Pharmacotherapy. 2023 Mar 2. doi: 10.1002/phar.2786. Online ahead of print.

ABSTRACT

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is associated with significant improvement in lung function in people with Cysfic Fibrosis (pwCF); however, some patients experience adverse effects (AEs) including hepatotoxicity. One potential strategy is dose reduction of ETI with the goal of maintaining therapeutic efficacy while resolving AEs. We report our experience of dose reduction in individuals who experienced AEs following ETI therapy. We provide mechanistic support for ETI dose reduction by exploring predicted lung exposures and underlying pharmacokinetics-pharmacodynamics (PK-PD) relationships.

METHOD: Adults prescribed ETI who underwent dose reduction due to the AEs were included in this case series, and their percent predicted forced expiratory volume in 1 second (ppFEV1 ) and self-reported respiratory symptoms were collected. The full physiologically-based pharmacokinetic (PBPK) models of ETI were developed incorporating physiological information and drug-dependent parameters. The models were validated against available pharmacokinetic and dose-response relationship data. The models were then used to predict lung concentrations of ETI at steady-state.

RESULTS: Fifteen patients underwent dose reduction of ETI due to AEs. Clinical stability without significant changes in ppFEV1 after dose reduction was observed in all patients. Resolution or improvement of AEs occurred in 13 of the 15 cases. The model-predicted lung concentrations of reduced-dose ETI exceeded the reported half maximal effective concentration (EC50 ) from measurement of in vitro chloride transport, providing a hypothesis as to why therapeutic efficacy was maintained.

CONCLUSION: Albeit in a small number of patients, this study provides evidence that reduced ETI doses in pwCF who have experienced AEs may be effective. The PBPK models enable exploration of a mechanistic basis for this finding by simulating target tissue concentrations of ETI that can be compared with drug efficacy in vitro.

PMID:36866442 | DOI:10.1002/phar.2786

Transpl Infect Dis. 2023 Mar 2:e14041. doi: 10.1111/tid.14041. Online ahead of print.

ABSTRACT

BACKGROUND: There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic-resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died.

METHODS: Phages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis.

RESULTS: Phage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O-antigen profiles of an early versus a late isolate.

CONCLUSIONS: This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.

PMID:36864824 | DOI:10.1111/tid.14041

J Transl Med. 2023 Mar 2;21(1):162. doi: 10.1186/s12967-023-04017-6.

ABSTRACT

Mammalian cells responding to specific perturbations of homeostasis can undergo a regulated variant of cell death that elicits adaptive immune responses. As immunogenic cell death (ICD) can only occur in a precise cellular and organismal context, it should be conceptually differentiated from instances of immunostimulation or inflammatory responses that do not mechanistically depend on cellular demise. Here, we critically discuss key conceptual and mechanistic aspects of ICD and its implications for cancer (immuno)therapy.

PMID:36864446 | PMC:PMC9979428 | DOI:10.1186/s12967-023-04017-6

World J Microbiol Biotechnol. 2023 Feb 18;39(4):103. doi: 10.1007/s11274-023-03548-w.

ABSTRACT

The ambiguous nature of pyocyanin was noted quite early after its discovery. This substance is a recognized Pseudomonas aeruginosa virulence factor that causes problems in cystic fibrosis, wound healing, and microbiologically induced corrosion. However, it can also be a potent chemical with potential use in a wide variety of technologies and applications, e.g. green energy production in microbial fuel cells, biocontrol in agriculture, therapy in medicine, or environmental protection. In this mini-review, we shortly describe the properties of pyocyanin, its role in the physiology of Pseudomonas and show the ever-growing interest in it. We also summarize the possible ways of modulating pyocyanin production. We underline different approaches of the researchers that aim either at lowering or increasing pyocyanin production by using different culturing methods, chemical additives, physical factors (e.g. electromagnetic field), or genetic engineering techniques. The review aims to present the ambiguous character of pyocyanin, underline its potential, and signalize the possible further research directions.

PMID:36864230 | DOI:10.1007/s11274-023-03548-w

J Cyst Fibros. 2023 Feb 28:S1569-1993(23)00057-7. doi: 10.1016/j.jcf.2023.02.007. Online ahead of print.

