Chin Med J (Engl). 2023 Sep 7. doi: 10.1097/CM9.0000000000002834. Online ahead of print.

NO ABSTRACT

PMID:37678334 | DOI:10.1097/CM9.0000000000002834

Curr Opin Pulm Med. 2023 Sep 6. doi: 10.1097/MCP.0000000000001017. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Highly effective modulators of cystic fibrosis transmembrane conductance regulator (CFTR) function have had dramatic impact on pulmonary and nutritional outcomes in persons with cystic fibrosis (pwCF). The impact on liver disease in pwCF was not the focus of the registration trials. The purpose of this review is to assess the current literature on the impact of HEMT on liver disease, progression, regression, and safety.

RECENT FINDINGS: Short-term studies of HEMT in pwCF have shown that there is no significant impact on the frequency of liver enzyme abnormalities. There is no evidence for significant improvement in liver enzymes over time on HEMT therapy. There is conflicting data on improvement in liver fibrosis determined by fibrosis indices (APRI and GPR) or elastography. One study showed improvement, and another showed worsening in younger (<20 years old) pwCF. There are reports of resolution or improvement in hepatic steatosis. There are rare reports of severe acute hepatitis and one report of hepatic decompensation leading to liver transplantation due to drug-induced liver disease.

SUMMARY: HEMT have not been shown to have a significant impact on improving liver disease or preventing fibrosis with short-term therapy. Longer studies are needed to assess the impact of HEMT on liver disease in pwCF.

PMID:37678151 | DOI:10.1097/MCP.0000000000001017

JAMA Otolaryngol Head Neck Surg. 2023 Sep 7. doi: 10.1001/jamaoto.2023.2701. Online ahead of print.

ABSTRACT

IMPORTANCE: Cystic fibrosis (CF) is a multiorgan genetic disease with progressive upper and lower airway involvement. The effects of CF transmembrane conductance regulator (CFTR) modifier therapies on CF-related upper airway disease, specifically chronic rhinosinusitis (CRS), are not characterized.

OBJECTIVE: To determine the outcome of elexacaftor-tezacaftor-ivacaftor (ETI) on CRS as measured by changes in sinus computed tomography (CT) metrics and on clinical parameters in individuals with CF.

DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal cohort study was conducted at the CF center of a tertiary care hospital between October 1, 2019, and July 31, 2021. A total of 64 participants with CF were included in the analysis.

INTERVENTION: Sinus CT was obtained within 1 month of initiation of ETI therapy (baseline), and within 1 month of 1 year of ETI therapy. Images were independently analyzed by pulmonology, radiology, and otolaryngology physicians, using the Lund-Mackay and Sheikh-Lind scoring systems. Percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), and microbiologic data collected at initiation of ETI therapy and 3-month intervals for 1 year were also measured.

MAIN OUTCOMES AND MEASURES: The study hypothesis was that ETI therapy will improve CRS as measured by changes in sinus CT at initiation and 1 year after ETI therapy and clinical parameters in individuals with CF.

RESULTS: Among the 64 participants (39 [60.9%] female; median age, 18.5 [IQR, 16.0-28.5] years; 64 [100%] White), improvement in CRS was noted by improvements in sinus CT scans using both sinus CT scoring systems after 1 year of ETI therapy. The reduction in the median total score using the Lund-Mackay sinus CT scoring system (from 5.8 [IQR, 5.0-7.0] to 3.3 [IQR, 2.6-4.2]) and the Sheikh-Lind scoring system (from 3.8 [IQR, 3.0-5.0] to 2.2 [IQR, 2.0-2.5]) was noted. Increases in ppFEV1 and BMI were also observed by 3 months of ETI therapy with persistent improvement through 1 year of treatment. Similarly, after 1 year of ETI therapy, participants with CF had reductions in positivity for Pseudomonas aeruginosa and Staphylococcus aureus in oropharyngeal cultures.

