Life (Basel). 2024 Nov 7;14(11):1445. doi: 10.3390/life14111445.

ABSTRACT

Cystic fibrosis (CF) is a rare autosomal recessive disease most commonly affecting the Caucasian population. CF diagnosis can be a challenge due to the large spectrum of pathogenic variants in the CFTR gene and the effects of complex alleles. Next-generation sequencing has improved our understanding of the contribution of these complex alleles to the wide spectrum of CF clinical symptoms and to the response to medications. Herein, we studied nine CF patients from six unrelated families carrying the complex allele p.[Ile148Thr;Ile1023_Val1024del] with a frequency of 0.18%. All patients were from Central Mexico. This complex allele was found in trans with Class I and II pathogenic variants such as p.(Phe508del), and p.(Phe1078Profs*77)]. A targeted search of a dataset of 2217 exomes from healthy individuals revealed that eight individuals (0.18%) carried the p.(Ile148Thr) variant, but only one (0.022%), who was also born in Central Mexico, was a carrier of the complex allele. These findings show an enrichment of this p.[Ile148Thr;Ile1023_Val1024del] complex allele in Mexican CF patients in this region of Mexico. Finally, protein modeling revealed that this complex allele disrupts the secondary structure of the CFTR protein and might alter the ion flow.

PMID:39598243 | DOI:10.3390/life14111445

J Clin Med. 2024 Nov 16;13(22):6905. doi: 10.3390/jcm13226905.

ABSTRACT

Background/Objectives:Pandoraea species are Gram-negative, aerobic, rod-shaped bacteria that belong to the Burkholderiaceae family and the Betaproteobacteria class. Despite their rare occurrence in the general population, they have been increasingly observed as the causes of infection in immunocompromised individuals or patients with severe comorbidities. The present review seeks to examine all documented cases of Pandoraea spp. infections in humans, focusing on data related to epidemiology, microbiology, antimicrobial susceptibility, treatment options, and mortality rates. Methods: A systematic review was conducted through a literature search of the PubMed/MedLine and Scopus databases. This review is subjected to certain limitations regarding the data accuracy or pathogen identification molecular techniques applied in the studies. Results: In total, 29 studies provided information on 43 patients with Pandoraea spp. infections. The mean age of the patients was 42 years, and 58% were male. Cystic fibrosis was these patients' most prevalent risk factor (39.5%). The most frequently reported types of infection were lower respiratory tract infections (74.41%) and bacteremia (30.23%), followed by infective endocarditis, pancreatitis, upper respiratory tract infection, and osteomyelitis (4.65%). P. apista was the most regularly isolated species (37.2%), while antimicrobial resistance was lower for carbapenems, especially for imipenem (17.14%). The most commonly administered antibiotics included carbapenems (82%), cephalosporins, and trimethoprim/sulfamethoxazole (35.89%). The infection outcome primarily depended on the type of infection; mortality rates were high (30.23%) and particularly elevated for bloodstream infections. The protocol for this review was registered in Prospero (ID: CRD42024579385). Conclusions: Due to Pandoraea's unique antimicrobial resistance pattern and capacity to induce severe infection, clinicians should include it when making a differential diagnosis, especially in patients with severe comorbidities and immunodeficiency.

PMID:39598047 | DOI:10.3390/jcm13226905

J Clin Med. 2024 Nov 15;13(22):6887. doi: 10.3390/jcm13226887.

