Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Is Elevated in Patients with Asthma and Airway Obstruction.

Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma. Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect (76.4±51.4 ng/mL vs. 39.3±27.4 ng/mL, P=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 75% of vital capacity %predicted (r=-0.3373, P=0.0078 and r=-0.2900, P=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect. Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

Liver and spleen elastography of dogs affected by brachycephalic obstructive airway syndrome and its correlation with clinical biomarkers.

The purpose of this study is to determine whether the brachycephalic obstructive airway syndrome (BOAS) is correlated to alterations in liver and spleen elasticity. Forty-eight brachycephalic and 22 mesocephalic dogs were submitted to a BOAS functional assessment, laboratory tests, abdominal ultrasound and liver and spleen Acoustic Radiation Force Impulse (ARFI) elastography. Dogs clinically affected by BOAS had higher values of liver stiffness (p < 0.001) than healthy dogs: medial lobes (1.57 ± 0.37 m/s), left and right lateral lobes (1.54 ± 0.50 m/s, 1.23 ± 0.28 m/s, respectively) and caudate lobe (1.28 ± 0.42 m/s). Compared to the mesocephalic group, the brachycephalic group (BOAS clinically affected and unaffected dogs) had higher spleen (2.51 ± 0.45 m/s; p < 0.001) and liver stiffness (p < 0.001): medial lobes (1.53 ± 0.37 m/s), left and right lateral lobes (1.47 ± 0.47 m/s, 1.20 ± 0.30 m/s, respectively) and caudate lobe (1.23 ± 0.40 m/s). Principal component analysis explained 70% of the variances composed by liver stiffness increase, erythrocytes and alanine aminotransferase reduction. Brachycephalic dogs had higher spleen and liver stiffness and a subacute inflammatory state, which represent another BOAS systemic effect. Consequently, these dogs can be at higher risk of hepatic disorders compared with mesocephalic dogs, similarly to humans affected by sleep apnea syndrome.

Involvement of hemostasis in pathophysiology of RAO in horses.

Recurrent Airway Obstruction (RAO), also called severe asthma or heaves, is a chronic disease in adult horses caused by aeroallergens from straw or hay. Disturbances in hemostasis (intensified coagulation and depressed fibrinolysis) are considered one of the prominent reasons of inflammatory process, injury and dysfunction of the lungs. The aim of the study was to evaluate chosen parameters of hemostasis in horses with active form of RAO. Ten RAO-horses (group R) and ten healthy horses (group C) were exposed to straw and hay allergen challenge. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen concentration (Fb), stabilized fibrin degradation product (d-dimer), antithrombin (AT), protein C and coagulation factors II through XII were assessed in plasma obtained from blood of all the horses. Exposure to aeroallergens resulted in prolongation of aPTT in both groups of animals; it was evident in the group R and moderate in the group C. There were no differences in PT and TT. Concentrations of fibrinogen and d-dimer and activity of protein C in both groups were increased but lay within or near to reference values. The activity of AT was depressed in RAO-horses. All exposed horses showed increased activity of coagulation factors II, VIII and X but they had no changes in activity of factor V. Factors VII and XII displayed a reduction in activity. The decrease in factor IX activity was noted in the group C only. Various changes were observed in activity of factor XI; in horses with RAO it was elevated but in healthy horses it was declined. The changes of the parameters tested in RAO-horses indicate the involvement of coagulation and fibrinolysis which apparently remained under control of efficient and active mechanisms of general hemostasis.

Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life.

