demonstrated that increased waist circumference correlated with development of OSA and obesity was correlated with OSA severity.²³ In a prospective study looking at the relationship between change in weight and change in OSA severity, measured as the apnea-hypopnea index (AHI), a 10% weight gain predicted a 32% increase in the AHI and a sixfold increase in the diagnosis of OSA.²⁴ These studies demonstrate a clear association between increasing weight and risk of OSA and OSA severity.

To assess the relationship between weight and OSA in pwCF, a retrospective study using polysomnography (PSG) data from 2009 to 2022 in pediatric and adult pwCF found that the AHI was higher among overweight and obese individuals compared to those who were normal weight.²⁵ Additional risk factors for OSA in pwCF include tonsillar hypertrophy, chronic sinusitis in the pediatric population, and crowded oropharynx in the adult population.²⁵ This study suggests that the relationship between elevated body weight and OSA observed in the general population is also observed in pwCF.²⁵ The prevalence of OSA is higher in pediatric pwCF compared to the general population,²⁶ suggesting that there are likely other CF-specific risk factors for OSA in pwCF. Overall, these studies indicate a higher prevalence of OSA in pwCF with overweight or obesity.

While weight gain is a significant risk factor for development of OSA, poor overall quantity and quality of sleep also results in weight gain. Poor quality or insufficient sleep can increase ghrelin (a hormone associated with hunger) and decrease leptin (a satiety hormone).²⁷ Consequently, poor sleep may lead to increased appetite and weight gain.²⁸ Studies have also demonstrated that although poor sleep results in an increased intake, it does not change energy expenditure and therefore can also lead to weight gain.²⁸ In addition, a study by Greer and colleagues demonstrated that insufficient sleep may also lead to preferential selection of foods that lead to weight gain.²⁹ Therefore, it is vital to screen and evaluate for causes of sleep disruption, including OSA.

3 SCREENING AND DIAGNOSIS FOR OSA IN pwCF

Presently, there are no guidelines available for screening pwCF for OSA. A study by Thomas and colleagues sought to characterize current sleep screening practices in CF programs across the nation using an online survey, to which approximately 50% of the programs responded.³⁰ The study demonstrated that sleep screening varied drastically across different programs.³⁰ In addition, formal sleep screening was performed with questionnaires in only 5% of the pediatric and 3% of the adult programs.³⁰ The questionnaires utilized were the Munich Chronotype Questionnaire (MCTQ), which is used primarily to collect sleep schedules and Pediatric Sleep Questionnaire (PSQ), which is used in pediatric population suspected of having OSA.³⁰ No formal questionnaires used to assess OSA in adults were reported in the study.³⁰

Presently, United States Preventive Services Task Force (USPSTF) guidelines state that there is insufficient evidence to screen for OSA in adults who are at low risk or do not have signs or symptoms of OSA.³¹ On the other hand, the American Academy of Sleep Medicine (AASM) states it is imperative to identify adults with symptoms of OSA such as snoring, excessive daytime sleepiness, or witnessed pauses in breathing.³² It also emphasizes that is important to screen high risk groups, specifically those with BMI ≥ 30 kg/m², impaired glucose tolerance or type 2 diabetes, congestive heart failure, atrial fibrillation, resistant hypertension, nocturnal dysrhythmias, stroke, pulmonary hypertension, and so forth.³² In addition, the American Thoracic Society (ATS) guidelines on long-term noninvasive ventilator (NIV) use in adults with chronic stable hypercapnic chronic obstructive lung disease (COPD) does recommend screening for OSA.³³ There are several screening questionnaires for OSA, such as the Berlin Questionnaire (BQ) and the STOP-BANG Questionnaire (SBQ) which have been validated in non-CF populations and can be used to screen those at high risk for OSA.³¹ A positive screen should prompt a comprehensive sleep evaluation including confirmatory testing with a PSG or for uncomplicated adult patients, a home sleep apnea test (HSAT).³⁴ The AASM recommends PSG be used for the diagnosis of OSA for patients with awake hypoventilation or suspicion of nocturnal hypoventilation, significant cardiorespiratory disease, insomnia, or other sleep-related symptoms.³⁴

