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Background: Chronic obstructive pulmonary disease (COPD) is associated with airflow limitation resulting from a combination of small airway disease (SAD) and parenchymal destruction. Although various diagnostic methods for SAD exist, access to these tools can be limited. Objectives: This study aimed to explore the correlation between handgrip strength (HGS) and SAD in COPD patients. Design: Cross-sectional prospective study. Methods: HGS was measured using a hand dynamometer. SAD was evaluated using impulse oscillometry, with results reported as the difference between respiratory resistance at 5 and 20 Hz (R5–R20). SAD was defined as R5–R20 ⩾0.07 kPa/L/s. The receiver operator characteristic (ROC) curves, sensitivity, and specificity values were calculated to determine the optimal cutoff value of HGS for predicting SAD. Results: Sixty-four patients (90.6% male) were included. The average age was 72.1 ± 8.3 years, and body mass index was 23.4 ± 4.2 kg/m2. FEV1 was 71.6 ± 21.3%, and HGS was 30.2 ± 8.1 kg. R5–R20 was 0.11 ± 0.08 kPa/L/s. SAD was found in 64.1% of patients. A negative correlation between HGS and R5–R20 was observed (r = −0.332, p = 0.007). The best cutoff value for HGS in detecting SAD was determined to be 28.25 kg, with a sensitivity of 73.9%, specificity of 65.9%, and an area under ROC curve of 0.685 (95% CI 0.550–0.819, p = 0.015). Conclusion: SAD is common in COPD patients, and HGS is significantly negatively correlated with SAD. This tool might serve as an alternative or adjunctive assessment for small airway dysfunction in COPD patients. Registration: This study was registered with ClinicalTrials.gov with number NCT06223139. Plain language summary: Association of handgrip strength with small airway disease in COPD In chronic obstructive pulmonary disease (COPD), the condition of small airways (those less than 2 mm wide) is closely linked to disease severity. Small airway disease (SAD) leads to reduced lung function, increased retention of excess gas in the lung, and poorer health in COPD patients. While various diagnostic methods exist for SAD, they may not always be accessible. This study investigated handgrip strength as a potential alternative way to assess SAD. Our findings show a significant negative correlation between handgrip strength and SAD in COPD patients. This suggests that handgrip strength could be used alongside existing methods to evaluate small airway dysfunction in these patients. [ABSTRACT FROM AUTHOR]

Background: Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear. Case presentation: A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25–75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV1 coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25–75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively. Conclusions: This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs. [ABSTRACT FROM AUTHOR]

Abstract Impulse oscillometry (IOS) is a sensitive tool for assessing small airway function in patients with chronic obstructive pulmonary disease (COPD). This study aimed to differentiate between COPD, small airway disease (SAD), and normal groups using IOS, and to evaluate the clinical applicability of IOS. This retrospective cohort study was conducted from January 2020 to February 2022. The eligible population comprised adult patients who simultaneously underwent IOS and pulmonary function tests. The diagnostic value of IOS in differentiating SAD and/or COPD from control was analyzed, and the correlations among IOS parameters, lung function, and radiological assessment results were determined. Among the enrolled 306 patients, 38 (12.4%) had SAD and 134 (43.8%) had COPD. The remainder comprised the control group without COPD and/or SAD. Abnormal airway resistance according to IOS parameters was detected in 17.2% of the patients in the control group, 47.2% of those in the SAD group, and 55.2% of those in the COPD group. Airway resistance estimated by IOS were significantly higher in the SAD and COPD groups than in the control group and correlated with lung function and radiological airway wall thickness. We developed a composite index called the IOS severity index (IOSsi) using IOS parameters that can predict SAD and COPD, and IOSsi showed significantly differentiation of SAD and/or COPD from control. Especially, IOSsi value ≥ 4 was associated with an increased risk of SAD and/or COPD and also with risk for moderate-to-severe exacerbation in patients with COPD. IOS may be a useful tool to differentiate disease status and evaluate disease severity and prognosis in patients with SAD and/or COPD, and a prognostic factor of COPD.

Abstract Background Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear. Case presentation A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25–75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV1 coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25–75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively. Conclusions This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs.

Although the small airway component of chronic asthma is becoming a more important topic, its impact in the daily assessment of pediatric asthma is limited. The intrinsic airway autonomic control in asthma suggests some potential mechanisms by which more distal obstruction may dominate in some situations. We suggest theoretical possibilities for small airway dominance and present clinical data supporting this possibility.

Abstract There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph

Objective: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis. Materials and methods: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Results: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15–1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Conclusions: Our results suggest that acromegaly may be associated with bronchiectasis. [ABSTRACT FROM AUTHOR]

Di Zhang,1,&ast; Yu Guan,1,&ast; Xiuxiu Zhou,1 Mingzi Zhang,2 Yu Pu,1 Pengchen Gu,2 Yi Xia,1 Yang Lu,2 Jia Chen,2 Wenting Tu,1 Kunyao Huang,2 Jixin Hou,2 Hua Yang,2 Chicheng Fu,2 Qu Fang,2 Chuan He,2 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Scientific Research Department, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan; Shiyuan Liu, Department of Radiology, Second Affiliated Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +13564684699 ; +13761304518, Fax +86 21 63587668, Email czyxfl@smmu.edu.cn; radiology_cz@163.comPurpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted.Results: The RSA and RSA% were significantly different among the three groups (p< 0.05) and related to FEV1/FVC (r = − 0.70, p < 0.001; r = − 0.67, p < 0.001), FEV1% predicted (r = − 0.60, p = 0.002; r = − 0.57, p = 0.004), MEF50% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001), MEF75% predicted (r = − 0.71, p < 0.001; r = − 0.60, p = 0.002) and MMEF 75/25% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001).Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.Keywords: COPD, small airway disease, CT, fluid dynamics

Background: Professional cycling puts significant demands on the respiratory system. Exercise-induced bronchoconstriction (EIB) is a common problem in professional athletes. Small airways may be affected in isolation or in combination with a reduction in forced expiratory volume at the first second (FEV1). This study aimed to investigate isolated exercise-induced small airway dysfunction (SAD) in professional cyclists and assess the impact of this phenomenon on exercise capacity in this population. Materials and Methods: This research was conducted on professional cyclists with no history of asthma or atopy. Anthropometric characteristics were recorded, the training age was determined, and spirometry and specific markers, such as fractional exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), were measured for all participants. All of the cyclists underwent cardiopulmonary exercise testing (CPET) followed by spirometry. Results: Compared with the controls, 1-FEV3/FVC (the fraction of the FVC that was not expired during the first 3 s of the FVC) was greater in athletes with EIB, but also in those with isolated exercise-induced SAD. The exercise capacity was lower in cyclists with isolated exercise-induced SAD than in the controls, but was similar to that in cyclists with EIB. This phenomenon appeared to be associated with a worse ventilatory reserve (VE/MVV%). Conclusions: According to our data, it appears that professional cyclists may experience no beneficial impacts on their respiratory system. Strenuous endurance exercise can induce airway injury, which is followed by a restorative process. The repeated cycle of injury and repair can trigger the release of pro-inflammatory mediators, the disruption of the airway epithelial barrier, and plasma exudation, which gradually give rise to airway hyper-responsiveness, exercise-induced bronchoconstriction, intrabronchial inflammation, peribronchial fibrosis, and respiratory symptoms. The small airways may be affected in isolation or in combination with a reduction in FEV1. Cyclists with isolated exercise-induced SAD had lower exercise capacity than those in the control group. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. METHODS: Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. RESULTS: A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. CONCLUSION: We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.

