Sci Rep. 2024 Jul 31;14(1):17622. doi: 10.1038/s41598-024-68166-4.

ABSTRACT

The black fungus Exophiala causes a wide range of infections from superficial to subcutaneous, but also invasive fungal infections in immunocompromised patients as well as healthy individuals. In addition, Exophiala, is a common colonizer of the air ways of patients with cystic fibrosis. However, the source of infection and mode of transmission is still unclear. The aim of this study was to investigate the presence of Exophiala in samples collected from Swedish indoor environments. We found that the Exophiala species were commonly found in dishwashers and that Exophiala dermatitidis was the most common Exophiala species, being identified in 70% (26 out of the 37) of samples. Almost all E. dermatitidis isolates had the ability to grow at 42 °C (P = 0.0002) and were catalase positive. Voriconazole and posaconazole exhibited the lowest MICs, while caspofungin and anidulafungin lack the antifungal activities in vitro. Future studies are needed to illuminate the transmission mode of the fungi.

PMID:39085337 | DOI:10.1038/s41598-024-68166-4

J Med Internet Res. 2024 Jul 31;26:e50527. doi: 10.2196/50527.

ABSTRACT

BACKGROUND: Patient-driven innovation in health care is an emerging phenomenon with benefits for patients with chronic conditions, such as cystic fibrosis (CF). However, previous research has not examined what may facilitate or hinder the implementation of such innovations from the provider perspective.

OBJECTIVE: The aim of this study was to explain variations in the adoption of a patient-driven innovation among CF clinics.

METHODS: A comparative multiple-case study was conducted on the adoption of a patient-controlled app to support self-management and collaboration with health care professionals (HCPs). Data collection and analysis were guided by the nonadoption, abandonment, spread, scale-up, and sustainability and complexity assessment tool (NASSS-CAT) framework. Data included user activity levels of patients and qualitative interviews with staff at 9 clinics (n=8, 88.9%, in Sweden; n=1, 11.1%, in the United States). We calculated the maximum and mean percentage of active users at each clinic and performed statistical process control (SPC) analysis to explore how the user activity level changed over time. Qualitative data were subjected to content analysis and complexity analysis and used to generate process maps. All data were then triangulated in a cross-case analysis.

RESULTS: We found no evidence of nonadoption or clear abandonment of the app. Distinct patterns of innovation adoption were discernable based on the maximum end-user activity for each clinic, which we labeled as low (16%-23%), middle (25%-47%), or high (58%-95%) adoption. SPC charts illustrated that the introduction of new app features and research-related activity had a positive influence on user activity levels. Variation in adoption was associated with providers' perceptions of care process complexity. A higher perceived complexity of the value proposition, adopter system, and organization was associated with lower adoption. In clinics that adopted the innovation early or those that relied on champions, user activity tended to plateau or decline, suggesting a negative impact on sustainability.

CONCLUSIONS: For patient-driven innovations to be adopted and sustained in health care, understanding patient-provider interdependency and providers' perspectives on what generates value is essential.

PMID:39083342 | DOI:10.2196/50527

Inflamm Bowel Dis. 2024 Jul 31:izae165. doi: 10.1093/ibd/izae165. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the effect of overweight and obesity at the start of anti-TNF therapy on treatment response and relapse rate in children with inflammatory bowel disease (IBD).

METHODS: This multicenter, retrospective cohort study included 22 IBD centers in 14 countries. Children diagnosed with IBD in whom antitumor necrosis factor (anti-TNF) was introduced were included; those who were overweight/obese were compared with children who were well/undernourished.