Given the above data, presence of COPD and increasing prevalence of obesity in pwCF it is appropriate to, at minimum, screen pwCF for symptoms and signs of OSA.³⁵ There are no CF-specific guidelines for screening for OSA in pwCF and the recommendation for screening are based on the USPSTSF recommendation statement in screening for OSA in general adult population.³⁵ SBQ is a screening tool that consists of four yes/no questions (snoring, feeling tired, observed apneas, presence of hypertension) and four objective patient attributes (BMI, age >50, neck size, and gender).³⁴ A metanalysis by Chiu and colleagues with 108 studies and 47,989 participants, demonstrated that when comparing BQ, STOP questionnaire (SQ), Epworth Sleepiness Score (ESS), and SBQ, the SBQ had the highest sensitivity and diagnostic odds ratio for detecting the presence of OSA. However, AASM clinical practice guidelines recommended that any questionnaire should be taken into context with patient's entire clinical presentation.³⁴

For diagnosis of OSA, the AASM strongly recommends that objective testing be used to diagnose OSA In adults and not rely solely on questionnaires and prediction algorithms.³⁴ Although a HSAT can be utilized for the diagnosis of OSA in an uncomplicated adult patients, it is not recommended for those with increased risk of non-OSA SDB.³⁴ Persons with CF are at increased risk for sleep-related hypoxemia and nocturnal hypoventilation.^{36, 37} In addition, there is also high prevalence of insomnia, restless leg syndrome (RLS), and opioid use, which can lead to non-OSA SDB.^38-42 Therefore, the best diagnostic test for OSA in pwCF would be PSG. A PSG is an overnight, attended, in-laboratory sleep study that monitors electroencephalography (EEG) to determine sleep staging, electromyography (EMG) to detect muscle atonia, airflow measures using thermistor or nasal pressure monitor, respiratory effort, electro-oculography (EOG) to determine eye movements during sleep and wakefulness, electrocardiography (ECG) for monitoring cardiac rhythm, and pulse oximetry.⁴³ Additional monitoring for hypoventilation can be performed using transcutaneous pCO₂ or end-tidal pCO₂ during a diagnostic PSG.⁴⁴ PSG is the gold standard diagnostic test for OSA and would allow for the diagnosis of nocturnal hypoxemia, nocturnal hypoventilation, in addition to OSA.

4 TREATMENT OF OSA IN pwCF

There are no CF-specific guidelines available to treat OSA. Therefore, guidelines for the treatment of OSA in general population can used in pwCF. Overall, there are medical, behavioral, and surgical options available to treat OSA. The recommended first-line therapy for moderate or severe OSA is positive airway pressure (PAP) therapy.^{45, 46} In addition, PAP therapy is strongly recommended to treat OSA in adults with excessive daytime sleepiness.⁴⁵ The AASM also suggests using PAP therapy to treat OSA in adults with impaired sleep-related quality of life or comorbid hypertension.⁴⁵ Moreover AASM strongly recommends that education on what OSA is, consequences if left untreated, explanation on PAP therapy, and benefits of PAP therapy be discussed at the start of PAP therapy.⁴⁵ A meta-analysis of 18 randomized-controlled trials (RCT) evaluating educational, behavioral, and troubleshooting at the time of PAP initiation versus PAP analysis alone, demonstrated clinically significant improvement in PAP adherence with all three of the interventions.⁴⁵

Oral appliance therapy (OAT) can be used to treat OSA if the patient is intolerant of PAP therapy or prefers an alternative to PAP therapy.⁴⁷ OAT is a titratable device and should be customized for the patient by a qualified dentist.⁴⁷ When an OAT is employed, follow-up testing should be conducted to confirm treatment efficacy.⁴⁷

Although PAP is recommended as the initial therapy, the AASM also provides guidance on referring patients with OSA for surgical consultation. Adults with OSA and BMI < 40 kg/m² who prefer alternate therapy to PAP or inadequate adherence to PAP therapy should be referred to sleep surgeon to discuss other treatment options.⁴⁸ The AASM also recommends discussing a referral to a bariatric surgeon for patient with OSA and BMI ≥ 35 kg/m² as a part of a patient-oriented discussion or as an alternative treatment option.⁴⁸

Although weight loss medications are presently not in guidelines for treatment of OSA, they can lead to significant weight loss, leading to improvement of a major risk factors that can lead to OSA. A recent scoping review by Le and colleagues that reviewed total of nine studies demonstrated that there is some early evidence to suggest that that glucagon-like peptide 1 (GLP-1) receptor agonists may lead to reduction in AHI and improvement in OSA.⁴⁹ More rigorous studies are needed before these can become an adjuvant therapy in treatment of OSA.

