Much of the total disease burden and cost of chronic obstructive pulmonary disease (COPD) is associated with acute exacerbations of COPD (AECOPD). Serum amyloid A (SAA) is a novel candidate ...exacerbation biomarker identified by proteomic screening.
To assess SAA as a biomarker of AECOPD.
Biomarkers were assessed (1) cross-sectionally (stable vs. AECOPD; 62 individuals) and (2) longitudinally with repeated measures (baseline vs. AECOPD vs. convalescence; 78 episodes in 37 individuals). Event severity was graded (I, ambulatory; II, hospitalized; III, respiratory failure) based on consensus guidelines.
Presumptively newly acquired pathogens were associated with onset of symptomatic AECOPD. In the cross-sectional study, both SAA and C-reactive protein (CRP) were elevated at AECOPD onset compared with stable disease (SAA median, 7.7 vs. 57.6 mg/L; P < 0.01; CRP median, 4.6 vs. 12.5 mg/L; P < 0.01). Receiver operator characteristics analysis was used to generate area-under-curve values for event severity. SAA discriminated level II/III events (SAA, 0.88; 95% confidence interval, 0.80-0.94 vs. CRP, 0.80; 95% confidence interval, 0.70-0.87; P = 0.05). Combining SAA or CRP with major symptoms (Anthonisen criteria, dyspnea) did not further improve the prediction model for severe episodes. IL-6 and procalcitonin were not informative.
SAA is a novel blood biomarker of AECOPD that is more sensitive than CRP alone or in combination with dyspnea. SAA may offer new insights into the pathogenesis of AECOPD.
Neutrophilic inflammation persists in COPD despite best current therapies and it is particularly resistant to inhaled glucocorticosteroids. Persistent neutrophil activation not only contributes to ...matrix breakdown, but can maintain inflammation through the release of endogenous damage associated molecule patterns (DAMPs). Inhibiting excessive neutrophilic inflammation is challenging as many pathogen recognition receptors can initiate migration and the targeting of downstream signaling molecules may compromise essential host defense mechanisms. Here, we discuss new strategies to combat this inflammation in COPD by focusing on the anti-inflammatory role of ALX/FPR2 receptors. ALX/FPR2 is a promiscuous G-protein coupled receptor (GPCR) responding to lipid and peptide agonists that can either switch on acute inflammation or promote resolution of inflammation. We highlight this receptor as an emerging target in the pathogenesis of COPD because known ALX/FPR2 endogenous agonists are enriched in COPD. Serum Amyloid A (SAA) has recently been discovered to be abundantly expressed in COPD and is a potent ALX/FPR2 agonist that unlike almost all other inflammatory chemoattractants, is induced by glucocorticosteroids. SAA not only initiates lung inflammation via ALX/FPR2 but can allosterically modify this receptor so that it no longer transduces pro-resolving signals from endogenous lipoxins that would otherwise promote tissue healing. We propose that there is an imbalance in endogenous and microbial ALX/FPR2 receptor agonists in the inflamed COPD lung environment that oppose protective anti-inflammatory and pro-resolution pathways. These insights open the possibility of targeting ALX/FPR2 receptors using synthetic agonists to resolve persistent neutrophilic inflammation without compromising essential host defense mechanisms.
In chronic obstructive pulmonary disease (COPD), loss of computed tomography (CT)-measured intercostal mass correlates with spirometric severity. Intercostal muscle ultrasound offers a repeatable and ...radiation-free alternative, however requires validation. We aimed to determine the reliability of parasternal intercostal muscle ultrasound, and the concurrent validity of parasternal ultrasound with clinicometric parameters. Twenty stable COPD patients underwent ultrasound measurement of thickness and echogenicity of 2
and 3
parasternal intercostal muscles, dominant pectoralis major and quadriceps, and diaphragm thickness; spirometry; and chest CT. Intra-rater intraclass correlation (ICC) for ultrasound intercostal thickness was 0.87-0.97 depending on site, with echogenicity ICC 0.63-0.91. Inter-rater ICC was fair to excellent. Ultrasound intercostal thickness moderately correlated with FEV
% predicted (r = 0.33) and quadriceps thickness (r = 0.31). Echogenicity correlated negatively with FEV
% predicted (r = -0.32). CT-measured lateral intercostal mass correlate negatively with parasternal ultrasound intercostal thickness. These data confirm ultrasound of parasternal intercostal musculature is reproducible. Lower intercostal muscle quantity and quality reflects greater COPD spirometric severity. This novel tool may have biomarker potential for both the systemic effects of COPD on muscle as well as local disruption of respiratory mechanics. The negative correlation between CT and ultrasound measurements may reflect complex site-dependent interactions between respiratory muscles and the chest wall.
Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus ...to perform endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA). In cases of suspected lung cancer, a combination of the two techniques is now recommended by consensus guidelines. EBUS TBNA is usually performed by pulmonologists; however, the learning curve for EUS-B-FNA, which may be performed during the same procedure, has not been described.A multicentre, observational Australian study, using prospectively collected data from three experienced pulmonologists was conducted. Cumulative sum (cusum) analysis was used to generate visual learning curves.A total of 152 target lesions were sampled in 137 patients, with an overall sensitivity for malignancy of 94.8%. The sensitivity for malignant lesions outside of the 2009 International Association for the Study of Lung Cancer lymph node map (largely intraparenchymal lesions) was 92.9%. All three operators were competent by conventional cusum criteria. There was one case of pneumothorax, and no episodes of mediastinitis or oesophageal perforation were observed.Our data suggest that experienced pulmonologists can safely and accurately perform EUS-B-FNA, with a high diagnostic sensitivity for both lymph node and non-nodal lesions.
The Lc petunia system, which displays enhanced, light-induced vegetative pigmentation, was used to investigate how high light affects anthocyanin biosynthesis, and to assess the effects of ...anthocyanin pigmentation upon photosynthesis. Lc petunia plants displayed intense purple anthocyanin pigmentation throughout the leaves and stems when grown under high-light conditions, yet remain acyanic when grown under shade conditions. The coloured phenotypes matched with an accumulation of anthocyanins and flavonols, as well as the activation of the early and late flavonoid biosynthetic genes required for flavonol and anthocyanin production. Pigmentation in Lc petunia only occurred under conditions which normally induce a modest amount of anthocyanin to accumulate in wild-type Mitchell petunia Petunia axillarisx(Petunia axillarisxPetunia hybrida cv. 'Rose of Heaven'). Anthocyanin pigmentation in Lc petunia leaves appears to screen underlying photosynthetic tissues, increasing light saturation and light compensation points, without reducing the maximal photosynthetic assimilation rate (Amax). In the Lc petunia system, where the bHLH factor Leaf colour is constitutively expressed, expression of the bHLH (Lc) and WD40 (An11) components of the anthocyanin regulatory system were not limited, suggesting that the high-light-induced anthocyanin pigmentation is regulated by endogenous MYB transcription factors.
Summary In many patients the optimal method of investigation of peripheral pulmonary lesions (PPL) is not clear. We performed a prospective randomized pragmatic trial to determine the comparative ...effectiveness of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) and CT-guided percutaneous needle biopsy (CT-PNB) for the investigation of PPL. Overall complication rates were higher in those undergoing CT-PNB (27% v 3%, p = 0.03), while diagnostic accuracy of EBUS-TBLB was shown to be non-inferior to that of CT-PNB. Expected diagnostic accuracy and complication rates are likely to differ for individual patients on the basis of specific complex clinicoradiologic factors, which will influence the cost-benefit analysis between EBUS-TBLB and CT-PNB for individual patients. Further studies are required to examine the effect of these factors on clinical decision-making.
Objectives
To design and evaluate 3D‐printed nasal swabs for collection of samples for SARS‐CoV‐2 testing.
Design
An iterative design process was employed. Laboratory evaluation included in vitro ...assessment of mock nasopharyngeal samples spiked with two different concentrations of gamma‐irradiated SARS‐CoV‐2. A prospective clinical study compared SARS‐CoV‐2 and human cellular material recovery by 3D‐printed swabs and standard nasopharyngeal swabs.
Setting, participants
Royal Melbourne Hospital, May 2020. Participants in the clinical evaluation were 50 hospital staff members attending a COVID‐19 screening clinic and two inpatients with laboratory‐confirmed COVID‐19.
Intervention
In the clinical evaluation, a flocked nasopharyngeal swab sample was collected with the Copan ESwab and a mid‐nasal sample from the other nostril was collected with the 3D‐printed swab.