ABSTRACT

Background/Objectives: The extensive range of instruments designed for evaluating functional performance (FP) in chronic respiratory diseases (CRD) other than chronic obstructive pulmonary disease (COPD) presents a challenge in selecting the most appropriate one. Therefore, this systematic review aimed to summarise FP instruments, their measurement properties, their minimum clinically important differences, and their associations with CRD course-related events or prognosis in non-COPD CRD. Methods: Studies employing patient-reported or performance-based instruments to assess FP in non-COPD CRD were systematically identified in the PubMed, PEDro, Embase, and Cochrane Library databases. COPD-exclusive studies or those solely reporting exercise capacity tests were excluded. Examination focused on measurement properties and associations with CRD course-related events or prognosis. The risk of bias was evaluated using the COSMIN, Downs and Black, and PEDro checklists based on the study design. Results: A total of 216 studies across seven CRD categories [asthma, bronchiectasis, cystic fibrosis, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), pre-/post-lung-transplantation] from various study types were included. Thirty-three instruments were identified, with the SF-36 questionnaire's physical function domain being the most commonly used patient-reported tool. The 1 min sit-to-stand test was the most extensively studied performance-based measure, with its measurement properties frequently reported in non-COPD CRD studies. Associations with events were infrequently documented, primarily in ILD and PAH studies related to mortality. Conclusions: Despite the prevalent use of FP instruments, limited information exists concerning their measurement properties and clinical implications. This review furnishes a concise summary of available evidence, aiding informed clinical decisions when selecting FP tools for non-COPD CRD.

PMID:39598031 | DOI:10.3390/jcm13226887

Microorganisms. 2024 Nov 13;12(11):2307. doi: 10.3390/microorganisms12112307.

ABSTRACT

This study aimed to observe the therapeutic effect of Lactiplantibacillus plantarun HFY11 (LP-HFY11) on lincomycin hydrochloride-induced diarrhea in mice. The results showed that LP-HFY11 alleviated weight loss and intestinal and colon tissue lesions caused by diarrhea. The serum assay showed that LP-HFY11 decreased interleukin 17A (IL-17A), IL-6, 5-hydroxytryptamine, and malondialdehyde levels and increased total antioxidant capacity in mice with diarrhea. LP-HFY11 also downregulated the mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR), epidermal growth factor receptor (EGFR), and transforming growth factor beta 1 (TGFβ1) and upregulated the expression of recombinant sodium/hydrogen exchanger 1 (NHE1) and NHE4 in the colon tissues of mice with diarrhea. In conclusion, the study showed that LP-HFY11 could effectively inhibit diarrhea, and the effect was better than that of the drug Bifidobacterium tetragenous viable bacteria tablets (Bifidobacterium-TVBT).

PMID:39597698 | DOI:10.3390/microorganisms12112307

Int J Mol Sci. 2024 Nov 20;25(22):12461. doi: 10.3390/ijms252212461.

ABSTRACT

Adenoviral vectors (AdVs) are effective vectors for gene therapy due to their broad tropism, large capacity, and high transduction efficiency, making them widely used as oncolytic vectors and for creating vector-based vaccines. This review also considers the application of adenoviral vectors in oncolytic virotherapy and gene therapy for inherited diseases, analyzing strategies to enhance their efficacy and specificity. However, despite significant progress in this field, the use of adenoviral vectors is limited by their high immunogenicity, low specificity to certain cell types, and limited duration of transgene expression. Various strategies and technologies aimed at improving the characteristics of adenoviral vectors are being developed to overcome these limitations. Significant attention is being paid to the creation of tissue-specific promoters, which allow for the controlled expression of transgenes, as well as capsid modifications that enhance tropism to target cells, which also play a key role in reducing immunogenicity and increasing the efficiency of gene delivery. This review focuses on modern approaches to adenoviral vector modifications made to enhance their effectiveness in gene therapy, analyzing the current achievements, challenges, and prospects for applying these technologies in clinical practice, as well as identifying future research directions necessary for successful clinical implementation.

PMID:39596526 | DOI:10.3390/ijms252212461

Int J Mol Sci. 2024 Nov 8;25(22):11999. doi: 10.3390/ijms252211999.