RESULTS: Six hundred thirty-seven children (370 [58%] males; mean age 11.5 ± 3.5 years) were included; 140 (22%) were in the overweight/obese group (OG) and 497 (78%) had BMI ≤1 SD (CG). The mean follow-up time was 141 ± 78 weeks (median 117 weeks). There was no difference in the loss of response (LOR) to anti-TNF between groups throughout the follow-up. However, children in OG had more dose escalations than controls. Male sex and lack of concomitant immunomodulators at the start of anti-TNF were risk factors associated with the LOR. There was no difference in the relapse rate in the first year after anti-TNF introduction; however, at the end of the follow-up, the relapse rate was significantly higher in the OG compared with CG (89 [64%] vs 218 [44%], respectively, P < .001). Univariate and multivariate analysis revealed that being overweight/obese, having UC, or being of male sex were factors associated with a higher risk for relapse.

CONCLUSIONS: Overweight/obese children with IBD were not at a higher risk of LOR to anti-TNF. Relapse in the first year after anti-TNF was introduced, but risk for relapse was increased at the end of follow-up.

PMID:39083286 | DOI:10.1093/ibd/izae165

Curr Opin Pulm Med. 2024 Aug 1. doi: 10.1097/MCP.0000000000001110. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: In 2019, the United States Food and Drug Administration approved a breakthrough therapeutic for cystic fibrosis, elexacaftor-tezacaftor-ivacaftor (ETI), because of its profound effect on lung function in large phase III clinical trials. ETI acts directly on the dysfunctional protein that causes the systemic manifestations of cystic fibrosis and also leads to improvement in nonpulmonary symptoms of cystic fibrosis. Transplant recipients were excluded from the pivotal clinical trials of ETI but may stand to benefit from correction of the underlying protein defect. Drug interactions between the three drugs in ETI and immunosuppression medications are one of the primary concerns about using ETI after transplant. No rigorous studies exist to assess the safety of ETI in transplant recipients.

RECENT FINDINGS: Multiple recent publications describe the use of ETI after solid organ transplantation, including lung and nonlung transplants, and the real-world evidence for drug interactions between ETI and immunosuppression medications. In nonlung transplant recipients, the pulmonary benefits of ETI have been confirmed, but adverse events occur and may have implications for their transplanted organ (e.g. liver biopsy in the setting of elevated transaminases). Lung transplant recipients may have higher rates of ETI discontinuation than nontransplant recipients given a lack of direct pulmonary benefit and frequency of side effects. Drug interactions have not been difficult to manage, with most studies reporting variable rates of mild to moderate increased tacrolimus levels after initiation of ETI.

SUMMARY: Limited data exist to support the use of ETI after solid organ transplantation and further research is warranted. Given the unknown risks and benefits, case by case consideration of ETI use is indicated when extra-pulmonary manifestations are present in lung transplant recipients with cystic fibrosis. Given the proven benefit in cystic fibrosis lung disease, benefits likely outweigh the risks of ETI for nonlung solid organ transplant recipients.

PMID:39082904 | DOI:10.1097/MCP.0000000000001110

Acta Myol. 2024 Jun;43(2):78-82. doi: 10.36185/2532-1900-506.

ABSTRACT

Neuromuscular diseases (NMDs) comprise a heterogeneous group of conditions characterized by extreme progressive muscle weakness leading to respiratory failure. Noninvasive mechanical ventilation (NIV) has emerged as a cornerstone in the management of respiratory complications associated with NMDs. This review aims to elucidate the role of NMV in respiratory function, improving quality of life, and prolonging survival in individuals with NMD. The physiological basis of respiratory impairment in NMDs, principles of NMV application, evidence supporting its efficacy, patient selection criteria, and potential challenges in its application are discussed.

PMID:39082325 | DOI:10.36185/2532-1900-506

Curr Opin Pulm Med. 2024 Jul 31. doi: 10.1097/MCP.0000000000001108. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Lung transplantation (LTX) has transformed care for people with cystic fibrosis (pwCF) suffering from advanced cystic fibrosis lung disease (ACFLD), and it has evolved into an accepted therapy for patients with ACFLD across all ages. We review cystic fibrosis as a major indication for LTX, particularly highlighting outcomes including survival, a changing landscape over time, and factors affecting sequelae following LTX in cystic fibrosis.

