Small Airway Dysfunction Research Articles

Potential pre-COPD indicators in association with COPD development and COPD prediction models in Chinese: a prospective cohort study

Lung injury might take place before chronic obstructive pulmonary disease (COPD) occurs. A clearer definition of "pre-COPD" based on the effects of potential indicators on increasing risk of COPD development and a prediction model involving them are lacking. A total of 3526 Chinese residents without COPD aged 40 years or older derived from the national cross-sectional survey of COPD surveillance in 2014-2015 were followed up for a mean of 3.59 years. We examined the associations of chronic bronchitis, preserved ratio impaired spirometry (PRISm), low peak expiratory flow (PEF), spirometric small airway dysfunction (sSAD), low maximal mid-expiratory flow (MMEF), low forced expiratory flow 50% of pulmonary volume (FEF50), and low FEF75 with subsequent COPD and constructed a prediction model with LASSO-Cox regression. 235 subjects in the cohort developed COPD during the follow-up. Subjects with PRISm, low PEF, sSAD, low MMEF, low FEF50, and low FEF75 had an increased risk of developing COPD (adjusted hazard ratio [HR] ranging from 1.57 to 3.01). Only chronic bronchitis (HR 2.84 [95% CI 1.38-5.84] and 2.94 [1.43-6.04]) and sSAD/low MMEF (HR 2.74 [2.07-3.61] and 2.38 [1.65-3.43]) showed effects independent of the other indicators and their concurrence had the strongest effect (HR 5.89 and 4.80). The prediction model including age, sex, low MMEF, low FEF50, and indoor exposure to biomass had good performance both internally and temporally. The corrected C-index was 0.77 (0.72-0.81) for discrimination in internal validation. For temporal validation, the area under the receiver operating characteristic curve was 0.73 (0.63-0.83). Good calibration was indicated in plot for internal validation and by Hosmer-Lemeshow test for temporal validation. Individuals with concurrent chronic bronchitis and sSAD/low MMEF indicating pre-COPD optimally require more high attention from physicians. Our prediction model could serve as a multi-dimension tool to predict COPD comprehensively. The Ministry of Finance and the Ministry of Science and Technology of the People's Republic of China and the National Natural Science Foundation of China.

Fitness for Work in the Long Journey of Tuberculosis Infection to Chronic Posttuberculosis Disease Case Report and Literature Review

Abstract The long journey of tuberculosis (TB) from exposure to latent or progressive TB infection, from primary stage to second stage of illness with or without infectious status, and then to chronic post-TB sequelae is very complex and still unclear, including a various spectrum of stages and manifestations. A case report of a 55 year-old woman with personal history of pleural effusion, in her youth, 2 previous episodes of COVID-19 infections, having no exposure to active smoking but occupational exposure to wood dust, hot steam, barbeque smoke, was admitted to Constanta Clinical Pneumology Hospital in October 2022 for hemoptysis and fatigue. Clinical and paraclinical investigations highlighted an acute evolutive episode of Pulmonary TB with metastatic bilateral nodular pattern, negative smears, positive cultures and positive QuantiFERON TB Gold in Tube (QFT-GIT). TB standard regimen of therapy was started, based on QFT-GIT positivity, and after it ended, chronic obstructive pulmonary disease was detected by spirometry and small airways dysfunction by impulse oscillometry. TB illness does not stop after directly observed therapy ends. So, systematical screening of pulmonary, bronchial or pleural sequelae should be performed and identified syndromes need to be treated, as well as reintegration in the job process by a careful monitoring.

The Role of Small Airway Disease in Pulmonary Fibrotic Diseases.

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.

