Search Results (22)

Background and Objectives: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition associated with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema, and with liver involvement through a distinct toxic gain-of-function mechanism. Despite its clinical relevance, AATD remains underdiagnosed and exhibits marked phenotypic heterogeneity. Artificial intelligence (AI) has shown growing potential in respiratory medicine, yet its application to AATD is still limited. This systematic review synthesizes the clinical evidence on AI in AATD, primarily in the respiratory domain and, where available, in hepatic outcomes. Materials and Methods: We conducted a PRISMA-guided search (PubMed, Web of Science, IEEE Xplore) for original, peer-reviewed articles (January 2014–September 2025) applying AI to detection, classification, stratification, or prediction tasks in AATD. Results: Six studies met eligibility criteria. Supervised models (e.g., XGBoost, penalized regression, Transformer-based architectures) and one unsupervised approach were identified. Applications included screening in COPD populations, prediction of emphysema progression from CT, proteomic modeling of lung function, identification of clinical subgroups, and prediction of clinical outcomes in AATD-associated liver disease. External validation and genotype diversity remained limited across studies. Conclusions: Although AI shows promise in improving detection, prognosis, and patient stratification in AATD across both respiratory and hepatic manifestations, the current evidence remains limited. Broader, multicenter validation in genotype-diverse cohorts is required to confirm its clinical utility and support the implementation of precision medicine in AATD. Full article

Chronic obstructive pulmonary disease (COPD) is a leading chronic disease worldwide, with significant healthcare utilization, morbidity, and mortality. Irreversible airflow obstruction identified on spirometry establishes the diagnosis of COPD, but the disease entity encompasses a heterogeneous collection of lung diseases, including chronic bronchitis and emphysema. Despite the enormous burden of COPD, there are no pharmacological therapies that slow its progression or reduce mortality, indicating the need for a deeper understanding. There are sex differences concerning COPD prevalence, pathology, and symptoms. Historically thought to primarily affect males, its effect on females has increased significantly over time due to a rising prevalence of smoking and exposure to harmful pollutants among females. Over the past decade, the age-adjusted prevalence of COPD has been consistently higher in females than in males. Despite this, the impacts of biological sex continue to be confusing and poorly defined. The primary goal of this review is to organize and collate sex-dependent factors that may contribute to disease differences in males and females, thereby identifying future research questions in this area. Full article

Injuries to humans caused by wild animals, particularly bears, are rarely mentioned in the literature. Such injuries are frequent in Siberia, which is a territory surrounded by dense forests inhabited by brown bears. In the last 4 months alone (September–December 2023), four bear attacks on humans were registered in Khakassia, Russia. This article presents a clinical case of rehabilitating a patient after a bear attack, who suffered multiple fragmentary fractures of the facial skeleton with displaced bone fragments, subcutaneous emphysema of the soft tissues of the face, damage to the parietal and right occipital regions and paranasal sinus hemorrhage on the left side. The nature of the injuries was enhanced by trauma to the upper extremity caused by the patient defending himself against the animal. In addition to the damage to his face, the bear tried to open his cranium, as evidenced by four furrows caused by its canines, including two each on the frontal and occipital bones of the skull. The patient’s complex treatment included both maxillofacial and reconstructive surgeries, and outpatient treatment involved the formation of normotrophic scars using a neodymium laser and injections of a heterogeneous composition consisting of microparticles of “crosslinked” collagen of animal origin placed in a gel identical to the natural extracellular matrix. Full article

