Anal Chem. 2023 Apr 4. doi: 10.1021/acs.analchem.2c05603. Online ahead of print.

ABSTRACT

Hydrogen cyanide (HCN) is a well-known toxic compound in many fields. The trace amount of endogenous HCN in human exhalation has been associated with the presence of Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) patients. Online monitoring of HCN profile is promising to screen PA infection rapidly and accurately. In this study, a gas flow-assisted negative photoionization (NPI) mass spectrometry method was developed for monitoring the single-exhalation HCN profile. The sensitivity could be optimized by introducing helium to eliminate the humidity influence and reduce the low mass cutoff effect, with improvements of a factor 150 observed. By employing a purging gas procedure and minimizing the length of the sample line, the residual and response time were greatly reduced. The limit of detection (LOD) of 0.3 ppbv and time resolution of 0.5 s were achieved. HCN profiles of exhalations from different volunteers before or after gargling with water were detected to show the performance of the method. All profiles showed a sharp peak and a stable end-tidal plateau, representing the concentration of oral cavity and end-tidal gas, respectively. The HCN concentration based on the plateau of the profile showed better reproducibility and accuracy, which indicates this method has potential application in the detection of PA infection in CF patients.

PMID:37014131 | DOI:10.1021/acs.analchem.2c05603

JAMA Netw Open. 2023 Apr 3;6(4):e238306. doi: 10.1001/jamanetworkopen.2023.8306.

ABSTRACT

IMPORTANCE: A recent National Academies of Sciences, Engineering, and Medicine study found that transplant outcomes varied greatly based on multiple factors, including race, ethnicity, and geographic location. They proposed a number of recommendations including studying opportunities to improve equity in organ allocation.

OBJECTIVE: To evaluate the role of donor and recipient socioeconomic position and region as a mediator of observed racial and ethnic differences in posttransplant survival.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included lung transplant donors and recipients with race and ethnicity information and a zip code tabulation area-defined area deprivation index (ADI) from September 1, 2011, to September 1, 2021, whose data were in the US transplant registry. Data were analyzed from June to December 2022.

EXPOSURES: Race, neighborhood disadvantage, and region of donors and recipients.

MAIN OUTCOMES AND MEASURES: Univariable and multivariable Cox proportional hazards regression were used to study the association of donor and recipient race with ADI on posttransplant survival. Kaplan-Meier method estimation was performed by donor and recipient ADI. Generalized linear models by race were fit, and mediation analysis was performed. Bayesian conditional autoregressive Poisson rate models (1, state-level spatial random effects; 2, model 1 with fixed effects for race and ethnicity, 3; model 2 excluding region; and 4: model 1 with fixed effects for US region) were used to characterize variation in posttransplant mortality and compared using ratios of mortality rates to the national average.

RESULTS: Overall, 19 504 lung transplant donors (median [IQR] age, 33 [23-46] years; 3117 [16.0%] Hispanic individuals, 3667 [18.8%] non-Hispanic Black individuals, and 11 935 [61.2%] non-Hispanic White individuals) and recipients (median [IQR] age, 60 [51-66] years; 1716 [8.8%] Hispanic individuals, 1861 [9.5%] non-Hispanic Black individuals, and 15 375 [78.8%] non-Hispanic White individuals) were included. ADI did not mediate the difference in posttransplant survival between non-Hispanic Black and non-Hispanic White recipients; it mediated only 4.1% of the survival difference between non-Hispanic Black and Hispanic recipients. Spatial analysis revealed the increased risk of posttransplant death among non-Hispanic Black recipients may be associated with region of residence.

CONCLUSIONS AND RELEVANCE: In this cohort study of lung transplant donors and recipients, socioeconomic position and region of residence did not explain most of the difference in posttransplant outcomes among racial and ethnic groups, which may be due to the highly selected nature of the pretransplant population. Further research should evaluate other potentially mediating effects contributing to inequity in posttransplant survival.

PMID:37074716 | PMC:PMC10116361 | DOI:10.1001/jamanetworkopen.2023.8306

Front Immunol. 2023 Apr 3;14:1114239. doi: 10.3389/fimmu.2023.1114239. eCollection 2023.

