Airway Dysfunction Research Articles

Identification and treatment of persistent small airway dysfunction in paediatric patients with asthma: a retrospective cohort study

BackgroundAsthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities.MethodsThis retrospective cohort study included 248 children with asthma (aged 4–11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman’s rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher’s exact test.ResultsAsthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082–2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365–0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170–2.305) and with worse asthma control (OR 3.893, 95% CI 1.699–8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month.ConclusionsPaediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

Proteomic and metabolomic proof of concept for unified airways in chronic rhinosinusitis and asthma

BackgroundThe pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) with comorbid asthma remains unclear. ObjectiveTo assess upper and lower airway unity and identify a possible common pathogenesis in CRSwNP with asthma. MethodsThis study analyzed the expression of proteins and metabolites in nasal lavage fluid cells (NLFCs) and induced sputum cells (ISCs). Differentially expressed proteins and their function-related metabolites in the upper and lower airways of patients having CRSwNP with or without asthma were identified; relevant signaling pathways were analyzed, and key pathway-related proteins were identified. Parallel reaction monitoring was used to verify these target proteins. ResultsProtein or metabolite expression between NLFCs and ISCs was highly correlated and conservative on the basis of expression profiles and weighted gene coexpression network analysis. There were 17 differentially coexpressed proteins and their function-related 13 metabolites that were identified in the NLFCs and ISCs of CRSwNP, whereas 11 proteins and 11 metabolites were identified in CRSwNP with asthma. An asthma pathway was involved in the copathogenesis of upper and lower airways in whether CRSwNP or CRSwNP with asthma. The asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase, as the core of the protein-metabolism interaction networks between the upper and lower airways, were both highly coexpressed in NLFCs and ISCs in patients having either CRSwNP or CRSwNP with asthma by parallel reaction monitoring validation. ConclusionProteomics and metabolomics reveal upper and lower airway unity. Asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase from the upper airway could be used to assess the potential risk of lower airway dysfunction in CRSwNP.

Combined effect of changes in NO2, O3, PM2.5, SO2 and CO concentrations on small airway dysfunction.

When multiple complex air pollutants are combined in real-world settings, the reliability of estimating the effect of a single pollutant is questionable. This study aimed to investigate the combined effects of changes in air pollutants on small airway dysfunction (SAD). We analysed Korea National Health and Nutrition Examination Survey (KNHANES) V-VIII database from 2010 to 2018 to elucidate the associations between annual changes in air pollutants over a previous 5-year period and small airway function. We estimated the annual concentrations of five air pollutants: NO2, O3, PM2.5, SO2 and CO. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%-75%) <65% was defined as SAD. Using the quantile generalized-Computation (g-Computation) model, the combined effect of the annual changes in different air pollutants was estimated. A total of 29,115 individuals were included. We found significant associations between SAD and the quartiles of annual changes in NO2 (OR = 1.10, 95% CI = 1.08-1.12), O3 (OR = 1.03, 95% CI = 1.00-1.05), PM2.5 (OR = 1.03, 95% CI = 1.00-1.05), SO2 (OR = 1.04, 95% CI = 1.02-1.08) and CO (OR = 1.16, 95% CI = 1.12-1.19). The combined effect of the air pollutant changes was significantly associated with SAD independent of smoking (OR = 1.31, 95% CI = 1.26-1.35, p-value <0.001), and this trend was consistently observed across the entire study population and various subgroup populations. As the estimated risk of SAD, determined by individual-specific combined effect models, increased and the log odds for SAD increased linearly. The combined effect of annual changes in multiple air pollutant concentrations were associated with an increased risk of SAD.

Improved small airway dysfunction in severe asthma with clinical remission by anti-interleukin-5/interleukin-5 receptor α

Improved small airway dysfunction in severe asthma with clinical remission by anti-interleukin-5/interleukin-5 receptor α

Distinct roles for type I and type III interferons in virulent human metapneumovirus pathogenesis.

Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and both neutralizing antibodies and T cells contribute to protection. However, little is known about mechanisms of pathogenesis and most published work is based on a few extensively passaged, laboratory-adapted strains of HMPV. In this study, we isolated and characterized a panel of low passage HMPV clinical isolates representing all four genetic subgroups. The clinical isolates exhibited lower levels of in vitro replication compared to a lab-adapted strain. We compared disease phenotypes using a well-established mouse model. Several virulent isolates caused severe weight loss, lung pathology, airway dysfunction, and fatal disease in mice, which was confirmed in three inbred mouse strains. Disease severity did not correlate with lung viral titer, as virulent strains exhibited restricted replication in the lower airway. Virulent HMPV isolates were associated with markedly increased proinflammatory cytokine production and neutrophil influx; however, depletion of neutrophils or genetic ablation of inflammasome components did not reverse disease. Virulent clinical isolates induced markedly increased type I and type III interferon (IFN) secretion in vitro and in vivo. STAT1/2-deficient mice lacking both type I and type III IFN signaling showed reduced disease severity and increased lung viral replication. Inhibition of type I IFN signaling using a blocking antibody or genetic ablation of the type I IFN receptor reduced pathology with minimal effect on viral replication. Conversely, blockade of type III IFN signaling with a neutralizing antibody or genetic ablation of the IFN-lambda receptor had no effect on pathogenesis but restored viral replication. Collectively, these results demonstrate distinct roles for type I and type III IFN in HMPV pathogenesis and immunity.

Investigating the dynamic relationship of sleep-disordered breathing, orthodontic treatment needs, and dental esthetics in the general population.

Sleep-disordered breathing (SDB) is characterized by upper airway dysfunction and is linked to severe health issues. Individuals with SDB have distinct craniofacial morphology for which orthodontists are most suitable for the management due to their dental expertise. This study aims to discern key differences in dental parameters between individuals with and without SDB. The present study is a cross-sectional observational study conducted for 12 months. Out of 70 participants, 35 were placed in the SDB group as per the Berlin questionnaire (BQ) and 35 in the control aged 18-22 years. Criteria excluded individuals with preexisting illnesses, missing teeth, tonsillectomy, orthodontic or jaw surgeries, cleft lip/palate, or craniofacial anomalies. Dental assessments included interdental width, palatal vault depth and shape, molar relation, overjet, and overbite. In addition, self-perceived orthodontic treatment needs were evaluated as a secondary measure. In the SDB group, interdental distances were significantly reduced in the canine, first premolars, second premolars, and molar regions by 2, 3, 4, and 1.8 mm, respectively. A noticeable V-shaped arch was observed. Overjet and overbite increased by 42.85% and 31.42%, respectively, with Class 1 malocclusion more prevalent than Class 2. The Berlin questionnaire identified 54.3% as high-risk SDB. The Index of Orthodontic Treatment Need-Esthetic Component (IOTN-AC) revealed that 68.6% of snoring participants required orthodontic treatment. Individuals with SDB exhibit a constricted maxilla and reduced interdental measurements, indicating a moderate risk. The Berlin questionnaire proves valuable in assessing SDB severity. Moreover, individuals displaying signs of SDB often present a high prevalence of orthodontic treatment needs, as indicated by the IOTN-AC.

Development and evaluation of a computerized algorithm for the interpretation of pulmonary function tests.

Pulmonary function tests (PFTs) are usually interpreted by clinicians using rule-based strategies and pattern recognition. The interpretation, however, has variabilities due to patient and interpreter errors. Most PFTs have recognizable patterns that can be categorized into specific physiological defects. In this study, we developed a computerized algorithm using the python package (pdfplumber) and validated against clinicians' interpretation. We downloaded PFT reports in the electronic medical record system that were in PDF format. We digitized the flow volume loop (FVL) and extracted numeric values from the reports. The algorithm used FEV1/FVC<0.7 for obstruction, TLC<80%pred for restriction and <80% or >120%pred for abnormal DLCO. The algorithm also used a small airway disease index (SADI) to quantify late expiratory flattening of the FVL to assess small airway dysfunction. We devised keywords for the python Natural Language Processing (NLP) package (spaCy) to identify obstruction, restriction, abnormal DLCO and small airway dysfunction in the reports. The algorithm was compared to clinicians' interpretation in 6,889 PFTs done between March 1st, 2018, and September 30th, 2020. The agreement rates (Cohen's kappa) for obstruction, restriction and abnormal DLCO were 94.4% (0.868), 99.0% (0.979) and 87.9% (0.750) respectively. In 4,711 PFTs with FEV1/FVC≥0.7, the algorithm identified 190 tests with SADI < lower limit of normal (LLN), suggesting small airway dysfunction. Of these, the clinicians (67.9%) also flagged 129 tests. When SADI was ≥ LLN, no clinician's reports indicated small airway dysfunction. Our results showed the computerized algorithm agreed with clinicians' interpretation in approximately 90% of the tests and provided a sensitive objective measure for assessing small airway dysfunction. The algorithm can improve efficiency and consistency and decrease human errors in PFT interpretation. The computerized algorithm works directly on PFT reports in PDF format and can be adapted to incorporate a different interpretation strategy and platform.

