A smartphone-based algorithm comprising cough analysis and patient-reported symptoms identifies acute exacerbations of asthma: a prospective, double blind, diagnostic accuracy study.

Objective: Early and accurate recognition of asthma exacerbations reduces the duration and risk of hospitalization. Current diagnostic methods depend upon patient recognition of symptoms, expert clinical examination, or measures of lung function. Here, we aimed to develop and test the accuracy of a smartphone-based diagnostic algorithm that analyses five cough events and five patient-reported features (age, fever, acute or productive cough and wheeze) to detect asthma exacerbations.Methods: We conducted a double-blind, prospective, diagnostic accuracy study comparing the algorithm with expert clinical opinion and formal lung function testing. Results: One hundred nineteen participants >12 years with a physician-diagnosed history of asthma were recruited from a hospital in Perth, Western Australia: 46 with clinically confirmed asthma exacerbations, 73 with controlled asthma. The groups were similar in median age (54yr versus 60yr, p=0.72) and sex (female 76% versus 70%, p=0.5). The algorithm's positive percent agreement (PPA) with the expert clinical diagnosis of asthma exacerbations was 89% [95% CI: 76%, 96%]. The negative percent agreement (NPA) was 84% [95% CI: 73%, 91%]. The algorithm's performance for asthma exacerbations diagnosis exceeded its performance as a detector of patient-reported wheeze (sensitivity, 63.7%). Patient-reported wheeze in isolation was an insensitive marker of asthma exacerbations (PPA=53.8%, NPA=49%). Conclusions: Our diagnostic algorithm accurately detected the presence of an asthma exacerbation as a point-of-care test without requiring clinical examination or lung function testing. This method could improve the accuracy of telehealth consultations and might be helpful in Asthma Action Plans and patient-initiated therapy.

Risk factors associated with 31-day unplanned hospital readmission in newborns: a systematic review.

The purpose of this study is to synthesize evidence on risk factors associated with newborn 31-day unplanned hospital readmissions (UHRs). A systematic review was conducted searching CINAHL, EMBASE (Ovid), and MEDLINE from January 1st 2000 to 30th June 2021. Studies examining unplanned readmissions of newborns within 31 days of discharge following the initial hospitalization at the time of their birth were included. Characteristics of the included studies examined variables and statistically significant risk factors were extracted from the inclusion studies. Extracted risk factors could not be pooled statistically due to the heterogeneity of the included studies. Data were synthesized using content analysis and presented in narrative and tabular form. Twenty-eight studies met the eligibility criteria, and 17 significant risk factors were extracted from the included studies. The most frequently cited risk factors associated with newborn readmissions were gestational age, postnatal length of stay, neonatal comorbidity, and feeding methods. The most frequently cited maternal-related risk factors which contributed to newborn readmissions were parity, race/ethnicity, and complications in pregnancy and/or perinatal period. CONCLUSION: This systematic review identified a complex and diverse range of risk factors associated with 31-day UHR in newborn. Six of the 17 extracted risk factors were consistently cited by studies. Four factors were maternal (primiparous, mother being Asian, vaginal delivery, maternal complications), and two factors were neonatal (male infant and neonatal comorbidities). Implementation of evidence-based clinical practice guidelines for inpatient care and individualized hospital-to-home transition plans, including transition checklists and discharge readiness assessments, are recommended to reduce newborn UHRs. WHAT IS KNOWN: • Attempts have been made to identify risk factors associated with newborn UHRs; however, the results are inconsistent. WHAT IS NEW: • Six consistently cited risk factors related to newborn 31-day UHRs. Four maternal factors (primiparous, mother being Asian, vaginal delivery, maternal complications) and 2 neonatal factors (male infant and neonatal comorbidities). • The importance of discharge readiness assessment, including newborn clinical fitness for discharge and parental readiness for discharge. Future research is warranted to establish standardised maternal and newborn-related variables which healthcare providers can utilize to identify newborns at greater risk of UHRs and enable comparison of research findings.

Stratifying asthma severity in children using cough sound analytic technology.

