Biomedicines. 2021 Jul 2;9(7):772. doi: 10.3390/biomedicines9070772.

ABSTRACT

Although bronchiectasis pathophysiology has been historically understood around the presence of airway neutrophilic inflammation, recent experiences are consistent with the identification of a type 2 inflammation (T2) high endotype in bronchiectasis. In order to evaluate prevalence and clinical characteristics of bronchiectasis patients with a T2-high endotype and explore their response to biologicals, two studies were carried out. In a cross-sectional study, bronchiectasis adults without asthma underwent clinical, radiological, and microbiological assessment, along with blood eosinophils and oral fractional exhaled nitric oxide (FeNO) evaluation, during stable state. Prevalence and characteristics of patients with a T2- high endotype (defined by the presence of either eosinophils blood count ≥300 cells·µL-1 or oral FeNO ≥ 25 dpp) were reported. A case series of severe asthmatic patients with concomitant bronchiectasis treated with either mepolizumab or benralizumab was evaluated, and patients' clinical data pre- and post-treatment were analyzed up to 2 years of follow up. Among bronchiectasis patients without asthma enrolled in the cross-sectional study, a T2-high endotype was present in 31% of them. These patients exhibited a more severe disease, high dyspnea severity, low respiratory function, and high impact on quality of life. Among the five patients with severe eosinophilic asthma and concomitant bronchiectasis included in the series, treatment with either mepolizumab or benralizumab significantly reduced the exacerbation rate with an effect that persists for up to 2 years of follow up. If validated across different settings, our data suggest the need to design randomized controlled trials on biological treatments targeting the T2-high endotype in bronchiectasis patients.

PMID:34356836 | DOI:10.3390/biomedicines9070772

Antibiotics (Basel). 2021 Jul 15;10(7):863. doi: 10.3390/antibiotics10070863.

ABSTRACT

Drug resistance represents a great concern among people with cystic fibrosis (CF), due to the recurrent and prolonged antibiotic therapy they should often undergo. Among Multi Drug Resistance (MDR) determinants, Resistance-Nodulation-cell Division (RND) efflux pumps have been reported as the main contributors, due to their ability to extrude a wide variety of molecules out of the bacterial cell. In this review, we summarize the principal RND efflux pump families described in CF pathogens, focusing on the main Gram-negative bacterial species (Pseudomonas aeruginosa, Burkholderia cenocepacia, Achromobacter xylosoxidans, Stenotrophomonas maltophilia) for which a predominant role of RND pumps has been associated to MDR phenotypes.

PMID:34356783 | DOI:10.3390/antibiotics10070863

Antibiotics (Basel). 2021 Jul 7;10(7):828. doi: 10.3390/antibiotics10070828.

ABSTRACT

The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. To date, these patients are excluded from treatment with Trikafta in Italy, where the CF patients carrying F508del/unknown represent about 1.3% (71 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment. This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine.

PMID:34356748 | DOI:10.3390/antibiotics10070828

Antibiotics (Basel). 2021 Jul 7;10(7):827. doi: 10.3390/antibiotics10070827.

ABSTRACT

Pseudomonas aeruginosa is one of the most dominant pathogens in cystic fibrosis (CF) airway disease and contributes to significant inflammation, airway damage, and poorer disease outcomes. The CF airway is now known to be host to a complex community of microorganisms, and polymicrobial interactions have been shown to play an important role in shaping P. aeruginosa pathogenicity and resistance. P. aeruginosa can cause chronic infections that once established are almost impossible to eradicate with antibiotics. CF patients that develop chronic P. aeruginosa infection have poorer lung function, higher morbidity, and a reduced life expectancy. P. aeruginosa adapts to the CF airway and quickly develops resistance to several antibiotics. A perplexing phenomenon is the disparity between in vitro antimicrobial sensitivity testing and clinical response. Considering the CF airway is host to a diverse community of microorganisms or 'microbiome' and that these microorganisms are known to interact, the antimicrobial resistance and progression of P. aeruginosa infection is likely influenced by these microbial relationships. This review combines the literature to date on interactions between P. aeruginosa and other airway microorganisms and the influence of these interactions on P. aeruginosa tolerance to antimicrobials.

