Health Sci Rep. 2022 Apr 20;5(3):e581. doi: 10.1002/hsr2.581. eCollection 2022 May.

ABSTRACT

BACKGROUND AND AIMS: Sputum neutrophil elastase (NE) is a marker of neutrophilic airway inflammation in bronchiectasis. Yet, not much is known about its role in pediatric bronchiectasis severity. This study aimed to assess the sputum NE value as a biomarker of clinical and radiological severity in pediatric bronchiectasis.

METHODS: This was a cross-sectional study assessing sputum NE in a total of 50 bronchiectasis patients under the age of 18 years-30 patients with cystic fibrosis (CF) and 20 patients with non-CF bronchiectasis were included. Bronchiectasis severity was assessed using Shwachman-Kulczycki (SK) score, CF-ABLE score, and CF risk of disease progression score, among CF patients, and bronchiectasis severity index (BSI) and FACED criteria among non-CF bronchiectasis patients, associations between sputum NE and bronchiectasis severity were assessed in both patient groups.

RESULTS: Sputum NE was directly correlated with C-reactive protein (r = 0.914, p < 0.001), (r = 0.786, p < 0.001), frequency of exacerbations (r = 0.852, p < 0.001) (r = 0.858, p < 0.001), exacerbations severity (r = 0.735, p = 0.002), (r = 0.907, p < 0.001), and the number of hospital admissions (r = 0.813, p < 0.001), (r = 0.612, p =0.004) in the last year among CF, and non-CF bronchiectasis patients, respectively. Additional linear correlations were found between sputum NE, CF risk of disease progression score (p < 0.001), CF-ABLE score (p < 0.001), and lower forced expiratory volume 1% of predicted (p = 0.017; ρ = -0.8) among CF patients. Moreover, sputum NE was positively correlated with the neutrophil count (p = 0.018), and BSI severity score (p = 0.039; ρ = 0.465) among non-CF bronchiectasis patients.

CONCLUSIONS: Sputum NE may be considered a good biomarker of bronchiectasis severity in both CF and non-CF bronchiectasis patients, as confirmed by the exacerbations rate, CF risk of disease progression, and BSI scores.

PMID:35509417 | PMC:PMC9059204 | DOI:10.1002/hsr2.581

Front Microbiol. 2022 Apr 18;13:868435. doi: 10.3389/fmicb.2022.868435. eCollection 2022.

ABSTRACT

BACKGROUND: The prevalence of nontuberculous mycobacteria (NTM) in patients with chronic respiratory disease has increased. The implication of NTM in non-CF bronchiectasis remained controversial. This study investigated the impact of NTM in non-CF bronchiectasis in Taiwan.

METHODS: Clinical manifestation, imaging, and microbiological data were retrieved from the Chang Gung Research Database, the largest electronic medical record-based database in Taiwan. Patients with bronchiectasis during 2001-2016 were included. Cox proportional hazard model was employed to compare outcomes between patients with negative and positive NTM isolates after 1:1 propensity score matching.

RESULTS: A total of 19,647 non-CF bronchiectasis patients were enrolled and 11,492 patients were eligible for analysis after exclusion screening. Finally, patients with negative and positive NTM isolates-650 each-were analyzed after propensity score matching. The patients with negative NTM isolates were divided into three groups: Pseudomonas aeruginosa isolates (n = 53); fungus isolates (n = 26); and concomitant P. aeruginosa and fungus isolates (n = 8). The patients with positive NTM isolates were divided into five groups: single NTM isolate (n = 458); multiple NTM isolates (n = 60); concomitant NTM and P. aeruginosa isolates (n = 89); concomitant NTM and fungus isolates (n = 33); and concomitant NTM, P. aeruginosa, and fungus isolates (n = 10). Patients with P. aeruginosa isolates; concomitant NTM and P. aeruginosa isolates; concomitant NTM, P. aeruginosa, and fungus isolates had independently associated with respiratory failure and death. Patients with single or multiple NTM isolates were not related to ventilator use, but both were independent risk factor for mortality.

CONCLUSION: NTM, either combined with P. aeruginosa or fungus, exhibited more frequent exacerbations in non-CF bronchiectasis patients. Moreover, NTM predicted mortality in non-CF bronchiectasis patients and were also correlated to respiratory failure while concomitantly isolated with P. aeruginosa and fungus.

PMID:35509319 | PMC:PMC9058169 | DOI:10.3389/fmicb.2022.868435

J Cyst Fibros. 2022 May 1:S1569-1993(22)00104-7. doi: 10.1016/j.jcf.2022.04.015. Online ahead of print.

