Airways Of Individuals Research Articles

Aerosol dynamics model for the simulation of hygroscopic growth and deposition of inhaled NaCl particles in the human respiratory tract

The purpose of the present work is the implementation of the aerosol dynamics model ADiC, specifically its heat/vapor transport and phase transition components, into the stochastic lung deposition model IDEAL. The combined ADiC/IDEAL model allows the simultaneous calculation of relative humidity, hygroscopic growth and deposition of inhaled NaCl aerosols in individual airways of the human lung along randomly selected particle paths and randomly selected times during the inhalation phase. Hygroscopic growth decreases deposition of submicron particles compared to hydrophobic particles with equivalent diameters due to a less efficient diffusion mechanism, while the more efficient impaction and sedimentation mechanisms increase total deposition for micrometer particles. Due to the variability and asymmetry of the human airway system, individual trajectories of inhaled particles are associated with individual growth factors. For a realistic breathing scenario, particles are inhaled at different times during the inspiratory phase and hence experience individual growth factors, thereby further enhancing the variability of individual growth factors and resulting deposition patterns. While nanometer particles adopt their equilibrium growth factor value already within the mouth and pharynx/larynx during the inspiratory phase, micrometer particles approach this value at the end of inspiration, thus further increasing in size during the exhalation phase. In summary, individual hygroscopic growth factors vary for different paths and different inhalation times. For model validation purposes, theoretical predictions were compared with human experimental deposition data and previous hygroscopic growth model simulations for total deposition of ultrafine and micrometer-sized NaCl particles.

Comparison of low- and ultralow-dose computed tomography protocols for quantitative lung and airway assessment.

Quantitative computed tomography (CT) measures are increasingly being developed and used to characterize lung disease. With recent advances in CT technologies, we sought to evaluate the quantitative accuracy of lung imaging at low- and ultralow-radiation doses with the use of iterative reconstruction (IR), tube current modulation (TCM), and spectral shaping. We investigated the effect of five independent CT protocols reconstructed with IR on quantitative airway measures and global lung measures using an invivo large animal model as a human subject surrogate. A control protocol was chosen (NIH-SPIROMICS+TCM) and five independent protocols investigating TCM, low- and ultralow-radiation dose, and spectral shaping. For all scans, quantitative global parenchymal measurements (mean, median and standard deviation of the parenchymal HU, along with measures of emphysema) and global airway measurements (number of segmented airways and pi10) were generated. In addition, selected individual airway measurements (minor and major inner diameter, wall thickness, inner and outer area, inner and outer perimeter, wall area fraction, and inner equivalent circle diameter) were evaluated. Comparisons were made between control and target protocols using difference and repeatability measures. Estimated CT volume dose index (CTDIvol) across all protocols ranged from 7.32mGy to 0.32mGy. Low- and ultralow-dose protocols required more manual editing and resolved fewer airway branches; yet, comparable pi10 whole lung measures were observed across all protocols. Similar trends in acquired parenchymal and airway measurements were observed across all protocols, with increased measurement differences using the ultralow-dose protocols. However, for small airways (1.9±0.2mm) and medium airways (5.7±0.4mm), the measurement differences across all protocols were comparable to the control protocol repeatability across breath holds. Diameters, wall thickness, wall area fraction, and equivalent diameter had smaller measurement differences than area and perimeter measurements. In conclusion, the use of IR with low- and ultralow-dose CT protocols with CT volume dose indices down to 0.32mGy maintains selected quantitative parenchymal and airway measurements relevant to pulmonary disease characterization.

Regulatory T-Cell Distribution within Lung Compartments in COPD

ABSTRACTThe importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF+ cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17+ cells only in small airways. A decrease in the density of Treg+, TGF-β+ and IL-10+ in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF+ cells were also increased in COPD; however, changes in Treg inhibitory associated cytokines were not observed in this compartment. Therefore, our results suggest that difference in Treg+ cell distributions in lung compartments and the decrease in TGF-β+ and IL-10+ cells in the airways may lead to the obstruction in smokers.

Reproducibility of airway luminal size in asthma measured by HRCT.

Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American Lung Association Airways Clinical Research Centers. Reproducibility of airway luminal size in asthma measured by HRCT. J Appl Physiol 123: 876-883, 2017. First published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.-High-resolution CT (HRCT) is a well-established imaging technology used to measure lung and airway morphology in vivo. However, there is a surprising lack of studies examining HRCT reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel-arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal continuous positive airway pressure (CPAP) device on airway reactivity to methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures provided an opportunity for the current analysis. We assessed the reproducibility of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were calculated for individual airway segments, individual lung lobes, both lungs, and air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC (95% CI) for airway luminal size at functional residual capacity ranged from 0.91 (0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63) agreement. The ICC for air trapping at functional residual capacity was 0.89 (0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95 (0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to reproducibly image unstimulated airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability.NEW & NOTEWORTHY There is a surprising lack of studies examining the reproducibility of high-resolution CT in asthma. The current study examined reproducibility of airway measurements. In stable well-controlled asthmatic subjects, it is possible to reproducibly image airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability.

Abstract 5002: Premalignant squamous cell lung carcinoma lesions have distinct molecular subtypes associated with histologic progression

Abstract Background: Squamous cell carcinoma (SCC) of the lung is a leading cause of cancer mortality in the US due to late stage diagnosis and lack of effective treatments. Lung SCC arises in the epithelial layer of the bronchial airways and is often preceded by the development of premalignant lesions (PMLs). The molecular events involved in the progression of PMLs to lung SCC are not clearly understood, and not all PMLs go on to form carcinoma. By molecularly characterizing PMLs and non-lesion areas in the airway of individuals with PMLs, we hypothesize that we will be able to identify subgroups of PMLs that are more likely to progress. Methods: We used mRNA sequencing to profile biopsies obtained from high-risk smokers undergoing lung cancer screening by auto-fluorescence bronchoscopy and CT at the Roswell Park Cancer Institute in Buffalo, NY. For each subject (n=30), we sampled bronchial biopsies repeatedly over time (394 +/- 170 days) with serial bronchoscopies (6 +/- 5 biopsies/subject) as the biopsied area progressed towards or regressed away from frank malignancy. mRNA-Seq (n=197 biopsies) data was aligned to hg19 using STAR, and gene/transcript levels were summarized using RNA-Seq using RSEM and Ensembl 74 annotation. Immune, stromal, and epithelial cells content were inferred using the ESTIMATE algorithm and pathway activity of in vitro derived oncogenic signatures was estimated using GSVA for each sample. Molecular subtypes were derived using non-negative matrix factorization (NMF) and consensus clustering. Linear modeling was used to associate PML outcome metrics and pathway activity scores with subtype membership. Results: We identified six distinct molecular subtypes of bronchial biopsies using NMF across the 10% most variable genes (n=2,322 gene). One subtype contained samples with stable high-grade histology (p<0.01). This subtype was also enriched for basal epithelial cell content and oncogenic pathway activity including AKT and EGFR (p<0.01). Another subtype was enriched for immune cell content and had elevated expression of immune-related pathways including chemokine, cytokine, and T-cell receptor signaling. Increased immune infiltrate was also observed in H&E stains from biopsies taken adjacent to the sequenced biopsy. Conclusions: Molecular classification of premalignant lesions may lead to biomarkers of disease progression that could be used to stratify patients into prevention trials and to monitor efficacy of the treatment. Additionally, the results suggest that personalized interventions targeting specific cancer-related pathways or the immune system may be have potential therapeutic benefits. Citation Format: Jennifer E. Beane, Sarah Mazzilli, Joshua Campbell, Christopher Moy, Michael Schaffer, Catalina Perdomo, David Jenkins, Gang Liu, Sherry Zhang, Hanqiao Liu, Jessica Vick, Evan Johnson, Suso Platero, Marc Lenburg, Mary Reid, Samjot S. Dhillon, Avrum Spira. Premalignant squamous cell lung carcinoma lesions have distinct molecular subtypes associated with histologic progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5002. doi:10.1158/1538-7445.AM2017-5002

Application of Euclidean distance mapping for assessment of basement membrane thickness distribution in asthma.

