Search Results (2,597)

Background/Objectives: Thoraco-abdominal asynchrony (TAA) is a key mechanical consequence of severe chronic obstructive pulmonary disease (COPD), particularly during acute exacerbations (AECOPD), when dynamic hyperinflation and diaphragmatic dysfunction impair the coordination between rib cage and abdominal motion. Continuous, non-invasive monitoring of respiratory mechanics may provide valuable information on clinical evolution during hospitalization. This study aimed to evaluate Global Phase Delay (GPD) as a longitudinal marker of TAA in hospitalized AECOPD patients and to explore its ability to reflect disease severity and short-term clinical evolution using repeated measurements obtained with thoracic and abdominal respiratory belts using respiratory inductance plethysmography (RIP). Methods: We conducted an observational longitudinal study in hospitalized adults with AECOPD. Respiratory inductance plethysmography signals were recorded daily over four consecutive days using thoracic and abdominal RIP belts. Five-breath sequences were analyzed to derive GPD, phase angle, and loop rotation direction through automated MATLAB processing. Clinical data included demographics, lung function, blood gases, dyspnea severity, and need for intermediate respiratory care unit (IRCU) admission. Temporal changes in TAA indices and subgroup differences (FEV₁ < 35%, IRCU admission) were assessed using repeated-measures ANOVA. Results: Twenty-one patients were included. On admission, mean absolute GPD was 49 ± 58°, with larger delays observed in patients with more severe airflow limitation and in those requiring IRCU support. During hospitalization, GPD showed a significant reduction over time (p < 0.05), particularly in these subgroups, indicating progressive improvement in thoraco-abdominal synchrony. Directional analysis of GPD revealed heterogeneous patterns consistent with different underlying mechanical behaviors. Conclusions: Serial assessment of TAA using respiratory bands and GPD provides clinically meaningful information on the evolution of respiratory mechanics during AECOPD hospitalization. This approach may support bedside monitoring and help track patient response to treatment, offering potential value for individualized respiratory management. Full article

Background: Patients with coexisting lung cancer and COPD are highly susceptible to unplanned readmissions. This study aimed to develop and internally validate a robust predictive nomogram based on the “inflammation-nutrition-tumor” framework to quantify this risk. Methods: A retrospective cohort of 207 clinical episodes from male patients with lung cancer and COPD was analyzed. Participants were categorized into Planned Readmission (PR, n = 165) and Unplanned Readmission (UR, n = 42) groups. Independent risk factors were identified via univariate and multivariable analyses using Generalized Estimating Equations (GEE). A nomogram was subsequently constructed, and its performance was rigorously evaluated using the Area Under the Curve (AUC), calibration plots, and Decision Curve Analysis (DCA). Results: Multivariable GEE analysis demonstrated that the Systemic Immune-Inflammation Index (SII) was a highly significant independent risk factor (OR for a 500-unit increase = 1.490, 95% CI: 1.234–1.798, p < 0.001). Advanced cancer stage (III–IV) was also a significant predictor (OR = 3.590, 95% CI: 1.301–9.909, p = 0.014), while prealbumin (OR = 0.950, 95% CI: 0.896–1.007, p = 0.087) was identified as a key nutritional predictor. The integrated four-variable nomogram (age, cancer stage, SII, prealbumin) demonstrated good discriminative ability with an AUC of 0.809 (95% CI: 0.733–0.885). The calibration plot indicated excellent agreement, and DCA confirmed a substantial clinical net benefit. Conclusions: This SII-based nomogram provides a reliable and practical tool for individualized risk stratification, facilitating targeted clinical interventions to mitigate unplanned readmission rates in this vulnerable population. Full article

