J Clin Med. 2021 Oct 26;10(21):4952. doi: 10.3390/jcm10214952.

ABSTRACT

The ventilator bundle consists of multiple methods to reduce ventilator-associated pneumonia (VAP) rates in Intensive Care Units (ICU). The aim of the study was to evaluate how the continuous automatic pressure control in tapered cuffs of endotracheal/tracheostomy tubes applied along with continuous automatic subglottic secretion suction affect the incidence of VAP. In the prospective cohort (n = 198), the standard VAP bundle was modified by continuous automatic pressure control in taper-shaped cuff of endotracheal/tracheostomy tubes and subglottic secretion suction. VAP incidence, time to VAP onset, invasive mechanical ventilation days/free days, length of ICU stay, ICU mortality, and multidrug-resistant bacteria were assessed and compared to the retrospective cohort (n = 173) with the standard bundle (intermittent cuff pressure of standard cuff, lack of subglottic secretion suction). A smaller incidence of VAP (9.6% vs. 19.1%) and early onset VAP (1.5% vs. 8.1%) was found in the prospective compared to the retrospective cohort (p < 0.01). Patients in the prospective cohort were less likely to develop VAP (RR = 0.50; 95% CI: 0.29 to 0.85) and early-onset VAP (RR = 0.19; 95% CI: 0.05 to 0.64) and had longer time to onset VAP (median 9 vs. 5 days; p = 0.03). There was no significant difference (p > 0.05) between both cohorts in terms of invasive mechanical ventilation days/free days, length of ICU stay, ICU mortality and multidrug-resistant bacteria. Modification of the bundle for prevention of VAP can reduce early-onset VAP and total incidence of VAP and delay the time of VAP occurrence.

PMID:34768471 | DOI:10.3390/jcm10214952

J Clin Med. 2021 Oct 23;10(21):4884. doi: 10.3390/jcm10214884.

ABSTRACT

(1) Background: Pulmonary exacerbation (PEx) is one of the main factors affecting the quality of life and life expectancy in patients with cystic fibrosis (CF). Our study aimed to evaluate the change in selected pulmonary function parameters, including lung clearance index (LCI), in patients with CF diagnosed with PEx. (2) Methods: We enrolled 40 children with CF aged 6-17. They performed spirometry and multiple breath nitrogen washout (MBNW) tests during a stable condition period at the beginning and the end of intravenous antibiotic treatment. (3) Results: LCI increased by 65% and FEV1 decreased by ≥10% in 40% of patients with CF during PEx. An absolute change in LCI between a stable condition period and PEx was 1.05 (±1.92) units, which corresponds to a relative change of 11.48% (±18.61) of the baseline. The relative decrease in FEV1 was -9.22% (±12.00) and the z-score was -0.67 (±1.13). After the PEx treatment, FEV1 increased by 11.05% (±9.04) on average, whereas LCI decreased by 1.21 ± 1.59 units on average, which represented 9.42% ± 11.40 compared to the value at the beginning of PEx. (4) Conclusions: The change in LCI captures a higher proportion of events with functional impairment than FEV1 in school-age children with CF.

PMID:34768401 | DOI:10.3390/jcm10214884

J Clin Med. 2021 Oct 20;10(21):4815. doi: 10.3390/jcm10214815.

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is a serious, mechanistically not entirely resolved side effect of L-asparaginase-containing treatment for acute lymphoblastic leukemia (ALL). To find new candidate variations for AP, we conducted a genome-wide association study (GWAS).

METHODS: In all, 1,004,623 single-nucleotide variants (SNVs) were analyzed in 51 pediatric ALL patients with AP (cases) and 1388 patients without AP (controls). Replication used independent patients.

RESULTS: The top-ranked SNV (rs4148513) was located within the ABCC4 gene (odds ratio (OR) 84.1; p = 1.04 × 10-14). Independent replication of our 20 top SNVs was not supportive of initial results, partly because rare variants were neither present in cases nor present in controls. However, results of combined analysis (GWAS and replication cohorts) remained significant (e.g., rs4148513; OR = 47.2; p = 7.31 × 10-9). Subsequently, we sequenced the entire ABCC4 gene and its close relative, the cystic fibrosis associated CFTR gene, a strong AP candidate gene, in 48 cases and 47 controls. Six AP-associated variants in ABCC4 and one variant in CFTR were detected. Replication confirmed the six ABCC4 variants but not the CFTR variant.