BACKGROUND: Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life. METHODS: We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV1%:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months). RESULTS: FEV1% improved significantly after MEP. Mean FEF25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/µL (8.4 ± 5.2%) decreasing to 151 ± 384/µL (1.6 ± 1.6%) (p < 0.0001), FENO levels decreased likewise. MEP treatment also led to a significant ACT improvement (mean pre:14.2 ± 4.4; mean post:20.5 ± 28) and exacerbations significantly fell from 3.8 ± 1.9 to 0.8 ± 1.1 (p < 0.0001). 74% of patients were steroid-dependent before MEP. 45.4% and 46.4% of them showed a suspension and dose reduction respectively (p < 0.0001). A significant number reduced also ICS doses. Only 67% of subjects used SABA as needed before MEP, falling to 20% after MEP. About 40% of patients highlighted a maintenance therapy step-down. Subjects showing an omalizumab treatment failure before MEP had a similar positive response when compared with omalizumab untreated patients. CONCLUSION: In real-life, MEP improved significantly all outcomes even small airway obstruction, suggesting its possible role also in distal lung region treatment. Furthermore, it demonstrated its high effectiveness in OC/ICS-sparing, in reducing SABA as needed and in stepping-down maintenance therapy. MEP is a valid alternative for patients with previous omalizumab treatment failure.

Increased levels of inflammatory biomarker CX3CL1 in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the concentration of CX3CL1 in serum of patients with chronic obstructive pulmonary disease (COPD), and to evaluate the associations between the CX3CL1 level and systemic inflammation, small airway obstruction, and COPD assessment test (CAT) scores in COPD patients. METHODS: Enzyme-linked immunosorbent assay were utilized to detect the CX3CL1 protein in serum separately from 64 patients with COPD and 53 healthy controls. RESULTS: Compared with healthy non-smokers, healthy smokers and COPD non-smokers, serum CX3CL1 protein levels were significantly elevated in COPD smokers (258.33 ±â€¯56.27 pg/mL versus 177.32 ±â€¯43.21 pg/mL, 185.64 ±â€¯47.03 pg/mL, and 226.55 ±â€¯51.79 pg/mL, P < 0.05). Correlation analysis indicated that serum CX3CL1 in COPD smokers was negatively correlated with FEV1/FVC (justified r = -0.319, P < 0.001), FEV1/Pre (justified r = -0.476, P < 0.001), FEV3/FVC (justified r = -0.354, P < 0.001), MMEF25-75/Pre (justified r = -0.428, P < 0.001), but positively correlated with CRP (justified r = 0.331, P < 0.001) and MMP-12 (justified r = 0.352, P < 0.001). However, our results showed no significant correlation between serum CX3CL1 of COPD smokers and the diffusing capacity of the lung for carbon monoxide (DLCO) (justified r = 0.0397, P = 0.6025), but a positive correlation with COPD assessment test (CAT) scores (justified r = 0.367, P < 0.001). Finally, through multivariate linear analysis, statistical results demonstrated age (ß = -0.2694, P = 0.005), FEV1/Pred (ß = -0.2653, P = 0.003), CRP (ß = 0.1427, P = 0.0478) and MMP-12 (ß = 0.430, P < 0.001) are independent parameters associated with CX3CL1. CONCLUSION: The results demonstrated that elevated circulating CX3CL1 level is associated with the systemic inflammation, small airway obstruction, and CAT scores in COPD patients, suggesting that CX3CL1 may play crucial roles in the pathogenesis of COPD. Blocking CX3CL1 might prevent the progression of chronic obstructive pulmonary disease.

Relationship between airway obstruction and C-reactive protein levels in a community-based population of Korea.

OBJECTIVE: To examine the relationship between high-sensitivity C-reactive protein (hs-CRP) levels and lung function in a community-based cohort of South Korea.DESIGN: The Ansung-Ansan cohort database (an ongoing prospective study of a community-based population) was used in the analysis. We defined airway obstruction as the ratio between forced expiratory volume in 1 sec:forced vital capacity ratio (FEV1:FVC) of <95% of the predicted value for a healthy person. We also used the serum level of hs-CRP as a marker of inflammation. Multivariate analysis was performed with adjustment for the clinical characteristics of the participants.RESULTS: A total of 5528 individuals were eligible for the study. The average age was 55.1 years, and 47.8% were males. The prevalence of airway obstruction was 9.0%, and the mean hs-CRP level was 1.51 mg/dl. Serum hs-CRP levels increased with the severity of airway obstruction, and the latter worsened with an increase in the hs-CRP level. In multivariate analysis, as the hs-CRP level increased, FEV1 and FVC decreased. A higher FEV1:FVC ratio was associated with lower hs-CRP levels in males.CONCLUSION: Higher hs-CRP levels were associated with decreased FEV1 and FVC in a general population of Korea. The FEV1:FVC ratio decreased with an increase in the hs-CRP level in males.