Abnormal thickening of the airway basement membrane is one of the hallmarks of airway remodeling in asthma. The present protocols for measuring the basement membrane involve the use of stained tissue sections and measurements of the basement membrane thickness at certain intervals, followed by the calculation of the geometric mean thickness for each airway. This report describes an automated, unbiased approach which uses color segmentation to identify structures of interest on stained sections and Euclidean distance mapping to measure the thickness distribution of airway structures. This method was applied to study the thickness distribution of the basement membrane and airway epithelium in lungs donated for research from seven nonasthmatic and eight asthmatic age- and sex-matched donors. A total of 60 airways were assessed. We report that the thickness and thickness distribution of the basement membrane and airway epithelium are increased in large and small airways of asthmatics compared with nonasthmatics. Using this method we were able to demonstrate the heterogeneity in the thickness of the basement membrane and airway epithelium within individual airways of asthmatic subjects. This new computational method enables comprehensive and objective quantification of airway structures, which can be used to quantify heterogeneity of airway remodeling in obstructive lung diseases such as asthma and chronic obstructive pulmonary disease.NEW & NOTEWORTHY The described application of Euclidean distance mapping provides an unbiased approach to study the extent and thickness distribution of changes in tissue structures. This approach will enable researchers to use computer-aided analysis of structural changes within lung tissue to understand the heterogeneity of airway remodeling in lung diseases.

The effects of over-the-counter jaw-repositioning mouthguards on aerobic performance.

Though jaw-repositioning devices have been found to increase size of upper respiratory airways in individuals, the effects of jaw-repositioning mouthguards on respiratory function during exercise have not been fully explored. The purpose of this study is to determine the effects of over-the-counter (OTC) jaw-repositioning mouthguards on respiratory function and aerobic performance in male athletes. College-aged, male athletes (N.=20) participated in this randomized, crossover, controlled study. Each subject completed one testing session per condition: a no mouthguard control (CON), a placebo mouthguard (PLA), an OTC self-adapted jaw-repositioning mouthguard (SA), and an OTC custom-fitted jaw-repositioning mouthguard (CF). Each testing session consisted of respiratory flow dynamic tests at rest. Ventilation and gas exchange were assessed during a graded maximal treadmill test. Peak blood lactate values were obtained from 0-10 min post-exercise. At rest, the CON had significantly higher peak expiratory flow rate values than the other conditions (P<0.03). Maximum voluntary ventilation values for PLA and SA were significantly lower compared to CON (P<0.02) at rest. No significant differences were observed between conditions for ventilation, oxygen consumption, or carbon dioxide production during any submaximal stage (P=0.81) nor at maximal aerobic capacity (P=0.35). Peak lactate and adjusted peak lactate values were not significantly different between conditions (P=0.30 and P=0.63, respectively). The OTC jaw-repositioning mouthguards in this study did not enhance aerobic performance. It is important to acknowledge that negative effects on aerobic performance were not observed, thus providing additional support for encouraging the use of this safety device in sports.

Secretory IgA Deficiency in Individual Small Airways Is Associated with Persistent Inflammation and Remodeling.

Maintenance of a surface immune barrier is important for homeostasis in organs with mucosal surfaces that interface with the external environment; however, the role of the mucosal immune system in chronic lung diseases is incompletely understood. We examined the relationship between secretory IgA (SIgA) on the mucosal surface of small airways and parameters of inflammation and airway wall remodeling in chronic obstructive pulmonary disease (COPD). We studied 1,104 small airways (<2 mm in diameter) from 50 former smokers with COPD and 39 control subjects. Small airways were identified on serial tissue sections and examined for epithelial morphology, SIgA, bacterial DNA, nuclear factor-κB activation, neutrophil and macrophage infiltration, and airway wall thickness. Morphometric evaluation of small airways revealed increased mean airway wall thickness and inflammatory cell counts in lungs from patients with COPD compared with control subjects, whereas SIgA level on the mucosal surface was decreased. However, when small airways were classified as SIgA intact or SIgA deficient, we found that pathologic changes were localized almost exclusively to SIgA-deficient airways, regardless of study group. SIgA-deficient airways were characterized by (1) abnormal epithelial morphology, (2) invasion of bacteria across the apical epithelial barrier, (3) nuclear factor-κB activation, (4) accumulation of macrophages and neutrophils, and (5) fibrotic remodeling of the airway wall. Our findings support the concept that localized, acquired SIgA deficiency in individual small airways of patients with COPD allows colonizing bacteria to cross the epithelial barrier and drive persistent inflammation and airway wall remodeling, even after smoking cessation.