CONCLUSIONS: Genetic variation within the ABCC4 gene was associated with AP during the treatment of ALL. No association of AP with CFTR was observed. Larger international studies are necessary to more conclusively assess the risk of rare clinical phenotypes.

PMID:34768335 | DOI:10.3390/jcm10214815

J Clin Transl Endocrinol. 2021 Oct 26;26:100270. doi: 10.1016/j.jcte.2021.100270. eCollection 2021 Dec.

ABSTRACT

Cystic Fibrosis (CF) requires lifetime multidisciplinary care to manage both pulmonary and extra pulmonary manifestations. The median age of survival for people with CF is rising and the number of adults with CF is expected to increase dramatically over the coming years. People with CF have better outcomes when managed in specialty centers, however access can be limited. Telemedicine and technology-based care solutions may help to overcome barriers to availability and improve access. This review outlines the use of telehealth for CF management. Telehealth has been utilized for CF across a broad variety of indications, even prior to the COVID-19 pandemic, and in general has been well accepted by patients and providers. There are a paucity of data, however, related to health outcomes, and the healthcare utilization specific to CF and its related comorbidities. Future studies are needed to address the questions of health outcomes, cost, burdens of telehealth and barriers to implementation.

PMID:34765457 | PMC:PMC8571077 | DOI:10.1016/j.jcte.2021.100270

Evid Based Complement Alternat Med. 2021 Nov 2;2021:7254391. doi: 10.1155/2021/7254391. eCollection 2021.

ABSTRACT

OBJECTIVE: To explore the clinical manifestations, imaging features, and gene mutation characteristics of 6 children with cystic fibrosis (CF) so as to improve the understanding and diagnosis awareness of CF in children and reduce the missed diagnosis and misdiagnosis.

METHODS: The clinical manifestations, imaging, and gene mutation data of six children with CF were collected and retrospectively analyzed.

RESULTS: Among the 6 cases of CF, there were 4 males and 2 females. Among the 6 children with CF, 5 cases presented with recurrent respiratory tract infection. Etiology suggested 3 cases of Pseudomonas aeruginosa and 2 cases of Staphylococcus aureus. 3 cases had pancreatic exocrine dysfunction, manifested as diarrhea and aliphatic diarrhea, of which 1 case had high lipase in blood examination, and pancreatic ultrasound showed rough and enhanced pancreatic echo, considering pancreatic cystic fibrosis. 2 cases of CF combined with pseudo-Bartter syndrome (PBS); 1 case involved only the biliary tract and started with cholestasis without other systemic involvement. In 2 cases of sweat test, sweat chloride ions were all >60 mmol/L. 3 cases underwent fiberoptic bronchoscopy, and a large number of sticky secretions were visible under the bronchoscopy. CT of the chest revealed thickening of the bronchial wall (3 cases), bronchiectasis (1 case), atelectasis (1 case), and thin bronchial lumen (2 cases). 1 patient was found to have small airway lesions and mosaic perfusion during follow-up. All 6 children with CF underwent genetic testing. A total of 12 CF transmembrane conductance regulator (CFTR) gene mutations were found, of which 4 mutations were not reported in the literature.

CONCLUSION: CF is a disease caused by CFTR mutation. The incidence of this disease in China is low, and the clinical manifestations have great differences. The main symptoms are respiratory symptoms. Some children have gastrointestinal symptoms and/or PBS, and some children only show a single systemic lesion.

PMID:34765005 | PMC:PMC8577894 | DOI:10.1155/2021/7254391

Front Physiol. 2021 Oct 26;12:695767. doi: 10.3389/fphys.2021.695767. eCollection 2021.

