Respiration. 2022;101(3):307-320. doi: 10.1159/000518896. Epub 2022 Jan 21.

ABSTRACT

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases.

PMID:35231915 | DOI:10.1159/000518896

Am J Respir Cell Mol Biol. 2022 Mar;66(3):340-343. doi: 10.1165/rcmb.2021-0263LE.

NO ABSTRACT

PMID:35230232 | DOI:10.1165/rcmb.2021-0263LE

Pediatr Pulmonol. 2022 Mar 1. doi: 10.1002/ppul.25876. Online ahead of print.

ABSTRACT

OBJECTIVES: While eradicating new-onset Pseudomonas aeruginosa in children with cystic fibrosis is an important issue, there is no clear evidence about the best treatment approach. This retrospective observational cohort study aims to compare the effectiveness of intravenous therapy versus inhalation with/without oral therapy in the eradication of new-onset P aeruginosa, determine the factors affecting the treatment success and assess lung function at baseline and post-treatment.

METHODS: Of 399 children, 110 (140 episodes) with either the first P aeruginosa isolation or a new isolation after at least 1 year free of infection, were included. Different eradication regimens (intravenous therapy or inhaled tobramycin or inhaled tobramycin plus oral ciprofloxacin) were compared. Eradication success was accepted as remaining free of infection with a negative culture for 12 months. Demographic, clinical and microbiological characteristics of children, effectiveness of different eradication strategies, time to a new P aeruginosa isolation, and the relationship between lung function and the type of eradication regimen were determined.

RESULTS: Of 140 episodes, intravenous therapy was administered in 53 and inhalation therapy (in combination with or without oral ciprofloxacin) in 87. Total success rate of eradication was 60.7%. Eradication was achieved in 56.6% of children with intravenous therapy, 59.7% with inhaled tobramycin therapy, 72% with inhaled tobramycin plus oral ciprofloxacin therapy. Success rates of different eradication regimens did not differ significantly (p=0.419). Lung function by the end of the first year was worse in the intravenous group compared to the inhalation group (p=0.017 for FEV1, p=0.015 for FVC).

CONCLUSION: No advantage of intravenous therapy was demonstrated compared to inhalation therapy in terms of eradication success. This article is protected by copyright. All rights reserved.

PMID:35229497 | DOI:10.1002/ppul.25876

Clin Respir J. 2022 Mar 1. doi: 10.1111/crj.13484. Online ahead of print.

ABSTRACT

OBJECTIVES: The COVID-19 pandemic has resulted in unprecedent changes to clinical practice, and as the impact upon delivery of exercise services for people with cystic fibrosis (CF) in the United Kingdom was unknown, this was characterised via a national survey.

METHODS: An electronic survey was distributed to healthcare professionals involved in the exercise management of CF via established professional networks.

RESULTS: In total, 31 CF centres participated. Findings included significant reductions in exercise testing and widespread adaptation to deliver exercise training using telehealth methods. Promisingly, 71% stated that they would continue using virtual methods of engaging patients in future practice.

CONCLUSION: These findings highlight adaptation to the COVID-19 pandemic and the need to develop sustainable and standardised telehealth services to manage patients moving forwards.

PMID:35229472 | DOI:10.1111/crj.13484

Clin Transl Immunology. 2022 Feb 21;11(2):e1376. doi: 10.1002/cti2.1376. eCollection 2022.

ABSTRACT

OBJECTIVES: Post-infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post-transcriptional gene regulation in order to characterise PiBO.

METHODS: A total of 39 patients with well-defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next-generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein-protein interaction network analysis respectively.

RESULTS: Patients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL-1β, IL-6, IL-8 and TGF-β compared to controls.Next-generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for Padj ≤ 0.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR-335-5p, miR-186-5p, miR-30b-5p and miR-30c-5p were further validated using qRT-PCR. Interestingly, these miRNAs are functionally implicated in cytokine-cytokine receptor interaction, TGF-β signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1).

CONCLUSION: Our results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics.

