Children (Basel). 2023 Jan 18;10(2):177. doi: 10.3390/children10020177.

ABSTRACT

BACKGROUND: An inconclusive diagnosis of cystic fibrosis (CF) after positive newborn screening (NBS) may cause parental distress. We compared the psychological impact of CF transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID), and clear CF diagnosis, on parents.

METHODS: The participants were administered the Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, and the Italian version of the Impact of Event Scale-Revised as quantitative tools and semi-structured interviews as qualitative tools. Parental experience, child representation, relationships, future information, and perception of health status were investigated. Interviews were recorded and transcribed verbatim maintaining anonymity.

RESULTS: Thirty-two families were enrolled: sixteen with CF and CRMS/CFSPID, respectively. Anxiety and depression values were high in both groups, as were the measurement of traumatic impact subscales: avoidance, intrusiveness, and hyperarousal. The children's health was evaluated by respective parents as being nearly healthy.

CONCLUSIONS: Our results highlight negative psychological impacts, including emotional and affective representations, on parents of children with inconclusive CF diagnosis compared with those with clear diagnosis.

PMID:36832306 | DOI:10.3390/children10020177

Diagnostics (Basel). 2023 Feb 17;13(4):763. doi: 10.3390/diagnostics13040763.

ABSTRACT

The diagnosis of cystic fibrosis has improved in the last few years due to greater access to diagnostic tools and the evolution of molecular biology; the knowledge obtained has contributed to the understanding of its death profile. In this context, an epidemiological study was developed focusing on deaths from cystic fibrosis in Brazil from 1996 to 2019. The data were collected from the Data-SUS (Unified National Health System Information Technology Department from Brazil). The epidemiological analysis included patients' age groups, racial groups, and sex. In our data, between 1996 and 2019, Σ3050 deaths were recorded, totaling a ≅330% increase in the number of deaths resulting from cystic fibrosis. This fact might be related to a better diagnosis of the disease, mainly in patients from racial groups that are not commonly associated with cystic fibrosis, such as Black individuals, Hispanic or Latino (mixed individuals/Pardos) individuals, and American Indians (Indigenous peoples from Brazil). Regarding of race, the Σ of deaths was: nine (0.3%) in the American Indian group, 12 (0.4%) in the Asian group, 99 (3.6%) in the Black or African American group, 787 (28.6%) in the Hispanic or Latino group, and 1843 (67.0%) in the White group. The White group showed the highest prevalence of deaths, and the increase in mortality was ≅150 times in this group, while, in the Hispanic or Latino group, it was ≅75 times. Regarding sex, the numbers and percentage of deaths of both male (N = 1492; 48.9%) and female (N = 1557; 51.1%) patients were seen to be relatively close. As for age groups, the >60-year-old group presented the most significant results, with an increase of ≅60 times in the registered deaths. In conclusion, in Brazil, despite the number of deaths from cystic fibrosis being prevalent in the White group, it increased in all racial groups (Hispanic or Latino, Black or African American, American Indian, or Asian individuals) and was associated with older age.

PMID:36832251 | DOI:10.3390/diagnostics13040763

Cells. 2023 Feb 7;12(4):536. doi: 10.3390/cells12040536.

ABSTRACT

Gene therapy holds tremendous potential in the treatment of inherited diseases. Unlike traditional medicines, which only treat the symptoms, gene therapy has the potential to cure the disease by addressing the root of the problem: genetic mutations. The discovery of CRISPR/Cas9 in 2012 paved the way for the development of those therapies. Improvement of this system led to the recent development of an outstanding technology called prime editing. This system can introduce targeted insertions, deletions, and all 12 possible base-to-base conversions in the human genome. Since the first publication on prime editing in 2019, groups all around the world have worked on this promising technology to develop a treatment for genetic diseases. To date, prime editing has been attempted in preclinical studies for liver, eye, skin, muscular, and neurodegenerative hereditary diseases, in addition to cystic fibrosis, beta-thalassemia, X-linked severe combined immunodeficiency, and cancer. In this review, we portrayed where we are now on prime editing for human gene therapy and outlined the best strategies for correcting pathogenic mutations by prime editing.

PMID:36831203 | DOI:10.3390/cells12040536

Biomedicines. 2023 Feb 20;11(2):628. doi: 10.3390/biomedicines11020628.