Oscillometry-Defined Small Airway Dysfunction in Patients with Chronic Obstructive Pulmonary Disease.

The prevalence of small airway dysfunction (SAD) in patients with chronic obstructive pulmonary disease (COPD) across different ethnicities is poorly understood. This study aimed to estimate the prevalence of SAD in stable COPD patients. We conducted a cross-sectional study of 196 consecutive stable COPD patients. We measured pre- and post-bronchodilator (BD) lung function and respiratory impedance. The severity of COPD and lung function abnormalities was graded in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SAD was defined as either difference in whole-breath resistance at 5 and 19 Hz &gt; upper limit of normal or respiratory system reactance at 5 Hz &lt; lower limit of normal. The cohort consisted of 95.9% men, with an average age of 66.3 years. The mean forced expiratory volume 1 second (FEV1) % predicted was 56.4%. The median COPD assessment test (CAT) scores were 14. The prevalence of post-BD SAD across the GOLD grades 1 to 4 was 14.3%, 51.1%, 91%, and 100%, respectively. The post-BD SAD and expiratory flow limitation at tidal breath (EFLT) were present in 62.8% (95% confidence interval [CI], 56.1 to 69.9) and 28.1% (95% CI, 21.9 to 34.2), respectively. COPD patients with SAD had higher CAT scores (15.5 vs. 12.8, p&lt;0.01); poor lung function (FEV1% predicted 46.6% vs. 72.8%, p&lt;0.01); lower diffusion capacity for CO (4.8 mmol/min/kPa vs. 5.6 mmol/min/kPa, p&lt;0.01); hyperinflation (ratio of residual volume to total lung capacity % predicted: 159.7% vs. 129%, p&lt;0.01), and shorter 6-minute walk distance (367.5 m vs. 390 m, p=0.02). SAD is present across all severities of COPD. The prevalence of SAD increases with disease severity. SAD is associated with poor lung function and higher symptom burden. Severe SAD is indicated by the presence of EFLT.

Relationship between airway inflammation, small airway dysfunction, and frequency of acute exacerbations in patients with chronic obstructive pulmonary disease

ContextRecurrent exacerbations in COPD patients are associated with accelerated reduction in lung function. Airway inflammation and small airway dysfunction were recognized for a long time as an essential feature of COPD.AimTo study the relationship between neutrophilic airway inflammation, small airway dysfunction, and frequency of acute exacerbations in COPD patients.Settings and designThis was a cross-sectional study.Patients and methodsThirty COPD patients were enrolled and classified into two groups: infrequent exacerbators (IFE) “who developed ≤ 1 exacerbation per year” and frequent exacerbators (FE) “who developed ≥ 2 exacerbations per year” in the last year prior to this study. All patients included in the study underwent clinical evaluation, and assessment of small airway dysfunction by pulmonary function testing (MEF 25–75, RV/TLC, and DLCO) and paired inspiratory and expiratory HRCT-chest to measure the mean lung density (MLD) as well as assessment of neutrophilic airway inflammation by taking BAL via bronchoscopy and examined for differential cell count.ResultsThe small airway dysfunction is more severe in the case of the FE COPD group as there were statistically significant differences between FE and IFE COPD groups in %MEF 25–75 and RV/TLC (p = 0.038 and p = 0.030, respectively). The mean value of the BAL neutrophil % was higher in FE than in IFE COPD patients but without a significant statistical difference (p = 0.513). There were statistically significant negative correlations between %FEV1 (p = 0.026), %FVC (p = 0.020), and %MEF25–75 (p = 0.005) and MLD(E/I) in all studied COPD patients.ConclusionCOPD patients associated with small airway dysfunction and increased BAL neutrophil cell count are more prone to frequent exacerbations.Trial registrationClinicalTrials.gov NCT06040931. Registered 18 Sept 2023—Retrospectively registered.