5 MONITORING FOR OVERWEIGHT AND OBESITY IN pwCF

It is important that an assessment of body habitus for pwCF at a clinical visit entail more than just weight and height measurements. A nutrition history and physical exam inclusive of waist circumference and arm circumference can add a layer of understanding. Adiposity-relevant blood testing can also inform the clinician; these tests include many tests that are part of CF annual bloodwork including hemoglobin A1c (HbA1c), 2-h oral glucose tolerance test, fasting glucose, liver enzymes, and vitamin D.⁵⁰ Bloodwork for obesity that is not yet part of routine CF annual visit but can be considered on an individual basis includes thyroid stimulating hormone (TSH), lipid panel, fasting insulin testing, apolipoprotein B, and hormonal levels.⁵¹ The CF team can take these additional blood tests into account as indicated per patient. Persons with CF should be educated on possible adverse effects of higher adiposity on pulmonary function.¹⁰ They should also be informed about trends with hypertension, dyslipidemia, and insulin resistance in pwCF and obesity.¹⁰

6 DIETARY INTAKE RECOMMENDATIONS FOR OBESITY IN pwCF

Traditionally, the CF diet consisted of a high-calorie, high-fat, low nutrient density eating pattern with an emphasis on quantity of calories rather than quality to meet weight goals and optimize lung function.^{2, 6} Consuming a high-calorie, high-fat, low nutrient eating pattern is associated with weight gain and diseases of adiposity in people who have no absorption issues.⁵² Persons with CF who continue the legacy diet when on modulators are predisposed to overnutrition and adiposity.⁸ Dietary modification and exercise are fundamental for weight management of pwCF with overnutrition.⁵³

In adults over 20 years of age, it is reasonable to measure weight and height every 3 months at routine CF visits to screen for under or overnutrition.⁵³ Adults with CF and BMI ≥ 27 kg/m² or unintentional weight gain >5 kg from previously acceptable weight merit a focused nutrition assessment by a registered dietician or a trained physician with a focus in CF and nutrition.⁵³ A nutrition assessment should include a comprehensive history of weight across the lifespan, abdominal circumference, body composition, disease severity, laboratory values, micronutrient deficiencies, estimated energy expenditure compared to dietary intake, and food security status.⁵⁴ In addition, a patient's CF genetic mutations, utilization of CFTR modulators, presence of PI, use and dosing of pancreatic enzyme replacement therapy (PERT), and clinical status should also be considered as CF nutrition is highly individualized.⁵⁴

While there is a dearth of literature studying the optimal dietary patterns, it is reasonable to utilize evidence-based methods recommended to the general population for the CF community. The Academy of Nutrition and Dietetics' (AND) most recent guidelines emphasize advising CF patients use similar dietary guidelines as the general population.⁵⁵ In the general population, a diet rich in vegetables, fruits, whole grains, low-fat dairy, lean meats, seafood, legumes, and nuts with limited intake of added sugars, saturated fats, and processed foods have been associated with improved health outcomes (Table 1).^{42, 56} Moreover, it is recommended to choose oils low in saturated fats such as canola, corn, olive, peanut, safflower, soybean, and sunflower along with the oils naturally found in nuts, seeds, seafood and olives rather than those high in saturated fats, which include coconut oil, butter, or lard.⁴²

In general, weight loss can be effectively achieved by creating a negative energy balance.⁵² Patients may wish to utilize smart phone apps to track the calories they consume to help quantify their energy intake. Energy needs or expenditure based on age, sex, level of physical activity, disease severity, and presence of PI can be measured using indirect calorimetry (IC) or calculated using resting energy expenditure (REE) equations. In pwCF >20 years of age, energy requirements are underestimated by REE equation compared to IC (by 76%–78% in prelung transplant); therefore, using standard energy expenditure (SEE) equation × 1.25 can provide closer estimates.⁵⁴

Patients interested in weight loss should be recommended to follow a 500-kcal calorie deficit from their individualized calculated REE.⁵⁵ Improved underlying lung function and steatorrhea lead to reductions in energy needs.⁵⁴ Therefore, the REE should be evaluated multiple times through disease progression or improvement to tailor nutrition interventions.

