Methods Mol Biol. 2024;2734:151-169. doi: 10.1007/978-1-0716-3523-0_10.

ABSTRACT

The rise of bacteria resistant to the antibiotics currently in use (multiple drug-resistant, MDR) is a serious problem for patients affected by infections. This situation is even more worrying in the case of chronic bacterial infections, such as those caused by Pseudomonas aeruginosa (Pa), in patients with cystic fibrosis (CF). As an alternative to antibiotic treatments, the use of bacteriophages (phages) to fight bacterial infections has gained increasing interest in the last few years. Phages are viruses that specifically infect and multiply within the bacteria without infecting eukaryotic cells. It is well assumed that phage therapy has a high bacterial specificity, which, unlike antibiotics, should limit the damage to the endogenous microbiome. In addition, phages can kill antibiotic-resistant bacteria and perform self-amplification at the site of the infection.The protocol detailed in this chapter describes how the antimicrobial effect of phages can be studied in vivo in the zebrafish (Danio rerio) model infected with Pa. The same procedure can be applied to test the effectiveness of several different phages killing other bacterial species and for the rapid preclinical testing of phages to be used as personalized medicine.

PMID:38066368 | DOI:10.1007/978-1-0716-3523-0_10

Nat Commun. 2023 Dec 8;14(1):8135. doi: 10.1038/s41467-023-43863-2.

ABSTRACT

Staphylococcus aureus is a predominant cause of chronic lung infections. While the airway environment is rich in highly sialylated mucins, the interaction of S. aureus with sialic acid is poorly characterized. Using S. aureus USA300 as well as clinical isolates, we demonstrate that quorum-sensing dysfunction, a hallmark of S. aureus adaptation, correlates with a greater ability to consume free sialic acid, providing a growth advantage in an air-liquid interface model and in vivo. Furthermore, RNA-seq experiment reveals that free sialic acid triggers transcriptional reprogramming promoting S. aureus chronic lifestyle. To support the clinical relevance of our results, we show the co-occurrence of S. aureus, sialidase-producing microbiota and free sialic acid in the airway of patients with cystic fibrosis. Our findings suggest a dual role for sialic acid in S. aureus airway infection, triggering virulence reprogramming and driving S. aureus adaptive strategies through the selection of quorum-sensing dysfunctional strains.

PMID:38065959 | DOI:10.1038/s41467-023-43863-2

J Med Internet Res. 2023 Dec 8;25:e47873. doi: 10.2196/47873.

ABSTRACT

BACKGROUND: Probable sarcopenia is determined by a reduction in muscle strength assessed with the handgrip strength test or 5 times sit-to-stand test, and it is confirmed with a reduction in muscle quantity determined by dual-energy X-ray absorptiometry or bioelectrical impedance analysis. However, these parameters are not implemented in clinical practice mainly due to a lack of equipment and time constraints. Nowadays, the technical innovations incorporated in most smartphone devices, such as high-speed video cameras, provide the opportunity to develop specific smartphone apps for measuring kinematic parameters related with sarcopenia during a simple sit-to-stand transition.

OBJECTIVE: We aimed to create and validate a sit-to-stand video analysis-based app for diagnosing sarcopenia in community-dwelling older adults and to analyze its construct validity with health-related risk factors and frailty.

METHODS: A total of 686 community-dwelling older adults (median age: 72 years; 59.2% [406/686] female) were recruited from elderly social centers. The index test was a sit-to-stand video analysis-based app using muscle power and calf circumference as proxies of muscle strength and muscle quantity, respectively. The reference standard was obtained by different combinations of muscle strength (handgrip strength or 5 times sit-to-stand test result) and muscle quantity (appendicular skeletal mass or skeletal muscle index) as recommended by the European Working Group on Sarcopenia in Older People-2 (EWGSOP2). Sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC) of the receiver operating characteristic curve were calculated to determine the diagnostic accuracy of the app. Construct validity was evaluated using logistic regression to identify the risks associated with health-related outcomes and frailty (Fried phenotype) among those individuals who were classified as having sarcopenia by the index test.

RESULTS: Sarcopenia prevalence varied from 2% to 11% according to the different combinations proposed by the EWGSOP2 guideline. Sensitivity, specificity, and AUC were 70%-83.3%, 77%-94.9%, and 80.5%-87.1%, respectively, depending on the diagnostic criteria used. Likewise, positive and negative predictive values were 10.6%-43.6% and 92.2%-99.4%, respectively. These results proved that the app was reliable to rule out the disease. Moreover, those individuals who were diagnosed with sarcopenia according to the index test showed more odds of having health-related adverse outcomes and frailty compared to their respective counterparts, regardless of the definition proposed by the EWGSOP2.

