Large Airways Research Articles

Comparative spatial transcriptomic profiling of severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants infections in the lungs of cynomolgus macaques.

Recently emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants are generally less pathogenic than previous strains. However, elucidating the molecular basis for pulmonary immune response alterations is challenging owing to the virus's heterogeneous distribution within complex tissue structure. Here, we revealed the spatial transcriptomic profiles of pulmonary microstructures at the SARS-CoV-2 infection site in the nine cynomolgus macaques upon inoculation with the Delta and Omicron variants. Delta- and Omicron-infected lungs had upregulation of genes involved in inflammation, cytokine response, complement, cell damage, proliferation, and differentiation pathways. Depending on the tissue microstructures (alveoli, bronchioles, and blood vessels), there were differences in the types of significantly upregulated genes in each pathway. Notably, a limited number of genes involved in cytokine and cell damage response were differentially expressed between bronchioles of the Delta- and Omicron-infection groups. These results indicated that despite a significant antigenic shift in SARS-CoV-2, the host immune response mechanisms induced by the variants were relatively consistent, with limited transcriptional alterations observed only in large airways. This study may aid in understanding the pathogenesis of SARS-CoV-2 and developing a clinical strategy for addressing immune dysregulation by identifying potential transcriptional biomarkers within pulmonary microstructures during infection with emerging variants.

P423 A low-cost positive expiratory pressure device for people with cystic fibrosis in developing countries

Positive expiratory pressure (PEP) is a commonly used airway clearance technique, involving breathing against an expiratory pressure of 10 to 20 cmH2O. PEP temporarily increases functional residual capacity and allows an increased volume of air to accumulate behind airway obstructions, promoting the movement of secretions towards the large airways. The cost of PEP devices can prohibit their widespread use in developing countries, therefore a simple, low-cost PEP was designed and manufactured for this purpose, and pressure and flow were tested.

P226 Interpretation of spirometry parameters in adult patients with cystic fibrosis in North Macedonia

Assessment of lung function, the flow in large, medium and small airways through the analysis of functional diagnostics-spirometry and its parameters.

P188 Heterogeneity of large and small airway remodeling in human endstage explant cystic fibrosis lungs

The aim was to study heterogeneity in visible airway remodeling, ranging from little (bronchiolitic) to extensive bronchiectasis (bronchiectatic) and to investigate if this remodeling is associated with a different type of small airway disease.

Risky confirmation of a diagnosis: case series of three female patients with mediastinal mass syndrome

Mediastinal mass syndrome (MMS) is alife-threatening complication of anesthesia for which prevention and treatment are a complication-prone interdisciplinary task. Clinical symptoms vary from asymptomatic patients up to life-threatening cardiorespiratory impairments, depending on the extent and size of amediastinal tumor as well as the involvement of corresponding anatomical structures. Especially in the context of sedation or general anesthesia, there is aconsiderable risk of acute cardiopulmonary or respiratory decompensation related to tumor-induced compression of central blood vessels or even the large airways, which may result in severe complications, including death. In this case series three female patients are presented, who were each referred to this hospital with amediastinal tumor for interventional or surgical confirmation of the diagnosis. Based on the case histories, characteristic complications are demonstrated and strategies to avoid possible adverse events of MMS are discussed. The specific anesthesiological requirements for MMS, the safety aspects of the choice of surgical and anesthesia procedures, circulatory and airway management for the required single-lung ventilation, and various aspects of the selection of the anesthetic agents are discussed in this case series.