ABSTRACT

Previous studies have reported sex disparity in cystic fibrosis (CF) disease, with females experiencing more pulmonary exacerbations and frequent microbial infections resulting in shorter survival expectancy. This concerns both pubertal and prepubertal females, which is in support to the prominent role of gene dosage rather than the hormonal status. The underlying mechanisms are still poorly understood. The X chromosome codes for a large number of micro-RNAs (miRNAs) that play a crucial role in the post-transcriptional regulation of several genes involved in various biological processes, including inflammation. However, their level of expression in CF males and females has not been sufficiently explored. In this study, we compared in male and female CF patients the expression of selected X-linked miRNAs involved in inflammatory processes. Cytokine and chemokine profiles were also evaluated at both protein and transcript levels and cross-analyzed with the miRNA expression levels. We observed increased expression of miR-223-3p, miR-106a-5p, miR-221-3p and miR-502-5p in CF patients compared to healthy controls. Interestingly, the overexpression of miR-221-3p was found to be significantly higher in CF girls than in CF boys and this correlates positively with IL-1β. Moreover, we found a trend toward lower expression in CF girls than in CF boys of suppressor of cytokine signaling 1 (SOCS1) and the ubiquitin-editing enzyme PDLIM2, two mRNA targets of miR-221-3p that are known to inhibit the NF-κB pathway. Collectively, this clinical study highlights a sex-bias in X-linked miR-221-3p expression in blood cells and its potential contribution to sustaining a higher inflammatory response in CF girls.

PMID:37077918 | PMC:PMC10106689 | DOI:10.3389/fimmu.2023.1114239

Mycopathologia. 2023 Apr 3. doi: 10.1007/s11046-023-00725-1. Online ahead of print.

ABSTRACT

OBJECTIVE: Aspergillus fumigatus (A. fumigatus) has emerged as a significant pathogen in patients with cystic fibrosis (CF) and currently is within the top five isolated organisms reported in several international CF patient registries. A. fumigatus has been attributed to disease progression, although its role remains controversial. There is a paucity of reports on its infection dynamics, it was the aim of this study to examine time to first laboratory reports of A. fumigatus acquisition and to correlate this with patient gender and cystic fibrosis transmembrane conductance regulator (CFTR) mutation type.

METHODS: One hundred adult (≥ 18 years) CF patients were examined (50 females, 50 males; mean age 24.6 years ± 6.25 (SD), median age 24 years; maximum age 76 years). CFTR mutation groups consisted (i) F508del/F508del homozygous (n = 45), (ii) F508del/other heterozygous (n = 45) and (iii) others (n = 10). CFTR mutation type, patient gender, presence/absence of A. fumigatus and time (months) to first isolation of A. fumigatus were examined.

RESULTS: Microbiological data was examined from 100 patients from birth to present (31/12/2021), equating to 2455 patient years. A. fumigatus was isolated from 66/100 (66%) adult CF patients; (i) F508del/F508del homozygous (82%; 37/45), (ii) F508del/other heterozygous (56%; 25/45) and (iii) others (40%; 4/10). Within the F508del/other heterozygous group, 14 mutations were noted on the second allele, with R560T and R117H collectively accounting for 36% of the second mutations. Four unique allele/allele mutations were noted in the Other Mutations category. There was a trend to a higher A. fumigatus acquisition in F508del/F508del homozygous patients than with F508del/other patients (p = 0.0529). Of the 66 patients who were positive for A. fumigatus, 35(53%) were male and 31(47%) were female. The median and mean time to first isolation of A. fumigatus in all A. fumigatus-positive patients was 119.5 months and 128 months, respectively, shortest time was 12 months, longest time 288 months. There was a statistical significance in time-to-first isolation in relation to CFTR mutation group (p = 0.0272), whereby F508del homozygous individuals had their first isolation of A. fumigatus at 116.8 ± 7.9 months (mean ± standard error of the mean (SEM)) and F508del heterozygous patients had their first isolate of A. fumigatus at 150.4 months ± 13.7 months (mean ± SEM), approximately 2.75 years after their F508del homozygous peers. There was no significant difference (p = 0.12) in time to first acquisiton between males and females, whereby males had their first A. fumigatus isolate at 118 ± 9.4 months, whereas females had their first A. fumigatus isolate at 140 ± 10.8 months. The highest rate of first A. fumigatus isolation was from 4 years until 16 years and by the age of 16 years, approximately 85% of A. fumigatus-positive patients had recorded their first A. fumigatus isolate.

CONCLUSION: To minimise the risk of first acquisition of A. fumigatus, it is important that infection prevention educational messaging is delivered in the paediatric clinic, to enhance health literacy around A. fumigatus acquisition.