Increased Autophagy-Related 5 Gene Expression Is Associated with Collagen Expression in the Airways of Refractory Asthmatics.

Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis. Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic airways. This study aimed to determine if (1) collagen deposition in asthmatic airways is associated with ATG5 expression and (2) ATG5 protein expression is associated with asthma per se and severity. Gene expression of transforming growth factor beta 1, various asthma-related collagen types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III, alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and ATG5 were measured using mRNA isolated from bronchial biopsies of refractory asthmatic subjects and assessed for pairwise associations. Protein expression of ATG5 in the airways was measured and associations were assessed for asthma per se, severity, and lung function. In refractory asthmatic individuals, gene expression of ATG5 was positively associated with COL5A1 in the airways. No association was detected between ATG5 protein expression and asthma per se, severity, and lung function. Positive correlation between the gene expression patterns of ATG5 and COL5A1 suggests that dysregulated autophagy may contribute to subepithelial fibrosis in the airways of refractory asthmatic individuals. This finding highlights the therapeutic potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat refractory asthmatic individuals.

Cystic Fibrosis Mice Develop Spontaneous Chronic Bordetella Airway Infections.

Chronic pulmonary disease and infection is the primary cause of morbidity and mortality in people with cystic fibrosis (CF). Though Pseudomonas aeruginosa, is most commonly found in the airways of individuals with CF, there is increasing appreciation for the diversity of the CF microbiome, including other taxa such as Bordetella. Here we describe the identification and impact of Bordetella pseudohinzii infection in CF mice, which previously have not been thought to develop spontaneous airway infections. We determined that CF mice are more susceptible to the B. pseudohinzii infections, and less able to resolve the infection than non-CF mice. Moreover, in both CF and non-CF mice, B. pseudohinzii infections lead to markedly reduced respiratory rates and a CF-specific immune response. These results establish the CF mouse model as an important tool for the study of CF-relevant infection and highlight the potential contribution of Bordetella to CF clinical pathology.

Introducing the microbiome, lessons from the healthy lung and CF

The microbiome of the upper respiratory tract (URT), including the nasopharyngeal and oropharyngeal microbiota, is a dynamic community of microorganisms as diverse as the gastrointestinal microbiome. Until recently, the lower airways of healthy individuals were considered to be effectively sterile. This has been challenged by recent studies, and the best evidence suggest the lungs of healthy individuals are transiently colonized by microbes of the URT. In cystic fibrosis the chronic colonization of the lower airways by bacterial pathogens is the leading cause of morbidity and mortality. It is now well established that the lower airways in CF patients are colonized by a more complex polymicrobial community comprised primarily of bacteria found in the URT along with the traditional pathogens associated with CF airway disease. This community may include pathogens missed by conventional CF microbiology and organisms that can act synergistically with P. aeruginosa. These observations now guide disease management in some patients and are being applied to other respiratory diseases. Considering respiratory infections as polymicrobial diseases offers new avenues to for treatment and possible new directions for developing new therapies. The CF airways have been the focus of molecular microbiome studies, however, there remain many challenges that must be overcome if microbiome profiling is going to inform clinical practice.

Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood.

BackgroundInnate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.MethodsNasal airway secretions were obtained from children (≤3 yrs. old) during PCR-confirmed RV infections (n = 10) and age-matched controls (n = 10). Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC) differentiated at air-liquid interface (ALI). Bioinformatics tools were used to determine the unified (nasal and bronchial) signature airway secretory miRNAome and changes during RV infection in children.ResultsMultiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV.ConclusionsComparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway secretion of EVs containing miR-155, which is predicted in silico to regulate antiviral immunity. Further characterization of the airway secretory microRNAome during health and disease may lead to completely new strategies to treat and monitor respiratory conditions in all ages.