The combined effect of oxidative stress and TRPV1 on temperature-induced asthma: Evidence in a mouse model

Temperature is one of the possible activators for asthma. As global warming continues, the health hazard of high temperatures is increasing. It is unclear, nevertheless, how high temperatures affect asthma. The research aims to examine how asthma is affected by high temperatures and underlying molecular mechanisms. The BALB/c mice were adopted in a model of asthma. The mice were exposed at 24 °C, 38 °C and 40 °C for 4h on weekdays from day 1 to day 30. After the experiment, the lung function was measured in vivo, and then serum protein, pulmonary inflammation and immunohistochemistry assay was assessed in vitro. As the temperature increased from 24 °C to 40 °C, there was a significant increase in serum protein, while there is no discernible difference in serum protein of OVA-sIgE and OVA-sIgG between the OVA (38 °C) group and OVA (24 °C) group. The immunohistochemistry assay showed a change in the pro-inflammatory cytokines. The histopathological analysis exhibited the change of airway structure after high-temperature exposure, especially for exposure at 40 °C. The results of signals protein showed a remarkable rise of TRPV1 for OVA+40 °C. Our results revealed that high temperatures may make asthmatic airway dysfunction severe, and the higher the temperature, the more serious asthma. The oxidative stress and TRPV1 receptor can be a potential drug target for asthma. It will provide a new tool for precision medicine in asthma.

Physiological Characterization of Preserved Ratio Impaired Spirometry in the CanCOLD Study: Implications for Exertional Dyspnea and Exercise Intolerance.

Rationale: It is increasingly recognized that adults with preserved ratio impaired spirometry (PRISm) are prone to increased morbidity. However, the underlying pathophysiological mechanisms are unknown. Objectives: Evaluate the mechanisms of increased dyspnea and reduced exercise capacity in PRISm. Methods: We completed a cross-sectional analysis of the CanCOLD (Canadian Cohort Obstructive Lung Disease) population-based study. We compared physiological responses in 59 participants meeting PRISm spirometric criteria (post-bronchodilator FEV1 < 80% predicted and FEV1/FVC ⩾ 0.7), 264 control participants, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing. Measurements and Main Results: Individuals with PRISm had lower total lung, vital, and inspiratory capacities than healthy controls (all P < 0.05) and minimal small airway, pulmonary gas exchange, and radiographic parenchymal lung abnormalities. Compared with healthy controls, individuals with PRISm had higher dyspnea/[Formula: see text]o2 ratio at peak exercise (4.0 ± 2.2 vs. 2.9 ± 1.9 Borg units/L/min; P < 0.001) and lower [Formula: see text]o2peak (74 ± 22% predicted vs. 96 ± 25% predicted; P < 0.001). At standardized submaximal work rates, individuals with PRISm had greater Vt/inspiratory capacity (Vt%IC; P < 0.001), reflecting inspiratory mechanical constraint. In contrast to participants with PRISm, those with COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas exchange abnormalities. Despite these physiological differences among the three groups, the relationship between increasing dyspnea and Vt%IC during cardiopulmonary exercise testing was similar. Resting IC significantly correlated with [Formula: see text]o2peak (r = 0.65; P < 0.001) in the entire sample, even after adjusting for airflow limitation, gas trapping, and diffusing capacity. Conclusions: In individuals with PRISm, lower exercise capacity and higher exertional dyspnea than healthy controls were mainly explained by lower resting lung volumes and earlier onset of dynamic inspiratory mechanical constraints at relatively low work rates. Clinical trial registered with www.clinicaltrials.gov (NCT00920348).

CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways.

Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel by genetic mutations causes the inherited disease cystic fibrosis (CF). CF lung disease that involves multiple disorders of epithelial function likely results from loss of CFTR function as an anion channel conducting chloride and bicarbonate ions and its function as a cellular regulator modulating the activity of membrane and cytosol proteins. In the absence of CFTR activity, abundant mucus accumulation, bacterial infection and inflammation characterize CF airways, in which inflammation-associated tissue remodeling and damage gradually destroys the lung. Deciphering the link between CFTR dysfunction and bacterial infection in CF airways may reveal the pathogenesis of CF lung disease and guide the development of new treatments. Research efforts towards this goal, including high salt, low volume, airway surface liquid acidosis and abnormal mucus hypotheses are critically reviewed.

