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Background: Obesity can lead to increased airway resistance, especially in the peripheral airways. Impulse oscillometry (IOS) may detect small airway changes in asthma. In this study, we aimed to investigate the effect of obesity on the small airways of the lungs in asthmatic patients by IOS measurements. Methods: One hundred newly diagnosed asthmatic patients (28 male) were divided into three groups (BMI (< 25.0 kg/m2: Group-1; 25.0 to 29.9 kg/m2: Group-2; ≥30 kg/m2: Group-3). Demographic data, comorbidities, Beck anxiety and depression questionnaires, PFTs, and IOS measurements of the patients were recorded. Results: There was no detected significant difference concerning age, gender, smoking history, pack year, comorbidities (except hypertension and anxiety), asthma cardinal symptoms (except dyspnea), and pulmonary function tests among groups (p > 0.05). There were significant differences regarding R5, R5%, R20%, X5, X20, Fres, and R5-R20 among the three groups. Group 1 significantly differed about R5-R20, X5, AX, and Fres compared to groups 2 and 3 in pairwise comparisons. Based on these results, a difference was detected between BMI < 25 and ≥ 25. There was only one significant variable (R20%) between BMI < 30 and ≥ 30. When performing a correlation test between IOS parameters and BMI, it was observed to be significantly correlated (p < 0.05) except X5% and X20% (p > 0.05). Conclusion: Obesity and being overweight affected peripheral airways and reactance; however, obesity also affects central airways, based on our results. In addition, it was thought that IOS may detect earlier than PFTs on small airway changes. [ABSTRACT FROM AUTHOR]

In contrast to pig large airways, the pH of airway surface liquid (ASL) in pig small airways is regulated by CFTR-mediated HCO–3 secretion and the vacuolar-type H+ ATPase (V-ATPase) proton secretion. We hypothesized that, in cystic fibrosis (CF), the ASL pH of small airways is acidic, and the V-ATPase is internalized. We quantified proton secretion during the addition of an alkaline test solution by measuring changes in a pH-dependent fluorescent dye generated by porcine small airway epithelia in the absence and presence of bafilomycin A1. The pH-dependent translocation of V-ATPase in ex vivo and in vivo preparations was measured using immunolocalization of V-ATPase. We found that bafilomycin-sensitive proton secretion stopped when the ASL pH was less than 7.10. In non-CF pigs and mice, we found that V-ATPase was localized in the apical membrane, and internalized when the lungs were instilled with a pH 6.8 solution. Studies in which we immediately fixed lungs from pigs revealed apical V-ATPase detection in non-CF piglets and less apical detection in CF piglets. Our data suggest that V-ATPase in small airways is internalized when the ASL pH is acidic. The decrease in apical localization of V-ATPase in CF pigs is consistent with an acidic ASL pH. NEW & NOTEWORTHY: In this study, we describe that vacuolar-type H+ ATPase (V-ATPase) internalizes when the airway surface liquid (ASL) pH in pig small airways is less than 7.10. Furthermore, we found that V-ATPase is not localized to the apical membrane in the small airways of newborn cystic fibrosis pigs. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease is caused by the inhalation of noxious particles such as cigarette smoke. The pathophysiological features include airway inflammation, alveolar destruction, and poorly reversible airflow obstruction. A subgroup of patients with chronic obstructive pulmonary disease has higher blood eosinophil counts, associated with an increased response to inhaled corticosteroids and increased biomarkers of pulmonary type 2 inflammation. Emerging evidence shows that patients with chronic obstructive pulmonary disease with increased pulmonary eosinophil counts have an altered airway microbiome. Higher blood eosinophil counts are also associated with increased lung function decline, implicating type 2 inflammation in progressive pathophysiology in chronic obstructive pulmonary disease. We provide a narrative review of the role of eosinophils and type 2 inflammation in the pathophysiology of chronic obstructive pulmonary disease, encompassing the lung microbiome, pharmacological targeting of type 2 pathways in chronic obstructive pulmonary disease, and the clinical use of blood eosinophil count as a chronic obstructive pulmonary disease biomarker. [ABSTRACT FROM AUTHOR]

Background: Severe asthma is a challenging condition that often resists traditional treatments and requires high-dose inhaled corticosteroids and other controllers to manage uncontrolled symptoms. Recent advances include the use of biologic agents targeting specific inflammation pathways, which have improved symptom control and quality of life, although their effects on small airways remain less understood. Methods: This prospective observational study, conducted at Tor Vergata University Hospital in Rome from July 2021 to March 2024, aims to evaluate the efficacy of treatments in patients with uncontrolled severe asthma. It involves baseline assessments and follow-ups at 1 and 3 months post-biological therapy initiation, focusing on both spirometric and non-spirometric (oscillometry) measurements of the small airways to provide a comprehensive evaluation of respiratory function. Results: This study, conducted from July 2021 to March 2024, enrolled 40 patients with severe asthma, ultimately analyzing data from 31 participants who underwent biological therapy. The results showed significant improvements in asthma symptoms, the ACT scores increased significantly from visit 1 to visit 2 (p = 0.00008) and from visit 1 to visit 3 (p = 0.00047), and pulmonary function tests, with notable increases in FEV1 (from visit 1 (74.97 ± 23.43%) to visit 2 (82.96 ± 26.57%, p = 0.041) and to visit 3 (88.89 ± 31.41%, p = 0.003)) and quality of life scores, and substantial reductions in specific airway resistance and small airway dysfunction markers (the PEF, %pr post-BD showed significant improvement from visit 1 to visit 3 (p = 0.012)). However, oscillometric measurements showed no significant changes post-therapy. Conclusions: The study concluded that there was an improvement in the small airways measured by non-oscillometric values, without significant improvements in oscillometric parameters. Additionally, a significant improvement in symptoms was observed after the first month of therapy. There was also a significant increase in respiratory function after one to three months of therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Obesity can lead to increased airway resistance, especially in the peripheral airways. Impulse oscillometry (IOS) may detect small airway changes in asthma. In this study, we aimed to investigate the effect of obesity on the small airways of the lungs in asthmatic patients by IOS measurements. Methods One hundred newly diagnosed asthmatic patients (28 male) were divided into three groups (BMI ( 0.05). There were significant differences regarding R5, R5%, R20%, X5, X20, Fres, and R5-R20 among the three groups. Group 1 significantly differed about R5-R20, X5, AX, and Fres compared to groups 2 and 3 in pairwise comparisons. Based on these results, a difference was detected between BMI 0.05). Conclusion Obesity and being overweight affected peripheral airways and reactance; however, obesity also affects central airways, based on our results. In addition, it was thought that IOS may detect earlier than PFTs on small airway changes.

