ACS Med Chem Lett. 2023 Apr 27;14(6):794-801. doi: 10.1021/acsmedchemlett.3c00089. eCollection 2023 Jun 8.

ABSTRACT

New derivatives of aminoglycosides with a side chain 1,2-aminoalcohol at the 5" position of ring III were designed, synthesized, and biologically evaluated. The novel lead structure (compound 6), exhibiting substantially enhanced selectivity toward eukaryotic versus prokaryotic ribosome, high readthrough activity, and considerably lower toxicity than the previous lead compounds, was discovered. Balanced readthrough activity and toxicity of 6 were demonstrated in three different nonsense DNA-constructs underlying the genetic diseases, cystic fibrosis and Usher syndrome, and in two different cell lines, baby hamster kidney and human embryonic kidney cells. Molecular dynamics simulations within the A site of the 80S yeast ribosome demonstrated a remarkable kinetic stability of 6, which potentially determines its high readthrough activity.

PMID:37312846 | PMC:PMC10258827 | DOI:10.1021/acsmedchemlett.3c00089

Microbiome. 2023 Jun 13;11(1):132. doi: 10.1186/s40168-023-01543-9.

ABSTRACT

BACKGROUND: Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota.

RESULTS: Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage.

CONCLUSIONS: Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract.

PMID:37312128 | DOI:10.1186/s40168-023-01543-9

Folia Microbiol (Praha). 2023 Jun 13. doi: 10.1007/s12223-023-01070-y. Online ahead of print.

ABSTRACT

The polymicrobial biofilm (PMBF) is formed when microbes from multiple species co-aggregate into an envelope made of extra polymeric substances (EPS) that keep the microbes safe from external stresses. The formation of PMBF has been linked to a variety of human infections, including cystic fibrosis, dental caries, urinary tract infections, etc. Multiple microbial species co-aggregation during an infection results in a recalcitrant biofilm formation, which is a seriously threatening phenomenon. It is challenging to treat polymicrobial biofilms since they contain multiple microbes which show drug resistance to various antibiotics/antifungals. The present study discusses various approaches by which an antibiofilm compound works. Depending on their mode of action, antibiofilm compounds can block the adhesion of cells to one another, modify membranes/walls, or disrupt quorum-sensing systems.

PMID:37310652 | DOI:10.1007/s12223-023-01070-y

Genet Med. 2023 Jun 9:100867. doi: 10.1016/j.gim.2023.100867. Online ahead of print.

NO ABSTRACT

PMID:37310422 | DOI:10.1016/j.gim.2023.100867

Antimicrob Agents Chemother. 2023 Jun 13:e0037923. doi: 10.1128/aac.00379-23. Online ahead of print.

ABSTRACT

We conducted in vitro antimicrobial susceptibility testing of 267 Achromobacter isolates for 16 antibiotics from 2017 to 2022. The highest susceptibility was found for piperacillin-tazobactam (70%) and ceftazidime-avibactam (62%). Between 30% and 49% of strains were susceptible to tigecycline, ceftazidime, and meropenem. We applied species-specific Achromobacter xylosoxidans breakpoints for piperacillin-tazobactam, meropenem, and trimethoprim-sulfamethoxazole and EUCAST pharmacokinetic/pharmacodynamic (PK/PD) breakpoints for the others. A. xylosoxidans was the most frequently isolated species, followed by Achromobacter insuavis and Achromobacter ruhlandii.

PMID:37310234 | DOI:10.1128/aac.00379-23

Respir Med Res. 2023 Apr 21;84:101020. doi: 10.1016/j.resmer.2023.101020. Online ahead of print.

ABSTRACT

BACKGROUND: Changes in respiratory functions negatively affect the physical activity (PA) levels of patients with bronchiectasis. Therefore, detecting the most frequently used assessments of PA is essential as determining related factors and improving PA. This review study aimed to investigate the PA levels, compare levels with the recommended PA guidelines, determine the outcome measurements of PA and examine the determinants related to PA in patients with bronchiectasis.

METHOD: This review was conducted using databases of MEDLINE, Web of Science, and PEDro. The searched terms were the variations of the words "bronchiectasis" and "physical activity". Full texts of cross-sectional studies and clinical trials were included. Two authors independently screened the studies for inclusion.