RECENT FINDINGS: Although some populations such as those undergoing lung retransplantation exhibit inferior posttransplant outcomes, LTX for pwCF provides an excellent long-term survival that has significantly improved over time, likely due to specialized cystic fibrosis center care and recognition of common comorbidities in pwCF post-LTX. There are gaps in post-LTX outcomes for pwCF, including that identified between Canada and the United States, and that seen in adolescents - both of which are likely multifactorial. In particular, the revolution in cystic fibrosis medical therapy with CFTR modulator therapy has resulted in a dramatic decline in programs performing LTX for cystic fibrosis. How durable this effect will remains to be seen.

SUMMARY: Overall, LTX remains a well accepted ultimate therapy option in patients with ACFLD if compatible with the individual's goals of care, offering an improved quality of life and maximization of overall survival.

PMID:39082306 | DOI:10.1097/MCP.0000000000001108

Kidney Int Rep. 2024 Apr 24;9(7):2286-2289. doi: 10.1016/j.ekir.2024.04.044. eCollection 2024 Jul.

NO ABSTRACT

PMID:39081754 | PMC:PMC11284363 | DOI:10.1016/j.ekir.2024.04.044

ERJ Open Res. 2024 Jul 22;10(4):00372-2024. doi: 10.1183/23120541.00372-2024. eCollection 2024 Jul.

ABSTRACT

ASPEN trial participant characteristics highlight the heterogeneity of non-cystic fibrosis bronchiectasis and global variations in clinical practice patterns https://bit.ly/447XeP0.

PMID:39081500 | PMC:PMC11288401 | DOI:10.1183/23120541.00372-2024

Ital J Pediatr. 2024 Jul 30;50(1):138. doi: 10.1186/s13052-024-01713-x.

ABSTRACT

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor (ETI) is a transmembrane conductance regulator modulator that significantly improves lung function in patients affected by cystic fibrosis (CF). This triple drug is currently not indicated in liver transplant patients, as clinical trials including subjects with previous solid organ transplantation are lacking.

CASE PRESENTATION: We report on a liver transplant girl with CF-related advanced pulmonary disease meeting clinical criteria for lung transplant, who started the triple modulator because she could not get on the lung transplant waiting list due to psycho-social motivations. Since initiation of ETI therapy, she has experienced a significant improvement in respiratory function and quality of life, without adverse effects.

CONCLUSIONS: This case shows that ETI therapy can represent a lifesaving drug for individuals without alternatives, even in liver transplant patients. The clinical benefits of the modulator overcome risks, which may be limited with a close drug monitoring of immunosuppressants serum levels and functional liver tests.

PMID:39080772 | DOI:10.1186/s13052-024-01713-x

J Cyst Fibros. 2024 Jul 29:S1569-1993(24)00782-3. doi: 10.1016/j.jcf.2024.06.014. Online ahead of print.

ABSTRACT

BACKGROUND: We undertook a human-centered design approach to design the OUTREACH study of home spirometry as a CF clinical trial endpoint. We conducted a qualitative needs assessment to elicit the perspectives of people with CF (PwCF) and research coordinators (RCs) about home spirometry in the research setting and co-produced written and video home spirometry instructions in partnership with representatives from these stakeholder groups.

METHODS: We conducted 7 focus groups of PwCF (N = 27), caregivers of children with CF (N = 6), or RCs (N = 24) to elicit current experiences, barriers and facilitators of home spirometry across 6 target areas, followed by discussion and prioritization. The co-production team, composed of 3 PwCF, 3 RCs and study team members created written and video training materials.

RESULTS: While most PwCF and caregivers found home spirometry convenient, many experienced technical barriers, reported a "learning curve", and expressed uncertainty about the quality and reliability of measurements. Major barriers identified by RCs included tailoring participant training to individual needs, scheduling remote coaching, and performing effective coaching remotely. Participants offered age-specific recommendations in key domains: training materials and procedures, remote coaching, monitoring progress and maintaining engagement. Co-produced training materials included handouts and videos on how to perform spirometry, and troubleshooting, cleaning, and maintaining home spirometers.