Small airway dysfunction (SAD) is a pathological process that affects the bronchioles and non-cartilaginous airways below 2 mm in diameter. This short review presents a link between SAD and IPF. Pathomorphological changes of small airways in fibrotic lungs are discussed. Additionally, functional abnormalities related to SAD measured by spirometry and oscillometry are presented. The problem of early detection and treatment of SAD as a procedure potentially capable of mitigating fibrosis is mentioned.

Introduction: E-cigarettes and heated tobacco products (HTPs) are gaining worldwide significance. The tobacco industry is promoting these products as healthier alternatives to conventional cigarettes. Methods: In this four-arm crossover study, we examined the acute effects of cigarette smoking, vaping IQOS, or vaping e-cigarettes (with or without nicotine) on hemodynamics, arterial stiffness, and small airways. Twenty subjects (10 male, 10 female), all occasional smokers, completed each study arm. There was at least a 48 h washout period before each test day. Arterial stiffness and peripheral and central hemodynamics were assessed using Mobil-O-Graph™ (I.E.M., Germany), whereas tremoFlo® c-100 (Thoracic Medical Systems Inc) was used to evaluate the effects on the small airways and resistance. Results: Cigarettes, IQOS, e-cigarettes containing nicotine, and nicotine-free e-cigarettes had similar effects on peripheral and central hemodynamics as well as on arterial stiffness. We observed a significant increase in all parameters. However, only nicotine-containing products lead to increased bronchial obstruction, higher reactance, and a higher tidal volume. Conclusion: Therefore, we concluded that cigarettes, IQOS, and e-cigarettes have similar effects on hemodynamics. No differences were observed between the nicotine-containing and nicotine-free e-cigarettes. All nicotine-containing products also influence small airways. These findings suggest that e-cigarettes and HTPs are not healthier alternatives than conventional cigarettes. [ABSTRACT FROM AUTHOR]

Objective: Adverse respiratory outcomes in post-9/11 veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registrywere compared to thosewithout elevated urinary metals. Methods: Veterans completed questionnaires, underwent pulmonary physiology tests (pulmonary function and oscillometry), and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses, and physiology measures were compared in veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. Results: Among 402 study participants, 24% had elevated urinemetals, often just exceeding upper limits of reference values. Compared to veterans without elevated metals, those with elevated metals had had higher FEV1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. Conclusions: Mild systemic metal elevations in post-9/11 veterans are not associated with adverse respiratory health outcomes. [ABSTRACT FROM AUTHOR]

If multiple-breath washout (MBW)-derived acinar ventilation heterogeneity (Sacin) really represents peripheral units, the N2 phase-III of the first MBW exhalation should be curvilinear. This is essentially due to the superposed effect of gas diffusion and convection resulting in an equilibration of N2 concentrations between neighboring lung units throughout exhalation. We investigated this in smokers with computed tomography (CT)-proven functional small airway disease. Instantaneous N2-slopes were computed over 40-ms intervals throughout phase-III and normalized by mean phase-III N2 concentration. N2 phase-III (concave) curvilinearity was quantified as the rate at which the instantaneous N2-slope decreases past the phase-II peak over a 1-s interval; for a linear N2 phase-III unaffected by diffusion, this rate would amount to 0 L−1/s. N2 phase-III curvilinearity was obtained on the experimental curves and on existing model simulations of N2 curves from a normal peripheral lung model and one with missing terminal bronchioles (either 50% or 30% TB left). In 46 smokers [66 (±8) yr; 49 (±26) pack·yr] with CT-based evidence of peripheral lung destruction, instantaneous N2-slope decrease was compared between those with (fSAD+fEmphys) > 20% [−0.26 ± 0.14 (SD) L−1/s; n = 24] and those with (fSAD+fEmphys) < 20% [−0.16 ± 0.12 (SD) L−1/s; n = 22] (P = 0.014). Experimental values fell in the range predicted by a realistic peripheral lung model with progressive reduction of terminal bronchioles: values of instantaneous N2-slope decrease obtained from model simulations were −0.09 L−1/s (normal lung; 100% TB left), −0.17 L−1/s (normal lung 50% TB left), and −0.29 L−1/s (30% TB left). In smokers with CT-based evidence of functional small airway alterations, it is possible to demonstrate that Sacin really does represent the most peripheral airspaces. NEW & NOTEWORTHY: In smokers with computed tomography-based evidence of functional small airway alterations by parametric response mapping, it is possible to demonstrate that the multiple-breath washout-derived Sacin, an index of acinar ventilation heterogeneity, actually does represent the most peripheral airspaces. This is done by verifying on experimental N2 washout curves of the first breath, N2 phase-III concavity predicted by the diffusion-convection interdependence model. [ABSTRACT FROM AUTHOR]

The fact that some SARS-CoV-2 pneumonia patients benefit from changing body position, and some from continuous positive airways pressure (CPAP), indicates the functional character of hypoxia. We hypothesize that such effects could be explained by the closure of small airways. To prove the hypothesis, we evaluated the patency of small airways in 30 oxygen-dependent, spontaneously breathing patients with SARS-CoV-2 pneumonia during their hospital stay using the FOT method and then compared the results with data obtained three months later. During the acute period, total resistance (R5) and peripheral resistance (R5-20) rose above the upper limit of normal (ULN) in 28% and 50% of all patients, respectively. Reactance indices X5, AX and Fres exceeded ULN in 55%, 68% and 66% of cases. Significant correlations were observed between PaO2/FiO2, the time spent in the hospital and R5, X5, AX and Fres. After 3 months, 18 patients were re-examined. During the hospital stay, 11 of them had risen above the upper limit of normal (ULN), for both resistance (R5-20) and reactance (X5, AX) values. Three months later, ULN for R5-20 was exceeded in only four individuals, but ULN for X5 and AX was exceeded in five individuals. Lung function examination revealed a combined restrictive/obstructive ventilatory failure and reduced CO transfer factor. We interpret these changes as lung tissue remodeling due to the process of fibrosis. We conclude that during acute period of SARS-CoV-2 pneumonia, dilated pulmonary blood vessels and parenchymal oedema induce functional closure of small airways, which in turn induce atelectasis with pulmonary right-to-left shunting, followed by the resulting hypoxemia. [ABSTRACT FROM AUTHOR]

Introduction: Impaired lung function has been observed in patients following COVID‐19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID‐19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID‐19 infection, focusing on the relationship between time and symptoms. Material and Method: The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date. Result: The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways. Conclusion: The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post‐COVID‐19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post‐COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). Methods Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-β expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. Results The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. Conclusion LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).