Introduction: Asthma is a common childhood respiratory disorder characterized by wheeze, cough and respiratory distress responsive to bronchodilator therapy. Asthma severity can be determined by subjective, manual scoring systems such as the Pulmonary Score (PS). These systems require significant medical training and expertise to rate clinical findings such as wheeze characteristics, and work of breathing. In this study, we report the development of an objective method of assessing acute asthma severity based on the automated analysis of cough sounds.Methods: We collected a cough sound dataset from 224 children; 103 without acute asthma and 121 with acute asthma. Using this database coupled with clinical diagnoses and PS determined by a clinical panel, we developed a machine classifier algorithm to characterize the severity of airway constriction. The performance of our algorithm was then evaluated against the PS from a separate set of patients, independent of the training set.Results: The cough-only model discriminated no/mild disease (PS 0-1) from severe disease (PS 5,6) but required a modified respiratory rate calculation to separate very severe disease (PS > 6). Asymptomatic children (PS 0) were separated from moderate asthma (PS 2-4) by the cough-only model without the need for clinical inputs.Conclusions: The PS provides information in managing childhood asthma but is not readily usable by non-medical personnel. Our method offers an objective measurement of asthma severity which does not rely on clinician-dependent inputs. It holds potential for use in clinical settings including improving the performance of existing asthma-rating scales and in community-management programs.AbbreviationsAMaccessory muscleBIbreathing indexCIconfidence intervalFEV1forced expiratory volume in one secondLRlogistic regressionPEFRpeak expiratory flow ratePSpulmonary scoreRRrespiratory rateSDstandard deviationSEstandard errorWAWestern Australia.

Selective cleavage of fibrinogen by diverse proteinases initiates innate allergic and antifungal immunity through CD11b.

Proteinases are essential drivers of allergic airway disease and innate antifungal immunity in part through their ability cleave the clotting factor fibrinogen (FBG) into fibrinogen cleavage products (FCPs) that signal through Toll-like receptor 4 (TLR4). However, the mechanism by which FCPs engage TLR4 remains unknown. Here, we show that the proteinases from Aspergillus melleus (PAM) and other allergenic organisms rapidly hydrolyze FBG to yield relatively few FCPs that drive distinct antifungal mechanisms through TLR4. Functional FCPs, termed cryptokines, were characterized by rapid loss of the FBG α chain with substantial preservation of the ß and γ chains, including a γ chain sequence (Fibγ390-396) that binds the integrin Mac-1 (CD11b/CD18). PAM-derived cryptokines could be generated from multiple FBG domains, and the ability of cryptokines to induce fungistasis in vitro and innate allergic airway disease in vivo strongly depended on both Mac-1 and the Mac-1-binding domain of FBG (Fibγ390-396). Our findings illustrate the essential concept of proteinase-activated immune responses and for the first time link Mac-1, cryptokines, and TLR4 to innate antifungal immunity and allergic airway disease.

Risk factors associated with 30-day all-cause unplanned hospital readmissions at a tertiary children's hospital in Western Australia.

AIM: To identify risk factors associated with 30-day all-cause unplanned hospital readmission at a tertiary children's hospital in Western Australia. METHODS: An administrative paediatric inpatient dataset was analysed retrospectively. Patients of all ages discharged between 1 January 2010 and 31 December 2014 were included. Demographic and clinical information at the index admission was examined using multivariate logistic regression analysis. RESULTS: A total of 3330 patients (4.55%) experienced at least one unplanned readmission after discharge. Readmission was more likely to occur in patients who were either older than 16 years (odds ratio (OR) = 1.46; 95% confidence interval (CI) 1.07-1.98), utilising private insurance as an inpatient (OR = 1.16; 95% CI 1.00-1.34), with greater socio-economic advantage (OR = 1.20; 95% CI 1.02-1.41), admitted on Friday (OR = 1.21; 95% CI 1.05-1.39), discharged on Friday/Saturday/Sunday (OR = 1.26, 95% CI 1.10-1.44; OR = 1.34, 95% CI 1.15-1.57; OR = 1.24, 95% CI 1.05-1.47, respectively), with four or more diagnoses at the index admission (OR = 2.41; 95% CI 2.08-2.80) or hospitalised for 15 days or longer (OR = 2.39; 95% CI 1.88-2.98). Area under receiver operating characteristic curve of the predictive model is 0.645. CONCLUSIONS: A moderate discriminative ability predictive model for 30-day all-cause same hospital readmission was developed. A structured discharge plan is suggested to be commenced from admission to ensure continuity of care for patients identified as being at higher risk of readmission. A recommendation is made that a designated staff member be assigned to co-ordinate the plan, including assessment of patients' and primary carers' readiness for discharge. Further research is required to establish comprehensive paediatric readmission rates by accessing linkage data to capture different hospital readmissions.

