Small Airways Research Articles

Personalized pulmonary rehabilitation program for patients with post-acute sequelae of COVID-19: A proof-of-concept retrospective study.

Long-COVID patients present with a decline in physical fitness. The aim of this study is to reveal the impact of pulmonary rehabilitation (PR) on physical fitness, quality of life (QoL), and parameters of quantified thorax CT. Long-COVID patients enrolled in a 3-month PR program were retrospectively studied. PR included endurance and resistance training three times a week. Assessments pre- and post-rehabilitation included quantified chest CT, pulmonary function tests (PFT), six-minute walk test (6MWT), cardiopulmonary exercise test, and questionnaires: Hospital Anxiety and Depression Scale, post-COVID-19 Functional Status scale, Borg score, and EuroQol. Seventeen subjects (5M/12F), mean age 42 ± 13 years, were included. PR improved all questionnaires' results significantly. Only significant difference in PFT parameters was correlation between baseline total lung capacity (TLC) and difference in TLC pre- and post-rehabilitation (p = 0.002). 6MWT increased from 329 to 365 m (p < 0.001), VO2max changed from 21 to 24 mL/kg/min (p = 0.007), peak load increased from 116 to 141 Watt (p < 0.001). Blood volume in small pulmonary vessels of 1.25 to 5 mm2 in cross-sectional area (BV5%) was higher than observed in patients with acute COVID-19 infection. After rehabilitation, BV5% decreased from 65% to 62% (p = 0.020). These changes correlated directly with changes in TLC (p = 0.039). Quantified CT airway volume increased after rehabilitation (p = 0.013). After rehabilitation, TLC tended to normalize due to (re)opening of small airways, with decline in air trapping and recruitment of alveoli. Furthermore, this study revealed that pulmonary rehabilitation can improve QoL and physical fitness in long-COVID patients.

Comparison of Forced Expiratory Flow (FEF) 25-75% between Post-COVID-19 Patients with Different Severity at Universitas Gadjah Mada Academic Hospital

Introduction: Shortness of breath is the most distressing long COVID-19 symptom associated with the decline of small airway function, as shown by a decrease in forced expiratory flow (FEF) 25-75% value in the spirometry test. This study aimed to compare FEF 25-75% values as a predictor of small airway disease between mild-moderate and severe-critical long COVID-19 patients. Methods: This study used a prospective cohort design that included 24 post-hospitalized COVID-19 patients who came to the long COVID-19 clinic at Universitas Gadjah Mada Academic Hospital (UGM AH), Yogyakarta. The subjects were divided into mild-moderate and severe-critical groups based on the World Health Organization (WHO) classification. The subjects were tested for spirometry three months after the onset of COVID-19 symptoms. The comparison of both severity groups used the percent prediction of FEF 25-75% spirometry results. The value was interpreted as abnormal if the predicted FEF 25-75% value was below 65%. Results: There were three (25%) and two (16.67%) subjects with FEF 25-75% predicted below normal values in the mild-moderate and severe-critical groups consecutively, which showed a decline in small airway function. This study showed no statistically significant differences (p-value = 0.882) between the means of FEF 25-75% predicted values of the two groups. Conclusion: A small proportion of post-COVID-19 syndrome patients had small airway disease, and there were no statistical differences in small airway function between the groups.

The Unveiled Triad: Clinical, Radiological and Pathological Insights into Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) is a diffuse parenchymal lung disease (DLPD) characterized by complex interstitial lung damage with polymorphic and protean inflammatory aspects affecting lung tissue targets including small airways, the interstitium, alveolar compartments and vascular structures. HP shares clinical and often radiological features with other lung diseases in acute or chronic forms. In its natural temporal evolution, if specific therapy is not initiated promptly, HP leads to progressive fibrotic damage with reduced lung volumes and impaired gas exchange. The prevalence of HP varies considerably worldwide, influenced by factors like imprecise disease classification, diagnostic method limitations for obtaining a confident diagnosis, diagnostic limitations in the correct processing of high-resolution computed tomography (HRCT) radiological parameters, unreliable medical history, diverse geographical conditions, heterogeneous agricultural and industrial practices and occasionally ineffective individual protections regarding occupational exposures and host risk factors. The aim of this review is to present an accurate and detailed 360-degree analysis of HP considering HRCT patterns and the role of the broncho-alveolar lavage (BAL), without neglecting biopsy and anatomopathological aspects and future technological developments that could make the diagnosis of this disease less challenging.