CONCLUSIONS: The OUTREACH design was improved by incorporating results of the needs assessment. The home spirometry training materials are freely available for public use. We hope our results and materials can help to inform the design and success of remote clinical trials of the future.

PMID:39079878 | DOI:10.1016/j.jcf.2024.06.014

J Cyst Fibros. 2024 Jul 29:S1569-1993(24)00799-9. doi: 10.1016/j.jcf.2024.07.015. Online ahead of print.

ABSTRACT

BACKGROUND: We characterized people with cystic fibrosis (CF) ineligible by genotype (not age) for currently approved CFTR modulator therapy using data from the US CF Foundation Patient Registry (CFFPR).

METHODS: We summarized clinical characteristics using CFFPR data from 2017 to 2022. Annual rate of change in percent predicted of forced expiratory volume in one second (ppFEV1) was estimated using generalized estimating equations.

RESULTS: A total of 2,790 individuals with CF met inclusion criteria. In 2022, 12 % were less than 6 years old, 16 % were age 6-12 years, 18 % age 12-18 years and 54 % were ≥18 years. The proportion identified as White was 74 %, 17 % Black, and 26 % as Hispanic. The median (IQR) age at diagnosis was 1.2 (0.5, 9.1) months for children and 3.1 (0.3, 17.4) years for adults. Median (IQR) ppFEV1 among children was 91.9 (80.3; 102.4) and among adults, 74.3 (52.4; 90.4). Pancreatic enzymes were prescribed for 77.8 %. Population-level average (95 % CI) rates of decline in ppFEV1 among the pancreatic insufficient population was -1.5 per year (-1.8; -1.2) for ages 6 to <11 years, -2.2 per year (-2.6; -1.8) for ages 12 to <18 years, and -1.5 per year (-1.7; -1.3) for adults.

CONCLUSIONS: We describe the CFTR modulator ineligible population in the US in 2017-2022. With a growing pipeline of therapies aimed at improving CFTR function for those who cannot benefit from modulators due to ineligibility, characterization of both the size and outcomes of these populations are critical to inform optimal clinical development plans and future clinical trials.

PMID:39079877 | DOI:10.1016/j.jcf.2024.07.015

JMIR Form Res. 2024 Jul 30;8:e54322. doi: 10.2196/54322.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a genetic disease affecting the respiratory and digestive systems, with recent treatment advances improving life expectancy. However, many people with CF lack adequate physical activity (PA). PA can enhance lung function and quality of life, but barriers exist. The Cystic Fibrosis Decisional Balance of Physical Activity questionnaire assesses the decisional balance for PA in adults with CF, but it is not optimal for clinical use. A digital app might overcome this limitation by improving the efficiency of administration, interpretation of results, and communication between patients and health care professionals.

OBJECTIVE: This paper presents the development process and reports on the acceptability of a web app designed to measure and monitor the decisional balance for PA in people with CF.

METHODS: This study comprised two stages: (1) the co-design of a digital app and (2) the evaluation of its acceptability among health care professionals and people with CF. A participatory approach engaged stakeholders in the app's creation. The app's acceptability, based on factors outlined in the Unified Theory of Acceptance and Use of Technology 2, is vital for its successful adoption. Participants volunteered, gave informed consent, and were aged >18 years and fluent in French. Data collection was performed through qualitative interviews, video presentations, surveys, and individual semistructured interviews, followed by quantitative and qualitative data analyses.