ABSTRACT

LABELLED BACKGROUND: Haemoptysis is a life-threatening complication of cystic fibrosis (CF). One treatment is bronchial artery embolisation (BAE) using embolic-microspheres (EMs). During BAE, pulmonary arteries can be seen on digital subtracted angiography while iodine containing contrast material injection is performed in the bronchial artery. This suggests that EMs could go from bronchial to nontarget pulmonary arteries. The aim was to evaluate if EMs could be found inside pulmonary arteries on lung explants after BAE in transplanted CF patients.

METHODS: Retrospective observational study including patients with CF who underwent lung transplantation and had previously needed BAE. Clinical, chest CT angiography, and angiographic data were reviewed from medical records. Pathology examination of lung explants was performed to analyze the EMs anatomical localisation.

RESULTS: Eight patients were included between 2013 and 2015, four males with a mean age of 29 (19-45) years. All patients had bronchial artery hypertrophy on CT and bronchial-to-pulmonary artery shunting during BAE. On pathology examination, EM ≤800 µm were found in the pulmonary arteries in all patients and were responsible for distal branch occlusions. Two pulmonary infarcts were observed on CT angiography after BAE and confirmed histopathologically.

CONCLUSIONS: EM migration from the bronchial to pulmonary arteries is a common occurrence after BAE in patients with advanced stage CF. Although BAE is a highly effective means of controlling haemoptysis in CF, studies on the optimal particle size are needed to preserve pulmonary artery circulation, because these results suggest that low size EMs could lead to nontarget embolisation.

PMID:35508453 | DOI:10.1016/j.jcf.2022.04.015

Radiol Technol. 2022 May-Jun;93(5):490-493.

NO ABSTRACT

PMID:35508411

FP Essent. 2022 May;516:31-37.

ABSTRACT

Malabsorption syndromes are a heterogenous group of conditions that can cause distressing gastrointestinal symptoms. Celiac disease is most common and is triggered by exposure to gluten. Tissue transglutaminase immunoglobulin A is the diagnostic test of choice; management is gluten avoidance. Lactose intolerance is caused by absence or declining levels of the enzyme lactase. Diagnosis typically is clinical, but breath tests can be helpful if diagnosis is uncertain. Management is lactose avoidance. Bile acid malabsorption results in unabsorbed bile acids in the colon, leading to diarrhea. The 75selenium homotaurocholic acid test is most accurate but is not widely available. Therefore, a trial of bile acid sequestrants (typically cholestyramine) is a reasonable alternative when the diagnosis is suspected. Exocrine pancreatic insufficiency is caused by decreased production of pancreatic enzymes, typically occurring in patients with preexisting pancreatic damage from alcohol, surgery, radiation, diabetes, or cystic fibrosis. Diagnosis involves fecal fat or fecal elastase-1 tests. Management is pancreatic enzyme replacement. Small intestinal bacterial overgrowth is caused by pathologic overgrowth of the small bowel microbiome. Diagnosis is by jejunal biopsy or, more commonly, breath tests. Antibiotics (typically rifaximin) are the initial management. Other options include dietary changes, probiotics, and prokinetic drugs.

PMID:35507311

Andes Pediatr. 2022 Feb;93(1):110-116. doi: 10.32641/andespediatr.v93i1.3766. Epub 2022 Mar 29.

ABSTRACT

In the pediatric emergency department, dehydrated children are one of the most frequent causes for consultation, however, the coexistence of hyponatremia with hypochloremia and metabolic alkalosis is rare. The presence of metabolic alkalosis due to chloride depletion has been reported as a form of presentation of Cystic Fibrosis (CF).

OBJECTIVE: to describe a case of cystic fibrosis of unusual presen tation in a pediatric patient.

CLINICAL CASE: we report a 3-month-old previously healthy male infant who presented with internal environment abnormalities consisting of metabolic alkalosis, hypona tremia, hypokalemia, and extreme hypochloremia associated with septic shock due to mixed viral- bacterial pneumonia (Rhino/enterovirus, Streptococcus pneumoniae, and Staphylococcus aureus). Cys tic fibrosis (CF) was suspected, thus the diagnosis was corroborated by sweat test and genetic study which showed the pathogenic variants c.2834C>T (p.Ser945Leu) and c.3484C>T (p.Arg1162X), both heterozygous.

CONCLUSION: special attention should be paid to the existence of hypochloremia with metabolic alkalosis and hyponatremia associated or not with pulmonary disease, suspecting CF as the first option. This consideration becomes more relevant in those countries where the neonatal screening test is not widely available.