Small airway dysfunction and impulse oscillometry in adult patients with asthma: recent findings

Asthma is a respiratory disease affecting more than 300 million people around the world. Airflow obstruction and inflammation due to asthma usually involve large airways, but recently small airway involvement (internal diameter < 2 mm) has been shown to represent one of the main determinants of asthma and asthma control. In fact, compared to large airway involvement, small airway dysfunction (SAD) has been demonstrated across all the asthma severity in the majority of patients, as assessed with Global Initiative for Asthma (GINA) steps. Clinically, SAD is associated with, among other features, exercise-induced bronchoconstriction, asthma-related night awakenings, obesity/overweight, more severe airway hyperresponsiveness, worse asthma control, and more severe exacerbations. Impulse oscillometry (IOS), a forced oscillation technique (FOT) requiring less effort than spirometry from the patients, demonstrated to accurately measure SAD in children and adults. The fall in resistance from 5 Hz to 20 Hz (R5–R20), which is the most used index for the resistance of peripheral airways, is how SAD is usually identified by IOS. Other crucial parameters measured by IOS are the reactance at 5 Hz (X5), reflecting elastic recoil of the peripheral airways, the resonant frequency (Fres), which is the frequency at which the inertial properties of the airway and the capacitance of the lung periphery are equal, and the reactance area (AX), reflecting the elastic properties of the lung periphery. In this mini review, the latest findings on the utility of IOS to identify SAD and the associations between SAD and clinical features in adult asthmatic patients were addressed.

Small airways dysfunction: The importance of utilising Z-scores to define MMEF abnormalities in clinical practice

BackgroundThe 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. MethodsUsing 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. ResultsRecords 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. ConclusionWhen 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.

Evaluation of small airway dysfunction in patients with pneumoconiosis, a cross-sectional study

Objective: Pneumoconiosis is an irreversible, progressive parenchymal lung disease caused by inhalation of mineral dust. Inhaled particles in the working environment can cause inflammation and fibrosis in the lung, affecting all respiratory tracts, including the large and small airways. Our study aimed to evaluate the frequency and risk factors of small airway dysfunction (SAD) in patients diagnosed with pneumoconiosis. Methods: The study population consisted of 331 patients diagnosed with pneumoconiosis between 01/01/2018 and 31/05/2023. Pneumoconiosis was diagnosed with a history of occupational inorganic dust exposure, radiologic findings compatible with pneumoconiosis, and exclusion of other diagnoses. Two readers evaluated the chest radiographs of the patients according to the International Classification of Pneumoconiosis Radiographs of the International Labor Organization. SAD was defined as at least two FEF50, FEF75, and FEF25-75 measurements below 65% of their predicted values. Results: SAD was found in 47.7% of the patients. There was a statistically significant difference between age and the prevalence of SAD, but there was no statistically significant difference between smoking status and the prevalence of SAD. It was observed that 41.9% of the patients with pneumoconiosis who had never smoked had SAD. As the cigarette pack-years increased, the incidence of SAD increased. SAD was presented 38.7% in Stage 1, 50.7% in Stage 2, and 57.6% in Stage 3 pneumoconiosis cases. SAD was seen in 35.1% of pneumoconiosis cases without PMF. In pneumoconiosis patients with PMF, the frequency of SAD increased with increasing opacity size. Conclusion: It was found that the frequency of SAD increased as the stage of pneumoconiosis increased. In patients with pneumoconiosis, SAD was observed in both smokers and never smokers, independent of large airway obstruction. Therefore, early small airway dysfunction should be considered when monitoring the health of patients with pneumoconiosis.

Validity of fractional exhaled nitric oxide and small airway lung function measured by IOS in the diagnosis of cough variant asthma in preschool children with chronic cough

BackgroundTo investigate the role of combined impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) in the diagnosis of cough variant asthma (CVA) in preschool children.MethodsA total of 197 preschool-aged children with chronic cough were selected from the paediatric outpatient clinic. Allergy histories were collected for all children along with IOS and FeNO. Paediatric respiratory specialists divided the children into a CVA group (n = 90) and a noncough variant asthma (nCVA) group (n = 107) according to the diagnostic criteria for CVA After diagnostic treatment, the correlation between the FeNO and IOS values and the diagnosis in the two groups was analysed, and the area under the curve (AUC) of each index was calculated.Results(1) X5 was significantly different between the CVA group and the nCVA group (− 4.22 vs. − 3.64, p < 0.001), as was the FeNO value (29.07 vs. 16.64, p < 0.001). (2) Receiver operating characteristic (ROC) analysis showed that the AUCs of FeNO alone and X5 alone were 0.779 and 0.657, respectively, while the AUC of FeNO (cut-off value of 18 ppb) plus X5 (cut-off value of -4.15 cmH2O/(l/s)) reached 0.809.ConclusionsChildren with CVA may have small airway dysfunction at an early stage. For preschool children with chronic cough, the combination of FeNO and X5 can better identify those with CVA.Trial registration number: This trial was registered with and approved by the Chinese Clinical Trial Registry, with registration number ChiCTRcRRC-17011738, and was reviewed and approved by the Ethics Committee of Southwest Hospital.

