Search Results (642)

Background/Objectives: The stability and biological safety of newly developed formulations must be established to support their therapeutic efficacy and clinical translation in pulmonary drug delivery. Therefore, this follow-up study comprehensively evaluated the short- and long-term stability and the in vitro cytotoxicity of optimized, co-spray-dried theophylline (THN) dry powders for inhalation against A549 lung epithelial cells. Methods: Two established formulations were selected: THN-RAF (raffinose–leucine–glycine based) and THN-TRE (trehalose–leucine based). Stability was assessed under accelerated conditions (40 °C/75% RH, 3 months) and long-term desiccator storage (25 °C, 1 year) using laser diffraction, SEM, XRPD, FTIR, DSC, TGA, and Andersen Cascade Impaction. As THN-TRE had been previously confirmed to be cytocompatible, only THN-RAF and its components were evaluated against A549 human alveolar epithelial cells using the MTT assay. Results: Under accelerated conditions, both formulations exhibited pronounced recrystallization (Xc up to 89.9%), agglomeration (D [0.9] up to 217.08 µm for THN-TRE), and deterioration in aerodynamic performance (FPF as low as 11.55%, MMAD up to 6.68 µm). By contrast, long-term desiccator storage induced substantial recrystallization (Xc up to 80.7%) while preserving thermal, chemical, and aerodynamic performance (FPF ≈ 40%; MMAD 4.99–5.21 µm). THN-RAF was more resistant to stress-induced agglomeration than THN-TRE. Cytotoxicity assessment confirmed cytocompatibility of THN-RAF, with cell viability exceeding 70.99% at all tested concentrations (up to 500 µg/mL). Conclusions: These findings reveal a marked discrepancy between the outcomes of ICH accelerated testing and long-term desiccator storage. They underscore the importance of considering moisture-protective packaging configurations when designing stability protocols for amorphous inhalable formulations. Full article

Fibrosis emerges when normally self-limiting tissue repair fails to resolve and overlapping phases of injury, stromal activation, extracellular matrix (ECM) deposition and remodelling become sustained. MicroRNAs (miRNAs) shape this transition by coordinating signalling, cell-state and matrix programmes. Functionally, pro-fibrotic fibro-miRs amplify fibrogenic pathways, whereas anti-fibrotic miRNAs restrain fibroblast activation and ECM production; the miR-29 family is a principal member of the latter group. This review examines miR-29 family organisation, the regulation of miR-29b by transforming growth factor-β (TGF-β)/Smad and additional transcriptional and inflammatory inputs, and the molecular targets through which miR-29b controls collagen synthesis, processing and crosslinking. Direct canonical targets are distinguished from experimentally supported, predicted and indirect pathway components. Evidence is evaluated across fibroblasts and myofibroblasts, epithelial and endothelial cells, and pulmonary, hepatic, renal, cardiac, dermal and ocular fibrosis models. Therapeutic translation is considered in relation to miR-29b mimics and agomirs, local and tissue-targeted delivery, pharmacokinetics, dose control, off-target repression, immune activation and long-term safety. Overall, miR-29b remains a credible network-level anti-fibrotic candidate, but successful translation requires cell- and disease-specific target validation, selective delivery and preservation of physiological wound repair. Full article

High-throughput metagenomic sequencing and advances in mucosal immunology have refuted the traditional physiological concept of a sterile respiratory tract. The oral cavity has been recognized as a dynamic determinant of systemic health. As in other parts of the body, recent studies also suggest that pulmonary health may be linked to oral health. Under eubiotic conditions, the oral microbiome maintains local immunological homeostasis and colonization resistance. Oral dysbiosis, characterized by sequential shifts in microbial communities and the proliferation of the pathogenic red complex (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia), induces a state of chronic systemic inflammation, potentially involved in an infectious axis between the oral cavity and the lung. This review evaluates the tripartite systemic pathways of metastatic infection, metastatic injury, and metastatic inflammation that govern the translocation of oral pathobionts and their bioactive components, including lipopolysaccharides, outer membrane vesicles, and matrix metalloproteinases, to the lower respiratory tract via microaspiration and hematogenous circulation. The clinical implications across the chronic respiratory disease spectrum are examined, with a focus on how deficits in oral microbial diversity influence chronic obstructive pulmonary disease (COPD) pathogenesis, modulate the pulmonary virome and mycobiome, and stimulate maladaptive trained immunity. Furthermore, the contribution of biological aging is assessed, highlighting the roles of immunosenescence, inflammaging, and physiological reflex decline within the broader mucosal continuum. Finally, the clinical translation of this axis is analyzed, emphasizing the integration of saliva-based point-of-care nano-theranostics, metatranscriptomic profiling, and targeted interventions—such as professional oral biofilm management in intensive care settings and precision microbiome engineering—to preserve respiratory function and restore immune homeostasis. Full article