PMID:35506784 | DOI:10.32641/andespediatr.v93i1.3766

J Pharm Biomed Anal. 2022 Apr 27;216:114801. doi: 10.1016/j.jpba.2022.114801. Online ahead of print.

ABSTRACT

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel found on the apical surface of epithelial cells in the airway and gastrointestinal tract. A mutation in the CFTR protein is responsible for developing cystic fibrosis (CF) disease. Therefore, circulating CFTR protein could be a promising biomarker of CF disease. Multiple methodological challenges are associated with CF's available diagnostic and screening methods, such as low specificity and potential false discovery rate, mainly for ethnic groups whose CFTR mutations are not covered in the mutation panels. Herein, we have developed an absolute quantification (AQUA) method based on two CFTR signature peptides (SPs). A liquid chromatography-tandem spectrometry (LC-MS/MS) method in multiple reaction monitoring (MRM) mode (MRM transitions 1168.90 > 85.929 and 707.19 > 85.93 of SP1 and SP2, respectively) enabled the accurate quantification of CFTR protein in a dried blood spot (DBS). The method was validated successfully based on international guidelines in terms of signal linearity, precision (within-run CV 3.37-8.54%; between-run CV 5.15-11.06% for the selected SPs), and accuracy (within-run 93.4-105.59%; between-run 97.45-103.28% for the selected SPs). The level of soluble CFTR protein was evaluated as a potential biomarker for CF using patients (n = 39) and healthy controls (n = 30), were found to be in CF patients lower than controls. For instant, the level of signature peptide 1 (SP1) was 2.09 ± 0.55 nM, 68.77 ± 1.40 nM in CF patients compared to Ctrl, respectively; p < 0.0001. This study is the first to report CFTR levels in DBS using signature peptides by LC-MS/MS as a diagnostic marker for CF. The receiver operating characteristic (ROC) for CFTR SP1 and SP2 showed a significant area under the curves (AUC) 0.7714 (99% CI, p < 0.0001), and 0.8234 (99% CI, p < 0.0001), respectively. The presented MRM method provides a highly specific and sensitive approach to CFTR quantification in a DBS and could be applied in CF screening.

PMID:35504217 | DOI:10.1016/j.jpba.2022.114801

Respir Med Res. 2022 Apr 29;81:100881. doi: 10.1016/j.resmer.2021.100881. Online ahead of print.

ABSTRACT

Advances in the field of genetic susceptibility to respiratory diseases (e.g. pulmonary fibrosis, emphysema, cystic fibrosis, pulmonary hypertension) have led pneumologists to integrate the familial risk dimension and work with genetics clinical teams and laboratories. Paradoxically, while thoracic oncologists look on a daily basis for acquired oncogenic alterations in non small cell lung cancer (NSCLC), they know little about inherited, genetic susceptibility to the disease. As a result, collaboration networks with clinical cancer geneticists are poorly developed in thoracic oncology. Faced with this observation, it seemed important to us to address this issue in a very practical way with this "Q and A on Hereditary Lung Cancer" editorial.

PMID:35504062 | DOI:10.1016/j.resmer.2021.100881

BMC Pediatr. 2022 May 3;22(1):247. doi: 10.1186/s12887-022-03290-6.

ABSTRACT

BACKGROUND: This case report describes a child born with both cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (A1ATD). Both are autosomal recessive inherited diseases, mainly affecting the lungs and the liver. The combination of both diseases together is rare and may lead to a fulminant disease with limited life span. To the best of our knowledge, no case has been reported of a patient born with both diseases.

CASE PRESENTATION: After an uneventful pregnancy, a male baby was born with meconium ileus. The suspected diagnosis of CF was confirmed based on the sweat test and genetic analysis. The child developed persisting cholestasis, too severe to be likely caused by CF alone and indicating an associated problem. The diagnosis of A1ATD was established based on clinical suspicion (persisting cholestasis), decreased serum alpha-1 antitrypsin and genetic analysis. Supportive therapy was started, however the boy evolved to rapidly progressive liver disease leading to liver failure which necessitated an infant liver transplantation.

CONCLUSIONS: This case illustrates the complexity of care in case of two severe inherited diseases as well as post solid organ transplant care.

PMID:35505316 | DOI:10.1186/s12887-022-03290-6

Nat Commun. 2022 May 3;13(1):2313. doi: 10.1038/s41467-022-29689-4.