PMID:35228871 | PMC:PMC8859819 | DOI:10.1002/cti2.1376

Ann Allergy Asthma Immunol. 2022 Feb 25:S1081-1206(22)00121-1. doi: 10.1016/j.anai.2022.02.010. Online ahead of print.

ABSTRACT

BACKGROUND: Data regarding medication adherence in older adults with asthma before and during the COVID-19 pandemic is lacking.

OBJECTIVE: To evaluate medication adherence and determine factors associated with adherence in Medicare enrolled older adults with asthma before and during the COVID-19 pandemic.

METHODS: This was a retrospective cohort analysis of Medicare enrolled patients with asthma. Medication adherence was measured using proportion of days covered (PDC) rates for dates January-July 2019 and January-July 2020. Patients <65 years of age, with chronic obstructive pulmonary disease, or cystic fibrosis were excluded. Paired t-tests assessed change in adherence between 2019 and 2020. Logistic regression evaluated association of age, sex, depression, moderate/severe asthma, use of a 90-days' supply, having ≥3 albuterol fills, and number of medications, medication-related problems, prescribers, pharmacies, controller medication classes, and systemic corticosteroid fills with high adherence (PDC ≥80%).

RESULTS: Mean adherence to asthma controller medications ranged from 75-90%, in 2019. Adherence significantly decreased (p<0.001) to 51-70% for all controller medications, except theophylline in 2020. Similar results were observed among patients with moderate/severe asthma. In 2019 and 2020, number of controller medications, ≥3 albuterol fills, and having a 90 days' supply were associated with high adherence (p<0.001).

CONCLUSION: Adherence to asthma controller medications significantly decreased during the COVID-19 pandemic among Medicare enrolled patients with asthma. Patients with markers for more severe asthma, overuse of albuterol, and a 90-day supply of controller medications were more likely to have high adherence. These findings can be used to identify opportunities to improve adherence and prescribing among adult patients with asthma.

PMID:35227901 | DOI:10.1016/j.anai.2022.02.010

J Cyst Fibros. 2022 Feb 26:S1569-1993(22)00042-X. doi: 10.1016/j.jcf.2022.02.010. Online ahead of print.

ABSTRACT

BACKGROUND: Epithelial sodium channel (ENaC) inhibitors may offer clinical benefit in cystic fibrosis (CF); however, data are limited. We report the outcomes of a Phase I (NCT02679729) and a Phase Ib (NCT02950805) study of AZD5634, a novel inhaled ENaC inhibitor.

METHODS: A Phase I, first-in-human, single-blind, placebo-controlled, single ascending dose, sequential dose group study assessed the safety, tolerability, and pharmacokinetics of AZD5634 in healthy subjects (n=53) in part A following inhaled doses up to 1700 µg, and, in part B, following administration of single inhaled (1700 µg) and intravenous (65 µg) doses. A Phase Ib, randomized, double-blind, placebo-controlled, single-dose, 2-way cross-over study assessed the effects of a single dose (600 µg) of inhaled AZD5634 on mucociliary clearance (MCC), pharmacokinetics and safety and tolerability in patients with CF (n=11). Nasal potential difference (NPD) was assessed as an in situ target engagement exploratory biomarker.

RESULTS: Absolute bioavailability of AZD5634 after inhalation was approximately 3%, indicating minimal distribution into the systemic circulation. Urinary excretion was a minor elimination pathway. Administration of inhaled AZD5634 did not improve MCC in CF patients, but AZD5634 inhibited ENaC in the nasal epithelium, as measured by NPD. AZD5634 was safe and well tolerated in both studies.

CONCLUSIONS: AZD5634 showed favorable pharmacokinetics and safety in healthy subjects and patients with CF. However, despite achieving target engagement, proof of mechanism was not achieved after a single dose in patients with CF. Further evaluation into multiple dose studies is warranted to explore its therapeutic potential.

PMID:35227647 | DOI:10.1016/j.jcf.2022.02.010

Value Health. 2022 Mar;25(3):350-358. doi: 10.1016/j.jval.2021.11.1360. Epub 2021 Dec 22.