Rationale: Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. Objective: To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs. Methods: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n = 10); Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (n = 6), II (n = 6), and III/IV (n = 7) COPD; and controls (n = 10), which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways were compared between groups, and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology. Measurements and Main Results: The numbers of transitional bronchioles and terminal bronchioles per milliliter of lung were significantly lower in pre-COPD and GOLD stages I, II, and III/IV COPD compared with controls. In addition, the number of alveolar attachments of the transitional bronchioles and terminal bronchioles was also lower in pre-COPD and all COPD groups compared with controls. We did not find any differences between the pre-COPD and COPD groups in CT or microCT measures. The percentage of emphysema on CT showed the strongest correlation with the number of small airways in the COPD groups. Histopathology showed an increase in the mean chord length and a decrease in alveolar surface density in pre-COPD and all GOLD COPD stages compared with controls. Conclusions: Lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodeling even in the absence of physiologic airway obstruction. [ABSTRACT FROM AUTHOR]

Abstract Objectives Parametric response mapping (PRM) enables the evaluation of small airway disease (SAD) at the voxel level, but requires both inspiratory and expiratory chest CT scans. We hypothesize that deep learning PRM from inspiratory chest CT scans can effectively evaluate SAD in individuals with normal spirometry. Methods We included 537 participants with normal spirometry, a history of smoking or secondhand smoke exposure, and divided them into training, tuning, and test sets. A cascaded generative adversarial network generated expiratory CT from inspiratory CT, followed by a UNet-like network predicting PRM using real inspiratory CT and generated expiratory CT. The performance of the prediction is evaluated using SSIM, RMSE and dice coefficients. Pearson correlation evaluated the correlation between predicted and ground truth PRM. ROC curves evaluated predicted PRMfSAD (the volume percentage of functional small airway disease, fSAD) performance in stratifying SAD. Results Our method can generate expiratory CT of good quality (SSIM 0.86, RMSE 80.13 HU). The predicted PRM dice coefficients for normal lung, emphysema, and fSAD regions are 0.85, 0.63, and 0.51, respectively. The volume percentages of emphysema and fSAD showed good correlation between predicted and ground truth PRM (|r| were 0.97 and 0.64, respectively, p

BackgroundSulfur mustard (SM) exposure causes acute and chronic respiratory diseases. The extent of small airway dysfunction (SAD) in individuals exposed to SM is unclear. This study evaluated and compared SAD in SM-exposed and SM-unexposed participants using noninvasive lung function tests assessing small airway function.MethodsThis retrospective cohort study involved SM-exposed (n = 15, mean age: 53 ± 8 years) and SM-unexposed (n = 15, mean age: 53 ± 7 years) Kurdish-Swedish individuals in Sweden. Small airway resistance and reactance were assessed using impulse oscillometry (IOS). Nitrogen (N2) multiple breath washout (MBW) was employed to assess lung ventilation heterogeneity. The gas-exchanging capacity of the lungs was assessed using the diffusing capacity of the lungs for the carbon monoxide (DLCO) test. Lung function outcomes were reported as absolute values and z-scores. Group comparisons were performed using the Mann–Whitney U test.ResultsNo statistically significant differences in age, height, or body mass index were observed between the two groups. IOS showed significantly increased small airway resistance, while N2MBW exhibited significantly increased global and acinar ventilation heterogeneity in SM-exposed individuals compared to that in unexposed individuals. SAD was identified in 14 of 15 SM-exposed individuals, defined as at least one abnormal IOS difference between resistance at 5 and 20 Hz (R5-R20) and/or area of reactance (AX) or N2MBW lung’s acinar zone (Sacin), and DLCO adjusted to the alveolar volume (DLCO/VA) outcome. Of these 14 individuals, only 5 demonstrated concordant findings across the IOS and N2MBW tests.ConclusionExposure to SM was positively associated with long-term impairment of respiratory tract function in the small airways in the majority of the previously SM-exposed individuals in the present study. Furthermore, both IOS and N2MBW should be employed to detect SAD in SM-exposed survivors as they provide complementary information. Identifying and characterizing the remaining pathology of the small airways in survivors of SM exposure is a first step toward improved treatment and follow-up.

Introduction: Recent studies have indicated the significance of the peripheral airways in asthma control. Methods estimating airway resistance, air trapping, and ventilation inhomogeneity are useful for assessing this area of the lung and have proven utility in the evaluation of asthma; however, it is unclear which method is most effective at characterising uncontrolled asthma. Aim: To evaluate the diagnostic accuracy of various peripheral airway function measurements in the assessment of asthma control in children. Material and methods: Children with controlled (n = 35) and uncontrolled (n = 29) asthma performed a sequence of pulmonary function tests (i.e. spirometry, body plethysmography, oscillometry, nitrogen washout test, and exhaled nitric oxide). The diagnostic accuracy of each peripheral airway measure was evaluated by an area under the receiver operating characteristic curve (AUC). Results: Most peripheral airway parameters were significantly increased in children with uncontrolled asthma compared with children with controlled asthma. The measures with the highest diagnostic accuracy for asthma control were lung clearance index (LCI) (AUC = 0.76), with high specificity (0.97) and modest sensitivity (0.46), acinar ventilation heterogeneity (Sacin) (AUC = 0.73), with high sensitivity (0.85) and modest specificity (0.54), and resonance frequency (Fres) (AUC= 0.74), with perfect specificity (1.0) but low sensitivity (0.38). Conclusions: LCI, Sacin and Fres had the highest discriminative capacity for distinguishing children with controlled and uncontrolled asthma among all evaluated peripheral airways measures. Discrepancies in the performance (i.e. sensitivity and specificity) of each parameter suggest that a combination may be most effective in determining asthma control status. [ABSTRACT FROM AUTHOR]

