Peripheral Airways Research Articles

Lung deposition of inhaled once-daily long-acting muscarinic antagonists via standard jet nebulizer or dry powder inhaler, measured using functional respiratory imaging, in patients with chronic obstructive pulmonary disease.

Background:Data for bronchodilator deposition via nebulizers and dry powder inhalers (DPIs) in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD) are limited. We used functional respiratory imaging (FRI) to determine deposition patterns for revefenacin solution via a PARI LC® Sprint® nebulizer and tiotropium powder via HandiHaler® DPI.Methods:Ten patients with COPD, of whom 9 had severe airflow obstruction, were selected from FLUIDDA’s database. The study did not enroll patients. Drug deposition in the extrathoracic and intrathoracic regions, including the central and peripheral airways was simulated by FRI. The percentage of delivered dose and central-to-peripheral (C/P) deposition ratio for nebulizer and DPI were evaluated.Results:Mean ± standard deviation (SD) age was 64.7 ± 7.1 years, height was 168.8 ± 8.5 cm, and percent predicted forced expiratory volume in 1 s was 40.8 ± 12.3%; 50% of patients were men. At optimal inhalation flow, intrathoracic and peripheral deposition was three-fold higher for revefenacin via nebulizer than tiotropium via HandiHaler (mean ± SD 34.6 ± 8.53% versus 10.9 ± 5.67% and 18.2 ± 4.30% versus 5.8 ± 2.73% of delivered dose, respectively). Similar results were observed for suboptimal flow (mean ± SD percentage of revefenacin versus tiotropium: intrathoracic, 32.1 ± 8.3% versus 15.1 ± 5.9%; peripheral; 16.6 ± 4.1% versus 8.4 ± 2.9%). The C/P deposition ratio for nebulizer was similar to DPI (mean ± SD 0.915 ± 0.241 versus 0.812 ± 0.249 at optimal; 0.947 ± 0.253 versus 0.784 ± 0.219 at suboptimal flow), even though the mass median aerodynamic diameter of revefenacin was higher than tiotropium. C/P deposition ratio for revefenacin decreased after bronchodilation (0.915 ± 0.241 pre-bronchodilation versus 0.799 ± 0.192 post-bronchodilation), suggesting progressively better deposition in the peripheral region, assuming bronchodilation occurred during the nebulization process.Conclusions:These results demonstrate more efficient intrathoracic and peripheral deposition for revefenacin via standard jet nebulizer than tiotropium via HandiHaler, with similar C/P deposition ratio in patients with COPD. Nebulizers are an efficient alternative to DPIs for bronchodilator administration in patients with COPD.

Population rearrangement of B-lymphocytes expressing chemokine receptors in patients with chronic obstructive pulmonary disease

To date, there are no drugs that can prevent progressive destruction of lung tissue and small airway fibrosis in patients with chronic obstructive pulmonary disease (COPD). Therefore, molecular mechanisms of this disease are being studied. The aim of this study was to determine the chemokine receptor expression pattern of B-lymphocytes from peripheral blood and airways of patients with COPD. Peripheral blood was collected from 51 smokers with COPD, 21 healthy smokers, and 20 healthy non-smokers. Seven smokers with COPD and 7 healthy smokers were recruited to undergo bronchoscopy with bronchoalveolar lavage (BAL). The expression of chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5 on the surface of blood and BAL B-lymphocytes was determined by flow cytometry. It was found that the percentage of blood B-lymphocytes expressing chemokine receptors CCR5 and CXCR3 was higher in smokers with COPD compared with healthy smokers and healthy non-smokers. The percentage of CD27⁺ B-cells expressing CCR5 and CXCR3 receptors exceeded the proportion of CD27⁻ B-lymphocytes expressing these receptors in peripheral blood of patients with COPD and healthy controls. In smoking patients with COPD, the percentage of BAL B-cells expressing receptors CCR5 and CXCR3 was also increased compared with healthy smokers. There were no differences in the percentage of B-lymphocytes expressing receptors CXCR4, CXCR5, CCR6, and CCR7 in both peripheral blood and BAL between smokers with COPD and healthy smokers. A greater percentage of CD27⁻ B-lymphocytes than CD27⁺ B-cells expressed receptors CXCR4, CXCR5, CCR6, and CCR7 in the peripheral blood of smokers with COPD and healthy controls. The results of this study indicate a modification in the chemokine receptor profile of B-lymphocytes in COPD.