ABSTRACT

BACKGROUND: There are complex medical, psychological, social and economic aspects to becoming a parent with Cystic Fibrosis (CF). A shared decision-making (SDM) approach could help women with CF make informed decisions about their reproductive goals that are sensitive to their individual values and preferences. This study investigated capability, opportunity, and motivation to participate in SDM from the perspective of women with CF.

METHODS: Mixed-methods design. An international online survey was completed by 182 women with CF, to investigate participation in SDM in relation to reproductive goals, and measures of capability (information needs), opportunity (social environment) and motivation (SDM attitudes and self-efficacy) to engage in SDM. Twenty-one women were interviewed using a visual timelines method to explore their SDM experiences and preferences. Qualitative data were analysed thematically.

RESULTS: Women with higher decision self-efficacy reported better experiences of SDM relating to their reproductive goals. Decision self-efficacy was positively associated with social support, age, and level of education, highlighting inequalities. Interviews indicated that women were highly motivated to engage in SDM, but their capability was compromised by lack of information, perception of insufficient opportunities for focused discussions about SDM.

CONCLUSIONS: Women with CF are keen to engage in SDM about reproductive health, but currently lack sufficient information and support to do so. Interventions at patient, clinician and system levels are needed to support capability, opportunity and motivation to engage equitably in SDM in relation to their reproductive goals.

PMID:36863947 | DOI:10.1016/j.jcf.2023.02.007

J Cyst Fibros. 2023 Feb 27:S1569-1993(23)00056-5. doi: 10.1016/j.jcf.2023.02.005. Online ahead of print.

ABSTRACT

BACKGROUND: Extracellular vesicles (EVs) are emerging as biomarkers of disease with diagnostic potential in CF. With the advent of highly effective modulator therapy, sputum production is less common and there is a need to identify novel markers of CF disease progression, exacerbation and response to therapies in accessible fluids such as serum.

METHODS: We used size exclusion chromatography (SEC) to isolate and characterise EVs from the blood of PWCF of different ages and compared to ultracentrifugation (UC). We used nanoparticle tracking analysis to measure the number of EVs present in serum obtained from children and adults with CF. Mass spectrometry based proteomics was used to characterise protein expression changes between the groups.

RESULTS: EVs were successfully isolated in SEC fractions from 250 µl serum from PWCF in greater numbers (p <0.01) than density ultracentrifugation. There was not a significant difference in EV numbers between young children with CF and controls. However, there was significantly more EVs in adults compared to children (<6yrs) (p < 0.05). EVs from PWCF before and after Kaftrio treatment were also analysed. Significant protein expression changes were observed within all 3 group. The largest changes detected were between children and adults with CF (57 proteins had a 1.5 fold change in expression with 19 significant changes p < 0.05) and PWCF taking Kaftrio (24 significant changes in EV protein expression was observed 12 months post treatment).

CONCLUSION: In this pilot study, we performed an initial characterisation of EVs in serum from PWCF demonstrating the potential of serum EVs for further diagnostic investigation.

PMID:36858853 | DOI:10.1016/j.jcf.2023.02.005

J Cyst Fibros. 2023 Feb 27:S1569-1993(23)00060-7. doi: 10.1016/j.jcf.2023.02.008. Online ahead of print.

ABSTRACT

BACKGROUND: Higher growth percentiles are associated with more favorable lung function in cystic fibrosis (CF), prompting the creation of CF Foundation (CFF) nutritional guidelines.

OBJECTIVES: To describe early childhood growth trajectories within CF, to determine if growth trajectories are associated with differences in lung function at age six, and to identify factors that differ between trajectory groups.

METHODS: Retrospective cohort study of children diagnosed with CF and born 2000-2011 using the US CFF Patient Registry. Annualized growth parameters prior to age six were included in group-based trajectory modeling to identify unique early life growth trajectories. FEV1 percent predicted (FEV1pp) at age six was compared between trajectory groups using linear regression. Factors associated with group membership were identified using multinomial logistic regression.

RESULTS: 6,809 children met inclusion criteria. Six discrete growth trajectories were identified, including three groups that began with growth parameters >50th percentile, termed: "always high", "gradual decliner", "rapid decliner", and three which began with growth parameters <50th percentile, termed: "rapid riser", "gradual riser", "always low". FEV1pp at age six was highest for the Always High trajectory. The Always Low trajectory was nearly 10% lower than the Always High trajectory. Sex, ethnicity, newborn screening and pancreatic function were associated with trajectory class membership.