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment for emphysema. Lung cancer may be associated with emphysema due to common risk factors. Thus, a growing number of patients undergoing BLVR may develop lung cancer. Herein, we evaluated the effects of lung resection for non-small cell lung cancer in patients undergoing BLVR. The clinical data of patients undergoing BLVR followed by lung resection for NSCLC were retrospectively reviewed. For each patient, surgical and oncological outcomes were recorded to define the effects of this strategy. Eight patients were included in our series. In all cases but one, emphysema was localized within upper lobes; the tumor was detected during routine follow-up following BLVR and it did not involve the treated lobe. The comparison of pre- and post-BLVR data showed a significant improvement in FEV1 (29.7 ± 4.9 vs. 33.7 ± 6.7, p = 0.01); in FVC (28.5 ± 6.6 vs. 32.4 ± 6.1, p = 0.01); in DLCO (31.5 ± 4.9 vs. 38.7 ± 5.7, p = 0.02); in 6MWT (237 ± 14 m vs. 271 ± 15 m, p = 0.01); and a reduction in RV (198 ± 11 vs. 143 ± 9.8, p = 0.01). Surgical resection of lung cancer included wedge resection (n = 6); lobectomy (n = 1); and segmentectomy (n = 1). No major complications were observed and the comparison of pre- and post-operative data showed no significant reduction in FEV1% (33.7 ± 6.7 vs. 31.5 ± 5.3; p = 0.15) and in DLCO (38.7 ± 5.7 vs. 36.1 ± 5.4; p = 0.15). Median survival was 35 months and no cancer relapses were observed. The improved lung function obtained with BLVR allowed nonsurgical candidates to undergo lung resection for lung cancer. Full article

COPD is a heterogeneous disease, and its acute exacerbation is a major prognostic factor. We used cluster analysis to predict COPD exacerbation due to subtypes of mild–moderate airflow limitation. In all, 924 patients from the Korea COPD Subgroup Study cohort, with a forced expiratory volume (FEV1) ≥ 50% and documented age, body mass index (BMI), smoking status, smoking pack-years, COPD assessment test (CAT) score, predicted post-bronchodilator FEV1, were enrolled. Four groups, putative chronic bronchitis (n = 224), emphysema (n = 235), young smokers (n = 248), and near normal (n = 217), were identified. The chronic bronchitis group had the highest BMI, and the one with emphysema had the oldest age, lowest BMI, and highest smoking pack-years. The young smokers group had the youngest age and the highest proportion of current smokers. The near-normal group had the highest proportion of never-smokers and near-normal lung function. When compared with the near-normal group, the emphysema group had a higher risk of acute exacerbation (OR: 1.93, 95% CI: 1.29–2.88). However, multiple logistic regression showed that chronic bronchitis (OR: 2.887, 95% CI: 1.065–8.192), predicted functional residual capacity (OR: 1.023, 95% CI: 1.007–1.040), fibrinogen (OR: 1.004, 95% CI: 1.001–1.008), and gastroesophageal reflux disease were independent predictors of exacerbation (OR: 2.646, 95% CI: 1.142–6.181). The exacerbation-susceptible subtypes require more aggressive prevention strategies. Full article

Introduction: The study was designed to evaluate the frequency of detection and the characteristics of subsolid nodules (SSNs) in outpatients’ chest computed tomography (CT) scans from a private hospital in Southern Brazil. Methods: A retrospective analysis of all chest CT scans was performed in adult patients from ambulatory care (non-lung cancer screening population) over a thirty-day period. Inclusion criteria were age > 18 years and lung-scanning protocols, including standard-dose high-resolution chest CT (HRCT), enhanced CT, CT angiography, and low-dose chest CT (LDCT). SSNs main features collected were mean diameter, number, density (pure or heterogenous ground glass nodules and part-solid), and localization. TheLungRADS system and the updated Fleischner Society’s pulmonary nodules recommendations were used for categorization only for study purposes, although not specifically fitting the population. The presence of emphysema, as well as calcified and solid nodules were also addressed. Statistical analysis was performed using R software, categorial variables are shown as absolute or relative frequencies, and continuous variables as mean and interquartile ranges. Results: Chest computed tomography were performed in 756 patients during the study period (September 2019), and 650 met the inclusion criteria. The IQR for age was 53/73 years; most participants were female (58.3%) and 10.6% had subsolid nodules detected. Conclusions: The frequency of SSNs detection in patients in daily clinical practice, not related to screening populations, is not negligible. Regardless of the final etiology, follow-up is often indicated, given the likelihood of malignancy for persistent lesions. Full article