ABSTRACT

Background: Most cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to protein misfolding and degradation by the ubiquitin-proteasome system. Previous studies demonstrated that PIAS4 facilitates the modification of wild-type (WT) and F508del CFTR by small ubiquitin-like modifier (SUMO)-1, enhancing CFTR biogenesis by slowing immature CFTR degradation and producing increased immature CFTR band B. Methods: We evaluated two correction strategies using misfolding mutants, including the common variant, F508del. We examined the effects on mutant expression of co-expression with PIAS4 (E3 SUMO ligase), and/or the corrector, C18. To study the impact of these correction conditions, we transfected CFBE410- cells, a bronchial epithelial cell line, with a CFTR mutant plus: (1) empty vector, (2) empty vector plus overnight 5 μM C18, (3) PIAS4, and (4) PIAS4 plus C18. We assessed expression at steady state by immunoblot of CFTR band B, and if present, band C, and the corresponding C:B band ratio. The large PIAS4-induced increase in band B expression allowed us to ask whether C18 could act on the now abundant immature protein to enhance correction above the control level, as reported by the C:B ratio. Results: The data fell into three mutant CFTR categories as follows: (1) intransigent: no observable band C under any condition (i.e., C:B = 0); (2) throughput responsive: a C:B ratio less than control, but suggesting that the increased band C resulted from PIAS4-induced increases in band B production; and (3) folding responsive: a C:B ratio greater than control, reflecting C18-induced folding greater than that expected from increased throughput due to the PIAS4-induced band B level. Conclusion: These results suggest that the immature forms of CFTR folding intermediates occupy different loci within the energetic/kinetic folding landscape of CFTR. The evaluation of their properties could assist in the development of correctors that can target the more difficult-to-fold mutant conformations that occupy different sites within the CFTR folding pathway.

PMID:34764878 | PMC:PMC8576290 | DOI:10.3389/fphys.2021.695767

Nat Commun. 2021 Nov 11;12(1):6520. doi: 10.1038/s41467-021-26777-9.

ABSTRACT

Lung diseases, such as cystic fibrosis and COPD, are characterized by mucus obstruction and chronic airway inflammation, but their mechanistic link remains poorly understood. Here, we focus on the function of the mucostatic airway microenvironment on epigenetic reprogramming of airway macrophages (AM) and resulting transcriptomic and phenotypical changes. Using a mouse model of muco-obstructive lung disease (Scnn1b-transgenic), we identify epigenetically controlled, differentially regulated pathways and transcription factors involved in inflammatory responses and macrophage polarization. Functionally, AMs from Scnn1b-transgenic mice have reduced efferocytosis and phagocytosis, and excessive inflammatory responses upon lipopolysaccharide challenge, mediated through enhanced Irf1 function and expression. Ex vivo stimulation of wild-type AMs with native mucus impairs efferocytosis and phagocytosis capacities. In addition, mucus induces gene expression changes, comparable with those observed in AMs from Scnn1b-transgenic mice. Our data show that mucostasis induces epigenetic reprogramming of AMs, leading to changes favoring tissue damage and disease progression. Targeting these altered AMs may support therapeutic approaches in patients with muco-obstructive lung diseases.

PMID:34764283 | DOI:10.1038/s41467-021-26777-9

Nat Commun. 2021 Nov 11;12(1):6504. doi: 10.1038/s41467-021-26764-0.

ABSTRACT

The derivation of mature functional cholangiocytes from human pluripotent stem cells (hPSCs) provides a model for studying the pathogenesis of cholangiopathies and for developing therapies to treat them. Current differentiation protocols are not efficient and give rise to cholangiocytes that are not fully mature, limiting their therapeutic applications. Here, we generate functional hPSC-derived cholangiocytes that display many characteristics of mature bile duct cells including high levels of cystic fibrosis transmembrane conductance regulator (CFTR) and the presence of primary cilia capable of sensing flow. With this level of maturation, these cholangiocytes are amenable for testing the efficacy of cystic fibrosis drugs and for studying the role of cilia in cholangiocyte development and function. Transplantation studies show that the mature cholangiocytes generate ductal structures in the liver of immunocompromised mice indicating that it may be possible to develop cell-based therapies to restore bile duct function in patients with biliary disease.

PMID:34764255 | DOI:10.1038/s41467-021-26764-0

Eur Respir J. 2021 Nov 11;58(5):2101569. doi: 10.1183/13993003.01569-2021. Print 2021 Nov.

