J Appl Physiol (1985). 2021 May 27. doi: 10.1152/japplphysiol.00129.2021. Online ahead of print.

ABSTRACT

INTRODUCTION: Recent studies indicate limited utility of nitrogen multiple breath washout (N2MBW) in infancy and advocate for using sulphur hexafluoride (SF6)MBW in this age group. Modern N2MBW systems, such as EXHALYZER D® (ECO MEDICS AG, Duernten, Switzerland), use O2 and CO2 sensors to calculate N2 concentrations (in principle: N2%=100-CO2%-O2%). High O2 and CO2 concentrations have now been shown to significantly suppress signal output from the other sensor, raising apparent N2 concentrations. We examined whether improved Exhalyzer D® N2-signal, accomplished after thorough examination of this CO2 and O2 interaction on gas sensors and its correction, leads to better agreement between N2MBW and SF6MBW in healthy infants and toddlers.

METHOD: Within the same session 52 healthy children aged 1-36 months (mean 1.30 (SD 0.72) years) completed SF6MBW and N2MBW recordings (EXHALYZER D®, SPIROWARE® version 3.2.1) during supine quiet sleep. SF6 and N2 SPIROWARE® files were re-analyzed off-line with in-house software using identical algorithms as in SPIROWARE® with or without application of the new correction factors for N2MBW provided by ECO MEDICS AG. Results Applying the improved N2-signal significantly reduced mean (95% CI) differences between N2- and SF6MBW recorded functional residual capacity (FRC) and lung clearance index (LCI): for FRC, from 26.1 (21.0; 31.2) mL p<0.0001 to 1.18 (-2.3; 4.5) mL p=0.5, and for LCI, from 1.86 (1.68; 2.02) p<0.001 to 0.44 (0.33; 0.55) p<0.001.

CONCLUSION: Correction of N2-signal, for CO2 and O2 interactions on gas sensors resulted in markedly closer agreement between N2MBW and SF6MBW outcomes in healthy infants and toddlers.

PMID:34043468 | DOI:10.1152/japplphysiol.00129.2021

Clin Microbiol Rev. 2021 May 26:e0003019. doi: 10.1128/CMR.00030-19. Online ahead of print.

ABSTRACT

Stenotrophomonas maltophilia is an opportunistic pathogen of significant concern to susceptible patient populations. This pathogen can cause nosocomial and community-acquired respiratory and bloodstream infections and various other infections in humans. Sources include water, plant rhizospheres, animals, and foods. Studies of the genetic heterogeneity of S. maltophilia strains have identified several new genogroups and suggested adaptation of this pathogen to its habitats. The mechanisms used by S. maltophilia during pathogenesis continue to be uncovered and explored. S. maltophilia virulence factors include use of motility, biofilm formation, iron acquisition mechanisms, outer membrane components, protein secretion systems, extracellular enzymes, and antimicrobial resistance mechanisms. S. maltophilia is intrinsically drug resistant to an array of different antibiotics and uses a broad arsenal to protect itself against antimicrobials. Surveillance studies have recorded increases in drug resistance for S. maltophilia, prompting new strategies to be developed against this opportunist. The interactions of this environmental bacterium with other microorganisms are being elucidated. S. maltophilia and its products have applications in biotechnology, including agriculture, biocontrol, and bioremediation.

PMID:34043457 | DOI:10.1128/CMR.00030-19

Epidemiology. 2021 Jul 1;32(4):e15. doi: 10.1097/EDE.0000000000001346.

NO ABSTRACT

PMID:34042079 | DOI:10.1097/EDE.0000000000001346

J Cyst Fibros. 2021 May 23:S1569-1993(21)00132-6. doi: 10.1016/j.jcf.2021.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep concerns are commonly reported by children and youth with cystic fibrosis (CF). Understanding normative sleep in the home environment and as reported from the perspective of patients and parents is a first step in responding to an important clinical concern and developing a sleep intervention strategy. This systematic review aimed to describe actigraphic and self/parent reported measures of sleep quantity; quality; and determine factors associated with poor sleep quantity and/or quality in children and youth (0-25yrs.) with CF.

METHODS: Five online databases; Medline, Embase, CINAHL, PsycInfo, and CENTRAL were searched for relevant articles from inception-February 2020. Studies reporting primary data, using either qualitative/quantitative methods or both were eligible for inclusion. Eligible full text articles were independently screened by two reviewers. Data from included studies were independently extracted and synthesized by one reviewer and accuracy verified independently by a second reviewer.