The Fast and Easy Way for Double-Lumen Tube Intubation: Individual Angle-Modification.

To find the faster and easier way than the existing intubating technique for double-lumen tube, we modified the angle of double-lumen tube according to an individual’s upper airway anatomy and compared the time needed and the number of attempts for successful intubation between individually angle-modified and non-modified double-lumen tubes. Adult patients undergoing elective thoracic surgery were randomly allocated in either non-angle-modified (Group N, n = 54) or angle-modified (Group M, n = 54) groups. During mask ventilation in the sniffing position, angle-modification was performed in Group M as follows: the distal tip of the tube was placed at the level of the cricoid cartilage and the shaft was bent at the intersection of the oral and pharyngeal axes estimated from the patient’s surface anatomy. The time needed and the number of attempts for successful intubation and Cormack and Lehane (C-L) grade were recorded. Overall median intubation time (sec) was significantly shorter in Group M than in Group N [10.2 vs. 15.1, P<0.001]. In addition, Group M showed the shorter median intubation time (sec) in C-L grades I-III [8.2 vs. 11.1 in C-L grade I, (P = 0.003), 10.3 vs. 15.3 in II, (P = 0.001), and 11.8 vs. 27.9 in III, (P<0.001), respectively]. Moreover, all intubation was successfully performed at the first attempt in patients with C-L grades I-III in Group M (P = 0.027). Our study showed an individual angle-modification would be useful for the fast and easy intubation of double-lumen tube in patients with C-L grades I-III.Trial Registration: ClinicalTrials.gov NCT02190032

Auto-adjusting mandibular repositioning device for in-home use.

Obstructive Sleep Apnea (OSA) is a form of respiratory dysfunction that affects 20% of adults in the world. Among the first-line treatments that are used to mitigate the effects of OSA are continuous positive airway pressure (CPAP) and mandibular repositioning devices (MRD). Although CPAP provides a more efficacious therapy than MRDs, recent studies suggest that both are comparable in overall effectiveness due to greater patient preference and adherence to MRD therapy. In this paper, we present the Auto-Positioner, a novel add-on for MRDs that adjusts the extent to which the mandible (lower jaw) is advanced in response to respiratory signals indicating labored breathing during sleep, and to changes in sleeping position known to affect individual patient's airway patency.

Systems physiology of the airways in health and obstructive pulmonary disease.

Fresh air entering the mouth and nose is brought to the blood-gas barrier in the lungs by a repetitively branching network of airways. Provided the individual airway branches remain patent, this airway tree achieves an enormous amplification in cross-sectional area from the trachea to the terminal bronchioles. Obstructive lung diseases such as asthma occur when airway patency becomes compromised. Understanding the pathophysiology of these obstructive diseases thus begins with a consideration of the factors that determine the caliber of an individual airway, which include the force balance between the inward elastic recoil of the airway wall, the outward tethering forces of its parenchymal attachments, and any additional forces due to contraction of airway smooth muscle. Other factors may also contribute significantly to airway narrowing, such as thickening of the airway wall and accumulation of secretions in the lumen. Airway obstruction becomes particularly severe when these various factors occur in concert. However, the effect of airway abnormalities on lung function cannot be fully understood only in terms of what happens to a single airway because narrowing throughout the airway tree is invariably heterogeneous and interdependent. Obstructive lung pathologies thus manifest as emergent phenomena arising from the way in which the airway tree behaves a system. These emergent phenomena are studied with clinical measurements of lung function made by spirometry and by mechanical impedance measured with the forced oscillation technique. Anatomically based computational models are linking these measurements to underlying anatomic structure in systems physiology terms. WIREs Syst Biol Med 2016, 8:423-437. doi: 10.1002/wsbm.1347 For further resources related to this article, please visit the WIREs website.

Morphology of the Aging Lung on Computed Tomography.