Impaired function in the lung periphery following COVID-19 is associated with lingering breathing difficulties.

Lingering breathing difficulties are common after COVID-19. However, the underlying causes remains unclear, with spirometry often being normal. We hypothesized that small airway dysfunction (SAD) can partly explain these symptoms. We examined 48 individuals (32 women, 4 hospitalized in the acute phase) who experienced dyspnea and/or cough in the acute phase and/or aftermath of COVID-19, and 22 non-COVID-19 controls. Time since acute infection was, median (range), 65 (10-131) weeks. We assessed SAD using multiple breath washout (MBW) and impulse oscillometry (IOS) and included spirometry and diffusing-capacity test (DLCO). One-minute-sit-to-stand test estimated physical function, and breathing difficulties were defined as answering "yes" to the question "do you experience lingering breathing difficulties?" Spirometry, DLCO, and IOS were normal in almost all cases (spirometry: 90%, DLCO: 98%, IOS: 88%), while MBW identified ventilation inhomogeneity in 50%. Breathing difficulties (n = 21) was associated with increased MBW-derived Sacin . However, physical function did not correlate with SAD. Among individuals with breathing difficulties, 25% had reduced physical function, 25% had SAD, 35% had both, and 15% had normal lung function and physical function. Despite spirometry and DLCO being normal in almost all post-COVID-19 individuals, SAD was present in a high proportion and was associated with lingering breathing difficulties.

Association between handgrip strength and small airway disease in patients with stable chronic obstructive pulmonary disease.

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. This study aimed to explore the correlation between handgrip strength (HGS) and SAD in COPD patients. Cross-sectional prospective study. 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. 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). 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. This study was registered with ClinicalTrials.gov with number NCT06223139.

Pulmonary function characteristics in children with suspected asthma: implications for asthma diagnosis.

In children suspected of asthma, diagnosis is confirmed via variable expiratory airflow limitation. However, there is no single gold standard test for diagnosing asthma. This study aimed to evaluate the pulmonary function characteristics in children suspected of asthma without bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR). We utilized two separate real-world retrospective observational cohorts of children who underwent both spirometry and bronchial provocation testing for asthma. Spirometry parameters were collected and compared between definite asthma, probable asthma, and non-asthma groups. The original cohort comprised 1199 children who visited the Severance Hospital (Seoul, Korea) between January 2017 and December 2019. The external cohort included 105 children who visited the Gangnam Severance Hospital between January 2019 and December 2019. Probable asthma accounted for 16.8% and 32.4% of the original and external cohorts, respectively. This group showed a significantly higher FeNO level and prevalence of allergic sensitization. Baseline forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75), and FEF75 showed stepwise decrements from non-asthma, probable asthma, to definite asthma patients (P < 0.001). The probable asthma group showed significantly higher odds of abnormal FEV1/FVC (OR, 2.24 [95%CI, 1.43-3.52])and FEF25-75 (2.05 [1.13-3.73]) than the non-asthma group and lower odds of abnormal FEV1(0.05 [0.01-0.19]),FEV1 /FVC (0.27 [0.18-0.41]), FEF25-75 (0.17 [0.11-0.28]), and FEF75 (0.14 [0.08-0.24]) compared to the definite asthma group. The external cohort was consistent with the original cohort. We show evidence of airway dysfunction in children for whom a high clinical suspicion of asthma exists without evidence of BDR and BHR. Repeated pulmonary function tests that closely monitor for subtle lung function impairments and active utilization of additional tests, such as allergic screening and FeNO, should be considered to close the gap in diagnosing asthma.

Small airway dysfunction measured by impulse oscillometry is associated with exacerbations and poor symptom control in patients with asthma treated in a tertiary hospital subspecialist airways disease clinic.