7 MACRONUTRIENT COMPOSITION AND CALORIE DEFICIT IN pwCF

Reduced calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize.⁵⁷ Low-carbohydrate diets and low-fat diets have similar effects on weight loss in the general population.⁵⁷ The AND suggests consuming macronutrients (carbohydrates, protein, and fat) in the same percentage distribution as is recommended for the typical, age-matched population.⁵⁴

The one macronutrient that should be emphasized in weight loss in CF is protein, which provides enhanced satiety while preserving fat free mass. The optimal protein intake in pwCF is higher than that of healthy individuals and other inflammatory disease states given impaired protein digestibility, efficacy of PERT to increase digestion of dietary protein, and higher protein requirements given increased work of breathing, inflammatory state, and presence of acute exacerbations. The average healthy patient requires 0.8–1 g/kg/day of protein. While there is no optimal daily intake recommendations in CF, the Rutgers CF center recommends upwards of 1–1.2 g/kg/day during weight loss to prevent muscle loss in CF. Engelen and colleagues has shown that protein digestibility is reduced to 47% of that of healthy subjects in patients with PI, which can be improved to 90% of normal with adequate PERT.⁵⁸ Given this finding, ensuring adequate PERT intake and checking annual fecal elastase might allow for optimizing protein availability.

Goal weight or BMI in CF has not been established; however, in a study with homozygous F508del patients, there was a positive association between FEV1 and BMI only up to 23 kg/m² in adults.⁴ Therefore, it is important not to presume that a higher BMI will inevitably enhance lung function. In the general population, weight loss of 5% from initial body weight has been shown to lead to a reduction in rates of diabetes, hypertension and OSA and is associated with improvement in biochemical and physiological parameters resulting in health benefits.⁵⁹ It is likely that similar beneficial effects of significant weight loss may be seen in obese or overweight pwCF, but studies are needed to study the effects of weight loss in people with CF on these parameters.

8 PHYSICAL ACTIVITY RECOMMENDATIONS FOR OBESITY IN pwCF

Current government-sponsored guidelines in the United States for adults in the general populations include at least 150 minutes of moderate intensity or at least 75 minutes of vigorous intensity aerobic physical activity per week (Table 2).⁶⁰ Data specific to adults with CF have shown that they spend less time performing moderate to vigorous intensity activity compared to their healthy peers.⁶¹ Given this difference, a gradual increase in physical activity is recommended while emphasizing that any length of physical activity confers health benefits.⁶²

In adults with a BMI > 27 kg/m², the goal of physical activity is to preserve or build fat free mass (FFM) while maintaining or preventing increases in fat mass.⁶² Weight loss with dietary changes and/or pharmacotherapy is likely to result in loss of both FFM and fat mass, which may be associated with reductions in strength and function.⁶³ The combination of aerobic and resistant training programs allows for not only improvements in FEV1, but lean body mass and leg strength as well.⁹

9 ROLE OF WEIGHT LOSS MEDICATIONS IN pwCF

Medications serve only as an adjunct to behavioral changes to assist in weight management. The criteria for using approved medications in the general population is for adults with BMI ≥ 27 kg/m² with one or more obesity related comorbidities or BMI ≥ 30 kg/m² who have not lost at least 5% of their body weight after 3 months of lifestyle changes.⁵² The Food and Drug Administration (FDA) has approved five pharmacotherapies to manage weight in the general population (Table 3). Currently, none of these agents are FDA-approved specifically in pwCF, although medical therapy can be considered in select individuals as clinically appropriate. Weight loss therapy in pwCF needs to be balanced with the risk of declining BMI and lung function, and surgical therapies should be used with extreme caution given the risk of malabsorption and vitamin deficiencies postoperatively.¹⁰

10 CF-RELATED MEDICATION CONCERNS

When considering initiation of weight loss agents, patients should be evaluated by an obesity-trained physician with experience in prescribing and managing these medications in pwCF. An extensive discussion highlighting risks and benefits of weight loss agents while emphasizing that these drugs have not been studied in pwCF should take place. Weight-loss therapies in pwCF must be balanced between declining BMI affecting lung function and elevated BMI resulting in metabolic comorbidities.

