Respir Med Case Rep. 2021 Nov 10;34:101553. doi: 10.1016/j.rmcr.2021.101553. eCollection 2021.

ABSTRACT

The introduction of Cystic Fibrosis Trans Regulatory modulator (CFTRm) drugs has seen a transformation in Cystic Fibrosis (CF) treatment. This has led to a significant improvement in lung function and quality of life with the potential for a real impact on life expectancy. Transient mild to moderate hepatic transaminitis is a well-known side effect of CFTRm drugs, which often improves on cessation and may not recur following the re-institution of the drug. We describe a case of transaminitis developing nine months after the initiation of Kaftrio, which progressed to liver necrosis despite stopping Kaftrio and took many months to resolve. The patient had experienced significant improvement in lung function and overall health while on Kaftrio and deteriorated when it was stopped. He was keen to restart; however, Kaftrio was not reinstated due to the potential risk of acute liver failure.

PMID:34815934 | PMC:PMC8593462 | DOI:10.1016/j.rmcr.2021.101553

Ulster Med J. 2021 Sep;90(3):168-174. Epub 2021 Nov 11.

ABSTRACT

Antimicrobial resistance (AMR) has now emerged as a major global public health problem. Certain bacterial pathogens, particularly Gram negative organisms associated with patients with cystic fibrosis (CF), have become resistant to several classes of antibiotics resulting in pan-resistance, which creates a clinical treatment dilemma. This study wished to explore the production of antibacterial extracellular metabolites from plant pathogenic fungi. Fungal Culture Extracts (FCEs) were prepared from 10 fungi (Armillaria gallica, Clitocybe nebularis, Fusarium coeruleum, Fusarium oxysporum, Fusarium poae, Hymenoscyphus fraxineus, Nectria fuckeliana, Phytophthora infestans, Phytophthora ramorum, Postia placenta), which were tested for activity against the CF pathogens, Pseudomonas aeruginosa (PA) (n=8), Burkholderia cenocepacia (n=2) and Stenotrophomonas maltophilia (n=2). In addition, FCE were assessed for their ability to alter antibiotic susceptibility in PA (n=8), with six antipseudomonal antibiotics (ceftazidime, ciprofloxacin, colistin, meropenem, piperacillin/tazobactam, tobramycin). None of the FCEs showed inhibitory activity to the 12 bacterial isolates tested, with the exception of the FCE from Postia placenta, which showed inhibition against all 12 bacteria. An antagonistic interaction was observed, where a statistically significant decrease in mean zone sizes was noted with Armillaria gallica (p=0.03) and Phytophthora infestans (p=0.03) FCEs and their interaction with the fluoroquinolone antibiotic, ciprofloxacin. Given the increase in clinical morbidity and mortality associated with chronic lung infections with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia, coupled with the difficulty in treating such chronic infection due to overwhelming antimicrobial resistance, any novel substance showing inhibition of these organisms merits further investigation as a potential future antimicrobial agent, with potential clinical therapeutic application.

PMID:34815596 | PMC:PMC8581687

Respir Care. 2021 Nov 23:respcare.09270. doi: 10.4187/respcare.09270. Online ahead of print.

ABSTRACT

BACKGROUND: Physical activity (PA) and sedentary behavior (SB) have marked impact on key prognostic indicators such as aerobic capacity and lung function in people with cystic fibrosis (CF) and may have associations with sleep, well-being, and health-related quality of life (HRQOL).

METHODS: This observational study assessed PA, SB, aerobic capacity, spirometry, sleep, well-being, and HRQOL in adults with CF at University Hospital Limerick. PA and SB were assessed using an accelerometer that was worn for 7 days. A cardiopulmonary exercise test assessed aerobic capacity. Spirometry was performed according to American Thoracic Society guidelines. Well-being was measured by the AWESCORE, sleep quality by the Pittsburgh Sleep Quality Index (PSQI), and HRQOL using the CF Questionnaire-Revised.