Small airways dysfunction contributes to asthma pathophysiology and clinical outcomes including exacerbations and asthma control. Respiratory oscillometry is a simple, non-invasive and effort independent lung function test that provides vital information about small airway function. However, interpretation and clinical utility of respiratory oscillometry has been in part limited by lack of agreed parameters and the respective cutoffs. The aim of this study was to determine the prevalence of small airways dysfunction based on published impulse oscillometry (IOS) definition in patients with asthma referred to a tertiary asthma clinic and the extent to which it correlates with asthma clinical outcomes. We retrospectively reviewed the medical records of all patients with asthma managed in the severe asthma clinic between January 2019 and December 2022 who underwent routine lung function tests with oscillometry and spirometry. Small airways dysfunction was determined from various published IOS parameter cutoffs, and the data were analysed to determine correlations between IOS parameters and asthma outcomes. Amongst the 148 patients, the prevalence of small airways dysfunction ranged from 53% to 78% depending on the defining oscillometry parameter. All oscillometry parameters correlated with the severity of airflow obstruction (FEV1% predicted, p < 0.001). Several oscillometry parameters correlated with asthma symptom burden, the strongest correlation was seen for frequency dependent resistance (R5-R20) with scores of Asthma Control Questionnaire (ACQ6) (Spearman's rank coefficient 0.213, p = 0.028) and Asthma Control Test (ACT) (Spearman's rank coefficient -0.248, p = 0.012). R5-R20 was predictive of poor asthma control defined by ACQ6 >1.5 (OR 2.97, p = 0.022) or ACT <20 (OR 2.44, p = 0.055). Small airways dysfunction defined by R5-R20 and area under the reactance curve (AX) also significantly increases asthma exacerbation risk (OR 2.60, p = 0.02 and OR 2.31, p = 0.03 respectively). Respiratory oscillometry is a sensitive measure of small airways dysfunction that should complement spirometry in the routine assessment of asthma. Small airways dysfunction is highly prevalent in patients with asthma referred to a tertiary asthma clinic. R5-R20 was the metric most predictive in identifying patients at risk of asthma exacerbations and poor asthma control.

Effect of somatotypes on lung volumes, capacities and respiratory impedance: A pilot study.

The current morphological condition of an individual is described by a somatotype, which is a three-number scale. The endomorph, mesomorph and ectomorph components are presented in the same sequence, and each number corresponds to one of the three basic components of body composition. We recruited 50 healthy male subjects with a mean age of 24.10 ± 4.55 yrs. Somatotype was determined by the Heath and Carter method. Impulse oscillometry was performed followed by spirometry according to the European Respiratory Society (ERS) or American Thoracic Society (ATS) guidelines. Resistance at 5 Hz (R5) %pred, R20%pred, R5-R20, X5%pred, X20, area of reactance (Ax) and resonant frequency (Fres) were obtained by doing impulse oscillometry. Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio and maximum mid-expiratory flow (MMEF) were assessed by doing spirometry. Endomorphs (0.05 (0.00-0.09) vs 0.01 (0.00-0.04); P < 0.0001) and mesomorphs (0.04 (0.000.09) vs 0.01 (0.00-0.04); P = 0.002) had significantly higher R5-R20 than ectomorphs. Similarly, endomorphs (0.32 (0.07-0.82) vs 0.15 (0.08-0.35); P = 0.001) and mesomorphs (0.28 (0.17-0.64) vs 0.15 (0.08-0.35); P = 0.015) also showed significantly higher Ax than ectomorphs, Fres of endomorphs (15.37 (8.43-21.85) vs 10.08 (8.94-14.30); P < 0.0001) and mesomorphs (14.32 (10.24-20.86) vs 10.08 (8.94-14.30); P < 0.0001) were significantly high than ectomorphs. Moreover, spirometric measures reveal significant variation in which mesomorphs had significantly higher values of % predicted of FVC than ectomorphs (92.49 ± 7.211 vs 83.86 ± 7.861; P = 0.042) and the ratio of FEV1 to FVC was significantly higher in ectomorphs than in endomorphs (89.00 ± 5.80 vs 85.04 ± 5.73; P = 0.03). Peripheral airway dysfunction was observed in endomorphs and mesomorphs as compared to ectomorphs. Mesomorphs had a relatively higher FVC that may be due to their greater muscular strength.

Factors associated with small airway obstruction in COVID-19 survivors: A cross-sectional study among health-care providers.