ABSTRACT

OBJECTIVES: We propose a framework of health outcomes modeling with dynamic decision making and real-world data (RWD) to evaluate the potential utility of novel risk prediction models in clinical practice. Lung transplant (LTx) referral decisions in cystic fibrosis offer a complex case study.

METHODS: We used longitudinal RWD for a cohort of adults (n = 4247) from the Cystic Fibrosis Foundation Patient Registry to compare outcomes of an LTx referral policy based on machine learning (ML) mortality risk predictions to referral based on (1) forced expiratory volume in 1 second (FEV1) alone and (2) heterogenous usual care (UC). We then developed a patient-level simulation model to project number of patients referred for LTx and 5-year survival, accounting for transplant availability, organ allocation policy, and heterogenous treatment effects.

RESULTS: Only 12% of patients (95% confidence interval 11%-13%) were referred for LTx over 5 years under UC, compared with 19% (18%-20%) under FEV1 and 20% (19%-22%) under ML. Of 309 patients who died before LTx referral under UC, 31% (27%-36%) would have been referred under FEV1 and 40% (35%-45%) would have been referred under ML. Given a fixed supply of organs, differences in referral time did not lead to significant differences in transplants, pretransplant or post-transplant deaths, or overall survival in 5 years.

CONCLUSIONS: Health outcomes modeling with RWD may help to identify novel ML risk prediction models with high potential real-world clinical utility and rule out further investment in models that are unlikely to offer meaningful real-world benefits.

PMID:35227445 | DOI:10.1016/j.jval.2021.11.1360

Front Biosci (Landmark Ed). 2022 Feb 21;27(2):75. doi: 10.31083/j.fbl2702075.

ABSTRACT

The transport of chloride and bicarbonate across epithelia controls the pH and volume of the intracellular and luminal fluids, as well as the systemic pH and vascular volume. The anion exchanger pendrin (SLC26A4) and the cystic fibrosis transmembrane conductance regulator (CFTR) channel are expressed in the apical membrane of epithelial cells of various organs and tissues, including the airways, kidney, thyroid, and inner ear. While pendrin drives chloride reabsorption and bicarbonate, thiocyanate or iodide secretion within the apical compartment, CFTR represents a pathway for the apical efflux of chloride, bicarbonate, and possibly iodide. In the airways, pendrin and CFTR seems to be involved in alkalinization of the apical fluid via bicarbonate secretion, especially during inflammation, while CFTR also controls the volume of the apical fluid via a cAMP-dependent chloride secretion, which is stimulated by pendrin. In the kidney, pendrin is expressed in the cortical collecting duct and connecting tubule and co-localizes with CFTR in the apical membrane of β intercalated cells. Bicarbonate secretion occurs via pendrin, which also drives chloride reabsorption. A functional CFTR is required for pendrin activity. Whether CFTR stimulates pendrin via a direct molecular interaction or other mechanisms, or simply provides a pathway for chloride recycling across the apical membrane remains to be established. In the thyroid, CFTR and pendrin might have overlapping functions in driving the apical flux of iodide within the follicular lumen. In other organs, including the inner ear, the possible functional interplay between pendrin and CFTR needs to be explored.

PMID:35227018 | DOI:10.31083/j.fbl2702075

Arch Toxicol. 2022 Feb 28. doi: 10.1007/s00204-021-03213-x. Online ahead of print.

ABSTRACT

Enterotoxigenic Escherichia coli (ETEC) in humans and animals colonizes the intestine and thereafter secrets heat-stable enterotoxin (ST) with or without heat-labile enterotoxin (LT), which triggers massive fluid and electrolyte secretion into the gut lumen. The crosstalk between the cyclic nucleotide-dependent protein kinase/cystic fibrosis transmembrane conductance regulator (cAMP or cGMP/CFTR) pathway involved in ETEC-induced diarrhea channels, and the canonical Wnt/β-catenin signaling pathway leads to changes in intestinal stem cell (ISC) fates, which are strongly associated with developmental disorders caused by diarrhea. We review how alterations in enterotoxin-activated ion channel pathways and the canonical Wnt/β-catenin signaling pathway can explain inhibited intestinal epithelial activity, characterize alterations in the crosstalk of cyclic nucleotides, and predict harmful effects on ISCs in targeted therapy. Besides, we discuss current deficits in the understanding of enterotoxin-intestinal epithelial cell activity relationships that should be considered when interpreting sequelae of diarrhea.

