Int J Exerc Sci. 2021 Apr 1;14(3):177-186. eCollection 2021.

ABSTRACT

The purpose of the study was to assess whether there are differences in cardiorespiratory fitness between children with and without cystic fibrosis (CF). Ten children with CF attended at a referral center for the treatment of CF and 13 children without CF were evaluated. The average age of the children with CF was 10.40 (3.13) years and those without CF was 9.39 (3.25) years. The children performed the three-minute step test with monitoring of hemodynamic parameters and the rating of perceived exertion (RPE) every minute. Oxygen desaturation of 4% during the test occurred in three children with CF and none of the children reached a SatO2 percentage < 75%. After the step test, the findings showed that children with CF presented higher RPE scores during the test (p = 0.002) when compared to children without CF (p < 0.001). The RPE was the only parameter that changed during the test and demonstrated that children with cystic fibrosis tired more during the test when compared to children without CF despite the lack of changes in hemodynamic variables.

PMID:34055158 | PMC:PMC8136547

Front Pharmacol. 2021 May 14;12:592184. doi: 10.3389/fphar.2021.592184. eCollection 2021.

ABSTRACT

Decreased human epididymis protein 4 (HE4) plasma levels were reported in cystic fibrosis (CF) patients under CFTR potentiator ivacaftor therapy, which inversely correlated with lung function improvement. In this study, we investigated whether HE4 expression was affected via modulation of CFTR function in CF bronchial epithelial (CFBE) cells in vitro. HE4 protein levels were measured in the supernatants of CFBE 41o- cells expressing F508del-CFTR or wild-type CFTR (wt-CFTR) after administration of lumacaftor/ivacaftor or tezacaftor/ivacaftor, while HE4 expression in CFBE 41o- cells were also analyzed following application of adenylate cyclase activators Forskolin/IBMX or CFTRinh172. The effect of all of these compounds on CFTR function was monitored by the whole-cell patch-clamp technique. Induced HE4 expression was studied with interleukin-6 (IL-6) in F508del-CFTR CFBE 41o- cells under TNF-α stimulation for 1 h up to 1 week in duration. In parallel, plasma HE4 was determined in CF subjects homozygous for p.Phe508del-CFTR mutation receiving lumacaftor/ivacaftor (Orkambi®) therapy. NF-κB-mediated signaling was observed via the nuclear translocation of p65 subunit by fluorescence microscopy together with the analysis of IL-6 expression by an immunoassay. In addition, HE4 expression was examined after NF-κB pathway inhibitor BAY 11-7082 treatment with or without CFTR modulators. CFTR modulators partially restored the activity of F508del-CFTR and reduced HE4 concentration was found in F508del-CFTR CFBE 41o- cells that was close to what we observed in CFBE 41o- cells with wt-CFTR. These data were in agreement with decreased plasma HE4 concentrations in CF patients treated with Orkambi®. Furthermore, CFTR inhibitor induced elevated HE4 levels, while CFTR activator Forskolin/IBMX downregulated HE4 in the cell cultures and these effects were more pronounced in the presence of CFTR modulators. Higher activation level of baseline and TNF-α stimulated NF-κB pathway was detected in F508del-CFTR vs. wt-CFTR CFBE 41o- cells that was substantially reduced by CFTR modulators based on lower p65 nuclear positivity and IL-6 levels. Finally, HE4 expression was upregulated by TNF-α with elevated IL-6, and both protein levels were suppressed by combined administration of NF-κB pathway inhibitor and CFTR modulators in CFBE 41o- cells. In conclusion, CFTR dysfunction contributes to abnormal HE4 expression via NF-κB in CF.

PMID:34054511 | PMC:PMC8160512 | DOI:10.3389/fphar.2021.592184

Front Pharmacol. 2021 May 13;12:573065. doi: 10.3389/fphar.2021.573065. eCollection 2021.