PMID:37012557 | DOI:10.1007/s11046-023-00725-1

Clinics (Sao Paulo). 2023 Apr 1;78:100182. doi: 10.1016/j.clinsp.2023.100182. Online ahead of print.

ABSTRACT

BACKGROUND: Lung transplantation represents the definite treatment for CF patients with advanced-stage pulmonary disease. Recent major developments in the treatment of CF indicate the need for an evaluation of lung transplantation as the current best practice in end-stage disease. This systematic review was performed to evaluate the impact of lung transplantation on health-related quality of life in patients with CF.

METHODS: PubMed was searched for studies matching the eligibility criteria between January 2000 and January 2022. OVID (MEDLINE), Google Scholar, and EBSCOhost (EMBASE) as well as bibliographies of included studies were also reviewed. Applying predetermined eligibility criteria, the included studies were selected. Predetermined forms were used to conduct a quality appraisal and implement data tabulation. Results were synthesized by narrative review. This systematic review was prospectively registered in the PROSPERO register (CRD 42022341942).

RESULTS: Ten studies (1494 patients) were included. Lung transplantation results in improvements in HRQoL in CF patients relative to their baseline waitlisted state. Up to five years postoperatively CF patients retain their HRQoL at levels similar to the general population. There are several modulating factors that impact HRQoL outcomes in CF patients post-LTx. Compared to lung recipients with other diagnoses CF patients achieve either greater or equal levels of HRQoL.

CONCLUSION: Lung transplantation conveys improved HRQoL to CF patients with the advanced-stage pulmonary disease for up to five years, and to levels comparable to the general population and non-waitlisted CF patients. This systematic review quantifies, using current evidence, the improvements in HRQoL gained by CF patients following lung transplantation.

PMID:37011456 | DOI:10.1016/j.clinsp.2023.100182

Exp Mol Med. 2023 Apr 3. doi: 10.1038/s12276-023-00970-w. Online ahead of print.

ABSTRACT

In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers to the relationship between lung inflammatory diseases (COPD, asthma, and cystic fibrosis) and bone diseases, including osteopenia/osteoporosis. Compared to chronic lung diseases, the influence of ALI on the skeleton has not been investigated until now. Therefore, we investigated the effect of ALI on bone phenotypes in mice to elucidate the underlying mechanisms. In vivo bone resorption enhancement and trabecular bone loss were observed in LPS-induced ALI mice. Moreover, chemokine (C-C motif) ligand 12 (CCL12) accumulated in the serum and bone marrow. In vivo global ablation of CCL12 or conditional ablation of CCR2 in bone marrow stromal cells (BMSCs) inhibited bone resorption and abrogated trabecular bone loss in ALI mice. Furthermore, we provided evidence that CCL12 promoted bone resorption by stimulating RANKL production in BMSCs, and the CCR2/Jak2/STAT4 axis played an essential role in this process. Our study provides information regarding the pathogenesis of ALI and lays the groundwork for future research to identify new targets to treat lung inflammation-induced bone loss.

PMID:37009797 | DOI:10.1038/s12276-023-00970-w

Front Pediatr. 2023 Mar 16;11:1158309. doi: 10.3389/fped.2023.1158309. eCollection 2023.

NO ABSTRACT

PMID:37009299 | PMC:PMC10061068 | DOI:10.3389/fped.2023.1158309

Transplant Direct. 2023 Mar 29;9(4):e1464. doi: 10.1097/TXD.0000000000001464. eCollection 2023 Apr.

ABSTRACT

Enteric hyperoxalosis (EH) is an emerging cause of kidney transplantation (KT) dysfunction. We sought to determine the prevalence of EH and factors that affect plasma oxalate (POx) among at-risk KT candidates.

METHODS: We prospectively measured POx among KT candidates evaluated at our center from 2017 to 2020 with risk factors for EH namely bariatric surgery, inflammatory bowel disease, or cystic fibrosis. EH was defined by a POx ≥10 μmol/L. Period-prevalence of EH was calculated. We compared mean POx across 5 factors: underlying condition, chronic kidney disease (CKD) stage, dialysis modality, phosphate binder type, and body mass index.