The small airways (SA), i.e., branches of the tracheo-bronchial tree with a diameter of less than 2 millimetres, not only conduct airflow but also represent an important determinant of lung mechanics. Their involvement in broncho-obstructive diseases, such as asthma and COPD, correlates closely with worsening of the underlying disease. However, there is still no gold standard for functionally defining the presence of SA obstruction. The most widely used parameters in the clinical practice are based on the use of spirometry or the Impulse Oscillometry System, which provide non-concordant and complementary information on the function of SA. Further studies are required to define the standard criteria for SA obstruction. [ABSTRACT FROM AUTHOR]

Objectives: Impulse oscillometry (IOS) is a type of oscillation technique that measures the input impedance (Z) of the respiratory system and can be used to detect pathological changes in the small airways at an early stage. Although coronavirus disease 2019 (COVID-19) affects the vascular and parenchymal structures in the lung, chronic postinfection coughs also may be attributed to small airway pathologies. Our research aimed to use IOS for the assessment of the presence of small airway resistance (R) in patients who have had COVID-19. Methods: Thirty-eight patients with past COVID-19 infections and without any presence or medical treatment of an airway disease who presented to the post-COVID outpatient clinicwith coughing symptoms were included in the study. The control group consisted of 17 patients with no past COVID-19 infection and without an airway disease. IOS and spirometry were performed twice in the case group, at 3 and 6 months after COVID-19. Results: The mean age of the case group was 44.7 ± 12.3 years, whereas the mean age of the control group was 49.4 ± 11.8 years. The case group consisted of 38 patients, whereas 17 patients constituted the control group. No statistically significant differencewas found between the two groups in the first and second test measurements, performed 3 months apart (P > 0.05). Conclusions: The fact that there was no difference between respiratory system impedance, airway resistance, and spirometry values between groupswith and without pastCOVID-19 infections supported the hypothesis that small airways were not affected 3 months after COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: Parametric response mapping (PRM) enables the evaluation of small airway disease (SAD) at the voxel level, but requires both inspiratory and expiratory chest CT scans. We hypothesize that deep learning PRM from inspiratory chest CT scans can effectively evaluate SAD in individuals with normal spirometry. Methods: We included 537 participants with normal spirometry, a history of smoking or secondhand smoke exposure, and divided them into training, tuning, and test sets. A cascaded generative adversarial network generated expiratory CT from inspiratory CT, followed by a UNet-like network predicting PRM using real inspiratory CT and generated expiratory CT. The performance of the prediction is evaluated using SSIM, RMSE and dice coefficients. Pearson correlation evaluated the correlation between predicted and ground truth PRM. ROC curves evaluated predicted PRMfSAD (the volume percentage of functional small airway disease, fSAD) performance in stratifying SAD. Results: Our method can generate expiratory CT of good quality (SSIM 0.86, RMSE 80.13 HU). The predicted PRM dice coefficients for normal lung, emphysema, and fSAD regions are 0.85, 0.63, and 0.51, respectively. The volume percentages of emphysema and fSAD showed good correlation between predicted and ground truth PRM (|r| were 0.97 and 0.64, respectively, p < 0.05). Predicted PRMfSAD showed good SAD stratification performance with ground truth PRMfSAD at thresholds of 15%, 20% and 25% (AUCs were 0.84, 0.78, and 0.84, respectively, p < 0.001). Conclusion: Our deep learning method generates high-quality PRM using inspiratory chest CT and effectively stratifies SAD in individuals with normal spirometry. [ABSTRACT FROM AUTHOR]

Small airway disease (SAD) is a pathological condition that affects the bronchioles and non-cartilaginous airways 2 mm or less in diameter. These airways play a crucial role in respiratory function and are often implicated in various pulmonary disorders. Pulmonary fibrotic diseases are characterized by the thickening and scarring of lung tissue, leading to progressive respiratory failure. We aimed to present the link between SAD and fibrotic lung conditions. The evidence suggests that SAD may act as a precursor or exacerbating factor in the progression of fibrotic diseases. Patients with fibrotic conditions often exhibit signs of small airway dysfunction, which can contribute to worsening respiratory symptoms and decreased lung function. Moreover, individuals with advanced SAD are at a heightened risk of developing fibrotic changes in the lung. The interplay between inflammation, environmental factors, and genetic predisposition further complicates this association. The early detection and management of SAD can potentially mitigate the progression of fibrotic diseases, highlighting the need for comprehensive clinical evaluation and research. This review emphasizes the need to understand the evolving connection between SAD and pulmonary fibrosis, urging further detailed research to clarify the causes and potential treatment between the two entities. [ABSTRACT FROM AUTHOR]

Background. Small airway involvement is important in determining the phenotypes of bronchial asthma. Establishing the mechanisms of dysfunction of small airways will make it possible to predict the course and control bronchial asthma.The aim. To study the relationship between the modification of the composition of fatty acids, lipid inflammatory mediators (eicosanoids, plasmalogens) and the functional state of small airways and to identify lipid biomarkers for the development of small airway dysfunction in bronchial asthma associated with obesity.Materials and methods. The study included 85 patients with mild, partially controlled asthma. Of these, 39 patients with normal body weight (Group 1) and 46 patients with grade 1–2 obesity (Group 2). The control group consisted of 30 healthy volunteers. The function of the small airways was assessed according to spirometry and body plethysmography. The composition of fatty acids and plasmalogens in blood plasma was assessed by gas chromatography-mass spectrometry. In the blood serum, the content of thromboxane B2 and leukotriene B4 was determined. Statistical processing was performed using the Statistica 6.1 program (StatSoft Inc., USA). Relationships between pairs of traits were examined using the Spearman correlation test (r). Differences were considered statistically significant at p

The fact that some SARS-CoV-2 pneumonia patients benefit from changing body position, and some from continuous positive airways pressure (CPAP), indicates the functional character of hypoxia. We hypothesize that such effects could be explained by the closure of small airways. To prove the hypothesis, we evaluated the patency of small airways in 30 oxygen-dependent, spontaneously breathing patients with SARS-CoV-2 pneumonia during their hospital stay using the FOT method and then compared the results with data obtained three months later. During the acute period, total resistance (R5) and peripheral resistance (R5-20) rose above the upper limit of normal (ULN) in 28% and 50% of all patients, respectively. Reactance indices X5, AX and Fres exceeded ULN in 55%, 68% and 66% of cases. Significant correlations were observed between PaO2/FiO2, the time spent in the hospital and R5, X5, AX and Fres. After 3 months, 18 patients were re-examined. During the hospital stay, 11 of them had risen above the upper limit of normal (ULN), for both resistance (R5-20) and reactance (X5, AX) values. Three months later, ULN for R5-20 was exceeded in only four individuals, but ULN for X5 and AX was exceeded in five individuals. Lung function examination revealed a combined restrictive/obstructive ventilatory failure and reduced CO transfer factor. We interpret these changes as lung tissue remodeling due to the process of fibrosis. We conclude that during acute period of SARS-CoV-2 pneumonia, dilated pulmonary blood vessels and parenchymal oedema induce functional closure of small airways, which in turn induce atelectasis with pulmonary right-to-left shunting, followed by the resulting hypoxemia.