RESULTS: In total, 11 health care professionals, 6 people with CF, and 5 researchers were involved in the co-design phase. Results of this phase led to the coconstruction of an app named MUCO_BALAD, designed for people with CF aged ≥18 years, health care professionals, and researchers to monitor the decisional balance for PA in people with CF. In the acceptability evaluation phase, the sample included 47 health care professionals, 44 people with CF, and 12 researchers. The analysis revealed that the acceptability measures were positive and that app acceptability did not differ according to user types. Semistructured interviews helped identify positive and negative perceptions of the app and the interface, as well as missing functionalities.

CONCLUSIONS: This study assessed the acceptability of an app and demonstrated promising qualitative and quantitative results. The digital tool for measuring the decisional balance in PA for people with CF is encouraging for health care professionals, people with CF, and researchers, according to the valuable insights gained from this study.

PMID:39078689 | DOI:10.2196/54322

Nucleic Acids Res. 2024 Jul 30:gkae640. doi: 10.1093/nar/gkae640. Online ahead of print.

ABSTRACT

A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient transduction of airway epithelia to achieve therapeutic correction. Hypertonic saline (HTS) is frequently administered to people with CF to enhance mucus clearance. HTS transiently disrupts epithelial cell tight junctions, but its ability to improve gene transfer has not been investigated. Here, we asked if increasing the concentration of NaCl enhances the transduction efficiency of three gene therapy vectors: adenovirus, AAV, and lentiviral vectors. Vectors formulated with 3-7% NaCl exhibited markedly increased transduction for all three platforms, leading to anion channel correction in primary cultures of human CF epithelial cells and enhanced gene transfer in mouse and pig airways in vivo. The mechanism of transduction enhancement involved tonicity but not osmolarity or pH. Formulating vectors with a high ionic strength solution is a simple strategy to greatly enhance efficacy and immediately improve preclinical or clinical applications.

PMID:39077931 | DOI:10.1093/nar/gkae640

Oncoimmunology. 2024 Jul 27;13(1):2385124. doi: 10.1080/2162402X.2024.2385124. eCollection 2024.

ABSTRACT

Doxorubicin is a prototypical inducer of immunogenic cell death (ICD) that sensitizes to subsequent immunotherapy by PD-1 blockade. However, this systemic drug combination fails against glioblastoma, hidden behind the blood-brain barrier (BBB). A recent work delineates a biophysical method for BBB permeabilization that yields effective preclinical effects of chemoimmunotherapy.

PMID:39076248 | PMC:PMC11285269 | DOI:10.1080/2162402X.2024.2385124

BMJ Open Respir Res. 2024 Jul 29;11(1):e002033. doi: 10.1136/bmjresp-2023-002033.

ABSTRACT

BACKGROUND: Ivacaftor approval was extended to people with cystic fibrosis (CF) with ≥1 of 28 additional ivacaftor-responsive mutations in the USA in 2017 based on preclinical in vitro data. This retrospective, observational study assessed real-world clinical response to ivacaftor in people with CF with ≥1 of these mutations, using data from the US Cystic Fibrosis Foundation Patient Registry.

METHODS: Participants aged ≥2 years with ≥1 of 28 eligible mutations initiating ivacaftor between May 2017 and December 2018 were included. Clinical outcomes data were evaluated for ≤1 year before and ≤2 years after ivacaftor initiation. Participants initiating ivacaftor between May and December 2017 (2017 cohort) were used for the primary analysis because up to 2 years of post-ivacaftor-initiation data were available. Analyses were descriptive; key outcomes included percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI) and BMI z-score, pulmonary exacerbations (PEx) and hospitalisations.

RESULTS: The study included 1004 eligible participants. In the 2017 cohort (n=613), mean absolute change in ppFEV1 from pre-ivacaftor initiation was 1.9 (95% CI 1.4, 2.4) and 1.8 (95% CI 1.0, 2.7) percentage points in years 1 and 2 post-ivacaftor initiation, respectively; mean absolute change in BMI was 0.6 (95% CI 0.5, 0.7) and 1.0 (95% CI 0.8, 1.2) kg/m2 in years 1 and 2, respectively; BMI z-score was unchanged. Annualised event rates of PEx and hospitalisations per patient-year were lower with ivacaftor (0.24 (95% CI 0.21, 0.26) and 0.28 (95% CI 0.25, 0.31), respectively) compared with pre-ivacaftor initiation (0.41 (95% CI 0.37, 0.46) and 0.45 (95% CI 0.41, 0.49), respectively).