Coronavirus disease 2019 (COVID-19) has been identified for more than two years, yet studies assessing post-infection lung function are limited. Reports on lung function in COVID-19 patients indicate that patients have restrictive defects and small airway dysfunction that can persist and are not necessarily related to the severity of the disease. The aim of this study was to assess the incidence of small airway obstruction and its incidence-associated factors among COVID-19 survivors to better describe the long-term effects of COVID-19. A cross-sectional study was conducted among COVID-19 survivors who less than 50 years at Medan Adventist Hospital between 2020-2022. The data were collected through interview, direct assessment and respiratory examination. A total of 89 COVID-19 survivors were recruited of which the majority of them were female with a mean age of 32.6-year-old with the largest group was 19-30 years. The comorbidities found among the survivors were heart and thyroid disorders, with the most common symptom of post-COVID-19 was fatigue. Most of them had mild COVID-19. The mean forced mid-expiratory flow (FEF25-75%) was 96.3±20.22, with an incidence rate of small airway obstruction was 19.1%. Univariate and multivariate analyses indicated no significant association between age, gender, comorbidities, history of oxygenation during COVID-19 treatment, COVID-19 severity and the type of post COVID-19 syndrome symptoms with the incidence of small airway obstruction. In conclusion, among COVID-19 survivors who were less than 50 years old, those studied variables seems have less association with the incidence of small airway obstruction. Nevertheless, a further study with a bigger sample size is important to be conducted.

Mucus Transpiration as the Basis for Chronic Cough and Cough Hypersensitivity.

Chronic cough is characterized by a state of cough hypersensitivity. We analyze the process of transpiration, by which water appears to evaporate from laryngeal and tracheal mucus as from the surface of a leaf, as a potential cause of cough hypersensitivity. In this process, osmotic pressure differences form across mucus, pulling water toward the air, and preventing mucus dehydration. Recent research suggests that these osmotic differences grow on encounter with dry and dirty air, amplifying pressure on upper airway epithelia and initiating a cascade of biophysical events that potentially elevate levels of ATP, promote inflammation and acidity, threaten water condensation, and diminish mucus water permeability. Among consequences of this inflammatory cascade is tendency to cough. Studies of isotonic, hypotonic, and hypertonic aerosols targeted to the upper airways give insights to the nature of mucus transpiration and its relationship to a water layer that forms by condensation in the upper airways on exhalation. They also suggest that, while hypertonic NaCl and mannitol may provoke cough and bronchoconstriction, hypertonic salts with permeating anions and non-permeating cations may relieve these same upper respiratory dysfunctions. Understanding of mucus transpiration and its role in cough hypersensitivity can lead to new treatment modalities for chronic cough and other airway dysfunctions promoted by the breathing of dry and dirty air.

Ferroptosis-related genes are considered as potential targets for CPAP treatment of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common syndrome characterized by upper airway dysfunction during sleep. Continuous positive airway pressure (CPAP) is the most frequently utilized non-surgical treatment for OSA. Ferroptosis play a crucial role in the physiological diseases caused by chronic intermittent hypoxia, but its involvement in the development of OSA and the exact mechanisms have incompletely elucidated. GSE75097 microarray dataset was used to identify differentially expressed genes between OSA patients and CPAP-treated OSA patients. Subsequently, Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, STRING database, and FerrDb database were conducted to analyze the biological functions of differentially expressed genes and screen ferroptosis-related genes. Finally, GSE135917 dataset employed for validation. There were 1,540 differentially expressed genes between OSA patients and CPAP-treated OSA patients. These differentially expressed genes were significantly enriched in the regulation of interleukin-1-mediated signaling pathway and ferroptosis-related signaling pathway. Subsequently, 13 ferroptosis-related genes (DRD5, TSC22D3, TFAP2A, STMN1, DDIT3, MYCN, ELAVL1, JUN, DUSP1, MIB1, PSAT1, LCE2C, and MIR27A) were identified from the interaction between differentially expressed genes and FerrDb database, which are regarded as the potential targets of CPAP-treated OSA. These ferroptosis-related genes were mainly involved in cell proliferation and apoptosis and MAPK signaling pathway. Furthermore, DRD5 and TFAP2A were downregulated in OSA patients, which showed good diagnostic properties for OSA, but these abnormal signatures are not reversed with short-term effective CPAP therapy. In summary, the identification of 13 ferroptosis-related genes as potential targets for the CPAP treatment of OSA provides valuable insights into the development of novel, reliable, and accurate therapeutic options.