ObjectiveThis study aimed to evaluate the efficacy of bronchoalveolar lavage (BAL) in the treatment of children with small airway diseases.MethodsChildren [n = 112; boys: 76, girls: 36 (ratio 2.1:1); age range: 1 month–10 years; median age: 12 months] with small airway diseases diagnosed by high-resolution computed tomography (HRCT) were enrolled in this study. The patients were assigned to either the BAL group (BAL and conventional therapy) or the control group (conventional therapy only). The duration of cough, fever, wheezing, hospitalization duration, disease course before admission, treatment cost, HRCT recovery time, and re-hospitalization rate were compared between the two groups.ResultsThe median disease course before admission of the BAL group patients was longer than that of the controls (p = 0.006). The duration of cough and wheezing in the BAL group was significantly longer than that in the control group (p = 0.012 and p = 0.001, respectively). The recovery time of cough, the re-hospitalization rate, and the total expenditure incurred for the BAL group were lower than those for the control group (p = 0.027, p = 0.026, and p = 0.000, respectively). At 2 months after discharge, the small airway lesions were found to be absorbed in 86.2% of BAL group patients vs. 64.1% of control group patients. At 6 months after discharge, the lesions were not fully absorbed in 3.4% of the BAL group patients compared to 20.5% in the control group patients.ConclusionBAL is suitable for patients with a long disease course before admission, a long duration of coughing, and recurrent wheezing. BAL treatment of small airway diseases in children can promote the disappearance of clinical symptoms, accelerate the improvement of imaging, reduce the rate of re-hospitalization, and reduce the cost of treatment.

Abstract Objective Diagnosis of small airway disease on computed tomography (CT) scans is challenging in patients with a history of chemical warfare exposure. We developed a software package based on different methodologies to identify and quantify small airway disease in CT images. The primary aim was to identify the best automatic methodology for detecting small airway disease in CT scans of Iran-Iraq War victims of chemical warfare. Methods This retrospective case–control study enrolled 46 patients with a history of chemical warfare exposure and 27 controls with inspiratory/expiratory (I/E) CT scans and spirometry tests. Image data were automatically segmented, and inspiratory images were registered into the expiratory images' frame using the locally developed software. Parametric response mapping (PRM) and air trapping index (ATI) mapping were performed on the CT images. Conventional QCT methods, including expiratory/inspiratory mean lung attenuation (E/I MLA) ratio, normal density E/I (ND E/I) MLA ratio, attenuation volume Index (AVI), %low attenuation areas (LAA)

Abstract Background Small airways disease (SAD), a novel finding described in post-acute COVID-19 patients, should be suspected when respiratory symptoms continue, air trapping persists on expiratory CT scans, and imaging findings fail to improve despite objectively better conventional pulmonary function test (PFT) parameters. The forced oscillation technique (FOT) and Multiple breathing washout (MBW) are both very sensitive methods for detecting anomalies in the peripheral airways. Case presentation We discuss the case of a 60-year-old Hispanic patient who had severe COVID-19 pneumonia and developed dyspnea, fatigue, and limited daily activity a year later. The PFTs revealed restrictive lung disease, as seen by significant diffusing capacity of the lungs for carbon monoxide (DLCO) decrease, severe desaturation, and poor 6-min walk test (6MWT) performance. The patient was treated with lowering corticosteroids as well as pulmonary rehabilitation (PR). During the 24-month follow-up, the dyspnea and fatigue persisted. On PFTs, 6MWT performance and restricted pattern improved slightly, but MBW discovered significant ventilatory inhomogeneity. FOT revealed substantial peripheral airway obstructive abnormalities. On CT scans, air trapping and ground-glass opacities (GGO) improved somewhat. The patient used a bronchodilator twice a day and low-dose inhaled corticosteroids (160 µg of budesonide and 4.5 µg of formoterol fumarate dihydrate) for nine months. PR sessions were resuming. The restricting parameters were stabilized and the DLCO had normalized after 36 months, with a 6MWT performance of 87% but significant desaturation. The CT scan revealed traction bronchiectasis, low GGO, and persistent air trapping. Without normalization, FOT and MBW scores improved, indicating small airway disease. Conclusions The necessity of integrating these tests when detecting SAD is emphasized in our paper. This article lays the foundation for future research into the best ways to manage and monitor SAD in post-acute COVID-19 patients.

Abstract Background We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. Methods We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. Results In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. Conclusion Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.

PurposeTo develop a convolutional neural network (CNN)-based deformable lung registration algorithm to reduce computation time and assess its potential for lobar air trapping quantification.Materials and methodsIn this retrospective study, a CNN algorithm was developed to perform deformable registration of lung CT (LungReg) using data on 9118 patients from the COPDGene Study (data collected between 2007 and 2012). Loss function constraints included cross-correlation, displacement field regularization, lobar segmentation overlap, and the Jacobian determinant. LungReg was compared with a standard diffeomorphic registration (SyN) for lobar Dice overlap, percentage voxels with nonpositive Jacobian determinants, and inference runtime using paired t tests. Landmark colocalization error (LCE) across 10 patients was compared using a random effects model. Agreement between LungReg and SyN air trapping measurements was assessed using intraclass correlation coefficient. The ability of LungReg versus SyN emphysema and air trapping measurements to predict Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages was compared using area under the receiver operating characteristic curves.ResultsAverage performance of LungReg versus SyN showed lobar Dice overlap score of 0.91-0.97 versus 0.89-0.95, respectively (P < .001); percentage voxels with nonpositive Jacobian determinant of 0.04 versus 0.10, respectively (P < .001); inference run time of 0.99 second (graphics processing unit) and 2.27 seconds (central processing unit) versus 418.46 seconds (central processing unit) (P < .001); and LCE of 7.21 mm versus 6.93 mm (P < .001). LungReg and SyN whole-lung and lobar air trapping measurements achieved excellent agreement (intraclass correlation coefficients > 0.98). LungReg versus SyN area under the receiver operating characteristic curves for predicting GOLD stage were not statistically different (range, 0.88-0.95 vs 0.88-0.95, respectively; P = .31-.95).ConclusionCNN-based deformable lung registration is accurate and fully automated, with runtime feasible for clinical lobar air trapping quantification, and has potential to improve diagnosis of small airway diseases.Keywords: Air Trapping, Convolutional Neural Network, Deformable Registration, Small Airway Disease, CT, Lung, Semisupervised Learning, Unsupervised Learning Supplemental material is available for this article. © RSNA, 2021 An earlier incorrect version of this article appeared online. This article was corrected on December 22, 2021.