Small airway dysfunction associated with poor short-term outcomes in patients undergoing thoracoscopic surgery for lung cancer

BackgroundAlthough small airway dysfunction is a common respiratory dysfunction, its prognosis after lung cancer surgery is often neglected. This study investigated the relationship between small airway dysfunction and outcomes in patients who underwent thoracoscopic surgery for lung cancer. MethodsA retrospective cohort study of patients who underwent thoracoscopic surgery was conducted between December 2019 and March 2021 at Ningbo First Hospital. We used univariate and multivariate analyses to assess the possible associations between postoperative outcomes and clinical variables, including small airway dysfunction. To balance the potential confounding factors, propensity score matching was performed to establish 1:1 small airway dysfunction and small airway normal function group matching. ResultsIn this study, 1,012 patients undergoing thoracoscopic surgery for lung cancer were enrolled. Small airway dysfunction was present in 18.7% of patients (189/1,012). The incidence of postoperative pulmonary complications in the small airway dysfunction group was higher than that of the small airway normal function group (16.4% vs 6.2%, P < .001). The most significant postoperative pulmonary complications were pneumonia (7.4% vs 2.4%, P < .001) in the small airway dysfunction and normal function groups, respectively. In addition, a significantly prolonged median hospital length of stay was observed in the small airway dysfunction group compared to the small airway normal function group (median [interquartile range], 9 [7–12] vs 8 [7–9], P < .001). After 1:1 propensity score matching, 298 patients (149 pairs) were included in the comparison between small airway dysfunction and small airway normal function, and this association remained. Postoperative pulmonary complications (13.4% vs 6.0%, P = .032) were still higher, and length of stay (median [interquartile range] 9 [7–11] vs 8 [6–10] days, P = .001) was still longer in the small airway dysfunction group. Multivariate analysis indicated that small airway dysfunction was the independent risk factor associated with both postoperative pulmonary complications (odds ratio = 2.694, 95% confidence interval: 1.640–4.426, P < .001) and prolonged length of stay (beta = 1.045, standard error = 0.159, 95% confidence interval: 0.733–1.357, P < .001). ConclusionOur study showed that small airway dysfunction increased the incidence of postoperative pulmonary complications and prolonged length of stay in patients undergoing thoracoscopic surgery for lung cancer.

Small airways in asthma: Pathophysiology, identification and management.

The aim of this review is to summarize the current evidence regarding small airway disease in asthma, focusing on recent advances in small airway pathophysiology, assessment and therapeutic implications. A search in Medline was performed, using the keywords "small airways", "asthma", "oscillometry", "nitrogen washout" and "imaging". Our review was based on studies from adult asthmatic patients, although evidence from pediatric populations is also discussed. In asthma, inflammation in small airways, increased mucus production and airway wall remodelling are the main pathogenetic mechanisms of small airway disease. Small airway dysfunction is a key component of asthma pathophysiology, leading to increased small airway resistance and airway closure, with subsequent ventilation inhomogeneities, hyperresponsiveness and airflow limitation. Classic tests of lung function, such as spirometry and body plethysmography are insensitive to detect small airway disease, providing only indirect measurements. As discussed in our review, both functional and imaging techniques that are more specific for small airways, such as oscillometry and the multiple breath nitrogen washout have delineated the role of small airways in asthma. Small airways disease is prevalent across all asthma disease stages and especially in severe disease, correlating with important clinical outcomes, such as asthma control and exacerbation frequency. Moreover, markers of small airways dysfunction have been used to guide asthma treatment and monitor response to therapy. Assessment of small airway disease provides unique information for asthma diagnosis and monitoring, with potential therapeutic implications.