ABSTRACT

Extensive evidence indicates that the compromise of airway epithelial barrier function is closely linked to the development of various diseases, posing a significant concern for global mortality and morbidity. Flavonoids, natural bioactive compounds, renowned for their antioxidant and anti-inflammatory properties, have been used for centuries to prevent and treat numerous ailments. Lately, a growing body of evidence suggests that flavonoids can enhance the integrity of the airway epithelial barrier. The objective of this study was to investigate the impact of selected flavonoids representing different subclasses, such as kaempferol (flavonol), luteolin (flavone), and naringenin (flavanone), on transepithelial electrical resistance (TEER), ionic currents, cells migration, and proliferation of a human bronchial epithelial cell line (16HBE14σ). To investigate the effect of selected flavonoids, MTT assay, trypan blue staining, and wound healing were assessed. Additionally, transepithelial resistance and Ussing chamber measurements were applied to investigate the impact of the flavonoids on the electrical properties of the epithelial barrier. This study showed that kaempferol, luteolin, and naringenin at micromolar concentrations were not cytotoxic to 16HBE14σ cells. Indeed, in MTT tests, a statistically significant change in cell metabolic activity for luteolin and naringenin was observed. However, our experiments showed that naringenin did not affect the proliferation of 16HBE14σ cells, while the effect of kaempferol and luteolin was inhibitory. Moreover, transepithelial electrical resistance measurements have shown that all of the flavonoids used in this study improved the epithelial integrity with the slightest effect of kaempferol and the significant impact of naringenin and luteolin. Finally, our observations suggest that luteolin increases the Cl- transport through cystic fibrosis transmembrane conductance regulator (CFTR) channel. Our findings reveal that flavonoids representing different subclasses exert distinct effects in the employed cellular model despite their similar chemical structures. In summary, our study sheds new light on the diverse effects of selected flavonoids on airway epithelial barrier function, underscoring the importance of further exploration into their potential therapeutic applications in respiratory health.

PMID:39596066 | DOI:10.3390/ijms252211999

Int J Mol Sci. 2024 Nov 5;25(22):11865. doi: 10.3390/ijms252211865.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive multisystem disorder caused by mutations in the cystic fibrosis conductance regulator (CFTR) anion channel. In the lungs specifically, CFTR mutations lead to changes in mucus viscosity and defective mucociliary clearance. Moreover, people with CF (pwCF) mount an insufficient immune response to invading pathogens, which predisposes individuals to chronic airway disease associated with chronic inflammation, colonization, and recurrent infections by mainly opportunistic pathogens. These chronic infections in the CF lung are typically polymicrobial and frequently harbour multidrug-resistant pathogens, making both treatment and eradication very challenging. During the last decade, the development of highly effective CFTR modulator therapy (HEMT) has led to a breakthrough in treatment options for pwCF. While the majority of pwCF now live longer and have fewer CF exacerbations, colonisation with common respiratory pathogens persists, thereby contributing to chronic inflammation and infection. Interestingly, there are limited reports examining the lung microbiome in the post-modulator era. Since ETI treatment is still quite novel and has only been used for about five years by now, this review will be one of the first discussing the current literature on the effect of ETI on CF pathogens. In addition, we will identify unanswered questions that remain from the effect of HEMT on the CF microbiome.

PMID:39595943 | DOI:10.3390/ijms252211865

Biomolecules. 2024 Oct 29;14(11):1378. doi: 10.3390/biom14111378.

ABSTRACT

VX-770 is a small-molecule CFTR potentiator that is highly efficacious in individuals with cystic fibrosis caused by mutations in CFTR that result in a defect in channel gating. While studies have reported on the mechanism of action of VX-770, there is still more to learn about the impact that it has on CFTR function in various contexts. The aim of the present study was to examine the longevity and stability of the effect of VX-770 on CFTR function in cultured airway epithelia and to measure the consequences of this interaction. The responses to acute and chronic VX-770 exposure were measured in cultures of expanded and re-differentiated primary human nasal epithelial cells. Acute VX-770 exposure resulted in an increase in CFTR-mediated currents in the absence of exogenous compounds that induce the phosphorylation/activation of CFTR, with acute exposure having the same effect as chronic exposure. The functional impact of VX-770 on CFTR was long-lasting in cultured airway epithelia, as they maintained an electrophysiological profile consistent with the saturation of CFTR with VX-770 over time periods of up to 4 days following a short (0.5 min) or low-dose (100 nM) exposure to VX-770 during an analysis in an Ussing chamber. Rinsing the apical surface prior to VX-770 exposure or exposure during the analysis in the Ussing chamber increased the interaction between VX-770 and the CFTR. Importantly, after short, low-dose exposures to VX-770, the CFTR channels in cultured epithelia appeared to remain saturated with VX-770 for extended periods of time, despite the repetitive rinsing of the apical surface. This finding has implications for patients discontinuing the use of VX-770-containing therapies.