CONCLUSIONS: Distinct early life growth trajectories were identified within CF. Trajectories that met CFF nutritional guideline recommendations were associated with higher FEV1pp at age six. CF care teams should continue to partner with families to encourage interventions to support optimal growth to improve lung function in CF.

PMID:36858852 | DOI:10.1016/j.jcf.2023.02.008

Lancet Oncol. 2023 Mar;24(3):e133-e143. doi: 10.1016/S1470-2045(22)00742-2.

ABSTRACT

As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and 3 immunotherapy clinical trials and clinical care. Additionally, investigational tools-including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents-offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.

PMID:36858729 | DOI:10.1016/S1470-2045(22)00742-2

Pediatr Pulmonol. 2023 Mar 1. doi: 10.1002/ppul.26382. Online ahead of print.

ABSTRACT

The cost of cystic fibrosis (CF) care is high with a mean annual expenditure of $131,000 and is driven largely by medications and hospital utilization This article is protected by copyright. All rights reserved.

PMID:36858451 | DOI:10.1002/ppul.26382

Urology. 2023 Feb 27:S0090-4295(23)00184-X. doi: 10.1016/j.urology.2023.02.017. Online ahead of print.

ABSTRACT

Congenital bilateral absence of the vas deferens (CBAVD) occurs in almost all men with Cystic Fibrosis. Prevailing theories on this pathophysiology relate to pathogenic mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene leading to agenesis or obliteration of vas deferens in utero. In this study, we present a case of two brothers with congenital anomalies of the vas deferens who were found to have carry a rare, heterozygous CFTR variant p.r347h without pulmonary or gastrointestinal signs or symptoms of CF.

PMID:36858322 | DOI:10.1016/j.urology.2023.02.017

Eur J Pharm Sci. 2023 Feb 27:106414. doi: 10.1016/j.ejps.2023.106414. Online ahead of print.

ABSTRACT

Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a highly abundant efflux transporter in the lungs, which protects cells from toxins and oxidative stress and has been implicated in the pathophysiology of chronic obstructive pulmonary disease and cystic fibrosis. There is evidence from in vitro studies that the inhaled glucocorticoid budesonide can inhibit MRP1 activity. We used positron emission tomography (PET) imaging with 6-bromo-7-[11C]methylpurine ([11C]BMP), which is transformed in vivo into a radiolabeled MRP1 substrate, to assess whether intratracheally (i.t.) aerosolized budesonide affects pulmonary MRP1 activity in rats. Three groups of rats (n = 5-6 each) underwent dynamic PET scans of the lungs after i.t. aerosolization of either [11C]BMP alone, or [11C]BMP mixed with either budesonide (0.04 mg, corresponding to the maximum soluble dose) or the model MRP1 inhibitor MK571 (2 mg). From PET-measured radioactivity concentration-time curves, the rate constant describing radioactivity elimination from the right lung (kE,lung) and the area under the curve (AUClung) were calculated from 0-5 min after start of the PET scan as measures of pulmonary MRP1 activity. Co-administration of MK571 resulted in a pronounced decrease in kE,lung (25-fold, p < 0.0001) and an increase in AUClung (5.3-fold, p < 0.0001) when compared with vehicle-treated animals. In contrast, in budesonide-treated animals kE,lung and AUClung were not significantly different from the vehicle group. Our results show that i.t. aerosolized budesonide at an approximately 5 times higher dose than the maximum clinical dose leads to no change in pulmonary MRP1 activity, suggesting a lack of an effect of inhaled budesonide treatment on the MRP1-mediated cellular detoxifying capacity of the lungs. However, the strong effect observed for MK571 raises the possibility for the occurrence of transporter-mediated drug-drug interactions at the pulmonary epithelium with inhaled medicines.

PMID:36858275 | DOI:10.1016/j.ejps.2023.106414

Am J Respir Crit Care Med. 2023 Mar 1. doi: 10.1164/rccm.202205-1010LE. Online ahead of print.