CONCLUSIONS: These real-world observational study findings support the effectiveness of ivacaftor in people with CF aged ≥2 years with selected CFTR mutations.

PMID:39074961 | DOI:10.1136/bmjresp-2023-002033

Virus Res. 2024 Jul 27:199442. doi: 10.1016/j.virusres.2024.199442. Online ahead of print.

ABSTRACT

INTRODUCTION: Pseudomonas aeruginosa is an organism well known for causing significant morbidity and mortality in people living with chronic lung conditions such as cystic fibrosis. We describe the safety, tolerability, and potential efficacy of bronchoscopic and nebulised bacteriophage administration, offering insights into a potential breakthrough for the treatment of chronic infections particularly in children and adolescents.

METHOD: A 12-year-old female (F12) and a 17-year-old male (M17), both diagnosed with cystic fibrosis and chronic P. aeruginosa lung infection, underwent bacteriophage treatment (BT). The administration involved bronchoscopic instillation and subsequent nebulisation. This was performed concurrently with intravenous antibiotics and regular physiotherapy delivered in an in-patient setting for 14 days. Microbiological, clinical, and lung function assessments were conducted to assess this treatment modality.

RESULTS: No adverse events (fever, localised reaction, wheeze or bronchospasm) occurred during BT. F12 demonstrated a 4% increase, while M17 showed a 5% improvement in FEV1% from their best FEV1% over the past three years following BT. A 12% (F12) and an 8% (M17) improvement from baseline FEV1% was observed. For F12 P. aeruginosa was not isolated from her sputum despite 12 previous hospitalisations for intravenous antibiotics.

CONCLUSION: Bronchoscopic and nebulised routes of bacteriophage administration were well-tolerated in these two adolescents. This early report underscores the potential of this treatment modality and encourages clinicians and researchers to actively explore this innovative approach.

PMID:39074617 | DOI:10.1016/j.virusres.2024.199442

Sci Rep. 2024 Jul 29;14(1):17422. doi: 10.1038/s41598-024-68511-7.

ABSTRACT

Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) improved cystic fibrosis (CF) patients' outcome. The elexacaftor/tezacaftor/ivacaftor (ETI) combination was safe and effective improving lung function in patients with different CFTR genotypes, including at least one F508del mutation. However, cases with liver damage were reported. We describe 105 CF patients heterozygous for F508del in trans with another CFTR mutation, treated for 1 year with ETI. We analyzed liver biochemical parameters and cholesterol metabolism, including lathosterol and phytosterols, surrogate markers of cholesterol de-novo synthesis and absorption, respectively. The treatment significantly improved sweat chloride, body mass index and forced expiratory volume in 1 s, whereas it caused a significant increase of total and conjugated bilirubin, ALT and GGT, even if no patients developed CF liver disease. Such alterations were less relevant than those previously observed in ETI-treated F508del homozygous patients. Furthermore, ETI treatment significantly increased serum cholesterol by enhancing its absorption (correlation between serum cholesterol and phytosterols). Whereas, we observed a normalization of de-novo biosynthesis (lathosterol reduction) that was not observed in homozygous patients. These data suggest that the second mutation in trans with the F508del contributes to reduce the liver cholesterol accumulation and thus, the triggering of liver inflammation. However, no differences in the alteration of biochemical indexes were observed between CF patients with and without liver steatosis, and between patients with different mutations in trans with the F508del. Such data suggest to further investigate the effects of ETI therapy on liver function indexes and new predictive biomarkers.