RESULT: The initial search identified 494 studies. A hundred articles were selected for full-text review. Following the application of the eligibility process, 15 articles were included. Twelve studies used activity monitors and five studies used questionnaires. The studies that used activity monitors presented daily step counts. The mean number of steps ranged between 4657 and 9164 for adult patients. It was approximately 5350 steps/day in older patients. One study investigated children's PA level reported 8229 steps/day. The functional exercise capacity, dyspnea, FEV1 and, quality of life as related determinants with PA have been reported in the studies.

CONCLUSION: PA levels of patients with non-cystic fibrosis bronchiectasis were lower than the recommended levels. The objective measurements were frequently used in PA assessment. In further studies, it is needed to investigate the related determinants of PA in patients.

PMID:37307618 | DOI:10.1016/j.resmer.2023.101020

Ann Intern Med. 2023 Jun 13. doi: 10.7326/L23-0112. Online ahead of print.

NO ABSTRACT

PMID:37307583 | DOI:10.7326/L23-0112

Aging Clin Exp Res. 2023 Jun 12. doi: 10.1007/s40520-023-02451-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Nowadays, smartphones are equipped with the most sophisticated hardware which provides the opportunity to develop specific smartphone apps to analyze kinetic and kinematic parameters during sit-to-stand test in a clinical setting. The aims were to ascertain whether a new Android video-analysis based-App is comparable to the previously validated Apple-App for measuring time, velocity and power during sit-to-stand test, to determine its reliability and discriminant validity.

METHODS: One-hundred sixty-one older adults (61-86 years) were recruited from an elderly social center. Sit-to-stand variables were simultaneously recorded through the Android and Apple-App. Their validity and inter-rater, intra-rater, and test-retest reliability was tested using an intraclass correlation coefficient (ICC2-1). Low gait speed (< 1.0 m/s), low physical performance (Short Physical Performance Battery < 10 points), and sarcopenia (EWGSOP2 guideline) were used to determine discriminant validity which was reported as the area under the curves (AUC) and their effect sizes (Hedges' g) for independent sample t-test.

RESULTS: Excellent reproducibility (ICC2-1 > 0.85) and strong agreement (ICC2-1 > 0.90) between operating systems for sit-to-stand variables derived from the App was found. Older adults classified as sarcopenic (11.2%), low physical performance (15.5%), or reduced gait speed (14.3%) showed worse sit-to-stand time, velocity and power with large effect sizes (Hedges' g: > 0.8) compared to their respective counterpart. These variables showed the acceptable-to-excellent ability to identify low gait speed, low physical performance, and sarcopenic older adults (AUC-range: 0.73-0.82).

CONCLUSION: The new Sit-to-Stand App running on the Android operating system is comparable to the previously validated Apple App. Excellent reproducibility and acceptable-to-excellent discriminant validity were found.