Deep learning-based reconstruction of chest ultra-high-resolution computed tomography and quantitative evaluations of smaller airways.

The full-iterative model reconstruction generates ultra-high-resolution computed tomography (U-HRCT) images comprising a 1024×1024 matrix and 0.25mm thickness while suppressing image noises, allowing evaluating small airways 1-2mm in diameter. However, this technique imposes huge computational burdens and requires a long reconstruction time. This study evaluated whether a recently-established deep learning-based reconstruction, Advanced intelligent Clear-IQ Engine (AiCE), allows quantitative morphological analyses of smaller airways with equal or better quality than the full-iterative model reconstruction while shortening the reconstruction time. In phantom tubes mimicking small airways, the measurement error of 0.5-mm-thickness wall was smaller on the AiCE-based than the full-iterative model-based U-HRCT. Moreover, in five patients with chronic obstructive pulmonary disease, the AiCE-based U-HRCT decreased the reconstruction time approximately by 90% with a modest improvement in image noise, contrast, and sharpness compared to the full-iterative model-based U-HRCT. Therefore, the AiCE-based U-HRCT can be readily used clinically for morphologically evaluating peripheral small airways.

Oscillometry and Asthma Control in Patients With and Without Fixed Airflow Obstruction

Asthma is defined by the presence of reversible airflow limitation, yet persistently abnormal spirometry may develop despite appropriate asthma treatment. Fixed airflow obstruction (FAO) describes abnormal postbronchodilator spirometry that is associated with greater symptom burden and disease severity. Respiratory oscillometry measures the mechanics of the entire airway tree, including peripheral airway changes that have been shown to influence asthma symptoms. To evaluate the relationship between abnormal oscillometry following bronchodilator and symptom control in adults with asthma. A prospective cohort of patients with asthma attending an airways clinic completed oscillometry (resistance and reactance), spirometry, and the Asthma Control Test. Postbronchodilator lung function below the lower limit of normal was considered abnormal. Spirometric FAO was defined as FEV1/forced vital capacity below the lower limit of normal. Spearman's rank coefficient and multiple linear regression were performed to assess associations of lung function parameters with Asthma Control Test. The discriminative ability of abnormal lung function to identify poor asthma control was determined using Cohen's kappa. Ninety patients with asthma were included; 48% had spirometric FAO. Only reactance parameters, not spirometry, significantly related to (rs ≥ 0.315; P < .05) and identified asthma control (r2= 0.236; P < .001). Lung function was more strongly associated with asthma control in patients with FAO compared with those without. Abnormal oscillometry identified an additional 24% of patients with poor asthma control as compared with spirometric FAO. Reactance related to asthma control, independently of spirometric FAO. Abnormal postbronchodilator reactance identified more patients with poor asthma control compared with spirometry. These findings confirm that oscillometry is a relevant lung function test in the clinical assessment of asthma.

The functions of CD4 T-helper lymphocytes in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) has been increasingly accounted for global morbidity and mortality worldwide. Although it is partially reversible, the obstructive ventilatory schema of COPD often causes chronic inflammation that primarily affects peripheral airways, pulmonary parenchyma, and the development of lung lymphoid follicles. Among various T-helper (Th) cell types associated with COPD, Th1, Th2 and Th17 cell numbers are increased in COPD patients, whereas Treg cell number is reduced. Here, we reviewed recent advance in understanding the roles of Th1/Th2 and Th17/Treg in the pathogenesis of COPD and discussed the potential underlying mechanism.