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.

Quantification of smooth muscle in human airways by polarization-sensitive optical coherence tomography requires correction for perichondrium.

Quantifying airway smooth muscle (ASM) in patients with asthma raises the possibility of improved and personalized disease management. Endobronchial polarization-sensitive optical coherence tomography (PS-OCT) is a promising quantitative imaging approach that is in the early stages of clinical translation. To date, only animal tissues have been used to assess the accuracy of PS-OCT to quantify absolute (rather than relative) ASM in cross sections with directly matched histological cross sections as validation. We report the use of whole fresh human and pig airways to perform a detailed side-by-side qualitative and quantitative validation of PS-OCT against gold-standard histology. We matched and quantified 120 sections from five human and seven pig (small and large) airways and linked PS-OCT signatures of ASM to the tissue structural appearance in histology. Notably, we found that human cartilage perichondrium can share with ASM the properties of birefringence and circumferential alignment of fibers, making it a significant confounder for ASM detection. Measurements not corrected for perichondrium overestimated ASM content several-fold (P < 0.001, paired t test). After careful exclusion of perichondrium, we found a strong positive correlation (r = 0.96, P < 0.00001) of ASM area measured by PS-OCT and histology, supporting the method's application in human subjects. Matching human histology further indicated that PS-OCT allows conclusions on the intralayer composition and in turn potential contractile capacity of ASM bands. Together these results form a reliable basis for future clinical studies.NEW & NOTEWORTHY Polarization-sensitive optical coherence tomography (PS-OCT) may facilitate in vivo measurement of airway smooth muscle (ASM). We present a quantitative validation correlating absolute ASM area from PS-OCT to directly matched histological cross sections using human tissue. A major confounder for ASM quantification was observed and resolved: fibrous perichondrium surrounding hyaline cartilage in human airways presents a PS-OCT signature similar to ASM for birefringence and optic axis orientation. Findings impact the development of automated methods for ASM segmentation.

Loss of Airway Phylogenetic Diversity Is Associated with Clinical and Pathobiological Markers of Disease Development in Chronic Obstructive Pulmonary Disease.

Rationale: The airway microbiome has the potential to shape chronic obstructive pulmonary disease (COPD) pathogenesis, but its relationship to outcomes in milder disease is unestablished. Objectives: To identify sputum microbiome characteristics associated with markers of COPD in participants of the Subpopulations and Intermediate Outcome Measures of COPD Study (SPIROMICS). Methods: Sputum DNA from 877 participants was analyzed using 16S ribosomal RNA gene sequencing. Relationships between baseline airway microbiota composition and clinical, radiographic, and mucoinflammatory markers, including longitudinal lung function trajectory, were examined. Measurements and Main Results: Participant data represented predominantly milder disease (Global Initiative for Chronic Obstructive Lung Disease stage 0-2 obstruction in 732 of 877 participants). Phylogenetic diversity (i.e., range of different species within a sample) correlated positively with baseline lung function, decreased with higher Global Initiative for Chronic Obstructive Lung Disease stage, and correlated negatively with symptom burden, radiographic markers of airway disease, and total mucin concentrations (P < 0.001). In covariate-adjusted regression models, organisms robustly associated with better lung function included Alloprevotella, Oribacterium, and Veillonella species. Conversely, lower lung function, greater symptoms, and radiographic measures of small airway disease were associated with enrichment in members of Streptococcus, Actinobacillus, Actinomyces, and other genera. Baseline sputum microbiota features were also associated with lung function trajectory during SPIROMICS follow-up (stable/improved, decline, or rapid decline groups). The stable/improved group (slope of FEV1 regression ⩾66th percentile) had greater bacterial diversity at baseline associated with enrichment in Prevotella, Leptotrichia, and Neisseria species. In contrast, the rapid decline group (FEV1 slope ⩽33rd percentile) had significantly lower baseline diversity associated with enrichment in Streptococcus species. Conclusions: In SPIROMICS, baseline airway microbiota features demonstrate divergent associations with better or worse COPD-related outcomes.