ABSTRACT

Mycobacterium chelonae is a rare cause of chronic disseminated cutaneous infections in immunocompromised patients. Multidrug-resistant M. chelonae infections present a challenge for treatment, and prolonged antimicrobial courses lead to significant toxicities and further antimicrobial resistance. We report a case of refractory cutaneous disseminated M. chelonae infection in a patient with seronegative arthritis on immunotherapy with tofacitinib that was treated with combination antimicrobial, surgical, and single bacteriophage therapy with excellent clinical response. The patient developed neutralizing antibodies against the bacteriophage but continues to have stable improvement of disease with negative biopsies and no evidence of bacterial resistance to the phage.

PMID:35504908 | DOI:10.1038/s41467-022-29689-4

J Cyst Fibros. 2022 Apr 30:S1569-1993(22)00102-3. doi: 10.1016/j.jcf.2022.04.013. Online ahead of print.

ABSTRACT

BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age.

METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (∼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life.

RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%.

CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.

PMID:35504829 | DOI:10.1016/j.jcf.2022.04.013

Elife. 2022 May 3;11:e76555. doi: 10.7554/eLife.76555. Online ahead of print.

ABSTRACT

Microbes frequently evolve in reproducible ways. Here, we show that differences in specific metabolic regulation rather than inter-strain interactions explain the frequent presence of lasR loss-of-function mutations in the bacterial pathogen Pseudomonas aeruginosa. While LasR contributes to virulence through its role in quorum sensing, lasR mutants have been associated with more severe disease. A model based on the intrinsic growth kinetics for a wild type strain and its LasR- derivative, in combination with an experimental evolution based genetic screen and further genetics analyses, indicated that differences in metabolism were sufficient to explain the rise of these common mutant types. The evolution of LasR- lineages in laboratory and clinical isolates depended on activity of the two-component system CbrAB, which modulates substrate prioritization through the catabolite repression control pathway. LasR- lineages frequently arise in cystic fibrosis lung infections and their detection correlates with disease severity. Our analysis of bronchoalveolar lavage fluid metabolomes identified compounds that negatively correlate with lung function, and we show that these compounds support enhanced growth of LasR- cells in a CbrB-controlled manner. We propose that in vivo metabolomes contribute to pathogen evolution, which may influence the progression of disease and its treatment.

PMID:35502894 | DOI:10.7554/eLife.76555

Chronic Illn. 2022 May 3:17423953221099042. doi: 10.1177/17423953221099042. Online ahead of print.

ABSTRACT

OBJECTIVES: Cystic Fibrosis (CF) care is entering a period of personalised medicine with the emergence of CF transmembrane conductance regulator (CFTR) modulator therapies. Anecdotally individuals are reporting life-changing effects of modulator therapies, proposing an important area of study.

METHODS: Twenty adult participants (males: 8, age range: 22-51 years, average FEV1: 53.45%) were recruited via social media to participate in a semi-structured interview; 17 participants were currently taking Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio).

RESULTS: An appreciation of a "normal life" post-modulator therapy is paramount, with improvements in symptoms and quality-of-life bringing a more urgent imperative for the provision of effective support to encourage positive health and lifestyle choices.

DISCUSSION: In this new era of CF care, there remains many challenges present for the CF community, with participants suggesting that proactive psychological support is required along with proactive awareness regarding health risk behaviours for the current and future CF generations.

PMID:35502821 | DOI:10.1177/17423953221099042

Expert Rev Clin Immunol. 2022 May 3. doi: 10.1080/1744666X.2022.2072297. Online ahead of print.

ABSTRACT

INTRODUCTION: The links between allergen exposure and sensitization are complex and depend not only on the type of allergen but on various genetic and environmental factors.

AREAS COVERED: This review discusses the link between allergen exposure and atopic sensitization for different types of allergens and the factors that mediate or affect this link. For the purposes of this review search of PubMed was undertaken to identify English language articles using the terms "sensitization" and "allergen exposure" and "children/or adolescents".

EXPERT OPINION: Regarding food sensitization, the available data for peanuts and eggs suggest that there is a window period between 4-6 months of age when the introduction of these foods may limit sensitization and clinically overt allergy to the respective foods. As far as it concerns aeroallergens, it seems that there is a complex and variable relationship between mite exposure and specific sensitization especially if the exposure occurs early in life. Early exposure to dog allergens does not seem to be associated with specific sensitization; regarding cats, the results are still inconsistent. Several factors may mediate the relationship between early exposure to allergens and the development of sensitization or clinical allergy.