PMID:39595555 | DOI:10.3390/biom14111378

Animals (Basel). 2024 Nov 5;14(22):3164. doi: 10.3390/ani14223164.

ABSTRACT

Relative humidity (RH) is measured in vivaria with a broad range to accommodate seasonal fluctuations. It is assumed that measurements in the room (macroenvironment) reflect those in the cage (microenvironment). However, there is limited data comparing RH in the macroenvironment to the microenvironment and how the mice may be affected by variations in RH that fall within husbandry recommendations. This study aimed to compare RH in the macroenvironment to that of the microenvironment in various group sizes of laboratory mice; and examine how variation in microenvironmental RH impacts pup survival. Temperature and RH were measured using a temperature/humidity data logger attached to a solid top cage lid. The lid was rotated across N = 48 breeding trios and N = 33 same sex cages on a C57BL/6J background. Further, once a week, a single breeding trio was selected (N = 23) to compare RH readings to weekly rates of pup loss in a larger breeding colony. Across all cages, RH was higher in the microenvironment than the macroenvironment. RH was universally higher in the summer than in the winter, and increased with group size. For breeding cages, as microenvironmental RH increased, the proportion of pups lost each week decreased in a linear relationship. No threshold of decreased mortality could be identified. These data highlight RH as a potential extrinsic factor. While these patterns are correlational, they warrant further research focused on the causative role of RH on mouse welfare.

PMID:39595217 | DOI:10.3390/ani14223164

Sci Rep. 2024 Nov 26;14(1):29298. doi: 10.1038/s41598-024-77246-4.

ABSTRACT

The triple combination elexacaftor-tezacaftor-ivacaftor (ETI) has provided unprecedented clinical benefits for people with cystic fibrosis (pwCF) and drastically transformed the outcome of this disease. We aimed to describe the evolution of lung bacterial colonization in 198 French adult pwCF taking into account the use of concomitantly respiratory treatment. We collected sputum cultures produced during the entire follow-up period starting 3 years before and ending 1 year after ETI initiation. All sputum cultures were centralized and analyzed at our bacteriological laboratory. Clinical data included pulmonary function, respiratory treatments, physiotherapy, number of IV antibiotics treatment, as well as inpatient stays. We observed a significant decrease in colonization prevalence by any CF pathogen after one year of treatment with ETI (p < 0.001). This decrease was confirmed for Pseudomonas aeruginosa, MRSA and MSSA, Stenotrophomonas maltophilia, Achromobacter spp. and nontuberculous mycobacteria (NTM). The maximal density of bacteria documented in sputum cultures decreased from 2.107 CFU/ml to 1.106 CFU/ml after one year of ETI. We also found a decrease in prevalence of Pseudomonas aeruginosa chronic colonization and in the density of Pseudomonas aeruginosa after one year of ETI. These results confirm the decrease in prevalence and bacterial density of lung colonisation for most of the CF pathogens, including Achromobacter spp, Stenotrophomonas maltophilia concomitantly to the clinical improvement. Further studies are needed to better understand the underlying mechanisms of these microbiological changes.

PMID:39592637 | DOI:10.1038/s41598-024-77246-4

J Assist Reprod Genet. 2024 Nov 26. doi: 10.1007/s10815-024-03333-0. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the genotype-phenotype correlations of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and their impact on male reproductive tract development in a cohort of Chinese patients with congenital absence of the vas deferens (CAVD).