Background and Clinical Significance: Oropharyngeal squamous cell carcinoma (OPSCC) and small-cell neuroendocrine carcinoma (SCNEC) are biologically distinct entities with markedly different prognostic and therapeutic implications. While HPV-negative OPSCC carries worse outcomes than HPV-positive disease, SCNEC is exceedingly rare, highly aggressive, and prone to early systemic dissemination. Their synchronous occurrence in the head and neck (HN) is exceptional and poses major diagnostic and therapeutic challenges. Case Presentation: A 54-year-old male, smoker and alcohol consumer, presented with a left tonsillar lesion and cervical lymphadenopathy. Biopsy confirmed p16-negative OPSCC. He underwent transoral robotic surgery with modified radical neck dissection. Histopathology unexpectedly revealed two distinct malignancies: keratinizing OPSCC in the tonsil and high-grade SCNEC in a cervical lymph node, confirmed by immunohistochemistry (synaptophysin, CD56, Ki-67 80%). Postoperative FDG-PET/CT performed within two months showed rapid systemic spread, including paravertebral, pulmonary, and pelvic nodal metastases. Despite recommendation for systemic therapy, the patient deteriorated quickly and died shortly thereafter. Conclusions: This study reports coexistence of p16-negative OPSCC and high-grade SCNEC in the HN. It highlights the diagnostic complexity, staging limitations, and therapeutic dilemmas of discordant histologies, while illustrating the fulminant clinical course typical of SCNEC of unknown origin. Early recognition, comprehensive pathology, and multidisciplinary management are essential, although prognosis remains dominated by the aggressive neuroendocrine component. Full article

Understanding how clinical pathways evolve over time is essential for characterizing care processes. It also helps identify potential shifts in diagnostic and organizational practices. This study provides a descriptive analysis of patient trajectories for four major respiratory conditions: lung cancer, interstitial fibrosis, chronic obstructive pulmonary disease (COPD), and pneumonia. Trajectories were compared between a pre-COVID-19 period (2018–2019) and a COVID-19 period (2020–2022) in a specialized hospital. Using process mining applied to administrative event logs, we examined three aspects of care: the structure and sequencing of activities, the timing of transitions between care encounters, and imaging timeliness. The analysis spanned inpatient, emergency department, and outpatient settings. Indicators of care duration and transition timing revealed heterogeneous temporal patterns. Several conditions showed shorter intervals in the COVID-19 period, whereas others varied little. Activity-level analyses complemented these findings. Process maps indicated stable structural components in many pathways, together with differences in timing and execution. In the emergency department, care shifted toward bedside radiography, whereas CT chest volumes remained relatively stable across periods and settings. Imaging timeliness stayed consistently high in the emergency department and relatively stable for most inpatient conditions. Outcome-related indicators, including 30-day readmission and prolonged care trajectories, showed only modest differences between periods. Overall, the study demonstrates the value of process mining for describing real-world clinical pathways and identifying temporal variations in care. These results provide a foundation for future work that integrates richer clinical information and analytical approaches capable of assessing causal relationships. Full article