ABSTRACT

In cystic fibrosis (CF), sustained infection and exuberant inflammation results in debilitating and often fatal lung disease. Advancement in CF therapeutics has provided successful treatment regimens for a variety of clinical consequences in CF; however effective means to treat the pulmonary infection and inflammation continues to be problematic. Even with the successful development of small molecule cystic fibrosis transmembrane conductance regulator (CFTR) correctors and potentiators, there is only a modest effect on established infection and inflammation in CF patients. In the pursuit of therapeutics to treat inflammation, the conundrum to address is how to overcome the inflammatory response without jeopardizing the required immunity to manage pathogens and prevent infection. The key therapeutic would have the capacity to dull the inflammatory response, while sustaining the ability to manage infections. Advances in cell-based therapy have opened up the avenue for dynamic and versatile immune interventions that may support this requirement. Cell based therapy has the capacity to augment the patient's own ability to manage their inflammatory status while at the same time sustaining anti-pathogen immunity. The studies highlighted in this manuscript outline the potential use of cell-based therapy for CF. The data demonstrate that 1) total bone marrow aspirates containing Cftr sufficient hematopoietic and mesenchymal stem cells (hMSCs) provide Cftr deficient mice >50% improvement in survival and improved management of infection and inflammation; 2) myeloid cells can provide sufficient Cftr to provide pre-clinical anti-inflammatory and antimicrobial benefit; 3) hMSCs provide significant improvement in survival and management of infection and inflammation in CF; 4) the combined interaction between macrophages and hMSCs can potentially enhance anti-inflammatory and antimicrobial support through manipulating PPARγ. These data support the development of optimized cell-based therapeutics to enhance CF patient's own immune repertoire and capacity to maintain the balance between inflammation and pathogen management.

PMID:34054509 | PMC:PMC8155373 | DOI:10.3389/fphar.2021.573065

J Cyst Fibros. 2021 May 27:S1569-1993(21)00129-6. doi: 10.1016/j.jcf.2021.05.002. Online ahead of print.

ABSTRACT

BACKGROUND: Over the last decades aggressive interventions have been successful to improve nutritional outcomes in people with cystic fibrosis (CF). As a result, with improvement of life expectancy and new CFTR modulators, overweight and obesity are progressively becoming a source of concern for adult population and in developed countries.

METHODS: This was a multicenter, observational, cross-sectional study of 321 adults with CF at three large CF centers in Italy. Patients were divided into three groups according to BMI classes, overweight and obesity (OW) group including patients with BMI ≥25 kg/m2, normal weight (NW) group with BMI 18.6-24.9 kg/m2 and underweight (UW) group with BMI ≤18.5 kg/m2.

RESULTS: We demonstrated that prevalence of OW in adults with CF in Italy is 22%. OW status is independently associated with male sex (OR 3.520, P = 0.001), pancreatic sufficiency (OR 2.873, P = 0.014) and older age at diagnosis (1.015, P = 0.042). BMI correlated with ppFEV1 (r = 0.337; P<0.0001) with median ppFEV1 significantly higher in patients with OW than comparisons. We also reported preliminary data on unfavorable cardiovascular risk factors in a subgroup of patients, where median blood levels [IQR] of cholesterol and systemic hypertension [%] were significantly higher in the OW group than in the NW and UW.

CONCLUSIONS: People with CF and OW is a relevant patient group that might deserve better definition and proper clinical management.

PMID:34053868 | DOI:10.1016/j.jcf.2021.05.002

Paediatr Anaesth. 2021 May 30. doi: 10.1111/pan.14229. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal intravenous device for antibiotic administration for children with respiratory disease is uncertain. We assessed the feasibility of a randomized controlled trial (RCT) comparing midline catheters with peripherally inserted central catheters (PICCs).

METHODS: Prospective, 2-arm, feasibility RCT in an Australian tertiary, pediatric hospital. Random assignment of 110 children (< 18 years) to receive (i) midline catheter, (ii) PICC. Primary outcome was feasibility (eligibility, recruitment, retention, protocol adherence and acceptability), and the primary clinical outcome was general anesthesia requirement for intravenous catheter insertion.