RESULTS: Thirty-three participants (13 males/20 females) were recruited. Mean age was 26.2 y (± 7.1 SD), with mean FEV1 72.9% of predicted (± 26.2 SD). Mean step count was 7,788 (± 3,583 SD). Over 75% of participants did not reach recommended PA targets (> 10,000 steps), with females being 25.5% less active than males. The PSQI indicated 48.5% of participants scored > 5, indicating poor sleep quality. Number of steps and SB demonstrated a moderate significant correlation with FEV1 (r = 0.45, P = .030; r = -0.37, P = .043, respectively) and sleep quality (r = -0.85, P < .001; r = 0.77, P < .001, respectively). ̇VO2 peak expressed relative to body weight, and as a percentage of predicted, was significantly positively correlated with step count (r = 0.48, P = .007; r = 0.42, P = .02, respectively) but did not correlate with SB (P = .96). ̇VO2 peak (L/min) strongly correlated with FEV1 (r = 0.75, P < .001).

CONCLUSIONS: Most participants did not meet PA targets. PA levels correlated to aerobic capacity, FEV1, and self-reported sleep quality, and this should be considered in longitudinal studies and in PA interventions.

PMID:34815328 | DOI:10.4187/respcare.09270

Orphanet J Rare Dis. 2021 Nov 23;16(1):491. doi: 10.1186/s13023-021-02124-5.

ABSTRACT

In the United States, approximately 7000 rare diseases affect 30 million patients, and only 10% of these diseases have existing therapies. Sound study design and causal inference methods are essential to demonstrate the therapeutic efficacy, safety, and effectiveness of new therapies. In the rare diseases setting, several factors challenge the use of typical parallel control designs: the small patient population size, genotypic and phenotypic diversity, and the complexity and incomplete understanding of the disorder's progression. Repeated measures, when spaced appropriately relative to disease progression and exploited in design and analysis, can increase study power and reduce variability in treatment effect estimation. This paper reviews these longitudinal designs and draws the parallel between some new and existing randomized studies in rare diseases and their less well-known controlled observational study designs. We show that self-controlled randomized crossover and N-of-1 designs have similar considerations as the observational case series and case-crossover designs. Also, randomized sequential designs have similar considerations to longitudinal cohort studies using sequential matching or weighting to control confounding. We discuss design and analysis considerations for valid causal inference and illustrate them with examples of analyses in multiple rare disorders, including urea cycle disorder and cystic fibrosis.

PMID:34814939 | DOI:10.1186/s13023-021-02124-5

Pediatrics. 2021 Nov 16:e2021051740. doi: 10.1542/peds.2021-051740. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) screen-positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children.

METHODS: Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive-screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes.

RESULTS: The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls.

CONCLUSIONS: Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.

PMID:34814176 | DOI:10.1542/peds.2021-051740

Pediatrics. 2021 Nov 2:e2021053822. doi: 10.1542/peds.2021-053822. Online ahead of print.

NO ABSTRACT

PMID:34814163 | DOI:10.1542/peds.2021-053822

Chronic Illn. 2021 Nov 23:17423953211060257. doi: 10.1177/17423953211060257. Online ahead of print.

ABSTRACT

OBJECTIVES: Cystic fibrosis is a chronic, genetic disease that primarily affects the respiratory system. The coronavirus disease 2019 pandemic has altered how people with cystic fibrosis receive healthcare. This paper explores the perceptions of cystic fibrosis healthcare providers and partners of women with cystic fibrosis regarding the use of telehealth in routine cystic fibrosis healthcare in the US.

METHODS: As part of a larger study examining fertility counseling for women with cystic fibrosis, we conducted qualitative, semi-structured interviews. Participants included partners of women with cystic fibrosis (n = 20) and cystic fibrosis healthcare providers (n = 20). We completed the interviews before and during the global coronavirus disease 2019 pandemic. We analyzed the data using thematic analysis.

RESULTS: When in-person healthcare could not be achieved safely, partners and healthcare providers found new value in telehealth. Three themes emerged: (1) increased connection between healthcare team and family, (2) increased efficiency of healthcare appointments, and (3) improved interdisciplinary collaboration. Partners found that telehealth allowed for more engagement in their significant others' healthcare. Providers reported enhanced efficiency and opportunities for collaboration across specialties that improved healthcare delivery and care coordination.

DISCUSSION: Results from this study highlighted the positive value of telehealth. Telehealth presents as a potential alternative to delivering outpatient care for people with chronic illnesses beyond the pandemic.

PMID:34812062 | DOI:10.1177/17423953211060257

Paediatr Anaesth. 2021 Nov 23. doi: 10.1111/pan.14341. Online ahead of print.