NO ABSTRACT

PMID:34764214 | DOI:10.1183/13993003.01569-2021

J Cyst Fibros. 2021 Nov 8:S1569-1993(21)02109-3. doi: 10.1016/j.jcf.2021.10.007. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies suggest that PAP-based CF protocols are suitable for newborn screening (NBS) for cystic fibrosis (CF) when newborns designated as CFSPID should not be detected. However, there are still discussions about the performance of IRT/PAP algorithms. We present the final results of a pilot study evaluating a IRT/PAP protocol with an IRT-dependent safety net (SN) conducted from 2008 to 2016 in southwestern Germany on nearly 500,000 newborns.

METHODS: To achieve reliable data, all newborns were screened using both the PAP-based and a DNA-based CFNBS algorithm. PAP quantification and genetic analysis of the four most common CFTR mutations in Germany were performed in all newborns with IRT≥99.0 percentile. NBS was rated positive if either PAP was ≥1.6 µg/l and/or at least one CFTR mutation was detected. In addition, an IRT-dependent SN resulted in positive rating for both protocols if IRT was ≥99.9 percentile. To evaluate the IRT/PAP protocol, its performance was compared to that of the IRT/DNA protocol.

RESULTS: The IRT/PAP protocol with IRT-based SN used in the study achieved a sensitivity of 94%, if false-negative detected neonates with meconium ileus and those designated as CFSPID were excluded from analysis. CF/CFSPID ratio was 92. However, PPV of the IRT/PAP+SN protocol was with 10.3% very low.

CONCLUSIONS: PAP-based CFNBS protocols can be used, if less detection of CFSPID is desired. The IRT/PAP protocol with IRT-dependent SN evaluated here achieved adequate sensitivity but should probably be used in combination with a third-tier test to also achieve an acceptable PPV.

PMID:34764021 | DOI:10.1016/j.jcf.2021.10.007

Schmerz. 2021 Nov 11. doi: 10.1007/s00482-021-00603-z. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a rare genetic multisystemic disorder with progressive abdominal and pulmonary involvement. Pain is still an underestimated symptom in CF patients.

METHODS: A comprehensive review of guidelines and scientific literature on the topic was performed and combined with findings from pain management in a young CF patient with progressive thoracic pain.

RESULTS: German CF guidelines do not cover diagnosis and management of pain in these patients. Studies from Europe and the United States report interactions between intensity of pain and mortality in CF, but do not include data on the efficacy of pain management. These data and clinical observations of a CF patient with episodes of intense thoracic pain are used to illustrate the specific challenges in pain relief.

CONCLUSION: Pain management in CF requires meticulous monitoring as well as an interdisciplinary approach and should be implemented in the German CF guidelines. The authors also want to suggest recommendations for the treatment of thoracic pain in CF. The range and severity of organ involvement complicates the use both of opioids and non-opioids. Especially opioid treatment carries the risk of hypoxia and opioid-induced constipation (OIC) and needs close medical supervision.

PMID:34762202 | DOI:10.1007/s00482-021-00603-z

J Physiol. 2021 Nov 11. doi: 10.1113/JP282143. Online ahead of print.

ABSTRACT

KEY POINTS: The genetic disease cystic fibrosis is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), a gated pathway, which controls anion flow across epithelia lining ducts and tubes in the body. This study investigated CFTR function in nasal epithelial cells from people with cystic fibrosis and CFTR variants with a range of disease severity. CFTR function varied widely in nasal epithelial cells depending on the identity of CFTR variants, but was unaffected by conditional reprogramming culture, a cell culture technique used to grow large numbers of patient-derived cells. Assessment of CFTR function in vitro in nasal epithelial cells and epithelia, and in vivo in the nasal epithelium and sweat gland highlights the complexity of genotype-phenotype-CFTR function relationships.