RESULTS: This review found 31 articles that met inclusion criteria. Analysis found evidence demonstrating that actigraphic SE was lower, actigraphic nighttime awakenings were greater, and self/parent-reported measures of sleep quality were poorer in children and youth with CF. Study findings related to actigraphic TST, WASO, and self/parent-reported sleep duration were mixed. Thirteen factors demonstrated an association with poor quality sleep.

CONCLUSIONS: In children and youth with CF, evidence exists of objectively measured sleep disturbance and poor self/parent reported sleep quality. Further longitudinal and comparative research studies are warranted to better understand sleep disturbance in this population. Clinically, sleep assessment should be an integral part of routine CF care.

PMID:34039530 | DOI:10.1016/j.jcf.2021.05.005

Orthopedics. 2021 May-Jun;44(3):e440-e445. doi: 10.3928/01477447-20210415-03. Epub 2021 May 1.

ABSTRACT

Cystic fibrosis (CF) is a relatively common disease seen in Whites of northern European descent. Classically, it was a lethal disease and uncommon for the orthopedic practitioner to interact with CF patients. Recent pharmaceutical breakthroughs targeting the CF transmembrane conductance regulator (CFTR) gene have significantly prolonged patient life expectancy. This makes it increasingly likely that orthopedic surgeons will encounter CF patients in their clinic. In this article, the authors discuss pertinent musculoskeletal manifestations of the CF population, including the increased risk of decreased bone mineral density and bone mineral content, muscle deconditioning, spinal kyphosis, fractures, and elevated systemic inflammation predisposing these individuals to CF-related arthralgia. The diagnoses are grouped into subspecialties (arthroplasty, pediatrics, spine, sports, and trauma) most likely to evaluate the patient. Additionally, the authors review treatment options for these conditions and discuss the need for these patients to be seen in the perioperative period by their CF care team for patient optimization due to their diminished pulmonary function. Interspersed with this literature review, the authors present 2 unique cases. The first case details a patient with pain over her spine due to multilevel spinous process bursitis caused by a high-frequency chest wall oscillation system, which masquerades as an infection. The second case is a non-contact midsubstance rectus femoris tear in an athlete. These cases highlight the need for increased vigilance for uncommon diagnoses in the CF patient population. [Orthopedics. 2021;44(3):e440-e445.].

PMID:34039211 | DOI:10.3928/01477447-20210415-03

JAMA. 2021 May 26. doi: 10.1001/jama.2021.5086. Online ahead of print.

NO ABSTRACT

PMID:34037663 | DOI:10.1001/jama.2021.5086

Am J Physiol Lung Cell Mol Physiol. 2021 May 26. doi: 10.1152/ajplung.00298.2020. Online ahead of print.

ABSTRACT

The association of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) in the pathophysiology of cystic fibrosis (CF) is controversial. Previously, we demonstrated a close physical association between wild type (WT) CFTR and WT ENaC. We have also shown that the F508del CFTR fails to associate with ENaC unless the mutant protein is rescued pharmacologically or by low temperature. In this study, we present the evidence for a direct physical association between WT CFTR and ENaC subunits carrying Liddle's syndrome mutations. We show that all three ENaC subunits bearing Liddle's syndrome mutations (both point mutations and the complete truncation of the carboxy terminus), could be co-immunoprecipitated with WT CFTR. The biochemical studies were complemented by fluorescence lifetime imaging microscopy (FLIM), a distance-dependent approach that monitors protein-protein interactions between fluorescently labeled molecules. Our measurements revealed significantly increased FRET between CFTR and all tested ENaC combinations as compared to controls (ECFP and EYFP co-transfected cells). Our findings are consistent with the notion that CFTR and ENaC are within reach of each other even in the setting of Liddle's syndrome mutations, suggestive of a direct intermolecular interaction between these two proteins.

PMID:34037494 | DOI:10.1152/ajplung.00298.2020

J Pediatr Pharmacol Ther. 2021;26(4):379-383. doi: 10.5863/1551-6776-26.4.379. Epub 2021 May 19.

ABSTRACT

OBJECTIVE: This study aims to use and evaluate the Nephrotoxic Injury Negated by Just-in-time Action (NINJA) program in hospitalized patients with cystic fibrosis (CF) at Children's Healthcare of Atlanta.