CONCLUSIONS: The app showed good diagnostic performance for detecting sarcopenia in well-functioning Spanish community-dwelling older adults. Individuals with sarcopenia diagnosed by the app showed more odds of having health-related risk factors and frailty compared to their respective counterparts. These results highlight the potential use of this app in clinical settings.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05148351; https://clinicaltrials.gov/study/NCT05148351.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3390/s22166010.

PMID:38064268 | DOI:10.2196/47873

Cochrane Database Syst Rev. 2023 Dec 8;12:CD014084. doi: 10.1002/14651858.CD014084.pub2.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in paranasal sinuses determines chronic rhinosinusitis (CRS) and nasal polyposis. Endoscopic sinus surgery is used to open the sinuses and allow medical treatment to work properly.

OBJECTIVES: To determine the effects of sinus surgery alone or in combination with medical treatment (non-surgical) compared to medical treatment (non-surgical) alone on both nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis. Further, to evaluate the impact of sinus surgery (with or without medical treatment) on hospitalization rates, use of antibiotics and pulmonary exacerbation rates.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched other databases (Pubmed, Embase, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Virtual Health Library and ClinicalTrials.gov). Date of last search: 18 September 2022.

SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing groups who underwent endoscopic sinus surgery and groups with medical treatment alone.

DATA COLLECTION AND ANALYSIS: The review authors independently selected studies, extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE. They contacted the authors of the included study for additional information.

MAIN RESULTS: We identified 66 publications relating to 50 studies from electronic searches. Only one study fulfilled the inclusion criteria, and only limited information was available. In this study, 28 participants aged 19 to 28 years were randomized in equal numbers to either nasal irrigation alone or nasal irrigation with surgery (endoscopic polypectomy with extended sinusotomy). The certainty of the evidence was very low according to the GRADE approach. We are uncertain whether, compared to medical treatment alone, the addition of surgical intervention improves nasal symptoms, or reduces bacterial colonization, the use of antibiotics and pulmonary exacerbations. We are also uncertain whether the addition of surgery to medical treatment leads to changes in pulmonary function. There was one episode of bleeding during surgery that was corrected during the procedure with no further consequences. The study did not report on survival.

AUTHORS' CONCLUSIONS: Very low-certainty evidence means we are not certain if endoscopic sinus surgery to treat chronic rhinosinusitis with nasal polyposis in cystic fibrosis is effective. Future research should be multicentric to increase the number of participants and increase statistical power. Adequate randomization and allocation concealment are important to guarantee that the groups are similar. Blinding, however, may not be possible in an ethical trial; even without blinding, results can achieve high-level evidence if the outcomes used are objective parameters. Future research should follow participants of all ages for at least 12 months to evaluate the evolution of nasal polyposis, its recurrence and how symptoms may return. We also consider mortality an important outcome to be assessed. Future clinical research should consider the effects of cystic fibrosis transmembrane conductance regulators, a new group of drugs that may affect the development of nasal polyps.

PMID:38063253 | DOI:10.1002/14651858.CD014084.pub2

Eur Respir J. 2023 Dec 7;62(6):2302026. doi: 10.1183/13993003.02026-2023. Print 2023 Dec.

NO ABSTRACT

PMID:38061794 | DOI:10.1183/13993003.02026-2023

Sleep Breath. 2023 Dec 7. doi: 10.1007/s11325-023-02960-8. Online ahead of print.

ABSTRACT

PURPOSE: To describe sleep and quality of life of pediatric patients with chronic obstructive respiratory diseases and to ascertain whether or not sleep quality correlates with quality of life in this population.

METHODS: Participants aged 5 to 18 years with cystic fibrosis (CF), severe asthma, or postinfectious bronchiolitis obliterans (PIBO) receiving regular follow-up at a pediatric respiratory medicine center were recruited. Two questionnaires were used: the Brazilian version of the Sleep Disturbance Scale for Children (SDSC) and the Pediatric Quality of Life Inventory (Peds-QL).