ABSTRACT

INTRODUCTION: When performing computerized tomography chest imaging in children, obtaining high quality, motion-free images is important in the accurate diagnosis of underlying pathology. General anesthesia is associated with the development of atelectasis, which can impair accurate diagnosis by obscuring or altering the appearance of the lung parenchyma or airways. Recruitment maneuvers, performed by anesthesiologists, can be used to effectively re-expand atelectatic lung.

METHODS: The computerized tomography chest imaging in 44 children aged between 2 months and 7 years, undergoing serial imaging for monitoring of cystic fibrosis, were reviewed and graded for atelectasis. The first scan performed on each child was performed with a supraglottic airway device and a non-standardized recruitment maneuver. The second scan on each child was performed with a cuffed endotracheal tube and a standardized recruitment maneuver.

RESULTS: When a supraglottic airway device and a non-standardized recruitment maneuver were used, 77% of patients demonstrated atelectasis of any degree on their computerized tomography chest imaging, compared with only 39% when a cuffed endotracheal tube and standardized recruitment maneuver were used. The percentage of computerized tomography chest scans that were scored acceptable (with either a total combined lung atelectasis score of 0 or 1) improved from 37% to 75% when a cuffed endotracheal tube and standardized recruitment maneuver where used. In particular, the mean atelectasis score for both lungs improved from 2.91 (SD ± 2.6) to 1.11 (SD ± 1.9), with a mean difference of 1.8 (95% CI 0.82-2.77) (p 0.0004).

CONCLUSION: The use of a cuffed endotracheal tube and a standardized recruitment maneuver is an effective way to reduce atelectasis as a result of general anesthesia. Anesthesiologists can actively contribute towards improved image quality through their choice of airway and recruitment maneuver.

PMID:34811851 | DOI:10.1111/pan.14341

Sci Rep. 2021 Nov 22;11(1):22725. doi: 10.1038/s41598-021-02242-x.

ABSTRACT

We previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.

PMID:34811449 | DOI:10.1038/s41598-021-02242-x

Respiration. 2021 Nov 22:1-10. doi: 10.1159/000519751. Online ahead of print.

ABSTRACT

BACKGROUND: Inhalation therapy is one of the cornerstones of the daily treatment regimen in patients with cystic fibrosis (CF). Recommendations regarding the addition of bronchodilators, especially salbutamol are conflicting due to the lack of evidence. New diagnostic measures such as multiple-breath washout (<underline>MBW)</underline> and functional magnetic resonance imaging (MRI) have the potential to reveal new insights into bronchodilator effects in patients with CF.

OBJECTIVE: The objective of the study was to comprehensively assess the functional response to nebulized inhalation with salbutamol in children with CF.

METHODS: Thirty children aged 6-18 years with stable CF performed pulmonary function tests, MBW, and matrix pencil-MRI before and after standardized nebulized inhalation of salbutamol.

RESULTS: Lung clearance index decreased (improved) by -0.24 turnover (95% confidence interval [CI]: -0.53 to 0.06; p = 0.111). Percentage of the lung volume with impaired fractional ventilation and relative perfusion decreased (improved) by -0.79% (CI: -1.99 to 0.42; p = 0.194) and -1.31% (CI: -2.28 to -0.35; p = 0.009), respectively. Forced expiratory volume (FEV1) increased (improved) by 0.41 z-score (CI: 0.24-0.58; p < 0.0001). We could not identify specific clinical factors associated with a more pronounced effect of salbutamol.

CONCLUSIONS: There is a positive short-term effect of bronchodilator inhalation on FEV1 in patients with CF, which is independent of ventilation inhomogeneity. Heterogeneous response between patients suggests that for prediction of a therapeutic effect this should be tested by spirometry in every patient individually.

PMID:34808631 | DOI:10.1159/000519751

Antimicrob Agents Chemother. 2021 Nov 22:AAC0187521. doi: 10.1128/AAC.01875-21. Online ahead of print.