PMID:37306926 | DOI:10.1007/s40520-023-02451-6

Microbiol Spectr. 2023 Jun 12:e0035223. doi: 10.1128/spectrum.00352-23. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is the most common pathogen infecting cystic fibrosis (CF) lungs, causing acute and chronic infections. Intrinsic and acquired antibiotic resistance allow P. aeruginosa to colonize and persist despite antibiotic treatment, making new therapeutic approaches necessary. Combining high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses for drugs. This study screened a drug library of 3,386 drugs, mostly FDA approved, to identify antimicrobials against P. aeruginosa under physicochemical conditions relevant to CF-infected lungs. Based on the antibacterial activity, assessed spectrophotometrically against the prototype RP73 strain and 10 other CF virulent strains, and the toxic potential evaluated toward CF IB3-1 bronchial epithelial cells, five potential hits were selected for further analysis: the anti-inflammatory and antioxidant ebselen, the anticancer drugs tirapazamine, carmofur, and 5-fluorouracil, and the antifungal tavaborole. A time-kill assay showed that ebselen has the potential to cause rapid and dose-dependent bactericidal activity. The antibiofilm activity was evaluated by viable cell count and crystal violet assays, revealing carmofur and 5-fluorouracil as the most active drugs in preventing biofilm formation regardless of the concentration. In contrast, tirapazamine and tavaborole were the only drugs actively dispersing preformed biofilms. Tavaborole was the most active drug against CF pathogens other than P. aeruginosa, especially against Burkholderia cepacia and Acinetobacter baumannii, while carmofur, ebselen, and tirapazamine were particularly active against Staphylococcus aureus and B. cepacia. Electron microscopy and propidium iodide uptake assay revealed that ebselen, carmofur, and tirapazamine significantly damage cell membranes, with leakage and cytoplasm loss, by increasing membrane permeability. IMPORTANCE Antibiotic resistance makes it urgent to design new strategies for treating pulmonary infections in CF patients. The repurposing approach accelerates drug discovery and development, as the drugs' general pharmacological, pharmacokinetic, and toxicological properties are already well known. In the present study, for the first time, a high-throughput compound library screening was performed under experimental conditions relevant to CF-infected lungs. Among 3,386 drugs screened, the clinically used drugs from outside infection treatment ebselen, tirapazamine, carmofur, 5-fluorouracil, and tavaborole showed, although to different extents, anti-P. aeruginosa activity against planktonic and biofilm cells and broad-spectrum activity against other CF pathogens at concentrations not toxic to bronchial epithelial cells. The mode-of-action studies revealed ebselen, carmofur, and tirapazamine targeted the cell membrane, increasing its permeability with subsequent cell lysis. These drugs are strong candidates for repurposing for treating CF lung P. aeruginosa infections.

PMID:37306577 | DOI:10.1128/spectrum.00352-23

Front Cell Infect Microbiol. 2023 May 26;13:1183681. doi: 10.3389/fcimb.2023.1183681. eCollection 2023.

ABSTRACT

Pseudomonas aeruginosa is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The pqs QS system of P. aeruginosa is responsible for the biosynthesis of diverse 2-alkyl-4-quinolones (AQs), of which 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) function as QS signal molecules. Transcriptomic analyses revealed that HHQ and PQS influenced the expression of multiple genes via PqsR-dependent and -independent pathways whereas 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) had no effect on P. aeruginosa transcriptome. HQNO is a cytochrome bc 1 inhibitor that causes P. aeruginosa programmed cell death and autolysis. However, P. aeruginosa pqsL mutants unable to synthesize HQNO undergo autolysis when grown as colony biofilms. The mechanism by which such autolysis occurs is not understood. Through the generation and phenotypic characterization of multiple P. aeruginosa PAO1 mutants producing altered levels of AQs in different combinations, we demonstrate that mutation of pqsL results in the accumulation of HHQ which in turn leads to Pf4 prophage activation and consequently autolysis. Notably, the effect of HHQ on Pf4 activation is not mediated via its cognate receptor PqsR. These data indicate that the synthesis of HQNO in PAO1 limits HHQ-induced autolysis mediated by Pf4 in colony biofilms. A similar phenomenon is shown to occur in P. aeruginosa cystic fibrosis (CF) isolates, in which the autolytic phenotype can be abrogated by ectopic expression of pqsL.

PMID:37305419 | PMC:PMC10250642 | DOI:10.3389/fcimb.2023.1183681

Front Cell Infect Microbiol. 2023 May 25;13:1144157. doi: 10.3389/fcimb.2023.1144157. eCollection 2023.

ABSTRACT

Pseudomonas aeruginosa dominates the complex polymicrobial cystic fibrosis (CF) airway and is a leading cause of death in persons with CF. Interestingly, oral streptococcal colonization has been associated with stable CF lung function. The most abundant streptococcal species found in stable patients, Streptococcus salivarius, has been shown to downregulate pro-inflammatory cytokines in multiple colonization models. However, no studies have demonstrated how S. salivarius potentially improves lung function. Our lab previously demonstrated that the P. aeruginosa exopolysaccharide Psl promotes S. salivarius biofilm formation in vitro, suggesting a possible mechanism by which S. salivarius is incorporated into the CF airway microbial community. In this study, we demonstrate that co-infection of rats leads to enhanced S. salivarius colonization and reduced P. aeruginosa colonization. Histological scores for tissue inflammation and damage are lower in dual-infected rats compared to P. aeruginosa infected rats. Additionally, pro-inflammatory cytokines IL-1β, IL-6, CXCL2, and TNF-α are downregulated during co-infection compared to P. aeruginosa single-infection. Lastly, RNA sequencing of cultures grown in synthetic CF sputum revealed that P. aeruginosa glucose metabolism genes are downregulated in the presence of S. salivarius, suggesting a potential alteration in P. aeruginosa fitness during co-culture. Overall, our data support a model in which S. salivarius colonization is promoted during co-infection with P. aeruginosa, whereas P. aeruginosa airway bacterial burden is reduced, leading to an attenuated host inflammatory response.