Abstract Objective To investigated the dynamic ventilatory responses and their influence on functional exercise capacity in patients with long-COVID-19 syndrome (LCS). Results Sixteen LCS patients were subjected to resting lung function (spirometry and respiratory oscillometry-RO) and cardiopulmonary performance to exercise (Spiropalm®-equipped six-minute walk test-6MWT and cardiopulmonary exercise test-CPX). At rest, spirometry showed a normal, restrictive and obstructive pattern in 87.5%, 6.25% and 6.25% of participants, respectively. At rest, RO showed increased resonance frequency, increased integrated low-frequency reactance and increased difference between resistance at 4–20 Hz (R4-R20) in 43.7%, 50%, and 31.2% of participants, respectively. The median of six-minute walking distance (DTC6) was 434 (386–478) m, which corresponds to a value of 83% (78–97%) of predicted. Dynamic hyperinflation (DH) and reduced breathing reserve (BR) were detected in 62.5% and 12.5% of participants, respectively. At CPX, the median peak oxygen uptake (VO2peak) was 19 (14–37) ml/kg/min. There was a significant correlation of 6MWD with both R4-R20 (rs=-0.499, P = 0.039) and VO2peak (rs=0.628, P = 0.009). Our results indicate that DH and low BR are contributors to poor exercise performance, which is associated with peripheral airway disease. These are promising results considering that they were achieved with simple, portable ventilatory and metabolic systems.

Objective: Diagnosis of small airway disease on computed tomography (CT) scans is challenging in patients with a history of chemical warfare exposure. We developed a software package based on different methodologies to identify and quantify small airway disease in CT images. The primary aim was to identify the best automatic methodology for detecting small airway disease in CT scans of Iran-Iraq War victims of chemical warfare. Methods: This retrospective case–control study enrolled 46 patients with a history of chemical warfare exposure and 27 controls with inspiratory/expiratory (I/E) CT scans and spirometry tests. Image data were automatically segmented, and inspiratory images were registered into the expiratory images' frame using the locally developed software. Parametric response mapping (PRM) and air trapping index (ATI) mapping were performed on the CT images. Conventional QCT methods, including expiratory/inspiratory mean lung attenuation (E/I MLA) ratio, normal density E/I (ND E/I) MLA ratio, attenuation volume Index (AVI), %low attenuation areas (LAA) < -856 in exhale scans, and %LAA < -950 in inhale scans were also computed. QCT measurements were correlated with spirometry results and compared across the two study groups. Results: The correlation analysis showed a significant negative relationship between three air trapping (AT) measurements (PRM, ATI, and %LAAExp < -856) and spirometry parameters (Fev1, Fvc, Fev1/Fvc, and MMEF). Moreover, %LAAExp < -856 had the highest significant negative correlation with Fev1/Fvc (r = -0.643, P-value < 0.001). Three AT measurements demonstrated a significant difference between the study groups. The E/I ratio was also significantly different between the two groups (P-value < 0.001). Binary logistic regression models showed PRMFsad, %LAAExp < -856, and ATI as significant and strong predictors of the study outcome. Optimal cut-points for PRMFsad = 19%, %LAAExp < -856 = 23%, and ATI = 27% were identified to classify the participants into two groups with high accuracy. Conclusion: QCT methods, including PRM, ATI, and %LAAExp < -856 can greatly advance the identification and quantification of SAD in chemical warfare victims. The results should be verified in well-designed prospective studies involving a large population. [ABSTRACT FROM AUTHOR]

Background: Small airways disease (SAD), a novel finding described in post-acute COVID-19 patients, should be suspected when respiratory symptoms continue, air trapping persists on expiratory CT scans, and imaging findings fail to improve despite objectively better conventional pulmonary function test (PFT) parameters. The forced oscillation technique (FOT) and Multiple breathing washout (MBW) are both very sensitive methods for detecting anomalies in the peripheral airways. Case presentation: We discuss the case of a 60-year-old Hispanic patient who had severe COVID-19 pneumonia and developed dyspnea, fatigue, and limited daily activity a year later. The PFTs revealed restrictive lung disease, as seen by significant diffusing capacity of the lungs for carbon monoxide (DLCO) decrease, severe desaturation, and poor 6-min walk test (6MWT) performance. The patient was treated with lowering corticosteroids as well as pulmonary rehabilitation (PR). During the 24-month follow-up, the dyspnea and fatigue persisted. On PFTs, 6MWT performance and restricted pattern improved slightly, but MBW discovered significant ventilatory inhomogeneity. FOT revealed substantial peripheral airway obstructive abnormalities. On CT scans, air trapping and ground-glass opacities (GGO) improved somewhat. The patient used a bronchodilator twice a day and low-dose inhaled corticosteroids (160 µg of budesonide and 4.5 µg of formoterol fumarate dihydrate) for nine months. PR sessions were resuming. The restricting parameters were stabilized and the DLCO had normalized after 36 months, with a 6MWT performance of 87% but significant desaturation. The CT scan revealed traction bronchiectasis, low GGO, and persistent air trapping. Without normalization, FOT and MBW scores improved, indicating small airway disease. Conclusions: The necessity of integrating these tests when detecting SAD is emphasized in our paper. This article lays the foundation for future research into the best ways to manage and monitor SAD in post-acute COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. Methods: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. Results: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. Conclusion: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients. [ABSTRACT FROM AUTHOR]