ABSTRACT

The new breakthrough cystic fibrosis (CF) drug combination of ivacaftor (IVA), tezacaftor (TEZ), and elexacaftor (ELX), namely "caftor" drugs, directly modulates the activity and trafficking of the defective CF transmembrane conductance regulator protein (CFTR) underlying the CF disease. The role of therapeutic drug monitoring (TDM) of caftor drugs in clinical settings has recently been established. The availability of reliable and robust analytical methods for the quantification of IVA, TEZ, and ELX is essential to support dose-concentration-effect studies. We have developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the rapid and simultaneous quantification of IVA, TEZ, and ELX from the plasma of CF patients. The method was based on a rapid extraction protocol from 50 μL human plasma and separation on a reversed-phase C-18 HPLC column after the addition of deuterated internal standards. Accurate analyte quantification using multiple reaction monitoring (MRM) detection was then obtained using a Thermofisher Quantiva triple-quadrupole MS coupled to an Ultimate 3000 UHPLC. The method has been validated following international (EMA) guidelines for bioanalytical method validation and has been tested on plasma samples from 62 CF patients treated with the three-drug combination IVA/TEZ/ELX, marketed as Kaftrio® or Trikafta®, in steady-state condition. The assay was linear over wide concentration ranges (0.008-12 mg/L) in plasma for IVA, TEZ, and ELX, suitable for a broad range of plasma concentrations, and accurate and reproducible in the absence of matrix effects. The stability of analytes for at least 30 days at room temperature could allow for cost-effective shipment and storage. On the same day of sample collection, a sweat test was evaluated for 26 associated patients' samples, FEV1 (%) for 58, and BMI was calculated for 62. However, Spearman correlation showed no correlation between Cthrough plasma concentrations of analytes (IVA, TEZ, ELX) and sweat test, FEV1 (%), or BMI. Our method proved to be suitable for TDM and could be helpful in assessing dose-concentration-response correlations in larger studies.

PMID:36831163 | DOI:10.3390/biomedicines11020628

Biomedicines. 2023 Jan 23;11(2):321. doi: 10.3390/biomedicines11020321.

ABSTRACT

Fluid therapy is the cornerstone of early supportive therapy in acute pancreatitis (AP). Regrettably, the type of fluid is still debated among clinicians, despite recent evidence from randomized controlled trials (RCTs). We aimed to incorporate all evidence from RCTs comparing lactated Ringer's solution (LR) with normal saline (NS) in adult and pediatric AP patients, with particular emphasis on clinically relevant outcomes. We evaluated RCTs comparing intravenous fluid resuscitation with LR to NS in adult or pediatric AP patients according to a prospectively registered protocol (CRD42021224542). Moderate-to-severe AP (MSAP), mortality, length of hospitalization (LoH), need for intensive care, the incidence of systemic (organ failure, OF) and local complications (in total), necrosis and pseudocyst formation were analyzed separately. Risk ratio (RR) and median difference (MD) were calculated with 95% confidence intervals (CI) using a random effect model. Risk of bias and quality of evidence were assessed. Altogether, 8 eligible RCTs were found, including 557 patients (LR: 278; NS: 279). LR reduced the risk of MSAP by 31% (RR: 0.59, 95% CI: 0.36-0.97, high quality) and the risk of death by 62% (RR: 0.48; 95% CI: 0.24-0.98, very low quality). LR was associated with a significantly lower risk of need for intensive care (RR: 0.50, 95% CI: 0.33-0.77), OF (RR: 0.78, 95% CI: 0.61-0.99) and local complications (RR: 0.64, 95% CI: 0.46-0.89). No significant risk reduction was observed for LoH (MD: -0.57 days, CI: -1.33-0.19), necrosis, pseudocyst and inflammatory parameters by LR compared to NS. LR reduces severity, mortality, need of intensive care and systemic and local complications in AP.

PMID:36830858 | DOI:10.3390/biomedicines11020321

Biomolecules. 2023 Feb 10;13(2):350. doi: 10.3390/biom13020350.

ABSTRACT

Cystic fibrosis (CF) is a high-prevalence disease characterized by significant lung remodeling, responsible for high morbidity and mortality worldwide. The lung structural changes are partly due to proteolytic activity associated with inflammatory cells such as neutrophils and macrophages. Matrix metalloproteases (MMPs) are the major proteases involved in CF, and recent literature data focused on their potential role in the pathogenesis of the disease. In fact, an imbalance of proteases and antiproteases was observed in CF patients, resulting in dysfunction of protease activity and loss of lung homeostasis. Currently, many steps forward have been moved in the field of pharmacological treatment with the recent introduction of triple-combination therapy targeting the CFTR channel. Despite CFTR modulator therapy potentially being effective in up to 90% of patients with CF, there are still patients who are not eligible for the available therapies. Here, we introduce experimental drugs to provide updates on therapy evolution regarding a proportion of CF non-responder patients to current treatment, and we summarize the role of MMPs in pathogenesis and as future therapeutic targets of CF.