NO ABSTRACT

PMID:36857488 | DOI:10.1164/rccm.202205-1010LE

Microb Biotechnol. 2023 Mar 1. doi: 10.1111/1751-7915.14241. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic pathogen able to infect any human tissue. One of the reasons for its high adaptability and colonization of host tissues is its capacity of maintaining iron homeostasis through a wide array of iron acquisition and removal mechanisms. Due to their ability to cause life-threatening acute and chronic infections, especially among cystic fibrosis and immunocompromised patients, and their propensity to acquire resistance to many antibiotics, the World Health Organization (WHO) has encouraged the scientific community to find new strategies to eradicate this pathogen. Several recent strategies to battle P. aeruginosa focus on targeting iron homeostasis mechanisms, turning its greatest advantage into an exploitable weak point. In this review, we discuss the different mechanisms used by P. aeruginosa to maintain iron homeostasis and the strategies being developed to fight this pathogen by blocking these mechanisms. Among others, the use of iron chelators and mimics, as well as disruption of siderophore production and uptake, have shown promising results in reducing viability and/or virulence of this pathogen. The so-called 'Trojan-horse' strategy taking advantage of the siderophore uptake systems is emerging as an efficient method to improve delivery of antibiotics into the bacterial cells. Moreover, siderophore transporters are considered promising targets for the developing of P. aeruginosa vaccines.

PMID:36857468 | DOI:10.1111/1751-7915.14241

Arch Argent Pediatr. 2023 Mar 9:e202202905. doi: 10.5546/aap.2022-02905.eng. Online ahead of print.

ABSTRACT

Cystic fibrosis is the second most common genetic disease in infancy. It is the result of a mutated channel protein, the CFTR, which secretes chloride ions, fluidifying secretions. Recent improvements in the treatment have increased life expectancy in these patients. Nevertheless, liver involvement remains the third cause of death. Unfortunately, our understating of the physiopathology is still deficient. Biliary obstruction secondary to the presence of thick secretions is considered to lead to cirrhosis. However, treatment with ursodeoxycolic acid has not changed the natural history. Furthermore, the presence of portal hypertension in the absence of cirrhosis cannot be explained. Recently, the role of CFTR as modulator of immune tolerance has been proposed, which could explain the presence of a persistent portal inflammation leading to fibrosis, and the gut-liver axis would also have a role in disease presentation and progression.

PMID:36856762 | DOI:10.5546/aap.2022-02905.eng

NIHR Open Res. 2022 May 9;2:36. doi: 10.3310/nihropenres.13260.1.

ABSTRACT

BACKGROUND: Despite the importance of reducing treatment burden for people with cystic fibrosis (CF), it has not been fully understood as a concept. This study aims to quantify the treatment burden perceived by CF adults and explore the association between different validated treatment burden measures.

METHODS: This is a cross-sectional observational study of CF adults attending a single large UK adult center. Participants completed an online survey that contained three different treatment burden scales; CF Questionnaire-Revised (CFQ-R) subscale, CF Quality of Life (CFQoL) subscale, and the generic multimorbidity treatment burden questionnaire (MTBQ).

RESULTS: Among 101 participants, the median reported treatment burden by the CFQ-R subscale was 55.5 (IQR 33.3 - 66.6), the CFQoL subscale was 66.6 (IQR 46.6 - 86.6), and the MTBQ reversed global score was 84.6 (IQR 73.1 - 92.3). No correlation was found between respondents' demographic or clinical variables and treatment burden measured via any of the three measures. All treatment burden measures showed correlations against each other. More treatments were associated with high treatment burden as measured by the CFQ-R, CFQoL subscales, and the MTBQ. However, longer treatment time and more complex treatment plans were correlated with high treatment burden as measured by the CFQ-R and CFQoL subscales, but not with the MTBQ.

CONCLUSIONS: Treatment burden is a substantial issue in CF. Currently, the only available way to evaluate it is with the CF-specific quality of life measure treatment burden subscales (CFQ-R and CFQoL); both indicated that treatment burden increases with more treatments, longer treatment time, and more complex treatments.

PMID:36855412 | PMC:PMC7614250 | DOI:10.3310/nihropenres.13260.1

mSphere. 2023 Feb 28:e0005723. doi: 10.1128/msphere.00057-23. Online ahead of print.