ABSTRACT

The failure of antibiotic therapy in respiratory tract infections in cystic fibrosis is partly due to the high tolerance observed in Pseudomonas aeruginosa biofilms. This tolerance is mediated by changes in bacterial metabolism linked to growth in biofilms, opening up potential avenues for novel treatment approaches based on modulating metabolism. The goal of the present study was to identify carbon sources that increase the inhibiting and/or eradicating activity of tobramycin, ciprofloxacin and ceftazidime against P. aeruginosa PAO1 biofilms grown in a synthetic cystic fibrosis sputum medium (SCFM2) and to elucidate their mode of action. After screening 69 carbon sources, several combinations of antibiotics + carbon sources that showed markedly higher anti-biofilm activity than antibiotics alone were identified. D,L-malic acid and sodium acetate could potentiate both biofilm inhibiting and eradicating activity of ciprofloxacin and ceftazidime, respectively, while citric acid could only potentiate biofilm inhibitory activity of tobramycin. The mechanisms underlying the increased biofilm eradicating activity of combinations ciprofloxacin/D,L-malic acid and ceftazidime/sodium acetate are similar but not identical. Potentiation of ceftazidime activity by sodium acetate was linked to increased metabolic activity, a functional TCA cycle, increased ROS production and high intracellular pH, whereas the latter was not required for D,L-malic acid potentiation of ciprofloxacin. Finally, our results indicate that the potentiation of antibiotic activity by carbon sources is strain dependent.

PMID:34807756 | DOI:10.1128/AAC.01875-21

J Gastrointest Cancer. 2021 Nov 22. doi: 10.1007/s12029-021-00729-4. Online ahead of print.

ABSTRACT

It is thought that many of the idiopathic pancreatitis could have a genetic base. Approximately 50% of them correspond to CFTR (cystic fibrosis transmembrane conductance regulator gene) and SPINK-1 (serine protease inhibitor Kazal type 1) mutations. A recent study compares patients with acute pancreatitis and SPINK-1 mutation with patients with idiopathic acute pancreatitis. The study highlights a 12-fold increased risk of developing pancreatic cancer with SPINK-1 mutation versus the control group. Nonetheless, authors conclude that only specific pN34s mutation is related to pancreatic cancer. This relation is controversial, and international consensus guidelines for the follow-up in chronic pancreatitis with pancreatic cancer still do not recommend follow-up in SPINK-1 p. N34S mutation. We believe that developing prospective studies in which subgroups of patients with SPINK-1 mutation benefit from closer follow-ups would be necessary.

PMID:34807350 | DOI:10.1007/s12029-021-00729-4

Health Technol Assess. 2021 Nov;25(65):1-128. doi: 10.3310/hta25650.

ABSTRACT

BACKGROUND: People with cystic fibrosis are susceptible to pulmonary infection with Pseudomonas aeruginosa. This may become chronic and lead to increased mortality and morbidity. If treatment is commenced promptly, infection may be eradicated through prolonged antibiotic treatment.

OBJECTIVE: To compare the clinical effectiveness, cost-effectiveness and safety of two eradication regimens.

DESIGN: This was a Phase IV, multicentre, parallel-group, randomised controlled trial.

SETTING: Seventy UK and two Italian cystic fibrosis centres.

PARTICIPANTS: Participants were individuals with cystic fibrosis aged > 28 days old who had never had a P. aeruginosa infection or who had been infection free for 1 year.

INTERVENTIONS: Fourteen days of intravenous ceftazidime and tobramycin or 3 months of oral ciprofloxacin. Inhaled colistimethate sodium was included in both regimens over 3 months. Consenting patients were randomly allocated to either treatment arm in a 1 : 1 ratio using simple block randomisation with random variable block length.

MAIN OUTCOME MEASURES: The primary outcome was eradication of P. aeruginosa at 3 months and remaining free of infection to 15 months. Secondary outcomes included time to reoccurrence, spirometry, anthropometrics, pulmonary exacerbations and hospitalisations. Primary analysis used intention to treat (powered for superiority). Safety analysis included patients who had received at least one dose of any of the study drugs. Cost-effectiveness analysis explored the cost per successful eradication and the cost per quality-adjusted life-year.