RESULTS: A total of 46 individuals were included: 30 with CF, 9 with severe asthma, and 7 with PIBO. Almost two-thirds of the patients and their parents or guardians scored at least 39 points on the SDSC, suggesting poor sleep quality. Significantly higher overall median scores were observed in those with severe asthma. Patients and their parents or guardians scored a median of 77 and 80 points respectively on the Peds-QL, with parents of patients with CF scoring higher than any other group. There was a moderate inverse correlation between sleep disorders and quality of life (r = - 0.532 for patients and r = - 0.606 for parents; p < 0.001).

CONCLUSION: Children and adolescents with chronic obstructive respiratory diseases experience impairment in their sleep quality and quality of life. Sleep disorders and quality of life have a moderate negative correlation.

PMID:38062225 | DOI:10.1007/s11325-023-02960-8

Antimicrob Agents Chemother. 2023 Dec 7:e0099223. doi: 10.1128/aac.00992-23. Online ahead of print.

ABSTRACT

Vancomycin is the first-line agent to treat pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis (PwCF). However, there is no consensus on vancomycin initial dosing in this population among health institutions, and there is a large variability in initial dosing across the United States. In this study, we characterized the pharmacokinetics (PK) of vancomycin in PwCF using a population PK approach. The clinical PK data to develop the population PK model were obtained from vancomycin therapeutic monitoring data from PwCF undergoing treatment for infections due to MRSA. The population PK model was then used to perform comprehensive Monte Carlo simulations to evaluate the probability of target attainment (PTA) of 12 different initial dosing scenarios. The area under the curve to minimum inhibitory concentration (MIC) ratio ≥400 mg*h/L and <650 mg*h/L were used as efficacy and toxicity targets for PTA analysis. A total of 181 vancomycin plasma concentrations were included in the analysis. A one-compartment model with first-order elimination best described the data. Weight significantly influenced the vancomycin PK (P < 0.05). In the final model, clearance was estimated as 5.52 L/h/70 kg, and the volume of distribution was 31.5 L/70 kg. The PTA analysis showed that at MIC = 1 µg/mL, doses 1,500 q8h and 2,000 q12h showed the highest %PTA in achieving both efficacy and toxicity targets. The PTA results from this study may potentially inform the initial dosing regimens of vancomycin to treat pulmonary infections due to MRSA in PwCF.

PMID:38059634 | DOI:10.1128/aac.00992-23

mBio. 2023 Dec 7:e0292423. doi: 10.1128/mbio.02924-23. Online ahead of print.

ABSTRACT

As we rapidly approach a post-antibiotic era, bacteriophage (phage) therapy may offer a solution for treating drug-resistant bacteria. Mycobacterium abscessus is an emerging, multidrug-resistant pathogen that causes disease in people with cystic fibrosis, chronic obstructive pulmonary disease, and other underlying lung diseases. M. abscessus can survive inside host cells, a niche that can limit access to antibiotics. As current treatment options for M. abscessus infections often fail, there is an urgent need for alternative therapies. Phage therapy is being used to treat M. abscessus infections as an option of last resort. However, little is known about the ability of phages to kill bacteria in the host environment and specifically in an intracellular environment. Here, we demonstrate the ability of phages to enter mammalian cells and to infect and kill intracellular M. abscessus. These findings support the use of phages to treat intracellular bacterial pathogens.

PMID:38059609 | DOI:10.1128/mbio.02924-23

Am J Med Genet A. 2023 Dec 6. doi: 10.1002/ajmg.a.63489. Online ahead of print.

ABSTRACT

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate-cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate-cyclase 2C (GC-C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels. Thus far, management for CSD primarily consists of mitigating nutritional, electrolyte, and volume deficiencies with no known pathophysiology-driven treatments. For activating variants of GUCY2C, experimental compounds have shown efficacy in vitro for direct inhibition of GC-C but are not currently available for clinical use. However, Crofelemer, a CFTR inhibitory modulator with negligible systemic absorption, can theoretically help to treat this type of CSD. Herein, we describe and characterize the clinical course of a premature male infant with a de novo missense variant of GUCY2C not previously reported and highly consistent with CSD. With multi-disciplinary family-directed decision-making, a treatment for CSD was evaluated for the first time to our knowledge with Crofelemer.

PMID:38058249 | DOI:10.1002/ajmg.a.63489

Clin Exp Otorhinolaryngol. 2023 Nov;16(4):407-412. doi: 10.21053/ceo.2023.01130. Epub 2023 Nov 17.