Background: Diabetic foot infections (DFIs) are a major cause of hospitalization, limb loss, and mortality among patients with diabetic foot ulcers (DFUs). This study evaluated the risk of developing DFIs among patients with newly diagnosed DFUs across insurance categories. Methods: Adults ≥18 years with a new DFU diagnosis were identified in the PearlDiver insurance claims database (2010–2020) using validated ICD-9/10 codes. Insurance status at the index DFU was categorized as Medicaid, Medicare, commercial, or self-pay. Propensity score matching (1:3) based on age, sex, Charlson Comorbidity Index, and major comorbidities was used to compare Medicaid vs. non-Medicaid patients. Results: Among 258,122 patients with new DFUs, 20,638 (8.0%) were Medicaid beneficiaries. Medicaid patients were younger (50.1 ± 10.2 vs. 60.6 ± 12.1 years, p < 0.001) but had similar comorbidity burden compared with commercially insured and Medicare patients. In matched analysis post-matching, Medicaid insurance was independently associated with higher odds of DFI-related hospitalization within 12 months (aOR 1.18, 95% CI 1.14–1.24) and major amputation at 3 years (aOR 1.72, 95% CI 1.39–2.13). Higher CCI, chronic kidney disease, congestive heart failure, COPD, and peripheral vascular disease also predicted adverse outcomes. Conclusions: Medicaid insurance was independently associated with increased risks of DFI and major amputation among patients with newly diagnosed DFUs. These findings highlight infection as a potentially modifiable pathway driving limb loss and emphasize the need to improve early ulcer evaluation and infection management for Medicaid beneficiaries. Full article

Background: The use of HFNC (High Flow Nasal Cannula) in the management of acute respiratory failure has been fully established in clinical practice. Conversely, less data is available supporting its use in chronic hypoxemic–hypercapnic respiratory failure. The aim of the present study is to evaluate the efficacy of HFNC in chronic hypercapnic respiratory failure associated with stable COPD. Methods: In this retrospective single-center longitudinal observational study, 40 patients treated with HFNC at home followed at the COPD Clinic of Respiratory Diseases (University of Campania L. Vanvitelli Monaldi Hospital, Naples) were included. All patients are re-assessed at our clinic at T0, T3, T6 and T12 months through functional respiratory tests and blood gas analysis. Results: After 12 months, significant reductions in pCO₂ (arterial partial pressure of carbon dioxide) (from 58.5 to 48.0 mmHg) and lactates (from 1.60 to 0.90 mmol/L) were observed, and MIP and MEP improved significantly. Patients receiving HFNC flows ≥50 L/min experienced greater reductions in pCO₂ and fewer exacerbations. Multivariate analysis identified HFNC flow rate (p = 0.0046), hours of use/day (p = 0.0157), lactate levels (p = 0.0301), and FEV₁ (forced expiratory volume in 1 s) (p = 0.0491) as independent predictors of reduction in PaCO₂. Higher BMI and greater airway obstruction were associated with a reduced response. Conclusions: Treatment with HFNC represents a reasonable therapeutic choice to reduce AEs-COPD and reduce PaCO₂ and lactates in stable COPD patients. Full article

The aim of this study was to examine the factors associated with COVID-19-related fear in older adults from Kazakhstan, and to explore its associations with sociodemographic characteristics, health status and multiple domains of quality of life in a regional context. A total of 445 individuals aged 60 and above from both urban and rural locations in Kazakhstan participated in this cross-sectional study. To assess the quality of life among older people we used the OPQoL (Older People’s Quality of Life) Scale. Further variables were evaluated: sociodemographic (age, gender, education level, marital status, and place of residence); health-related (self-reported overall health, hypertension, diabetes, cerebrovascular disease, cardiovascular disease, and chronic obstructive pulmonary disease (COPD); and COVID-19-related fear variable. Female gender (OR = 2.344; p = 0.001), present hypertension (OR = 2.106; p = 0.008), the specialized secondary educational level (OR = 2.321; p = 0.012) and at the border of significance university educational level (OR = 1.832; p = 0.051) were variables significantly associated with the COVID-19-related fear in older adults. For individuals with reported COVID-19-related fear, advanced age was significantly negatively associated with leisure and activities domain (B = −0.747; p = 0.020) of OPQoL; better self-reported overall health was significantly positively associated with life overall domain (B = 0.691; p < 0.001), health domain (B = 1.320; p < 0.001), psychological and emotional well-being domain (B = 0.395; p = 0.001), home and neighborhood domain (B = 0.249; p = 0.036), independence, control over life and freedom domain (B = 1.082; p < 0.001), financial circumstances domain (B = 1.132; p < 0.001), and leisure and activities domain (B = 0.556; p = 0.026) of OPQoL; present hypertension was significantly negatively associated with health domain (B = −0.888; p = 0.004) of OPQoL; present cardiovascular disease was significantly negatively associated with life overall domain (B = −0.588; p = 0.027), health domain (B = −0.967; p = 0.009), and independence, control over life and freedom domain (B = −0.542; p = 0.039) of OPQoL; being single was significantly negatively associated with life overall domain (B = −0.481; p = 0.033), social relations domain (B = −0.671; p = 0.014) and financial circumstances domain (B = −0.694; p = 0.036) of OPQoL; and urban place of residency was significantly positively associated with health domain (B = 0.735; p = 0.011) and psychological and emotional well-being domain (B = 0.483; p = 0.010) of OPQoL. Our findings pointed that numerous variables were associated with the COVID-19-related fear and quality of life domains regarding COVID-19-related fear in older adults from Kazakhstan during pandemics. Full article