Prevalence of respiratory morbidities and lung function outcome in Traffic Police in eastern Nepal

Introduction: Outdoor air pollution is a cause for occupational lung disease. A community vulnerable to lung health hazards of outdoor air pollutants from vehicle emissions is traffic police, whose long duration of outdoor work, with no proper protective equipment, predisposes them to respiratory symptoms such as cough, dryness of nose, throat irritation and wheezing due to the air pollutants causing inflammation of the airways. The risks to lung function and development of respiratory disease are not known in traffic police in eastern Nepal. Objectives: To determine respiratory morbidities and lung function values of traffic police working in eastern Nepal. Methodology: This cross-sectional study was conducted for 6 months, from 1st January to 30th June 2022, in traffic police using a structured questionnaire adapted from American Thoracic Society and National Heart &amp; Lung Institute and portable spirometry, at the duty posts or office. Data were represented using descriptive statistics. Results: The study enrolled 129 traffic police in eastern Nepal, 109 (84.50%) were male and 20 (15.50%) females, mean age 34.50 (±8). Mean duration of active duty was 9.76 years (±6.19). Cough was present in 33 (25.58%), 50 (38.76%) phlegm, 37 (28.68%) dyspnea, and 28 (21.71%) noisy breathing. Mean FEV1% in ≤ 5 years exposure was 76.75 (±17.28), and 65.26 (±18.88) in &gt; 15 years. Mean FVC% in ≤ 5 years exposure was 81.81 (±20.56) and 76.18 (±19.77) in those working &gt;15 years. Mean FEF25-75% in ≤ 5 years was 73.69 (±23.73), which was 62.04 (±33.97) in those &gt; 15 years. The spirometry analysis suggested obstructive airways disease in 90 personnel (69.8%), restrictive disease in 80 (62%), mixed airways disease in 72 (55.8%), and small airways disease in 52 (40.3%). Conclusion: There was increased burden of respiratory problems such as cough with sputum production, noisy breathing, and dyspnea and lower lung volumes and flows among traffic police working in different parts of eastern Nepal. Long duration of exposure to traffic environments resulted in spirometry analyses suggestive of obstructive and restrictive airways diseases.

Effects of type 2 inflammation on bronchodilator responsiveness of large and small airways in chronic obstructive pulmonary disease

To investigate the impact of type 2 inflammation markers blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) on bronchodilator responsiveness (BDR) in patients with chronic obstructive pulmonary disease (COPD). This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October, 2019 to October, 2023, who all underwent bronchial dilation test (BDT) of the large and small airways. Based on smoking history, blood EOS, and FeNO, these patients were divided group A (blood EOS < 300/μL + FeNO < 35 ppb + smoking history < 20 pack-years), group B (blood EOS < 300/μL+FeNO < 35 ppb+smoking history ≥20 pack-years), group C (blood EOS ≥300/μL or FeNO≥35 ppb+smoking history ≥20 pack-years), and group D (blood EOS ≥300/μL or FeNO ≥35 ppb+smoking history < 20 pack-years) for analyzing the relationship between clinical indexes and BDR. BDR evaluation based on forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) yielded consistent results, all showing a younger mean age, higher FeNO levels, and higher blood EOS counts and percentages in patients positive for BDT (P < 0.05). The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D. The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D. In the overall patients, age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF (P < 0.05). Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients, and their clinical significance needs further investigation.

Effect of twice daily inhaled albuterol on cardiopulmonary exercise outcomes, dynamic hyperinflation, and symptoms in secondhand tobacco-exposed persons with preserved spirometry and air trapping: a randomized controlled trial