CONCLUSION AND RELEVANCE: This cohort study found that use of ETI therapy was associated with improved CRS outcomes in participants with CF as quantified by improved sinus CT scans measured by 2 radiographic scoring systems and was also associated with improved clinical outcomes. Despite improvement in CT scan scores, most people with CF continue to have scores that indicate severe sinus disease.

PMID:37676668 | DOI:10.1001/jamaoto.2023.2701

Infect Immun. 2023 Sep 7:e0022823. doi: 10.1128/iai.00228-23. Online ahead of print.

ABSTRACT

Staphylococcus aureus is a facultative intracellular pathogen in many host cell types, facilitating its persistence in chronic infections. The genes contributing to intracellular pathogenesis have not yet been fully enumerated. Here, we cataloged genes influencing S. aureus invasion and survival within human THP-1 derived macrophages using two laboratory strains (ATCC2913 and JE2). We developed an in vitro transposition method to produce highly saturated transposon mutant libraries in S. aureus and performed transposon insertion sequencing (Tn-Seq) to identify candidate genes with significantly altered abundance following macrophage invasion. While some significant genes were strain-specific, 108 were identified as common across both S. aureus strains, with most (n = 106) being required for optimal macrophage infection. We used CRISPR interference (CRISPRi) to functionally validate phenotypic contributions for a subset of genes. Of the 20 genes passing validation, seven had previously identified roles in S. aureus virulence, and 13 were newly implicated. Validated genes frequently evidenced strain-specific effects, yielding opposing phenotypes when knocked down in the alternative strain. Genomic analysis of de novo mutations occurring in groups (n = 237) of clonally related S. aureus isolates from the airways of chronically infected individuals with cystic fibrosis (CF) revealed significantly greater in vivo purifying selection in conditionally essential candidate genes than those not associated with macrophage invasion. This study implicates a core set of genes necessary to support macrophage invasion by S. aureus, highlights strain-specific differences in phenotypic effects of effector genes, and provides evidence for selection of candidate genes identified by Tn-Seq analyses during chronic airway infection in CF patients in vivo.

PMID:37676013 | DOI:10.1128/iai.00228-23

Prenat Diagn. 2023 Sep 6. doi: 10.1002/pd.6427. Online ahead of print.

ABSTRACT

OBJECTIVE: Carrier screening with reflex to single-gene noninvasive prenatal testing (sgNIPT) is an alternative approach for identifying pregnancies at risk for inherited autosomal recessive conditions without the need for a sample from the reproductive partner. This study is the largest clinical validation of this approach in a general population setting.

METHODS: The clinical performance of carrier screening with reflex to sgNIPT for cystic fibrosis, spinal muscular atrophy, alpha thalassemias, and beta hemoglobinopathies was assessed by collecting pregnancy outcome data on patients who underwent this testing and comparing the neonatal outcome to the assay-predicted fetal risk.

RESULTS: Of 42,067 pregnant individuals who underwent screening, 7538 carriers (17.9%) had reflex sgNIPT, and neonatal or fetal outcomes were obtained for 528 cases, including 25 affected pregnancies. Outcomes demonstrated high concordance with sgNIPT, for example, all pregnancies with 9 in 10 personalized fetal risk results were affected (positive predictive value (PPV) of 100% for the sub-group) and the sgNIPT assay showed a sensitivity of 96.0% (95% CI: 79.65%-99.90%), specificity of 95.2% (95% CI: 92.98%-96.92%), average PPV of 50.0% (95% CI: 35.23%-64.77%), and negative predictive value (NPV) of 99.8% (95% CI: 98.84%-99.99%). The end-to-end performance of carrier screening with reflex to sgNIPT was calculated to have a sensitivity of 92.4% and specificity of 99.9%, which are unaffected by partner carrier screening or misattributed paternity unlike a traditional carrier screening workflow, which has a 35% sensitivity and a maximum of 25% PPV (1 in 4) in a real-life setting.