A prospective multicentre study testing the diagnostic accuracy of an automated cough sound centred analytic system for the identification of common respiratory disorders in children.

BACKGROUND: The differential diagnosis of paediatric respiratory conditions is difficult and suboptimal. Existing diagnostic algorithms are associated with significant error rates, resulting in misdiagnoses, inappropriate use of antibiotics and unacceptable morbidity and mortality. Recent advances in acoustic engineering and artificial intelligence have shown promise in the identification of respiratory conditions based on sound analysis, reducing dependence on diagnostic support services and clinical expertise. We present the results of a diagnostic accuracy study for paediatric respiratory disease using an automated cough-sound analyser. METHODS: We recorded cough sounds in typical clinical environments and the first five coughs were used in analyses. Analyses were performed using cough data and up to five-symptom input derived from patient/parent-reported history. Comparison was made between the automated cough analyser diagnoses and consensus clinical diagnoses reached by a panel of paediatricians after review of hospital charts and all available investigations. RESULTS: A total of 585 subjects aged 29 days to 12 years were included for analysis. The Positive Percent and Negative Percent Agreement values between the automated analyser and the clinical reference were as follows: asthma (97, 91%); pneumonia (87, 85%); lower respiratory tract disease (83, 82%); croup (85, 82%); bronchiolitis (84, 81%). CONCLUSION: The results indicate that this technology has a role as a high-level diagnostic aid in the assessment of common childhood respiratory disorders. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (retrospective) - ACTRN12618001521213 : 11.09.2018.

Ascaris Larval Infection and Lung Invasion Directly Induce Severe Allergic Airway Disease in Mice.

Ascaris lumbricoides (roundworm) is the most common helminth infection globally and a cause of lifelong morbidity that may include allergic airway disease, an asthma phenotype. We hypothesize that Ascaris larval migration through the lungs leads to persistent airway hyperresponsiveness (AHR) and type 2 inflammatory lung pathology despite resolution of infection that resembles allergic airway disease. Mice were infected with Ascaris by oral gavage. Lung AHR was measured by plethysmography and histopathology with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains, and cytokine concentrations were measured by using Luminex Magpix. Ascaris-infected mice were compared to controls or mice with allergic airway disease induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Ascaris-infected mice developed profound AHR starting at day 8 postinfection (p.i.), peaking at day 12 p.i. and persisting through day 21 p.i., despite resolution of infection, which was significantly increased compared to controls and OVA/OVA mice. Ascaris-infected mice had a robust type 2 cytokine response in both the bronchoalveolar lavage (BAL) fluid and lung tissue, similar to that of the OVA/OVA mice, including interleukin-4 (IL-4) (P < 0.01 and P < 0.01, respectively), IL-5 (P < 0.001 and P < 0.001), and IL-13 (P < 0.001 and P < 0.01), compared to controls. By histopathology, Ascaris-infected mice demonstrated early airway remodeling similar to, but more profound than, that in OVA/OVA mice. We found that Ascaris larval migration causes significant pulmonary damage, including AHR and type 2 inflammatory lung pathology that resembles an extreme form of allergic airway disease. Our findings indicate that ascariasis may be an important cause of allergic airway disease in regions of endemicity.

Blocking KV1.3 channels inhibits Th2 lymphocyte function and treats a rat model of asthma.