BackgroundIn tobacco-exposed persons with preserved spirometry (active smoking or secondhand smoke [SHS] exposure), air trapping can identify a subset with worse symptoms and exercise capacity. The physiologic nature of air trapping in the absence of spirometric airflow obstruction remains unclear. The aim of this study was to examine the underlying pathophysiology of air trapping in the context of preserved spirometry and to determine the utility of bronchodilators in SHS tobacco-exposed persons with preserved spirometry and air trapping.MethodsWe performed a double-blinded placebo-controlled crossover randomized clinical trial in nonsmoking individuals at risk for COPD due to exposure to occupational SHS who had preserved spirometry and air trapping defined as either a residual volume-to-total lung capacity ratio (RV/TLC) > 0.35 or presence of expiratory flow limitation (EFL, overlap of tidal breathing on maximum expiratory flow-volume loop) on spirometry at rest or during cardiopulmonary exercise testing (CPET). Those with asthma or obesity were excluded. Participants underwent CPET at baseline and after 4-week trials of twice daily inhalation of 180 mcg of albuterol or placebo separated by a 2-week washout period. The primary outcome was peak oxygen consumption (VO2) on CPET. Data was analyzed by both intention-to-treat and per-protocol based on adherence to treatment prescribed.ResultsOverall, 42 participants completed the entire study (66 ± 8 years old, 91% female; forced expiratory volume in 1 s [FEV1] = 103 ± 16% predicted; FEV1 to forced vital capacity [FVC] ratio = 0.75 ± 0.05; RV/TLC = 0.39 ± 0.07; 85.7% with EFL). Adherence was high with 87% and 93% of prescribed doses taken in the treatment and placebo arms of the study, respectively (P = 0.349 for comparison between the two arms). There was no significant improvement in the primary or secondary outcomes by intention-to-treat or per-protocol analysis. In per-protocol subgroup analysis of those with RV/TLC > 0.35 and ≥ 90% adherence (n = 27), albuterol caused an improvement in peak VO2 (parameter estimate [95% confidence interval] = 0.108 [0.014, 0.202]; P = 0.037), tidal volume, minute ventilation, dynamic hyperinflation, and oxygen-pulse (all P < 0.05), but no change in symptoms or physical activity.ConclusionsAlbuterol may improve exercise capacity in the subgroup of SHS tobacco-exposed persons with preserved spirometry and substantial air trapping. These findings suggest that air trapping in pre-COPD may be related to small airway disease that is not considered significant by spirometric indices of airflow obstruction.

Chest CT at X-Ray Dose Using a Noise-Mitigating Weighted Projection: The Thoracic Tomogram. Diagnostic Performance for Pneumonia Detection in Hemato-Oncology Patients.

To compare the diagnostic performance of a thick-slab reconstruction obtained from an ultra-low-dose CT (termed thoracic tomogram) with standard-of-care low-dose CT (SOC-CT) for rapid interpretation and detection of pneumonia in hemato-oncology patients. Hemato-oncology patients with a working diagnosis of pneumonia underwent an SOC-CT followed by an ultra-low-dose CT, from which the thoracic tomogram (TT) was reconstructed. Three radiologists evaluated the TT and SOC-CT in the following categories: (I) infectious/inflammatory opacities, (II) small airways infectious/inflammatory changes, (III) atelectasis, (IV) pleural effusions, and (V) interstitial abnormalities. The TT interpretation time and radiation dose were recorded. Sensitivity, specificity, diagnostic accuracy, ROC, and AUC were calculated with the corresponding power analyses. The agreement between TT and SOC-CT was calculated by Correlation Coefficient for Repeated Measures (CCRM), and the Shrout-Fleiss intra-class correlations test was used to calculate interrater agreement. Forty-seven patients (mean age 58.7 ± 14.9 years; 29 male) were prospectively enrolled. Sensitivity, specificity, accuracy, AUC, and Power for categories I/II/III/IV/V were: 94.9/99/97.9/0.971/100, 78/91.2/86.5/0.906/100, 88.6/100/97.2/0.941/100, 100/99.2/99.3/0.995/100, and 47.6/100/92.2/0.746/87.3. CCRM between TT and SOC-CT for the same categories were .97/.81/.92/.96/.62 with an interobserver agreement of .93/.88/.82/.96/.61. Mean interpretation time was 18.6 ± 5.4 seconds. The average effective radiation dose of TT was similar to a frontal and lateral chest X-ray (0.27 ± 0.08 vs 1.46 ± 0.64 mSv for SOC-CT; P < .01). Thoracic tomograms provide comparable diagnostic information to SOC-CT for the detection of pneumonia in immunocompromised patients at one-fifth of the radiation dose with high interobserver agreement.

Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase.

Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50µl, 0.667IU) to induce emphysema. Treatment with PNU-282987 (2.0mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1β, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.

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.

Clinical features of Mycoplasma pneumoniae pneumonia in children without fever

BackgroundMycoplasma pneumoniae (MP) is one of the most common causes of community-acquired pneumonia in children. Most children have fever. In 2021, we found that the proportion of children without fever increased. The aim of this study is to summarize the differences in the clinical characteristics of children with MP pneumonia who are febrile or not, and to raise awareness of children who are not febrile.MethodDemographic information of the children was collected on admission. Clinical manifestations during the course of the disease and the first laboratory, imaging, and pulmonary function tests before discharge were recorded and compared.ResultsFrom August to December, a total of 542 people were included in the study. We found that older children were more likely to have fever. Inflammatory indicators including procalcitonin (P = 0.030), C-reaction protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), ferritin (P = 0.040) and the rate of atelectasis (P = 0.049) of febrile children were higher in febrile children. However, the elevated lactate dehydrogenase and pulmonary function impairment (P all > 0.05), especially the small airway function impairment, are no lower in afebrile children than in febrile children.ConclusionThe fever rate is lower in younger children, but wheezing is more common. In afebrile children, the impairment of organ and lung function was no less than in febrile children. Therefore, attention should also be paid to children who are not febrile.

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.

Real-Time Exposure to 3D-Printing Emissions Elicits Metabolic and Pro-Inflammatory Responses in Human Airway Epithelial Cells.

Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical and particle emission exposures during operation. Although the composition of 3D printer emissions varies depending on printer settings and materials, little is known about the impact that emissions from different filament types may have on respiratory health and underlying cellular mechanisms. In this study, we used an in vitro exposure chamber system to deliver emissions from two popular 3D-printing filament types, acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), directly to human small airway epithelial cells (SAEC) cultured in an air-liquid interface during 3D printer operation. Using a scanning mobility particle sizer (SMPS) and an optical particle sizer (OPS), we monitored 3D printer particulate matter (PM) emissions in terms of their particle size distribution, concentrations, and calculated deposited doses. Elemental composition of ABS and PLA emissions was assessed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, we compared the effects of emission exposure on cell viability, inflammation, and metabolism in SAEC. Our results reveal that, although ABS filaments emitted a higher total concentration of particles and PLA filaments emitted a higher concentration of smaller particles, SAEC were exposed to similar deposited doses of particles for each filament type. Conversely, ABS and PLA emissions had distinct elemental compositions, which were likely responsible for differential effects on SAEC viability, oxidative stress, release of inflammatory mediators, and changes in cellular metabolism. Specifically, while ABS- and PLA-emitted particles both reduced cellular viability and total glutathione levels in SAEC, ABS emissions had a significantly greater effect on glutathione relative to PLA emissions. Additionally, pro-inflammatory cytokines including IL-1β, MMP-9, and RANTES were significantly increased due to ABS emissions exposure. While IL-6 and IL-8 were stimulated in both exposure scenarios, VEGF was exclusively increased due to PLA emissions exposures. Notably, ABS emissions induced metabolic perturbation on amino acids and energy metabolism, as well as redox-regulated pathways including arginine, methionine, cysteine, and vitamin B3 metabolism, whereas PLA emissions exposures caused fatty acid and carnitine dysregulation. Taken together, these results advance our mechanistic understanding of 3D-printer-emissions-induced respiratory toxicity and highlight the role that filament emission properties may play in mediating different respiratory outcomes.

Risk factors for the development of bronchiolitis obliterans in children after suffering from adenovirus pneumonia.