PMID:39075279 | DOI:10.1038/s41598-024-68511-7

Pediatr Pulmonol. 2024 Jul 29. doi: 10.1002/ppul.27193. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate otorhinolaryngologic findings and the relationship between aminoglycoside (AG) exposure and hearing loss in paediatric patients with cystic fibrosis (cwCF). We also aimed to investigate the genetic predisposition to AG ototoxicity by screening for m.1555A>G mutations.

METHODS: CwCF who underwent otorhinolaryngologic and audiologic examinations were retrospectively included. Clinical characteristics, ear-nose-throat related symptoms, and a history of ototoxic drug exposure were recorded. m.1555A>G mutations were retrospectively screened among patients with audiologic evaluations.

RESULTS: Two hundred thirty-four cwCF were included in this study with a median age of 10.7 (range, 6.8-14.2) years. Nasal obstruction (14.1%) was the most common symptom. Fifty-two (22.2%) patients had chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). There was a positive correlation between CRSwNP and the symptom of nasal obstruction (r:.234, p < .001), snoring (r:.179, p = .006), and sleeping with mouth open (r:.138, p = .034). One hundred forty-nine (63.6%) patients had audiologic evaluations; 14 (9.4%) had hearing impairment. No statistical significance existed between ototoxicity and IV AG exposure (p = .90). Six (42.8%) of 14 patients did not receive ototoxic drugs. One hundred nineteen (50.8%) patients were screened for m.1555A>G mutations, and none were detected.

CONCLUSIONS: Almost a quarter of the study population had CRSwNP. Neither the relationship between AGs exposure and hearing loss nor the genetic predisposition to AG ototoxicity could be shown in cwCF.

PMID:39073400 | DOI:10.1002/ppul.27193

Rev Environ Health. 2024 Jul 30. doi: 10.1515/reveh-2024-0068. Online ahead of print.

ABSTRACT

Cystic fibrosis is the most common autosomal recessive disease in the Caucasian race. Its course is chronic and progressive, with pulmonary involvement being associated with greater morbidity and mortality. One of the factors most related to worse prognosis in these patients is respiratory exacerbations. Although limited, there is evidence demonstrating that increased exposure to environmental pollution, both acute and chronic, is associated with an increase in these exacerbations. It is crucial to fully understand this relationship in order to attempt to improve the respiratory health of these patients. That is why the available evidence is reviewed and measures are established to reduce exposure to pollutants.

PMID:39072532 | DOI:10.1515/reveh-2024-0068

Heliyon. 2024 Jul 4;10(13):e34105. doi: 10.1016/j.heliyon.2024.e34105. eCollection 2024 Jul 15.

ABSTRACT

Hypersecretion of airway mucus caused by goblet cell metaplasia is a characteristic of chronic pulmonary inflammatory diseases including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). Goblet cells originate from airway progenitor club cells. However, the molecular mechanisms and features of goblet cell metaplasia in lung disease are poorly understood. Herein, public single-cell RNA sequencing datasets of human lungs were reanalyzed to explore the transitional phase as club cells differentiate into goblet cells in asthma, CF, and COPD. We found that changes in club and goblet cells during pathogenesis and cellular transition were associated with signalling pathways related to immune response, oxidative stress, and apoptosis. Moreover, other key drivers of goblet cell specification appeared to be pathologically specific, with interleukin (IL)-13 and hypoxia inducible factor 1 (HIF-1)-induced genetic changes in asthma, cystic fibrosis transmembrane conductance regulator (CFTR) mutation being present in CF, and interactions with CD8+ T cells, mitophagy, and mitochondria-induced apoptosis in COPD. In conclusion, this study revealed the similarities and differences in goblet cell metaplasia in asthma, CF, and COPD at the transcriptome level, thereby providing insights into possible novel therapeutic approaches for these diseases.

PMID:39071568 | PMC:PMC11283004 | DOI:10.1016/j.heliyon.2024.e34105