ABSTRACT

The ability to generate a subpopulation of small colony variants (SCVs) is a conserved feature of Pseudomonas aeruginosa and could represent a key adaptive strategy to colonize and persist in multiple niches. However, very little is known about the role of the SCV phenotype, the conditions that promote its emergence, and its possible involvement in an adaptive strategy. In the present work, we investigated the in vitro selective conditions promoting the emergence of SCVs from the prototypical strain PA14, which readily forms SCVs in nonagitated standing cultures. We found that O2 limitation, which causes a redox imbalance, is the main factor selecting for the SCV phenotype, which promotes survival of the population via formation of a biofilm at the air-liquid interface to access the electron acceptor. When this selective pressure is relieved by aeration or supplementation of an alternative electron acceptor, SCVs are barely detectable. We also observed that SCV emergence contributes to redox rebalancing, suggesting that it is involved in an adaptive strategy. We conclude that selection for the SCV phenotype is an adaptive solution adopted by P. aeruginosa to access poorly available O2. IMPORTANCE The bacterium Pseudomonas aeruginosa is an opportunistic pathogen that thrives in many environments. It poses a significant health concern, notably because it is a causative agent of nosocomial infections and the most prevalent pathogen found in the lungs of people with cystic fibrosis. In infected hosts, its persistence is often related to the emergence of an alternative phenotype known as small colony variant (SCV). Identification of conditions selecting for the SCV phenotype contributes to knowledge regarding adaptive mechanisms exploited by P. aeruginosa to survive in multiple niches and persist during infections. Hindering this adaptation strategy could help control persistent P. aeruginosa infections.

PMID:36853007 | DOI:10.1128/msphere.00057-23

Am J Physiol Lung Cell Mol Physiol. 2023 Feb 28. doi: 10.1152/ajplung.00453.2021. Online ahead of print.

ABSTRACT

Electronic cigarettes (e-cigs) are often promoted as safe alternatives to smoking based on the faulty perception that inhaling nicotine is safe until other harmful chemicals in cigarette smoke are absent. Previously, others and we have reported that, similar to cigarette smoke, e-cig aerosols decrease CFTR-mediated ion transport across airway epithelium. However, it is unclear whether such defective epithelial ion transport by e-cig aerosols occurs in vivo and what the singular contribution of inhaled nicotine is to impairments in mucociliary clearance (MCC), the primary physiologic defense of the airways. Here, we tested the effects of nicotine aerosols from e-cigs in primary human bronchial epithelial (HBE) cells and two animal models, rats, and ferrets, known for their increasing physiologic complexity and potential for clinical translation followed by in vitro and in vivo electrophysiologic assays for CFTR activity and micro optical coherence tomography (μOCT) image analyses for alterations in airway mucus physiology. Data presented in this report indicate nicotine in e-cig aerosols causes 1) reduced CFTR and ENaC-mediated ion transport, 2) delayed MCC, and 3) diminished airway surface hydration, as determined by periciliary liquid depth analysis. Interestingly, the common e-cig vehicles vegetable glycerin and propylene glycol did not affect CFTR function or MCC in vivo despite their significant adverse effects in vitro. Overall, our studies contribute to an improved understanding of inhaled nicotine effects on lung health among e-cig users and inform pathologic mechanisms involved in altered host defense and increased risk for tobacco-associated lung diseases.

PMID:36852921 | DOI:10.1152/ajplung.00453.2021

Curr Drug Saf. 2023 Feb 28. doi: 10.2174/1574886318666230228120550. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis is an autosomal recessive disease that causes respiratory tract infection. These patients use nebulized antibiotics such as tobramycin and gentamicin plus amikacin. Due to the high price of tobramycin and the inaccessibility of this drug in Iran at different periods, we aimed to compare the efficacy and safety of nebulized plus amikacin and tobramycin in patients with cystic fibrosis.

METHOD: In this analytic cross-sectional study, data were collected from the records of all patients with cystic fibrosis. They were divided into two groups by their type of nebulized antibiotic. Group 1 included 41 patients who received 80 mg gentamicin and 500mg amikacin as a nebulized antibiotic every other month, whereas, group 2 consisted of 9 patients who received 300 mg nebulized tobramycin. Collected data were pulmonary function parameters, body mass index, the frequency of hospitalization, infection progress, Shwachman-Kulczycki score, and renal complications. The data were compared in terms of efficacy and renal adverse effects by independent t-test and repeated measure ANOVA.

