Tuberculosis (TB) can progress despite substantial systemic immune activation, indicating that protection and immunopathology are shaped not only by the magnitude of host responses but also by their organization within individual lesions. TB granulomas are heterogeneous tissue ecosystems in which cellular composition, necrosis, vascular access, extracellular-matrix remodeling, metabolic stress, and local drug exposure vary across lesions and over time. Spatial and single-cell technologies now enable these features to be investigated at increasing resolution; however, spatial or molecular association alone does not establish mechanism, causality, or therapeutic relevance. Here, we propose the Necro-Mosaic framework as a hypothesis-generating, lesion-aware approach for investigating programmed cell death (PCD)-associated processes in TB. The framework is neither a mutually exclusive taxonomy nor a clinical classification system. It considers three non-exclusive, mechanistically framed axes: F-axis, involving ferroptosis-associated lipid-peroxidation injury and membrane damage; P-axis, involving coordinated inflammatory cell-death activity with PANoptosis-like features; and N-axis, involving neutrophil-associated extracellular activity, including NET-associated structures and effector processes. The anatomical distribution, co-occurrence, temporal sequence, and biological consequences of these axis-associated processes remain empirical questions. A single lesion may therefore exhibit one axis-associated pattern, several overlapping patterns, or no interpretable pattern. We distinguish pathway capacity, pathway engagement, and mechanism-specific execution and specify the measurements and controls required to support each level of inference in situ. The framework also defines evidence as established, emerging, or hypothesis-generating according to the strength, reproducibility, resolution, and causal support of the available data. We propose falsifiable predictions to determine whether F-, P-, or N-axis-associated processes act as drivers, amplifiers, or downstream correlates of destructive lesion evolution. Although lesion-resolved host-directed therapy (HDT) is an important long-term objective, current evidence does not support assigning lesion-level mechanistic profiles from blood alone or using these axes to select clinical treatment. Progress will require prospective longitudinal studies, lesion-anchored multimodal validation, perturbation and rescue experiments, spatial pharmacology, and explicit assessment of antimicrobial-preservation and safety risks. By prioritizing testable mechanisms over fixed spatial categories, Necro-Mosaic provides a structured framework for determining how PCD-associated processes may contribute to TB lesion heterogeneity and for identifying which observations are sufficiently validated to support future translational studies.

Tuberculosis (TB) remains the leading infectious cause of death worldwide, yet immunological protection against Mycobacterium tuberculosis (Mtb) remain poorly understood. We performed integrated single-cell transcriptomics and functional T-cell cloning on paired bronchoalveolar lavage (BAL) and peripheral blood samples from those exposed to TB, using IGRA and PET-CT to study potentially protective responses across the spectrum of TB infection/disease. Recent Mtb exposure alone was sufficient to remodel the pulmonary T-cell compartment. Longitudinal follow-up demonstrated that all participants who progressed to active TB had baseline PET-CT abnormalities, showing that PET-CT scan can be used to find those at high risk of progression. Furthermore, those who were PET-positive, but did not progress to active TB provide a natural model for protection, and exhibited enrichment of pulmonary cytotoxic CD8-associated T cells, identifying a candidate protective immune program. TAR-seq identified a discrete population of clonally expanded Mtb-responsive T cells and enabled direct linkage of antigen-responsive TCRs to transcriptional state through T cell cloning. Functional T-cell cloning further established a framework connecting antigen specificity, TCR sequence, and pulmonary cell state. Together, these findings provide a comprehensive atlas of human pulmonary T-cell immunity across the spectrum of TB, identify pulmonary immune features associated with durable control of infection, and establish an integrated platform for defining protective T-cell responses to inform next-generation TB vaccine development.