ABSTRACT: Dysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes a wide spectrum of disease, including cystic fibrosis (CF) and CFTR-related diseases (CFTR-RDs). Here, we investigate genotype-phenotype-CFTR function relationships using human nasal epithelial (hNE) cells from a small cohort of non-CF subjects and individuals with CF and CFTR-RDs and genotypes associated with either residual or minimal CFTR function using electrophysiological techniques. Collected hNE cells were either studied directly with the whole-cell patch-clamp technique or grown as primary cultures at an air-liquid interface after conditional reprogramming. The properties of cAMP-activated whole-cell Cl- currents in freshly isolated hNE cells identified them as CFTR-mediated. Their magnitude varied between hNE cells from individuals within the same genotype and decreased in the rank order: non-CF > CFTR residual function > CFTR minimal function. CFTR-mediated whole-cell Cl- currents in hNE cells isolated from fully differentiated primary cultures were identical to those in freshly isolated hNE cells both in magnitude and behaviour, demonstrating that conditional reprogramming culture is without effect on CFTR expression and function. For the cohort of subjects studied, CFTR-mediated whole-cell Cl- currents in hNE cells correlated well with CFTR-mediated transepithelial Cl- currents measured in vitro with the Ussing chamber technique, but not with those determined in vivo with the nasal potential difference assay. Nevertheless, they did correlate with the sweat Cl- concentration of study subjects. Thus, this study highlights the complexity of genotype-phenotype-CFTR function relationships, but emphasizes the value of conditionally reprogrammed hNE cells in CFTR research and therapeutic testing. This article is protected by copyright. All rights reserved.

PMID:34761808 | DOI:10.1113/JP282143

Ann Med. 2021 Dec;53(1):2034-2040. doi: 10.1080/07853890.2021.1999490.

ABSTRACT

BACKGROUND: The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality.

METHODS AND PATIENTS: Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality.

RESULTS: A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p<.0001; p<.0001; p=.0007, respectively). The AUC for overall mortality was similar for BSI, FACED score, and DSP (0.80 versus 0.85, p=.491; 0.85 versus 0.83, p=.831).

CONCLUSION: DSP had comparable predictive power for mortality as the well-validated BSI and FACED scores and is relatively easy to use in clinical practice.KEY MESSAGEDistance-saturation product (DSP) comprised with the product of distance walked, and lowest oxygen saturation during the 6-min walk test, which is common used in clinical practice.DSP demonstrated strong and comparable predictive power of mortality as the well-validated BSI and FACED scores in non-CF bronchiectasis patients.

PMID:34761709 | DOI:10.1080/07853890.2021.1999490

ERJ Open Res. 2021 Nov 8;7(4):00367-2021. doi: 10.1183/23120541.00367-2021. eCollection 2021 Oct.

ABSTRACT

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in vitro model to evaluate phage inhalation. Eight phages, most of which target pathogens common in cystic fibrosis, were aerosolised by jet nebuliser and administered to a real-scale computed tomography-derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebuliser and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titre reduction, primarily associated with the nebulisation process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.

PMID:34760998 | PMC:PMC8573233 | DOI:10.1183/23120541.00367-2021

ERJ Open Res. 2021 Nov 8;7(4):00426-2021. doi: 10.1183/23120541.00426-2021. eCollection 2021 Oct.

ABSTRACT

BACKGROUND: Airway clearance is a fundamental component of bronchiectasis care. Lung clearance index (LCI) is a measurement of ventilation inhomogeneity. Its responsiveness to long-term airway clearance is unknown. We aimed to compare two methods of daily airway clearance over 4 weeks: autogenic drainage (AD) and oscillating positive airway pressure (oPEP), and to determine effects of airway clearance on LCI and clinical outcomes.

METHODS: Adults with bronchiectasis naive to airway clearance were randomised to daily airway clearance with either AD or oPEP. Difference in LCI as primary outcome, spirometry, sputum volume and purulence, and quality of life were at randomisation and after 4 weeks of airway clearance.

RESULTS: 51 patients (32 women and 19 men, mean age 66.2±12.8 years) were randomised and 49 completed the study (25 AD and 24 oPEP). The LCI and forced expiratory volume in 1 s did not change between visits between groups (difference between groups 0.02), nor between visits in either group. Sputum quantity decreased in 12 out of 24 (50%) of the oPEP group, and in six out of 25 (24%) of the AD group (p=0.044). The "treatment burden" worsened or was unchanged in 70% of participants randomised to AD and 55% randomised to oPEP (p=0.038).

CONCLUSION: Sputum quantity decreased in more participants randomised to oPEP group after 1 month of daily airway clearance, with a better treatment burden. The effects of 4 weeks of airway clearance on LCI were not significant in either treatment group.