Lack of Benefit of Heliox During Mechanical Ventilation of Subjects With Severe Air-Flow Obstruction.

BACKGROUND: The value of heliox (helium-oxygen mixture) for patients with severe air-flow obstruction is uncertain. The purpose of this study was to determine whether heliox could reduce the degree of hyperinflation and hypercapnia in mechanically ventilated patients with severe air-flow obstruction. METHODS: This was a single-center, prospective observational study conducted in a medical ICU of an academic medical center. We assessed the impact of heliox (65-70% helium, 30-35% oxygen) on airway pressures and arterial blood gases of 13 subjects undergoing mechanical ventilation for severe asthma (n = 8) or exacerbation of COPD (n = 5). RESULTS: As compared with ventilation with air-O2, heliox resulted in a reduction in peak airway pressure (54.1 ± 12.6 cm H2O vs 47.9 ± 10.8 cm H2O, P < .001) and PaCO2 (64.3 ± 14.9 mm Hg vs 62.3 + 15.1 mm Hg, P = .01). In contrast, there was no change in plateau pressure (25.3 ± 5.5 cm H2O vs 25.8 ± 5.6 cm H2O, P = .14) or total PEEP (13.4 ± 3.8 cm H2O vs 13.3 ± 4.1 cm H2O, P = .79) in response to heliox. CONCLUSIONS: In mechanically ventilated subjects with severe air-flow obstruction, administration of heliox had no effect on indices of dynamic hyperinflation (plateau pressure and total PEEP) and resulted in only a small reduction in PaCO2 .

Establishment of a Rabbit Model of Chronic Obstructive Sleep Apnea and Application in Cardiovascular Consequences.

BACKGROUND: Although obstructive sleep apnea (OSA) has been recognized as a major risk factor for cardiovascular complications and its clinical features are well characterized, it is difficult to replicate the OSA hypoxic model in humans. We aimed to establish an experimental rabbit model for chronic OSA and to explore its application to measure blood pressure (BP), myocardial systolic function, and oxidative stress. METHODS: The rabbit model for OSA was established by repeatedly closing the airway and then reopening it. A tube specially designed with a bag that could be alternately inflated and deflated according to a predetermined time schedule, resulting in recurrent airway occlusions and chronic intermittent hypoxia (CIH) imitating OSA patterns in humans, was used. Twenty-four rabbits were randomly divided into obstruction, sham, and control groups, and their upper airways were alternately closed for 15 s and then reopened for 105 s in a 120-s-long cycle, for 8 h each day over 12 consecutive weeks. Before and after the experiment, the BP of each rabbit was monitored. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and reactive oxygen species (ROS) contents, as well as Na+-K+-ATPase/Ca2+-ATPase activities in cardiac muscle were examined. In addition, cardiac functional parameters were measured using echocardiography. RESULTS: After 3 months, all rabbits in the obstruction group manifested sleepiness performance similar to that observed in OSA patients. Traces of airflow and SpO2showed that this model mimicked the respiratory events involved in OSA, including increased respiratory effort and decreased oxygen saturation. Gradually, the BP rose each month. CIH led to obvious oxidative stress and injured myocardial systolic performance. The serum levels of IL-6 and TNF-α increased significantly (64.75 ± 9.05 pg/ml vs. 147.00 ± 19.24 pg/ml and 59.38 ± 8.21 pg/ml vs. 264.75 ± 25.54 pg/ml, respectively, both P < 0.001). Compared with the sham and the control groups, myocardial activities of Na+-K+-ATPase/Ca2+-ATPase and SOD in the obstruction group decreased markedly, while ROS and MDA content increased. CONCLUSIONS: These results show that the rabbit model for OSA simulates the pathophysiological characteristics of OSA in humans, which implies that this animal model is feasible and useful to study the mechanisms involved in the cardiovascular consequences of OSA.