Background: The small airways comprise the largest cross-sectional area of the lungs, however, assessing and reporting abnormalities for this region of the bronchial tree has been practically and scientifically uncertain. Methods: Using routinely collected spirometry data for patients with either asthma or COPD, the accuracy of % predicted values for defining small airways dysfunction was assessed. A z-score of ≤ −1.645 of the maximal-mid expiratory flow (MMEF) was used as the gold standard for defining abnormality in the small airways. Results: Records of 3396 patients were included in the analysis. The false positive (FP) rates were 24.6 %, 16.1 %, 11.5 %, or 7.9 % when the % predicted value of 80 %, 70 %, 65 %, or 60 % were used, respectively. Sex, age, and BMI were associated with FP rates. Males were more likely to be categorised as FP with odds ratio (OR) between 1.10 and 1.49 across % predicted groups. Age was associated with FP rates with an OR between 1.01 and 1.08. The BMI was also associated with FP rates with an OR of 1.03 across all % predicted groups. Assessing the association of age groups with FP rate showed that those above 60 years old were more likely to be categorised as FP with an OR between 1.23 and 73.2 compared to those less than 30 years old. Conclusion: When assessing the small airways in clinical practice or for scientific purposes, the % predicted values overestimate the actual impairment leading to FP interpretation. Utilising z-score values are recommended to assess the small airways using the spirometric index, MMEF.

Background: Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma. Objectives: We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control. Method: Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry. Results: 53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways. Conclusions: The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system. [ABSTRACT FROM AUTHOR]

The aim of present study was to establish the relationship between the level of blood serum cytokines and indexes of pulmonary function as well as to identify the markers of evolving dysfunction of small airways in obese patients with partially controlled mild bronchial asthma. We have examined 53 patients with mild asthma of partially controlled clinical course complicated with obesity (I-II degree). The control group consisted of 25 healthy volunteers. All participants underwent spirometry, bodyplethysmography. Tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), interleukins (IL) IL2, IL-4, IL-6, IL-10, IL-17A were determined in blood serum. In the patients with partially controlled mild asthma, an increase in IL-17A by 55.8%, and IL-4 by 44.9% was detected, regardless of body mass. According to the results of cluster analysis, two sub-groups were discerned, depending on the state of the small airways and the levels of pro- and anti-inflammatory cytokines. The dysfunction of small airways was shown to be accompanied by hypercytokinemia being more common in bronchial asthma with predominant Th1-and Th17-immune responses. We have revealed an association between IL-17A, IL-6 levels and functional indices reflecting the state of the small airways, as well as correlation between IFNγ and the indices of bronchial obstruction. The features of pulmonary function were found to be dependent on the cytokine status in mild asthma with obesity. Two immuno-functional variants were identified, differing in activity of systemic inflammation, type of immune response, and functional state of the small airways. The revealed relationships allow us to consider IL-17A, IL-6 and IFNγ as markers of small airways dysfunction in mild asthma of partially controlled clinical course associated with obesity.

Alfredo Chetta,1 Nicola Facciolongo,2 Cosimo Franco,3 Laura Franzini,4 Alessio Piraino,4 Carmelina Rossi4 1Clinica Pneumologica, Università di Parma, Parma, Italy; 2UOC Pneumologia, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; 3UOC Pneumologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy; 4Chiesi Italia SpA, Medical Affairs, Parma, ItalyCorrespondence: Alfredo Chetta, Tel +39 0521.703478, Email alfredoantonio.chetta@unipr.itAbstract: In recent years, the perspective of management of respiratory disease has been gradually changing in light of the increasing evidence of small airways as the major site of airflow obstruction contributing to the development of both COPD and asthma already in early stages of disease. First and foremost, the evidence is redefining disease severity, identifying small airways disease phenotypes and early signs of disease, and revising prevalence and overall epidemiological data as well. Much effort has been put toward the instrumental assessment of small airways’ involvement and early detection. Several clinical trials have evaluated the advantage of extra-fine formulations which can best target the small airways in uncontrolled asthma and severe COPD. Here, we briefly present a practical overview of the role of the small airways in disease, the most appropriate diagnostic methods for quantifying their impairment, and provide some insight into the costs of respiratory management in Italy, especially in sub-optimally controlled disease.Keywords: asthma, chronic obstructive pulmonary disease, small airways, impulse oscillometry, cost, extrafine particles

Idiopathic pulmonary fibrosis (IPF) is a pathological condition of unknown etiology that results from injury to the lung and an ensuing fibrotic response that leads to the thickening of the alveolar walls and obliteration of the alveolar space. The pathogenesis is not clear, and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to cystic fibrosis lung disease. The ATP12A gene encodes the α-subunit of the nongastric H+, K+-ATPase, which functions to acidify the airway surface fluid and impairs mucociliary transport function in patients with cystic fibrosis. It is hypothesized that the ATP12A protein may play a role in the pathogenesis of IPF. The authors’ studies demonstrate that ATP12A protein is overexpressed in distal small airways from the lungs of patients with IPF compared with normal human lungs. In addition, overexpression of the ATP12A protein in mouse lungs worsened bleomycin induced experimental pulmonary fibrosis. This was prevented by a potassium competitive proton pump blocker, vonoprazan. These data support the concept that the ATP12A protein plays an important role in the pathogenesis of lung fibrosis. Inhibition of the ATP12A protein has potential as a novel therapeutic strategy in IPF treatment. [ABSTRACT FROM AUTHOR]