RESULT: A total of 50 cystic fibrosis patients were evaluated and there was no significant difference between group 1 and group 2 in terms of pulmonary function, frequency of hospitalizations, body mass index, Shwachman-Kulczycki score, infection progress, and renal complications. Notably, pulmonary function factors were reduced in both groups over time during their treatment.

CONCLUSION: Nebulized tobramycin and gentamicin plus amikacin had similar efficacy against pseudomonas aeruginosa in cystic fibrosis and had no serious renal complications.

PMID:36852787 | DOI:10.2174/1574886318666230228120550

Protein Sci. 2023 Feb 27:e4611. doi: 10.1002/pro.4611. Online ahead of print.

ABSTRACT

Protein-protein interactions that involve recognition of short peptides are critical in cellular processes. Protein-peptide interaction surface areas are relatively small and shallow, and there are often overlapping specificities in families of peptide-binding domains. Therefore, dissecting selectivity determinants can be challenging. PDZ domains are a family of peptide-binding domains located in several intracellular signaling and trafficking pathways. These domains are also directly targeted by pathogens, and a hallmark of many oncogenic viral proteins is a PDZ-binding motif. However, amidst sequences that target PDZ domains, there is a wide spectrum in relative promiscuity. For example, the viral HPV16 E6 oncoprotein recognizes over double the number of PDZ domain-containing proteins as the cystic fibrosis transmembrane conductance regulator (CFTR) in the cell, despite similar PDZ targeting-sequences and identical motif residues. Here, we determine binding affinities for PDZ domains known to bind either HPV16 E6 alone or both CFTR and HPV16 E6, using peptides matching WT and hybrid sequences. We also use energy minimization to model PDZ-peptide complexes and use sequence analyses to investigate this difference. We find that while the majority of single mutations had marginal effects on overall affinity, the additive effect on the free energy of binding accurately describes the selectivity observed. Taken together, our results describe how complex and differing PDZ interactomes can be programmed in the cell. This article is protected by copyright. All rights reserved.

PMID:36851847 | DOI:10.1002/pro.4611

Viruses. 2023 Feb 14;15(2):537. doi: 10.3390/v15020537.

ABSTRACT

Influenza infection is a cause of exacerbations in patients with chronic pulmonary diseases. The aim of this study was to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. Using the Chang Gung Research Database, we identified patients with bronchiectasis and influenza-related infection (ICD-9-CM 487 and anti-viral medicine) between 2008 and 2017. The main outcomes were influenza-related hospitalization and in-hospital mortality rate. Eight hundred sixty-five patients with bronchiectasis and influenza infection were identified. Five hundred thirty-six (62%) patients with bronchiectasis were hospitalized for influenza-related infection and 118 (22%) patients had respiratory failure. Compared to the group only seen in clinic, the hospitalization group was older, with more male patients, a lower FEV1, higher bronchiectasis aetiology comorbidity index (BACI), and more acute exacerbations in the previous year. Co-infections were evident in 55.6% of hospitalized patients, mainly caused by Pseudomonas aeruginosa (15%), fungus (7%), and Klebsiella pneumoniae (6%). The respiratory failure group developed acute kidney injury (36% vs. 16%; p < 0.001), and shock (47% vs. 6%; p < 0.001) more often than influenza patients without respiratory failure. The overall mortality rate was 10.8% and the respiratory failure group exhibited significantly higher in-hospital mortality rates (27.1% vs. 6.2%; p < 0.001). Age, BACI, and previous exacerbations were independently associated with influenza-related hospitalization. Age, presence of shock, and low platelet counts were associated with increased hospital mortality. Influenza virus caused severe exacerbation in bronchiectasis, especially in those who were older and who had high BACI scores and previous exacerbations. A high risk of respiratory failure and mortality were observed in influenza-related hospitalization in bronchiectasis. We highlight the importance of preventing or treating influenza infection in bronchiectasis.

PMID:36851751 | DOI:10.3390/v15020537