Background: Atrial stiffness can be estimated non-invasively using speckle-tracking echocardiography (STE) and has recently emerged as an outcome predictor. We aimed to assess left atrial (LA) and right atrial (RA) phasic function; the LA stiffness index (LASI), the RA stiffness index (RASI) and their sum; and the biatrial stiffness index (BASI) in dilated cardiomyopathy (DCM), and to test whether combining the two atria adds prognostic information over either index alone. Methods: A total of 121 patients with non-ischaemic DCM in sinus rhythm were followed prospectively for a composite endpoint of all-cause death, non-fatal cardiac arrest, or hospitalisation for heart failure decompensation. LASI was defined as the mitral E/e′ ratio divided by LA reservoir strain, RASI as the tricuspid Et/e′t ratio divided by RA reservoir strain, and BASI as the sum of the two. Cox models were adjusted for NYHA class, LV ejection fraction (LVEF), maximal LA volume (LAVmax) and pulmonary artery systolic pressure (PASP). Results: After 19 ± 11 months, 55 patients reached the endpoint. LA reservoir and contraction strain, all three components of RA strain and all three stiffness indices were significantly impaired in patients with events. All stiffness indices were independent outcome predictors in multivariable Cox regression (HR 2.79 [95% CI, 1.35–5.75], p = 0.006 for LASI, HR 1.84 [95% CI, 1.02–3.29], p = 0.04 for RASI and HR 2.74 [95% CI, 1.36–5.51], p = 0.005 for BASI). BASI showed the greatest increase in risk prediction (Δ likelihood ratio χ² test = 10.3, p = 0.001) over NYHA class, left ventricular ejection fraction, LA maximal volume and pulmonary artery systolic pressure. BASI showed the highest discrimination (AUC = 0.73); however, it was not significantly better than LASI or RASI alone. Conclusions: Left and right atrial stiffness are both associated with adverse outcome in DCM and add prognostic information to an LV-centred risk model. Their unweighted sum performs at least as well as either component and offers a single parsimonious measure, whose incremental clinical value remains to be established in larger, externally validated cohorts. Full article

The pulmonary microvasculature plays an essential role in maintaining alveolar integrity, but the direct effects of inhaled corticosteroids (ICS) on pulmonary endothelial cell function remain poorly understood. We investigated the effects of budesonide, formoterol, and their combination on endothelial network formation, apoptosis, migration, proliferation, and efferocytosis using human pulmonary microvascular endothelial cells (HPMEC-ST1.6R), A549 alveolar epithelial cells, and phagocytic cell models. Budesonide, alone or combined with formoterol, altered endothelial network formation on Matrigel by reducing total tubule length and the number of junctions while increasing tubule thickness, indicating reduced branching complexity. Budesonide also decreased epithelial secretion of the pro-angiogenic mediators VEGF, IL-8, and MCP-1. An independent set of experiments showed that fluticasone propionate similarly reduced VEGF, IL-8, MCP-1, TNF-α, and IL-6, supporting a class effect of corticosteroids on the epithelial secretome. Despite reducing angiogenic responses, budesonide protected endothelial cells from apoptosis, reduced caspase-3/7 activity, accelerated wound closure without affecting proliferation, preserved endothelial spheroid integrity, and enhanced efferocytosis. Formoterol alone had minimal effects and did not consistently enhance budesonide responses. Together, these in vitro findings suggest that, in the cell models studied, pulmonary endothelial responses to the ICS/LABA combinations tested are determined predominantly by the corticosteroid component, which suppresses pro-angiogenic mediator secretion while preserving endothelial survival and repair. As an exploratory cell-based study, these observations are hypothesis-generating and require confirmation in primary cells and in vivo models before clinical inferences can be drawn. Full article

Tuberculosis (TB) and chronic obstructive pulmonary disease (COPD) remain global public health challenges, yet the mechanisms underlying their comorbidity remain poorly understood. COPD is associated with an increased risk of active TB, but the cellular and molecular basis of this association remains unclear. A growing body of evidence suggests that TB is not limited to an intramacrophage infection but is accompanied by a disruption of the local immune balance in lung tissue. This review analyzes the early interface of host–Mycobacterium tuberculosis (Mtb) interaction—from pattern recognition signaling pathways and metabolic reprogramming of macrophages to epithelial barrier responses and the delayed αβ T cell response. This review evaluates γδ T cells, particularly phosphoantigen (pAg)-reactive Vγ9Vδ2 cells, as a candidate early integrative component of the host response, positioned between macrophage infection, epithelial stress, mycobacterial antigens, and bacille Calmette–Guérin (BCG)-induced trained immunity. Available evidence suggests that COPD-associated immune alterations may impair mucociliary clearance, antimicrobial peptide production, phagocytosis, and innate T cell responses while favoring cytotoxic reactions, the IL-17A–G-CSF–neutrophil axis, and protease-mediated tissue damage; however, direct mechanistic evidence in patients with TB–COPD remains limited. It is important to note the differences in data obtained from studies in humans, primates, mice, and in vitro: the Vγ9Vδ2 system has no direct analog in laboratory mice, which represents a key limitation for preclinical studies. A key unresolved question remains the nature and functional consequences of γδ T cell changes in patients with coexisting COPD and TB infection. The answer to this question could inform new strategies for the prevention and treatment of TB in patients with COPD, including BCG revaccination, pAg-mediated immunomodulation, and the development of biomarkers to distinguish between protective and harmful early immune responses. Full article