RESULTS: Of 40 KT candidates screened, 23 had EH for a 4-y period prevalence of 58%. Mean POx was 21.6 ± 23.5 μmol/L ranging from 0 to 109.6 μmol/L. 40% of screened had POx >20 μmol/L. Sleeve gastrectomy was the most common underlying condition associated with EH. Mean POx did not differ by underlying condition (P = 0.27), CKD stage (P = 0.17), dialysis modality (P = 0.68), phosphate binder (P = 0.58), and body mass index (P = 0.56).

CONCLUSIONS: Bariatric surgery and inflammatory bowel disease were associated with a high prevalence of EH among KT candidates. Contrary to prior studies, sleeve gastrectomy was also associated with hyperoxalosis in advanced CKD. POx concentrations observed in EH reached levels associated with tissue and potentially allograft deposition. Concentrations can be as high as that seen in primary hyperoxaluria. More studies are needed to assess if POx is indeed a modifiable factor affecting allograft function in patients with EH.

PMID:37009166 | PMC:PMC10065837 | DOI:10.1097/TXD.0000000000001464

ERJ Open Res. 2023 Mar 27;9(2):00473-2022. doi: 10.1183/23120541.00473-2022. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: Bronchial artery dilatation (BAD) is associated with haemoptysis in advanced cystic fibrosis (CF) lung disease. Our aim was to evaluate BAD onset and its association with disease severity by magnetic resonance imaging (MRI).

METHODS: 188 CF patients (mean±sd age 13.8±10.6 years, range 1.1-55.2 years) underwent annual chest MRI (median three exams, range one to six exams), contributing a total of 485 MRI exams including perfusion MRI. Presence of BAD was evaluated by two radiologists in consensus. Disease severity was assessed using the validated MRI scoring system and spirometry (forced expiratory volume in 1 s (FEV1) % pred).

RESULTS: MRI demonstrated BAD in 71 (37.8%) CF patients consistently from the first available exam and a further 10 (5.3%) patients first developed BAD during surveillance. Mean MRI global score in patients with BAD was 24.5±8.3 compared with 11.8±7.0 in patients without BAD (p<0.001) and FEV1 % pred was lower in patients with BAD compared with patients without BAD (60.8% versus 82.0%; p<0.001). BAD was more prevalent in patients with chronic Pseudomonas aeruginosa infection versus in patients without infection (63.6% versus 28.0%; p<0.001). In the 10 patients who newly developed BAD, the MRI global score increased from 15.1±7.8 before to 22.0±5.4 at first detection of BAD (p<0.05). Youden indices for the presence of BAD were 0.57 for age (cut-off 11.2 years), 0.65 for FEV1 % pred (cut-off 74.2%) and 0.62 for MRI global score (cut-off 15.5) (p<0.001).

CONCLUSIONS: MRI detects BAD in patients with CF without radiation exposure. Onset of BAD is associated with increased MRI scores, worse lung function and chronic P. aeruginosa infection, and may serve as a marker of disease severity.

PMID:37009019 | PMC:PMC10052726 | DOI:10.1183/23120541.00473-2022

Front Mol Biosci. 2023 Mar 17;10:1155705. doi: 10.3389/fmolb.2023.1155705. eCollection 2023.

ABSTRACT

Most of the 2,100 CFTR gene variants reported to date are still unknown in terms of their disease liability in Cystic Fibrosis (CF) and their molecular and cellular mechanism that leads to CFTR dysfunction. Since some rare variants may respond to currently approved modulators, characterizing their defect and response to these drugs is essential for effective treatment of people with CF (pwCF) not eligible for the current treatment. Here, we assessed how the rare variant, p.Arg334Trp, impacts on CFTR traffic and function and its response to existing CFTR modulators. To this end, we performed the forskolin-induced swelling (FIS) assay on intestinal organoids from 10 pwCF bearing the p.Arg334Trp variant in one or both alleles of the CFTR gene. In parallel, a novel p.Arg334Trp-CFTR expressing CFBE cell line was generated to characterize the variant individually. Results show that p.Arg334Trp-CFTR does not significantly affect the plasma membrane traffic of CFTR and evidences residual CFTR function. This CFTR variant is rescued by currently available CFTR modulators independently of the variant in the second allele. The study, predicting clinical benefit for CFTR modulators in pwCF with at least one p.Arg334Trp variant, demonstrates the high potential of personalized medicine through theranostics to extend the label of approved drugs for pwCF carrying rare CFTR variants. We recommend that this personalized approach should be considered for drug reimbursement policies by health insurance systems/national health services.