PMID:35226135 | DOI:10.1007/s00204-021-03213-x

J Pulm Med Respir Care. 2022;4(1):1008.

ABSTRACT

The efficacy of pediatric oral drug delivery using dry powder inhalers, such as Turbuhaler®, is dependent on the age and health of the test subjects. The available clinical data for these studies is scant and rarely provide correlations between the health condition and the regional lung deposition. In particular, the data and the correlations for pre-school children are minimal. Deposition simulations were performed using the newly developed Quasi-3D whole lung model to analyze the effect of health conditions on the regional lung deposition from the Turbuhaler® in 3-year-old children. The healthy lung model was created from CT scan data. Cystic-fibrosis models were created by uniformly constricting the airways to various degrees. The simulated drug deposition outcomes were validated against the available experimental data. The results show that, while the dose deposited in the lungs exhibits minor variations, the Peripheral:Central (P/C) ratio is strongly affected by both the health condition and the inflow variations. The above ratio is reduced by ~30% for the severely diseased case, compared to its healthy counterpart, for the same inhalation profile. This indicates that lower doses reach the peripheral lung, in pediatric cystic-fibrosis subjects, thus requiring a larger therapeutic dose.

PMID:35224564 | PMC:PMC8871561

JAMIA Open. 2022 Feb 9;5(1):ooac005. doi: 10.1093/jamiaopen/ooac005. eCollection 2022 Apr.

ABSTRACT

The coronavirus disease 2019 pandemic has resulted in large-scale changes to incorporate telemedicine for the delivery of care. People with cystic fibrosis (CF) have care considerations that pose challenges to telemedicine; they include frequent visits for pulmonary disease progression, medication management, and evaluation by a multidisciplinary team of providers. We share our center's experience with video visits replacing in-person clinic evaluation, using quality improvement strategies to create a replicable workflow. Key considerations include incorporation of the multidisciplinary team into the visit, limitations of remote delivery of care, as well as patient and staff perceptions of this care model. Results revealed that video visits were convenient, efficacious, and comparable to in-person visits, with interest for its continued incorporation into the traditional CF care model.

PMID:35224457 | PMC:PMC8867557 | DOI:10.1093/jamiaopen/ooac005

Case Rep Infect Dis. 2022 Feb 16;2022:4378442. doi: 10.1155/2022/4378442. eCollection 2022.

ABSTRACT

Pyogenic spondylodiscitis is rarely caused by Burkholderia cepacia complex. B. cepacia is widespread in the environment and recognized as an opportunistic pathogen for patients with cystic fibrosis and immune disorders. A female in her mid-30s with underlying hyperthyroidism, but otherwise immunocompetent, was admitted to the hospital with persistent lower back pain after elective bariatric surgery in Mexico. Lumbar MRI showed L2/L3 osteomyelitis and discitis. Culture of disk aspiration grew Burkholderia cepacia complex sensitive to cefepime, ceftazidime, ciprofloxacin, gentamicin, imipenem, levofloxacin, and trimethoprim-sulfamethoxazole. The infection failed to respond to cefepime; however, she was successfully treated with levofloxacin monotherapy.

PMID:35223115 | PMC:PMC8865995 | DOI:10.1155/2022/4378442

Front Genet. 2022 Feb 11;13:775123. doi: 10.3389/fgene.2022.775123. eCollection 2022.