PMID:37305417 | PMC:PMC10248150 | DOI:10.3389/fcimb.2023.1144157

Front Vet Sci. 2023 May 26;10:1179836. doi: 10.3389/fvets.2023.1179836. eCollection 2023.

ABSTRACT

The study of biliary physiology and pathophysiology has long been hindered by the lack of in vitro models that accurately reflect the complex functions of the biliary system. Recent advancements in 3D organoid technology may offer a promising solution to this issue. Bovine gallbladder models have recently gained attention in the investigation of human diseases due to their remarkable similarities in physiology and pathophysiology with the human gallbladder. In this study, we have successfully established and characterized bovine gallbladder cholangiocyte organoids (GCOs) that retain key characteristics of the gallbladder in vivo, including stem cell properties and proliferative capacity. Notably, our findings demonstrate that these organoids exhibit specific and functional CFTR activity. We believe that these bovine GCOs represent a valuable tool for studying the physiology and pathophysiology of the gallbladder with human significance.

PMID:37303723 | PMC:PMC10250713 | DOI:10.3389/fvets.2023.1179836

Cureus. 2023 May 9;15(5):e38778. doi: 10.7759/cureus.38778. eCollection 2023 May.

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is an underdiagnosed lung condition in patients with asthma and cystic fibrosis. Its clinical and diagnostic manifestations result from an allergic response to multiple antigens expressed by Aspergillus fumigatus, which colonize the bronchial mucus. This report presents the case of a 73-year-old female patient referred to our hospital for uncontrolled asthma for 35 years. The diagnosis of ABPA was made on the basis of clinical symptoms, peripheral blood eosinophilia, elevated total serum immunoglobulin E, positive aspergillus serology, and bronchiectasis with mucoid impaction. Systemic corticosteroids and antifungal therapy came up with satisfactory clinical results.

PMID:37303384 | PMC:PMC10250130 | DOI:10.7759/cureus.38778

Int Forum Allergy Rhinol. 2023 Jun 10. doi: 10.1002/alr.23209. Online ahead of print.

ABSTRACT

BACKGROUND: Triple combination therapy of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to reduce morbidity and mortality in people with cystic fibrosis (PwCF). Although patient BMI favorably increases with ETI treatment, factors contributing to this improvement are poorly characterized. Olfaction contributes to appetite stimulation and anticipation of eating, where higher rates of olfactory impairment (OI) in PwCF may contribute to malnutrition and BMI instability in this population.

METHODS: We performed a prospective cohort study analyzing 41 CF patient responses to the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the Sino-Nasal Outcome Test 22 (SNOT-22) and used Generalized estimating equations (GEE) to understand the change in survey variables from being untreated (baseline) to undergoing 3 months of ETI therapy (follow-up).

RESULTS: Patients reported significant improvement in their sense of smell at follow-up (p = 0.0036). Their improvements in sense of smell were not confounded by changes in rhinologic or extra-nasal rhinologic symptoms. Self-reported QoL improved after 3 months on ETI (p = <0.0001) as did BMI (p = <0.0001), but improved sense of smell did not independently mediate these changes in QoL and BMI.

CONCLUSION: Our results support the impression that ETI therapy improves CF-associated rhinologic symptoms and reverses OI, while contributing to improvement in rhinologic QoL. Sense of smell is not an independent mediator of improved QoL and BMI in this population, suggesting that other factors may have a stronger role in these realms. However, given the subjective improvement in sense of smell, additional evaluation of OI using psychophysical chemosensory assessment will clarify the connection between olfaction, BMI, and QoL in PwCF. This article is protected by copyright. All rights reserved.