METHODS: A total of 121 Chinese CAVD patients underwent genetic testing for CFTR and ADGRG2 mutations, semen analysis, scrotal and transrectal ultrasound examinations, and reproductive hormone measurements. The genotype-phenotype correlations were analyzed, focusing on the impact of CFTR variants on the presence or absence of the epididymis, vas deferens, seminal vesicles, and other related structures.

RESULTS: CFTR mutations were identified in 72.7% (88/121) of CAVD patients, with the IVS9-5 T variant being the most prevalent (54.5%, 66/121). Six novel CFTR variants (CFTR: L218Ffs*15, V1007Ffs*40, V938M, A566V, S605P, H949P) were identified in Chinese men. Patients with CFTR homozygous IVS9-5 T variants had a significantly lower rate of epididymal absence compared to those with one 5 T and one non-5 T variant or two non-5 T variants (p = 0.016). Notably, patients carrying at least one non-5 T variant were associated with an 8.17-fold increased risk of epididymal partial absence compared to those having the homozygous 5 T mutation (95% confidence interval 1.52-59.58, p = 0.009).

CONCLUSION: This study provides novel insights into the genotype-phenotype correlations of CFTR variants in Chinese CAVD patients, highlighting the differential impact of 5 T and non-5 T variants on male reproductive tract development. These findings provide additional information that may be helpful for genetic counseling, clinical management, and the development of personalized diagnostic and therapeutic strategies for CAVD patients.

PMID:39592508 | DOI:10.1007/s10815-024-03333-0

J Cyst Fibros. 2024 Nov 26:S1569-1993(24)01814-9. doi: 10.1016/j.jcf.2024.11.006. Online ahead of print.

ABSTRACT

BACKGROUND: This report summarizes the 2023 inaugural annual meeting of the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health (PRIME) working group. This workshop focused on mental health and elexacaftor/tezacaftor/ivacaftor (ETI).

METHODS: We reviewed existing literature and identified key gaps and study design considerations in preclinical work, pharmacokinetics/pharmacodynamics, mood/anxiety, quality of life/self-perception, neuropsychological symptoms, sleep, and symptom management.

RESULTS: Limited studies have identified behavioral changes with modulator exposure in rodent models of depression, anxiety, and cognition. Longitudinal human studies reporting mean changes generally show no change or improvement. However, case reports and single-center studies identify subgroups reporting new or worsening symptoms.

CONCLUSIONS: Future studies should focus on understanding the role of CFTR in the nervous system, defining ETI impacts in preclinical models, and mechanistic investigations. Innovative methods with larger samples and comprehensive assessments are needed to determine the incidence of new/worsening symptoms throughout the lifespan and effective management strategies.

PMID:39592379 | DOI:10.1016/j.jcf.2024.11.006

Paediatr Respir Rev. 2024 Oct 18:S1526-0542(24)00078-2. doi: 10.1016/j.prrv.2024.10.002. Online ahead of print.

ABSTRACT

Climate change may have devastating effects on the pathogenesis of non-cystic fibrosis bronchiectasis in children since it affects the biological cycle of the respiratory pathogens and alters the human respiratory defense mechanisms. Bronchiectasis in children has been identified as an emerging global epidemic that has attracted the attention of the medical community over recent years. Pediatric pulmonologists should be aware of the consequences of climate change on children with bronchiectasis and plan strategies to ameliorate these effects.

PMID:39592275 | DOI:10.1016/j.prrv.2024.10.002

J Child Health Care. 2024 Nov 26:13674935241303539. doi: 10.1177/13674935241303539. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) affects not just patients but also their families, highlighting the need for a comprehensive care approach. This descriptive qualitative study aimed to explore the informational needs of family caregivers of children with CF, focusing on how these needs can be addressed within a Patient and Family-Centered Care (PFCC) framework. The study was conducted at a public hospital in Brazil. Thirteen caregivers were interviewed, and their responses were analyzed using content analysis guided by PFCC principles. Analysis revealed three primary themes: Types of Information for Family Caregivers of Children and Adolescents with CF; sources of Information for Family caregivers of Children and Adolescents with CF; and Beyond Information: the need for emotional support and family-centered care in CF management. Caregivers sought comprehensive information about CF management from healthcare professionals and informal sources like social media. Our findings emphasize the diverse and evolving informational needs of family caregivers. Overall, this study underscores the necessity of incorporating PFCC principles, especially those addressing information sharing, in managing CF, extending beyond medical treatment to include emotional support and active family participation in care and decision-making processes.