ABSTRACT

Congenital bilateral absence of the vas deferens (CBAVD) is clinically characterized by the absence of the bilateral vas deferens; the main clinical manifestation is infertility, accounting for 1-2% of male infertility cases. CBAVD may be accompanied by congenital abnormalities in the urogenital system and cystic fibrosis (CF)-related clinical manifestations. CBAVD can develop as a mild manifestation of CF or can be isolated. The main pathogenic mechanism of CBAVD is gene mutation, and CBAVD and CF have a common genetic mutation background. CFTR mutation is the main pathogenic cause of CBAVD and CF, and ADGRG2 mutation is the second most common cause. Although lack of the vas deferens in CBAVD patients causes infertility due to the inability to release sperm, the testes of CBAVD patients have spermatogenic function. Therefore, CBAVD patients can achieve fertility through sperm retrieval surgery and assisted reproductive technology (ART). However, gene mutations in CBAVD patients can have an impact on the ART outcome, and there is a risk of passing on gene mutations to offspring. For CBAVD patients and their spouses, performing genetic counseling (which currently refers mainly to CFTR mutation screening) helps to reduce the risks of genetic mutations being passed on to offspring and of offspring having CF with concomitant CBAVD.

PMID:35222530 | PMC:PMC8873976 | DOI:10.3389/fgene.2022.775123

Front Pharmacol. 2022 Feb 10;13:839972. doi: 10.3389/fphar.2022.839972. eCollection 2022.

ABSTRACT

Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use in pediatrics is approved for children older than 1 year, for the short-term treatment of symptomatic gastroesophageal reflux disease (GERD), healing of erosive esophagitis, treatment of peptic ulcer disease, and eradication of Helicobacter pylori. PPIs are also considered the standard of care for pediatric eosinophilic esophagitis. Despite the strict range of indications, the use of this class of molecules has increased in all pediatric age ranges. The long-term gastric acid suppression in children has been linked to increased risks of gastrointestinal and lower respiratory tract infections, bone fractures, and allergy. This study aims to provide a comprehensive overview of the mechanism of actions, use (and misuse) in infants and children, and safety of PPIs.

PMID:35222047 | PMC:PMC8866943 | DOI:10.3389/fphar.2022.839972

Stud Appl Math. 2021 Nov;147(4):1369-1387. doi: 10.1111/sapm.12433. Epub 2021 Aug 13.

ABSTRACT

We develop the first molecular dynamics model of airway mucus based on the detailed physical properties and chemical structure of the predominant gel-forming mucin MUC5B. Our airway mucus model leverages the LAMMPS open-source code [https://lammps.sandia.gov], based on the statistical physics of polymers, from single molecules to networks. On top of the LAMMPS platform, the chemical structure of MUC5B is used to superimpose proximity-based, non-covalent, transient interactions within and between the specific domains of MUC5B polymers. We explore feasible ranges of hydrophobic and electrostatic interaction strengths between MUC5B domains with 9 nanometer spatial and 1 nanosecond temporal resolution. Our goal here is to propose and test a mechanistic hypothesis for a striking clinical observation with respect to airway mucus: a 10-fold increase in non-swellable, dense structures called flakes during progression of cystic fibrosis disease. Among the myriad possible effects that might promote self-organization of MUC5B networks into flake structures, we hypothesize and confirm that the clinically confirmed increase in mucin concentration, from 1.5 to 5 mg/mL, alone is sufficient to drive the structure changes observed with scanning electron microscopy images from experimental samples. We post-process the LAMMPS simulated datasets at 1.5 and 5 mg/mL, both to image the structure transition and compare with scanning electron micrographs and to show that the 3.33-fold increase in concentration induces closer proximity of interacting electrostatic and hydrophobic domains, thereby amplifying the proximity-based strength of the interactions.

PMID:35221375 | PMC:PMC8871504 | DOI:10.1111/sapm.12433

J Cyst Fibros. 2022 Feb 24:S1569-1993(22)00040-6. doi: 10.1016/j.jcf.2022.02.008. Online ahead of print.

NO ABSTRACT

PMID:35221249 | DOI:10.1016/j.jcf.2022.02.008

EBioMedicine. 2022 Feb 22;77:103894. doi: 10.1016/j.ebiom.2022.103894. Online ahead of print.