Lung disease progression in alpha-1 antitrypsin deficiency (AATD) is heterogenous and manifests in different ways. Blood biomarkers are an attractive method of monitoring diseases as they are easy to obtain and repeatable. In non-AATD COPD, blood biomarker panels have predicted disease severity, progression, and mortality. We measured a panel of seven serum biomarkers in 200 AATD patients and compared levels between those with COPD and those without. We assessed whether biomarkers were associated with baseline lung function parameters (FEV1 and TLco) or absolute change in these parameters. In total, 111 patients with a severely deficient genotype of AATD (PiZZ) and COPD were included in the analyses. Pearson’s correlation coefficient was measured for biomarker correlations and models were compared using ANOVA. CRP and CCL18 were significantly higher in the serum of AATD COPD versus AATD with no COPD. Biomarkers were not predictive of cross-sectional lung function measurements, however, CC16 was significantly associated with an absolute change in TLco (p = 0.018). An addition of biomarkers to the predictive model for TLco added significant value over covariates alone (R² 0.13 vs. 0.02, p = 0.028). Our findings suggest that CC16 is predictive of emphysema progression in AATD COPD. Proteomics data may reveal alternative candidate biomarkers and further work should include the use of longitudinal biomarker measurements. Full article

COPD, one of world’s leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies. Full article

Cathepsin G (CatG) is a pro-inflammatory neutrophil serine protease that is important for host defense, and has been implicated in several inflammatory disorders. Hence, inhibition of CatG holds much therapeutic potential; however, only a few inhibitors have been identified to date, and none have reached clinical trials. Of these, heparin is a well-known inhibitor of CatG, but its heterogeneity and bleeding risk reduce its clinical potential. We reasoned that synthetic small mimetics of heparin, labeled as non-saccharide glycosaminoglycan mimetics (NSGMs), would exhibit potent CatG inhibition while being devoid of bleeding risks associated with heparin. Hence, we screened a focused library of 30 NSGMs for CatG inhibition using a chromogenic substrate hydrolysis assay and identified nano- to micro-molar inhibitors with varying levels of efficacy. Of these, a structurally-defined, octasulfated di-quercetin NSGM 25 inhibited CatG with a potency of ~50 nM. NSGM 25 binds to CatG in an allosteric site through an approximately equal contribution of ionic and nonionic forces. Octasulfated 25 exhibits no impact on human plasma clotting, suggesting minimal bleeding risk. Considering that octasulfated 25 also potently inhibits two other pro-inflammatory proteases, human neutrophil elastase and human plasmin, the current results imply the possibility of a multi-pronged anti-inflammatory approach in which these proteases are likely to simultaneously likely combat important conditions, e.g., rheumatoid arthritis, emphysema, or cystic fibrosis, with minimal bleeding risk. Full article

Since COPD is a heterogeneous disease, a specific anti-inflammatory therapy for this disease has not been established yet. Oxidative stress is recognized as a major predisposing factor to COPD related inflammatory responses, resulting in pathological features of small airway fibrosis and emphysema. However, little is known about effects of oxidative stress on airway smooth muscle. Cigarette smoke increases intracellular Ca²⁺ concentration and enhances response to muscarinic agonists in human airway smooth muscle. Cigarette smoke also enhances proliferation of these cells with altered mitochondrial protein. Hydrogen peroxide and 8-isoprostans are increased in the exhaled breath condensate in COPD. These endogenous oxidants cause contraction of tracheal smooth muscle with Ca²⁺ dynamics through Ca²⁺ channels and with Ca²⁺ sensitization through Rho-kinase. TNF-α and growth factors potentiate proliferation of these cells by synthesis of ROS. Oxidative stress can alter the function of airway smooth muscle through Ca²⁺ signaling. These phenotype changes are associated with manifestations (dyspnea, wheezing) and pathophysiology (airflow limitation, airway remodeling, airway hyperresponsiveness). Therefore, airway smooth muscle is a therapeutic target against COPD; oxidative stress should be included in treatable traits for COPD to advance precision medicine. Research into Ca²⁺ signaling related to ROS may contribute to the development of a novel agent for COPD. Full article