Allergic asthma is a chronic inflammatory disease of the airways. Of the different lower airway-infiltrating immune cells that participate in asthma, T lymphocytes that produce Th2 cytokines play important roles in pathogenesis. These T cells are mainly fully differentiated CCR7(-) effector memory T (TEM) cells. Targeting TEM cells without affecting CCR7(+) naïve and central memory (TCM) cells has the potential of treating TEM-mediated diseases, such as asthma, without inducing generalized immunosuppression. The voltage-gated KV1.3 potassium channel is a target for preferential inhibition of TEM cells. Here, we investigated the effects of ShK-186, a selective KV1.3 channel blocker, for the treatment of asthma. A significant proportion of T lymphocytes in the lower airways of subjects with asthma expressed high levels of KV1.3 channels. ShK-186 inhibited the allergen-induced activation of peripheral blood T cells from those subjects. Immunization of F344 rats against ovalbumin followed by intranasal challenges with ovalbumin induced airway hyper-reactivity, which was reduced by the administration of ShK-186. ShK-186 also reduced total immune infiltrates in the bronchoalveolar lavage and number of infiltrating lymphocytes, eosinophils, and neutrophils assessed by differential counts. Rats with the ovalbumin-induced model of asthma had elevated levels of the Th2 cytokines IL-4, IL-5, and IL-13 measured by ELISA in their bronchoalveolar lavage fluids. ShK-186 administration reduced levels of IL-4 and IL-5 and induced an increase in the production of IL-10. Finally, ShK-186 inhibited the proliferation of lung-infiltrating ovalbumin-specific T cells. Our results suggest that KV1.3 channels represent effective targets for the treatment of allergic asthma.

Airway surface mycosis in chronic TH2-associated airway disease.

BACKGROUND: Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. OBJECTIVE: To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. METHODS: Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. RESULTS: Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). CONCLUSIONS: The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with TH2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients.

Autologous Rib Grafts in the Management of the Crooked Nose.

Rhinoplasty is arguably one of the most challenging procedures a facial plastic surgeon performs. Numerous techniques have been developed since the inception of rhinoplasty to aid in correction of aesthetic and functional issues. Congenital, iatrogenic, and traumatic etiologies can all lead to a crooked nose. Autologous rib or costal cartilage grafting is a powerful tool that can aid the surgeon in successful correction of the crooked nose.

Seeking common pathophysiology in asthma, atopy and sinusitis.

Asthma and chronic sinusitis are inexplicably common airway diseases that are linked to atopy and allergic inflammation. T helper type 2 (Th2) cells and the associated cytokines are believed to play crucial pathogenic roles in asthma, but the environmental factors that instigate allergic airway disease remain poorly understood. Environmental proteinases are highly allergenic and are candidate inducers of airway Th2 responses. Determining the proteinases and their sources that are relevant to airway disease, however, remains challenging. In this Opinion, we summarize the evidence that implicates fungi as both a relevant source of allergenic proteinases and a potential cause of asthma, atopy and chronic sinusitis through airway infection. Clarification of the extrinsic causes of these processes will markedly improve diagnosis, prognosis and therapy.

IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps.

RATIONALE: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. OBJECTIVES: The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. METHODS: Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. CONCLUSIONS: These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

PeptiVAX: A new adaptable peptides-delivery platform for development of CTL-based, SARS-CoV-2 vaccines.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a threat to public health and the global economy, necessitating the development of various vaccination strategies. Mutations in the SPIKE protein gene, a crucial component of mRNA and adenovirus-based vaccines, raised concerns about vaccine efficacy, prompting the need for rapid vaccine updates. To address this, we leveraged PeptiCRAd, an oncolytic vaccine based on tumor antigen decorated oncolytic adenoviruses, creating a vaccine platform called PeptiVAX. First, we identified multiple CD8 T-cell epitopes from highly conserved regions across coronaviruses, expanding the range of T-cell responses to non-SPIKE proteins. We designed short segments containing the predicted epitopes presented by common HLA-Is in the global population. Testing the immunogenicity, we characterized T-cell responses to candidate peptides in peripheral blood mononuclear cells (PBMCs) from pre-pandemic healthy donors and ICU patients. As a proof of concept in mice, we selected a peptide with epitopes predicted to bind to murine MHC-I haplotypes. Our technology successfully elicited peptide-specific T-cell responses, unaffected by the use of unarmed adenoviral vectors or adeno-based vaccines encoding SPIKE. In conclusion, PeptiVAX represents a fast and adaptable SARS-CoV-2 vaccine delivery system that broadens T-cell responses beyond the SPIKE protein, offering potential benefits for vaccine effectiveness.