Frequency of peripheral blood eosinophilia and obstructive airway disease in sarcoidosis

There is limited information about peripheral blood eosinophilia (PBE) and airway obstruction in sarcoidosis. Since pulmonary sarcoidosis affects the airways, it is often confused with asthma. The aims of the study are to investigate airway obstruction and PBE in sarcoidosis patients and to examine the similarity of clinical presentation with asthma. The patients matching the ATS/ERS/WASOG diagnosis criteria and were between 18 and 80 years of age were included consecutively between 2018 and 2020. Other diseases causing granulomas were excluded. A total of 84 patients were included of which 26 (31%) had a PBE level of ≥300 μL with no significant difference seen between sarcoidosis stage and PBE (p > 0.05). A significant (p < 0.05) decrease was only seen in FEV1 as the stage of sarcoidosis progressed. Respectively 31 (36.9%), 12 (14.3%) and 4 (4.8%) patients had an obstructive, restrictive and mixed respiratory function disorder. Twenty-four (28.6%) subjects with sarcoidosis had history of asthma. Spring fever, eczema, and skin/nose allergy were noticed in 17 (20.2%) of the patients. Mild PBE may be seen in sarcoidosis. Patients applying with PBE, airway obstruction, bronchial hyperreactivity along with spring fever, eczema, skin/nose allergy, wheezing, chest tightness, shortness of breath and cough may be also evaluated in terms of sarcoidosis.

Standard spirometry to assess emphysema in patients with chronic obstructive pulmonary disease: the Emphysema Severity Index (ESI).

BackgroundChronic obstructive pulmonary disease (COPD) is a generic term identifying a condition characterized by variable changes in peripheral airways and lung parenchyma. Standard spirometry cannot discriminate the relative role of conductive airways inflammatory changes from destructive parenchymal emphysema changes. The aim of this study was to quantify the emphysema component in COPD by a simple parameter (the Emphysema Severity Index - ESI), previously proved to reflect CT-assessed emphysema.MethodsESI was obtained by fitting the descending limb of MEFV curves by a fully automated procedure providing a 0 to 10 score of emphysema severity. ESI was computed in COPD patients enrolled in the CLIMA Study.ResultsThe vast majority of ESI values ranged from 0 to 4, compatible with no-to-mild/moderate emphysema component. A limited proportion of patients showed ESI values >4, compatible with severe-to-very severe emphysema. ESI values were greatly dispersed within each GOLD class indicating that GOLD classification cannot discriminate emphysema and conductive airways changes in patients with similar airflow limitation. ESI and diffusing capacity (DLCO) were significantly correlated (p<0.001). However, the great dispersion in their correlation suggests that ESI and DLCO reflect partially different anatomo-functional determinants in COPD.ConclusionsAirflow limitation has heterogenous determinants in COPD. Inflammatory and destructive changes may combine in CT densitometric alterations that cannot be detected by standard spirometry. ESI computation from spirometric data helps to define the prevailing pathogenetic mechanism underlying the measured airflow limitation. ESI could be a reliable advancement to select large samples of patients in clinical or epidemiological trials, and to compare different pharmacological treatments.

Frequency of peripheral blood eosinophilia and obstructive airway disease in sarcoidosis.

There is limited information about peripheral blood eosinophilia (PBE) and airway obstruction in sarcoidosis. Since pulmonary sarcoidosis affects the airways, it is often confused with asthma. The aims of the study are to investigate airway obstruction and PBE in sarcoidosis patients and to examine the similarity of clinical presentation with asthma. The patients matching the ATS/ERS/WASOG diagnosis criteria and were between 18 and 80 years of age were included consecutively between 2018 and 2020. Other diseases causing granulomas were excluded. A total of 84 patients were included of which 26 (31%) had a PBE level of ≥300 µL with no significant difference seen between sarcoidosis stage and PBE (p > 0.05). A significant (p < 0.05) decrease was only seen in FEV1 as the stage of sarcoidosis progressed. Respectively 31 (36.9%), 12 (14.3%) and 4 (4.8%) patients had an obstructive, restrictive and mixed respiratory function disorder. Twenty-four (28.6%) subjects with sarcoidosis had history of asthma. Spring fever, eczema, and skin/nose allergy were noticed in 17 (20.2%) of the patients. Mild PBE may be seen in sarcoidosis. Patients applying with PBE, airway obstruction, bronchial hyperreactivity along with spring fever, eczema, skin/nose allergy, wheezing, chest tightness, shortness of breath and cough may be also evaluated in terms of sarcoidosis.