Background: COPD is a multifactorial chronic lung disease driven by an abnormal inflammatory reaction. It is well recognized that genetic factors play a role in susceptibility to COPD. Hence, polymorphism in pro-inflammatory cytokines, including interleukin-1 (IL-1), may confer a risk for the development of COPD. Methods: We genotyped 163 patients with COPD and 174 control individuals using a TaqMan genotyping assay for IL1B -511 C>T SNP and a PCR-RFLP-based method for IL1B +3953 C>T SNP and VNTR polymorphism in IL1RN in order to elucidate their possible role as candidate risk factors of COPD in a Bulgarian population. Results: The genotypes containing at least one variant T allele of IL1B -511 C>T SNP demonstrated a 2.1-fold higher risk for COPD after adjustment for age, sex, and smoking status (p = 0.011). The genotype with at least one T allele of IL1B +3953 C>T appeared to be protective, with a 2.21-fold lower risk for COPD after adjustment for sex, age, and smoking status (p = 0.007). The IL1B T_C haplotype showed a 1.70-fold higher risk of COPD (p = 0.018) in comparison to the C_T haplotype. Carriers of the VNTR IL1RN 1*3 genotype develop COPD earlier compared to 1*1 (p = 0.099). Patients with the 2*2 genotype had slightly higher FEV1/FVC (%) in comparison to 1*2 carriers (p = 0.09). Conclusions: To our knowledge, this study is the first to provide exploratory evidence on the T_C haplotype of IL1B -511 C>T; +3953 C>T that may be a predisposing factor for COPD in Bulgarian population. We suggest that the VNTR polymorphism of the IL1RN gene does not affect the risk for COPD but may lead to early disease development. Full article

Background: Coronary artery disease (CAD) commonly coexists with chronic obstructive pulmonary disease (COPD), but may be under-recognised, since symptoms such as dyspnoea and chest discomfort are often attributed to lung disease. We hypothesised that coronary artery disease is highly prevalent in patients with COPD, even in the absence of typical angina symptoms. Methods: This study aimed to detect CAD in patients with COPD. We conducted a single-centre observational study, including 76 patients with no known previous cardiovascular events. To detect ischaemic heart disease, three methods were used, according to standard clinical indications: coronary angiography, coronary CT, and calcium score analysis on chest CT. The findings were categorised according to lesion severity and vessel involvement. Results: A substantial proportion of patients with COPD harboured previously undiagnosed atherosclerotic coronary disease (78%). However, most detected disease was non-obstructive atherosclerosis (56%), whereas severe stenosis was present in approximately one-third of patients (32%). Single-vessel disease accounted for 37% of cases, while the remaining patients exhibited multi-vessel involvement. Nevertheless, only a small proportion of patients had typical angina symptoms (11.8%), and the most frequent complaint was effort dyspnoea (50%). Patients not receiving inhaled corticosteroid therapy were more likely to have extensive coronary artery disease (χ² (6)= 14.228, p = 0.027). Conclusions: These findings support our hypothesis that atherosclerotic coronary disease is often under-recognised in patients with COPD. ICS-containing therapy appeared to be associated with less extensive coronary artery involvement; however, this observation should be interpreted cautiously. Full article