Maximum mid-expiratory flow (MMEF) is one of the pulmonary function tests that report small airway disease. Our study aimed to investigate the role of MMEF values in asthma control, the prevalence of small airway disease, and their effect on asthma control in patients with asthma with normal forced expiratory volume in one second (FEV1) values. Patients who presented to the Chest Diseases outpatient clinic of our hospital between 2018 and 2019 and were diagnosed as having asthma were included in the study. The characteristics of the patients, pulmonary function tests, their asthma treatment, and asthma control test (ACT) scores were recorded. Patients with FEV1 <80 in the pulmonary function test, those with additional lung disease, those who had an attack in the last 4 weeks, and patients who smoked were excluded from the study. MMEF <65 was defined as small airway disease. The MMEF% and MMEF (L/s) values of the group with uncontrolled asthma were found to be statistically significantly lower than those of the controlled asthma group (p = 0.016 and p = 0.003, respectively). MMEF% and MMEF (L/s) values in those with wheezing were found to be significantly lower compared with those without wheezing (p = 0.025 and p = 0.049, respectively). The MMEF% and MMEF (L/s) values of the patients with nocturnal symptoms were found to be statistically significantly lower than in patients without nocturnal symptoms (p = 0.023 and p = 0.041, respectively). ACT values of patients with MMEF <65 were found to be statistically lower than those of patients with MMEF >65 (0.047). Considering small airway disease in patients with asthma may be beneficial in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To investigated the dynamic ventilatory responses and their influence on functional exercise capacity in patients with long-COVID-19 syndrome (LCS). Results: Sixteen LCS patients were subjected to resting lung function (spirometry and respiratory oscillometry-RO) and cardiopulmonary performance to exercise (Spiropalm®-equipped six-minute walk test-6MWT and cardiopulmonary exercise test-CPX). At rest, spirometry showed a normal, restrictive and obstructive pattern in 87.5%, 6.25% and 6.25% of participants, respectively. At rest, RO showed increased resonance frequency, increased integrated low-frequency reactance and increased difference between resistance at 4–20 Hz (R4-R20) in 43.7%, 50%, and 31.2% of participants, respectively. The median of six-minute walking distance (DTC6) was 434 (386–478) m, which corresponds to a value of 83% (78–97%) of predicted. Dynamic hyperinflation (DH) and reduced breathing reserve (BR) were detected in 62.5% and 12.5% of participants, respectively. At CPX, the median peak oxygen uptake (VO2peak) was 19 (14–37) ml/kg/min. There was a significant correlation of 6MWD with both R4-R20 (rs=-0.499, P = 0.039) and VO2peak (rs=0.628, P = 0.009). Our results indicate that DH and low BR are contributors to poor exercise performance, which is associated with peripheral airway disease. These are promising results considering that they were achieved with simple, portable ventilatory and metabolic systems. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease. Not all patients with COPD respond to available drugs. Identifying respondents to therapy is critical to delivering the most appropriate treatment and avoiding unnecessary medication. Recognition of individual patients’ dominant characteristics by phenotype is a useful tool to better understand their disease and tailor treatment accordingly. To look for a suitable phenotype, it is important to understand what makes COPD complex and heterogeneous. The pathology of COPD includes small airway disease and/or emphysema. Thus, COPD is not a single disease entity. In addition, there are two types (panlobular and centrilobular) of emphysema in COPD. The coexistence of different pathological subtypes could be the reason for the complexity and heterogeneity of COPD. Thus, it is necessary to look for the phenotype based on the difference in the underlying pathology. Review of the literature has shown that clinical manifestation and therapeutic response to pharmacological therapy are different depending on the presence of computed tomography–defined airway wall thickening in COPD patients. Defining the phenotype of COPD based on the underlying pathology is encouraging as most clinical manifestations can be distinguished by the presence of increased airway wall thickness. Pharmacological therapy has shown significant effect on COPD with airway wall thickening. However, it has limited use in COPD without an airway disease. The phenotype of COPD based on the underlying pathology can be a useful tool to better understand the disease and adjust treatment accordingly.

Summary: Background: After COVID-19 infection, persistent exercise intolerance, changes in lung function have been shown. Our aim is to investigate the correlation between impulse oscillometry (IOS) parameters and exercise capacity by using incremental and endurance shuttle walk tests (ISWT, ESWT) and investigate the factors and parameters which might have an effect on both IOS parameters and exercise capacity tests. Method: The patients who had a history of COVID-19 were enrolled into cross-sectional study according to inclusion criteria. The IOS parameters, ISWT, ESWT, smoking status, time since COVID-19 diagnosis, length of hospital stay, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), body mass index (BMI), fat-free mass index (FFMI), dyspnea, hospital anxiety-depression and fatigue severity scores were recorded. Results: The study comprised 72 patients, 71% of whom were male, with a mean age of 54 ± 10 years. After COVID-19 diagnosis, the median duration was 3 (min: 1, max: 5) months and 51 (71%) of the patients were hospitalized. The FEV1 and FVC values were in normal range. The area of reactance (AX), resonance frequency (Fres), reactance at 20 Hz (X20) and the difference between resonance at 20 and 5 Hz (R5–20) correlated with both ISWT and ESWT. The FEV1 correlated with all IOS parameters (p < 0.05). Reactance correlated with FFMI (p = 024, r = 0.267), different according to hospitalization (p = 0.02). Conclusion: In COVID-19 survivors, there could be correlations between IOS parameters and exercise capacity; and between these parameters and FEV and FVC. Furthermore, small airway disease with normal spirometric functions could be related to decreased exercise capacity in COVID-19 survivors regardless of concomitant diseases, BMI, smoking status and time since COVID-19 diagnosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Small airway dysfunction is a pathological component of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), and impulse oscillometry is an easy-to-administer, effort-independent non-invasive test reflecting small airway dysfunction. We aimed to compare the impulse oscillometry (IOS) measurements between COPD and IPF patients and investigate their correlation with severity of both diseases and other conventional parameters. PATIENTS AND METHODS: This was a prospective, longitudinal study. We longitudinally evaluated the baseline demographic characteristics, COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale, Pulmonary Function Test (PFT), Carbon Monoxide Diffusing Capacity (DLCO), Hemogram and Impulse Oscillometry measurements of the patients diagnosed with COPD and IPF. RESULTS: The study included 60 IPF patients and 48 COPD patients. The CAT and mMRC scores were higher in COPD patients. The majority of COPD patients were classified into Category B (46%), while 68% of IPF patients had Stage 1 GAP. The mean FEF 25-75%, which is typically considered to reflect small airway disease, was 93% in IPF patients, while it was significantly lower in COPD patients (29%). Impulse oscillometry measurements were consistent with spirometry parameters. IOS resistance and reactance values were significantly higher in COPD patients than in IPF patients. CONCLUSIONS: IOS is advantageous in COPD and IPF patients who cannot exhale due to severe dyspnea, as it is easy to administer and reflects small airway resistance better. Diagnosis of small airway dysfunction may be beneficial in the management of patients with IPF and COPD. [ABSTRACT FROM AUTHOR]