Chronic lung diseases, including asthma, chronic obstructive pulmonary disease, bronchiectasis, and idiopathic pulmonary fibrosis, are clinically distinct but share epithelial injury, host-defense, inflammatory, and remodeling processes. We integrated European-ancestry genome-wide association study (GWAS) summary statistics for these four diseases using genomic structural equation modeling to construct a multivariate chronic lung disease (mvCLD) factor. Variant-level association testing was combined with genomic control assessment, locus annotation, GWAS-by-subtraction, fine-mapping, transcriptomic prioritization, pathway enrichment, single-cell spatial mapping, and heritability partitioning. For discovery, across 6,255,777 autosomal variants, mvCLD identified 2067 genome-wide significant variants, 30 loci, and 53 lead variants. Five lead variants were genome-wide significant for mvCLD but not for any component disease and showed high-confidence fine-mapping support. For gene prioritization, transcriptomic and gene-level analyses prioritized 21 candidate genes, including ORMDL3, GSDMB, IL18RAP, IL18R1, IL1R1, SMAD3, and CLEC16A. In exploratory functional analyses, enrichment analyses converged on interleukin, cytokine-receptor, JAK-STAT, interleukin-4/interleukin-13, thymic stromal lymphopoietin, asthma, and lung fibrosis pathways. Exploratory single-cell spatial mapping, based on a mouse embryonic atlas, showed the strongest overall enrichment in the lung annotation, although cross-dataset cell-type and tissue analyses did not reach significance after false discovery rate correction; heritability partitioning implicated conserved and active regulatory elements. These findings support a shared epithelial–immune and cytokine-regulatory genetic architecture across major chronic lung diseases and nominate biologically coherent candidate genes and pathways for future functional and translational studies. Full article

Background/Objectives: Amb a 1 is the major allergenic component of Ambrosia artemisiifolia pollen and a clinically relevant marker of genuine ragweed sensitization. Heart failure is increasingly recognized as a systemic syndrome shaped by immune activation, endothelial dysfunction, fibrosis, neurohormonal imbalance, pulmonary comorbidity, and environmental exposures. This narrative review aims to synthesize the translational evidence linking Amb a 1-specific IgE, IgE-mediated inflammation, allergic airway disease, and cardiovascular remodeling in heart failure. Methods: A targeted narrative review was performed, integrating evidence on component-resolved ragweed diagnosis, IgE-FcεRI signaling, mast cell and eosinophil biology, pollen exposure, cardiovascular inflammation, and heart failure pathophysiology. Results: No dedicated clinical studies have validated Amb a 1-specific IgE as a diagnostic, prognostic, or therapeutic biomarker in heart failure. However, adjacent evidence supports biologically plausible links between allergen-specific IgE responses and cardiovascular dysfunction, including mast cell activation, cytokine release, endothelial perturbation, oxidative stress, microvascular dysfunction, pulmonary-cardiac interaction, and myocardial fibrosis. Amb a 1-specific IgE may therefore identify a seasonally vulnerable heart failure phenotype, particularly in patients with allergic rhinitis, asthma, eosinophilic inflammation, or recurrent symptom worsening during ragweed season. A systemic/indirect pathway operating through allergic airway disease is distinguished from a postulated direct cardiac pathway; the latter remains strictly speculative, as no direct evidence demonstrates that inhaled Amb a 1 reaches or activates cardiac mast cells in vivo. Conclusions: Amb a 1-specific IgE should not currently be used to infer cardiac causality or modify heart failure therapy. Prospective, phenotype-rich, exposure-informed studies are needed to determine whether ragweed sensitization has clinically meaningful implications for heart failure endotyping, seasonal risk assessment, and cardio-allergology care. These findings may inform patient-centered heart failure management by improving the interpretation of seasonal dyspnea, allergic comorbidity, and symptom fluctuations in ragweed-endemic regions. Full article