Environmental and health impacts of household energy conversion on PAHs and their derivatives in PM2.5 in typical areas of northern China

Heavy use of solid fuels in rural households of northern China emits huge amounts of fine particulate matter (i.e., PM2.5) that pose notable indoor air pollution and severe inhalation health risks. In this study, the environmental and health benefits of clean energy substitution were accessed by monitoring indoor and personal exposure to polycyclic aromatic hydrocarbons (PAHs) and their derivatives, and pulmonary function and biological parameters. After substitutions of traditional lump coal and biomass fuels by clean coal, indoor concentrations of parent PAHs (p-PAHs), alkylated PAHs (a-PAHs), oxygenated PAHs (o-PAHs), and nitro PAHs (n-PAHs) reduced by 71 %, 32 %, 70 %, and 76 %, while personal exposure concentrations decreased by 82 %, 87 %, 93 %, and 86 %, respectively. However, the proportion of low molecular weight PAHs increases, especially for 2-ring a-PAHs and 3-ring n-PAHs. Domestic solid fuel burning induces greater damage to the small airway than the large airway. Pulmonary function parameter reductions in the clean coal group are much less than those in the other two fuel groups. Salivary interleukin-6 (IL-6) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) significantly correlated with PAH species, among which p-PAHs and PAHs derivatives strongly with IL-6 and 8-OHdG, respectively. The correlation between PAHs and biomarkers in urine is insignificant. In addition, the use of clean coal can reduce the cancer risk for the four classes of PAHs by 60 %–97 %, mainly owing to the lower contributions from p-PAHs and o-PAHs. The result of the study provides scientific support for clean energy retrofit and an understanding of health benefits from solid fuel substitutions.

Associations between short-term exposure to ambient air pollution and lung function in adults.

Evidence of the acute effects of high-level air pollution on small airway function and systemic inflammation in adults is scarce. To examined the associations of short-term (i.e., daily) exposure to multiple air pollutants with lung function and inflammatory markers. We assessed short-term (daily) effects of air pollutants, including particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5) and 10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO), on lung function and peripheral immune cell counts over various lag times using generalized linear regression models. A total of 4764 adults were included from the general community-dwelling population in Shanghai, China. Exposure to air pollutants and lung function were negatively correlated. Decline in FEF between 25% and 75% of vital capacity (FEF25-75%) were found associated with PM2.5, SO2, and CO, and decline in forced expiratory volume in 3 s (FEV3) to forced vital capacity (FVC) ratio were associated with all examined pollutants, indicating obstruction in small airways. Obstructed airflow in large and middle airways as indicated by decline in FEV1/FVC were also associated with all pollutants. In subgroup analysis, significant negative associations between the five pollutants and SAD parameters were found only in males but not in females. The difference in the associations of SO2 with FEF75% between males and females achieved statistical significance. Additionally, all examined pollutants were significantly associated with lower peripheral neutrophil count. Acute exposure to air pollutants were associated with airflow-limitation. Both small airways and proximal airways were affected. Acute exposure to air pollutants were accompanied with a lower neutrophil count.

A case of large airway and orbital hemangiomas with facial capillary malformation.

Infantile hemangiomas (IHs) are the most common pediatric vascular tumors, although their genetic etiology is largely unknown. Congenital capillary malformations (CMs) are associated with known somatic pathogenic variants, including GNAQ, GNA11, PIK3CA, and PIK3R1. Co-occurrence of a facial CM such as port wine stain and IH is not associated with any recognized vascular anomaly syndromes and rarely reported in the literature. We describe a case of a 5-week-old female patient with a large facial CM and extensive IHs of the lower lip, airway, and orbit who presented with airway compromise and responded to propranolol therapy.

Low-dose blood BTEX are associated with pulmonary function through changes in inflammatory markers among US adults: NHANES 2007–2012