Clinical implications of concentration of alveolar nitric oxide in asthmatic and non-asthmatic subacute cough

Asthma is an important cause of subacute cough. The concentration of alveolar nitric oxide (CANO) is a sensitive inflammatory indicator in peripheral airways, and it has received much less attention than the fraction of exhaled nitric oxide (FeNO50). The main objective of this study was to explore the correlation between CANO and clinical parameters in asthmatic and non-asthmatic subacute cough, which might promote understanding of the clinical utility of CANO in these special patient populations. 155 patients with subacute cough were included consecutively, of which 25 were diagnosed as asthmatic. Data for demographic characteristics, FeNO50, CANO, baseline spirometry, bronchial provocation test (or bronchodilation test) and response dose ratio (RDR) were collected. Differences between the asthmatic and non-asthmatic groups were analyzed. Spearman’s correlation coefficient (ρ) was used to evaluate the correlation between FeNO50, CANO and other clinical parameters. In patients with subacute cough, baseline CANO values did not differ between asthmatic and non-asthmatic patients (4.4(1.3, 11.4) versus 4.0(2.1, 6.8) ppb, P > 0.05). Besides, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO50. For asthmatic subacute cough, CANO was inversely correlated with FEV1/FVC (ρ = −0.69, P < 0.01) and small airway parameters including MEF25 (ρ = −0.47, P < 0.05) and MMEF (ρ = −0.45, P < 0.05). For non-asthmatic subacute cough, CANO was inversely correlated with MEF25 (ρ = −0.19, P < 0.05) and RDR (ρ = −0.21, P < 0.05). In subacute cough, asthmatic and non-asthmatic patients had similar values of baseline CANO. In both asthmatic and non-asthmatic subacute cough, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO50. A low CANO value in non-asthmatic subacute cough corresponded to a higher value of RDR, which implied a stronger tendency towards airway responsiveness.

Short-Term Acute Exposure to Wildfire Smoke and Lung Function among Royal Canadian Mounted Police (RCMP) Officers.

The increasing incidence of extreme wildfire is becoming a concern for public health. Although long-term exposure to wildfire smoke is associated with respiratory illnesses, reports on the association between short-term occupational exposure to wildfire smoke and lung function remain scarce. In this cross-sectional study, we analyzed data from 218 Royal Canadian Mounted Police officers (mean age: 38 ± 9 years) deployed at the Fort McMurray wildfires in 2016. Individual exposure to air pollutants was calculated by integrating the duration of exposure with the air quality parameters obtained from the nearest air quality monitoring station during the phase of deployment. Lung function was measured using spirometry and body plethysmography. Association between exposure and lung function was examined using principal component linear regression analysis, adjusting for potential confounders. In our findings, the participants were predominantly male (71%). Mean forced expiratory volume in 1 s (FEV1), and residual volume (RV) were 76.5 ± 5.9 and 80.1 ± 19.5 (% predicted). A marginal association was observed between air pollution and higher RV [β: 1.55; 95% CI: −0.28 to 3.37 per interquartile change of air pollution index], but not with other lung function indices. The association between air pollution index and RV was significantly higher in participants who were screened within the first three months of deployment (2.80; 0.91 to 4.70) than those screened later (−0.28; −2.58 to 2.03), indicating a stronger effect of air pollution on peripheral airways. Acute short-term exposure to wildfire-associated air pollutants may impose subtle but clinically important deleterious respiratory effects, particularly in the peripheral airways.

P077 PERIPHERAL AIRWAY IMPAIRMENT AND DYSANAPSIS DEFINE RISK OF UNCONTROLLED ASTHMA IN OBESE ASTHMATIC CHILDREN

Factors that determine the relationship between obesity and poor outcomes in asthmatic children are not well understood. Dysanapsis and peripheral airway impairment (PAI) could provide an explanation in the obese asthmatic. Our goal is to determine the effect of obesity on dysanapsis and PAI and establish the effect of obesity, dysanapsis, and PAI on risk of uncontrolled asthma.

Peripheral airways involvement in children with asthma exacerbation.