PMID:39589857 | DOI:10.1177/13674935241303539

Intern Emerg Med. 2024 Nov 26. doi: 10.1007/s11739-024-03822-1. Online ahead of print.

NO ABSTRACT

PMID:39589635 | DOI:10.1007/s11739-024-03822-1

Open Med (Wars). 2024 Nov 12;19(1):20241082. doi: 10.1515/med-2024-1082. eCollection 2024.

ABSTRACT

OBJECTIVE: To explore the role of cystic fibrosis transmembrane conduction regulator (CFTR)-Epithelial sodium channel (ENaC) in spinal cord edema after spinal cord injury (SCI) and the related mechanism.

METHODS: Lipopolysaccharide (LPS)-treated M1830 astrocytes were applied as the SCI in vitro model. Immunohistochemistry, real-time PCR, and Western blotting were utilized to detect CFTR and ENaC expression. Enzyme-linked immunosorbent assay was used to measure inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-18. Transmission electron microscope examined ultrastructure changes, while CFTR-172 or Capsazepine treatment assessed their effects on edema and inflammation. Western blot analysis was employed to evaluate the PI3K, p-PI3K, AKT, and p-AKT signaling pathways in treated cells.

RESULTS: LPS-treated M1830 cells exhibited increased levels of CFTR and pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-18, alongside decreased ENaC expression and suppressed p-PI3K/PI3K and p-AKT/AKT levels. Degeneration of the myelin sheath and axons was observed in LPS-treated M1830, while changes in ultrastructural were recovered after adding CFTR-172 or Capsazepine. The level of CFTR, TNF-α, IL-1β, IL-6, and IL-18 was decreased, while the level of ENaC, p-PI3K/PI3K, and p-AKT/AKT was increased obviously in LPS-treated M1830 with CFTR-172, Capsazepine, or IGF-1.

CONCLUSION: Down-regulation of CFTR and up-regulation of ENaC can attenuate inflammation in SCI by activating the PI3K/AKT signaling pathway, highlighting a new therapeutic approach for SCI treatment. These findings address a critical gap in current SCI treatments and suggest a novel intervention strategy targeting ion channel regulation.

PMID:39588386 | PMC:PMC11587918 | DOI:10.1515/med-2024-1082

ERJ Open Res. 2024 Nov 25;10(6):00412-2024. doi: 10.1183/23120541.00412-2024. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Bronchiectasis is a complex, chronic disease with geographic and ethnic diversity. While the most substantial cohort studies have been conducted in Europe and the USA, Canada also faces considerable challenges. The comprehensive Canadian Bronchiectasis and Nontuberculous Mycobacterial (NTM) Registry aims to 1) outline the clinical characteristics and natural history of bronchiectasis in Canada, 2) identify risk factors contributing to disease progression within Canadians, 3) integrate comprehensive clinical information to better understand the phenotypes of bronchiectasis and 4) support the development of large-scale, randomised controlled trials in Canada.

METHODS: The Canadian Bronchiectasis and NTM Registry is an ongoing prospective, longitudinal, multi-centre, observational cohort study. It aims to enrol at least 2000 participants to collect data such as medical history, aetiological assessments, lung function tests, microbiological profiles, radiographic evaluations, comorbidities and quality of life (QoL) metrics. Participants will undergo annual follow-ups to gather longitudinal information regarding outcomes, treatments and changes in QoL. The inclusion criteria are a diagnosis of bronchiectasis by clinical history and computed tomography and/or pulmonary NTM infection as defined by American Thoracic Society/Infectious Diseases Society of America guidelines. The study's protocol received ethical approval from the lead site, the University of Calgary, with future additional approval from local ethics committees at all participating centres.