The effects of blood benzene, toluene, ethylbenzene, and xylenes (BTEX) on lung function among general adults remain unknown. We enrolled 5519 adults with measured blood BTEX concentrations and lung function from the US National Health and Nutrition Examination Survey 2007-2012. Weighted linear models were fitted to assess the associations of BTEX with lung function and inflammation parameters (white blood cell five-part differential count and C-reactive protein). The mediating effect of inflammation between BTEX and lung function was also examined. Blood BTEX concentrations decreased yearly from 1999 and were extremely low from 2007 to 2012. Benzene and toluene exerted the greatest influence on lung function in terms of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), calculated FEV1:FVC ratio, peak expiratory flow rate (PEFR), and forced mid expiratory flow (FEF25-75%). Both ethylbenzene and all xylene isomers had no effects on FVC but reduced FEV1, FEV1:FVC ratio, PEFR, and FEF25-75%. Weighted quantile analyses demonstrated that BTEX mixture was associated with decreases in FVC, FEV1, FEV1:FVC ratio, PEFR, and FEF25-75%, with benzene weighted most heavily for all lung function parameters. BTEX also increased the levels of inflammation indicated by white blood cell five-part differential count and C-reactive protein, and increased levels of inflammation also reduced lung function. From multiple mediation analysis, inflammation mediated the effects of benzene on FEV1 and PEFR, the effects of toluene on FEV1, and the effects of ethylbenzene on FEV1 and PEFR. Low-dose exposure to BTEX was associated with reduced pulmonary function both in large and small airways. Inflammation could be involved in this pathogenesis.

Bidirectional Association Discovery Leads to Precise Identification of Lung Cancer Biomarkers and Genome Taxa Class.

Identifying proximity between pairs of expression vectors is one of the fundamental requirements in machine learning and data mining algorithms. We propose a new metric, Bidirectional Association Similarity (BiAS), to measure the degree of mutual association between a pair of features and present a generalized formulation to compute BiAS between two vectors. Using non-linear programming optimization, we establish soundness of BiAS against the Jaccard and cosine similarities and prove that mutually associative features must be similar. The reverse, however, is not true. Finally, we show that BiAS is a transitive relation and can suitably be incorporated with any clustering algorithm, just like other metrics, to identify groups of mutually associative features in an ensemble. Experiments on clustering and classification of genome sequences for taxa identification and finding biomarkers in large airway epithelial cells expressions from smokers diagnosed with lung cancer reveal that knowledge precision is further improved with BiAS compared to seven other well-established metrics including the Pearson correlation coefficient, cosine similarity and the Jaccard similarity. Remarkably, the 10 out of the top 11 lung-cancer biomarkers found in the study using BiAS has been corroborated through previously reported clinically-backed studies. Thus, bidirectional association mining turns out effective for bio-knowledge discovery.

Clinical Utility of Peak Flow Meter in Asthma Diagnosis and Monitoring in Low- and Middle-Income Countries

Low- and middle-income countries (LMICs) suffer a disproportionate burden of asthma-related deaths. This may be attributed to the underdiagnosis and undertreatment. It remains unclear the extent to which the access to utility of peak flow meters (PFMs) affect the mortality rates recorded across LMICs. The purpose of this narrative review was to offer a comprehensive overview of PFMs’ clinical value for diagnosing and monitoring asthma in low- and middle-income nations. Using the standards for conducting a narrative review, this paper carried out a literature search on three major databases: Google Scholar, ResearchGate, and PubMed. Search terms were created from the variables present in the topic and strung together to find relevant literature. Exclusion criteria were used to ensure that the chosen articles were relevant after a trickle of articles was collected from various databases on the internet. There is limited knowledge about the clinical utility of PFM in LMICs despite the evidence that it can be used to demonstrate large airway obstruction. There is also limited access to the device in most health facilities and patients for self-monitoring. There is a need for more awareness on the usefulness of peak flow among doctors on the utility of the device for asthma diagnosis and monitoring. There is also a need for more research to assess the impact of the poor use of the device on asthma diagnosis, management, and overall outcome.

Magnetic Resonance Imaging of Pediatric Lungs and Airways: New Paradigm for Practical Daily Clinical Use.