Background/Objectives: Patients with pre-existing chronic obstructive pulmonary disease (COPD) and/or chronic heart failure (CHF) are a particularly high-risk surgical population in whom postoperative pulmonary complications (PPCs) drive a disproportionate share of morbidity, prolonged stay and mortality. Prehabilitation—the structured optimization of functional reserve during the preoperative interval—has emerged as a proactive, largely non-pharmacological strategy to raise that reserve before the surgical insult. Yet the evidence base is organized predominantly by surgical procedure and enrolled in mixed populations, so the patients with the least physiological reserve—those with established COPD or CHF—remain comparatively understudied. This narrative review takes the comorbidity, rather than the incision, as its organizing axis. Methods: We summarize the pathophysiology that links chronic cardio-respiratory disease to perioperative respiratory failure; appraise the principal non-pharmacological interventions, with the respiratory components (inspiratory muscle training, pulmonary rehabilitation, breathing techniques) as the core and exercise, nutritional, psychological, and smoking-cessation elements as the multimodal context; and re-read the surgical evidence through the lens of the underlying disease. Results: A cross-surgical meta-analysis indicates that preoperative exercise training reduces PPCs (relative risk ≈ 0.52) with no significant difference in effect across surgery type or training modality, supporting a comorbidity-centered rather than procedure-centered framework. We address practical determinants of implementation—timing, patient selection, adherence, home-based and telemonitored delivery, and low-resource applicability—and highlight two cross-cutting problems: heterogeneity of intervention prescription and the lack of standardized PPC definitions. Conclusions: The scarcity of disease-specific evidence is itself the central finding, revealing a mismatch between clinical risk and research investment. Full article

Post-infarction left ventricular aneurysm is an uncommon but severe mechanical complication of transmural myocardial infarction, particularly in patients with delayed presentation or incomplete myocardial salvage. It may lead to profound distortion of left ventricular geometry, adverse remodelling, intraventricular thrombosis, mitral regurgitation, pulmonary hypertension, and advanced heart failure. We report the case of a 65-year-old male patient referred two months after a late-presenting anterior ST-segment elevation myocardial infarction caused by proximal occlusion of the left anterior descending coronary artery. At admission, the patient presented with severe decompensated heart failure, low-output status, multiorgan dysfunction, and a left ventricular ejection fraction of 12%. Transthoracic echocardiography and cardiac magnetic resonance imaging demonstrated a giant apical left ventricular aneurysm involving approximately 75% of the ventricular cavity, partial intraluminal thrombosis, extensive transmural scarring in the left anterior descending territory, and imaging features suggestive of a chronic contained free-wall rupture/pseudoaneurysmal component. Following multidisciplinary evaluation, the patient underwent surgical ventricular reconstruction using an endoventricular circular restoration technique guided by an intraventricular balloon sizer, combined with left internal thoracic artery bypass grafting to the left anterior descending artery. The early postoperative course required temporary inotropic, vasopressor, inhaled nitric oxide, and intra-aortic balloon pump support, followed by progressive haemodynamic recovery. The patient was discharged on postoperative day seven with functional improvement to NYHA class II. At six-month follow-up, he remained clinically stable without overt signs of heart failure, and echocardiography showed preserved ventricular geometry and improvement of left ventricular ejection fraction to 45%. This case highlights the potential role of carefully planned, balloon-guided surgical ventricular reconstruction in selected patients with giant post-infarction left ventricular aneurysms and end-stage heart failure when residual viable myocardium is present. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrosing interstitial lung disease characterized by excessive extracellular matrix (ECM) accumulation, disruption of lung architecture, and progressive loss of pulmonary function. IPF is frequently accompanied by comorbid conditions that exacerbate disease progression and negatively impact prognosis. To address the biological complexity of IPF, this study presents a comprehensive molecular systems architecture that enables a system-level understanding of biomolecular interactions within the fibrotic lung microenvironment in response to external and physiological triggers. Methods: A literature search is conducted using the Medical Subject Headings (MeSH) keywords in PubMed and MEDLINE to identify relevant peer-reviewed articles published from April 2008 to June 2025, with Google Scholar used solely to retrieve full-text versions of articles identified through this search. The systems biology tool CytoSolve^® was used to perform the systematic review and to support the curation and development of the molecular systems architecture of IPF pathogenesis. Full-length articles that contained Medical Subject Headings keywords relevant to IPF pathogenesis were selected for a comprehensive review. A total of 150 studies published between April 2008 and June 2025 met the inclusion criteria and were included in the systematic analysis. This systematic review was not registered. Results: Findings were synthesized qualitatively into a multilayered molecular interactome rather than through statistical meta-analysis. The architecture integrates interactions across sixteen lung-associated cell types, including epithelial, endothelial, mesenchymal, immune, and stromal populations. Key external triggers—such as bleomycin (BLM), asbestos, silica, radiation, cigarette smoke, Herpes virus, and genetic mutations (SFTPC I73T), along with hypoxia associated with comorbidities—initiate coordinated cellular responses that converge on three fundamental pathological processes: inflammation, myofibroblast differentiation, and tissue remodeling. These interconnected processes collectively drive the initiation and progression of IPF. Conclusions: This molecular systems architecture unifies triggers, cellular components, molecular pathways, and biological processes into a multilayered framework for identifying therapeutic targets, biomarkers, and rational single- and combination-treatment strategies in IPF. Full article