Risk Factors for Abnormal Small Airway Function Indicators in Nasal Polyp Patients with and without Asthma

Introduction: Small airway dysfunction (SAD) is associated with type 2 inflammation in patients who have non-asthmatic chronic rhinosinusitis with nasal polyps (CRSwNPs); however, the risk factors for abnormal small airway function indicators in CRSwNP patients with and without asthma remain unclear. Methods: We retrospectively analyzed 41 asthmatic and 109 non-asthmatic CRSwNP patients. Clinical characteristics were compared between groups, correlations between small airway function and clinical parameters were calculated, and independent risk factors for every small airway indicator were identified in each group. Results: Asthmatic CRSwNP patients had significantly reduced small airway function, and the proportion of patients with SAD was higher in asthmatic CRSwNP patients (65.85%) than in patients without asthma (9.17%). With regard to specific airway function indicators, age and a patient’s blood eosinophil (%) were identified as independent risk factors for lower FEF50% %pred and FEF25–75% pred, with age being an independent risk factor for FEF75% %pred in asthmatic CRSwNP patients. In non-asthmatic CRSwNP patients, allergic rhinitis comorbidity was found to be an independent risk factor for FEF50% %pred, FEF75% %pred, and FEF25–75% %pred. Conclusion: Physicians should pay greater attention to risk factors for abnormal small airway function indicators in patients with CRSwNPs to prevent the occurrence of SAD.

Impulse oscillometry defined small airway dysfunction in asthmatic patients with normal spirometry: Prevalence, clinical associations, and impact on asthma control

BackgroundThe small-airway dysfunction (SAD), detected with impulse oscillometry (IOS) methods, has been recently better characterized in patients with asthma. However, little is known about SAD in asthmatic patients with normal spirometry (NS). ObjectiveIn this study, we aimed to investigate, in an unselected sample of 321 patients with physician-diagnosed asthma and NS, prevalence, clinical characterization, and impact on asthma control of IOS-defined SAD. As a secondary objective of the study, we focused on comparing the difference between IOS- and spirometry-defined SAD. MethodsConsecutive patients with a previous diagnosis of asthma but normal spirometry at the moment of the enrollment were stratified by the presence of IOS-defined SAD (difference in resistance at 5 Hz and at 20 Hz [R5-R20] greater than 0.07 kPa x s x L−1). We have also assessed the presence of SAD defined by spirometry, according to FEF 25–75 < 65% of the predicted. Clinical and laboratory features were collected, and univariable and multivariable analyses were used to analyze cross-sectional associations between clinical variables and outcomes (SAD). ResultsIOS-defined SAD was present in 54.1% of the cohort. In contrast, spirometry-defined SAD was present in only 10% of patients. Subjects with IOS-defined SAD showed less well-controlled asthma and a higher mean inhaled corticosteroid dosage use compared with subjects without SAD (both P < .001). Overweight (odds ratio [OR], 1.14; 95% CI, 1.05–1.23), exacerbation history (OR, 3.06; 95% CI, 1.34–6.97), asthma-related night awakenings (OR, 6.88; 95% CI, 2.13–22.23), exercise-induced asthma symptoms (OR, 33.5; 95% CI, 9.51–117.8), and controlled asthma (OR, 0.22; 95% CI, 0.06–0.84) were independently associated with SAD. ConclusionsAsthmatic patients with IOS-defined SAD showed less well-controlled asthma, more severe exacerbations and higher mean inhaled corticosteroid dosage. We confirmed exercise-induced asthma, asthma-related night awakenings, exacerbation history, and overweight as independently associated with SAD, while showing well-controlled asthma as inversely associated. SAD may be overlooked by standard spirometry.

Small airway dysfunction and obesity in asthmatic patients: a dangerous liaison?