PMID:36830719 | DOI:10.3390/biom13020350

Biomolecules. 2023 Jan 27;13(2):242. doi: 10.3390/biom13020242.

ABSTRACT

Premature termination codons (PTCs) account for ~12% of all human disease mutations. Translation readthrough-inducing drugs (TRIDs) are prominent among the several therapeutic approaches being used to overcome PTCs. Ataluren is the only TRID that has been approved for treating patients suffering from a PTC disease, Duchenne muscular dystrophy, but it gives variable readthrough results in cells isolated from patients suffering from other PTC diseases. We recently elucidated ataluren's mechanism of action as a competitive inhibitor of release factor complex (RFC) catalysis of premature termination and identified ataluren's binding sites on the ribosome responsible for such an inhibition. These results suggest the possibility of discovering new TRIDs, which would retain ataluren's low toxicity while displaying greater potency and generality in stimulating readthrough via the inhibition of termination. Here we present a detailed description of a new in vitro plate reader assay that we are using both to screen small compound libraries for the inhibition of RFC-dependent peptide release and to better understand the influence of termination codon identity and sequence context on RFC activity.

PMID:36830611 | DOI:10.3390/biom13020242

Antibiotics (Basel). 2023 Feb 8;12(2):348. doi: 10.3390/antibiotics12020348.

ABSTRACT

The urgent need to combat antibiotic resistance and develop novel antimicrobial therapies has triggered studies on novel metal-based formulations. N-heterocyclic carbene (NHC) complexes coordinate transition metals to generate a broad range of anticancer and/or antimicrobial agents, with ongoing efforts being made to enhance the lipophilicity and drug stability. The lead silver(I) acetate complex, 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) (SBC3), has previously demonstrated promising growth and biofilm-inhibiting properties. In this work, the responses of two structurally different bacteria to SBC3 using label-free quantitative proteomics were characterised. Multidrug-resistant Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) are associated with cystic fibrosis lung colonisation and chronic wound infections, respectively. SBC3 increased the abundance of alginate biosynthesis, the secretion system and drug detoxification proteins in P. aeruginosa, whilst a variety of pathways, including anaerobic respiration, twitching motility and ABC transport, were decreased in abundance. This contrasted the affected pathways in S. aureus, where increased DNA replication/repair and cell redox homeostasis and decreased protein synthesis, lipoylation and glucose metabolism were observed. Increased abundance of cell wall/membrane proteins was indicative of the structural damage induced by SBC3 in both bacteria. These findings show the potential broad applications of SBC3 in treating Gram-positive and Gram-negative bacteria.

PMID:36830259 | DOI:10.3390/antibiotics12020348

Antibiotics (Basel). 2023 Feb 1;12(2):286. doi: 10.3390/antibiotics12020286.

ABSTRACT

The production and use of antibiotics increased significantly after the Second World War due to their effectiveness against bacterial infections. However, bacterial resistance also emerged and has now become an important global issue. Those most in need are typically high-risk and include individuals who experience burns and other wounds, as well as those with pulmonary infections caused by antibiotic-resistant bacteria, such as Pseudomonas aeruginosa, Acinetobacter sp, and Staphylococci. With investment to develop new antibiotics waning, finding and developing alternative therapeutic strategies to tackle this issue is imperative. One option remerging in popularity is bacteriophage (phage) therapy. This review focuses on Staphylococcus aureus and how it has developed resistance to antibiotics. It also discusses the potential of phage therapy in this setting and its appropriateness in high-risk people, such as those with cystic fibrosis, where it typically forms a biofilm.

PMID:36830196 | DOI:10.3390/antibiotics12020286

Antibiotics (Basel). 2023 Jan 20;12(2):217. doi: 10.3390/antibiotics12020217.