NO ABSTRACT

PMID:38056830 | PMC:PMC10710920 | DOI:10.21053/ceo.2023.01130

Curr Gastroenterol Rep. 2023 Dec 7. doi: 10.1007/s11894-023-00906-4. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: To discuss all the various motility disorders impacting people with Cystic Fibrosis (PwCF) and provide diagnostic and management approaches from a group of pediatric and adult CF and motility experts and physiologists with experience in the management of this disease.

RECENT FINDINGS: Gastrointestinal (GI) symptoms coexist with pulmonary symptoms in PwCF regardless of age and sex. The GI manifestations include gastroesophageal reflux disease, esophageal dysmotility gastroparesis, small bowel dysmotility, small intestinal bacterial overgrowth syndrome, distal idiopathic obstruction syndrome, constipation, and pelvic floor disorders. They are quite debilitating, limiting the patients' quality of life and affecting their nutrition and ability to socialize. This genetic disorder affects many organ systems and is chronic, potentially impacting fertility and future family planning, requiring a multidisciplinary approach. Our review discusses the treatments of motility disorders in CF, their prevalence and pathophysiology. We have provided a framework for clinicians who care for these patients that can help to guide their clinical management.

PMID:38057499 | DOI:10.1007/s11894-023-00906-4

Clin Nutr ESPEN. 2023 Dec;58:73-78. doi: 10.1016/j.clnesp.2023.08.028. Epub 2023 Aug 25.

ABSTRACT

BACKGROUND & AIMS: Malnutrition and cystic fibrosis related diabetes (CFRD) are common comorbidities in cystic fibrosis (CF). Cystic fibrosis transmembrane regulator (CFTR) modulators have shown beneficial effects on respiratory status. This study aims to determine the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on body mass index (BMI) and glycemic control.

METHODS: A retrospective, observational study of a cohort of 17 adult CF patients was conducted at the CF reference center of Ghent University Hospital. BMI evolution was analyzed 18 months before and 0, 3, 6, 12 and 18 months after the start of ETI. The evolution of insulin dependence and the 2 h oral glucose tolerance test (OGTT) results were described until 36 months after start of ETI, in a small subgroup of ten patients with CFRD or impaired glucose tolerance (IGT).

RESULTS: A significant increase in mean BMI of 1.2 kg/m2 (±1.3 SD) was observed. Most weight gain was observed in the first 3 months after starting treatment. This effect was sustained during the observed period of 18 months. Six patients had insulin dependent CFRD, of which three were able to stop insulin after starting ETI. Two patients with CFRD treated with dietary measures showed an initial normalization of the 2 h OGTT, but deterioration at 36 month follow-up.

CONCLUSIONS: After initiation of ETI an increase in BMI was observed in adults with CF. ETI can have a beneficial impact on glucose metabolism in patients with CFRD, leading to a possible need for reduction or cessation of insulin therapy.

PMID:38057039 | DOI:10.1016/j.clnesp.2023.08.028

Eur J Pediatr. 2023 Dec 6. doi: 10.1007/s00431-023-05359-5. Online ahead of print.

ABSTRACT

The identification of cystic fibrosis screening-positive, inconclusive diagnosis (CFSPID) in infants is a controversial outcome of newborn screening for cystic fibrosis (CF). Today, despite improvements in the knowledge of CFSPID and the description of several cohorts, little data are available on cohorts with a follow-up period of more than 6 years. In this study, we report the outcomes of an Italian cohort of CFSPID individuals with CFSPID or formerly CFTR-related disorders (CFTR-RD) (CFSPID > CFTR-RD) or diagnosed with CF (CFSPID > CF). This was an observational and multicentre Italian study collecting clinical data on CFSPID born between the period January 1, 2011, and December 13, 2019. A total of 268 participants were included: 243 with persistent CFSPID, 7 with CFSPID > CFTR-RD, and 18 with CFSPID > CF. The trend of sweat chloride (SC) values, percentage of definitive diagnoses, lung function in school-aged children, and development of CF-related complications were evaluated. At the end of the observation period, almost 80% of the individuals with CFSPID did not have a conclusive diagnosis. A total of 29 children (10.8%) transitioned to a diagnosis of CF for pathological SC values (≥ 60 mmol/L) or multi-organ involvement, and 18 (6.7%) to CFTR-RD. Children who were followed up for > 6 years (median age, 7.5 years; range, 6.04-10.5) had normal lung function and were pancreatic sufficient, and the evolution in CF was only present in two cases.