PMID:37006619 | PMC:PMC10063961 | DOI:10.3389/fmolb.2023.1155705

J Pediatr Rehabil Med. 2023 Mar 29. doi: 10.3233/PRM-210089. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to compare the result of the six-minute walk test (6MWT) in patients with cystic fibrosis (CF) aged < 20 years old and individuals without CF.

METHODS: In this cross-sectional study, 50 children and adolescents with CF and 20 children and adolescents without CF underwent the 6MWT. Vital signs before and immediately after the 6MWT and six-minute walk distance (6MWD) were evaluated.

RESULTS: The mean change in heart rate, percentage of peripheral oxygen saturation (SpO2%), systolic blood pressure, respiratory rate, and dyspnea severity during the 6MWT was significantly higher in patients with CF. In the case group, 6MWD was associated with regular chest physical therapy (CPT) and forced expiratory volume (FEV)> 80% . Patients with CF receiving regular CPT or mechanical vibration and with FEV in the first second > 80% showed better physical capacity during the 6MWT (smaller Sp02% decline and lower dyspnea perception).

CONCLUSION: Children and adolescents with CF have lower physical capacity compared to individuals without CF. CPT and mechanical vibration could be used to increase physical capacity in this population.

PMID:37005903 | DOI:10.3233/PRM-210089

Eur Respir J. 2023 Apr 1;61(4):2300216. doi: 10.1183/13993003.00216-2023. Print 2023 Apr.

NO ABSTRACT

PMID:37003613 | DOI:10.1183/13993003.00216-2023

Eur Respir J. 2023 Apr 1;61(4):2201307. doi: 10.1183/13993003.01307-2022. Print 2023 Apr.

ABSTRACT

The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel for transport of chloride and bicarbonate anions. Functional roles of CFTR have been identified in a broad range of cell types including epithelial, endothelial, immune and structural cells. While CFTR has been investigated largely in the context of inborn dysfunction in cystic fibrosis, recent evidence shows that CFTR is also affected by acquired dysfunction in COPD. In patients with COPD and smokers, CFTR impairment has been demonstrated in the upper and lower airways, sweat glands and intestines, suggesting both pulmonary and systemic defects. Cigarette smoke, a key factor in COPD development, is the major cause of acquired CFTR dysfunction. Inflammation, bacterial byproducts and reactive oxygen species can further impair CFTR expression and function. CFTR dysfunction could contribute directly to disease manifestation and progression of COPD including disturbed airway surface liquid homeostasis, airway mucus obstruction, pathogen colonisation and inflammation. Mucus plugging and neutrophilic inflammation contribute to tissue destruction, development of dysfunction at the level of the small airways and COPD progression. Acquired CFTR dysfunction in extrapulmonary organs could add to common comorbidities and the disease burden. This review explores how CFTR dysfunction may be acquired and its potential effects on patients with COPD, particularly those with chronic bronchitis. The development of CFTR potentiators and the probable benefits of CFTR potentiation to improve tissue homeostasis, reduce inflammation, improve host defence and potentially reduce remodelling in the lungs will be discussed.

PMID:37003609 | DOI:10.1183/13993003.01307-2022

Pulm Pharmacol Ther. 2023 Mar 30:102214. doi: 10.1016/j.pupt.2023.102214. Online ahead of print.

ABSTRACT

BACKGROUND: Several clinical guidelines recommend chronic inhaled therapy for pwCF (people with cystic fibrosis) and chronic Pseudomonas aeruginosa infection of the lungs.

METHODS: To demonstrate what kind of therapy regimens are used in Germany, we retrospectively analysed chronic inhaled antibiotic therapy within the cohort of the German CF Registry in 2020. For comparison we also analysed the use of inhaled antibiotics in pwCF with intermittent Pseudomonas or without Pseudomonas infection.

RESULTS: A total of 1960 pwCF had chronic P. aeruginosa infection and were retrospectively evaluated. Almost 90% (n = 1751) received at least one inhaled antibiotic. The most commonly used inhaled antibiotic was colistin solution for inhalation (55.2%), followed by aztreonam solution for inhalation (32.6%) and tobramycin solution for Inhalation (30%). Almost 56% of adults and 44% of children alternated two antibiotics for inhalation. In children, alternating colistin + tobramycin was the most often used regimen. In adults, only 23% used colistin + tobramycin; there was a wide range of treatment regimens among adults using two inhaled antibiotics alternately. 2456 pwCF had no Pseudomonas infection, but almost 24% had a chronic inhaled antibiotic therapy, while 56% of 361 pwCF and intermittent chronic Pseudomonas infection had a chronic inhaled antibiotic therapy.