Post-tuberculosis lung disease (PTLD) is associated with persistent respiratory symptoms, reduced exercise capacity, impaired quality of life, and psychological morbidity despite successful completion of anti-tubercular therapy. Although pulmonary rehabilitation (PR) is an established therapeutic intervention, comparative evidence on home-based PR (HBPR) and hospital-based PR (HPR), particularly beyond 12 weeks, remains limited. So, to compare the effects of HBPR and HPR on clinical, functional, psychological, and pulmonary function outcomes in patients with PTLD, the study was done over a period of 24 weeks. This prospective comparative study included 50 patients with PTLD, of whom 30 underwent structured HBPR with weekly follow-up and 20 underwent supervised HPR. Allocation was based on feasibility and participant preference. Allocation was based on feasibility and participant preference. Participants were assessed at baseline, 12 weeks, and 24 weeks using the modified Medical Research Council (mMRC) dyspnea grade, body mass index (BMI), St. George's Respiratory Questionnaire (SGRQ), Depression Anxiety Stress Scale-21 (DASS-21), spirometry, and six-minute walk distance (6MWD). Changes within groups were analyzed for 0-12 weeks, 12-24 weeks, and 0-24 weeks, and change scores were compared between groups. Both rehabilitation strategies significantly improved dyspnea, nutritional status, quality of life, psychological well-being, pulmonary function, and exercise capacity over 24 weeks. In the HBPR group, mean 6MWD increased from 258.17±82.72 m to 377.00±82.38 m, while in the HPR group it increased from 308.00±118.84 m to 429.00±114.57 m (both p<0.001). Mean SGRQ scores improved from 44.67±9.28 to 29.73±7.00 in the HBPR group and from 38.70±10.35 to 25.10±8.30 in the HPR group (both p<0.001). Significant improvements were also observed in BMI, DASS-21 scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of vital capacity predicted values. Although the greatest gains occurred during the first 12 weeks, several outcomes continued to improve between 12 and 24 weeks. Change-score analysis demonstrated comparable improvements between HBPR and HPR across most outcomes. This study concluded that both home-based and HPR significantly improved clinical, functional, psychological, and pulmonary outcomes in PTLD. Benefits extended beyond 12 weeks, with comparable improvements observed between rehabilitation strategies.

Sarcoidosis is a systemic granulomatous disorder, and chylothorax is a rare but severe pleural complication of this disease and exhibits a prominent diagnostic overlap with tuberculosis. The present study reported the case of a 48-year-old woman who was admitted in May 2018 with chronic cough and chest tightness. After hospitalization for 17 days, comprehensive examinations excluded tuberculosis and malignancy, and the patient was finally diagnosed with sarcoidosis complicated with pleural effusion. Treatment with prednisone combined with therapeutic thoracentesis was initiated to relieve symptoms. Chylothorax developed on hospital day 22, and a low-fat diet was added to the treatment regimen; however, 20 days after therapy initiation, the persistent chylothorax showed no notable improvement. Following multidisciplinary consultation, methotrexate was added as adjuvant therapy to control sarcoidosis activity. The patient's symptoms then improved, and the patient was discharged on hospital day 49 with oral medications. Clinical remission was achieved at the 3-month follow-up; however, new tuberculous lesions were identified in the left lung at the 6-month follow-up. Methotrexate was discontinued immediately, prednisone was gradually tapered to a maintenance dose, and standardized anti-tuberculosis therapy was initiated. At the 12-month follow-up, pulmonary tuberculosis had achieved clinical cure following a 6-month course of treatment. Anti-tuberculosis therapy was continued for an additional 3 months as consolidation treatment before discontinuation, whereas maintenance-dose prednisone was continued to control the underlying sarcoidosis. No evidence of sarcoidosis or tuberculosis recurrence was identified at the 25- or 39-month follow-up. Prednisone was gradually tapered and ultimately withdrawn, and the patient achieved a favorable long-term outcome. The present case report describes a patient with sarcoidosis-associated chylothorax who developed new-onset pulmonary tuberculosis during immunosuppressive treatment, highlighting the challenges associated with the differential diagnosis and clinical management of complicated sarcoidosis. Although combination therapy with prednisone and methotrexate was temporally associated with improvement of the chylothorax, clinicians should remain aware regarding the risk of opportunistic infections.