ABSTRACT

Patients with cystic fibrosis (CF) are repeatedly exposed to antibiotics, especially during the pulmonary exacerbations of the disease. However, the available therapeutic strategies are frequently inadequate to eradicate the involved pathogens and most importantly, facilitate the development of antimicrobial resistance (AMR). The evaluation of AMR is demanding; conventional culture-based susceptibility-testing techniques cannot account for the lung microenvironment and/or the adaptive mechanisms developed by the pathogens, such as biofilm formation. Moreover, features linked to modified pharmaco-kinetics and pulmonary parenchyma penetration make the dosing of antibiotics even more challenging. In this review, we present the existing knowledge regarding AMR in CF, we shortly review the existing therapeutic strategies, and we discuss the future directions of antimicrobial stewardship. Due to the increasing difficulty in eradicating strains that develop AMR, the appropriate management should rely on targeting the underlying resistance mechanisms; thus, the interest in novel, molecular-based diagnostic tools, such as metagenomic sequencing and next-generation transcriptomics, has increased exponentially. Moreover, since the development of new antibiotics has a slow pace, the design of effective treatment strategies to eradicate persistent infections represents an urgency that requires consorted work. In this regard, both the management and monitoring of antibiotics usage are obligatory and more relevant than ever.

PMID:36830128 | DOI:10.3390/antibiotics12020217

Antibiotics (Basel). 2023 Jan 18;12(2):200. doi: 10.3390/antibiotics12020200.

ABSTRACT

Pseudomonas aeruginosa has the genetic potential to acquire colistin resistance through the modification of lipopolysaccharide by the addition of 4-amino-4-deoxy-L-arabinose (L-Ara4N) or phosphoethanolamine (PEtN), mediated by the arn operon or the eptA gene, respectively. However, in vitro evolution experiments and genetic analysis of clinical isolates indicate that lipopolysaccharide modification with L-Ara4N is invariably preferred over PEtN addition as the colistin resistance mechanism in this bacterium. Since little is known about eptA regulation in P. aeruginosa, we generated luminescent derivatives of the reference strain P. aeruginosa PAO1 to monitor arn and eptA promoter activity. We performed transposon mutagenesis assays to compare the likelihood of acquiring mutations leading to arn or eptA induction and to identify eptA regulators. The analysis revealed that eptA was slightly induced under certain stress conditions, such as arginine or biotin depletion and accumulation of the signal molecule diadenosine tetraphosphate, but the induction did not confer colistin resistance. Moreover, we demonstrated that spontaneous mutations leading to colistin resistance invariably triggered arn rather than eptA expression, and that eptA was not induced in resistant mutants upon colistin exposure. Overall, these results suggest that the contribution of eptA to colistin resistance in P. aeruginosa may be limited by regulatory restraints.

PMID:36830112 | DOI:10.3390/antibiotics12020200

Bioengineering (Basel). 2023 Feb 11;10(2):242. doi: 10.3390/bioengineering10020242.

ABSTRACT

We report the implementation of a pediatric home spirometry program at our institution. A respiratory therapist provided either a virtual or an in-person initiation visit that included a coached spirometry session. Families were instructed to perform daily uncoached spirometry sessions for 5 days. The program's quality assurance component was deemed not to be human research by the local IRB. In total, 52 subjects completed an initiation visit (34 with at least 3 additional uncoached spirometry sessions). The clinic spirometry and coached (same-day) sessions and uncoached (same-week) sessions were completed by 12 and 17 subjects, respectively. The median (99% CI) coefficients of variation for FEV1% of the uncoached maneuvers were 3.5% (2.9-5.9%). The median (IQR) FEV1% and FEV1 (mL) absolute differences between coached and uncoached home spirometry were -2% (-4 and +3%) and -25 mL (-93 and +93 mL), respectively. The median (IQR) absolute differences in FEV1% and FEV1 (mL) between coached or uncoached home spirometry and clinic spirometry were -6% (-10 and -2%) and -155 mL (-275 and -88 mL), and -4% (-10 and +5%), and -110 mL (-280 and +9 mL), respectively. Differences in absolute FEV1 (L) and FEV1% were found among different modalities of spirometry performed by people with cystic fibrosis. Understanding the variability of uncoached home spirometry and the differences among coached and uncoached home spirometry, hospital and coached home spirometry, and hospital and uncoached home spirometry for any given individual is crucial to effectively utilize this tool in clinical care.

PMID:36829736 | DOI:10.3390/bioengineering10020242

Paediatr Respir Rev. 2023 Feb 10:S1526-0542(23)00004-0. doi: 10.1016/j.prrv.2023.02.001. Online ahead of print.