ObjectiveThe literature provides some evidence of peripheral airways key role in the pathogenesis of asthma. However, the extent to which lung periphery including acinar zone contribute to asthma activity and control in pediatric population is unclear. Therefore, the aim of the study was to estimate peripheral airways involvement in children with asthma exacerbation and stable asthma simultaneously via different pulmonary function tests.MethodsChildren with asthma exacerbation (n = 20) and stable asthma (n = 22) performed spirometry, body plethysmography, exhaled nitric oxide, impulse oscillometry (IOS), and multiple‐breath washout (MBW).ResultsPeripheral airway's function indexes were increased in children with asthma, particularly in group with asthma exacerbation when compared with stable asthma group. The prevalence of abnormal results was significantly higher in asthma exacerbation. All children with asthma exacerbation had conductive ventilation inhomogeneity; 76% had acinar ventilation inhomogeneity. According to IOS measurements, resistance and reactance were within normal range, but other IOS parameters were significantly higher in children with asthma exacerbation compared with stable asthma group. The 36% of children with acute asthma had air trapping.ConclusionSignificant involvement of peripheral airways was observed in children with asthma, particularly in asthma exacerbation, which determine lung periphery as important additional target for therapy and provide new insights into pathophysiological process of pediatric asthma.

Real-Life Effectiveness of Mepolizumab on Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity in Patients with Severe Eosinophilic Asthma.

Severe eosinophilic asthma (SEA) is associated with high peripheral blood and airway eosinophilia, recurrent disease exacerbations and severe airflow limitation. Eosinophilic inflammation is also responsible for small airway disease (SAD) development. SEA patients experience poor disease control and response to standard therapy and are prime candidates for anti-IL5 biologicals, such as mepolizumab, but the effect of treatment on SAD is unclear. We investigated the effect of mepolizumab on lung function in SEA patients, focusing on SAD parameters, and searched for an association between patients’ phenotypic characteristics and changes in small airways function. In this real-life study, data from 105 patients with SEA were collected at baseline and after 6, 12 and 18 months of mepolizumab treatment. Along with expected improvements in clinical and lung function parameters brought by Mepolizumab treatment, FEF2525-75% values showed a highly significant, gradual and persistent increase (from 32.7 ± 18.2% at baseline to 48.6 ± 18.4% after 18 months) and correlated with ACT scores at 18 months (r = 0.566; p ≤ 0.0001). A patient subgroup analysis showed that changes in FEF25-75% values were higher in patients with a baseline peripheral blood eosinophil count ≥400 cells/μL and oral corticosteroid use. Mepolizumab significantly improves small airway function. This effect correlates with clinical benefits and may represent an accessible parameter through which to evaluate therapeutic response. This study provides novel insights into the phenotypic characteristics associated with the improved functional outcome provided by mepolizumab treatment.

The molecular and cellular mechanisms associated with the destruction of terminal bronchioles in COPD.

Peripheral airway obstruction is a key feature of chronic obstructive pulmonary disease (COPD), but the mechanisms of airway loss are unknown. This study aims to identify the molecular and cellular mechanisms associated with peripheral airway obstruction in COPD. Ten explanted lung specimens donated by patients with very severe COPD treated by lung transplantation and five unused donor control lungs were sampled using systematic uniform random sampling (SURS), resulting in 240 samples. These samples were further examined by micro-computed tomography (CT), quantitative histology and gene expression profiling. Micro-CT analysis showed that the loss of terminal bronchioles in COPD occurs in regions of microscopic emphysematous destruction with an average airspace size of ≥500 and <1000 µm, which we have termed a "hot spot". Based on microarray gene expression profiling, the hot spot was associated with an 11-gene signature, with upregulation of pro-inflammatory genes and downregulation of inhibitory immune checkpoint genes, indicating immune response activation. Results from both quantitative histology and the bioinformatics computational tool CIBERSORT, which predicts the percentage of immune cells in tissues from transcriptomic data, showed that the hot spot regions were associated with increased infiltration of CD4 and CD8 T-cell and B-cell lymphocytes. The reduction in terminal bronchioles observed in lungs from patients with COPD occurs in a hot spot of microscopic emphysema, where there is upregulation of IFNG signalling, co-stimulatory immune checkpoint genes and genes related to the inflammasome pathway, and increased infiltration of immune cells. These could be potential targets for therapeutic interventions in COPD.