METHODS: This was a single-center study evaluating patients with CF who were hospitalized and admitted to the pulmonary service 4 months pre- and post-NINJA implementation. Postimplementation patients with high nephrotoxic medication (NTMx) exposure were identified using an electronic reporting tool that triggered the pharmacist to alert the medical team and recommend Monday/Wednesday/Friday serum creatinine (SCr) monitoring. High NTMx exposure was defined as 3 or more NTMxs given concurrently, or at least 3 consecutive days of IV aminoglycosides or vancomycin. Outcomes assessed were rate of SCr monitoring, NTMx exposure, and days of acute kidney injury (AKI) pre- and post-NINJA implementation.

RESULTS: A total of 19 patients and 25 high-NTMx exposures were identified both pre- and post-NINJA implementation. The SCr monitoring increased from 13% to 50% of NTMx exposure days in the pre- versus post-NINJA time frame. More NTMx exposure days occurred in the post-NINJA time frame, from 250 exposure days per 1000 patient days pre-NINJA to 521 post-NINJA. An increased incidence of AKI events and AKI days were noted post-implementation; however, these differences were not significantly different between the 2 groups.

CONCLUSIONS: Increased SCr monitoring for patients with NTMx exposure using NINJA uncovered more episodes of AKI. Increased prevalence of NTMx use was associated with increased rates of AKI. Increased SCr monitoring as a result of NINJA implementation may allow for earlier detection of AKI.

PMID:34035683 | PMC:PMC8139561 | DOI:10.5863/1551-6776-26.4.379

Respir Care. 2021 May 25:respcare.08755. doi: 10.4187/respcare.08755. Online ahead of print.

ABSTRACT

In patients with cystic fibrosis (CF), despite the availability of many different pharmacologic agents, lung function deteriorates and lung disease progresses and leads to hypercapnic respiratory failure in some patients. In such cases, noninvasive ventilation (NIV) seems to be a promising technique that can be used on demand. This review summarizes the current applications of NIV in clinical settings as well as findings of the clinical trials that involved the delivery of NIV on variable occasions, such as an adjunct to physiotherapy, in nocturnal hypoventilation, and acute and chronic respiratory failure. NIV has been used in patients with CF and with advanced lung disease who are not considered candidates for lung transplantation. It can stabilize lung function, although its effect on hypercapnia is not always evident. Nocturnal NIV has been used in patients with CF and with hypoventilation during sleep but without clear benefits on daytime PCO2 NIV as an adjunct to chest physiotherapy may be helpful when desaturation is observed during physiotherapy and when there are signs of respiratory muscle fatigue. NIV use in CF has been increasing, mainly in adult CF centers, and offers patients an opportunity to reach lung transplantation or to overcome acute hypercapnic respiratory failure.

PMID:34035149 | DOI:10.4187/respcare.08755

J Cyst Fibros. 2021 May 22:S1569-1993(21)00130-2. doi: 10.1016/j.jcf.2021.05.003. Online ahead of print.

ABSTRACT

BACKGROUND: Epidemiology and potential risk factors for cystic fibrosis arthropathy (CFA) were studied in a relevant cystic fibrosis (CF) patient cohort.

METHODS: Cohort study of patients included in the German CF registry in 2016-2017. Descriptive analysis, exploratory tests and multivariable logistic regression were used to assess prevalence of CFA and associated potential risk factors for adult patients with/without chronic Pseudomonas aeruginosa infection.

RESULTS: 6069 CF patients aged from 0 to 78 years were analysed. CFA was observed in 4.9% of the patients. Prevalence was significantly higher in adult patients (8.4%) compared to patients <18 years (0.7%; p<0.0001). Logistic regression analyses in adult patients (n=3319) showed that CFA was significantly associated with increasing age (OR=1.04; 95% CI: 1.02-1.05; p<0.0001), female gender (OR=2.10; 95%CI:1.52-2.90; p<0.0001), number of hospitalizations (OR=1.24; 95%CI:1.12-1.36; p<0.0001), chronic P. aeruginosa infection (OR=1.83; 95%CI:1.28-2.61; p=0.0009), CF-related diabetes (OR=1.69; 95%CI:1.23-2.33; p=0.0013), pancreatic insufficiency (OR=2.39; 95%CI:1.28-4.46; p=0.0060) and sinusitis/polyps (OR=1.91; 95%CI:1.39-2.62; p<0.0001). In a subgroup analysis of adults without chronic P. aeruginosa infection (n=1550) CFA was also significantly associated with increasing age, female gender, increasing number of hospitalizations, pancreatic insufficiency as well as sinusitis/polyps; antimycotic treatment associated only in this subgroup while association with CF-related diabetes was not significant.