ABSTRACT

Nontuberculous mycobacteria (NTM) can cause severe pulmonary disease in people with cystic fibrosis (pwCF). These infections present unique challenges for diagnosis and treatment, prompting a recent interest in understanding NTM transmission and pathogenesis during chronic infection. Major gaps remain in our knowledge regarding basic pathogenesis, immune evasion strategies, population dynamics, recombination potential, and the evolutionary implications of host and antibiotic pressures of long-term NTM infections in pwCF. Phylogenomic techniques have emerged as an important tool for tracking global patterns of transmission and are beginning to be used to ask fundamental biological questions about adaptation to the host during pathogenesis. In this review, we discuss the burden of NTM lung disease (NTM-LD), highlight the use of phylogenomics in NTM research, and address the clinical implications associated with these studies.

PMID:36828670 | DOI:10.1016/j.prrv.2023.02.001

Respir Med. 2023 Feb 22:107169. doi: 10.1016/j.rmed.2023.107169. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) and Primary ciliary dyskinesia (PCD) are both rare chronic diseases, inherited disorders associated with multiple complications, namely respiratory complications, due to impaired mucociliary clearance that affect severely patients' lives. Although both are classified as rare diseases, PCD has a much lower prevalence than CF, particularly among Caucasians. As a result, CF is well studied, better recognized by clinicians, and with some therapeutic approaches already available. Whereas PCD is still largely unknown, and thus the approach is based on consensus guidelines, expert opinion, and extrapolation from the larger evidence base available for patients with CF. Both diseases have some clinical similarities but are very different, necessitating different treatment by specialists who are familiar with the complexities of each disease.This review aims to provide an overview of the knowledge about the two diseases with a focus on the similarities and differences between both in terms of disease mechanisms, common clinical manifestations, genetics and the most relevant therapeutic options. We hoped to raise clinical awareness about PCD, what it is, how it differs from CF, and how much information is still lacking. Furthermore, this review emphasises the fact that both diseases require ongoing research to find better treatments and, in particular for PCD, to fill the medical and scientific gaps.

PMID:36828173 | DOI:10.1016/j.rmed.2023.107169

J Allergy Clin Immunol. 2023 Feb 22:S0091-6749(23)00217-8. doi: 10.1016/j.jaci.2023.01.035. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is one of the most common life limiting autosomal recessive disorders and is caused by genetic defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Some of the features of this multisystem disease can be present in primary immunodeficiency (PID).

OBJECTIVE: We hypothesized that a 'carrier' CFTR status might be associated with worse outcome regarding structural lung disease in patients with PID.

METHODS: A within-cohort and population level statistical genomic analysis of a large European cohort of PID patients was performed using genome sequence data. Genomic analysis of variant pathogenicity was performed.

RESULTS: Compared to the general population, p.Phe508del carriage was enriched in lung-related PID. Additionally, carriage of several pathogenic CFTR gene variants were increased in PID associated with structural lung damage, compared to PID patients without the structural lung damage. We identified three additional biallelic cases including several variants not traditionally considered as CF-causing.

CONCLUSION: Genome sequencing identified cases of CFTR dysfunction in PID, driving an increased susceptibility to infection. Large national genomics services provide an opportunity for precision medicine by interpreting subtle features of genomic diversity when treating traditional Mendelian disorders.

PMID:36828084 | DOI:10.1016/j.jaci.2023.01.035

Microbiologyopen. 2023 Feb;12(1):e1311. doi: 10.1002/mbo3.1311.

ABSTRACT

Universal stress proteins (USPs) are ubiquitously expressed in bacteria, archaea, and eukaryotes and play a lead role in adaptation to environmental conditions. They enable adaptation of bacterial pathogens to the conditions encountered in the human niche, including hypoxia, oxidative stress, osmotic stress, nutrient deficiency, or acid stress, thereby facilitating colonization. We previously reported that all six USP proteins encoded within a low-oxygen activated (lxa) locus in Burkholderia cenocepacia showed increased abundance during chronic colonization of the cystic fibrosis (CF) lung. However, the role of USPs in chronic cystic fibrosis infection is not well understood. Structural modeling identified surface arginines on one lxa-encoded USP, USP76, which suggested it mediated interactions with heparan sulfate. Using mutants derived from the B. cenocepacia strain, K56-2, we show that USP76 is involved in host cell attachment. Pretreatment of lung epithelial cells with heparanase reduced the binding of the wild-type and complement strains but not the Δusp76 mutant strain, indicating that USP76 is directly or indirectly involved in receptor recognition on the surface of epithelial cells. We also show that USP76 is required for growth and survival in many conditions associated with the CF lung, including acidic conditions and oxidative stress. Moreover, USP76 also has a role in survival in macrophages isolated from people with CF. Overall, while further elucidation of the exact mechanism(s) is required, we can conclude that USP76, which is upregulated during chronic infection, is involved in bacterial survival within CF macrophages, a hallmark of Burkholderia infection.