PMID:34356747 | DOI:10.3390/antibiotics10070827

Clin Chest Med. 2021 Sep;42(3):517-530. doi: 10.1016/j.ccm.2021.04.010.

ABSTRACT

Women with cystic fibrosis (CF) face several unaddressed concerns related to their health. These areas of concern include explanations and guidance on a sex disparity in outcomes, timing of puberty, effects of contraception, prevalence of infertility and impact of pregnancy, and prevention of urinary incontinence and osteoporosis. These understudied topics leave women with numerous unanswered questions about how to manage sexual and reproductive health in the setting of CF. Because people with CF are living longer and healthier lives, there is an increasing awareness of these important aspects of care and multiple ongoing studies to address these understudied topics.

PMID:34353456 | DOI:10.1016/j.ccm.2021.04.010

Life Sci. 2021 Aug 2:119871. doi: 10.1016/j.lfs.2021.119871. Online ahead of print.

ABSTRACT

Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.

PMID:34352260 | DOI:10.1016/j.lfs.2021.119871

J Appl Physiol (1985). 2021 Aug 5. doi: 10.1152/japplphysiol.00338.2021. Online ahead of print.

ABSTRACT

RATIONALE: Nitrogen multiple-breath washout is an established technique to assess functional residual capacity and ventilation inhomogeneity in the lung. Accurate measurement of gas concentrations is essential for the appropriate calculation of clinical outcomes.

OBJECTIVES: We investigated the accuracy of oxygen and carbon dioxide gas sensor measurements used for the indirect calculation of nitrogen concentration in a commercial multiple-breath washout device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and its impact on functional residual capacity and lung clearance index.

METHODS: High precision calibration gas mixtures and mass spectrometry were used to evaluate sensor output. We assessed the impact of corrected signal processing on multiple-breath washout outcomes in a dataset of healthy children and children with cystic fibrosis using custom analysis software.

RESULTS: We found inadequate correction for the cross sensitivity of the oxygen and carbon dioxide sensors in the Exhalyzer D device. This results in an overestimation of expired nitrogen concentration, and consequently multiple-breath washout outcomes. Breath-by-breath correction of this error reduced the mean (SD) cumulative expired volume by 19.6 (5.0)%, functional residual capacity by 8.9 (2.2)%, and lung clearance index by 11.9 (4.0)%. It also substantially reduced the level of the tissue nitrogen signal at the end of measurements.

CONCLUSIONS: Inadequate correction for cross sensitivity in the oxygen and carbon dioxide gas sensors of the Exhalyzer D device leads to an overestimation of functional residual capacity and lung clearance index. Correction of this error is possible and could be applied by re-analyzing the measurements in an updated software version.

PMID:34351818 | DOI:10.1152/japplphysiol.00338.2021

ERJ Open Res. 2021 Aug 2;7(3):00096-2021. doi: 10.1183/23120541.00096-2021. eCollection 2021 Jul.

ABSTRACT

Although it is of great importance for healthcare professionals to ensure that patients' needs and concerns are valued and that they feel confident in the quality of the care they receive, there have been few studies specifically addressing the opinions, experiences and needs of patients with bronchiectasis, and more importantly the emotional impact of the disease, diagnosis and treatment. Using enterprise grade social listening tools, a comprehensive search around bronchiectasis was performed in five languages, on different social media platforms between January 2018 and December 2019 to obtain the perspectives of patients and caregivers from nine countries on symptoms, treatments and burden of the disease. Over 27 000 mentions of bronchiectasis were identified on social media channels, 38.8% of which were posted by patients and caregivers. Approximately 1600 posts were found on bronchiectasis symptoms, out of which persistent cough, shortness of breath and mucus production (22%, 20% and 18%, respectively) were the most commonly discussed. The research revealed that existing diagnostic tests often delay diagnosis or provide inaccurate results, leading to multiple rounds of consults and substantial delays in treatment initiation and management of the disease. Misdiagnosis was common across different age groups, especially among patients without severe symptoms, and this was associated with an emotional burden of anger, confusion, frustration and anxiety. Analysis of social media presents a new approach to derive insights on patients' experiences and emotions with bronchiectasis and has the potential to complement more traditional approaches to drive more patient-focused drug development.