DISCUSSION: The outcomes of the registry will be instrumental in uncovering the clinical traits and natural history of bronchiectasis. This longitudinal study will be used for analysis to form evidence-based clinical practices and serve as a resource in Canada to inform future studies in NTM and bronchiectasis.

PMID:39588081 | PMC:PMC11587054 | DOI:10.1183/23120541.00412-2024

Oncoimmunology. 2024 Dec 31;13(1):2425465. doi: 10.1080/2162402X.2024.2425465. Epub 2024 Nov 4.

ABSTRACT

Apoptosis, necroptosis and pro-inflammatory NF-κB-dependent signaling are repressed by receptor-interacting serine/threonine-protein kinase 1 (RIPK1). A recent paper in Immunity describes a small molecule inducing the proteolytic degradation of RIPK1. In preclinical experiments, this RIPK1 inhibitor improved the anticancer efficacy of radiotherapy, immunotherapy (with PD-1 blockade) and radioimmunotherapy (with CTLA-4 blockade).

PMID:39585102 | PMC:PMC11540075 | DOI:10.1080/2162402X.2024.2425465

Am J Respir Crit Care Med. 2024 Nov 25. doi: 10.1164/rccm.202410-2080ST. Online ahead of print.

ABSTRACT

Background: There is increasing interest in the use of home-based monitoring in people with chronic lung diseases to improve access to care, support patient self-management, and facilitate the collection of information for clinical care and research. However, integration of home-based monitoring into clinical and research settings requires careful consideration of test performance and other attributes. There is no published guidance from professional respiratory societies to advance the science of home-based monitoring for chronic lung disease. Methods: An international multidisciplinary panel of 32 clinicians, researchers, patients, and caregivers developed a multidimensional framework for the evaluation of home-based monitoring in chronic lung disease developed through consensus using a modified Delphi survey. We also present an example of how the framework could be used to evaluate home-based monitoring using spirometry and pulse oximetry in adults with asthma, bronchiectasis/cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and interstitial lung disease (ILD). Results: The PANACEA framework includes seven domains (test Performance, disease mANAgement, Cost, patient Experience, clinician Experience, researcher Experience, and Access) to assess the degree to which home-based monitoring assessments meet the conditions for clinical and research use in chronic lung disease. Knowledge gaps and recommendations for future research of home spirometry and pulse oximetry in asthma, bronchiectasis/CF, COPD, and ILD were identified. Conclusion: The development of the PANACEA framework allows standardized evaluation of home-based monitoring in chronic lung diseases to support clinical application and future research.

PMID:39585746 | DOI:10.1164/rccm.202410-2080ST

Int J Neonatal Screen. 2024 Nov 22;10(4):76. doi: 10.3390/ijns10040076.

ABSTRACT

The California Genetic Disease Screening Program (GDSP) employs a fixed immunoreactive trypsinogen (IRT) cutoff followed by molecular testing to screen newborns for cystic fibrosis (CF). The cutoffs approximate a 1.6% yearly IRT screen-positive rate; however, seasonal variation in IRT population means has led us to develop a model to establish fixed IRT cutoffs that anticipate seasonal variation and minimize missed cases below cutoff. We utilized an ARIMA model to fit monthly IRT screen-positive percentiles and estimated regular seasonal expectations. We established a retrospective cohort followed for at least 1.5 years to capture missed false-negative CF cases. We compared missed CF cases identified by seasonal cutoffs vs. floating cutoffs. GDSP screened 7,410,003 newborns, from July 2007 to December 2022, and missed 36 CF cases below the fixed cutoff; five of the 36 were within 3 ng/mL below the cutoff. There was a regular, seasonal cycle that varied from 1.4% in summer to 1.8% in winter. We would have missed 59 CF cases using a 1.6% daily floating cutoff. California would need to use a 4% daily floating cutoff to improve our current detection rate, which would double the number of specimens sent for costly molecular analysis.

PMID:39584999 | DOI:10.3390/ijns10040076