PMID:37301999 | DOI:10.1002/alr.23209

Int J Mol Sci. 2023 Jun 1;24(11):9609. doi: 10.3390/ijms24119609.

ABSTRACT

Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations that generate a premature termination codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ribosome's capacity to skip a PTC, thus generating a full-length protein. "TRIDs" are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We investigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2'-O-methyltransferase.

PMID:37298560 | DOI:10.3390/ijms24119609

J Clin Med. 2023 May 26;12(11):3704. doi: 10.3390/jcm12113704.

ABSTRACT

We characterized the fatty acid profiles in the erythrocyte membrane of pediatric patients with cystic fibrosis (CF) receiving highly concentrated docosahexaenoic acid (DHA) supplementation (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day (n = 11) or matching placebo (n = 11) for 12 months. The mean age was 11.7 years. The DHA group showed a statistically significant improvement in n-3 polyunsaturated fatty acids (PUFAs), which was observed as early as 6 months and further increased at 12 months. Among the n-3 PUFAs, there was a significant increase in DHA and eicosapentaenoic acid (EPA). Additionally, a statistically significant decrease in n-6 PUFAs was found, primarily due to a decrease in arachidonic acid (AA) levels and elongase 5 activity. However, we did not observe any changes in linoleic acid levels. The long-term administration of DHA over one year was safe and well tolerated. In summary, the administration of a high-rich DHA supplement at a dose of 50 mg/kg/day for one year can correct erythrocyte AA/DHA imbalance and reduce fatty acid inflammatory markers. However, it is important to note that essential fatty acid alterations cannot be fully normalized with this treatment. These data provide timely information of essential fatty acid profile for future comparative research.

PMID:37297899 | DOI:10.3390/jcm12113704

APMIS. 2023 Jun 9. doi: 10.1111/apm.13331. Online ahead of print.

ABSTRACT

Ceftolozane-tazobactam is a new β-lactam/β-lactamase inhibitor combination approved by the U.S. Food and Drug Administration in 2019 for the treatment of hospital-acquired and ventilator-associated pneumonia. The combination is a particularly potent inhibitor of penicillin-binding proteins with higher affinity than other β-lactam agents. Persons with cystic fibrosis (pwCF) often harbour resistant Gram-negative bacteria in the airways and need antibiotics to prevent declining lung function. To test whether the introduction of ceftolozane-tazobactam in the period 2015-2020 led to a bacterial population level increase in cephalosporin resistance in a Danish CF population. In vitro, activity of ceftolozane-tazobactam was evaluated by susceptibility testing of clinical Pseudomonas aeruginosa isolated from pwCF from January 1, 2015, to June 1, 2020. Six thousand three hundred thirty two isolates collected from 210 adult pwCF were included. Thirty pwCF were treated with ceftolozane-tazobactam at least once. Ceftolozane-tazobactam exposure did not increase cephalosporin resistance on an individual or population level. However, resistance to ceftolozane-tazobactam was recorded despite no prior exposure in four pwCF. Compared to ceftazidime, ceftolozane-tazobactam had a better in vitro activity on P. aeruginosa. The percentage of non-mucoid P. aeruginosa isolates susceptible to ceftolozane-tazobactam were higher or equal to 5 other β-lactams. Ceftolozane-tazobactam expands the armamentaria against P. aeruginosa with acceptable levels for a selection of drug resistance.

PMID:37294911 | DOI:10.1111/apm.13331

Cochrane Database Syst Rev. 2023 Jun 9;6:CD014605. doi: 10.1002/14651858.CD014605.pub2.

ABSTRACT

BACKGROUND: Although exercise is recommended as part of the cystic fibrosis (CF) therapeutic routine, adherence to exercise is still limited. Digital health technologies can provide easy-to-access health information and may help improve healthcare and outcomes in individuals with long-term conditions. However, its effects for delivering and monitoring exercise programs in CF have not yet been synthesized.