PMID:34350285 | PMC:PMC8326711 | DOI:10.1183/23120541.00096-2021

ERJ Open Res. 2021 Aug 2;7(3):00856-2020. doi: 10.1183/23120541.00856-2020. eCollection 2021 Jul.

ABSTRACT

INTRODUCTION: Little is known about cystic fibrosis (CF) in low- to middle-income settings. This study aimed to describe the spectrum and outcomes of CF in South Africa (SA) from the recently established SA CF registry (SACFR).

METHODS: Demographic, diagnosis and clinical data were extracted from the SACFR. Cross-sectional univariable and multivariable regression analysis of best forced expiratory volume in 1 s (FEV1; age≥6 years) and nutrition (all ages) in 2018 was conducted to investigate factors associated with severe lung disease (SLD; FEV1 ≤3.0 z-score) and undernutrition.

RESULTS: By December 2018, ancestry of 447 individuals included in the SACFR was Caucasian (315; 70%), mixed (87; 19%) and black African (41; 9%). Median diagnosis age was 7.6 months (IQR 2.7-37.1). Genotype was p.Phe508del homozygous (220; 49%); p.Phe508del heterozygous (144; 32%) and neither p.Phe508del or unknown Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) variant in 83 (19%); the second most frequent CFTR variant was 3120+1G>A, common in black Africans. Median age of patients in 2018 was 14.7 years (IQR 7.4-24.4). SLD was independently associated with chronic methicillin-resistant Staphylococcus aureus (MRSA) (adjusted odds ratio( aOR) 16.75; 95% CI 1.74-161.50), undernutrition (aOR 5.20; 95% CI 2.23-12.13) and age (aOR 2.23 per 10 years; 95% CI 1.50-3.31). Undernutrition was associated in univariable analysis with low weight at diagnosis, non-Caucasian ancestry, chronic P. aeruginosa infection and lower socioeconomic status.

CONCLUSION: Interventions targeting MRSA infection and nutrition are needed to improve CF outcomes in SA. Most people with CF in SA are eligible for highly effective CFTR modulator therapy.

PMID:34350279 | PMC:PMC8326682 | DOI:10.1183/23120541.00856-2020

Front Pharmacol. 2021 Jul 19;12:695181. doi: 10.3389/fphar.2021.695181. eCollection 2021.

ABSTRACT

Provision of the latest innovative and advanced therapies for rare diseases (RDs) patients, following the international therapeutic recommendations, is crucial and necessary for both practitioners and patients. The goal is to assess the access of Bulgarian patients with the most cost-consuming RDs to medicines and to compare the pharmacotherapeutic patterns in Bulgaria and the relevant European professional associations. Pharmaco-therapeutic guidelines for treating the most cost-consuming RDs in Bulgaria were analyzed to assess their compliance with the European ones. Market entrance was evaluated through analysis of the availability of medicines in the Positive Drug List (PDL) and their date of inclusion since marketing authorization. Guidelines' compliance index was calculated and patient access was analyzed through evaluation of the National Health Insurance Fund (NHIF) standards, which provide additional criteria for treatment initiation. The analyzed guidelines follow the adopted recommendations by the relevant European professional associations. NHIF have exclusion and inclusion criteria for initiating treatment with medicines for rare diseases and for continuation. The average time-lag between centralized procedure approval and inclusion in the Bulgarian PDL for orphan medicinal products (MPs) is 6.75 years (SD = 4.96) with the longest time observed for eptacog alfa (20 years) and the shortest for rurioctocog alfa pegol, octocog alfa and simoctocog alfa (1 year). Bulgarian patients with cystic fibrosis with pulmonary manifestation had a wait time of only 1.6 years to get access to innovative, centrally authorized medicines, whereas the period for access to acromegaly treatment was 8.2 years. The main factors influencing market entrance and patient access are the time to inclusion in the PDL and the NHIF criteria.