PMID:34760994 | PMC:PMC8573225 | DOI:10.1183/23120541.00426-2021

Front Microbiol. 2021 Aug 20;12:691608. doi: 10.3389/fmicb.2021.691608. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa is one of the most critical opportunistic pathogens in humans, able to cause both lethal acute and chronic lung infections. In previous work, we indicated that the small RNA ErsA plays a role in the regulatory network of P. aeruginosa pathogenicity in airways infection. To give further insight into the lifestyle functions that could be either directly or indirectly regulated by ErsA during infection, we reanalyzed the categories of genes whose transcription appeared dysregulated in an ersA knock-out mutant of the P. aeruginosa PAO1 reference strain. This preliminary analysis indicated ErsA as a candidate co-modulator of denitrification and in general, the anaerobiosis response, a characteristic physiologic state of P. aeruginosa during chronic infection of the lung of cystic fibrosis (CF) patients. To explain the pattern of dysregulation of the anaerobic-lifestyle genes in the lack of ErsA, we postulated that ErsA regulation could target the expression of Anr, a well-known transcription factor that modulates a broad regulon of anoxia-responsive genes, and also Dnr, required for the transcription activation of the denitrification machinery. Our results show that ErsA positively regulates Anr expression at the post-transcriptional level while no direct ErsA-mediated regulatory effect on Dnr was observed. However, Dnr is transcriptionally downregulated in the absence of ErsA and this is consistent with the well-characterized regulatory link between Anr and Dnr. Anr regulatory function is critical for P. aeruginosa anaerobic growth, both through denitrification and fermentation of arginine. Interestingly, we found that, differently from the laboratory strain PAO1, ErsA deletion strongly impairs the anaerobic growth by both denitrification and arginine fermentation of the RP73 clinical isolate, a multi-drug resistant P. aeruginosa CF-adapted strain. This suggests that P. aeruginosa adaptation to CF lung might result in a higher dependence on ErsA for the transduction of the multiple signals to the regulatory network of key functions for survivance in such a complex environment. Together, our results suggest that ErsA takes an upper place in the regulatory network of airways infection, transducing host inputs to biofilm-related factors, as underlined in our previous reports, and to functions that allow P. aeruginosa to thrive in low-oxygen conditions.

PMID:34759894 | PMC:PMC8575079 | DOI:10.3389/fmicb.2021.691608

Front Psychol. 2021 Oct 25;12:722740. doi: 10.3389/fpsyg.2021.722740. eCollection 2021.

ABSTRACT

Objective: Chronic physical illness affects not only patients but also their partners. Dyadic coping (DC)-the ways couples cope in dealing with a stressor such as chronic illness-has received increased attention over the last three decades. The aim of the current study was to summarize the state of research on DC in couples with chronic physical illnesses. Methods: We conducted a systematic review of qualitative, quantitative, and mixed-methods studies published between 1990 and 2020, assessing DC in couples affected by severe physical illnesses. We used DC and related search terms for the literature search in Psycinfo, Psyndex, and Medline. Five thousand three hundred thirty studies were identified in three electronic databases and 49 of these were included in the review (5,440 individuals reported on 2,820 dyads). We excluded studies on cancer, cardiovascular disease, and multiple sclerosis because of existing reviews in the respective fields. Half of the studies included were on diabetes. Other studies were on arthritis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, human immunodeficiency virus (HIV), Huntington's disease, lupus erythematosus, Parkinson's disease, renal diseases, stroke, and endometriosis. Two raters extracted data using a predefined protocol, including study quality. Results were collated in a narrative synthesis organized by illness and DC operationalization. Results: Overall, DC was associated with beneficial outcomes in physical health, well-being, and relationship satisfaction. Differential effects became apparent for certain chronic conditions potentially depending on certain disease characteristics, such as early-onset, sudden-onset, or life-threatening conditions. Conclusion: Facing challenges together as a couple seemed indispensable for adapting to a diverse range of demands related to chronic illnesses with some specific demands of particular chronic diseases. There is a need for the development of truly dyadic interventions with an eye on the specific challenges of the various chronic conditions.