OBJECTIVES: To evaluate the benefits and harms of digital health technologies for delivering and monitoring exercise programs, increasing adherence to exercise regimens, and improving key clinical outcomes in people with CF.

SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 November 2022.

SELECTION CRITERIA: We included randomized controlled trials (RCTs) or quasi-RCTs of digital health technologies for delivering or monitoring exercise programs in CF.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. physical activity, 2. self-management behavior, and 3. pulmonary exacerbations. Our secondary outcomes were 4. usability of technologies, 5. quality of life, 6. lung function, 7. muscle strength, 8. exercise capacity, 9. physiologic parameters, and 10.

ADVERSE EVENTS: We used GRADE to assess certainty of evidence.

MAIN RESULTS: We identified four parallel RCTs (three single-center and one multicenter with 231 participants aged six years or older). The RCTs evaluated different modes of digital health technologies with distinct purposes, combined with diverse interventions. We identified important methodologic concerns in the RCTs, including insufficient information on the randomization process, blinding of outcome assessors, balance of non-protocol interventions across groups, and whether the analyses performed corrected for bias due to missing outcome data. Non-reporting of results may also be a concern, especially because some planned outcome results were reported incompletely. Furthermore, each trial had a small number of participants, resulting in imprecise effects. These limitations on the risk of bias, and on the precision of effect estimates resulted in overall low- to very low-certainty evidence. We undertook four comparisons and present the findings for our primary outcomes below. There is no information on the effectiveness of other modes of digital health technologies for monitoring physical activity or delivering exercise programs in people with CF, on adverse events related to the use of digital health technologies either for delivering or monitoring exercise programs in CF, and on their long-term effects (more than one year). Digital health technologies for monitoring physical activity Wearable fitness tracker plus personalized exercise prescription compared to personalized exercise prescription alone One trial (40 adults with CF) evaluated this outcome, but did not report data for any of our primary outcomes. Wearable fitness tracker plus text message for personalized feedback and goal setting compared to wearable fitness tracker alone The evidence is very uncertain about the effects of a wearable fitness tracker plus text message for personalized feedback and goal setting, compared to wearable technology alone on physical activity measured by step count at six-month follow-up (mean difference [MD] 675.00 steps, 95% confidence interval [CI] -2406.37 to 3756.37; 1 trial, 32 participants). The same study measured pulmonary exacerbation rates and reported finding no difference between groups. Web-based application to record, monitor, and set goals on physical activity plus usual care compared to usual care alone Using a web-based application to record, monitor, and set goals on physical activity plus usual care may result in little to no difference on time spent in moderate-to-vigorous physical activity measured via accelerometry compared to usual care alone at six-month follow-up (MD -4 minutes/day, 95% CI -37 to 29; 1 trial, 63 participants). Low certainty-evidence from the same trial suggests that the intervention may result in little to no difference on pulmonary exacerbations during 12 months of follow-up (median 1 respiratory hospitalization, interquartile range [IQR] 0 to 3) versus control (median 1 respiratory hospitalization, IQR 0 to 2; P = 0.6). Digital health technologies for delivering exercise programs Web-based versus face-to-face exercise delivery The evidence is very uncertain about the effects of web-based compared to face-to-face exercise delivery on adherence to physical activity as assessed by the number of participants who completed all exercise sessions after three months of intervention (risk ratio 0.92, 95% CI 0.69 to 1.23; 1 trial, 51 participants).

AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of an exercise program plus the use of a wearable fitness tracker integrated with a social media platform compared with exercise prescription alone and on the effects of receiving a wearable fitness tracker plus text message for personalized feedback and goal setting, compared to a wearable fitness tracker alone. Low-certainty evidence suggests that using a web-based application to record, monitor, and set goals on physical activity plus usual care may result in little to no difference in time spent in moderate-to-vigorous physical activity, total time spent in activity, pulmonary exacerbations, quality of life, lung function, and exercise capacity compared to usual care alone. Regarding the use of digital health technologies for delivering exercise programs in CF, the evidence is very uncertain about the effects of using a wearable fitness tracker plus personalized exercise prescription compared to personalized exercise prescription alone. Further high-quality RCTs, with blinded outcome assessors, reporting the effects of digital health technologies on clinically important outcome measures, such as physical activity participation and intensity, self-management behavior, and the occurrence of pulmonary exacerbations in the long term are needed. The results of six ongoing RCTs identified through our searches may help clarify the effects of different modes of digital health technologies for delivering and monitoring exercise programs in people with CF.