CONCLUSION: In all three groups the most commonly used inhaled antibiotic was colistin solution for inhalation. Almost 56% of adults and 44% of children with chronic Pseudomonas infection alternated two antibiotics for inhalation. It will be interesting to see how the introduction of the highly effective modulator elexacaftor/tezacaftor/ivacaftor will change the use of inhaled antibiotics.

PMID:37003541 | DOI:10.1016/j.pupt.2023.102214

Am J Otolaryngol. 2023 Mar 22;44(4):103858. doi: 10.1016/j.amjoto.2023.103858. Online ahead of print.

ABSTRACT

PURPOSE: There are limited guidelines for diagnosing and managing chronic rhinosinusitis (CRS) in the cystic fibrosis (CF) population. While CF patients are known to have significant opacification on paranasal computed tomography (CT), limited evidence suggests that CT findings are not indicative of patients' symptom burden and therefore not a reliable indicator for surgical intervention. This provides a diagnostic challenge for otolaryngologists taking care of this patient population. The purpose of this study is to better define the relationship between objective imaging findings and patients' symptom severity in the CF-CRS population with the goal of providing more selective and effective patient care.

MATERIALS AND METHODS: In this retrospective cohort study, 67 patients with CF CRS had their CT scans scored according to a modified Lund Mackay CT score (LMCTS), which was compared to their Sinonasal Outcome Test scores (SNOT-22). Total SNOT-22 and individual domains were evaluated. Pearson's correlation was performed.

RESULTS: The overall mean SNOT-22 score was 32.3. The mean LMCTS was 17.6. These metrics correlate with relatively low subjective symptom scores in comparison to the high objective presence of sinus disease. While patients had high LMCTS, there was no correlation found between LMCTS and total SNOT-22 or individual SNOT-22 domains.

CONCLUSIONS: CT findings in CF CRS patients do not accurately reflect patients' symptom burden and should not be used as a primary driver in the clinical management of these patients.

PMID:37001393 | DOI:10.1016/j.amjoto.2023.103858

Ann Am Thorac Soc. 2023 Apr;20(4):512-513. doi: 10.1513/AnnalsATS.202212-1051ED.

NO ABSTRACT

PMID:37000148 | DOI:10.1513/AnnalsATS.202212-1051ED

Ann Agric Environ Med. 2023 Mar 31;30(1):31-44. doi: 10.26444/aaem/161583. Epub 2023 Mar 2.

ABSTRACT

INTRODUCTION AND OBJECTIVE: For many years vitamin D3 was known only as a regulator of the calcium-phosphate and water-electrolyte balances. Recent studies have paid special attention to other biological effects of calcitriol (the bioactive form of vitamin D3) with particular emphasis on its influence on immune function. Thus, any alterations, especially deficiencies, in the physiological level of calcitriol have serious health consequences. The aim of the study was to summarise the current state of knowledge concerning the role of vitamin D3 in selected pulmonary diseases.

REVIEW METHODS: The review was based on data obtained from articles published in PubMed between 2000-2022. Papers were reviewed for scientific merit and relevance.

BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: In the reviewed literature, much attention was paid to clinical studies focused on the role of vitamin D3 in the pathogenesis of selected respiratory diseases. As revealed in research over the last two decades, vitamin D3 deficiency increases the risk and worsens the course of asthma, cystic fibrosis, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, as well as COVID-19. Surprisingly, vitamin D supplementation has not always proved to be an effective therapeutic strategy. The review also presents the unique concept of the possibility of using vitamin D3 in the prevention and treatment of pulmonary fibrosis in the course of hypersensitivity pneumonitis.

SUMMARY: Due to the multiplicity and variety of factors that affect the metabolism of vitamin D3, effective counteracting, and even more eliminating the negative consequences of disorders in the level and activity of calcitriol in the respiratory tract, seems to be a breakneck action. On the other hand, only a deep understanding of the role of calcitriol in the pathogenesis of lung diseases provides the chance to develop an effective therapy.

PMID:36999853 | DOI:10.26444/aaem/161583

Inquiry. 2023 Jan-Dec;60:469580231159488. doi: 10.1177/00469580231159488.