Chorioamnionitis, Inflammation and Neonatal Apnea: Effects on Preterm Neonatal Brainstem and on Peripheral Airways: Chorioamnionitis and Neonatal Respiratory Functions.

Background: The present manuscript aims to be a narrative review evaluating the association between inflammation in chorioamnionitis and damage on respiratory centers, peripheral airways, and lungs, explaining the pathways responsible for apnea in preterm babies born by delivery after chorioamnionitis. Methods: A combination of keywords and MESH words was used, including: “inflammation”, “chorioamnionitis”, “brainstem”, “cytokines storm”, “preterm birth”, “neonatal apnea”, and “apnea physiopathology”. All identified papers were screened for title and abstracts by the two authors to verify whether they met the proper criteria to write the topic. Results: Chorioamnionitis is usually associated with Fetal Inflammatory Response Syndrome (FIRS), resulting in injury of brain and lungs. Literature data have shown that infections causing chorioamnionitis are mostly associated with inflammation and consequent hypoxia-mediated brain injury. Moreover, inflammation and infection induce apneic episodes in neonates, as well as in animal samples. Chorioamnionitis-induced inflammation favors the systemic secretion of pro-inflammatory cytokines that are involved in abnormal development of the respiratory centers in the brainstem and in alterations of peripheral airways and lungs. Conclusions: Preterm birth shows a suboptimal development of the brainstem and abnormalities and altered development of peripheral airways and lungs. These alterations are responsible for reduced respiratory control and apnea. To date, mostly animal studies have been published. Therefore, more clinical studies on the role of chorioamninitis-induced inflammation on prematurity and neonatal apnea are necessary.

A scintigraphy study of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in patients with moderate-to-very severe chronic obstructive pulmonary disease

BackgroundTriple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β2-agonists (ICS/LAMA/LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) with continued symptoms or exacerbations, despite treatment with LAMA/LABA or ICS/LABA. The pulmonary, extrathoracic, and regional lung deposition patterns of a radiolabeled ICS/LAMA/LABA triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate (BGF 320/18/9.6 μg), delivered via a single Aerosphere metered dose inhaler (MDI) were previously assessed in healthy volunteers and showed good deposition to the central and peripheral airways (whole lung deposition: 37.7%). Here, we report the findings assessing BGF in patients with moderate-to-very severe COPD.MethodsThis phase I, single-dose, open-label gamma scintigraphy imaging study (NCT03906045) was conducted in patients with moderate-to-very severe COPD. Patients received two actuations of BGF MDI (160/9/4.8 μg per actuation) radiolabeled with technetium‑99‑pertechnetate, not exceeding 5 MBq per actuation. Immediately following each inhalation, patients performed a breath-hold of up to 10 s, then exhaled into an exhalation filter. Gamma scintigraphy imaging of the anterior and posterior views of the lungs and stomach, and a lateral head and neck view, were performed immediately after exhalation. The primary objective of the study was to assess the pulmonary deposition of BGF. Secondary objectives assessed the deposited dose of radiolabeled BGF in the oropharyngeal and stomach regions, on the actuator, and on the exhalation filter in addition to regional airway deposition patterns in the lungs.ResultsThe mean BGF emitted dose deposited in the lungs was 32.1% (standard deviation [SD] 15.6) in patients with moderate-to-very severe COPD, 35.2% (SD 12.8) in patients with moderate COPD, and 28.7% (SD 18.4) in patients with severe/very severe COPD. Overall, the mean normalized outer/inner ratio was 0.55 (SD 0.19), while the standardized central/peripheral ratio was 2.21 (SD 1.64).ConclusionsRadiolabeled BGF 320/18/9.6 μg was efficiently delivered and deposited throughout the entire lung, including large and small airways, in patients with moderate-to-very severe COPD, with similar deposition in patients with moderate COPD and patients with severe/very severe COPD.Trial registration: ClinicalTrials.gov, NCT03906045. Registered 8 April 2019, https://clinicaltrials.gov/ct2/show/NCT03906045