CONCLUSION: This study builds upon earlier findings to confirm that carrier testing with reflex to sgNIPT is highly accurate for general population screening. Given this high accuracy and an NPV of 99.8%, this workflow should be considered as an option for most of the general pregnant population. When the biological partner sample is unavailable, this workflow should be recommended as the first-line approach.

PMID:37674263 | DOI:10.1002/pd.6427

Int J Biol Macromol. 2023 Sep 4:126652. doi: 10.1016/j.ijbiomac.2023.126652. Online ahead of print.

ABSTRACT

Channelopathies arise from ion channel dysfunction. Successful treatment entails delivery of functional ion channels to replace dysfunctional ones. Glycine receptor (GlyR)-rich cell membrane fragments (CMF) were previously delivered to target cell membranes using fusogenic liposomes. Here, cystic fibrosis transmembrane conductance regulator (CFTR)-bearing CMF were similarly delivered to target cells. We studied the effect of lipid composition on liposomes' ability to incorporate CMF and fuse with target cell membranes to deliver functional CFTR. Four formulations were prepared using thin-film hydration out of different lecithin sources, egg and soy lecithin (EL and SL), in the presence and absence of cholesterol (CHOL): EL + CHOL, EL-CHOL, SL + CHOL, and SL-CHOL. EL liposomes incorporated more CMF than SL liposomes, with CHOL only increasing CMF incorporation in SL liposomes. SL + CHOL fused better with target cell membranes than EL + CHOL. SL + CHOL and EL + CHOL equally delivered CFTR to target cell membranes, owing to the former's superior fusogenic capacity and the latter's superior CMF-incorporation capacity. SL-CHOL and EL-CHOL delivered CFTR to a lesser extent, indicating the importance of CHOL for fusion. Patch-clamp electrophysiology and confocal laser scanning microscopy (CLSM) confirmed CFTR delivery to target cell membranes by SL + CHOL. Therefore, CMF-bearing fusogenic liposomes offer a promising universal platform for the treatment of channelopathies.

PMID:37673169 | DOI:10.1016/j.ijbiomac.2023.126652

Respir Res. 2023 Sep 6;24(1):217. doi: 10.1186/s12931-023-02516-0.

ABSTRACT

Cystic fibrosis (CF) is caused by defects of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR-modulating drugs may overcome specific defects, such as the case of Trikafta, which is a clinically approved triple combination of Elexacaftor, Tezacaftor and Ivacaftor (ETI) that exhibited a strong ability to rescue the function of the most frequent F508del pathogenic variant even in genotypes with the mutated allele in single copy. Nevertheless, most rare genotypes lacking the F508del allele are still not eligible for targeted therapies. Via the innovative approach of using nasal conditionally reprogrammed cell (CRC) cell-based models that mimic patient disease in vitro, which are obtainable from each patient due to the 100% efficiency of the cell culture establishment, we theratyped orphan CFTR mutation L1077P. Protein studies, Forskolin-induced organoid swelling, and Ussing chamber assays congruently proved the L1077P variant function rescue by ETI. Notably, this rescue takes place even in the context of a single-copy L1077P allele, which appears to enhance its expression. Thus, the possibility of single-allele treatment also arises for rare genotypes, with an allele-specific modulation as part of the mechanism. Of note, besides providing indication of drug efficacy with respect to specific CFTR pathogenic variants or genotypes, this approach allows the evaluation of the response of single-patient cells within their genetic background. In this view, our studies support in vitro guided personalized CF therapies also for rare patients who are nearly excluded from clinical trials.

PMID:37674160 | DOI:10.1186/s12931-023-02516-0

PLoS Comput Biol. 2023 Sep 6;19(9):e1011424. doi: 10.1371/journal.pcbi.1011424. Online ahead of print.