Background/Objectives: An increasing proportion of patients with Type 2 diabetes mellitus (T2DM) are classified as high risk, often presenting with multimorbidity, functional vulnerability, and complex treatments. This study compared the sociodemographic, functional, clinical, therapeutic, and healthcare utilization profiles of high-risk chronic patients with and without T2DM in primary health care. Methods: A cross-sectional study included adults classified as high-risk chronic patients in primary health care electronic health records in the Madrid Region (30 April 2021). Sociodemographic, functional, clinical, lifestyle, pharmacological variables, and primary health care services utilization were analyzed. Multivariate logistic regression identified factors independently associated with T2DM. Results: Among 163,188 high-risk chronic patients, 41.5% had T2DM. Patients with T2DM were older, more often male, and had a comparable deprivation index values to non-diabetic patients. They showed higher functional dependency and greater need for informal caregiving. Clinically, patients with T2DM had a higher burden of chronic conditions and a predominance of cardiometabolic, hematological and renal comorbidities, whereas non-diabetic patients exhibited more neuropsychiatric, chronic infectious, oncological and respiratory profiles. Polypharmacy was more frequent in T2DM patients, who also showed lower medication adherence. In the explanatory model, older age (OR 1.02/year), cardiometabolic comorbidities (ORs ~1.2–1.6), highest quartile of morbidity complexity (OR 1.27), polypharmacy (OR 1.34), and concern about medications (OR 1.08) were associated with T2DM, while female sex (OR 0.660), depression (OR 0.888), COPD (0.704), neoplasms (0.688), and higher medication adherence (OR 0.53) were associated with not having T2DM. Conclusions: High-risk chronic patients with T2DM exhibit distinct sociodemographic, functional, and clinical profiles compared with those without T2DM, characterized by greater complexity, cardiometabolic burden, therapeutic intensity and use of healthcare services, supporting the need for tailored, integrated primary health care strategies. Full article

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide, yet only a fraction of smokers develops the disease, suggesting protective mechanisms in resilient individuals. Identifying airway-localized molecular signatures may improve our understanding of disease pathomechanisms and support hypothesis generation for biomarker research. In this pilot study, induced sputum from smokers with COPD (n = 28) and smokers without COPD (n = 16; Global Initiative for Chronic Obstructive Lung Disease (GOLD)-defined pre-COPD) was analyzed by untargeted proteomics, metabolomics, and lipidomics. After quality control, 1180 proteins, 187 metabolites, and 1234 lipids were retained. Analyses included univariate models with false discovery rate adjustment and multivariate analyses (PCA, PLS-DA), followed by pathway enrichment and protein interaction network analysis. While few features remained significant after FDR correction, consistent cross-omics patterns were observed. COPD was characterized by ↑ glutathione, creatine, and L-arginine; ↓ CCDC88A and ↑ STAT3 and SYDE2; and broad lipid remodeling involving phosphatidylcholines, sphingolipids, and eicosanoids. Network analysis highlighted STAT3 as a highly connected node linking COPD-related genes. These findings suggest that the multi-omic profiling of induced sputum can capture coherent airway-localized molecular signatures such as oxidative stress, cytoskeletal remodeling, and Rho-family GTPase signaling. However, the results should be interpreted as exploratory and require validation in functional studies. Full article

Lung diseases are among the leading causes of death worldwide. Nowadays, to detect lung diseases, a specialist uses auscultation to make a diagnosis. Newer auscultation devices based on stethoscopes allow these sounds to be recorded for later analysis. However, the diagnosis process is time-consuming and relies on medical expertise to generate an accurate diagnosis. For these reasons, automated and objective diagnostic systems are crucial for the early detection of lung diseases and preventing them from worsening. In this study, a computer-aided diagnostic system that integrates the Radial Short-Time Fourier Transform (RSTFT) with a Convolutional Neural Network (CNN) enhanced by attention mechanisms is presented. The RSTFT is employed to convert lung sound recordings from a public dataset into angular frequency representations, which are used as input to the CNN. The network automatically extracts discriminative features and classifies the recordings into five categories: Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, pneumonia, asthma, and healthy lungs. Experimental results demonstrate that the proposed method outperforms several state-of-the-art approaches in terms of accuracy, precision, recall, and F1-score. These findings indicate that the proposed RSTFT–CNN framework provides an effective and reliable solution for the automated diagnosis of lung diseases, offering valuable support for clinical decision-making and early intervention. Full article