RESULTS: Between 5 October 2010 and 27 January 2017, 286 patients were randomised: 137 patients to intravenous antibiotics and 149 patients to oral antibiotics. The numbers of participants achieving the primary outcome were 55 out of 125 (44%) in the intravenous group and 68 out of 130 (52%) in the oral group. Participants randomised to the intravenous group were less likely to achieve the primary outcome; although the difference between groups was not statistically significant, the clinically important difference that the trial aimed to detect was not contained within the confidence interval (relative risk 0.84, 95% confidence interval 0.65 to 1.09; p = 0.184). Significantly fewer patients in the intravenous group (40/129, 31%) than in the oral group (61/136, 44.9%) were hospitalised in the 12 months following eradication treatment (relative risk 0.69, 95% confidence interval 0.5 to 0.95; p = 0.02). There were no clinically important differences in other secondary outcomes. There were 32 serious adverse events in 24 participants [intravenous: 10/126 (7.9%); oral: 14/146 (9.6%)]. Oral therapy led to reductions in costs compared with intravenous therapy (-£5938.50, 95% confidence interval -£7190.30 to -£4686.70). Intravenous therapy usually necessitated hospital admission, which accounted for a large part of this cost.

LIMITATIONS: Only 15 out of the 286 participants recruited were adults - partly because of the smaller number of adult centres participating in the trial. The possibility that the trial participants may be different from the rest of the cystic fibrosis population and may have had a better clinical status, and so be more likely to agree to the uncertainty of trial participation, cannot be ruled out.

CONCLUSIONS: Intravenous antibiotics did not achieve sustained eradication of P. aeruginosa in a greater proportion of cystic fibrosis patients. Although there were fewer hospitalisations in the intravenous group during follow-up, this confers no advantage over the oral therapy group, as intravenous eradication frequently requires hospitalisation. These results do not support the use of intravenous antibiotics to eradicate P. aeruginosa in cystic fibrosis.

FUTURE WORK: Future research studies should combine long-term follow-up with regimens to reduce reoccurrence after eradication.

TRIAL REGISTRATION: Current Controlled Trials ISRCTN02734162 and EudraCT 2009-012575-10.

FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 65. See the NIHR Journals Library website for further project information.

PMID:34806975 | DOI:10.3310/hta25650

Am J Rhinol Allergy. 2021 Nov 20:19458924211059606. doi: 10.1177/19458924211059606. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic sinus surgery is a well-established treatment for chronic rhinosinusitis in patients with cystic fibrosis, though its benefits seem to be limited to improving sinonasal symptoms rather than affecting lung function.

OBJECTIVE: This study aims to identify clinical and demographic factors that may influence sinonasal and pulmonary outcomes after surgery.

METHODS: This is a six-year retrospective analysis of adult cystic fibrosis patients who underwent endoscopic sinus surgery at a tertiary care center. 22-Item Sino-Nasal Outcomes Test scores and mean forced expiratory volume data at baseline and three to six months after surgery were analyzed using t-test and stepwise regression with the following covariates: age, gender, lung transplant, revision surgery, and pseudomonas on sinus culture.

RESULTS: 119 surgeries were performed on 88 patients, with 69% on patients with transplant. The overall mean (Standard Deviation) improvement in 22-Item Sino-Nasal Outcomes Test score was 9.42 (18.15) for the entire cohort (P < .001). Pseudomonas on culture was associated with less improvement in sinonasal scores (P = .002). There was no significant change in forced expiratory volume after surgery (P = .94). Revision surgery (P = .004) and older age (P = .007) were associated with less favorable change of pulmonary function on stepwise regression (P = .002). There was no correlation between change in sinonasal scores and pulmonary function.

CONCLUSION: Although surgery was associated with a clinically and statistically significant improvement in sinonasal scores in cystic fibrosis patients, patients with pseudomonas may experience less benefit. Revision surgery and older age may be associated with less favorable pulmonary outcomes. Awareness of such variables may help when deciding which cystic fibrosis patients should undergo surgery.

PMID:34806427 | DOI:10.1177/19458924211059606

J Adv Nurs. 2021 Nov 21. doi: 10.1111/jan.15099. Online ahead of print.

ABSTRACT

AIMS: Explore the knowledge, experiences, preferences, and concerns related to fertility preservation as an option for building a biological family among women with cystic fibrosis.

DESIGN: Convergent mixed methods study design.

METHODS: We recruited women with cystic fibrosis of childbearing age in the United States through cystic fibrosis centres, snowball sampling, and social media. Participants completed an anonymous survey about fertility and fertility preservation (n = 50). We also conducted audio-recorded, semi-structured interviews with a subset of women to gain a better understanding of their perspectives (n = 20). We transcribed the interviews verbatim and analysed them using thematic analysis.