Tracheobronchial mycosis in a retrospective case-series study of five status asthmaticus patients.

The etiology of status asthmaticus (SA), a complication of severe asthma, is unknown. Fungal exposure, as measured by fungal atopy, is a major risk factor for developing asthma, but the relationship of fungi in SA per se has not previously been reported. In this five patient retrospective case series study, lower respiratory tract cultures were performed on bronchoalveolar lavage or tracheal aspirate fluid, comparing standard clinical laboratory cultures with a specialized technique in which respiratory mucus was removed prior to culture. We show that mucolytic treatment allows an increased detection of fungal growth, especially yeast, from the lower airways of all SA patients. We also demonstrate that inhalation of the yeast Candida albicans readily induces asthma-like disease in mice. Our observations suggest that SA may represent a fungal infectious process, and support additional prospective studies utilizing anti-fungal therapy to supplement conventional therapy, broad-spectrum antibiotics and high-dose glucocorticoids, which can promote fungal overgrowth.

Fungal chitin from asthma-associated home environments induces eosinophilic lung infiltration.

Development of asthma and allergic inflammation involves innate immunity, but the environmental contributions remain incompletely defined. Analysis of dust collected from the homes of asthmatic individuals revealed that the polysaccharide chitin is environmentally widespread and associated with ß-glucans, possibly from ubiquitous fungi. Cell wall preparations of Aspergillus isolated from house dust induced robust recruitment of eosinophils into mouse lung, an effect that was attenuated by enzymatic degradation of cell wall chitin and ß-glucans. Mice expressing constitutively active acidic mammalian chitinase in the lungs demonstrated a significant reduction in eosinophil infiltration after fungal challenge. Conversely, chitinase inhibition prolonged the duration of tissue eosinophilia. Thus, fungal chitin derived from home environments associated with asthma induces eosinophilic allergic inflammation in the lung, and mammalian chitinases, including acidic mammalian chitinase, limit this process.

Proteinases as molecular adjuvants in allergic airway disease.

BACKGROUND: Asthma and related respiratory tract allergic diseases are among the most common chronic diseases of adults and children. Despite their importance, disease course cannot be predicted and treatment remains non-specific and potentially hazardous, with no means for cure. Improved clinical management of asthma will require an improved understanding of the fundamental factors that initiate allergic inflammation, especially T helper type 2 (T(H)2) cell induction. SCOPE OF REVIEW: In this review, we explore the Proteinase Hypothesis of allergic airway disease, considering specifically how organismal proteinases contribute to the expression of allergic disease and potentially important proteinase signaling pathways. MAJOR CONCLUSIONS: Proteinases from diverse sources (bacteria, fungi, plants) may cause occupational asthma by acting as immune adjuvant factors that specifically elicit T(H)2 cell-dependent allergic inflammation. However, more conventional allergic airway diseases (asthma, allergic sinusitis) are more likely to arise from contained fungal or viral infections of the airway in which proteinases are produced and serve as major virulence factors. Proteinases may elicit allergic disease by disrupting numerous cellular proteins, potentially including Toll like receptor (TLR) 4, but critical proteinase-activated signaling pathways remain largely unknown. GENERAL SIGNIFICANCE: Clarification of how proteinases cause allergic disease, specifically confirming an infectious basis for airway proteinase exposure, will likely radically advance how asthma and related respiratory tract disorders are diagnosed and treated. This article is part of a Special Issue entitled Biochemistry of Asthma.

The laryngeal saccule: clinical significance.

The association between the laryngeal saccule and a laryngocele is an important clinical relationship. Here, we describe this and other clinical correlations of the saccule including infection and carcinoma and suggest that these should be discussed in medical gross anatomy courses. We also briefly present some descriptive information on the anatomy and function of the saccule in humans and other higher primates.