Cognitive impairment is a serious comorbidity in chronic obstructive pulmonary disease (COPD), consistently associated with adverse clinical outcomes, including impaired self-management, poor treatment adherence, reduced participation in pulmonary rehabilitation, and increased risk of mortality. Despite this, it remains inconsistently recognised and insufficiently addressed during routine COPD assessment. This narrative review synthesises current evidence on the recognition and management of cognitive impairment in COPD, with a particular focus on understanding why it continues to be under-recognised and inadequately managed in clinical practice. Across care settings, cognitive concerns are commonly identified informally, assessed selectively, or deferred altogether, even when clinicians acknowledge their relevance to respiratory assessment, treatment implementation, and patient engagement. This persistent evidence–practice gap suggests the influence of factors extending beyond disease- or patient-related explanations alone. Emerging evidence indicates that clinician-level determinants, particularly clinical confidence, play a central role in shaping cognitive care practices. Limited clinical confidence appears to mediate the translation of existing knowledge and competence into clinical action, influencing decisions to initiate assessment, communicate cognitive concerns, assume clinical ownership, and pursue follow-up or referral. These confidence-related barriers are further reinforced by educational limitations, time constraints, diagnostic ambiguity, particularly in the early cognitive impairment stage, and the absence of clear operational guidance within COPD-specific frameworks. Conceptualising cognitive care through the lens of clinical confidence provides a coherent explanation for the underrecognition of cognitive impairment in COPD. It also helps account for observed variability in clinical decision-making, highlighting clinical confidence as a modifiable intermediary between knowledge, competence, and practice and a potential target for strengthening integrated, patient-centred COPD care. Full article

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory respiratory disorder with a globally increasing prevalence. Current therapeutic strategies are limited by drug resistance and safety concerns. Studies suggest that inhibiting the secretion of inflammatory cytokines represents a promising approach for COPD treatment. Phosphodiesterase-4 (PDE4) inhibitors have emerged as potent anti-inflammatory agents for respiratory diseases. In this study, we integrated a marine-derived natural product with computer-aided drug design to develop 32 novel PDE4 inhibitors. Compound B7 exhibited potent PDE4 inhibitory activity and a favorable safety profile. In rat model of COPD, B7 significantly reduced inflammatory cell infiltration and cytokine levels, ameliorated pathological changes in the lung, decreased the percentage of goblet cell positivity, and reduced expiratory resistance. Furthermore, in vitro mechanistic studies revealed that B7 exerts its anti-inflammatory effects by activating the cAMP-PKA-CREB signaling pathway and suppressing the NF-κB pathway in RAW264.7 cells. In conclusion, B7 demonstrates potential as a safe and effective PDE4-targeted candidate for the treatment of COPD. Full article

Objective: Acute exacerbations (AECOPD) are primary determinants of clinical instability in chronic obstructive pulmonary disease (COPD), and the “frequent exacerbator” (≥2/year) phenotype markedly increases morbidity and healthcare utilization. In this study, we evaluated the association between the Systemic Immune-Inflammation Index (SII), calculated from routine hemogram parameters during the stable period, and the occurrence of frequent exacerbations within the subsequent 1 year, and aimed to define a clinically applicable SII threshold (cut-off). Materials and Methods: In this retrospective observational cohort study conducted at a tertiary care center, patients who attended the outpatient clinic between January 2020 and February 2025 and had COPD confirmed by post-bronchodilator spirometric criteria (FEV₁/FVC < 70%) were identified through electronic medical records. The index date was defined as a routine outpatient visit during stable COPD; patients were followed for AECOPD for 365 days after the index date. The stable period was defined as a visit occurring ≥4 weeks after the last exacerbation and without signs of acute infection. Patients with positive COVID-19 PCR results were excluded due to the uncertainty in distinguishing exacerbation from COVID-19. The primary endpoint was the development of frequent exacerbations (≥2 AECOPD) within 365 days. AECOPD was defined as an acute worsening of dyspnea, cough, and/or sputum requiring additional pharmacotherapy (systemic corticosteroids and/or antibiotics). SII, NLR, PLR, LMR, and PPN were calculated using hemogram parameters. Groups (<2 vs. ≥2 exacerbations) were compared; a ROC–Youden analysis was performed to determine cut-offs. After ROC-based dichotomization, univariate and multivariable logistic regression analyses were used to evaluate associations; multicollinearity was assessed using the VIF. To address potential optimism bias, diagnostic performance metrics (AUC, sensitivity, specificity) were internally validated using 1000 stratified bootstrap replicates. Results: A total of 159 patients were included. The cohort was predominantly male (91.2%). Demographic characteristics and most spirometric parameters were similar between groups; a trend toward lower absolute FVC was observed in the ≥2 exacerbation group (p = 0.051). Platelet counts were higher in the ≥2 exacerbation group (p = 0.029). In the ROC analysis, AUC values ranged from 0.505 to 0.591 across indices. For the SII, the AUC was 0.591 (95% CI: 0.500–0.677; p = 0.049), and the optimal cut-off was 1082.79. The LMR cut-off was 1.76; however, the LMR did not demonstrate statistically significant discriminatory performance in the ROC analysis (AUC 0.535; p = 0.448). In univariate analyses, SII > 1082.79 (OR = 3.028, 95% CI: 1.522–6.027; p = 0.002) was associated with frequent exacerbations. In a multivariable logistic regression adjusted for cardiovascular disease and overall comorbidity status, SII > 1082.79 remained independently associated (OR = 3.029, 95% CI: 1.485–6.179; p = 0.002). Other hemogram-derived indices did not retain independent prognostic significance in this outpatient cohort. Conclusion: SII measured during stable COPD was independently associated with frequent exacerbations over the subsequent 1 year. The SII > 1082.79 threshold may offer a practical risk stratification approach to flag “high-risk” patients in outpatient care. However, given the modest discriminative performance and the single-cohort derivation, this cut-off should be considered exploratory despite the use of bootstrap internal validation. Because this was a single-center study with a predominantly male cohort, the generalizability—particularly to female patients and other settings—requires prospective external validation. Full article