ABSTRACT

Chronic Pseudomonas aeruginosa (Pa) lung infections are the leading cause of mortality among cystic fibrosis (CF) patients; therefore, the eradication of new-onset Pa lung infections is an important therapeutic goal that can have long-term health benefits. The use of early antibiotic eradication therapy (AET) has been shown to clear the majority of new-onset Pa infections, and it is hoped that identifying the underlying basis for AET failure will further improve treatment outcomes. Here we generated machine learning models to predict AET outcomes based on pathogen genomic data. We used a nested cross validation design, population structure control, and recursive feature selection to improve model performance and showed that incorporating population structure control was crucial for improving model interpretation and generalizability. Our best model, controlling for population structure and using only 30 recursively selected features, had an area under the curve of 0.87 for a holdout test dataset. The top-ranked features were generally associated with motility, adhesion, and biofilm formation.

PMID:37672526 | DOI:10.1371/journal.pcbi.1011424

Pediatr Pulmonol. 2023 Sep 6. doi: 10.1002/ppul.26659. Online ahead of print.

ABSTRACT

INTRODUCTION: Exercise intolerance is common in chronic airway diseases (CAD), but its mechanisms are still poorly understood. The aim of this study was to evaluate exercise capacity and its association with lung function, ventilatory limitation, and ventilatory efficiency in children and adolescents with cystic fibrosis (CF) and asthma when compared to healthy controls.

METHODS: Cross-sectional study including patients with mild-to-moderate asthma, CF and healthy children and adolescents. Anthropometric data, lung function (spirometry) and exercise capacity (cardiopulmonary exercise testing) were evaluated. Primary outcomes were peak oxygen consumption (VO2 peak), forced expiratory volume in 1 s (FEV1 ), breathing reserve (BR), ventilatory equivalent for oxygen consumption (VE /VO2 ) and for carbon dioxide production (VE /VCO2 ), both at the ventilatory threshold (VT1 ) and peak exercise.

RESULTS: Mean age of 147 patients included was 11.8 ± 3.0 years. There were differences between asthmatics and CF children when compared to their healthy peers for anthropometric and lung function measurements. Asthmatics showed lower VO2 peak when compared to both healthy and CF subjects, although no differences were found between healthy and CF patients. A lower BR was found when CF patients were compared to both healthy and asthmatic. Both CF and asthmatic patients presented higher values for VE /VO2 and VE /VCO2 at VT1 when compared to healthy individuals. For both VE /VO2 and VE /VCO2 at peak exercise CF patients presented higher values when compared to their healthy peers.

CONCLUSION: Patients with CF achieved good exercise capacity despite low ventilatory efficiency, low BR, and reduced lung function. However, asthmatics reported reduced cardiorespiratory capacity and normal ventilatory efficiency at peak exercise. These results demonstrate differences in the mechanisms of ventilatory limitation to maximum exercise testing in children and adolescents with CAD.

PMID:37671821 | DOI:10.1002/ppul.26659

Pediatr Pulmonol. 2023 Sep 6. doi: 10.1002/ppul.26662. Online ahead of print.

NO ABSTRACT

PMID:37671806 | DOI:10.1002/ppul.26662

Pediatrics. 2023 Sep 6:e2023062985. doi: 10.1542/peds.2023-062985. Online ahead of print.

ABSTRACT

Treatment, prognosis, and quality of life for people with cystic fibrosis (CF) have improved steadily since the initial description of the disease, but most dramatically in the past decade. In 2021, the median predicted survival increased to 53 years, compared with 17 years in 1970. The recent improvement in outcomes is attributable to the advent of cystic fibrosis transmembrane regulator (CFTR) modulators, small molecules that enhance the function of defective CFTR protein. The first CFTR modulator, ivacaftor, received Food and Drug Administration approval in 2011 to treat a single CFTR variant, comprising only 4% of those affected by CF. With the demonstration of efficacy, drug approval has been expanded to other variants. Multiple CFTR modulators used in combination with ivacaftor augment efficacy and increase the number of CFTR variants amenable to therapy. Approval of elexecaftor/tezecaftor/ivacaftor in 2019 increased the number of individuals who could benefit from highly effective modulator therapy (HEMT) to ∼90% of the CF population in the United States. HEMT has been dramatically effective, with overall improvements in lung function, quality of life, nutritional status, and, in women, increased fertility. HEMT may delay the onset of other CF-related comorbidities. Although off-target effects, including hepatotoxicity, drug-drug interactions, and putative mental health issues can complicate use, modulator therapy has been generally well tolerated. Ten percent of people with CF have variants that are not amenable to modulator treatment. HEMT, despite its great cost and limited global access, has brought legitimate hope and changed the lives of a significant majority of individuals and families affected by CF in North America.