Background: Lung cancer represents a heterogeneous group of neoplasms, with the highest frequency and mortality in both sexes combined. In a clinical scenario characterized by the widespread of multidetector-row spiral CT, core-needle biopsy under tomographic guidance is one of the main and safest methods to obtain tissue specimens, even though there are relatively high rates of pneumothorax (0–60% incidence) and pulmonary hemorrhage (4–27% occurrence rates). The aim of this retrospective study is to assess the diagnostic accuracy of CT-guided core-needle biopsy in the diagnosis of primary lung malignancies and to compare our results with evidence from the literature. Materials and Methods: Our analysis included 350 thoracic biopsies, performed from 2017 to 2022 with a 64-row CT guidance and 16/18 G needles mounted on a biopsy gun. We included in the final cohort all samples with evidence of primary lung malignancies, precursor lesions, and atypia, as well as inconclusive and negative diagnoses. Results: There was sensitivity of 90.07% (95% CI 86.05–93.25%), accuracy of 98.87% (95% CI 98.12–99.69%), positive predictive value of 100%, and negative value of 98.74% (95% CI 98.23–99.10%). Specificity settled at 100% (93.84–100%). The AUC was 0.952 (95% CI 0.924–0.972). Only three patients experienced major complications after the procedure. Among minor complications, longer distances from the pleura, the presence of emphysema, and the lower dimensions of the lesions were correlated with the development of pneumothorax after the procedure, while longer distances from the pleura and the lower dimensions of the lesions were correlated with intra-alveolar hemorrhage. Immunohistochemistry analysis was performed in 51% of true positive cases, showing TTF-1, CK7, and p40 expression, respectively, in 26%, 24%, and 10% of analyzed samples. Conclusions: The CT-guided thoracic core-needle biopsy is an extremely accurate and safe diagnostic procedure for the histological diagnosis of lung cancer, a first-level interventional radiology exam for peripheral and subpleural lesions of the lung, which is also able to provide adequate samples for advanced pathologic assays (e.g., FISH, PCR) to assess molecular activity and genetic sequencing. Full article

Chronic obstructive pulmonary disease (COPD) and emphysema are characterized by functional and structural damage which increases the spaces for gaseous diffusion and impairs oxygen exchange. Here we explore the potential for hyperpolarized (HP) ³He MRI to characterize lung structure and function in a large-scale population-based study. Participants (n = 54) from the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study, a nested case-control study of COPD among participants with 10+ packyears underwent HP ³He MRI measuring p_AO₂, apparent diffusion coefficient (ADC), and ventilation. HP MRI measures were compared to full-lung CT and pulmonary function testing. High ADC values (>0.4 cm²/s) correlated with emphysema and heterogeneity in p_AO₂ measurements. Strong correlations were found between the heterogeneity of global p_AO₂ as summarized by its standard deviation (SD) (p < 0.0002) and non-physiologic p_AO₂ values (p < 0.0001) with percent emphysema on CT. A regional study revealed a strong association between p_AO₂ SD and visual emphysema severity (p < 0.003) and an association with the paraseptal emphysema subtype (p < 0.04) after adjustment for demographics and smoking status. HP noble gas p_AO₂ heterogeneity and the fraction of non-physiological p_AO₂ results increase in mild to moderate COPD. Measurements of p_AO₂ are sensitive to regional emphysematous damage detected by CT and may be used to probe pulmonary emphysema subtypes. HP noble gas lung MRI provides non-invasive information about COPD severity and lung function without ionizing radiation. Full article

Chronic obstructive pulmonary disease (COPD) is a complex heterogeneous disease state with multiple phenotypic presentations that include chronic bronchitis and emphysema. Although COPD is a lung disease, it has systemic manifestations that are associated with a dysregulated metabolome in extrapulmonary compartments (e.g., blood and urine). In this scoping review of the COPD metabolomics literature, we identified 37 publications with a primary metabolomics investigation of COPD phenotypes in human subjects through Google Scholar, PubMed, and Web of Science databases. These studies consistently identified a dysregulation of the TCA cycle, carnitines, sphingolipids, and branched-chain amino acids. Many of the COPD metabolome pathways are confounded by age and sex. The effects of COPD in young versus old and male versus female need further focused investigations. There are also few studies of the metabolome’s association with COPD progression, and it is unclear whether the markers of disease and disease severity are also important predictors of disease progression. Full article