Background: The Japanese drug use system allowed the once-daily use of inhaled corticosteroid fluticasone furoate (FF) combined with a long-acting beta-2 agonist vilanterol (VI) and a long-acting muscarinic antagonist umeclidinium (UMEC) against asthma on 18 February 2021. We investigated the real-world effects of these drugs (FF/UMEC/VI) mainly on lung function tests. Methods: This was an open-label, uncontrolled, within-group time-series (before-after) study. Prior asthma treatment (inhaled corticosteroid with/without a long-acting beta-2 agonist with/without a long-acting muscarinic antagonist) was switched to FF/UMEC/VI 200/62.5/25 μg. Subjects were evaluated by lung function tests prior to, and 1–2 months after, initiation of FF/UMEC/VI 200/62.5/25 μg. Patients were asked questions regarding the asthma control test and preference for drugs. Results: Overall, 114 asthma outpatients (97% Japanese) were enrolled from February 2021 to April 2022: 104 subjects completed the study. Forced expiratory volume in 1 s, peak flow, and asthma control test score of FF/UMEC/VI 200/62.5/25 μg-treated subjects were significantly increased (p < 0.001, p < 0.001, and p < 0.01, respectively). In contrast with FF/VI 200/25 μg, instantaneous flow at 25% of the forced vital capacity and expiratory reserve volume were significantly increased by FF/UMEC/VI 200/62.5/25 μg (p < 0.01, p < 0.05, respectively). Sixty-six percent of subjects declared they wanted to continue FF/UMEC/VI 200/62.5/25 μg in the future. Adverse effects, mainly local, were seen in 30% of patients, but no serious adverse effects were seen. Conclusion: Once-daily FF/UMEC/VI 200/62.5/25 μg was effective against asthma without serious adverse events. This is the first report that demonstrated FF/UMEC/VI dilated peripheral airways using lung function tests. This evidence on drug effects may improve our understanding of pulmonary physiology and the pathophysiology of asthma. [ABSTRACT FROM AUTHOR]

BackgroundSmall airways play a major role in the pathogenesis and prognosis of chronic obstructive pulmonary disease (COPD) and asthma. More data on small airway dysfunction (SAD) using spirometry and impulse oscillometry (IOS) in these populations are required. The objective of this study was to compare the two methods, spirometry and IOS, for SAD detection and its prevalence defined by spirometry and IOS in subjects with COPD and asthma with and without fixed airflow obstruction (FAO).DesignThis is a cross-sectional study.MethodsSpirometric and IOS parameters were compared across four groups (COPD, asthma with FAO, asthma without FAO, and healthy subjects). SAD defined by spirometry and IOS criteria were compared.ResultsA total of 262 subjects (67 COPD, 55 asthma with FAO, 101 asthma without FAO, and 39 healthy controls) were included. The prevalence of SAD defined by using IOS and spirometry criteria was significantly higher in patients with COPD (62.7 and 95.5%), asthma with FAO (63.6 and 98.2%), and asthma without FAO (38.6 and 19.8%) in comparison with healthy control (7.7 and 2.6%). IOS is more sensitive than spirometry in the detection of SAD in asthma without FAO (38.6% vs. 19.8%, p = 0.003) However, in subjects with FAO (COPD and asthma with FAO), spirometry is more sensitive than IOS to detect SAD (95.5% vs. 62.7%, p

Objective. It is unclear whether Benralizumab effectiveness in severe eosinophilic asthma can be influenced by nasal polyposis (NP) or allergic status associations. We evaluated whether Benralizumab long-term efficacy in asthma outcomes could be different in subjects with atopy (SAEA) compared to the effectiveness in those without allergies (SNAEA) and in individuals with NP compared to those without NP. Methods. This observational retrospective study considered 95 consecutive patients divided into allergic (SAEA; n:65[68.4%]; skin prick tests positive [SPT] and/or IgE values ≥100 UI/mL), and non-allergic (SNAEA; n:30[31.6%], SPT negative and normal IgE levels<100 UI/ mL). Overall population was also divided into two groups according to NP presence (NP+:39[41%] and NP-:56[59%]). Benralizumab treatment mean was19.7±7.2 months (range 12-35). Results. No differences in Benralizumab effectiveness were found in asthma outcomes in patients with/without NP. SNOT-22 improvement was higher in NP+ (-22±24) compared to NP- groups (6.33±15.5;p=0.055). FEV1 (16.33±19.22%), ACT(7.45±3.95) increases and frequency of SABA use (3.37±4.99) reduction were higher in SAEA compared to what obtained in non-allergic subjects (FEV1:8.15±15.6%,p=0.043; ACT:4.89±3.57,p=0.005; SABA use:- 1.16±1.84;p=0.015). 93.8% of SAEA patients whereas only 72.2% of SNAEA individuals reduced OC doses at least half after Benralizumab (p=0.035). These results were partially confirmed by linear regression models showing associations between allergic status and FEV1, ACT and SABA use changes (β=8.37;p=0.048, β=2.056;p=0.033 and β=- 2.184;p=0.042 respectively). Conclusion. Benralizumab effectiveness in asthma appears to be independent of NP presence. The allergic eosinophilic disease, compared to just eosinophilic asthma, may be a more severe phenotype. Benralizumab may have greater efficacy in SAEA on some outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements. Methods Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity. Results We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in “normal” smokers. Concavity measures were not related to either MBNW or IOS measurements. Conclusion Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction.

Background: There is a lack of early and precise biomarkers for personalized respiratory medicine. Breath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and are derived from an area of high clinical interest previously difficult to access, making them a potential source of biomarkers reflecting pathological processes in the small airways. Research question: Our aim was to investigate if PExA method is useful for discovery of biomarkers that reflect pathology of small airways. Methods and analysis: Ten healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI ≥ 2.9 z-score), were examined in a cross-sectional design, using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc.). Results: Two hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n = 14) than in never smokers (n = 16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity. Conclusion: The applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement. Key messages: Key question: Can the PExA method identify individual protein profiles that reflect pathology of small airways, using the SOMAscan platform? What is the bottom line?: Two hundred-seven proteins were detected in up to 80% of the PEx samples, with a strong overrepresentation of proteins related to innate immune responses, including nine proteins that that discriminated subjects with asthma and high LCI as compared to healthy controls. Why read on: The results support that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement. [ABSTRACT FROM AUTHOR]