Asthma is a chronic condition characterized by inflammation throughout the entire bronchial airways. Recent findings suggest that ventilation inhomogeneity and small airway dysfunction (SAD) play a particularly significant role in asthma development and clinical manifestations. Obesity is a considerable risk factor for asthma development and morbidity in children and adults. A growing body of evidence suggests that SAD is linked to more severe asthma and poor asthma control in obese patients. However, the knowledge about the relationship between peripheral airway compromise and obesity in asthma is limited, mainly because of the historical lack of access to non-invasive assessment methods for studying SAD. Conventional lung function measurements, like spirometry, cannot accurately assess small airway function. However, in recent years, new specialized tests available in outpatient settings have been found to distinguish SAD from large airway obstruction more accurately compared to spirometry. Therefore, understanding the degree of peripheral airway implication in the underlying pathology is critical for effective asthma control and therapeutic decisions. This review highlights recent findings on the impact of SAD on asthma patients who are obese. Additionally, it explores how new diagnostic methods, such as impulse oscillometry (IOS), may be used in outpatient settings to detect small airway impairment in obese asthma at an early stage, potentially leading to improved asthma treatment.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer

Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5±8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p=0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p=0.046; for FEF50%, r=-0.142, p=0.008; and for FEF25-75%, r=-0.124, p=0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p>0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p=0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P=0.041) were associated with postoperative complications. Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

Detection of small airway dysfunction in bronchial asthma and its clinical application

Bronchial asthma is a common chronic inflammatory airway disease. Small airway dysfunction (SAD) can be present in asthmatics with different phenotypes, clinical stages and varied severity, and has implication for drug efficacy and patient prognosis. Currently, there is no consensus on the criteria for SAD, and its inflammatory mechanism remains unclear. In this paper, we reviewed the research advances in the evaluation, prevalence, pathogenesis, clinical features and treatment of SAD in asthmatics to improve awareness of the disease.

Prevalence of small airway dysfunction in the Swiss PneumoLaus Cohort.

Recent evidence identified exposure to particulate matter of size ≤2.5 µm (PM2.5) as a risk factor for high prevalence of small airway dysfunction (SAD). We assessed the prevalence of SAD in a European region with low air pollution levels. SAD was defined as a maximum mid-expiratory flow (MMEF) <65% of predicted value (PV) or MMEF <lower limit of normal (LLN) measured by spirometry in the Swiss PneumoLaus cohort. We performed bivariate and multivariable analysis with MMEF criteria, age, sex, body mass index, respiratory symptoms and smoking status. Mean PM2.5 values were obtained from a Swiss national database. Among 3351 participants (97.6% Caucasian, 55.7% female sex, mean age 62.7 years), we observed MMEF <65% PV in 425 (12.7%) and MMEF <LLN in 167 (5.0%) individuals. None of the participants had both MMEF <LLN and ≥65% PV. MMEF <65% PV and MMEF <LLN were significantly associated with age, smoking status, cough, sputum and dyspnoea, whereas a positive association with MMEF <65% PV was observed for individuals aged >65 years only. In an area where ambient PM2.5 concentration was <15 µg·m-3 during the observation period (2010 and 2020), ≥72% of participants with SAD were ever-smokers. The observed low prevalence of SAD of 5.0-12.7% depending on criteria employed may be related to lower PM2.5 exposure. Smoking was the main factor associated with SAD in an area with low PM2.5 exposure. Employing a MMEF threshold <65% PV carries a risk of SAD overdiagnosis in elderly individuals.

Activation of the Complement and Coagulation Systems in the Small Airways in Asthma

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.

Detection of Small Airway Dysfunction in Asthmatic Patients by Spirometry and Impulse Oscillometry System

Background: There is no gold standard in diagnosing SAD. Indicators of SAD are considered: (a) a value <65% of predicted values of two of three measures, FEF25-75, FEF50 e FEF75 (FEF+); (b) a value of FEV3/FEV6 < LLN (FEV3/FEV6+); (c) an IOS value of R5-R20 >0.07 kPa·s·L−1 (R5-R20+). Aim and Objectives: The aim of the study was to ascertain, in asthmatic patients, whether spirometry and IOS indicators agree in detecting SAD. We also assessed the relationship between spirometry and IOS indicators and clinical features of asthma. Methods: We prospectively recruited adult asthmatic patients. Anthropometric and clinical characteristics were recorded. All patients performed spirometry and IOS tests. Results: We enrolled 301 asthmatic patients (179 females; mean age 50 ± 16 years) with normal to moderately severe degree of airway obstruction; 91% were non-smokers, 74% were atopic, 28% had an exacerbation in the previous year, and 18% had a poor asthma control by ACT. SAD was diagnosed in 62% of patients through FEF+, in 40% through FEV3/FEV6+ and in 41% through R5-R20+. κ values were 0.49 between FEF+ and FEV3/FEV6+, 0.20 between FEF+ and R5-R20+, 0.07 between FEV3/FEV6+ and R5-R20+. R5-R20+ but not FEF+ and FEV3/FEV6+ was significantly associated with ACT score (p < 0.05). Conclusions: Our study shows that in mild to moderately severe asthmatic patients, spirometry and IOS indicators are complementary in diagnosing SAD. Additionally, IOS indicator, but not spirometry ones, was related to asthma control.