Association of serum ferritin levels with smoking and lung function in the Korean adult population: analysis of the fourth and fifth Korean National Health and Nutrition Examination Survey.

BACKGROUND: Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and serum ferritin concentration in a large cohort representative of the Korean adult population. MATERIALS AND METHODS: Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40 years with serum ferritin levels and spirometric data were selected for this study. RESULTS: The mean age was 56.5 years for men (43%) and 56.9 years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable regression analysis, serum ferritin was positively associated with forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex, height, and weight. CONCLUSION: Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive severity. While smoking amount was inversely related to lung function, higher levels of serum ferritin were associated with enhanced spirometric results in a representative sample of the general Korean adult population. Future prospective studies will be needed to clarify the causality between serum ferritin and lung functions and their role in COPD morbidity.

Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. METHODS: Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay. Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test. Pearson's partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD. RESULTS: First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007). Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), FEV1/Pre (justified r=-0.308, P<0.001; justified r=-0.295, P=0.001, respectively) and SAO indicators such as FEV3/FVC, MMEF25-75/Pre (justified r=-0.289, P=0.001; justified r=-0.273, P=0.002, respectively), but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively). Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1. CONCLUSION: Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD.

Serum 8-hydroxy-2-deoxyguanosine as a marker of DNA oxidative damage in horses with recurrent airway obstruction.

BACKGROUND: It has been reported that equine recurrent airway obstruction (RAO) is a state of oxidative stress. Oxidant-antioxidant imbalance is known to increase the conversion of deoxyguanosine to 8-hydroxy-2-deoxyguanosine (8-OHdG) in DNA. 8-OHdG can easily be measured using ELISA tests in serum or urine samples. In this study, we analysed serum 8-OHdG levels in horses with recurrent airway obstruction and in healthy controls. RESULTS: The study material consisted of seven healthy horses and seven horses with symptomatic RAO. All horses were exposed to moldy hay and straw for 48 h to induce clinical exacerbation of RAO. The serum 8-OHdG levels were determined using the ELISA Highly Sensitive 8-OHdG kit. The difference between the levels of 8-OHdG in healthy and RAO-affected horses was significant. The median level of 8-OHdG was 0.044 ng/ml in the healthy controls versus 0.498 ng/ml in RAO horses (P = 0.0021). CONCLUSIONS: The results of the study strongly suggest that DNA damage coexists in the course of equine RAO. We therefore propose that future research should aim at the development of new drugs that target pro-inflammatory molecules, since DNA damage appears to be the result of chronic inflammation.

Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men-the British Regional Heart Study.

AIMS: The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men. METHODS AND RESULTS: Prospective study of 3242 men aged 60-79 years without prevalent HF or myocardial infarction followed up for an average period of 13 years, in whom 211 incident HF cases occurred. Incident HF was examined in relation to % predicted FEV1 and FVC. The Global Initiative on Obstructive Lung Diseases spirometry criteria were used to define airway obstruction. Reduced FEV1, but not FVC in the normal range, was significantly associated with increased risk of HF after adjustment for established HF risk factors including inflammation. The adjusted HRs comparing men in the 6-24th percentile with the highest quartile were 1.91 (1.24 to 2.94) and 1.30 (0.86 to 1.96) for FEV1 and FVC, respectively. FEV1 and FVC were inversely associated with NT-proBNP and cTnT, although the association between FEV1 and incident HF remained after adjustment for NT-proBNP and cTnT. Compared with normal subjects (FEV1/FVC ≥0.70 and FVC≥80%), moderate or severe (FEV1/FVC <0.70 and FEV1 <80%) airflow obstruction was independently associated with HF ((adjusted relative risk 1.59 (1.08 to 2.33)). Airflow restriction (FEV1/FVC ≥0.70 and FVC <80%) was not independently associated with HF. CONCLUSIONS: Reduced FEV1 reflecting airflow obstruction is associated with cardiac dysfunction and increased risk of incident HF in older men.

Changes in Expression of Genes Regulating Airway Inflammation Following a High-Fat Mixed Meal in Asthmatics.