The small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree. Recently, this has become particularly relevant as measurements of small airways using airway oscillometry for example, are strong determinants of asthma control and exacerbations in moderate-to-severe asthma. The small airways can be assessed using spirometry as forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25–75) and has been deemed more accurate in detecting small airways dysfunction than forced expiratory volume in 1 s (FEV1). Oscillometry as the heterogeneity in resistance between 5 and 20 Hz (R5–R20), low frequency reactance at 5 Hz (X5) or area under the reactance curve between 5 Hz and the resonant frequency can also be used to assess the small airways. The small airways can also be assessed using the multiple breath nitrogen washout (MBNW) test giving rise to values including functional residual capacity, lung clearance index and ventilation distribution heterogeneity in the conducting (Scond) and the acinar (Sacin) airways. The ATLANTIS group showed that the prevalence of small airways disease in asthma defined on FEF25–75, oscillometry and MBNW all increased with progressive GINA asthma disease stages. As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti–alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma. [ABSTRACT FROM AUTHOR]

No abstract available. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Long-term efficacy of Benralizumab in real life is not clearly known. We assessed the long-term effectiveness persistence to anti-IL-5R treatment in a group of severe eosinophilic asthmatics. PATIENTS AND METHODS: We retrospectively analyzed 95 individuals affected by severe asthma (36 males = 37.9%; mean age 58.1 ± 12.2) treated with Benralizumab (mean time 19.7 ± 7.2 months, range 12-35). Outcomes were evaluated at the beginning and at the end of patients' treatment periods. RESULTS: Mean baseline blood eosinophils were 897.5 ± 720.1 cells/µL (11 ± 5.6%) decreasing to 7.4 ± 20.6 cells/µL (0.97 ± 0.26%; p < 0.0001) a fter B enralizumab. F ENO l ikewise decreased from 63.9 ± 68.4 to 28.4 ± 23.6 ppb, while FEV1% significantly improved (p < 0.0001). Mean FEF25-75 also increased from 45.8 ± 24.6% to 60.7 ± 24.6%, whereas RAW dropped from 202.15 ± 109.6% to 135.2 ± 54.75% (p < 0.0001). Also, lung volumes greatly decreased. ACT/ACQ significantly improved, while exacerbations number fell from 4.1 ± 2.4, before anti-IL-5R, to 0.33 ± 0.77, after treatment (p < 0.0001). Rhinitis severity levels and SNOT-22 also changed favorably. Patients that took long-term OCs were 71.6% before treatment, decreasing to 23.2% after Benralizumab (p < 0.0001), with an OCs dose reduction from 14.8 ± 8.9 to 1.45 ± 2.8 mg/day (p < 0.0001). 51.6% of subjects used SABA as needed before Benralizumab, falling to 4.2% after treatment. Several patients showed a reduction of ICS doses, SAEuropean BA use and maintenance therapy step-down. Clinical/biological response with anti-IL-5R remained constant or even improved in terms of exacerbations or maintenance therapy reductions over time. On the contrary, FEF25-75% improvement slowed down in the long-term. No relationship was found between baseline blood eosinophil number and therapeutic response. CONCLUSIONS: Long-term Benralizumab effectiveness persistence in all outcomes in real life was confirmed. [ABSTRACT FROM AUTHOR]

The airways smaller than 2 mm diameter are named small airways. They are essential for the transport and exchange of oxygen and carbon dioxide and at the same time play a relevant role in pulmonary mechanics, contributing to the subdivision of lung volumes. Measurement of small airway function is, therefore, crucial in patients with respiratory disease. This overview focuses on the physiological aspects of the small airways, considered as air ducts as well as determinants of pulmonary mechanics, the most common tools for evaluating their function and treatment implications. [ABSTRACT FROM AUTHOR]

Purpose: Air monitoring has been the accepted exposure assessment of toxic metals from, e.g., welding, but a method characterizing the actual dose delivered to the lungs would be preferable. Sampling of particles in exhaled breath can be used for the biomonitoring of both endogenous biomarkers and markers of exposure. We have explored a new method for the sampling of metals in exhaled breath from the small airways in a study on welders. Methods: Our method for particle sampling, Particles in Exhaled Air (PExA®), is based on particle counting and inertial impaction. We applied it on 19 stainless steel welders before and after a workday. In parallel, air monitoring of chromium, manganese and nickel was performed as well as blood sampling after work. Results: Despite substantial exposure to welding fumes, we were unable to show any significant change in the metal content of exhaled particles after, compared with before, exposure. However, the significance might be obscured by a substantial analytical background noise, due to metal background in the sampling media and possible contamination during sampling, as an increase in the median metal contents were indicated. Conclusions: If efforts to reduce background and contamination are successful, the PExA® method could be an important tool in the investigations of metals in exhaled breath, as the method collects particles from the small airways in contrast to other methods. In this paper, we discuss the discrepancy between our findings and results from studies, using the exhaled breath condensate (EBC) methodology. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 may lead to a large spectrum of respiratory manifestations, including pulmonary sequelae. We conducted a single-center longitudinal study of survivors from severe COVID-19 cases who underwent a chest CT during hospitalization (CTH). Three months after being discharged, these patients were evaluated by a clinical examination, pulmonary function tests and a chest-CT scan (CTFU). Sixty-two patients were enrolled. At follow-up, 27% complained of exertional dyspnoea and 12% of cough. Dyspnoeic patients had a lower forced expiratory flow (FEF)25–75 (p = 0.015), while a CT scan (p = 0.016 showed that patients with cough had a higher extent of bronchiectasis. Lung volumes and diffusion of carbon monoxide (DLCO) at follow-up were lower in patients who had been invasively ventilated, which correlated inversely with the length of hospitalization and ground-glass extension at CTH. At follow-up, 14.5% of patients had a complete radiological resolution, while 85.5% presented persistence of ground-glass opacities, and 46.7% showed fibrotic-like alterations. Residual ground-glass at CTFU was related to the length of hospitalization (r = 0.48; p = 0.0002) and to the need for mechanical ventilation or high flow oxygen (p = 0.01) during the acute phase. In conclusion, although patients at three months from discharge showed functional impairment and radiological abnormalities, which correlated with a prolonged hospital stay and need for mechanical ventilation, the persistence of respiratory symptoms was related not to parenchymal but rather to airway sequelae. [ABSTRACT FROM AUTHOR]

Abstract Follow-up studies of COVID-19 patients have found lung function impairment up to six months after initial infection, but small airway function has not previously been studied. Patients (n = 20) hospitalised for a severe SARS-CoV-2 infection underwent spirometry, impulse oscillometry, and multiple measurements of alveolar nitric oxide three to six months after acute infection. None of the patients had small airway obstruction, nor increased nitric oxide concentration in the alveolar level. None of the patients had a reduced FEV1/FVC or significant bronchodilator responses in IOS or spirometry. In conclusion, we found no evidence of inflammation or dysfunction in the small airways.