SECONDARY OUTCOMES: insertion time, treatment delays, infusion efficiency, device failure, complications, and cost.

RESULTS: There was 80% recruitment, 100% retention, no missing data, and high patient/staff acceptability. Mean patient experience assessed on a 0-10 numeric rating scale was 8.0 (PICC) and 9.0 (midline catheters) respectively. Participant eligibility was not achieved (49% of screened patients) and moderate protocol-adherence across groups (89% PICC vs 76% midline catheter). Insertion of midline catheter for pulmonary optimisation reduced the requirement for general anesthesia compared to PICCs (10% vs 69%; odds ratio=0.01, 95% confidence interval: 0.00-0.09). Midline catheters failed more frequently (18.1 vs 5.5 PICCs per 1,000 catheter-days), however this reduced over trial duration. Midline catheter insertion compared to PICCs saved AUD$1,451 per pulmonary optimisation episode.

CONCLUSION: An efficacy trial is feasible with expanded eligibility criteria and intensive staff training when introducing a new device. Midline catheter for peripherally compatible infusions is acceptable to patients and staff, might negate the need for general anesthesia and results in significant cost savings.

PMID:34053159 | DOI:10.1111/pan.14229

Curr Opin Microbiol. 2021 May 27;62:45-50. doi: 10.1016/j.mib.2021.04.009. Online ahead of print.

ABSTRACT

The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and cystic fibrosis (CF) share a common immunological signature marked by TH2 and TH17 cell predominant immune responses, the production of IgE antibody, and a typical inflammatory cell infiltrate that includes eosinophils and other innate immune effector cells. Severe forms of these disorders have long been recognized as being related to hypersensitivity reactions to environmental fungi. Increasingly however,environmental fungi are assuming a more primary role in the etiology of these disorders, with airway mycosis, a type of non-invasive airway fungal infection, recognized as an essential driving factor in at least severe subsets of allergic airway diseases. In this review, we consider recent progress made in understanding the immune mechanisms that drive airway mycosis-related diseases, improvements in immune-based diagnostic strategies, and therapeutic approaches that target key immune pathways.

PMID:34052540 | DOI:10.1016/j.mib.2021.04.009

J Microbiol Methods. 2021 May 26:106252. doi: 10.1016/j.mimet.2021.106252. Online ahead of print.

ABSTRACT

Slow growing, mucoid isolates of Pseudomonas aeruginosa require adaptation of the protocol used for automated antimicrobial susceptibility testing (AST). In the present study we used a water soluble tetrazolium salt WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) in combination with menadione for possibly improving AST of slow growing and biofilm-forming P. aeruginosa isolates from cystic fibrosis (CF) patients. WST-1 and menadione addition ensures sensitive detection of microbial growth increase in the presence of antibiotics that may remain undetected with the automated VITEK® 2 method. We observed that 32.8% of P. aeruginosa isolates from CF and bronchiectasis patients produced an elevated absorbance signal intensity thereby increasing the sensitivity while maintaining the accuracy of VITEK 2. Our study merits future investigation with other slow growing pathogenic bacterial species.

PMID:34051278 | DOI:10.1016/j.mimet.2021.106252

J Cyst Fibros. 2021 May 25:S1569-1993(21)00118-1. doi: 10.1016/j.jcf.2021.04.008. Online ahead of print.

ABSTRACT

BACKGROUND: Mechanisms governing the diversity of CFTR gene expression throughout the body are complex. Multiple intronic and distal regulatory elements are responsible for regulating differential CFTR expression across tissues.

METHODS: Drawing on published data, 18 high-priority genomic regions were identified and interrogated for CFTR-enhancer function using CRISPR/dCas9-based epigenome editing tools. Each region was evaluated by dCas9p300 and dCas9KRAB for its ability to enhance or repress CFTR expression, respectively.