CONCLUSION: CFA is a frequent and clinically relevant co-morbidity particularly in adult CF patients. CFA is significantly more common in patients with chronic P. aeruginosa colonization but associations with other indicators for a more severe disease course were identified regardless of P. aeruginosa colonization status.

PMID:34034985 | DOI:10.1016/j.jcf.2021.05.003

J Cyst Fibros. 2021 May 22:S1569-1993(21)00133-8. doi: 10.1016/j.jcf.2021.05.006. Online ahead of print.

ABSTRACT

Vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide with potent anti-inflammatory, bronchodilatory and immunomodulatory functions, is secreted by intrinsic neurons innervating all exocrine glands, including the pancreas, in which it exerts a regulatory function in the secretion of insulin and glucagon. Cystic fibrosis-related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF), impacting approximately 50% of adult patients. We recently demonstrated a 50% reduction of VIP abundance in the lungs, duodenum and sweat glands of C57Bl/6 CF mice homozygous for the F508del-CFTR disease-causing mutation. VIP deficiency resulted from a reduction in VIPergic and cholinergic innervation, starting before signs of CF disease were observed. As VIP functions as a neuromodulator with insulinotropic effect on pancreatic beta cells, we sought to study changes in VIP in the pancreas of CF mice. Our goal was to examine VIP content and VIPergic innervation in the pancreas of 8- and 17-week-old F508del-CFTR homozygous mice and to determine whether changes in VIP levels would contribute to CFRD development. Our data showed that a decreased amount of VIP and reduced innervation are found in CF mice pancreas, and that these mice also exhibited reduced insulin secretion, up-regulation of glucagon production and high random blood glucose levels compared to same-age wild-type mice. We propose that low level of VIP, due to reduced innervation of the CF pancreas and starting at an early disease stage, contributes to changes in insulin and glucagon secretion that can lead to CFRD development.

PMID:34034984 | DOI:10.1016/j.jcf.2021.05.006

Eur J Gastroenterol Hepatol. 2021 May 21. doi: 10.1097/MEG.0000000000002185. Online ahead of print.

ABSTRACT

Gut involvement is frequent in immunologic disorders, especially with inflammatory manifestations but also with cancer. In the last years, advances in functional and genetic testing have improved the diagnostic and therapeutic approach to immune dysregulation syndromes. CTLA-4 deficiency is a rare disease with variable phenotype, ranging from absence of symptoms to severe multisystem manifestations and complications. We describe a rare case of CTLA-4 deficiency in a boy with gastric cancer, very early onset inflammatory bowel disease and polyautoimmunity, the second-ever reported in the literature with the same characteristics. A 17-year-old boy was referred to Bambino Gesù Children's Hospital of Rome, a tertiary care center, for a gastric mass and a long-term history of very early onset inflammatory bowel disease, diabetes mellitus type 1, polyarthritis and psoriasis. Histology of gastric biopsies revealed the presence of neoplastic signet ring cells. Imaging staging showed localized cancer; therefore, the patient underwent subtotal gastrectomy with termino-lateral gastro-jejunal anastomosis. Immunological work up and genetic testing by next-generation sequencing panels for primary immunodeficiencies led to the diagnosis of CTLA-4 deficiency. Good disease control was obtained with the administration of Abatacept. The patient experienced an asymptomatic SARS-CoV-2 infection without any concern. Eighteen months after treatment initiation, the patient is alive and well. Immunologic and genetic testing, such as next-generation sequencing, should always be part of the diagnostic approach to patients with complex immune dysregulation syndrome, severe clinical course, poor response to treatments or cancer. The early recognition of the monogenic disease is the key for disease management and targeted therapy.

PMID:34034269 | DOI:10.1097/MEG.0000000000002185

Phytomedicine. 2021 May 4;87:153583. doi: 10.1016/j.phymed.2021.153583. Online ahead of print.

ABSTRACT

BACKGROUND: A key clinical feature of COVID-19 is a deep inflammatory state known as "cytokine storm" and characterized by high expression of several cytokines, chemokines and growth factors, including IL-6 and IL-8. A direct consequence of this inflammatory state in the lungs is the Acute Respiratory Distress Syndrome (ARDS), frequently observed in severe COVID-19 patients. The "cytokine storm" is associated with severe forms of COVID-19 and poor prognosis for COVID-19 patients. Sulforaphane (SFN), one of the main components of Brassica oleraceae L. (Brassicaceae or Cruciferae), is known to possess anti-inflammatory effects in tissues from several organs, among which joints, kidneys and lungs.