Consumption of a high fat meal can increase neutrophilic airway inflammation in asthma subjects. This study investigates the molecular mechanisms driving airway neutrophilia following a high fat meal in asthmatics. Subjects with asthma (n = 11) and healthy controls (n = 8) consumed a high-fat/energy meal, containing total energy (TE) of 3846 kJ and 48 g of total fat (20.5 g saturated). Sputum was induced at 0 and 4 h, and gene expression was examined by microarray and quantitative real-time PCR (qPCR). Following the high fat dietary challenge, 168 entities were significantly differentially expressed greater than >1.5 fold in subjects with asthma, whereas, in healthy controls, only 14 entities were differentially expressed. Of the 168 genes that were changed in asthma, several biological processes were overrepresented, with 25 genes involved in "immune system processes". qPCR confirmed that S100P, S100A16, MAL and MUC1 were significantly increased in the asthma group post-meal. We also observed a strong correlation and a moderate correlation between the change in NLRP12 and S100A16 gene expression at 4 h compared to baseline, and the change in total and saturated non-esterified plasma fatty acid levels at 2 h compared to baseline. In summary, our data identifies differences in inflammatory gene expression that may contribute to increased airway neutrophilia following a high fat meal in subjects with asthma and may provide useful therapeutic targets for immunomodulation. This may be particularly relevant to obese asthmatics, who are habitually consuming diets with a high fat content.

Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

BACKGROUND: Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. OBJECTIVE: To investigate the association between serum progranulin levels and various clinical features in patients with asthma. METHODS: Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. RESULTS: Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P < .001) after adjustment for other variables, such as age, sex, smoking status, blood neutrophil count, and current use of systemic corticosteroids. CONCLUSION: Although the exact mechanism of the anti-inflammatory action of progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma.

Blood lipid levels associate with childhood asthma, airway obstruction, bronchial hyperresponsiveness, and aeroallergen sensitization.

BACKGROUND: Studies of children's blood lipid profiles in relation to asthma are few, and the results are ambiguous. OBJECTIVE: We sought to examine whether the lipid profile is associated with concurrent asthma, altered lung function, and allergic sensitization in children. METHODS: High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured at ages 5 to 7 years in the Copenhagen Prospective Studies on Asthma in Childhood2000 at-risk birth cohort. Asthma and allergic rhinitis were diagnosed based on predefined algorithms at age 7 years along with assessments of lung function, bronchial responsiveness, fraction of exhaled nitric oxide (Feno), and allergic sensitization. Associations between lipid levels and clinical outcomes were adjusted for sex, passive smoking, and body mass index. RESULTS: High levels of low-density lipoprotein cholesterol were associated with concurrent asthma (adjusted odds ratio [aOR], 1.93; 95% CI, 1.06-3.55; P = .03) and airway obstruction: 50% of forced expiratory flow (aß coefficient, -0.13 L/s; 95% CI, -0.24 to -0.03 L/s; P = .01) and specific airway resistance (aß coefficient, 0.06 kPa/s; 95% CI, 0.00-0.11 kPa/s; P = .05). High levels of high-density lipoprotein cholesterol were associated with improved specific airway resistance (aß coefficient, -0.11 kPa/s; 95% CI, -0.21 to -0.02; P = .02), decreased bronchial responsiveness (aß coefficient, 0.53 log-µmol; 95% CI, 0.00-1.60 log-µmol; P = .05), decreased risk of aeroallergen sensitization (aOR, 0.27; 95% CI, 0.01-0.70; P = .01), and a trend of reduced Feno levels (aß coefficient, -0.22 log-ppb; 95% CI, -0.50 to 0.01 log-ppb; P = .06). High triglyceride levels were associated with aeroallergen sensitization (aOR, 2.01; 95% CI, 1.14-3.56; P = .02) and a trend of increased Feno levels (aß coefficient, 0.14 log-ppb; 95% CI, -0.02 to 0.30 log-ppb; P = .08). CONCLUSION: The blood lipid profile is associated with asthma, airway obstruction, bronchial responsiveness, and aeroallergen sensitization in 7-year-old children. These findings suggest that asthma and allergy are systemic disorders with commonalities with other chronic inflammatory disorders.