As the population becomes older, recognition of the pulmonary computed tomography (CT) features of "normal" aging is likely to become increasingly important to differentiate from clinically significant disease. Several studies have evaluated the appearances of the lung parenchyma and large and small airways in asymptomatic older individuals and found increased prevalence of cysts, reticular pattern, air trapping, bronchial dilation, and bronchial wall thickening in older individuals compared with younger individuals. Objective differences in CT lung parenchymal attenuation and complexity have also been described. The CT appearances of the aging lung are illustrated, and the histopathologic and functional changes are discussed.

Effects of using the simplified airway risk index vs usual airway assessment on unanticipated difficult tracheal intubation - a cluster randomized trial with 64,273 participants

BackgroundUnanticipated difficult intubation remains a challenge in anaesthesia. The Simplified Airway Risk Index (SARI) is a multivariable risk model consisting of seven independent risk factors for difficult intubation. Our aim was to compare preoperative airway assessment based on the SARI with usual airway assessment. MethodsFrom 01.10.2012 to 31.12.2013, 28 departments were cluster-randomized to apply the SARI model or usual airway assessment. The SARI group implemented the SARI model. The Non-SARI group continued usual airway assessment, thus reflecting a group of anaesthetists’ heterogeneous individual airway assessments. Preoperative prediction of difficult intubation and actual intubation difficulties were registered in the Danish Anaesthesia Database for both groups. Patients who were preoperatively scheduled for intubation by advanced techniques (e.g. video laryngoscopy; flexible optic scope) were excluded from the primary analysis. Primary outcomes were the proportions of unanticipated difficult and unanticipated easy intubation. ResultsA total of 26 departments (15 SARI and 11 Non-SARI) and 64 273 participants were included. In the primary analyses 29 209 SARI and 30 305 Non-SARI participants were included.In SARI departments 2.4% (696) of the participants had an unanticipated difficult intubation vs 2.4% (723) in Non-SARI departments. Odds ratio (OR) adjusted for design variables was 1.03 (95% CI: 0.77–1.38). The proportion of unanticipated easy intubation was 1.42% (415) in SARI departments vs 1.00% (302) in Non-SARI departments. Adjusted OR was 1.26 (0.68–2.34). ConclusionsUsing the SARI compared with usual airway assessment we detected no statistical significant changes in unanticipated difficult- or easy intubations. Clinical trial registration. NCT01718561.

Sputum Gene Expression of IL-13 Receptor α2 Chain Correlates with Airflow Obstruction and Helper T-Cell Type 2 Inflammation in Asthma.

BRP-39/YKL-40 is a chitinase-like protein that plays a critical role in IL-13-induced inflammation. It correlates positively with asthma severity and airway remodeling ( 1 ) via binding to IL-13 receptor α2 chain (IL-13Rα2). Because the relationship of IL-13Rα2 to human asthma has never been evaluated previously, we sought to determine the relationship between IL-13Rα2, YKL-40, and asthma. We evaluated 112 patients (69% women) with a mean age of 46.7 years. Subjects completed an asthma phenotyping protocol that included analysis of sputum gene expression by Affymetrix 1.0 ST gene array (Affymetrix, Santa Clara, CA) and YKL-40 protein levels. IL-13Rα2 gene expression was readily detectable in the sputum and correlated negatively with prebronchodilator (BD) FEV1 (rs = -0.282, P < 0.01), post-BD FEV1 (rs = -0.268, P < 0.01), pre-BD FEV1/FVC ratio (rs = -0.228, P < 0.05), and post-BD FEV1/FVC ratio (rs = -0.242, P < 0.01). IL-13Rα2 gene expression correlated positively with gene expression of IL-13 (rs = 0.484, P < 0.001), IL-5 (rs = 0.237, P < 0.05), and IL-8 (rs = 0.218, P < 0.05). Regression analysis showed that the post-BD FEV1/FVC ratio is significantly associated with IL-13Rα2 expression and CHI3L1 expression in sputum after controlling for IL-4, IL-5, IL-13, and transforming growth factor-β1 gene expression (all P < 0.01). Sputum YKL-40 gene expression positively correlated with IL-8 expression (rs = 0.357, P < 0.001) and negatively correlated with pre- and post-BD FEV1/FVC ratios (rs = -0.299, P < 0.001 and rs = -0.305, P < 0.01, respectively). Sputum and serum YKL-40 protein levels were not associated with IL-13Rα2 expression. This analysis demonstrates that IL-13Rα2 is associated with reduced lung function, helper T-cell type 2 gene expression, and airflow obstruction in the airway of individuals with asthma, which might in turn be driven by airway remodeling. Future studies will be required to define the proinflammatory and remodeling effects of this receptor that up to now has been considered solely a modulator of IL-13-induced inflammation.