BackgroundAerobika® oscillating positive expiratory pressure (OPEP) device promotes airway clearance in many respiratory diseases. However, studies have yet to focus on its effectiveness in improving small airway resistance via impulse oscillometry (IOS) measurement in COPD subjects. We aim to evaluate the improvement of small airway resistance (via IOS), lung function (spirometry), exercise capacity [via 6-min walking test (6MWT)], symptoms [COPD assessment test (CAT)] and severe exacerbation events among COPD subjects using Aerobika® OPEP.MethodsThis was a prospective, single-arm interventional study among COPD subjects with small airway disease. Subjects were instructed to use twice daily Aerobika® OPEP (10 min each session); for 24 weeks; as an additional to standard therapy. IOS, spirometry, 6MWT, CAT score and severe exacerbation events were evaluated at baseline, 12 weeks and 24 weeks.ResultsFifty-three subjects completed the study. Aerobika® usage showed improvement of IOS parameters; e.g. measurement of airway resistance at 5 Hz (R5), cmH20/L/s, (12-week p = 0.008, 24-week p

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Background: The small airway disease has been recognized as a central feature of chronic obstructive pulmonary disease (COPD). Triple fixed combination beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) is provided as a pressurized single-dose inhaler based on an extra-fine formulation, which has been approved for patients with COPD experiencing frequent disease exacerbations. Methods: The aim of our real-life single-center observational study was to investigate, in 22 patients with COPD, the effects of BDP/FF/G on lung function, respiratory symptoms, health status, and exacerbation rate. Several clinical and lung functional parameters were evaluated at baseline and after 12 months of treatment with combined inhaled triple therapy. Results: With respect to baseline, after 12 months of treatment with BDP/FF/G, significant changes were recorded with regard to forced expiratory flow at 75% of forced vital capacity (FVC) (p < 0.01), forced expiratory flow at 50% of FVC (p < 0.01), forced expiratory flow at 25% of FVC (p < 0.05), and forced mid-expiratory flow between 25% and 75% of FVC (p < 0.01). Moreover, we observed reductions of total resistance (p < 0.01), effective resistance (p < 0.01), and effective specific resistance (p < 0.01). In the same period, residual volume diminished (p < 0.01) and forced expiratory volume in 1 s increased (p < 0.01). Moreover, in a subgroup of 16 patients, an enhancement of diffusion lung capacity (p < 0.01) was also detected. These functional results were paralleled by concomitant clinical effects, as evidenced by the improvements of modified British Medical Research Council (mMRC) dyspnea scale (p < 0.001), COPD Assessment Test (CAT) score (p < 0.0001), and COPD exacerbations (p < 0.0001). Conclusion: In conclusion, the valuable findings of our observational study consist in the corroboration in a real-life context of the therapeutic effects evidenced by randomized controlled trials with regard to the use of the triple inhaled BDP/FF/G therapy in patients with COPD. [ABSTRACT FROM AUTHOR]

Purpose: Available clinical data have revealed that coronavirus disease 2019 (COVID-19) is associated with a risk of pulmonary microthrombosis and small airway disease. These patients present with varying degrees of perfusion abnormalities. The purpose of this study was to evaluate the use of a ventilation/perfusion single-photon emission computed tomography/computed tomography (VQ SPECT/CT) in the detection and follow-up of persistent lung perfusion abnormalities that were suspected to be due to pulmonary microthrombosis, small airway disease, or both. Methods : A retrospective study was conducted at the department of nuclear medicine of Universitas Academic Hospital in Bloemfontein, South Africa. We reviewed the studies of 78 non-hospitalized patients with COVID-19 infection referred to our department from July 2020 to June 2021 for a perfusion only SPECT/CT study or a VQ SPECT/CT study. Pulmonary embolism was suspected in all 78 cases. Results: Seventy-eight patients were studied. The median (interquartile range) age was 45 (41–58) years, and the majority (n = 69; 88.5%) were females. Twenty-two (28.2%) of these patients had matching VQ defects with mosaic attenuation on CT. All nine of the patients who had follow-up studies had these abnormalities persistently, even after 1 year. Conclusion: We confirm that the VQ scan is a safe and effective tool to identify and follow-up recovered COVID-19 patients with persistent ventilation and perfusion abnormalities suspicious of small airway disease and pulmonary microthrombosis. [ABSTRACT FROM AUTHOR]

Abstract Objective Exercise has been demonstrated to be beneficial for improving physical capacity and quality of life in people with scleroderma, although knowledge of its impact on the respiratory system is limited. This study evaluated the impact of therapist-oriented home rehabilitation (TOHR) on impulse oscillometry (IOS) and lung ultrasound (LUS) findings in patients with scleroderma-associated interstitial lung disease (ILD). Results Twelve women with scleroderma underwent spirometry, IOS, and LUS before and after performing TOHR. Regarding spirometry, a normal pattern and restrictive damage were observed in five (41.7%) and seven (58.3%) participants pre-TOHR and post-TOHR, respectively. For IOS, an abnormal result was detected in nine (75%) pre-TOHR participants and six (50%) post-TOHR participants. Heterogeneity of resistance between 4–20 Hz (R4-R20) > 20% of the predicted value was observed in eight (66.7%) pre-TOHR participants and three (25%) post-TOHR participants (P = 0.031). An abnormal LUS result was observed in nine (75%) participants both pre-TOHR and post-TOHR. The main change observed was B-lines > 2, which was noted in nine (75%) participants both pre-TOHR and post-TOHR. Our findings suggest that TOHR for women with scleroderma-associated ILD improves the resistance and reactance measured by IOS, including small airway disease. Trial Registration ClinicalTrials.gov ID: NCT05041868 Registered on: 13th September 2021.

Abstract Background Cystinosis is a rare autosomal recessive disorder involving lysosomal storage of the amino acid cystine due to a defect in the membrane transport protein, cystinosin. The disease results in intracellular accumulation of cystine in all organs and tissues. Pulmonary complications targeting the respiratory system occurs commonly in adults who have not received lifelong cysteamine therapy. The respiratory insufficiency is fatal at adulthood. However, little is known about the pulmonary dysfunction in children. The study included 15 nephropathic cystinosis children to evaluate the pulmonary complications through detailed history taking, clinical examination, chest radiograph and Pulmonary function test (Impulse oscillometry {IOS}). Results Out of the cohort of 15 cystinosis patients, 13 patients did not show symptoms suggestive of chest affection. While 1 patient had recurrent Aspiration and 1 patient had history of pneumonia requiring hospital admission. All patients showed normal respiratory rate for age, normal breath sound and normal Chest X-ray finding apart from conical chest configuration. IOS done showed small airway disease in 12 patients, decreased compliance in 2 patients, while only 1patient had normal IOS. Conclusion Small airway affection was detected in most of cystinosis children by means of IOS in spite of the absence of chest manifestations and suggestive history which highlight the importance of respiratory assessment and follow up of cystinosis patients not only by history, and examination but most important pulmonary function tests.