Background: Psychosocial assessment is a core component of lung transplant candidate evaluation, but total scores and broad candidate categories do not necessarily show how individual psychosocial concerns co-occur or which modifiable domains require further clinical attention. This study describes the development and internal evaluation of a clinical decision-support application that reorganizes Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) data into structured multidomain profiles. Methods: The application was developed using a retrospective single-center dataset of 496 adult lung transplant candidates. It integrates the SIPAT total score and candidate category with seven SIPAT-derived domain indicators, domain burden scores, cohort-referenced z-scores, graphical displays, and a ranked summary of domains for clinical review. All seven indicator targets were prespecified deterministic functions of SIPAT items or domain scores obtained during the same assessment. Random forest algorithms with sigmoid calibration were used to transform these targets into percentage-scaled display values; they were not trained using independently assessed clinical outcomes. Analyses included descriptive statistics, Spearman correlations, exploratory clustering, resampling-based cluster stability assessment, threshold sensitivity analyses, and subgroup analyses by age, sex, and primary pulmonary diagnosis. Results: Upper display-band classifications were identified for depression-related concerns in 32 candidates (6.5%), anxiety-related concerns in 11 (2.2%), nicotine-related concerns in 56 (11.3%), alcohol-related concerns in 22 (4.4%), illicit drug-use concerns in 11 (2.2%), social-support deficits in 40 (8.1%), and non-adherence-related concerns in 7 (1.4%). Exploratory clustering yielded a low-burden majority group (n = 432), a nicotine-dominant group (n = 53), and a small multidomain-elevation group (n = 11). The generated percentage-scaled indicators were positively associated with their conceptually corresponding SIPAT domains (Spearman’s ρ = 0.321–0.774) and with the total SIPAT score (ρ = 0.406–0.802; all p < 0.001). Sensitivity analyses showed that the smaller clusters were less stable under bootstrap resampling. These findings demonstrate internal alignment with the source instrument but do not constitute validation against independent clinical outcomes. Conclusions: The application provides an early-stage framework for organizing and visualizing SIPAT information and identifying domains that may warrant additional clinical assessment. Its outputs should be interpreted as SIPAT-derived decision-support indicators, not as independently validated probabilities of future clinical events. Prospective studies are required to evaluate usability, clinical impact, and associations with longitudinal outcomes. Full article

Background: Post-COVID-19 syndrome represents a global health problem, manifesting with persistent multiple organ symptoms, including respiratory ones. This review aimed to evaluate the efficacy of different pulmonary rehabilitation interventions in the management of the disease, including its particularities. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement and prospectively registered in the PROSPERO database (CRD420261292824). PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 2021 to January 2026. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Cochrane Risk of Bias 2 (RoB 2) tool. Twenty randomized controlled trials involving 2101 adult patients with post-COVID-19 syndrome met the eligibility criteria and were included in the qualitative synthesis. Results: Pulmonary rehabilitation (PR) demonstrated significant improvements in exercise capacity, with notable increases in 6MWT and VO₂max. Respiratory and peripheral muscle strength significantly increased. The quality of life, dyspnea and fatigue consistently improved. The results for intrinsic pulmonary function, anxiety, and depression were heterogeneous, suggesting benefits more related to reconditioning. Conclusions: Pulmonary rehabilitation is an essential and efficient component in post-COVID-19 syndrome, improving physical function, respiratory and peripheral muscle strength, the quality of life, fatigue and dyspnea. Telerehabilitation is a viable alternative. Adapting protocols is crucial, recognizing that most benefits derive from physical reconditioning and muscle training, not necessarily from major structural pulmonary changes. Full article