ABSTRACT

BACKGROUND: Interleukin-6 (IL-6) is elevated in SARS-CoV-2 infection. IL-6 regulates acute-phase proteins, such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the protease-anti-protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS) compared to non-SARS-CoV-2 ARDS (nsARDS) and the effects of tocilizumab (IL-6 receptor antagonist) on anti-protease defence in SARS-CoV-2 infection.

METHODS: Levels and activity of AAT and neutrophil elastase (NE) were measured in plasma, airway tissue and tracheal secretions (TA) of people with SARS-CoV-2 ARDS or nsARDS. AAT and IL-6 levels were evaluated in people with moderate SARS-CoV-2 infection who received standard of care +/- tocilizumab.

FINDINGS: AAT plasma levels doubled in SARS-CoV-2 ARDS. In lung parenchyma AAT levels were increased, as was the percentage of neutrophils involved in NET formation. A protease-anti-protease imbalance was detected in TA with active NE and no active AAT. The airway anti-protease, secretory leukoprotease inhibitor was decreased in SARS-CoV-2-infected lungs and cleaved in TA. In nsARDS, plasma AAT levels were elevated but TA samples had less AAT cleavage, with no detectable active NE in most samples Induction of AAT in ARDS occurred mainly through IL-6. Tocilizumab down-regulated AAT during SARS-CoV-2 infection.

INTERPRETATION: There is a protease-anti-protease imbalance in the airways of SARS-CoV-2-ARDS patients. This imbalance is a target for anti-protease therapy.

PMID:35217407 | DOI:10.1016/j.ebiom.2022.103894

Int J Mol Sci. 2022 Feb 11;23(4):2026. doi: 10.3390/ijms23042026.

ABSTRACT

Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental prevention, embracing the principles of green chemistry. In this work, we propose the covalent attachment of xylitol to ibuprofen to produce an IBU-xylitol ester prodrug. Xylitol was chosen as a hydrophilizer for the final prodrug, enhancing the water solubility of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) extensively used as an analgesic, anti-inflammatory, and antipyretic. Despite being the third-most-prescribed medicine in the world, the aqueous solubility of ibuprofen is just 21 mg/L. This poor water solubility greatly limits the bioavailability of ibuprofen. We aimed to functionalize ibuprofen with xylitol using the reusable immobilized N435 biocatalyst. Instead of a biphasic media, we proposed a monophasic reaction environment. The characterization of the IBU-xylitol ester was performed by 1H, 13C-NMR, DEPT, COSY, HMQC, HMBC, FTIR, and MS spectroscopy. Preliminary in vitro tests showed that this enzymatically synthesized prodrug of ibuprofen reduced the expression of the interleukin 8 genes in human bronchial epithelial cells (IB3-1) from cystic fibrosis (CF) patients.

PMID:35216142 | DOI:10.3390/ijms23042026

Nutrients. 2022 Feb 18;14(4):853. doi: 10.3390/nu14040853.

ABSTRACT

Nutrition is important in cystic fibrosis (CF) because the disease is associated with a higher energy consumption, special nutritional deficiencies, and malabsorption mainly related to pancreatic insufficiency. The clinical course with deterioration of lung function has been shown to relate to nutrition. Despite general recommendation of high energy intake, the clinical deterioration is difficult to restrain suggesting that special needs have not been identified and specified. It is well-known that the CF phenotype is associated with lipid abnormalities, especially in the essential or conditionally essential fatty acids. This review will concentrate on the qualitative aspects of fat metabolism, which has mainly been neglected in dietary fat recommendations focusing on fat quantity. For more than 60 years it has been known and confirmed that the patients have a deficiency of linoleic acid, an n-6 essential fatty acid of importance for membrane structure and function. The ratio between arachidonic acid and docosahexaenoic acid, conditionally essential fatty acids of the n-6 and n-3 series, respectively, is often increased. The recently discovered relations between the CFTR modulators and lipid metabolism raise new interests in this field and together with new technology provide possibilities to specify further specify personalized therapy.

PMID:35215502 | DOI:10.3390/nu14040853