Background: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) frequently coexist, yet the shared genetic variants underlying these conditions remain poorly understood. This study aimed to investigate shared genetic variants underlying lung function and glucose levels in middle-aged Chinese twins. Methods: In this exploratory analysis, we reanalyzed genotype data from a previously published northern Chinese twin sample, including 139 dizygotic and 238 monozygotic twin pairs from the Qingdao Twin Registry. Lung function traits (FEV1, FVC, and FEV1/FVC) and fasting plasma glucose (FPG) were jointly analyzed using a twin-based bivariate genome-wide association approach, followed by functional annotation and gene-based analyses. Variants showing suggestive associations were further examined in an independent UK Biobank Chinese sample. Results: A significant negative correlation between the FEV1/FVC ratio and FPG was revealed. The analysis identified 29 SNPs reaching genome-wide significance, with association signals primarily clustering at the 2q33.1 locus. Functional annotation indicated that most associated variants were non-coding, with several SNPs overlapping regulatory elements annotated to the SPATS2L locus. Gene-based analysis further supported the involvement of SPATS2L in the shared genetic architecture of the two traits. In the validation analysis, seven variants at the 2q33.1 locus showed nominal associations with consistent effect directions. Conclusions: This exploratory bivariate analysis provides evidence supporting shared genetic variants underlying pulmonary function and glucose regulation and offers insight into the genetic basis of COPD–T2DM comorbidity. Full article

Background/Objectives: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder classically associated with emphysema and COPD. However, emerging evidence indicates that its clinical spectrum extends to airway-predominant diseases such as bronchiectasis and asthma, where protease–antiprotease imbalance and neutrophilic inflammation may drive tissue injury. This narrative review aims to synthesize current evidence on the relationship between AATD and airway diseases beyond emphysema, focusing on epidemiological patterns, underlying mechanisms, diagnostic strategies, and therapeutic implications. Methods: A narrative synthesis of the literature was performed, integrating data from registries, with observational and translational studies addressing the prevalence, pathobiology, and therapeutic implications of AATD in bronchiectasis, asthma, and severe asthma. Epidemiologic and mechanistic insights were analyzed to identify overlapping pathways and evidence gaps. Results: Evidence supports a non-negligible prevalence of bronchiectasis and asthma among AATD individuals, particularly in severe or heterozygous genotypes. Neutrophil elastase overactivity, impaired mucociliary clearance, and chronic neutrophilic inflammation emerge as shared mechanisms promoting bronchial remodeling and airflow limitation. In asthma, AATD appears linked to T2-low, steroid-resistant phenotypes and persistent obstruction, whereas in severe asthma cohorts, up to 20% may carry non-PiMM SERPINA 1 variants. No randomized trials have evaluated augmentation therapy and standardized screening algorithms are lacking. Conclusions: AATD represents a systemic disorder with clinically relevant airway manifestations beyond COPD and emphysema. Targeted testing should be considered in patients with idiopathic bronchiectasis or severe asthma. Future genotype-stratified, prospective studies are required to clarify causality, define biomarkers of disease activity, and evaluate the potential role of anti-protease-based therapeutic strategies. Full article