RESULTS: Multiple genomic regions were tested for enhancer activity using CRISPR/dCas9 epigenome editing. dCas9p300 mediates a significant increase in CFTR mRNA levels when targeted to the promoter and a region 44 kb upstream of the transcriptional start site in a CFTR-low expressing cell line. Multiple gRNAs targeting the promoter induced a robust increase in CFTR protein levels. In contrast, dCas9KRAB-mediated repression is much more robust with 10 of the 18 evaluated genomic regions inducing CFTR protein knockdown. To evaluate the therapeutic efficacy of modulating CFTR gene regulation, dCas9p300 was used to induce elevated levels of CFTR from the endogenous locus in ΔF508/ΔF508 human bronchial epithelial cells. Ussing chamber studies demonstrated a synergistic increase in ion transport in response to CRISPR-induced expression of ΔF508 CFTR mRNA along with VX809 treatment.

CONCLUSIONS: CRISPR/dCas9-based epigenome-editing provides a previously unexplored tool for interrogating CFTR enhancer function. Here, we demonstrate that therapeutic interventions that increase the expression of CFTR may improve the efficacy of CFTR modulators. A better understanding CFTR regulatory mechanisms could uncover novel therapeutic interventions for the development of cystic fibrosis therapies.

PMID:34049825 | DOI:10.1016/j.jcf.2021.04.008

Ann Allergy Asthma Immunol. 2021 May 25:S1081-1206(21)00412-9. doi: 10.1016/j.anai.2021.05.022. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) patients often have a history of antibiotic adverse drug reactions (ADRs) that pose a barrier to receiving recommended first-line treatment. Targeted antibiotic allergy evaluations are increasingly recognized as an important strategy for optimization of antimicrobial stewardship.

OBJECTIVE: To improve first-line antibiotic use in CF patients with antibiotic ADRs by streamlining access to antibiotic allergy evaluations and standardizing documentation of plans for antibiotic reintroduction.

METHODS: We incorporated allergy evaluations into a multidisciplinary CF clinic and utilized telemedicine when allergy evaluations could not be performed during CF clinic. Standard documentation of antibiotic allergy plans was utilized to enable safe reintroduction of first-line antibiotics by CF providers.

RESULTS: Strategies utilized in this study allowed 81.3% (26/32) of CF patients to receive allergy evaluations and antibiotic allergy plans for prioritized antibiotics (penicillin, cephalosporin, sulfonamide), with removal of 41.0% (16/39) of prioritized antibiotic ADRs. Only 5.1% (2/39) of prioritized antibiotic ADRs evaluated required strict avoidance after evaluation. Nine patients received at least one prioritized antibiotic, with 66.6% (6/9) of these patients given the antibiotic after only one allergy evaluation visit. Additionally, these strategies allowed allergy evaluations of 23 non-prioritized antibiotics to occur, with removal of the ADR in 39.1% (9/23) and use of 77.8% (7/9) of non-prioritized antibiotics after removal.

CONCLUSION: Incorporating allergy evaluations into a multidisciplinary CF clinic can liberalize first-line antibiotic use in CF patients. Standard documentation of antibiotic allergy plans allowed antibiotic reintroduction to occur even prior to complete removal of documented antibiotic ADRs.

PMID:34048884 | DOI:10.1016/j.anai.2021.05.022

Pediatr Pulmonol. 2021 May 28. doi: 10.1002/ppul.25513. Online ahead of print.

ABSTRACT

INTRODUCTION: Hypersensitivity pneumonitis (HP) in children is a severe interstitial lung disease and potentially, a chronic condition, if not treated appropriately. No evidence-based guidelines are available; in particular, the role of systemic glucocorticoid therapy is unclear.

METHODS: The aim of this randomized, double-blind, placebo-controlled, parallel-group, multi-center, phase II trial in pediatric HP was to assess the outcome of HP in children after 6 months of treatment and to compare 3 months of treatment with oral prednisolone or placebo.

RESULTS: After 1.5 years and the inclusion of only four children, we terminated the study prematurely. Two of the children randomized to prednisolone did not achieve the predefined response of FVC to normal. One child treated with placebo recovered to normal, similar to another child treated with prednisolone. All children treated with steroids developed drug-related side effects.