PMID:36825886 | DOI:10.1002/mbo3.1311

Res Sq. 2023 Feb 17:rs.3.rs-2540755. doi: 10.21203/rs.3.rs-2540755/v1. Preprint.

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, to improve base editor RNP delivery, we optimized S10 to derive the S315 peptide. Following intratracheal aerosol of Cy5-labeled peptide cargo in rhesus macaques, we confirmed delivery throughout the respiratory tract. Subsequently, we targeted CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieved editing efficiencies of up to 5.3% in rhesus airway epithelia. Moreover, we documented persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restored anion channel function in cultured human airway epithelial cells. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.

PMID:36824928 | PMC:PMC9949254 | DOI:10.21203/rs.3.rs-2540755/v1

Front Physiol. 2023 Feb 7;14:1104856. doi: 10.3389/fphys.2023.1104856. eCollection 2023.

ABSTRACT

Cystic fibrosis (CF) lung disease is characterised by recurring bacterial infections resulting in inflammation, lung damage and ultimately respiratory failure. Pseudomonas aeruginosa is considered one of the most important lung pathogens in those with cystic fibrosis. While multiple cystic fibrosis animal models have been developed, many fail to mirror the cystic fibrosis lung disease of humans, including the colonisation by opportunistic environmental pathogens. Delivering bacteria to the lungs of animals in different forms is a way to model cystic fibrosis bacterial lung infections and disease. This review presents an overview of previous models, and factors to consider when generating a new P. aeruginosa lung infection model. The future development and application of lung infection models that more accurately reflect human cystic fibrosis lung disease has the potential to assist in understanding the pathophysiology of cystic fibrosis lung disease and for developing treatments.

PMID:36824474 | PMC:PMC9942929 | DOI:10.3389/fphys.2023.1104856

Emerg Infect Dis. 2023 Mar;29(3):642-644. doi: 10.3201/eid2903.221564.

ABSTRACT

Inquilinus limosus is an environmental bacterium associated with respiratory tract colonization in cystic fibrosis patients. We report a case of I. limosus bacteremia in a patient in France who received a lung transplant and experienced chronic graft dysfunction and SARS-CoV-2 infection. This case suggests I. limosus displays virulence factors associated with invasion.

PMID:36823767 | DOI:10.3201/eid2903.221564

J Cyst Fibros. 2023 Feb 21:S1569-1993(23)00047-4. doi: 10.1016/j.jcf.2023.02.003. Online ahead of print.

ABSTRACT

BACKGROUND: The respiratory tract fungal microbiome in cystic fibrosis (CF) has been understudied despite increasing recognition of fungal pathogens in CF lung disease. We sought to better understand the fungal communities in adults with CF, and to define relationships between fungal profiles and clinical characteristics.

METHODS: We enrolled 66 adults with CF and collected expectorated sputum, spirometry, Cystic Fibrosis Questionnaire-revised, and clinical data. Fungi were molecularly profiled by sequencing of the internal transcribed spacer (ITS) region. Total fungal abundance was measured by quantitative PCR. Relative abundance and qPCR-corrected abundances were determined. Selective fungus culture identified cultivable fungi. Alpha diversity and beta diversity were measured and relationships with clinical parameters were interrogated.

RESULTS: Median age was 29 years and median FEV1 percent predicted 58%. Members of the Candida genus were the most frequent dominant taxa in CF sputum. Apiotrichum, Trichosporon, Saccharomyces cerevisiae, and Scedosporium were present in high relative abundance in few samples; whereas, Aspergillus species were detected at low levels. Higher FEV1% predicted and CFTR modulator use were associated with greater alpha-diversity. Chronic azithromycin use was associated with lower alpha-diversity. Patients with acute pulmonary had distinct fungal community composition compared to clinically stable subjects. Differing yeast species were mainly responsible for the community differences.

CONCLUSION: The respiratory tract fungal microbiome in adults with CF is associated with lung function, pulmonary exacerbation status, macrolide use, and CFTR modulator use. Future work to better understand fungal diversity in the CF airway and its impact on lung health is necessary.

PMID:36822979 | DOI:10.1016/j.jcf.2023.02.003