Ozone-Induced Type 2 Immunity in Nasal Airways. Development and Lymphoid Cell Dependence in Mice.

Inhalation exposures to ozone commonly encountered in photochemical smog cause airway injury and inflammation. Elevated ambient ozone concentrations have been epidemiologically associated with nasal airway activation of neutrophils and eosinophils. In the present study, we elucidated the temporal onset and lymphoid cell dependency of eosinophilic rhinitis and associated epithelial changes in mice repeatedly exposed to ozone. Lymphoid cell-sufficient C57BL/6 mice were exposed to 0 or 0.5 parts per million (ppm) ozone for 1, 2, 4, or 9 consecutive weekdays (4 h/d). Lymphoid cell-deficient, Rag2(-/-)Il2rg(-/-) mice were similarly exposed for 9 weekdays. Nasal tissues were taken at 2 or 24 hours after exposure for morphometric and gene expression analyses. C57BL/6 mice exposed to ozone for 1 day had acute neutrophilic rhinitis, with airway epithelial necrosis and overexpression of mucosal Ccl2 (MCP-1), Ccl11 (eotaxin), Cxcl1 (KC), Cxcl2 (MIP-2), Hmox1, Il1b, Il5, Il6, Il13, and Tnf mRNA. In contrast, 9-day ozone exposure elicited type 2 immune responses in C57BL/6 mice, with mucosal mRNA overexpression of Arg1, Ccl8 (MCP-2), Ccl11, Chil4 (Ym2), Clca1 (Gob5), Il5, Il10, and Il13; increased density of mucosal eosinophils; and nasal epithelial remodeling (e.g., hyperplasia/hypertrophy, mucous cell metaplasia, hyalinosis, and increased YM1/YM2 proteins). Rag2(-/-)Il2rg(-/-) mice exposed to ozone for 9 days, however, had no nasal pathology or overexpression of transcripts related to type 2 immunity. These results provide a plausible paradigm for the activation of eosinophilic inflammation and type 2 immunity found in the nasal airways of nonatopic individuals subjected to episodic exposures to high ambient ozone.

The Oropharyngeal Airway in Young Adults with Skeletal Class II and Class III Deformities: A 3-D Morphometric Analysis

Objectives1) To determine the accuracy and reliability of an automated anthropometric measurement software for the oropharyngeal airway and 2) To compare the anthropometric dimensions of the oropharyngeal airway in skeletal class II and III deformity patients.MethodsCone-beam CT (CBCT) scans of 62 patients with skeletal class II or III deformities were used for this study. Volumetric, linear and surface area measurements retroglossal (RG) and retropalatal (RP) compartments of the oropharyngeal airway was measured with the 3dMDVultus software. Accuracy of automated anthropometric pharyngeal airway measurements was assessed using an airway phantom.ResultsThe software was found to be reasonably accurate for measuring dimensions of air passages. The total oropharyngeal volume was significantly greater in the skeletal class III deformity group (16.7 ± 9.04 mm3) compared with class II subjects (11.87 ± 4.01 mm3). The average surface area of both the RG and RP compartments were significantly larger in the class III deformity group. The most constricted area in the RG and RP airway was significantly larger in individuals with skeletal class III deformity. The anterior-posterior (AP) length of this constriction was significantly greater in skeletal class III individuals in both compartments, whereas the width of the constriction was not significantly different between the two groups in both compartments. The RP compartment was larger but less uniform than the RG compartment in both skeletal deformities.ConclusionSignificant differences were observed in morphological characteristics of the oropharyngeal airway in individuals with skeletal class II and III deformities. This information may be valuable for surgeons in orthognathic treatment planning, especially for mandibular setback surgery that might compromise the oropharyngeal patency.