PMID:34349654 | PMC:PMC8326790 | DOI:10.3389/fphar.2021.695181

NPJ Biofilms Microbiomes. 2021 Aug 4;7(1):63. doi: 10.1038/s41522-021-00234-3.

ABSTRACT

The exopolysaccharide Psl contributes to biofilm structure and antibiotic tolerance and may play a role in the failure to eradicate Pseudomonas aeruginosa from cystic fibrosis (CF) airways. The study objective was to determine whether there were any differences in Psl in P. aeruginosa isolates that were successfully eradicated compared to those that persisted, despite inhaled tobramycin treatment, in children with CF. Initial P. aeruginosa isolates were collected from children with CF undergoing eradication treatment, grown as biofilms and labeled with 3 anti-Psl monoclonal antibodies (Cam003/Psl0096, WapR001, WapR016) before confocal microscopy visualization. When grown as biofilms, P. aeruginosa isolates from children who failed antibiotic eradication therapy, had significantly increased Psl0096 binding compared to isolates from those who cleared P. aeruginosa. This was confirmed in P. aeruginosa isolates from the SickKids Eradication Cohort as well as the Early Pseudomonas Infection Control (EPIC) trial. Increased anti-Psl antibody binding was associated with bacterial aggregation and tobramycin tolerance. The biofilm matrix represents a potential therapeutic target to improve P. aeruginosa eradication treatment.

PMID:34349133 | DOI:10.1038/s41522-021-00234-3

J Cyst Fibros. 2021 Aug 1:S1569-1993(21)01302-3. doi: 10.1016/j.jcf.2021.07.004. Online ahead of print.

ABSTRACT

To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV1%), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI. Results: From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1). Conclusions: We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk.

PMID:34348871 | DOI:10.1016/j.jcf.2021.07.004

J Cyst Fibros. 2021 Aug 1:S1569-1993(21)01304-7. doi: 10.1016/j.jcf.2021.07.006. Online ahead of print.

ABSTRACT

Superior efficacy of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) over tezacaftor/ivacaftor (TEZ/IVA) in people with cystic fibrosis (CF) and Phe508del/Phe508del genotype was shown in clinical trials. We utilized intestinal organoid approach to compare in vitro responses to these 2 CFTR modulator drug combinations and to check potential inter-individual variability in therapeutic response to the triple combination. Organoids from 17 subjects with Phe508del/Phe508del were screened with forskolin induced swelling assay. Significantly larger swelling, when exposed to ELX/TEZ/IVA as compared to TEZ/IVA, was observed in 16 of them. However, 1 sample showed no additional effect of ELX. The finding of unique CFTR variants in this sample indicates that genetic traits other than CF-causing CFTR mutation are worth exploring as they may have an impact on the definitive modulator drug response.

PMID:34348870 | DOI:10.1016/j.jcf.2021.07.006

BMC Pulm Med. 2021 Aug 4;21(1):256. doi: 10.1186/s12890-021-01622-3.

ABSTRACT

BACKGROUND: Functional Respiratory Imaging (FRI) combines HRCT scans with computational fluid dynamics to provide objective and quantitative information about lung structure and function. FRI has proven its value in pulmonary diseases such as COPD and asthma, but limited studies have focused on cystic fibrosis (CF). This study aims to investigate the relation of multiple FRI parameters to validated imaging parameters and classical respiratory outcomes in a CF population.

METHODS: CF patients aged > 5 years scheduled for a chest CT were recruited in a cross-sectional study. FRI outcomes included regional airway volume, airway wall volume, airway resistance, lobar volume, air trapping and pulmonary blood distribution. Besides FRI, CT scans were independently evaluated by 2 readers using the CF-CT score. Spirometry and the 6-Minute Walk Test (6MWT) were also performed. Statistical tests included linear mixed-effects models, repeated measures correlations, Pearson and Spearman correlations.