ABSTRACT

Cystic Fibrosis (CF) is a genetic disorder that primarily impacts the respiratory and gastrointestinal systems. With advances in treatment and medications, the life expectancy of people with CF is continuing to increase with current life expectancy at 47 years of age. Given the increased life expectancy, people with CF are interested in childbearing but may have CF specific fertility issues that should be addressed by their CF healthcare provider. Currently, these conversations are not occurring or are suboptimal. This study aimed to investigate the practices of cystic fibrosis (CF) healthcare providers regarding fertility and fertility preservation (FP) discussions among women with CF. This was a qualitative, descriptive study. Twenty CF healthcare providers were interviewed including nurses, nurse practitioners, social workers, and dieticians among other disciplines. The semi-structured interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. Four themes emerged from the provider interviews about their fertility and FP discussion practices: (1) Change over Time; (2) CF Team Provides Primary Care including Reproductive Health Care; (3) Patient Support and Advocacy; and (4) Barriers and Facilitators to FP Discussions. The results of this study demonstrate an opportunity for CF healthcare providers to deliver patient-centered care. However, CF providers need to be educated on fertility and FP options. Additionally, there is a need for a more standardized structure of care to address the reproductive health of women with CF. The findings from this study may also be useful to non-CF providers who deliver care to women whose chronic illnesses impact their reproductive health.

PMID:36999667 | DOI:10.1177/00469580231159488

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Feb 28;48(2):275-284. doi: 10.11817/j.issn.1672-7347.2023.220372.

ABSTRACT

Mucociliary clearance system is the primary innate defense mechanism of the lung. It plays a vital role in protecting airways from microbes and irritants infection. Mucociliary clearance system, which is mediated by the actions of airway and submucosal gland epithelial cells, plays a critical role in a multilayered defense system via secreting fluids, electrolytes, antimicrobial and anti-inflammatory proteins, and mucus onto airway surfaces. Changes in environment, drugs or diseases can lead to mucus overproduction and cilia dysfunction, which in turn decrease the rate of mucociliary clearance and enhance mucus gathering. The dysfunction of mucociliary clearance system often occurs in several respiratory diseases, such as primary ciliary dysfunction, cystic fibrosis, asthma and chronic obstructive pulmonary disease, which are characterized by goblet cell metaplasia, submucosal gland cell hypertrophy, mucus hypersecretion, cilia adhesion, lodging and loss, and airway obstruction.

PMID:36999475 | DOI:10.11817/j.issn.1672-7347.2023.220372

BMC Pulm Med. 2023 Mar 30;23(1):105. doi: 10.1186/s12890-023-02398-4.

ABSTRACT

BACKGROUND: Low muscle mass is common in patients approaching lung transplantation and may be linked to worse post-transplant outcomes. Existing studies assessing muscle mass and post-transplant outcomes include few patients with cystic fibrosis (CF).

METHODS: Between May 1993 and December 2018, 152 adults with CF received lung transplants at our institution. Of these, 83 met inclusion criteria and had usable computed tomography (CT) scans. Using Cox proportional hazards regression, we evaluated the association between pre-transplant thoracic skeletal muscle index (SMI) and our primary outcome of death after lung transplantation. Secondary outcomes, including days to post-transplant extubation and post-transplant hospital and intensive care unit (ICU) length of stay, were assessed using linear regression. We also examined associations between thoracic SMI and pre-transplant pulmonary function and 6-min walk distance.

RESULTS: Median thoracic SMI was 26.95 cm2/m2 (IQR 23.97, 31.32) for men and 22.83 cm2/m2 (IQR 21.27, 26.92) for women. There was no association between pre-transplant thoracic SMI and death after transplant (HR 1.03; 95% CI 0.95, 1.11), days to post-transplant extubation, or post-transplant hospital or ICU length of stay. There was an association between pre-transplant thoracic SMI and pre-transplant FEV1% predicted (b = 0.39; 95% CI 0.14, 0.63), with higher SMI associated with higher FEV1% predicted.

CONCLUSIONS: Skeletal muscle index was low for men and women. We did not identify a significant relationship between pre-transplant thoracic SMI and post-transplant outcomes. There was an association between thoracic SMI and pre-transplant pulmonary function, confirming the potential value of sarcopenia as a marker of disease severity.

PMID:36997883 | DOI:10.1186/s12890-023-02398-4