PMID:37671451 | DOI:10.1542/peds.2023-062985

Turk J Phys Med Rehabil. 2022 Dec 2;69(2):200-206. doi: 10.5606/tftrd.2023.10361. eCollection 2023 Jun.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the muscle thickness, strength, and diaphragmatic function and relate them with clinical findings.

PATIENTS AND METHODS: The cross-sectional study was conducted with 54 participants (27 males, 27 females; mean age; 24.5±5.3 years; range, 18 to 45 years) between January 2017 and October 2017. Of the participants, 31 were adult CF patients, and 23 were age-and sex-matched controls. Patient demographics, 6-min walk distance, body mass index (BMI), and fat-free mass index (FFMI) were evaluated. Each patient underwent pulmonary function tests. Quadriceps femoris thickness and diaphragm thickening fraction were assessed by ultrasonography. Upper extremity strength was measured with a handheld dynamometer.

RESULTS: There was no difference between the patients' and controls' BMI (p=0.052). However, patients' FFMI was lower than the controls' (p=0.010). The FFMI correlated with pulmonary function tests. Patients' both right and left quadriceps femoris muscles were thinner than the controls (p=0.001 and p=0.001, respectively). Patients with pancreatic insufficiency had thinner muscles than patients without pancreatic insufficiency. The control group had a stronger handgrip than CF patients (33.5±10.1 vs. 24.5±9.2 kg, p=0.003).

CONCLUSION: Peripheral muscle wasting and weakness and lower functional capacity are highly prevalent in CF patients.

PMID:37671376 | PMC:PMC10475901 | DOI:10.5606/tftrd.2023.10361

Curr Dev Nutr. 2023 Jul 31;7(9):101985. doi: 10.1016/j.cdnut.2023.101985. eCollection 2023 Sep.

ABSTRACT

Unintentional weight loss is common in persons with chronic and acute disease and is often caused by insufficient intake or malabsorption. A new lysophosphatidylcholine (LPC)-rich structured lipid powder has micelle-like activity that facilitates digestion and absorption, independent of lipase and bile acids. The aim of this secondary analysis was to determine if recycled LPC increased fat absorption of coingested food. Fasting plasma fatty acid (FA) concentrations were measured at baseline and 3 mo in children (n = 84) with cystic fibrosis and pancreatic insufficiency. Plasma palmitic acid was selected because of its dietary prevalence and was a minor component of the LPC product. Palmitic acid increased 15% in the LPC product-treated total subjects (P = 0.01) and 23% in the subgroup with more severe malabsorption (P = 0.007), with no change in either group on placebo. Total FAs increased 11% (P = 0.009) and 20% (P = 0.005), respectively. Increased palmitic acid and total FA suggest that LPC provided by the product created an intraluminal environment that increased coingested dietary fat absorption and provided more calories. This trial was registered at clinicaltrials.gov as NCT00406536.

PMID:37671264 | PMC:PMC10475471 | DOI:10.1016/j.cdnut.2023.101985

Int J Stem Cells. 2023 Sep 6. doi: 10.15283/ijsc23036. Online ahead of print.