RESULTS: For the quantitative arm, 78% of women indicated that they would like to have a child in the future; however, 74% reported never having had conversations about fertility preservation with their providers. For the qualitative arm, four major themes emerged: (1) Women with cystic fibrosis have inadequate knowledge about fertility and fertility preservation; (2) fertility is a low priority area for the cystic fibrosis care team; (3) women with cystic fibrosis recommend that the cystic fibrosis care team provide specific fertility resources; and (4) providers and literature lack information on fertility and cystic fibrosis. Integrated findings identified that while the majority of women with cystic fibrosis want to become mothers in the future, including post-lung transplantation, they have not received education on fertility preservation, and there is a general lack of knowledge on the topic of fertility in cystic fibrosis.

CONCLUSION: Women with cystic fibrosis desire to have children but have little knowledge about fertility preservation, and cystic fibrosis providers do not initiate family planning discussions.

IMPACT: Findings from the study support that additional education is needed for women with cystic fibrosis who are considering parenthood. Clinical care models should include early, regular, and thoughtful discussions about reproductive health issues, including fertility preservation.

PMID:34806231 | DOI:10.1111/jan.15099

J Clin Transl Endocrinol. 2021 Oct 30;26:100272. doi: 10.1016/j.jcte.2021.100272. eCollection 2021 Dec.

ABSTRACT

Because nutritional status is intimately linked with pulmonary function and survival, nutrition has been at the mainstay of cystic fibrosis (CF) care. Body Mass Index (BMI) is traditionally used to define nutritional status because of the ease with which it can be calculated, but it has a number of limitations including its inability to differentiate fat mass (FM) from lean body mass (LBM), the latter thought to confer health advantage. A number of tools are available to quantify body composition including dual-energy x-ray absorptiometry (DXA), bioelectrical impedance, MRI, CT, air displacement plethysmography, and stable isotopes, and these have been used to varying degrees in studies of CF. In CF, LBM tends to be lower for a given BMI, particularly at lower BMI. In adults, lower fat-free mass (FFM) correlates with greater CF disease severity, lower pulmonary function and higher inflammatory markers. FFM is also positively associated with greater bone mineral density, while greater FM is associated with greater loss of lumbar spine bone mineral density over 2 years. In youth, LBM is positively associated with pulmonary function. The predictive value of body composition for functional and clinical outcomes and the role of improving LBM on these outcomes remain undefined. With improvements in BMI accompanying highly-effective modulator therapy, closer evaluations of body composition may inform risk for more traditional, non-CF adult outcomes in CF.

PMID:34804808 | PMC:PMC8586800 | DOI:10.1016/j.jcte.2021.100272

J Cyst Fibros. 2021 Nov 18:S1569-1993(21)02130-5. doi: 10.1016/j.jcf.2021.11.002. Online ahead of print.

ABSTRACT

Electrolyte disturbances are common in patients with cystic fibrosis (CF). Current guidelines on monitoring sodium status are based on research in a small group of infants and require blood sampling. The aim of this study was to evaluate urinary salt parameters as a surrogate for sodium-status in different age-groups. Blood and urine samples for electrolytes were collected from 222 patients followed at the Ghent University Hospital CF-center. Fractional sodium excretion (FENa) and several urinary parameters were calculated. Clinical characteristics did not differ according to sodium status, defined as FENa <0.5%. ROC analysis demonstrated that sodium/creatinine ratio (UNa/Creat) predicted the sodium status most accurately with high sensitivity and specificity (97 and 91% respectively). The UNa/Creat cut-off predicting a FENa <0.5% differed significantly according to age. The UNa/Creat is an excellent marker for the sodium status defined as a FENa <0.5%. However, different cut-offs according to age category should be applied.

PMID:34802939 | DOI:10.1016/j.jcf.2021.11.002

Disabil Rehabil. 2021 Nov 22:1-14. doi: 10.1080/09638288.2021.2003876. Online ahead of print.

ABSTRACT

PURPOSE: Patient empowerment may be particularly important in children and young people (CYP) with CF, due to high treatment burden and limited peer support opportunities. This review aimed to meta-synthesize the qualitative literature pertaining to empowerment in CYP with CF.