Chest wall tuberculosis (TB) is a rare manifestation of extrapulmonary TB and may present a significant diagnostic challenge, particularly in low-incidence TB countries such as the United Arab Emirates. We report two unusual cases of chest wall TB with distinct clinical presentations. The first case presented as a slowly enlarging chest wall mass that clinically and radiologically mimicked a soft-tissue neoplasm and was ultimately diagnosed as giant tuberculous lymphadenitis. The second case presented as a large posterolateral chest wall abscess without evidence of active pulmonary TB. Both patients were managed surgically for diagnostic and therapeutic purposes, and histopathological examination established the diagnosis of chest wall TB. Both patients received a 6-month course of anti-tuberculous therapy with complete recovery. These cases highlight the diverse clinical spectrum of chest wall TB and emphasize that the disease should be considered in the differential diagnosis of chest wall masses and abscesses, even in low-incidence TB settings. Histopathological confirmation remains essential for establishing the diagnosis and guiding appropriate management.

Tuberculous pericarditis (TBP) is a potentially severe manifestation of extrapulmonary tuberculosis that may lead to pericardial effusion and constrictive physiology and, in some patients, progress to fixed constrictive pericarditis. Diagnosis can be particularly challenging in young immunocompetent patients without overt pulmonary involvement. We report the case of a 20-year-old immunocompetent man presenting with a one-month history of weight loss, profuse night sweats, nocturnal fever, and typical pericarditic chest pain. Clinical examination revealed fever and signs of systemic venous congestion. Transthoracic echocardiography demonstrated marked pericardial thickening, moderate circumferential effusion, septal bounce, approximately 25% respiratory variation in transmitral flow, annulus reversus, and annulus paradoxus, supporting the presence of pericardial effusion with constrictive physiology. Contrast-enhanced computed tomography confirmed diffuse pericardial thickening and effusion without calcification or pulmonary parenchymal involvement. At the same time, cardiac magnetic resonance demonstrated intense late gadolinium enhancement of the thickened pericardium, supporting active pericardial inflammation. Xpert Mycobacterium tuberculosis/Rifampicin assay (Xpert MTB/RIF; Cepheid, Sunnyvale, CA, USA) testing of the pericardial fluid detected Mycobacterium tuberculosis, subsequently confirmed by positive mycobacterial culture. Following multidisciplinary discussion, a six-month antituberculous regimen combined with adjunctive corticosteroid therapy was initiated, with close clinical and multimodality imaging follow-up and reassessment for pericardiectomy according to clinical evolution. This case highlights the complementary value of echocardiography, computed tomography, and cardiac magnetic resonance in characterizing tuberculous pericardial disease associated with constrictive physiology and defining its inflammatory substrate. Identification of active pericardial inflammation in the presence of constrictive physiology may indicate a potentially reversible component; however, actual reversibility requires confirmation during longer-term follow-up.

There is an unmet need for therapies targeting chronic neutrophilic inflammation in bronchiectasis. In the phase II, dose-finding AIRLEAF study, the dipeptidyl peptidase 1 (cathepsin C) inhibitor verducatib (BI 1291583) reduced the pulmonary exacerbation risk in people with bronchiectasis and demonstrated a similar safety profile to placebo; these results support the investigation of verducatib in a phase III study. Here, we describe the design of the randomised, placebo-controlled phase III AIRTIVITY study (ClinicalTrials.gov identifier NCT06872892), assessing the efficacy, safety and tolerability of verducatib in people with bronchiectasis. In AIRTIVITY, approximately 1680 adults and 75 adolescents (aged 12-<18 years) with bronchiectasis with a broad range of aetiologies are randomised 2:1 to receive oral verducatib 2.5 mg or placebo for at least 52 weeks and up to 76 weeks. Unlike previous studies of bronchiectasis, people with cystic fibrosis bronchiectasis are included. The primary objective is to demonstrate the superiority of verducatib compared with placebo on the annualised rate of pulmonary exacerbations up to 76 weeks. The main secondary objective is to demonstrate a reduction in lung function decline, an improvement in respiratory symptoms, a prolongation in time to first pulmonary exacerbation and a reduction in annualised rate of severe pulmonary exacerbations for verducatib versus placebo. All pulmonary exacerbations are adjudicated. If the efficacy of verducatib is demonstrated and there is a favourable benefit-risk ratio, the AIRTIVITY results will provide confirmatory evidence for the use of verducatib 2.5 mg in a large and broad bronchiectasis population, independent of underlying aetiology.