DISCUSSION: This uncompleted study illustrates the urgent medical need for evidence-based treatment protocols for this condition. We discuss the hurdles which were specific for completion of this trial in a rare condition. Among other options, we suggest the inclusion of children into an all-age study of HP, as in adults the same questions are unanswered.

PMID:34048641 | DOI:10.1002/ppul.25513

Drug Deliv Transl Res. 2021 May 28. doi: 10.1007/s13346-021-01002-8. Online ahead of print.

ABSTRACT

The major pathogen found in the lungs of adult cystic fibrosis (CF) patients is Pseudomonas aeruginosa, which builds antibiotic-resistant biofilms. Pulmonary delivery of antibiotics by inhalation has already been proved advantageous in the clinic, but the development of novel anti-infective aerosol medicines is complex and could benefit from adequate in vitro test systems. This work describes the first in vitro model of human bronchial epithelial cells cultivated at the air-liquid interface (ALI) and infected with P. aeruginosa biofilm and its application to demonstrate the safety and efficacy of aerosolized anti-infective nanocarriers. Such a model may facilitate the translation of novel therapeutic modalities into the clinic, reducing animal experiments and the associated problems of species differences. A preformed biofilm of P. aeruginosa PAO1 was transferred to filter-grown monolayers of the human CF cell line (CFBE41o-) at ALI and additionally supplemented with human tracheobronchial mucus. This experimental protocol provides an appropriate time window to deposit aerosolized ciprofloxacin-loaded nanocarriers at the ALI. When applied 1 h post-infection, the nanocarriers eradicated all planktonic bacteria and reduced the biofilm fraction of the pathogen by log 6, while CFBE41o- viability and barrier properties were maintained. The here described complex in vitro model approach may open new avenues for preclinical safety and efficacy testing of aerosol medicines against P. aeruginosa lung infection.

PMID:34047967 | DOI:10.1007/s13346-021-01002-8

ERJ Open Res. 2021 May 24;7(2):00758-2020. doi: 10.1183/23120541.00758-2020. eCollection 2021 Apr.

ABSTRACT

Potent CFTR modulators improve CF manifestations far beyond expectations, including reduction of risk of typical complications. This is the first report of a patient who developed life-threatening ABPA and emphysema after overwhelming improvement. https://bit.ly/2P96PTy.

PMID:34046494 | PMC:PMC8141834 | DOI:10.1183/23120541.00758-2020

ERJ Open Res. 2021 May 24;7(2):00574-2020. doi: 10.1183/23120541.00574-2020. eCollection 2021 Apr.

ABSTRACT

Nontuberculous mycobacterial (NTM) pulmonary disease (PD) is an emerging condition with heterogeneous manifestations from both the microbiological and the clinical point of view. Diagnostic and therapeutic guidelines are available but there are still unmet patients' and physicians' needs, including therapy-related adverse events, symptom control, management of comorbidities, risk of re-exposure to the pathogen and unfavourable outcomes. In the present review, we provide currently available evidence for an integrated approach to NTM-PD beyond antibiotic therapy. This includes 1) avoiding exposure to environments where mycobacteria are present and careful evaluation of lifestyle and habits; 2) implementing a personalised pulmonary rehabilitation plan and airway clearance techniques to improve symptoms, exercise capacity, health-related quality of life (QoL) and functional capacity in daily living activities; 3) a nutritional evaluation and intervention to improve health-related QoL and to control gastrointestinal side-effects during antimicrobial therapy, particularly in those with low body mass index and history of weight loss; and 4) managing comorbidities that affect disease outcomes, including structural lung diseases, immune status evaluation and psychological support when appropriate.

PMID:34046491 | PMC:PMC8141831 | DOI:10.1183/23120541.00574-2020

Front Cell Dev Biol. 2021 May 11;9:678209. doi: 10.3389/fcell.2021.678209. eCollection 2021.