Accuracy, interpretability and usability study of a wireless self-guided fetal heartbeat monitor compared to cardiotocography.

Fetal Cardiography is usually performed using in-hospital Cardiotocographic (CTG) devices to assess fetal wellbeing. New technologies may permit home-based, self-administered examinations. We compared the accuracy, clinical interpretability, and user experience of a patient-administered, wireless, fetal heartbeat monitor (HBM) designed for home use, to CTG. Initially, participants had paired HBM and CTG examinations performed in the clinic. Women then used the HBM unsupervised and rated the experience. Sixty-three women had paired clinic-based HBM and CTG recordings, providing 6982 fetal heart rate measures for point-to-point comparison from 126 min of continuous recording. The accuracy of the HBM was excellent, with limits of agreement (95%) for mean fetal heart rate (FHR) between 0.72 and -1.78 beats per minute. The FHR was detected on all occasions and confirmed to be different from the maternal heart rate. Both methods were equally interpretable by Obstetricians, and had similar signal loss ratios. Thirty-four (100%) women successfully detected the FHR and obtained clinically useful cardiographic data using the device at home unsupervised. They achieved the required length of recording required for non-stress test analysis. The monitor ranked in the 96-100th percentile for usability and learnability. The HBM is as accurate as gold-standard CTG, and provides equivalent clinical information enabling use in non-stress test analyses conducted outside of hospitals. It is usable by expectant mothers with minimal training.

Consistency of pediatric pain ratings between dyads: an updated meta-analysis and metaregression.

Accurate assessment of pediatric pain remains a challenge, especially for children who are preverbal or unable to communicate because of their health condition or a language barrier. A 2008 meta-analysis of 12 studies found a moderate correlation between 3 dyads (child-caregiver, child-nurse, and caregiver-nurse). We updated this meta-analysis, adding papers published up to August 8, 2021, and that included intraclass correlation/weighted kappa statistics (ICC/WK) in addition to standard correlation. Forty studies (4,628 children) were included. Meta-analysis showed moderate pain rating consistency between child and caregiver (ICC/WK = 0.51 [0.39-0.63], correlation = 0.59 [0.52-0.65], combined = 0.55 [0.48-0.62]), and weaker consistency between child and health care provider (HCP) (ICC/WK = 0.38 [0.19-0.58], correlation = 0.49 [0.34-0.55], combined = 0.45; 95% confidence interval 0.34-0.55), and between caregiver and HCP (ICC/WK = 0.27 [-0.06 to 0.61], correlation = 0.49 [0.32 to 0.59], combined = 0.41; 95% confidence interval 0.22-0.59). There was significant heterogeneity across studies for all analyses. Metaregression revealed that recent years of publication, the pain assessment tool used by caregivers (eg, Numerical Rating Scale, Wong-Baker Faces Pain Rating Scale, and Visual Analogue Scale), and surgically related pain were each associated with greater consistency in pain ratings between child and caregiver. Pain caused by surgery was also associated with improved rating consistency between the child and HCP. This updated meta-analysis warrants pediatric pain assessment researchers to apply a comprehensive pain assessment scale Patient-Reported Outcomes Measurement Information System to acknowledge psychological and psychosocial influence on pain ratings.

Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer.

Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A-dependent emphysema. However, whether and how they alter the immune responses to lung cancer remains unknown. Here, we show that exposure to nCB particles increased PD-L1+ PD-L2+ CD206+ antigen-presenting cells (APCs), exhausted T cells, and Treg cells. Lung macrophages that harbored nCB particles showed selective mitochondrial structure damage and decreased oxidative respiration. Lung macrophages sustained the HIF1α axis that increased glycolysis and lactate production, culminating in an immunosuppressive microenvironment in multiple mouse models of non-small cell lung cancers. Adoptive transfer of lung APCs from nCB-exposed wild type to susceptible mice increased tumor incidence and caused early metastasis. Our findings show that nCB exposure metabolically rewires lung macrophages to promote immunosuppression and accelerates the development of lung cancer.