PMID:35502686 | DOI:10.1080/1744666X.2022.2072297

Pediatr Pulmonol. 2022 May 2. doi: 10.1002/ppul.25954. Online ahead of print.

ABSTRACT

At the start of the COVID-19 pandemic, individuals with cystic fibrosis (CF) and their families were encouraged to shield as it was feared SARS-CoV-2 infection would have devastating consequences This article is protected by copyright. All rights reserved.

PMID:35502455 | DOI:10.1002/ppul.25954

Pediatr Pulmonol. 2022 May 2. doi: 10.1002/ppul.25948. Online ahead of print.

ABSTRACT

People with cystic fibrosis (CF) have an amazing outlook with the treatment availability of highly effective modulators. Unfortunately, not all PwCF are eligible for modulators leading to continued pulmonary exacerbations and advanced lung disease. Additionally, optimizing diagnosis and evaluation for CF in the newborn period continues to be an area of focus for research. This review article will work to cover articles published in 2021 with high clinical relevance related to the above topics, however due to the extensive body of research published, this review will not be comprehensive. This article is protected by copyright. All rights reserved.

PMID:35501666 | DOI:10.1002/ppul.25948

Arch Bronconeumol. 2022 Apr 15:S0300-2896(22)00291-5. doi: 10.1016/j.arbres.2022.03.011. Online ahead of print.

ABSTRACT

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities.

PMID:35501222 | DOI:10.1016/j.arbres.2022.03.011

Transplant Proc. 2022 Apr 29:S0041-1345(22)00213-5. doi: 10.1016/j.transproceed.2022.02.056. Online ahead of print.

ABSTRACT

BACKGROUND: Lung transplantation remains the ultimate treatment for patients who have exhausted all other therapeutic options in the course of end-stage lung disease due to cystic fibrosis (CF). The aim of the study was to assess the results of lung transplantations performed via mini-thoracotomy in a single center.

METHODS: This retrospective study assesses the survival and need for reoperation among 56 primary lung transplant recipients due to CF in a single center between 2018 and 2021. Intraoperative death was also assessed, yet it was established as an exclusion criterion for the post-transplant survival analysis.

RESULTS: Only one patient died intraoperatively (1.79%). Reoperation at an early postoperative stage was required among 2 patients (3.58%), due to vascular complication for one and pulmonary leakage for the other. Mortality at 30 days was 0%. In-hospital mortality was low (3.58%). Survival at 1, 2, and 3 years was respectively 87%, 85%, and 75%. Mean forced expiratory volume in 1 second as a percentage of predicted value at discharge was approximately 60% and did not decrease after 12 and 24 months. Mean BMI at 12-month follow-up was 20.11 (range, 13-28.7) with 71.4% of patients being qualified as presenting within the normal range of 18.5 to 24.9.

CONCLUSIONS: Double lung transplantation is a safe and feasible surgical option. Despite being more technically difficult and challenging than clamshell approach for surgeons, it is more beneficial for patients.

PMID:35501172 | DOI:10.1016/j.transproceed.2022.02.056

Life Sci Alliance. 2022 May 2;5(9):e202101326. doi: 10.26508/lsa.202101326. Print 2022 Sep.

ABSTRACT

Mutations in the CFTR anion channel cause cystic fibrosis (CF) and have also been related to higher cancer incidence. Previously we proposed that this is linked to an emerging role of functional CFTR in protecting against epithelial-mesenchymal transition (EMT). However, the pathways bridging dysfunctional CFTR to EMT remain elusive. Here, we applied systems biology to address this question. Our data show that YAP1 is aberrantly active in the presence of mutant CFTR, interacting with F508del, but not with wt-CFTR, and that YAP1 knockdown rescues F508del-CFTR processing and function. Subsequent analysis of YAP1 interactors and roles in cells expressing either wt- or F508del-CFTR reveal that YAP1 is an important mediator of the fibrotic/EMT processes in CF. Alongside, five main pathways emerge here as key in linking mutant CFTR to EMT, namely, (1) the Hippo pathway; (2) the Wnt pathway; (3) the TGFβ pathway; (4) the p53 pathway; and (5) MYC signaling. Several potential hub proteins which mediate the crosstalk among these pathways were also identified, appearing as potential therapeutic targets for both CF and cancer.

PMID:35500936 | DOI:10.26508/lsa.202101326

Indian J Pediatr. 2022 Apr 30. doi: 10.1007/s12098-022-04204-1. Online ahead of print.

NO ABSTRACT

PMID:35499799 | DOI:10.1007/s12098-022-04204-1