ABSTRACT

The differentiation of pluripotent stem cells has been used to study disease mechanisms and development. We previously described a method for differentiating human pluripotent stem cells (hPSCs) into salivary gland epithelial progenitors (SGEPs). Here, cystic fibrosis transmembrane conductance regulator (CFTR) knockout hPSCs were differentiated into SGEPs derived from CFTR knockout hESCs (CF-SGEPs) using the same protocol to investigate whether the hPSC-derived SGEPs can model the characteristics of CF. CF-a disease that affects salivary gland (SG) function-is caused by mutations of the CFTR gene. Firstly, we successfully generated CFTR knockout hPSCs with reduced CFTR protein expression using the CRISPR-Cas9 system. After 16 days of differentiation, the protein expression of CFTR decreased in SGEPs derived from CFTR knockout hESCs (CF-SGEPs). RNA-Seq revealed that multiple genes modulating SG development and function were down-regulated, and positive regulators of inflammation were up-regulated in CF-SGEPs, correlating with the salivary phenotype of CF patients. These results demonstrated that CFTR suppression disrupted the differentiation of hPSC-derived SGEPs, which modeled the SG development of CF patients. In summary, this study not only proved that the hPSC-derived SGEPs could serve as manipulable and readily accessible cell models for the study of SG developmental diseases but also opened up new avenues for the study of the CF mechanism.

PMID:37670513 | DOI:10.15283/ijsc23036

Psychol Health. 2023 Sep 4:1-23. doi: 10.1080/08870446.2023.2254318. Online ahead of print.

ABSTRACT

OBJECTIVE: Previous research exploring patient-practitioner communication in relation to adherence in cystic fibrosis (CF) is limited. This UK study explored the views of adults with CF on how treatment adherence (related to all CF treatments) is discussed in routine CF care.

METHODS: 12 White British adults (ten females; aged 20-37 years; mean 30.1 years) with CF participated in semi-structured interviews.

RESULTS: Three overarching themes were developed through reflexive thematic analysis: (1) 'The power of language'; (2) 'Healthcare professionals do not recognise the importance of context'; and (3) '"Admitting" non-adherence is difficult'. The way in which adherence is discussed in adult CF care is viewed as paternalistic and infantilising. Participants reported that healthcare professionals do not always consider the desire to balance treatment-taking with living a normal life. Unwelcome responses from healthcare professionals, and the inability to accurately self-report the amount of treatment taken made it difficult to 'admit' non-adherence.

CONCLUSIONS: A culture change is needed in CF care such that people who struggle to take their treatments are not labelled as disobedient, wilfully disobeying orders from healthcare professionals in positions of authority. Instead, an open, honest, non-judgemental approach, as recommended by healthcare agencies for over a decade, should be adopted.

PMID:37667520 | DOI:10.1080/08870446.2023.2254318

BMC Infect Dis. 2023 Sep 4;23(1):573. doi: 10.1186/s12879-023-08537-w.

ABSTRACT

Immune checkpoint inhibitors (ICIs) are drugs growingly employed in cancer immunotherapy which have significantly improved the prognosis of several tumours. ICIs act by restoring the "exhausted" immune system and increasing the number of T cells active against pathogens losing tolerogenic signalling, which has been linked to an increased risk of infectious events. We present the case of a 67-year-old man with locally advanced lung adenocarcinoma treated with the anti-PD-L1 durvalumab. Three months after immunotherapy started, an apparent radiological progression was found with elements suggesting a parenchymal superinfection associated with weight loss, asthenia, and sputum emission. A bronchoalveolar lavage resulted positive for Mycobacterium chimaera, and treatment with amikacin iv (for eight weeks) and daily azithromycin, ethambutol, and rifampicin was started. Thirteen months after treatment started, the patient is alive with a stable lung condition. The case highlights the risk of non-tuberculous mycobacteria lung disease (NTM-LD) in patients receiving ICIs treatment. We hypothesise that durvalumab induced an exaggerated immune response toward the mycobacteria, leading to immunopathology and overt clinical manifestations. Clinicians should be aware of this possibility in patients receiving ICIs developing new signs/symptoms related to the respiratory tract, especially in countries with a high prevalence of NTM-LD.