The role of small airway function parameters in preschool asthmatic children

BackgroundSmall airways are the major sites of inflammation and airway remodeling in all severities of asthma patients. However, whether small airway function parameters could reflect the airway dysfunction feature in preschool asthmatic children remain unclear. We aim to investigate the role of small airway function parameters in evaluating airway dysfunction, airflow limitation and airway hyperresponsiveness (AHR).MethodsEight hundred and fifty-one preschool children diagnosed with asthma were enrolled retrospectively to investigate the characteristics of small airway function parameters. Curve estimation analysis was applied to clarify the correlation between small and large airway dysfunction. Spearman’s correlation and receiver-operating characteristic (ROC) curves were employed to evaluate the relationship between small airway dysfunction (SAD) and AHR.ResultsThe prevalence of SAD was 19.5% (166 of 851) in this cross-sectional cohort study. Small airway function parameters (FEF25-75%, FEF50%, FEF75%) showed strong correlations with FEV1% (r = 0.670, 0.658, 0.609, p<0.001, respectively), FEV1/FVC% (r = 0.812, 0.751, 0.871, p<0.001, respectively) and PEF% (r = 0.626, 0.635, 0.530, p<0.01, respectively). Moreover, small airway function parameters and large airway function parameters (FEV1%, FEV1/FVC%, PEF%) were curve-associated rather than linear-related (p<0.001). FEF25-75%, FEF50%, FEF75% and FEV1% demonstrated a positive correlation with PC20 (r = 0.282, 0.291, 0.251, 0.224, p<0.001, respectively). Interestingly, FEF25-75% and FEF50% exhibited a higher correlation coefficient with PC20 than FEV1% (0.282 vs. 0.224, p = 0.031 and 0.291 vs. 0.224, p = 0.014, respectively). ROC curve analysis for predicting moderate to severe AHR showed that the area under the curve (AUC) was 0.796, 0.783, 0.738, and 0.802 for FEF25-75%, FEF50%, FEF75%, and the combination of FEF25-75% and FEF75%, respectively. When Compared to children with normal lung function, patients with SAD were slightly older, more likely to have a family history of asthma and airflow obstruction with lower FEV1% and FEV1/FVC%, lower PEF% and more severe AHR with lower PC20 ( all p<0.05).ConclusionSmall airway dysfunction is highly correlated with large airway function impairment, severe airflow obstruction and AHR in preschool asthmatic children. Small airway function parameters should be utilized in the management of preschool asthma.

Clinical implications of the concentration of alveolar nitric oxide in non-small cell lung cancer.

Clinical implications of the concentration of alveolar nitric oxide in non-small cell lung cancer.

Might It Be Appropriate to Anticipate the Use of Long-Acting Muscarinic Antagonists in Asthma?

A growing number of clinical trials are documenting that adding a long-acting muscarinic antagonist (LAMA) to established asthma treatment with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) is a treatment option that improves the health of patients with uncontrolled severe asthma even when therapy is optimized. These favorable results are the reasonwhy the leading guidelines recommend triple therapy with ICS + LABA + LAMA in patients with asthma uncontrolled by medium- to high-dose ICS-LABA. However, we suggest adding LAMAs to ICS-LABAs at an earlier clinical stage. Such action could positively influence airflow limitation, exacerbations, and eosinophilic inflammation, conditions that are associated with acetylcholine (ACh) activity. It could also interrupt the vicious cycle related to a continuous release of ACh leading to the progressive expansion of neuronal plasticity resulting in small airway dysfunction. The utility of an earlier use of triple therapy in asthma should, in any case, be confirmed by statistically powered trials.