PMID:34759866 | PMC:PMC8573212 | DOI:10.3389/fpsyg.2021.722740

Adv Ther. 2021 Nov 10. doi: 10.1007/s12325-021-01961-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF.

METHODS: This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases). Included patients with IPF received at least one dose of pirfenidone tablets or capsules from July 2017 to June 2019 in three populations: the inclusion population (patients treated at least once with pirfenidone during the study period, n = 288); the potential switch population (patients treated with pirfenidone during the switch period starting April 2018, n = 256); the newly treated population (patients who initiated pirfenidone during the study period, n = 162). Each of those last two populations included three subgroups (tablets, capsules, and substitution).

RESULTS: In 288 patients treated, 162 newly initiated pirfenidone during the study period: there were no meaningful differences in the baseline characteristics with the 256 patients treated during the potential switch period. In the newly treated population, 30.3% started pirfenidone treatment with tablet formulation. In the potential switch population, 44.9% of patients shifted from capsule to tablet. Half of the patients shifted to tablet formulation within the first 10 months. The mean treatment duration was 21.5 months with a mean dose of 2106.7 mg/day; 46.5% of patients discontinued treatment, mainly because of adverse events. There were fewer discontinuations in the tablets and substitution subgroups than in the capsules-only subgroup. The most reported adverse event was skin rash (11.5%). No new adverse event was identified.

CONCLUSIONS: This real-life cohort assessing the characteristics of the prescription of pirfenidone tablets and capsules suggests a good acceptability of the tablet formulation by patients with IPF.

TRIAL REGISTRATION: Clinical trial registered with www.clinicaltrials.gov (NCT04238871).

PMID:34757602 | DOI:10.1007/s12325-021-01961-x

J Cyst Fibros. 2021 Oct 29:S1569-1993(21)02105-6. doi: 10.1016/j.jcf.2021.10.003. Online ahead of print.

ABSTRACT

In this case report the potential drug-drug interaction between cytochrome P450 (CYP) 3A4 substrates tezacaftor-ivacaftor and CYP3A4/5 inhibitor clofazimine is investigated in a patient with cystic fibrosis. Exposure to tezacaftor, ivacaftor and its metabolites was assessed by determination of the area under the plasma concentration versus time curve (AUC0-24 h for tezacaftor and AUC0-12 h for ivacaftor and its metabolite) before start of clofazimine and 8 and 115 days after start of clofazimine. The AUC-ratio at day 115 and pre-start was 1.09, 1.45 and 0.747 for ivacaftor, hydroxymethyl ivacaftor and tezacaftor, respectively. This case suggests that clofazimine exhibits no clinically relevant increase in exposure to tezacaftor and ivacaftor.

PMID:34756823 | DOI:10.1016/j.jcf.2021.10.003

J Cyst Fibros. 2021 Oct 28:S1569-1993(21)02107-X. doi: 10.1016/j.jcf.2021.10.005. Online ahead of print.

ABSTRACT

BACKGROUND: The cystic fibrosis (CF) sweat gland is defective in β-adrenergically-stimulated sweat secretion in the coil and chloride reabsorption in the duct. Whereas chloride reabsorption is regularly assessed by quantitative pilocarpine iontophoresis (QPIT), the measurement of β-adrenergic sweat secretion is not yet established in clinical practice.

METHODS: A novel sweat bubble imaging protocol was developed that determines sweat secretion rates by automatic recording, processing and quality control of the kinetics of sweat droplet formation.

RESULTS: Treatment of CF patients with the CFTR modulators elexacaftor, tezacaftor and ivacaftor reduced the sweat chloride concentration measured in QPIT in the majority of patients to values in the intermediate or normal range. In contrast, the β-adrenergically-stimulated sweat secretion rate assayed by the automated bubble sweat test was normalized in only 3 patients, slightly increased in 12 patients and remained undetectable in 8 patients.

CONCLUSIONS: β-adrenergic sweat stimulation in the coil is apparently rather stringent in its requirements for a wild type CFTR conformation whereas chloride reabsorption in the duct tolerates residual structural and functional deficits of native or pharmacologically rescued mutant CFTR in the apical membrane.

PMID:34756683 | DOI:10.1016/j.jcf.2021.10.005