RESULTS: 39 CT scans of 24 (17M/7F) subjects were analyzed. Patients were 24 ± 9 years old and had a ppFEV1 of 71 ± 25% at the time of the first CT. All FRI parameters showed significant low-to-moderate correlations with the total CF-CT score, except for lobar volume. When considering the relation between FRI parameters and similar CF-CT subscores, significant correlations were found between parameters related to airway volume, air trapping and airway wall thickening. Air trapping, lobar volume after normal expiration and pulmonary blood distribution showed significant associations with all spirometric parameters and oxygen saturation at the end of 6MWT. In addition, air trapping was the only parameter related to the distance covered during 6MWT. A subgroup analysis showed considerably higher correlations in patients with mild lung disease (ppFEV1 ≥ 70%) compared to patients with moderate to severe lung disease (ppFEV1 < 70%) when comparing FRI to CF-CT scores.

CONCLUSIONS: Multiple structural characteristics determined by FRI were associated with abnormalities determined by CF-CT score. Air trapping and pulmonary blood distribution appeared to be the most clinically relevant FRI parameters for CF patients due to their associations with classical outcome measures. The FRI methodology could particularly be of interest for patients with mild lung disease, although this should be confirmed in future research.

PMID:34348676 | DOI:10.1186/s12890-021-01622-3

Pediatr Pulmonol. 2021 Aug 4. doi: 10.1002/ppul.25613. Online ahead of print.

ABSTRACT

Care for people with cystic fibrosis (PWCF) is highly complex and requires a multi-disciplinary approach where the pharmacist plays a vital role. The purpose of this manuscript is to serve as a guideline for pharmacists and pharmacy technicians who provide care for PWCF by providing background and current recommendations for the use of cystic fibrosis (CF)-specific medications in both the acute and ambulatory care settings. The article explores current literature surrounding the role of pharmacists and pharmacy technicians, proven pharmacy models to emulate and pharmacokinetic idiosyncrasies unique to the CF population while also identifying areas of future research. Clinical recommendations for the use of CF specific medications are broken down by organ system including mechanism of action, adverse events, dosages, and monitoring parameters. The article also includes quick reference tables essential to the acute and chronic medication therapy management of PWCF. This article is protected by copyright. All rights reserved.

PMID:34347382 | DOI:10.1002/ppul.25613

J Appl Genet. 2021 Aug 4. doi: 10.1007/s13353-021-00651-2. Online ahead of print.

ABSTRACT

Based on a macroscopic analysis of the heart of Frederic Chopin performed in 2014, it can be stated with high probability that the composer suffered from a long lasting tuberculosis as a primary disease, which was the cause of progressive deterioration of his physical condition and numerous symptoms mainly from the respiratory tract. Tuberculous pericarditis rapidly progressing within a rather short period of time, a relatively rare complication of diffuse tuberculosis, might have been an immediate cause of death. This would aptly coincide with a startling opinion that in an autopsy picture the composer's heart had been more affected by the disease than the lungs.

PMID:34347238 | DOI:10.1007/s13353-021-00651-2

J Clin Microbiol. 2021 Aug 4:JCM0094621. doi: 10.1128/JCM.00946-21. Online ahead of print.

ABSTRACT

Objective: Achromobacter spp. are increasingly reported among cystic fibrosis patients. Genotyping requires time consuming methods such as Multilocus-Sequence-Typing or Pulsed-Field-Gel-Electrophoresis. Therefore, data on the prevalence of the multiresistant epidemic clones, especially A. xylosoxidans ST137 (AxST137) and the Danish Epidemic Strain A. ruhlandii (DES) are lacking. We recently developed and published a database for Achromobacter species identification by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS, Bruker Daltonics). The aim of this study was to evaluate the ability of the MALDI-TOF MS to distinguish these multiresistant epidemic clones within Achromobacter species. Methods: All the spectra of A.xylosoxidans (n=1571) and A.ruhlandii (n=174) used to build the local database were analysed by ClinProTools™, MALDI Biotyper® PCA, MALDI Biotyper® dendrogram and flexAnalysis™ softwares for biomarker peaks detection. Two-hundred-two isolates (including 48 isolates of AxST137 and 7 of DES) were tested. Results: Specific biomarker peaks were identified: absent peak at m/z 6651 for AxST137 isolates and present peak at m/z 9438 for DES isolates. All tested isolates were well typed by our local database and clustered within distinct groups (ST137 or non-ST137 and DES or non-DES) no matter the MALDI-TOF software or only by simple visual inspection of the spectra by any user. Conclusions: The use of MALDI-TOF MS allowed identifying isolates of A. xylosoxidans belonging to the AxST137 clone which spread in France and Belgium (the Belgian epidemic clone) and of A. ruhlandii belonging to the DES clone. This tool will help implementation of segregation measures to avoid inter-patient transmission of these resistant clones.