CONCLUSION: Most Italian preschool and school-aged children with CFSPID did not have a conclusive diagnosis, and progression to CF was unlikely in children > 6 years of age. An annual follow-up could be indicated to identify early evolution in clinical features consistent with a CFTR-RD.

WHAT IS KNOWN: • Cystic Fibrosis newborn screening identifies also subjects with an inconclusive diagnosis (CFSPID). • Over time a variable percentage of CFSPIDs will be diagnosed as CF. • Little data is available on CFSPIDs with a follow-up period of more than six years.

WHAT IS NEW: • 80% of Italian preschool and school-age CFSPIDs not have a conclusive diagnosis. • Italian preschool and school-age CFSPIDs have normal lung function and are pancreatic sufficient. • Annual follow-up after 6 years is recommended in CFSPID with abnormal LCI2.5 or with a CF-causing variant in trans with a VVCC.

PMID:38054992 | DOI:10.1007/s00431-023-05359-5

Heliyon. 2023 Nov 7;9(11):e21861. doi: 10.1016/j.heliyon.2023.e21861. eCollection 2023 Nov.

ABSTRACT

BACKGROUND & AIMS: Cystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in Cystic Fibrosis (CF). As advances in pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may underdiagnose liver fibrosis, particularly in its early stages. Newer modalities for the assessment of fibrosis may provide a more accurate assessment. FibroScan is validated in assessing fibrosis for several aetiologies including alcohol and fatty liver, the CFLD cohort have an entirely different phenotype so the cut off values are not transferrable. We appraised fibrosis assessment tools to improve diagnosis of CFLD.

METHODS: A prospective cohort (n = 114) of patients from the Manchester Adult Cystic Fibrosis Centre, UK were identified at annual assessment. Demographic data including co-morbidity, CFTR genotyping, biochemistry and imaging were used alongside current guidelines to group into CFLD and CF without evidence of liver disease. All patients underwent liver stiffness measurement (LSM) and assessment of serum-based fibrosis biomarker panels. A new diagnostic criterion was created and validated in a second, independent cohort.

RESULTS: 12 of 114 patient classified as CFLD according to the European Cystic Fibrosis Society best practice guidelines. No specific risk factors for development of CFLD were identified. Liver enzymes were elevated in patients with CFLD. Serum biomarker panels did not improve diagnostic criteria. LSM accurately predicted CFLD. A new diagnostic criterion was proposed and validated in a separate cohort, accurately predicating CFLD in 10 of 32 patients (31 %).

CONCLUSION: We present a cohort of patients with CF assessed for the presence of liver fibrosis using blood biomarkers and LSM based platforms. We propose a new, simplified diagnostic criteria, capable of accurately predicting liver disease in patients with CF.Clinical trials number: NCT04277819.

PMID:38053913 | PMC:PMC10694159 | DOI:10.1016/j.heliyon.2023.e21861

BMC Pulm Med. 2023 Dec 5;23(1):488. doi: 10.1186/s12890-023-02787-9.

ABSTRACT

OBJECTIVE: To evaluate the effect of Persian medicine Syrup 'compound honey syrup (CHS)' on fractional exhalation nitric oxide (FENO) changes in patients with cystic fibrosis (CF).

STUDY DESIGN: We conducted a before-after clinical trial on 70 CF patients. All patients received classical treatments for CF along with CHS (including honey, Ginger, cinnamon, saffron, cardamom and galangal), 5-10 cc (depending on the age and weight of patients) in 100 cc of warm boiled water twice a day, 30 min after meals. In this clinical trial, before and 12 weeks after the start of the CHS, FeNO test was evaluated.

RESULTS: From 70 patients were enrolled, 44 patients completed this 12-week course of treatment. At the end of the study, changes in FeNO was significantly different before and after treatment (P-value < 0.05). At the end of the study, no dangerous side effects of CHS was reported.

CONCLUSIONS: This study revealed that CHS can be effective as a complementary and safe drug in the medication of CF patients.

PMID:38053097 | DOI:10.1186/s12890-023-02787-9

Nat Commun. 2023 Dec 5;14(1):8051. doi: 10.1038/s41467-023-43904-w.