We previously reported pulmonary arterial remodelling and active endothelial-to-mesenchymal transition (EndMT) in smokers and patients with early chronic obstructive pulmonary disease (COPD). In the present study, we aimed to evaluate the role of different drivers of EndMT. Immunohistochemical staining for EndMT drivers, TGF-β1, pSMAD-2/3, SMAD-7, and β-catenin, was performed on lung resections from 46 subjects. Twelve were non-smoker-controls (NC), six normal lung function smokers (NLFS), nine patients with small-airway diseases (SAD), nine mild-moderate COPD-current smokers (COPD-CS) and ten COPD-ex-smokers (COPD-ES). Histopathological measurements were done using Image ProPlus softwarev7.0. We observed lower levels of total TGF-β1 (P<0.05) in all smoking groups than in the non-smoking control (NC). Across arterial sizes, smoking groups exhibited significantly higher (P<0.05) total and individual layer pSMAD-2/3 and SMAD-7 than in the NC group. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared with NC. Total β-catenin expression was significantly higher in smoking groups across arterial sizes (P<0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased total β-catenin was positively correlated with total S100A4 in small and medium arteries (r = 0.35, 0.50; P=0.02, 0.01, respectively), with Vimentin in medium arteries (r = 0.42, P=0.07), and with arterial thickness of medium and large arteries (r = 0.34, 0.41, P=0.02, 0.01, respectively). This is the first study uncovering active endothelial SMAD pathway independent of TGF-β1 in smokers, SAD, and COPD patients. Increased expression of β-catenin indicates its potential interaction with SMAD pathway, warranting further research to identify the deviation of this classical pathway., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Rationale: Constrictive bronchiolitis (ConB) is a relatively rare and understudied form of lung disease whose underlying immunopathology remains incompletely defined. Objectives: Our objectives were to quantify specific pathological features that differentiate ConB from other diseases that affect the small airways and to investigate the underlying immune and inflammatory phenotype present in ConB. Methods: We performed a comparative histomorphometric analysis of small airways in lung biopsy samples collected from 50 soldiers with postdeployment ConB, 8 patients with sporadic ConB, 55 patients with chronic obstructive pulmonary disease, and 25 nondiseased control subjects. We measured immune and inflammatory gene expression in lung tissue using the NanoString nCounter Immunology Panel from six control subjects, six soldiers with ConB, and six patients with sporadic ConB. Measurements and Main Results: Compared with control subjects, we found shared pathological changes in small airways from soldiers with postdeployment ConB and patients with sporadic ConB, including increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and lymphocyte infiltration. Using principal-component analysis, we showed that ConB pathology was clearly separable both from control lungs and from small airway disease associated with chronic obstructive pulmonary disease. NanoString gene expression analysis from lung tissue revealed T-cell activation in both groups of patients with ConB with upregulation of proinflammatory pathways, including cytokine-cytokine receptor interactions, NF-κB (nuclear factor-κB) signaling, TLR (Toll-like receptor) signaling, T-cell receptor signaling, and antigen processing and presentation. Conclusions: These findings indicate shared immunopathology among different forms of ConB and suggest that an ongoing T-helper cell type 1-type adaptive immune response underlies airway wall remodeling in ConB. [ABSTRACT FROM AUTHOR]

Excessive decrease in the flow of the late expiratory portion of a flow volume loop (FVL) or "flattening", reflects small airway dysfunction. The assessment of the flattening is currently determined by visual inspection by the pulmonary function test (PFT) interpreters and is highly variable. In this study, we developed an objective measure to quantify the flattening. We downloaded 172 PFT reports in PDF format from the electronic medical records and digitized and extracted the expiratory portion of the FVL. We located point A (the point of the peak expiratory flow), point B (the point corresponding to 75% of the expiratory vital capacity), and point C (the end of the expiratory portion of the FVL intersecting with the x -axis). We did a linear fitting to the A-B segment and the B-C segment. We calculated: 1) the AB-BC angle (∠ABC), 2) BC- x -axis angle (∠BCX), and 3) the log ratio of the BC slope over the vertical distance between point A and x -axis [log (BC/A-x)]. We asked an expert pulmonologist to assess the FVLs and separated the 172 PFTs into the flattening and the non-flattening groups. We defined the cutoff value as the mean minus one standard deviation using data from the non-flattening group. ∠ABC had the best concordance rate of 80.2% with a cutoff value of 149.7°. We then asked eight pulmonologists to evaluate the flattening with and without ∠ABC in another 168 PFTs. The Fleiss' kappa was 0.320 (lower and upper confidence intervals [CIs]: 0.293 and 0.348 respectively) without ∠ABC and increased to 0.522 (lower and upper CIs: 0.494 and 0.550) with ∠ABC. There were 147 CT scans performed within 6 months of the 172 PFTs. Twenty-six of 55 PFTs (47.3%) with ∠ABC <149.7° had CT scans showing small airway disease patterns while 44 of 92 PFTs (47.8%) with ∠ABC ≥149.7° had no CT evidence of small airway disease. We concluded that ∠ABC improved the inter-rater agreement on the presence of the late expiratory flattening in FVL. It could be a useful addition to the assessment of small airway disease in the PFT interpretation algorithm and reporting. [ABSTRACT FROM AUTHOR]

Abstract Background Physical effort is capable of triggering airway obstruction in asthmatics, the so-called exercise-induced bronchoconstriction in asthma (EIBa). This study was performed in subjects with mild persistent asthma, aiming to find predictors for developing EIBa. Methods In 20 subjects with mild asthma, measurements of baseline functional respiratory parameters and airways responsiveness by a methacholine challenge were obtained on the first day. A maximal, symptom-limited incremental cardiopulmonary exercise test (CPExT) was performed the day after, with subsequent, repeated maneuvers of maximal full forced expiration to monitor the FEV1 change at 1,3,5,7,10 and 15 min after the end of the exercise. Results 19 subjects completed the two-days protocol. No functional parameters both at rest and during effort were useful to predict EIBa after stopping exercise. In asthmatics with EIBa, mean Inspiratory Capacity (IC) did not increase with increasing ventilatory requirements during CPExT because 6 of them (50%) displayed dynamic pulmonary hyperinflation (DH), as documented by their progressive increase of end-expiratory lung volume. This subgroup, showing earlier post-exercise FEV1 fall, had significantly lower forced mean expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) at rest (p