ABSTRACT

Glioblastoma (GBM) is the most common and malignant primary brain tumor. Glioblastoma stem cells (GSCs) not only initiate and sustain uncontrolled cell proliferation but also resistant to conventional clinical therapies including temozolomide (TMZ) dependent chemotherapy and radiotherapy, implying that there is an urgent need to identify new therapeutic strategies especially specific targeting GSCs. Here, we provide evidence showing that ivacaftor commonly applied in cystic fibrosis therapy acts as a potent inhibitor for GSCs maintenance. We found that ivacaftor promotes cellular apoptosis in vitro and represses patient-derived xenograft (PDX) tumor growth in vivo. In addition, we demonstrate that ivacaftor decreases stemness marker gene expressions of GSCs, including CD133, CD44, and Sox2. In summary, our findings reveal that ivacaftor inhibits glioblastoma progression via specifically eliminating GSCs, which opens a new avenue for GBM clinical therapy in the future.

PMID:34046412 | PMC:PMC8147559 | DOI:10.3389/fcell.2021.678209

Nat Commun. 2021 May 27;12(1):3186. doi: 10.1038/s41467-021-23451-y.

ABSTRACT

Long-term infection of the airways of cystic fibrosis patients with Pseudomonas aeruginosa is often accompanied by a reduction in bacterial growth rate. This reduction has been hypothesised to increase within-patient fitness and overall persistence of the pathogen. Here, we apply adaptive laboratory evolution to revert the slow growth phenotype of P. aeruginosa clinical strains back to a high growth rate. We identify several evolutionary trajectories and mechanisms leading to fast growth caused by transcriptional and mutational changes, which depend on the stage of adaptation of the strain. Return to high growth rate increases antibiotic susceptibility, which is only partially dependent on reversion of mutations or changes in the transcriptional profile of genes known to be linked to antibiotic resistance. We propose that similar mechanisms and evolutionary trajectories, in reverse direction, may be involved in pathogen adaptation and the establishment of chronic infections in the antibiotic-treated airways of cystic fibrosis patients.

PMID:34045458 | DOI:10.1038/s41467-021-23451-y

Pediatr Clin North Am. 2021 Jun;68(3):633-649. doi: 10.1016/j.pcl.2021.02.012.

ABSTRACT

Millions of children and adolescents are living with a chronic condition. It is common for mental and behavioral health challenges to arise during their courses of illness. With the complexity of care needed, pediatric subspecialty providers have recognized the need to integrate behavioral health interventions into practice. Continued research in this area has allowed for focused behavioral interventions, particularly in diabetes and asthma. Adult congenital heart programs have adapted a similar model of care and have shown promising success in promotion of health. More established programs have been in existence for childhood cancer and cystic fibrosis.

PMID:34044990 | DOI:10.1016/j.pcl.2021.02.012

Cell Commun Signal. 2021 May 27;19(1):63. doi: 10.1186/s12964-021-00740-z.

ABSTRACT

BACKGROUND: Human airway epithelial (HAE) cellular models are widely used in applicative studies of the airway physiology and disease. In vitro expanded and differentiated primary HAE cells collected from patients seem to be an accurate model of human airway, offering a quicker and cheaper alternative to the induced pluripotent stem cell (iPSCs) models. However, the biggest drawback of primary HAE models is their limited proliferative lifespan in culture. Much work has been devoted to understand the factors, which govern the HAE cell proliferation and differentiation, both in vivo and in vitro. Here, I have summarized recent achievements in primary HAE culture, with the special emphasis on the models of conditionally reprogrammed cells (CRC), which allow longer in vitro proliferation and differentiation of HAE cells. The review compares the CRC HAE technique variants (feeder culture or HAE mono-culture), based on recently published studies exploiting this model. The advantages and limitations of each CRC HAE model variant are summarized, along with the description of other factors affecting the CRC HAE culture success (tissue type, sampling method, sample quality).