ABSTRACT

Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, we derive the S315 peptide as an improvement over S10 in delivering base editor RNP. Following intratracheal aerosol delivery of Cy5-labeled peptide in rhesus macaques, we confirm delivery throughout the respiratory tract. Subsequently, we target CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieve editing efficiencies of up-to 5.3% in rhesus airway epithelia. Moreover, we document persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restores anion channel function in cultured human airway epithelia. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.

PMID:38052872 | DOI:10.1038/s41467-023-43904-w

J Cyst Fibros. 2023 Dec 4:S1569-1993(23)01682-X. doi: 10.1016/j.jcf.2023.11.011. Online ahead of print.

NO ABSTRACT

PMID:38052705 | DOI:10.1016/j.jcf.2023.11.011

Microbiol Spectr. 2023 Dec 5:e0351123. doi: 10.1128/spectrum.03511-23. Online ahead of print.

ABSTRACT

Microbes produce a large array of extracellular molecules, which serve as signals and cues to promote polymicrobial interactions and alter the function of microbial communities. This has been particularly well studied in the human oral microbiome, where key metabolites have been shown to impact both health and disease. Here, we used an untargeted mass spectrometry approach to comprehensively assess the extracellular metabolome of the pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii during mono- and co-culture. We generated and made publicly available a metabolomic data set that includes hundreds of potential metabolites and leveraged this data set to identify an operon important for glutathione secretion in A. actinomycetemcomitans.

PMID:38051055 | DOI:10.1128/spectrum.03511-23

Pediatr Pulmonol. 2023 Dec 5. doi: 10.1002/ppul.26798. Online ahead of print.

ABSTRACT

INTRODUCTION: People with cystic fibrosis (pwCF) require a multidisciplinary care team due to disease complexity. The Cystic Fibrosis Foundation (CFF) notes that pharmacists are recommended, while other organizations consider pharmacists required. In 2016, the CFF initiated a grant program for CFF-accredited care centers and affiliate programs (CFF-ACCAP) to implement outpatient pharmacy services. The primary objective of this study was to compare surveys regarding pharmacy involvement in CFF-ACCAP pre- and post-grant implementation.

METHODS: This was an IRB-approved, survey-based study. The surveys were distributed via the CF pharmacist-pharmacy technician and center director e-mail exchanges.

RESULTS: There are currently 244 CFF-ACCAP and 158 pharmacists. Forty-two pharmacists completed the 2013 survey and 77 completed the 2023 survey. Practice site shifted from primarily the inpatient (58.5%) to outpatient settings (67.5%; p < .001). Most positions were created in the past 7 years (81%) with 50% currently or previously funded by the CFF grant program. CFF center director response decreased from 2013 to 2023 (106 vs. 48) but centers with a dedicated CF pharmacist increased from 2013 to 2023 (66%-86%; p = .014). In the 2023 survey, we received responses from 17 pharmacy technicians, who were newly included. Most of these technicians (64%) reported working in outpatient clinics.

CONCLUSIONS: Since 2013, pharmacy presence has grown at CFF-ACCAP, partly due to the CFF grant program. Despite pharmacists not being required members of the multidisciplinary care team, their presence is notable in 65% of CFF-ACCAP centers, where they contribute significantly to improving the care provided for pwCF.

PMID:38050809 | DOI:10.1002/ppul.26798

Eur J Pharm Biopharm. 2023 Dec 2:S0939-6411(23)00321-1. doi: 10.1016/j.ejpb.2023.12.001. Online ahead of print.

ABSTRACT

Mucus is a complex polymeric hydrogel that serves as a critical defense in several organs. In the lungs, it provides a formidable barrier against inhaled particles such as microorganisms. In addition, mucus is essential for normal lung physiology, as it promotes immune tolerance and facilitates a normal commensal pulmonary microbiome. Hypersecretion of airway mucus is a characteristic of numerous respiratory diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF), and creates pulmonary obstruction, limiting the effectiveness of inhaled therapies. Due to those alterations, therapeutic strategies must be optimal to limit airway obstruction and restore pulmonary function. Mucoactive drugs are common therapeutic options and are classified into different groups depending on their modes of action, i.e., expectorants, mucokinetics, mucoregulators and mucolytics. This review focuses on mucoactive drugs and their modes of action. A special focus will be made on two challenging pulmonary pathologies: COPD and CF, and on their clinical studies conducted with mucoactive drugs.

PMID:38048888 | DOI:10.1016/j.ejpb.2023.12.001