Results
In the laboratory evaluation, qualitative agreement with regard to SARS‐CoV‐2 detection in mock samples collected with 3D‐printed swabs and two standard swabs was complete. In the clinical evaluation, qualitative agreement with regard to RNase P detection (a surrogate measure of adequate collection of human cellular material) in samples collected from 50 hospital staff members with standard and 3D‐printed swabs was complete. Qualitative agreement with regard to SARS‐CoV‐2 detection in three pairs of 3D‐printed mid‐nasal and standard swab samples from two inpatients with laboratory‐confirmed SARS‐CoV‐2 was also complete.
Conclusions
Using 3D‐printed swabs to collect nasal samples for SARS‐CoV‐2 testing is feasible, acceptable to patients and health carers, and convenient.
Traffic pollution near childcare centres in Melbourne Walter, Clare; Schneider-Futschik, Elena; Irving, Louis
Australian and New Zealand journal of public health,
October 2019, 2019-Oct, 2019-10-00, 20191001, 2019-10-01, Letnik:
43, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Australia’s most common cause of general practitioner presentation in children under five is asthma and allergy. There is increasing evidence that exposure to traffic‐related air pollution (TRAP) is ...a significant contributor to the prevalence of asthma and allergy, and proximity to major roads correlates with exposure to TRAP. Childcare is an integral part of society where many children pass a significant amount of time. The siting of childcare centres is therefore a critical consideration for the healthy development of children and should be an important factor in urban growth planning.A study conducted by the World Health Organization (WHO) has found 90% of the world’s children are breathing toxic air, exceeding WHO Air Quality Guidelines. Australian air quality generally falls within WHO guidelines; however, there are hot spots in Australia – including Melbourne – that exceed legislated thresholds. Furthermore, conclusive evidence that there is no safe lower limit to the adverse effects of traffic pollution has brought the safety of these guidelines into question. A critical consideration for planning and health authorities should be to ensure the cleanest possible air for all people.
Chronic obstructive pulmonary disease (COPD) is an incurable inflammatory lung disease that afflicts millions of people worldwide, and it is the fourth leading cause of death. Systemic comorbidities ...affecting the heart, skeletal muscle, bone, and metabolism are major contributors to morbidity and mortality. Given the surprising finding in large prospective clinical biomarker studies that peripheral white blood cell count is more closely associated with disease than inflammatory biomarkers, we probed the role of blood growth factors. Using the SHIP-1-deficient COPD mouse model, which manifests a syndrome of destructive lung disease and a complex of comorbid pathologies, we have identified a critical and unexpected role for granulocyte-CSF (G-CSF) in linking these conditions. Deletion of G-CSF greatly reduced airway inflammation and lung tissue destruction, and attenuated systemic inflammation, right heart hypertrophy, loss of fat reserves, and bone osteoporosis. In human clinical translational studies, bronchoalveolar lavage fluid of patients with COPD demonstrated elevated G-CSF levels. These studies suggest that G-CSF may play a central and unforeseen pathogenic role in COPD and its complex comorbidities, and identify G-CSF and its regulators as potential therapeutic targets.
Patient-derived xenograft (PDX) models generated from surgical specimens are gaining popularity as preclinical models of cancer. However, establishment of PDX lines from small cell lung cancer (SCLC) ...patients is difficult due to very limited amount of available biopsy material. We asked whether SCLC cells obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) could generate PDX lines that maintained the phenotypic and genetic characteristics of the primary tumor. Following successful EBUS-TBNA sampling for diagnostic purposes, we obtained an extra sample for cytologic analysis and implantation into the flanks of immunodeficient mice. Animals were monitored for engraftment for up to 6 months. Histopathologic and immunohistochemical analysis, and targeted next-generation re-sequencing, were then performed in both the primary sample and the derivative PDX line. A total of 12 patients were enrolled in the study. EBUS-TBNA aspirates yielded large numbers of viable tumor cells sufficient to inject between 18,750 and 1,487,000 cells per flank, and to yield microgram quantities of high-quality DNA. Of these, samples from 10 patients generated xenografts (engraftment rate 83%) with a mean latency of 104 days (range 63-188). All but one maintained a typical SCLC phenotype that closely matched the original sample. Identical mutations that are characteristic of SCLC were identified in both the primary sample and xenograft line. EBUS-TBNA has the potential to be a powerful tool in the development of new targeting strategies for SCLC patients by providing large numbers of viable tumor cells suitable for both xenografting and complex genomic analysis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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