Abstract Introduction Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking. Methods Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed. Results Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p

This study was done in order to evaluate the effect of a novel pressure pulsation device (Pulsehaler™, Respinova Ltd., Israel) on the deposition pattern of inhaled aerosol in the lungs of COPD patients. Fifteen COPD patients were recruited to undergo spirometry and SPECT-CT lung scan following nebulization of radioactively labeled albuterol in saline solution with a jet nebulizer ("NEB") and with a combined Pulsehaler™/jet nebulizer ("PH + NEB") treatment. Central and peripheral segments of the coronal and transverse SPECT scans were evaluated for total counts and for the ratios between peripheral counts and central counts (penetration Index, "PI"). There was a significant improvement in FEV1 from before to after albuterol treatment in the PH + NEB group (151 ml ± 187, p < 0.008), but not in the NEB only group (66 ml ± 125, p = 0.06). FVC, FEF25–75, FEV1%, FVC%, FEF25, FEF50, and FEF75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF25-75 (PH + NEB > NEB, p = 0.0176), FEF75 (PH + NEB > NEB, p = 0.0028), but not for the other spirometry measures. Borg scores also were improved significantly improved in PH + NEB vs NEB (p = 0.0006). Total lung deposition and total body deposition were lower in the PH + NEB treatments vs the NEB treatments. However, PI values were 3.08 ± 0.67 times greater on average with the PH + NEB (p = 0.026) as compared to NEB only. The magnitude of the increased penetration index observed in this study indicates that pressure pulsations should be further explored as means to improve drug delivery into the distal small airways of the bronchial tree. Effects of the pressure pulsations on small airway patency could be the mechanism by which the effect was achieved. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements.Methods: Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity.Results: We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in "normal" smokers. Concavity measures were not related to either MBNW or IOS measurements.Conclusion: Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction. [ABSTRACT FROM AUTHOR]

Jie Gao,* Hai Gui Wu,* Feng Wu Department of Pulmonary and Critical Care Medicine, Huizhou the Third People’s Hospital, Guangzhou Medical College, Huizhou 516002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng WuHuizhou the Third People’s Hospital, 1# Xuebei Ave., Huizhou 516002 Guangdong, People’s Republic of ChinaTel +86-13502436132Fax +86-7522359648Email huizhouwufeng@126.comBackground: Cough variant asthma (CVA) is one kind of atypical asthma. The study was to compare spirometric parameters of small airways and the degree of bronchial hyper-responsiveness (BHR) between CVA and classic asthma (CA), and examine the relationship between BHR and small airways to determine the accuracy of these markers as indicators of CVA.Methods: A total of 825 asthmatic patients were screened for the study, and 614 were included. All patients performed spirometry and underwent a bronchial challenge with methacholine.Results: The number of small airways dysfunctions in the CVA group was less than those of the CA group with MMEF% predicted (70% vs 80.91%, P=0.002) and FEF50% predicted (62.71% vs 73.5%, P=0.004). The degree of small airways dysfunction was less in the CVA group compared with the CA group (P< 0.001). Significant positive correlations were observed between the FEV1 level below 20% of the baseline value (PD20) and MMEF% predicted (r=0.282, P< 0.001), FEF50% predicted (r=0.2522, P< 0.001), and FEF75% predicted (r=0.2504, P< 0.001) in patients with CVA. The area under curve (AUC) of MMEF, FEF50, and FEF75 (% predicted) was 0.615, 0.621, and 0.606, respectively. In addition, 0.17 mcg of PD20 was the best diagnostic value for CVA, with an AUC of 0.582 (P=0.001).Conclusion: Small airway dysfunction is milder in CVA. The value of BHR combined with small airways in CVA prediction, which was significant, but not enough to be clinically useful.Keywords: small airways, bronchial hyper-responsiveness, cough-variant asthma, classic asthma

Abstract Background The effects of triple therapy on gas trapping in COPD are not fully understood. We evaluated the effects of the long acting bronchodilator components of the extrafine single inhaler triple therapy beclometasone dipropionate/formoterol/glycopyrronium (BDP/F/G) pMDI on gas trapping. Methods This open-label, randomised, single centre, 2-way cross-over study recruited 23 COPD patients taking inhaled corticosteroid combination treatments and with residual volume (RV) > 120% predicted at screening. Inhaled BDP was taken during run-in and washout periods. Baseline lung function (spirometry, lung volumes, oscillometry) was measured over 12 h prior to randomisation to BDP/F/G or BDP/F for 5 days followed by washout and crossover. Lung function was measured prior to dosing on day 1 and for 12 h post-dose on day 5. Results Co-primary endpoint analysis: BDP/F/G had a greater effect than BDP/F on FEV1 area under the curve over 12 h (AUC0–12) (mean difference 104 mls, p = 0.0071) and RV AUC0–12 (mean difference − 163 mls, p = 0.0028). Oscillometry measurements showed a greater effect of BDP/F/G on the difference between resistance at 5 and 20 Hz (R5–R20) AUC0–12, which measures small airway resistance (mean difference − 0.045 kPa/L/s, p = 0.0002). Comparison of BDP/F with the baseline measurements (BDP alone) showed that F increased FEV1 AUC0–12 (mean difference 227 mls) and improved RV AUC0–12 (mean difference − 558 mls) and R5–R20 AUC0–12 (mean difference − 0.117 kPa/L/s), all p

Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airways. Inhaled bronchodilators and corticosteroids are the cornerstone of pharmacological long-term treatment for asthma and COPD. The efficacy of any topical inhaled medication is dependent upon successful distribution of the drug to the site of disease. Targeting small airways inflammation in severe asthma and COPD are critically important as the combined surface area of small airways far exceeds the surface area that large central airways provide. Small airway dysfunction in BA is associated with increased asthma symptoms, worse asthma control and an increased number of exacerbations. Chronic inflammation in COPD causes structural alterations and narrowing of particularly the small airways. The extrafine combination of beclomethasone dipropionate/formoterol (BDP/F) enables drug delivery to both the large and small airways, and allows the clinical benefits to be achieved with a lower corticosteroid dose. The use of extrafine BDP/F is more effective in achievement asthma control and reduce COPD exacerbations. If it is necessary to continue ICS as part of a double or triple COPD therapy extrafine fixed combination of BDP/F can be considered as the drug of choice and optimal replacement of the ICS molecule.