Bronchiolitis obliterans (BO) is an irreversible chronic obstructive lung disease in small airways. The aim of this study was to identify the relevant risk factors for the development of BO in children after suffering from adenovirus (ADV) pneumonia. An observational cohort study that included 112 children suffering from ADV pneumonia in our institution from March 2019 to March 2020 was performed. We divided the children into a BO group and a non-BO group based on whether they did develop BO or not. Univariate analysis and multivariate logistic regression analysis were applied to identify risk factors for the development of BO. The prediction probability model was evaluated by receiver operating characteristic (ROC) curve analysis. Twenty-eight children (25%) did develop BO after suffering from ADV pneumonia, while 84 children did not. Respiratory support (OR 6.772, 95% CI 2.060-22.260, P = 0.002), extended length of wheezing days (OR 1.112, 95% CI 1.040-1.189, P = 0.002) and higher lactic dehydrogenase (LDH) levels (OR 1.002, 95% CI 1.000-1.003, P = 0.012) were independently associated with the development of BO. The predictive value of this prediction probability model was validated by the ROC curve, with an area under the curve of 0.870 (95% CI 0.801-0.939, P < 0.001), a standard error of 0.035, a maximum Youden's index of 0.608, a sensitivity of 0.929, and a specificity of 0.679. After suffering an ADV pneumonia, children who have needed respiratory support, had a longer length of wheezing days or had higher LDH levels are more likely to develop BO.

Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis

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

Lung Involvement in Patients with Ulcerative Colitis: Relationship between Exhaled Nitric Oxide and Lung Function.

Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airway involvement. A reduction in CO diffusing capacity and functional alterations in small airways have been described. An extended analysis of fractional exhaled nitric oxide (FeNO) may distinguish the sites of production, and the presence of small airway inflammation may be a useful, non-invasive marker for patient follow-up. The aim of our study was to compare the PFTs as well as FeNO and CANO values of UC patients with different clinical disease activities and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. We enrolled 42 adult outpatients at different clinical activity stages of UC (39 ± 13 years) and a healthy control group of 41 subjects (29 ± 3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100, and 200 mL/s) were collected. All patients performed pulmonary function tests (PFTs) with static volumes and diffusing capacity (DLCO). FeNO and CANO values were significantly increased in UC patients when compared with controls (p = 0.0008 and p < 0.0001, respectively) and were proportional to disease activity (FeNO class 3: 28.1 ppb vs. classes 1-2: 7.7 ppb; CANO values class 3: 8.6 ppb vs. classes 1-2: 2.7 ppb (p < 0.0001)). TLC and DLCO were significantly reduced in severe (Mayo 3) UC patients (p = 0.010 and p = 0.003, respectively). The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with disease activity, suggesting the need for an integrated approach in routine assessment.

Comparison of particles in exhaled air and multiple breath washout for assessment of small airway function in children with cystic fibrosis.

The introduction of modulator therapy for cystic fibrosis (CF) has led to an increased interest in the detection of small airway disease (SAD) as sensitive marker of treatment response. The particles in exhaled air (PExA) method, which records exhaled particle mass (PEx ng/L) and number (PExNR), detects SAD in adult patients. Our primary aim was to investigate if PExA outcomes in children with CF are different when compared to controls and associated with more severe disease. Secondary aims were to assess feasibility and repeatability of PExA in children with CF and to correlate PExA to multiple breath nitrogen washout (MBNW) as an established marker of SAD. Thirteen healthy children (HC), 17 children with CF with normal lung function (CF-N) (FEV1 z-score ≥ -1.64) and six with airway obstruction (CF-AO) (FEV1 z-score < -1.64) between 8 and 18 years performed MBNW followed by PExA and spirometry. Children with CF repeated the measurements after 3 months. PEx ng/L and PExNR/L per liter of exhaled breath were similar between the three groups. The lung clearance index (LCI) was significantly higher in both CF-N and CF-AO compared to HC. All participants, except one, were able to perform PExA. Coefficient of variation for PEx ng/l was (median) 0.38, range 0-1.25 and PExNR/l 0.38, 0-1.09. Correlation between LCI and PEx ng/l was low, rs 0.32 (p = .07). PExA is feasible in children. In contrast to LCI, PExA did not differentiate healthy children from children with CF suggesting it to be a less sensitive tool to detect SAD.

Body composition and respiratory outcomes in children: a population-based prospective cohort study

BackgroundBody composition might influence lung function and asthma in children, but its longitudinal relations are unclear. We aimed to identify critical periods for body composition changes during childhood and adolescence...