PMID:37667178 | DOI:10.1186/s12879-023-08537-w

ISME J. 2023 Sep 4. doi: 10.1038/s41396-023-01503-z. Online ahead of print.

ABSTRACT

Once acquired, hypermutation is unrelenting, and in the long-term, leads to impaired fitness due to its cumulative impact on the genome. This raises the question of why hypermutators arise so frequently in microbial ecosystems. In this work, we explore this problem by examining how the transient acquisition of hypermutability affects inter- and intra-species competitiveness, and the response to environmental insults such as antibiotic challenge. We do this by engineering Pseudomonas aeruginosa to allow the expression of an important mismatch repair gene, mutS, to be experimentally controlled over a wide dynamic range. We show that high levels of mutS expression induce genomic stasis (hypomutation), whereas lower levels of induction lead to progressively higher rates of mutation. Whole-genome sequence analyses confirmed that the mutational spectrum of the inducible hypermutator is similar to the distinctive profile associated with mutS mutants obtained from the airways of people with cystic fibrosis (CF). The acquisition of hypermutability conferred a distinct temporal fitness advantage over the wild-type P. aeruginosa progenitor strain, in both the presence and the absence of an antibiotic selection pressure. However, over a similar time-scale, acquisition of hypermutability had little impact on the population dynamics of P. aeruginosa when grown in the presence of a competing species (Staphylococcus aureus). These data indicate that in the short term, acquired hypermutability primarily confers a competitive intra-species fitness advantage.

PMID:37666975 | DOI:10.1038/s41396-023-01503-z

J Cyst Fibros. 2023 Sep 2:S1569-1993(23)00875-5. doi: 10.1016/j.jcf.2023.08.006. Online ahead of print.

ABSTRACT

BACKGROUND: As the nutritional status of people with CF (PwCF) is associated with their socioeconomic status, it is important to understand factors related to food security and food access that play a role in the nutritional outcomes of this population. We assessed the contributions of CF program-level food insecurity screening practices and area-level food access for nutritional outcomes among PwCF.

METHODS: We conducted a cross-sectional analysis of 2019 data from the U.S. CF Patient Registry (CFFPR), linked to survey data on CF program-level food insecurity screening and 2019 patient zip code-level food access. Pediatric and adult populations were analyzed separately. Nutritional outcomes were assessed with annualized BMI percentiles (CDC charts) for children and BMI (kg/m2) for adults, with underweight status defined as BMIp <10% for children and BMI <18.5 kg/m2 for adults, and overweight or obese status defined as BMIp >85% for children and BMI >25 kg/m2 for adults. Analyses were adjusted for patient sociodemographic and clinical characteristics.

RESULTS: The study population included 11,971 pediatric and 14,817 adult PwCF. A total of 137 CF programs responded to the survey, representing 71% of the pediatric sample and 45% of the CFFPR adult sample. The joint models of nutritional status as a function of both program-level food insecurity screening and area-level food access produced the following findings. Among children with CF, screening at every visit vs less frequently was associated with 39% lower odds of being underweight (OR 0.61, p = 0.019), and the effect remained the same and statistically significant after adjusting for all covariates (aOR 0.61, p = 0.047). Residence in a food desert was associated both with higher odds of being underweight (OR 1.66, p = 0.036; aOR 1.58, p = 0.008) and with lower BMIp (-4.81%, p = 0.004; adjusted -3.73%, p = 0.014). Among adults with CF, screening in writing vs verbally was associated with higher odds of being overweight (OR 1.22, p = 0.028; aOR 1.36, p = 0.002) and higher BMI (adjusted 0.43 kg/m2, p = 0.032). Residence in a food desert was associated with higher odds of being underweight (OR 1.48, p = 0.025).