Dipeptidyl peptidase-4 (DPP-4) inhibitors agents have been shown to be safe and tolerable with lesser concerns about pancreatitis and gastrointestinal upset in PwCF as shown in a randomized, double-blind study with promising effects on blood sugar management in those affected by diabetes.⁶⁶ However, their effects on weight loss is nominal as these agents are considered weight neutral.⁶⁴ Kelly and colleagues demonstrated this effect in pwCF with PI in their study, which showed a 2.6 kg weight loss in their pwCF on Sitagliptin; however, it should be noted that the placebo group also boasted a 2.5 kg weight loss.⁶⁶ At this time, DPP-4 inhibitors should be considered for the treatment of PwCF in the setting of diabetes who are either high risk for the gastrointestinal complications associated with GLP-1 agents and not for the management of their weight.

Orlistat should not be utilized in pwCF as it can exaggerate the fat-soluble vitamin malabsorption and steatorrhea.^{10, 65} GLP-1 receptor agonists, which delay gastric emptying and suppress appetite, are highly effective for weight loss; however, these agents can be associated with pancreatitis and are therefore contraindicated in pwCF with prior history of acute pancreatitis (AP) or those who are pancreatic sufficient due to increased risk of AP. Some CF centers have experience utilizing phentermine in patients with and without PI in addition to GLP-1 receptor agonists receptor agonists in patients with PI.⁶⁷ GLP-1 should be prescribed case by case and monitored closely. Persons with CF initiated on weight loss medications should be seen at least monthly for the first 3 months and then at least every 3 months. The current guidelines for management of overweight and obesity in adults reviewed RCTs on weight loss interventions and found the best weight loss outcomes occur with frequent face-to-face visits (16 visits per year on average).⁵¹

11 ROLE OF THE CF-SPECIALIZED NUTRITIONIST

The role of a nutritionist in the management of CF has long been established, and nutritionists are well-positioned to work with the pwCF in their center to manage pancreatic insufficiency and undernutrition, increased rates of CF-related diabetes, and weight management.⁶⁸ Modifications to the recommended CF diet have already taken place.⁸ CF nutritionists are aware that obese individuals can be malnourished, particularly in micronutrients and can continue to enforce best practices.⁶⁹ It is best practice to work closely with nutrition colleagues to advise patients with overnutrition.

12 CONCLUSION

Much of CF care is evolving with the ubiquitous use of modulator therapy and the subsequent increase in lifespan. A visible adverse event with modulators has been precipitous weight gain in a portion of the population of pwCF. It is important for CF clinicians to monitor for and manage obesity as it is a known risk factor for multiple other diseases such as OSA across the lifespan. The prevalence of OSA has increased in pwCF and addressing this disease in pwCF is important as it can further worsen the adverse health-related consequences of obesity. A comprehensive approach to pwCF to optimize body weight is key. It is understandable that there has been hesitation on universal screening and management given the current lack of CF-specific studies addressing OSA and obesity. We believe that the interim recommendations that are discussed above should be followed while CF-specific research is being conducted.

AUTHOR CONTRIBUTIONS

Keerthana Kesavarapu: Writing—review & editing; writing—original draft; conceptualization; resources; project administration; data curation. Sreelatha Naik: Writing—original draft. Maya Ramagopal: Writing—review & editing. Matthew T. Scharf: Writing—original draft; writing—review & editing; resources; conceptualization; data curation. Sugeet Jagpal: Conceptualization; writing—original draft; data curation; resources; supervision; methodology; writing—review & editing. All authors have seen and approved the manuscript.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.