MATERIALS AND METHODS: This work was guided by the ENTREQ framework, with a search strategy based on the SPIDER framework. A systematic search of PsycInfo, Medline, CINAHL and ASSIA databases was conducted. Identified studies were quality assessed and data analysed using thematic synthesis. PROSPERO registration: CRD42019154014.

RESULTS: Seventeen studies met inclusion criteria, though none explicitly explored empowerment. Thematic synthesis identified six analytic themes: relational support, information and understanding and feeling heard and respected appeared to facilitate empowerment, while prejudices and assumptions were identified as potential barriers. Mastery and competence and Navigating being different appeared to be components of empowerment.

CONCLUSIONS: The findings provide an initial understanding of patient empowerment in CYP with CF. Potential clinical implications include the need for more CYP-friendly information, more shared decision making and more opportunities to experience mastery. The need for further research is highlighted, particularly relating to developmental influences and factors unique to CF, which are not adequately addressed in existing patient empowerment models.Implications for rehabilitationEmpowerment in children and young people with cystic fibrosis can be facilitated by supportive and respectful relationships with family, friends and clinical teams, that enable them to feel heard and understood.It can be further supported by providing developmentally appropriate information and opportunities for children and young people to experience mastery and competency in typical childhood activities.Prejudices and assumptions about the capabilities of children and young people with CF, even when based in good intentions, can act as a barrier to empowerment.Empowerment can shape (and be shaped by) the way the children and young people navigate differences associated with living with CF.

PMID:34802345 | DOI:10.1080/09638288.2021.2003876

J Cyst Fibros. 2021 Nov 17:S1569-1993(21)02133-0. doi: 10.1016/j.jcf.2021.11.005. Online ahead of print.

ABSTRACT

BACKGROUND: There is no data exclusively on the relationship between health-related quality-of-life (HRQOL) and lung disease severity in early school-aged children with cystic fibrosis (CF). Using data from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) we assessed the relationships between HRQOL, lung function and structure.

METHODS: 125 children aged 6.5-10 years enrolled in the AREST CF program were included from CF clinics at Royal Children's Hospital (RCH), Melbourne (n = 66) and Perth Children's Hospital (PCH), Perth (n = 59), Australia. Demographics, HRQOL measured by Cystic Fibrosis Questionnaire-Revised (CFQ-R), spirometry, multiple-breath washout (MBW) and chest CT were collected across two years. Correlation between CFQ-R scores and lung structure/function parameters and agreement between parent-proxy and child-reported HRQOL were evaluated.

RESULTS: No correlation was observed between most CFQ-R domain scores and FEV1 z-scores, excepting weak-positive correlation with parent CFQ-R Physical (rho = 0.21, CI 0.02-0.37), and Weight (rho = 0.21, CI 0.03-0.38) domain and child Body domain (rho = 0.26, CI 0.00-0.48). No correlation between most CFQ-R domain scores and LCI values was noted excepting weak-negative correlation with parent Respiratory (rho = -0.23, CI -0.41--0.05), Emotional (rho = -0.24, CI -0.43--0.04), and Physical (-0.21, CI -0.39--0.02) domains. Furthermore, structural lung disease on CT data demonstrated little to no association with CFQ-R parent and child domain scores. Additionally, no agreement between child self-report and parent-proxy CFQ-R scores was observed across the majority of domains and visits.

CONCLUSION: HRQOL correlated poorly with lung function and structure in early school-aged children with CF, hence clinical trials should consider these outcomes independently when determining study end-points.

PMID:34801433 | DOI:10.1016/j.jcf.2021.11.005

Thorac Surg Clin. 2022 Feb;32(1):43-49. doi: 10.1016/j.thorsurg.2021.09.006.

ABSTRACT

The many socioeconomic disparities in the myriad of diagnoses that make up benign lung diseases are unfortunately a global issue that was most recently highlighted by the COVID-19 pandemic of 2020. In this chapter, we will be reviewing the socioeconomic disparities in benign lung disease from both a United States perspective as well as a global perspective. We will cover the spectrum of infectious, obstructive, and restrictive lung disease and review the evidence on how social disparities affect these populations and their access to medical care.

PMID:34801194 | DOI:10.1016/j.thorsurg.2021.09.006