Disorders of the lungs and airways are among the most common indications for diagnostic imaging in infants and children. Traditionally, chest radiograph has been the first-line imaging test for detecting these disorders and when cross-sectional imaging is necessary, computed tomography (CT) has typically been the next step. However, due to concerns about the potentially harmful effects of ionizing radiation, pediatric imaging in general has begun to shift away from CT toward magnetic resonance imaging (MRI) as a preferred modality. Several unique technical challenges of chest MRI, including motion artifact from respiratory and cardiac motion as well as low signal-to-noise ratios secondary to relatively low proton density in the lung have slowed this shift in thoracic imaging. However, technical advances in MRI in recent years, including developments in non-Cartesian MRI data sampling methods such as radial, spiral, and PROPELLER imaging and the development of ultrashort TE and zero TE sequences that render CT-like high-quality imaging with minimal motion artifact have allowed for a shift to MRI for evaluation of lung and large airways in centers with specialized expertise. This article presents a practical approach for radiologists in current practice to begin to consider MRI for evaluation of the pediatric lung and large airways and begin to implement it in their practices. The current role for MRI in the evaluation of disorders of the pediatric lung and large airways is reviewed, and example cases are presented. Challenges for MRI of the lung and large airways in children are discussed, practical tips for patient preparation including sedation are described, and imaging techniques suitable for current clinical practice are presented.

The effect of fine-particle size and extrafine particle size inhaled corticosteroid in reducing airway resistance in asthmatic patients

Background Bronchial asthma is characterised by chronic inflammation of both large and small airways. Extra-fine formulation of inhaled corticosteroid (ICS) can achieve a higher peripheral lung deposition leading to improved asthma control. We investigated the effect of extra-fine and fine particle size inhaled ICS with airway resistance and severity of symptoms in asthmatic patients. Methods Prospective interventional study of outpatient asthmatics in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Subjects were grouped based on pre-existing inhalers; extra-fine and fine inhaled corticosteroid (ICS)/long acting beta agonist (LABA). Crossover was at week 7 and treatment regime continued for 7 weeks. Subjects were assessed at week 0, 6 and 13 using asthma control test (ACT) score, forced expiratory volume in 1 s (FEV1) and impulse oscillometry (IOS) Inhaler technique was assessed periodically. Results Thirty-four subjects were recruited. Median asthma duration was 20 years. Twenty subjects (58%) in fine ICS/LABA and 14 (42%) in extra-fine ICS/LABA group. Thirty-one subjects were analysed before crossver. There was a significant improvement of FEV1 in the extra-fine ICS/LABA group (1.7 ± 0.47 to 1.88 ± 0.5; p = 0.01). ACT score reduced significantly in extra-fine ICS/LABA group (23 ± 5 to 21 ± 4; p = 0.04) at week 0–6. Week 7–13 showed a significant improvement of ACT score (16.5 ± 3 to 20 ± 3; p = 0.01) and FEV1 (1.71 ± 0.96 to 1.81 ± 1.02: p = 0.01) in extra-fine ICS/LABA. There was no significant difference in (IOS) parameters between the groups. Conclusion There was an improvement of FEV1 and ACT score with extra-fine ICS/LABA with no benefit in airway resistance.

Upper airway dimensions and the skeletal parameters in orthodontic patients who developed moderate-severe COVID-19 symptoms during the pandemic.