Pulmonary effects of expiratory-assisted small-lumen ventilation during upper airway obstruction in pigs.

Novel devices for small-lumen ventilation may enable effective inspiration and expiratory ventilation assistance despite airway obstruction. In this study, we investigated a porcine model of complete upper airway obstruction. After ethical approval, we randomly assigned 13 anaesthetised pigs either to small-lumen ventilation following airway obstruction (n = 8) for 30 min, or to volume-controlled ventilation (sham setting, n = 5). Small-lumen ventilation enabled adequate gas exchange over 30 min. One animal died as a result of a tension pneumothorax in this setting. Redistribution of ventilation from dorsal to central compartments and significant impairment of the distribution of ventilation/perfusion occurred. Histopathology demonstrated considerable lung injury, predominantly through differences in the dorsal dependent lung regions. Small-lumen ventilation maintained adequate gas exchange in a porcine airway obstruction model. The use of this technique for 30 min by inexperienced clinicians was associated with considerable end-expiratory collapse leading to lung injury, and may also carry the risk of severe injury.

Transtracheal ventilation with a novel ejector-based device (Ventrain) in open, partly obstructed, or totally closed upper airways in pigs.

BACKGROUND: Transtracheal access and subsequent jet ventilation are among the last options in a 'cannot intubate-cannot oxygenate' scenario. These interventions may lead to hypercapnia, barotrauma, and haemodynamic failure in the event of an obstructed upper airway. The aim of the present study was to evaluate the efficacy and the haemodynamic effects of the Ventrain, a manually operated ventilation device that provides expiratory ventilation assistance. Transtracheal ventilation was carried out with the Ventrain in different airway scenarios in live pigs, and its performance was compared with a conventional jet ventilator. METHODS: Pigs with open, partly obstructed, or completely closed upper airways were transtracheally ventilated either with the Ventrain or by conventional jet ventilation. Airway pressures, haemodynamic parameters, and blood gases obtained in the different settings were compared. RESULTS: Mean (SD) alveolar minute ventilation as reflected by arterial partial pressure of CO2 was superior with the Ventrain in partly obstructed airways after 6 min in comparison with traditional manual jet ventilation [4.7 (0.19) compared with 7.1 (0.37) kPa], and this was also the case in all simulated airway conditions. At the same time, peak airway pressures were significantly lower and haemodynamic parameters were altered to a lesser extent with the Ventrain. CONCLUSIONS: The results of this study suggest that the Ventrain device can ensure sufficient oxygenation and ventilation through a small-bore transtracheal catheter when the airway is open, partly obstructed, or completely closed. Minute ventilation and avoidance of high airway pressures were superior in comparison with traditional hand-triggered jet ventilation, particularly in the event of complete upper airway obstruction.

Blood parameters as indicators of upper airway obstruction in children with adenoid or adenotonsillar hypertrophy.

UNLABELLED: Adenotonsillar hypertrophy (ATH) is the most common cause of obstructive sleep apnea in children. This study aimed to evaluate the blood parameters of children with ATH who underwent surgery. METHODS: The study included a review of the medical records of 130 children who underwent adenoidectomy or adenotonsillectomy with a diagnosis of adenoid hypertrophy and/or chronic tonsillitis. Patients were classified into 3 groups: group 1 (n=69) underwent adenoidectomy, group 2 (n=61) underwent adenotonsillectomy, and group 3 consisted of 82 healthy children. White blood cell count, platelet count, hemoglobin levels, mean platelet volume, and platelet distribution width values were the primary outcome measures. RESULTS: Mean platelet volume, platelet distribution width and hemoglobin values decreased in the groups that underwent surgery. Whereas the decrease in group 1 was insignificant, it was significant in group 2. White blood cell count values increased in both group 1 (adenoidectomy) and group 2 (adenotonsillectomy), but the increase in group 2 was significant. No significant difference in platelet count was detected before versus after the operation. CONCLUSIONS: Upper airway obstruction caused by ATH remarkably changes the blood parameters related to chronic hypoxia. Significant improvement can be achieved after adenotonsillectomy rather than adenoidectomy alone.