PURPOSE: The objective of the present study was to determine whether SFN is able to inhibit IL-6 and IL-8, two key molecules involved in the COVID-19 "cytokine storm".

METHODS: The effects of SFN were studied in vitro on bronchial epithelial IB3-1 cells exposed to the SARS-CoV-2 Spike protein (S-protein). The anti-inflammatory activity of SFN on IL-6 and IL-8 expression has been evaluated by RT-qPCR and Bio-Plex analysis.

RESULTS: In our study SFN inhibits, in cultured IB3-1 bronchial cells, the gene expression of IL-6 and IL-8 induced by the S-protein of SARS-CoV-2. This represents the proof-of-principle that SFN may modulate the release of some key proteins of the COVID-19 "cytokine storm".

CONCLUSION: The control of the cytokine storm is one of the major issues in the management of COVID-19 patients. Our study suggests that SFN can be employed in protocols useful to control hyperinflammatory state associated with SARS-CoV-2 infection.

PMID:34033999 | DOI:10.1016/j.phymed.2021.153583

Pediatr Pulmonol. 2021 May 25. doi: 10.1002/ppul.25459. Online ahead of print.

ABSTRACT

The outlook for those with cystic fibrosis (CF) has never been brighter with ever increasing life expectancy and the approval of the highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor. With that being said, the progressive pulmonary decline and importance of lung health, infection, and inflammation in CF remains. This review is the second part in a three-part CF Year in Review 2020. Part one focused on the literature related to CFTR modulators while part three will feature the multisystem effects related to CF. This review focuses on articles from Pediatric Pulmonology, including articles from other journals that are of particular interest to clinicians. Herein, we highlight studies published during 2020 related to CF pulmonary disease, infection, treatment, and diagnostics.

PMID:34033706 | DOI:10.1002/ppul.25459

Am J Respir Cell Mol Biol. 2021 May 25. doi: 10.1165/rcmb.2021-0183ED. Online ahead of print.

NO ABSTRACT

PMID:34033526 | DOI:10.1165/rcmb.2021-0183ED

Arch Argent Pediatr. 2021 Jun;119(2):e234-e238. doi: 10.5546/aap.2021.e234.

ABSTRACT

Drug reaction with eosinophilia and systemic symptoms or DRESS syndrome is among severe cutaneous drug reactions. This constitutes a clinical triad that includes fever, skin rash and systemic compromise, accompanied by eosinophilia and/ or atypical lymphocytes. We present the case of an 18-month-old female patient with cystic fibrosis, who develops this pathology during a trimethoprim-sulfamethoxazole cycle as an eradicating treatment of methicillin-resistant Staphylococcus aureus in bronchial secretions. Cystic fibrosis patients receive multiple antibiotic regimens according to bacteriology in sputum, to avoid impairment in their lung function and colonization by resistant germs. Due to the increased risk of drug hypersensitivity in cystic fibrosis, an ominous prognosis and high morbidity and mortality, knowledge and a high index of suspicion of this syndrome are necessary.

PMID:34033428 | DOI:10.5546/aap.2021.e234

Allergy. 2021 May 25. doi: 10.1111/all.14959. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic respiratory condition, frequently associated with asthma and affecting the majority of cystic fibrosis (CF) patients. Pseudomonas aeruginosa infections and biofilms have been implicated in recalcitrant CRS. One of the mechanisms of action for bacteria in CRS and CF is mucosal barrier disruption by secreted products that contributes to the inflammation. However, the role of biofilm and planktonic forms of P. aeruginosa in this process is not known. The aim is to determine the effect of P. aeruginosa exoproteins isolated from CF and non-CF CRS patients on the mucosal barrier.

METHODS: Exoproteins from 40 P. aeruginosa isolates were collected in planktonic and biofilm form and applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs). Mucosal barrier integrity was evaluated by transepithelial electrical resistance (TEER), passage of FITC-dextrans, and immunofluorescence of tight junction proteins. Cytotoxicity assays were performed to measure cell viability and IL-6 ELISA was carried out to evaluate pro-inflammatory effects.

RESULTS: Planktonic exoproteins from 20/40 (50%) clinical isolates had a significant detrimental effect on the barrier and significantly increased IL-6 production. Barrier disruption was characterised by a reduced TEER, increased permeability of FITC-dextrans and discontinuous immunolocalisation of tight junction proteins and was significantly more prevalent in isolates harvested from patients with comorbid asthma (p<0.05).