STENT-IN-STENT TECHNIQUE FOR MANAGEMENT OF PERIPHERAL MALIGNANT ENDOBRONCHIAL OBSTRUCTION

TOPIC: Procedures TYPE: Medical Student/Resident Case Reports INTRODUCTION: Airway stenting is used to restore patency of airways with malignant obstruction. Stent-in-stent (SIS) technique has been used in central airway obstruction. We describe a case of malignant endobronchial obstruction in the right upper lobe (RUL) managed with SIS technique. CASE PRESENTATION: 56-year-old male with history of Laryngeal Carcinoma managed with surgical resection and chemo-radiation was transferred for management of recurrent hemoptysis and right lung atelectasis. He was tachypneic and hypoxic requiring 2L oxygen. Labs revealed leukocytosis, hemoglobin of 9.6gm/dl and no coagulopathy. CT Chest showed right lung atelectasis due to right mainstem endobronchial mass. Rigid bronchoscopy (RB) demonstrated a friable mass in the right main stem with frank blood in the central airway. Initially Diode laser was employed for removal of the pedunculated tumor originating in the RUL, followed by debulking with RB and cryoprobe from the right main stem and bronchus intermedius (BI). Rigid tamponade and argon plasma coagulation were used for hemostasis. BF-P190 Olympus scope was used to identify the distal airway in the RUL posterior segment and a 7x22 mm iCAST stent was placed for airway patency. Right middle lobe (RML) and lower lobe (RLL) airways were not localized at the time. A staged RB was performed a few days later. BF-P190 Olympus scope was used for inspection which revealed occlusion of distal end of stent with tumor, advancement of scope with mild pressure through the tumor revealed sub segmental airways, under fluoroscopy guidance a second 7x22mm iCAST stent was placed overlapping with the first stent. Additional tumor debulking from the BI revealed RLL segmental branches. Under direct visualization a 10x38 mm iCAST stent was placed to restore airway patency to the RLL. He remained stable off oxygen post procedure, with reinflation of the right lung. He was discharged with bronchodilators and hypertonic saline with significant improvement in his quality of life. DISCUSSION: Rigid bronchoscopy and airway stenting is commonly used for management of complex central airway obstruction. iCAST stent is a balloon expandable stainless steel stent that is fully encapsulated in two layers of polytetrafluoroethylene. The stent deployment is through the scope with the smallest size of 5x16mm and largest 10x38mm. The smaller size stent can be upsized with a larger sized balloon with the stent shortening in length. We present a SIS placement of two 7x22 mm iCAST stents in the airway likely traversing through the right hilar mass to establish airway patency, resulting in complete reexpansion of the lung. CONCLUSIONS: Peripheral airway stenting of occluded airway due to malignancy can result in lung reinflation, resulting in increased pulmonary reserves for patient to tolerate chemotherapy and radiation. We used SIS technique for customization and appropriate stenting of distal airway. REFERENCE #1: Sethi, Sonali, et al. "Clinical Success Stenting Distal Bronchi for 'Lobar Salvage’ in Bronchial Stenosis:” Journal of Bronchology & Interventional Pulmonology, vol. 25, no. 1, 2018, pp. 9–16, doi:10.1097/LBR.0000000000000422. REFERENCE #2: Majid A, Kheir F, Chung J, Alape D, Husta B, Oh S, Folch E.. Covered Balloon-Expanding Stents in Airway Stenosis. J Bronchology Interv Pulmonol. 2017 Apr;24(2):174-177. doi: 10.1097/LBR.0000000000000364.J Bronchology Interv Pulmonol. 2017. PMID: 28323735 DISCLOSURES: No relevant relationships by Muhammad Arif, source=Web Response no disclosure submitted for Ali Saeed; No relevant relationships by Hursh Sarma, source=Web Response No relevant relationships by Andrew Talon, source=Web Response No relevant relationships by Cindrel Tharumia Jagadeesan, source=Web Response