Excessive decrease in the flow of the late expiratory portion of a flow volume loop (FVL) or “flattening”, reflects small airway dysfunction. The assessment of the flattening is currently determined by visual inspection by the pulmonary function test (PFT) interpreters and is highly variable. In this study, we developed an objective measure to quantify the flattening. We downloaded 172 PFT reports in PDF format from the electronic medical records and digitized and extracted the expiratory portion of the FVL. We located point A (the point of the peak expiratory flow), point B (the point corresponding to 75% of the expiratory vital capacity), and point C (the end of the expiratory portion of the FVL intersecting with the x-axis). We did a linear fitting to the A-B segment and the B-C segment. We calculated: 1) the AB-BC angle (∠ABC), 2) BC-x-axis angle (∠BCX), and 3) the log ratio of the BC slope over the vertical distance between point A and x-axis [log (BC/A-x)]. We asked an expert pulmonologist to assess the FVLs and separated the 172 PFTs into the flattening and the non-flattening groups. We defined the cutoff value as the mean minus one standard deviation using data from the non-flattening group. ∠ABC had the best concordance rate of 80.2% with a cutoff value of 149.7°. We then asked eight pulmonologists to evaluate the flattening with and without ∠ABC in another 168 PFTs. The Fleiss’ kappa was 0.320 (lower and upper confidence intervals [CIs]: 0.293 and 0.348 respectively) without ∠ABC and increased to 0.522 (lower and upper CIs: 0.494 and 0.550) with ∠ABC. There were 147 CT scans performed within 6 months of the 172 PFTs. Twenty-six of 55 PFTs (47.3%) with ∠ABC

Objective: Exercise has been demonstrated to be beneficial for improving physical capacity and quality of life in people with scleroderma, although knowledge of its impact on the respiratory system is limited. This study evaluated the impact of therapist-oriented home rehabilitation (TOHR) on impulse oscillometry (IOS) and lung ultrasound (LUS) findings in patients with scleroderma-associated interstitial lung disease (ILD). Results: Twelve women with scleroderma underwent spirometry, IOS, and LUS before and after performing TOHR. Regarding spirometry, a normal pattern and restrictive damage were observed in five (41.7%) and seven (58.3%) participants pre-TOHR and post-TOHR, respectively. For IOS, an abnormal result was detected in nine (75%) pre-TOHR participants and six (50%) post-TOHR participants. Heterogeneity of resistance between 4–20 Hz (R4-R20) > 20% of the predicted value was observed in eight (66.7%) pre-TOHR participants and three (25%) post-TOHR participants (P = 0.031). An abnormal LUS result was observed in nine (75%) participants both pre-TOHR and post-TOHR. The main change observed was B-lines > 2, which was noted in nine (75%) participants both pre-TOHR and post-TOHR. Our findings suggest that TOHR for women with scleroderma-associated ILD improves the resistance and reactance measured by IOS, including small airway disease. Trial Registration ClinicalTrials.gov ID: NCT05041868 Registered on: 13th September 2021. [ABSTRACT FROM AUTHOR]

Asthma affects all portions of the airways. Small airways, however, comprise a substantial component of the conducting lung air flow. In asthma, inflammatory processes can affect the whole respiratory tract, from central to peripheral/small airways. The emphasis in adult and pediatric respiratory disease clinics is to focus on large airway obstruction and reversibility. This information, although valuable, underemphasizes a large portion of the conduction airway of asthmatics. Standard descriptions of asthma management focus on a multiple medication approaches. We particularly focused on the management of asthma in the international guidelines for the Global Initiative for Asthma (GINA). Overall, however, minimal attention is placed on the small airway pool in asthma medical management. We took the opportunity to thoroughly review and present specific data from the adult asthma literature which supported the concept that small airway abnormalities may play a role in the pathogenesis and clinical expression of asthma. Based on the conclusions of the adult asthma literature, we here present a thorough review of the literature as it relates to small airway disease in children with asthma. We used, collectively, individual data sources of data to expand the information available from standard diagnostic techniques, especially spirometry, in the evaluation of small airway disease. As the pharmacological approaches to moderate to severe asthma are advancing rapidly into the realm of biologics, we sought to present potential pharmacological options for small airway dysfunction in pediatrics prior to biological modifier intervention. [ABSTRACT FROM AUTHOR]

Abstract Background Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype. We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers. Methods Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function. Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods. Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients. Results Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry (p

Kun Li,1,* Yanli Gao,1,* Zhenyu Pan,1 Xiuqin Jia,1 Yuchang Yan,1 Xiaohong Min,1 Kewu Huang,2 Tao Jiang1 1Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, Republic of China; 2Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao JiangDepartment of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel +86 13718875778Fax +86 1065935237Email jiangt8166@hotmail.comPurpose: To explore the influence of emphysema and air trapping heterogeneity on pulmonary function changes in patients with stable chronic obstructive pulmonary disease (COPD).Patients and methods: One hundred and seventy-nine patients with stable COPD were enrolled in this prospective study. All patients underwent low-dose inspiratory and expiratory CT scanning and pulmonary-function tests. CT quantitative data for the emphysema index (EI) on full-inspiration and air trapping (AT) on full-expiration were measured for the whole lung, the right and left lungs, and the cranial-caudal lung zones. The heterogeneity index (HI) values for emphysema and air trapping were determined as the ratio of the difference to the sum of the respective indexes. The cranial-caudal HI and left–right lung HI were compared between mild-to-moderate (GOLD stage I and II) and severe (GOLD stage III and IV) disease groups. The associations between HI and pulmonary-function measurements adjusted for age, sex, height, smoking history, EI and AT of the total lung were assessed using multiple linear regression analysis.Results: The absolute values for cranial-caudal HI (AT_CC_HI) and left–right lung HI (AT_LR_HI) on full-expiration were significantly larger in the mild-to-moderate group, while no significant intergroup differences were observed on full-inspiration. COPD patients with lower-zone and/or left-lung predominance showed significantly lower pulmonary function than those with upper-zone and/or right-lung predominance on full-expiration, whereas no significant differences were observed on full-inspiration. The absolute values of AT_CC_HI and AT_LR_HI significantly correlated with pulmonary-function measurements. Higher AT_CC_HI and lower AT_LR_HI absolute values indicated better pulmonary function, after adjusting for age, sex, height, smoking history, EI and AT of the total lung.Conclusion: Subjects with more heterogeneous distribution and/or upper-zone predominant and/or right-lung predominant patterns on full-expiration tend to have better pulmonary function. Thus, in comparison with emphysema heterogeneity, AT heterogeneity better reflects the pulmonary function changes in COPD patients.Keywords: pulmonary disease, chronic obstructive, small airway disease, heterogeneous distribution, tomography, X-Ray computed

Objective: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis., Materials and Methods: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia., Results: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15-1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia., Conclusions: Our results suggest that acromegaly may be associated with bronchiectasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gil, Han, Hong and Park.)