Background: Chronic obstructive pulmonary disease (COPD) continues to pose a therapeutic challenge. This may be connected with its nosological heterogeneity, broad symptomatology spectrum, varying disease course, and therapy response. The last three decades has been characterized by increased understanding of the pathobiology of COPD, with associated advances in diagnostic and therapeutic modalities; however, the identification of pathognomonic biomarkers that determine disease severity, affect disease course, predict clinical outcome, and inform therapeutic strategy remains a work in progress. Objectives: Hypothesizing that a multi-variable model rather than single variable model may be more pathognomonic of COPD emphysema (COPD-E), the present study explored for disease-associated determinants of disease severity, and treatment success in Taiwanese patients with COPD-E. Methods: The present single-center, prospective, non-randomized study enrolled 125 patients with COPD and 43 healthy subjects between March 2015 and February 2021. Adopting a multimodal approach, including bioinformatics-aided analyses and geospatial modeling, we performed an integrated analysis of selected epigenetic, clinicopathological, geospatial, and air pollutant variables, coupled with correlative analyses of time-phased changes in pulmonary function indices and COPD-E severity. Results: Our COPD cohort consisted of 10 non-, 57 current-, and 58 ex-smokers (median age = 69 ± 7.76 years). Based on the percentages of low attenuation area below − 950 Hounsfield units (%LAA_-950insp), 36 had mild or no emphysema (%LAA_-950insp < 6), 22 were moderate emphysema cases (6 ≤ %LAA_-950insp < 14), and 9 presented with severe emphysema (%LAA-950insp ≥ 14). We found that BMI, lnc-IL7R, PM_2.5, PM₁₀, and SO₂ were differentially associated with disease severity, and are highly-specific predictors of COPD progression. Per geospatial levels, areas with high BMI and lnc-IL7R but low PM_2.5, PM₁₀, and SO₂ were associated with fewer and ameliorated COPD cases, while high PM_2.5, PM₁₀, and SO₂ but low BMI and lnc-IL7R characterized places with more COPD cases and indicated exacerbation. The prediction pentad effectively differentiates patients with mild/no COPD from moderate/severe COPD cases, (mean AUC = 0.714) and exhibited very high stratification precision (mean AUC = 0.939). Conclusion: Combined BMI, lnc-IL7R, PM_2.5, PM₁₀, and SO₂ levels are optimal classifiers for accurate patient stratification and management triage for COPD in Taiwan. Low BMI, and lnc-IL7R, with concomitant high PM_2.5, PM₁₀, and SO₂ levels is pathognomonic of exacerbated/aggravated COPD in Taiwan. Full article

Introduction Older patients have an increased risk of morbidity and mortality after colorectal cancer (CRC) surgery. Existing CRC surgical prediction models have not incorporated geriatric predictors, limiting applicability for preoperative decision-making. The objective was to develop and internally validate a predictive model based on preoperative predictors, including geriatric characteristics, for severe postoperative complications after elective surgery for stage I–III CRC in patients ≥70 years. Patients and Methods: A prospectively collected database contained 1088 consecutive patients from five Dutch hospitals (2014–2017) with 171 severe complications (16%). The least absolute shrinkage and selection operator (LASSO) method was used for predictor selection and prediction model building. Internal validation was done using bootstrapping. Results: A geriatric model that included gender, previous DVT or pulmonary embolism, COPD/asthma/emphysema, rectal cancer, the use of a mobility aid, ADL assistance, previous delirium and polypharmacy showed satisfactory discrimination with an AUC of 0.69 (95% CI 0.73–0.64); the AUC for the optimism corrected model was 0.65. Based on these predictors, the eight-item colorectal geriatric model (GerCRC) was developed. Conclusion: The GerCRC is the first prediction model specifically developed for older patients expected to undergo CRC surgery. Combining tumour- and patient-specific predictors, including geriatric predictors, improves outcome prediction in the heterogeneous older population. Full article