CONCLUSION: Exoproteins from planktonic P. aeruginosa clinical isolates from asthmatic CRS patients have detrimental effects on the mucosal barrier and induce IL-6 production potentially contributing to the mucosal inflammation in CRS patients.

PMID:34033126 | DOI:10.1111/all.14959

World J Pediatr. 2021 May 25. doi: 10.1007/s12519-020-00388-8. Online ahead of print.

ABSTRACT

BACKGROUND: The timely and appropriate monitoring of pulmonary status is of utmost importance for patients with cystic fibrosis (CF). Computed tomography (CT) has been used in clinical and research settings for tracking lung involvement in CF patients. However, as CT delivers a considerable amount of radiation, its sequential use in CF patients remains a concern. The application of CT, therefore, should take into account its potential risks. This review aims to understand whether and to what extent the CT findings correlate with the findings from other monitoring tools in CF lung disease.

DATA SOURCES: PubMed was searched for articles about the correlation of chest CT findings with spirometric indices and with lung clearance index in children and adolescents with CF. The most relevant articles were reviewed and are presented herein.

RESULTS: Most studies have shown that forced expiratory volume in the first second (FEV1) and other spirometric indices correlate moderately with CT structural lung damage. However, at the individual level, there were patients with FEV1 within the normal range and abnormal CT and vice versa. Furthermore, longitudinal studies have indicated that the deterioration of structural lung damage does not occur in parallel with the progression of lung function. Lung clearance index is a better predictor of CT findings.

CONCLUSIONS: In general, the existing studies do not support the use of lung function tests as surrogates of chest CT.

PMID:34033063 | DOI:10.1007/s12519-020-00388-8

Clin Transplant. 2021 May 25:e14371. doi: 10.1111/ctr.14371. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is an inherited autosomal recessive disorder. Despite optimized therapy, the majority of affected individuals ultimately die of respiratory failure. As patients with CF are living longer, extra-pulmonary manifestations may develop including pancreatic failure, which manifests as exocrine insufficiency, and CF related diabetes (CFRD). Both of these can be managed through pancreas transplantation. Pancreas transplantation is usually performed in combination with another organ, most often with a kidney transplant for end-stage diabetic nephropathy. In the CF patient population, the two settings where inclusion of a pancreas transplant should be considered would be in combination with a lung transplant for CF pulmonary disease, or in combination with a liver for CF related liver disease with cirrhosis. This report will discuss this topic in detail, including a review of the literature regarding combinations of lung/pancreas and liver/pancreas transplant.

PMID:34032335 | DOI:10.1111/ctr.14371

Clin Exp Immunol. 2021 May 25. doi: 10.1111/cei.13624. Online ahead of print.

ABSTRACT

Advanced cystic fibrosis (CF) lung disease is commonly characterized by a chronic P. aeruginosa infection and destructive inflammation caused by neutrophils. However, the lack of convincing evidence from most informative biomarkers of severe lung dysfunction (SLD-CF) has hampered the formulation of a conclusive, targeted diagnosis of CF. The aim of this study was to determine whether SLD-CF is related to the high concentration of sputum inflammatory mediators and the presence of biofilm-forming bacterial strains. Forty-one patients with advanced CF lung disease were studied. The severity of pulmonary dysfunction was defined by FEV1 <40%. CRP and NLR (Neutrophil-Lymphocyte Ratio) were examined as representative blood-based markers of inflammation. Expectorated sputum was collected and analysed for cytokines and neutrophil-derived defence proteins. Isolated sputum bacteria were identified and their biofilm forming capacity was determined. There was no association between FEV1% and total number of sputum bacteria. However, in the high-biofilm forming group the median FEV1 was <40%. Importantly, high density of sputum bacteria was associated with increased concentration of neutrophil elastase and IL-8 and low concentration of IL-6 and IL-10. The low concentration of sputum IL-6 is unique for CF and distinct from that observed in other chronic pulmonary inflammatory diseases. These findings strongly suggest that expectorated sputum is an informative source of pulmonary biomarkers representative for advanced CF and may replace more invasive BAL analysis to monitor the disease. We recommend to use of the following inflammatory biomarkers: blood CRP, NLR and sputum elastase, IL-6, IL-8 and IL-10.

PMID:34031873 | DOI:10.1111/cei.13624