Large airway dimensions are associated with a rapid decline in the lung function and a higher risk of hospitalization. Therefore, the airway dimensions of healthy subjects who tested positive for coronavirus disease 2019 (COVID-19) may be associated with the severity of COVID-19 symptoms. The objectives of this study were to measure the upper airway dimensions and the craniofacial skeletal parameters in patients who tested positive for COVID-19, to compare the upper airway dimensions and the craniofacial skeletal parameters between patients who developed no/mild symptoms and those with moderate-severe COVID-19 symptoms, and to assess any association of the skeletal relationships (anteroposterior (AP) and vertical) and the upper airway dimensions with the severity of COVID-19 symptoms in adult subjects. A total of 204 orthodontic patients who tested positive for COVID-19 were evaluated. Of these, only 137 met the inclusion criteria. The sample was further subdivided into 2 groups based on the severity of symptoms: cases (moderate-severe symptoms; n = 56); and controls (asymptomatic/ mild symptoms; n = 81). The upper airway dimensions and the skeletal parameters were measured on lateral cephalograms. The nonparametric Mann-Whitney U test was used to detect differences between the cases and the controls. Binary logistic regression analysis was used to evaluate the association between the studied variables and the severity of symptoms. The cases had a reduced lower face height (LFH) and a reduced perpendicular distance from the hyoid bone to the line connecting the anteroinferior limit of the 3rd cervical vertebra (C3) and the retrognathion point (RGN) (HH1) as compared to the controls. Regression analysis revealed a significant association of LFH (p = 0.013), the vertical airway length (VAL) (p = 0.002) and HH1 (p = 0.021) with the severity of COVID-19 symptoms. The types of malocclusion were similar in the cases and the controls. Patients with reduced LFH and VAL, and a superiorly positioned hyoid bone in relation to the mandible developed more severe COVID-19 symptoms.

MR imaging of the airways.

The need for airway imaging is defined by the limited sensitivity of common clinical tests like spirometry, lung diffusion (DLCO) and blood gas analysis to early changes of peripheral airways and to inhomogeneous regional distribution of lung function deficits. Therefore, X-ray and computed tomography (CT) are frequently used to complement the standard tests.As an alternative, magnetic resonance imaging (MRI) offers radiation-free lung imaging, but at lower spatial resolution. Non-contrast enhanced MRI shows healthy airways down to the first subsegmental level/4th order (CT: eighth). Bronchiectasis can be identified by wall thickening and fluid accumulation. Smaller airways become visible, when altered by peribronchiolar inflammation or mucus retention (tree-in-bud sign).The strength of MRI is functional imaging. Dynamic, time-resolved MRI directly visualizes expiratory airway collapse down to the lobar level (CT: segmental level). Obstruction of even smaller airways becomes visible as air trapping on the expiratory scans. MRI with hyperpolarized noble gases (3He, 129Xe) directly shows the large airways and peripheral lung ventilation. Dynamic contrast-enhanced MRI (DCE MRI) indirectly shows airway dysfunction as perfusion deficits resulting from hypoxic vasoconstriction of the dependent lung volumes. Further promising scientific approaches such as non-contrast enhanced, ventilation-/perfusion-weighted MRI from periodic signal changes of respiration and blood flow are in development.In summary, MRI of the lungs and airways excels with its unique combination of morphologic and functional imaging capacities for research (e.g., in chronic obstructive lung disease or asthma) as well as for clinical imaging (e.g., in cystic fibrosis).

Morphologic Features in Congenital Pulmonary Airway Malformations and Pulmonary Sequestrations Correlate With Mutation Status: A Mechanistic Approach to Classification.

Congenital pulmonary airway malformations (CPAMs) have a range of morphologies with varying cyst sizes and histologic features (types 1 to 3). Evidence suggested they arise secondary to bronchial atresia, however, we recently showed that cases with type 1 and 3 morphology are driven by mosaic KRAS mutations. We hypothesized that 2 distinct mechanisms account for most CPAMs: one subset is secondary to KRAS mosaicism and another is due to bronchial atresia. Cases with type 2 histology, similar to sequestrations, would be related to obstruction and therefore negative for KRAS mutations regardless of cyst size. We sequenced KRAS exon 2 in type 2 CPAMs, cystic intralobar and extralobar sequestrations, and intrapulmonary bronchogenic cysts. All were negative. Most sequestrations had a large airway in the subpleural parenchyma adjacent to the systemic vessel, anatomically confirming bronchial obstruction. We compared morphology to type 1 and 3 CPAMs. On average, type 1 CPAMs had significantly larger cysts, but there remained substantial size overlap between KRAS mutant and wild-type lesions. Features of mucostasis were frequent in sequestrations and type 2 CPAMs, while their cysts were generally simple and round with flat epithelium. Features of cyst architectural and epithelial complexity were more common in type 1 and 3 CPAMs, which rarely showed mucostasis. Similarity in histologic features among cases that are negative for KRAS mutation support the hypothesis that, like sequestrations, the malformation of type 2 CPAMs is related to obstruction during development. A mechanistic approach to classification may improve existing subjective morphologic methods.

Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function

BackgroundAlpha-1-antitrypsin deficient (AATD) individuals are prone to develop early age of onset chronic obstructive pulmonary disease (COPD) more severe than non-genetic COPD. Here, we investigated the characteristics of lower respiratory tract of AATD individuals prior to the onset of clinically significant COPD.MethodsBronchoalveolar lavage was performed on 22 AATD with normal lung function and 14 healthy individuals. Cell counts and concentrations of proteases, alpha-1-antitrypsin and proinflammatory mediators were determined in the bronchoalveolar lavage fluid from study subjects. In order to determine the airway inflammation, we also analyzed immune cell components of the large airways from bronchial biopsies using immunohistochemistry in both study subjects. Finally, we made comparisons between airway inflammation and lung function rate of decline using four repeated lung function tests over one year in AATD individuals.ResultsAATD individuals with normal lung function had 3 folds higher neutrophil counts, 2 folds increase in the proteases levels, and 2–4 folds higher levels of IL-8, IL-6, IL-1β, and leukotriene B4 in their epithelial lining fluid compared to controls. Neutrophil elastase levels showed a positive correlation with the levels of IL-8 and neutrophils in AATD epithelial lining fluid. AATD individuals also showed a negative correlation of baseline FEV1 with neutrophil count, neutrophil elastase, and cytokine levels in epithelial lining fluid (p < 0.05). In addition, we observed twofold increase in the number of lymphocytes, macrophages, neutrophils, and mast cells of AATD epithelial lining fluid as compared to controls.ConclusionMild inflammation is present in the lower respiratory tract and airways of AATD individuals despite having normal lung function. A declining trend was also noticed in the lung function of AATD individuals which was correlated with pro-inflammatory phenotype of their lower respiratory tract. This results suggest the presence of proinflammatory phenotype in AATD lungs. Therefore, early anti-inflammatory therapies may be a potential strategy to prevent progression of lung disease in AATD individuals.

No: 5006 Large tube or narrow airway? Unanticipated difficult airway in an adult

No: 5006 Large tube or narrow airway? Unanticipated difficult airway in an adult

Quantifying airway remodelling for research or clinical purposes: How should we normalize for airway size?

Quantifying airway remodelling for research or clinical purposes: How should we normalize for airway size?

Phase diagrams of PEG1000,1500,2000,4000,6000 + lithium citrate + water ATPSs, and the partitioning of salbutamol at T = 298.15 K

Salbutamol is a drug used to treat the pulmonary diseases by ameliorate the medium and large airways in the lungs. Partitioning of salbutamol drug on the aqueous two-phase systems (ATPSs) of PEG1000,1500,2000,4000,6000 + trilithium citrate + water was determined at T = 298.15 K. The effect of molecular mass of polymer (MMP) on the binodal and tie-line compositions were studied. Results showed that the biphasic area was extended as the MMP was increased. The salting-out ability were quantified using the Setschenow model, and the binodal curves were modeled by a nonlinear 3-parameter equation. Furthermore, electrolyte Wilson along with the osmotic virial models have adequately been implemented to fit the tie-line compositions. Also, the studied ATPSs were implemented to study the partitioning of salbutamol drug on the salt-affluent and polymer-affluent phases. It is observed that, ATPSs of PEG1000 is premium to extract the salbutamol to the polymer-affluent phase, where, the ATPSs of PEG6000 is more favorable to extract the drug to the salt-affluent phase.