CONCLUSIONS: CRC HAE cultures are a useful technique in respiratory research, which in many cases exceeds the iPSCs and organoid culture methods. Until the current limitations of the iPSCs and organoid culture methods will be alleviated, the primary CRC HAE cultures might be a useful model in respiratory research. Airway epithelium (AE) is a type of tissue, which lines the whole length of human airways, from the nose to the bronchi. Improper functioning of AE causes several human airway disorders, such as asthma, chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Much work has been devoted to finding the best scientific model of human AE, in order to learn about its functioning in health and disease. Among the popular AE models are the primary in vitro cultured AE cells collected from human donors. Unfortunately, such human AE (HAE) cells do not easily divide (expand) in vitro; this poses a large logistic and ethical problem for the researchers. Here, I summarize recent achievements in the methods for in vitro culture of human AE cells, with special emphasis on the conditionally reprogrammed cell (CRC) models, which allow longer and more effective expansion of primary human AE cells in vitro. The review describes how the specific chemicals used in the CRC models work to allow the increased HAE divisions and compares the effects of the different so-far developed variants of the CRC HAE culture. The review also pinpoints the areas which need to be refined, in order to maximize the usefulness of the CRC AE cultures from human donors in research on human airway disorders. Video abstract.

PMID:34044844 | DOI:10.1186/s12964-021-00740-z

Pediatr Ann. 2021 May;50(5):e214-e221. doi: 10.3928/19382359-20210421-01. Epub 2021 May 1.

ABSTRACT

Allergic broncho-pulmonary aspergillosis (ABPA) is an immunologically mediated lung disease that usually occurs in people with a diagnosis of asthma or cystic fibrosis. It is a noninvasive lung disease caused by colonization of the airways with Aspergillus fumigatus. In people who are susceptible, Aspergillus leads to an exaggerated immune response and ultimately pulmonary inflammation and lung damage. Patients with ABPA typically present with poorly controlled asthma, recurrent pulmonary infiltrates, and bronchiectasis. Diagnosis of ABPA is established based on a combination of clinical manifestations as well as laboratory and radiological evaluations. Delay in diagnosis can result in airway destruction and pulmonary fibrosis, which may result in significant morbidity and mortality. This article discusses the clinical characteristics, diagnosis, and management of patients with ABPA. It aims to serve as a tool for pediatricians to aid in early recognition of this debilitating disease and consider referral, facilitating early diagnosis and treatment. [Pediatr Ann. 2021;50(5):e214-e221.].

PMID:34044705 | DOI:10.3928/19382359-20210421-01

Cogn Res Princ Implic. 2021 May 26;6(1):40. doi: 10.1186/s41235-021-00307-z.

ABSTRACT

Over-the-counter (OTC) drugs have many benefits but also carry risks, such as adverse drug reactions, which are more prevalent in older adults. Because these products do not require the oversight of a physician or pharmacist, labeling plays a key role in communicating information required for their safe and effective use. Research suggests that current labels are not terribly effective at communicating potential risk. One reason for their lack of effectiveness is that few consumers attend to critical information (active ingredients and warnings) when making purchases. In two experiments, we used a change detection task to objectively evaluate how novel label designs that employ highlighting and a warning label placed on the package's front impact attention to critical information among older participants (65 and older). The change detection task is a unique form of visual search which allowed us to assess the attentional priority of critical information among participants who were not explicitly instructed to search for this critical information. This unique aspect of the task is important given research suggesting that consumers rarely have the explicit goal of seeking out warnings and active ingredients when making OTC selections. Our results provide empirical support that both highlighting critical information and positioning it on the package's front increase its attentional prioritization relative to current, commercial practice. Given that attending to the critical information is prerequisite to utilizing that information, strategies that elicit attention in this way are likely to reduce medication errors.

PMID:34041617 | PMC:PMC8153101 | DOI:10.1186/s41235-021-00307-z

Pediatr Pulmonol. 2021 May 27. doi: 10.1002/ppul.25504. Online ahead of print.

ABSTRACT

Pulmonary physiology is a core element of pediatric pulmonology care and research. This article reviews some of the notable publications in physiology that were published in Pediatric Pulmonology in 2020.

PMID:34043883 | DOI:10.1002/ppul.25504