Background & objectives The co-presence of non-emphysematous airflow obstruction in interstitial Lung disease (ILD) is not elaborated. The present study aims the job with spirometry. Methods ILD affected individuals with or without airflow obstruction (FEV1/FVC<0.7 or >0.7) on spirometry were compared in terms of FEV1 and FEF25-75 derived variables [FEF25-75 (%-predicted), FEV1-FEF25-75 distance, reversibility of FEV1 and FEF25-75 to salbutamol and change in FEV1 and FEF25-75 in %-predicted values]. Those showing significant difference (P=0.0001) suggesting obstruction were selected to draw respective receiver operating curve (ROC) curves to identify the best cut-off value for individual parameters. The efficacy of each surrogate was tested to identify airflow obstruction in both the initial 'overlap' as well as the 'unmixed' ILD affected individual for the presence of airflow obstruction. Results FEV1/FVC identified 30 overlap from 235 ILDs. The FEF25-75 (%-predicted), FEV1-FEF25-75 distance, FEF25-75 reversibility (in ml) and FEV1 (%-predicted) were significantly (P<0.0001) different between the two groups. Of these, the FEF25-75 (%-predicted) had high specificity and sensitivity (93.33 and 79.47%) to identify airflow limitation in the initial unmixed ILD-group. The surrogates with their cut off values identified 92 extra individuals making it 122/235 (51.91%) of ILD having airflow obstruction. The 'unmixed' group showed higher frequency and degree of FEV1 reversibility. Interpretation & conclusions The findings of this study suggest that the airflow obstruction in ILD involves both the intrathoracic large and small airways. Although seemingly parallel, their relative status (qualitative and quantitative) needs research especially in light of the a etio pathology and the extent of involvement of ILD.

Introduction: Small airway disease (SAD) represents a common and critical feature of Chronic Obstructive Pulmonary Disease (COPD). Introduced in the '60s, SAD has gradually gained increasing interest as assessment methodologies have improved. Chronic exposure to smoking and noxious particles or gases induces inflammation and remodeling, leading to airway obstruction and SAD, eventually resulting in complete airway loss., Areas Covered: A literature search up to June 2024 was performed in PubMed to identify articles on SAD and airway diseases mainly COPD, but also to the extent that it seemed relevant in the uncontrolled/severe asthma field, where SAD is better studied. We provide clinicians and translational scientists with a comprehensive analysis of the existing literature on SAD in COPD, concentrating on the underlying pathophysiological mechanisms, diagnostic techniques, and current pharmacological approaches targeting airflow obstruction in small airways., Expert Opinion: Small airways are the primary site for the onset and progression of airflow obstruction in patients with COPD, with significant clinical consequences associated with poor lung function, hyperinflation, and impaired quality of life. The early identification of individuals with subclinical SAD may allow us to prevent its further progress from airway loss and potential development of emphysema and choose the appropriate therapeutic approach.

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Background: Physical effort is capable of triggering airway obstruction in asthmatics, the so-called exercise-induced bronchoconstriction in asthma (EIBa). This study was performed in subjects with mild persistent asthma, aiming to find predictors for developing EIBa. Methods: In 20 subjects with mild asthma, measurements of baseline functional respiratory parameters and airways responsiveness by a methacholine challenge were obtained on the first day. A maximal, symptom-limited incremental cardiopulmonary exercise test (CPExT) was performed the day after, with subsequent, repeated maneuvers of maximal full forced expiration to monitor the FEV1 change at 1,3,5,7,10 and 15 min after the end of the exercise. Results: 19 subjects completed the two-days protocol. No functional parameters both at rest and during effort were useful to predict EIBa after stopping exercise. In asthmatics with EIBa, mean Inspiratory Capacity (IC) did not increase with increasing ventilatory requirements during CPExT because 6 of them (50%) displayed dynamic pulmonary hyperinflation (DH), as documented by their progressive increase of end-expiratory lung volume. This subgroup, showing earlier post-exercise FEV1 fall, had significantly lower forced mean expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) at rest (p < 0.05) and higher airways responsiveness, expressed as PD20FEV1 (p < 0.05) as compared with other asthmatics with EIBa. Conclusions: No functional respiratory parameters seem to predict EIBa in mild asthmatics. However, in those with EIBa, a subgroup developed DH during exercise, and this was associated with a baseline reduced forced expiratory flow rates at lower lung volumes and higher airway hyperresponsiveness, suggesting a prominent small airways impairment. [ABSTRACT FROM AUTHOR]

Abstract Objective There has been growing interest in studying small airway disease through measures of ventilation distribution, thanks to the resurgence of the nitrogen single-breath washout (N2SBW) test. Therefore, this study evaluated the contribution of the N2SBW test to the detection of pulmonary involvement in patients with rheumatoid arthritis (RA). Results Twenty-one patients with RA underwent clinical evaluation, pulmonary function tests (PFTs), including the N2SBW test, and computed tomography (CT). The main tomographic findings were air trapping and bronchiectasis (57.1% and 23.8% of cases, respectively). According to the phase III slope of the N2SBW (phase III slope), 11 and 10 patients had values 120% predicted, respectively. Five patients with limited involvement on CT had a phase III slope > 120%. The residual volume/total lung capacity ratio was significantly different between patients with phase III slopes 120% (P = 0.024). Additionally, rheumatoid factor positivity was higher in patients with a phase III slope > 120% (P = 0.021). In patients with RA and airway disease on CT, the N2SBW test detects inhomogeneity in the ventilation distribution in approximately half of the cases, even in those with normal conventional PFT results.

Abstract Background It is known that small airway disease is present across all asthma severities; however, its prevalence and clinical characteristics in cough variant asthma (CVA) have not been fully illuminated. Methods A total of 77 CVA patients with preserved proximal airway function (FEV1/FVC > 70%) were enrolled in this study. The correlation between forced expiratory flow at 50% (FEF50%) and FEF25–75% in the CVA population was first evaluated. FEF50% was determined to be an easy and feasible parameter for identifying small airway disease. CVA with small airway disease is defined as FEF50% 70%. Demographic features, clinical characteristics, lung function and induced sputum test results were determined at the initial visit and at the final visit 1 year later. Results FEF50% is a good marker for small airway disease. The cutoff value of 70% is more sensitive than the previously published 60% for identifying more patients with small airway problems early. Nearly half of the CVA population (45.4%) in our cohort had small airway disease. In both group, symptoms improved greatly after anti-asthmatic treatment. Interestingly, the changes in symptom scores [Asthma Control Test (ACT) and ACQ] were even greater in the CVA with small airway disease group than in the control group because of the higher medication usage in this subpopulation in real life. However anti-asthmatic therapy can not reverse small airway dysfunction. At last visit, FEF50% of CVA with small airway diseases was 57.2% ± 10.5%, still much lower than the control group (FEF50% = 92.6% ± 16.5%). Conclusions In our cohort, nearly half of the CVA population had small airway disease. Their demographic features, clinical characteristics, airway eosinophils and drug responsiveness were quite similar between two groups, which means these indices can not be used as markers to identify small airway obstruction. We found FEF50% is an easy and feasible marker for early identification. Regular anti-asthmatic medication helped to improve clinical scores in patients with small airway disease, but the obstruction could not be reversed over 1-year period.