PMID:34346714 | DOI:10.1128/JCM.00946-21

Prenat Diagn. 2021 Aug 4. doi: 10.1002/pd.6027. Online ahead of print.

ABSTRACT

OBJECTIVE: We investigated the cost-effectiveness of three sequential prenatal cystic fibrosis (CF) carrier screening strategies: genotyping both partners, genotyping one partner then sequencing the second, and sequencing both partners.

METHOD: A decision-analytic model compared the strategies in a theoretical cohort of 4 million pregnant couples in the US population and five racial/ethnic sub-populations. Inputs were obtained from literature and varied in sensitivity analysis. Outcomes included cost per quality-adjusted life year (QALY), missed carrier couples, affected newborns, missed prenatal diagnoses, terminations, and procedure-related losses. The cost-effectiveness threshold was $100,000/QALY.

RESULTS: Sequencing both partners identified 1,099 carrier couples that were missed by genotyping both partners, leading to 273 fewer missed prenatal diagnoses, 152 more terminations, and 152 fewer affected newborns. A similar trend was observed in the genotyping followed by sequencing strategy. The incremental cost-effectiveness ratio of genotyping followed by sequencing compared to genotyping both partners was $180,004/QALY and the incremental cost-effectiveness ratio of sequencing both partners compared to genotyping followed by sequencing was $17.6 million/QALY. Sequencing both partners was cost-effective below $339 per test, genotyping/sequencing between $340-1,837, and genotyping both partners above $1,838. Sequencing was not cost-effective among five racial/ethnic sub-populations.

CONCLUSION: Despite improved outcomes, sequencing for prenatal CF carrier screening was not cost-effective compared to genotyping. The clinical significance of the incremental cost-effectiveness of CF carrier screening is a matter of deliberation for public policy debate. This article is protected by copyright. All rights reserved.

PMID:34346064 | DOI:10.1002/pd.6027

Adv Nanobiomed Res. 2021 May 6;1(6):2000111. doi: 10.1002/anbr.202000111. eCollection 2021 Jun.

ABSTRACT

Air-liquid interface (ALI) culture models currently represent a valid instrument to recreate the typical aspects of the respiratory tract in vitro in both healthy and diseased state. They can help reducing the number of animal experiments, therefore, supporting the 3R principle. This review discusses ALI cultures and co-cultures derived from immortalized as well as primary cells, which are used to study the most common disorders of the respiratory tract, in terms of both pathophysiology and drug screening. The article displays ALI models used to simulate inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, lung cancer, and viral infections. It also includes a focus on ALI cultures described in literature studying respiratory viruses such as SARS-CoV-2 causing the global Covid-19 pandemic at the time of writing this review. Additionally, commercially available models of ALI cultures are presented. Ultimately, the aim of this review is to provide a detailed overview of ALI models currently available and to critically discuss them in the context of the most prevalent diseases of the respiratory tract.

PMID:34345878 | PMC:PMC7611446 | DOI:10.1002/anbr.202000111

Cureus. 2021 Jul 1;13(7):e16087. doi: 10.7759/cureus.16087. eCollection 2021 Jul.

ABSTRACT

Acute respiratory failure in cystic fibrosis carries a high risk of mortality. The optimal mode of mechanical ventilation (MV) in this population is not well established. In this case series, we identified patients with cystic fibrosis who were ventilated with high-frequency percussive ventilation (HFPV) at our institution and describe their characteristics and outcomes. The use of high-frequency percussive ventilation has been sparsely described in the literature. This case series could serve as hypothesis-generating for future research.

PMID:34345563 | PMC:PMC8325394 | DOI:10.7759/cureus.16087