PMID:37294546 | DOI:10.1002/14651858.CD014605.pub2

Pediatr Pulmonol. 2023 Jun 9. doi: 10.1002/ppul.26550. Online ahead of print.

ABSTRACT

BACKGROUND: Tracheobronchomalacia (TBM) is estimated to be present in 1 in 2100 children. Previous reports suggest the prevalence is higher in children with cystic fibrosis (CF). This has clinical implications with potential to influence airway clearance and lung health.

AIM: To determine the prevalence and clinical associations of TBM in Western Australian children with CF.

METHODS: Children with CF born between 2001 and 2016 were included. Operation reports from bronchoscopies performed until the age of 4 were retrospectively reviewed. Data were collected on the presence, persistence defined as a repeat diagnosis, and severity of TBM. Data on genotype, pancreatic status, and symptoms at CF diagnosis were extracted from the medical record. Associations between categorical variables were compared using χ2 and Fisher's exact test.

RESULTS: Of 167 children (79 male), 68 (41%) were diagnosed with TBM at least once, with TBM persistent in 37 (22%) and severe in 31 (19%). TBM was significantly associated with pancreatic insufficiency (χ2 = 7.874, p < 0.05, odds ratio [OR] 3.4), delta F508 gene mutation (χ2 = 6.489, p < 0.05, OR 2.3), and a presentation of meconium ileus (χ2 = 8.615, p < 0.05, OR 5.0). Severe malacia was less likley in females (χ2 = 4.523, p < 0.05, OR 0.42) . No significant relationship was found with respiratory symptoms at the time of CF diagnosis (χ2 = 0.742, p = 0.39).

CONCLUSIONS: TBM was common in this group of children under the age of 4 with CF. A high index of suspicion for airway malacia should be considered in children with CF, particularly those who present with meconium ileus and have gastrointestinal symptoms at diagnosis.

PMID:37294078 | DOI:10.1002/ppul.26550

Pediatr Pulmonol. 2023 Jun 9. doi: 10.1002/ppul.26541. Online ahead of print.

ABSTRACT

BACKGROUND: International consensus statements on depression and anxiety in adolescents and adults with cystic fibrosis (awCF) recommend assessment for comorbid substance misuse. However, at CF centers, the frequency and impact of substance misuse have not been well characterized, and best practices for prevention, identification, and evidence-based treatment have not been routinely implemented.

METHODS: Medical records of 148 awCF over 3 years were reviewed to determine the prevalence of substance misuse (alcohol or opiates) and its relationship with clinical variables and healthcare utilization. Independent sample t test for continuous outcomes and χ2 test for binary outcomes were used to compare groups with and without substance misuse.

RESULTS: Substance misuse was documented in 28 (19%) awCF, equally distributed between alcohol (n = 13) and opiates (n = 15). Adults with substance misuse were more likely to be male. The prevalence of diagnosed anxiety and depression did not differ significantly between groups, but those with substance misuse had more severe anxiety (Generalized Anxiety Disorder-7 Item [GAD-7]: 10.0 ± 6.1 vs. 3.3 ± 4.4; p < 0.001) and depressive symptoms (Patient Health Questionnaire-9: 10.4 ± 6.5 vs. 4.0 ± 4.8; p < 0.001). Adults with substance misuse had higher annual rates of missed outpatient CF visits, more frequent "sick" visits, more frequent and longer hospitalizations, and a higher mortality rate.

CONCLUSIONS: In awCF, substance misuse is common and associated with adverse indicators of emotional and physical health, including via proxy of service utilization, suggesting that systematic approaches to addressing substance misuse in CF clinics should be considered. Prospective, longitudinal study is warranted to elucidate the complex relationships between depression, anxiety, substance misuse, and health outcomes in individuals with CF.

PMID:37294071 | DOI:10.1002/ppul.26541