CONCLUSIONS: Food insecurity screening and local food access are independent predictors of nutritional status among PwCF. More frequent screening is associated with less underweight among children with CF, whereas screening in writing (vs verbally) is associated with higher BMI among adults. Limited food access is associated with higher odds of being underweight in both children and adults with CF, and additionally with lower BMI among children with CF. Study results highlight the need for standardized, evidence-based food insecurity screening across CF care programs and for equitable food access to optimize the nutritional outcomes of PwCF.

PMID:37666711 | DOI:10.1016/j.jcf.2023.08.006

J Cyst Fibros. 2023 Sep 2:S1569-1993(23)00879-2. doi: 10.1016/j.jcf.2023.08.010. Online ahead of print.

ABSTRACT

BACKGROUND: In persons with cystic fibrosis (pwCF), little is known about the prevalence or impact of HPV on quality of life and attitudes towards vaccination.

METHODS: We conducted a national online survey of adult pwCF. We sought to determine the prevalence of self-reported HPV infection, disease-associated complications and effects on quality of life. Additionally, we investigated factors associated with vaccination status.

RESULTS: A total of 235 adult pwCF across Canada (≥18 years, 68% female) completed the survey. Forty-eight percent of female pwCF had a history of abnormal Pap smear, with 62% self-reporting a 'no' or 'low' chance of risk of HPV-associated disease. Across participants, 12% reported at least one HPV-associated complication including anogenital warts (58%), HPV-associated malignancies (34%) and cervical dysplasia requiring colposcopy (69%). Only 19% reported discussions with their CF care provider around HPV complications. Across both sexes, pwCF experienced high psychosocial burden in the domains of 'worries and concerns', 'sexual impact' and 'self-image'. Sixty percent of adult pwCF were unvaccinated for HPV. Eighty-one percent reported never having discussed HPV vaccination with their CF care provider, with similar rates in vaccinated and unvaccinated groups. Barriers to vaccination included: lack of discussions with healthcare providers (31%), insured coverage (based on age) (19%) and perceived side effects/risk (10%).

CONCLUSIONS: Across adult pwCF, we found high prevalence of HPV disease and associated HPV-psychosocial burden and low vaccination uptake. Given the limited medical discussions reported, incorporation of HPV prevention and management should be prioritized by CF care providers as part of comprehensive multimodal care.

PMID:37666710 | DOI:10.1016/j.jcf.2023.08.010

J Cyst Fibros. 2023 Sep 2:S1569-1993(23)00876-7. doi: 10.1016/j.jcf.2023.08.007. Online ahead of print.

ABSTRACT

BACKGROUND: Nontuberculous mycobacteria (NTM) are an important cause of airway infections in people with cystic fibrosis (pwCF). Isolation of NTM from respiratory specimens of pwCF do not mandate treatment in the absence of clinical and radiologic features of NTM pulmonary disease (NTM-PD), as some pwCF clear the infection without treatment and others do not appear to progress to NTM-PD despite persistent infection. An evidence-based protocol to standardize diagnosis of NTM-PD is needed to systematically identify pwCF who may benefit from treatment.

METHODS: In this multicenter observational study, eligible pwCF who are 6 years of age and older and who have had a recent positive NTM culture are systematically evaluated for NTM-PD. Participants are identified based on positive NTM culture results obtained during routine clinical care and following enrollment are evaluated for NTM-PD and CF-related comorbidities. Participants are followed in PREDICT until they meet NTM-PD diagnostic criteria and are ready to initiate NTM treatment, or until study termination. Active participants who have not met these criteria are re-consented every 5 years to enable long-term participation.

RESULTS: The primary endpoint will summarize the proportion of participants who meet the NTM-PD diagnosis definition. The time from enrollment to NTM-PD diagnosis will be derived from Kaplan-Meier estimates.

CONCLUSION: A prospective protocol to identify NTM-PD in pwCF will test if this standardized approach defines a cohort with signs and symptoms associated with NTM-PD, to assist with clinical decision making and to build a framework for future therapeutic trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02073409.

PMID:37666709 | DOI:10.1016/j.jcf.2023.08.007