Bronchial Asthma and Salivary Surfactant Protein D: Review Article

Background: Chronic bronchial inflammation underlies asthma, which is a complex disease with varied and largely reversible blockage of the respiratory route. Asthma is a major public health issue that affects people of all ages around the world. Many countries are seeing an increase in the prevalence of this disease, particularly among children. Among children, asthma is the most frequent long-term condition, accounting for more than half of all missed school days, emergency room consultations, and hospitalizations. Surfactant Protein D, a pattern-recognition molecule, dampens elevated levels of particular antibodies, alveolar macrophage accumulation, eosinophilia, and subepithelial fibrosis and mucous metaplasia, as well as airway hyper-reactivity in allergic asthma in vivo. Objective: In order to discover the connection between children's bronchial asthma and surfactant protein D. Conclusion: Salivary SP-D is a simple, low-cost, quick, and noninvasive way to collect saliva from children. Salivary SP-D levels may be linked to asthma exacerbation severity and peripheral airway resistance.

A Pilot Study to Estimate the Impact of High Matrix Image Reconstruction on Chest Computed Tomography

Objectives:The objectives of the study were to estimate the impact of high matrix image reconstruction on chest computed tomography (CT) compared to standard image reconstruction.Material and Methods:This retrospective study included patients with interstitial or parenchymal lung disease, airway disease, and pulmonary nodules who underwent chest CT. Chest CT images were reconstructed using high matrix (1024 × 1024) or standard matrix (512 × 512), with all other parameters matched. Two radiologists, blinded to reconstruction technique, independently examined each lung, viewing image sets side by side and rating the conspicuity of imaging findings using a 5-point relative conspicuity scale. The presence of pulmonary nodules and confidence in classification of internal attenuation was also graded. Overall image quality and subjective noise/artifacts were assessed.Results:Thirty-four patients with 68 lungs were evaluated. Relative conspicuity scores were significantly higher using high matrix image reconstruction for all imaging findings indicative of idiopathic lung fibrosis (peripheral airway visualization, interlobular septal thickening, intralobular reticular opacity, and end-stage fibrotic change; P ≤ 0.001) along with emphysema, mosaic attenuation, and fourth order bronchi for both readers (P ≤ 0.001). High matrix reconstruction did not improve confidence in the presence or classification of internal nodule attenuation for either reader. Overall image quality was increased but not subjective noise/artifacts with high matrix image reconstruction for both readers (P < 0.001).Conclusion:High matrix image reconstruction significantly improves the conspicuity of imaging findings reflecting interstitial lung disease and may be useful for diagnosis or treatment response assessment.

Peripheral Airway Impairment and Dysanapsis Define Risk of Uncontrolled Asthma in Obese Asthmatic Children

Factors that determine the relationship between obesity and poor outcomes in asthmatic children are not well understood. Dysanapsis and peripheral airway impairment (PAI) could provide an explanation in the obese asthmatic patient. To determine the effect of obesity on increased dysanapsis and PAI and establish the effect of obesity, dysanapsis, and PAI on increased risk of uncontrolled asthma. We evaluated 206 children with moderate to severe asthma, aged 4-18 years, to determine the relationship of body mass index (BMI) to increased dysanapsis and PAI, using reference values. We examined the probability of obesity, dysanapsis, and PAI increasing the risk of uncontrolled asthma by BMI categorically and BMI z scores using generalized linear model analyses. Compared with normal-weight children, overweight and obese children had increased forced vital capacity % predicted and obesity increased odds of dysanapsis by 2.32 (P=.04), while PAI showed an age-dependent effect, with increased odds of 2.09 for children younger than 12 years (P=.08) and 54.14 for those 12 years and older (P= .003). For each unit increase in BMI z score, there was an increased odds ratio of 1.57 for dysanapsis (P= .009), greater in males, OR of 3.10, P = .009, and of 1.39 for PAI for those younger than 12 years (P= .042) and of 4.60 for those 12 years and older (P= .002). Obesity's relationship to uncontrolled asthma was indirect, as not significant when adjusted for the direct effect of dysanapsis and PAI, which were highly significant predictors, with increased odds of 28.01 for dysanapsis for those younger than 12 years (P < .001) and of 3.09 for PAI (P= .005). Overweight and obesity significantly increase odds of dysanapsis and PAI, in an age and gender-specific manner, increasing the probability of uncontrolled asthma.