Respiratory diseases are diverse and complex, and even the same disease may exhibit heterogeneity. Current treatments are often hampered by limited efficacy and insufficient targeting. In recent years, regenerative therapies have gradually gained attention, and stem cell-based therapies have shown potential in respiratory diseases. However, their basic research clinical validation, and translational pathways remain to be further explored. This review outlines the classification of stem cells, their mechanisms of action, research progress in various respiratory diseases, as well as future challenges and perspectives. It aims to summarize the current status and potential value of stem cell-based therapies in respiratory diseases and to inform related basic, clinical, and translational research.

Cystic fibrosis transmembrane conductance regulator-related disorder (CFTR-RD) is an increasingly recognized genetic condition characterized by CFTR dysfunction without fulfilling the diagnostic criteria for cystic fibrosis. With the widespread application of genetic testing, an increasing number of patients with CFTR protein dysfunction have been identified; however, many do not meet the typical diagnostic criteria for cystic fibrosis. CFTR-RD may involve multiple organ systems and presents with heterogeneous and complex clinical manifestations, posing significant challenges for diagnosis and management. Here, we report the case of an adolescent male with bronchiectasis, elevated liver enzyme levels, and pancreatic exocrine insufficiency. Genetic analysis revealed a maternally inherited heterozygous intronic CFTR variant. Based on the clinical manifestations and laboratory findings, the patient was highly suspected of having CFTR-RD despite not fulfilling the diagnostic criteria for cystic fibrosis. This case underscores the importance of recognizing CFTR-RD in patients with multisystem involvement and atypical features of cystic fibrosis, and highlights the value of multidisciplinary evaluation in establishing an accurate diagnosis and developing an individualized treatment strategy.

Pneumoconiosis complicated with pulmonary tuberculosis is characterized by high prevalence and disability rates, as well as difficulty in early diagnosis, constituting a serious public health problem. The Chinese Society of Tuberculosis (Chinese Medical Association) and the Society of Labor Hygiene and Occupational Diseases (Chinese Preventive Medicine Association) organized multidisciplinary experts in respiratory diseases, occupational diseases, tuberculosis and other related fields to formulate the Chinese expert consensus on the diagnosis and treatment of pneumoconiosis complicated with tuberculosis. This consensus aims to enhance professional practitioners' understanding of the disease, improve the capacity for early clinical diagnosis, and further advance the prevention and treatment of pneumoconiosis complicated with pulmonary tuberculosis in China. It summarizes 12 key clinical issues and proposes 13 targeted recommendations to address difficulties and misconceptions in clinical practice. This consensus was registered on the International Practice Guidelines Registry Platform (PREPARE-2024CN271). It aims to enhance the standardized diagnosis and treatment of pneumoconiosis complicated by pulmonary tuberculosis, improve patient outcomes, and provide practical guidance for the prevention and control of occupational and infectious diseases in China. The main recommendations are as follows.Recommendation 1: Clinicians and pathologists are advised to pay attention to the mixed pathological features of pneumoconiosis complicated with pulmonary tuberculosis. For patients with pneumoconiosis presenting atypical imaging manifestations or poor response to conventional treatment, pathological specimens should be actively obtained to confirm the diagnosis. Combined use of acid-fast staining, Mycobacterium tuberculosis culture or molecular pathological detection is recommended to increase the detection rate (2C).Recommendation 2: When performing chest CT examinations and dynamic follow-up for pneumoconiosis patients, clinicians and radiologists should focus on multifocal and polymorphic lesions, as well as short-term imaging changes suggestive of active tuberculosis (2C).Recommendation 3: For patients with suspected pulmonary tuberculosis complicated with pneumoconiosis: (1) Be aware that sputum bacteriological tests may yield false-negative results due to dust interference. Repeated sampling or combined detection methods are recommended, including bacteriological and molecular tests on bronchoalveolar lavage fluid (BALF) obtained via bronchoscopy. Results of immunological assays such as the interferon-γ release assay (IGRA) and tuberculin skin test (TST)shall also be combined for comprehensive judgment. (2) In cases with atypical imaging findings and clinical symptoms, bronchoscopy-guided pathological sampling (e.g., EBUS-GS [endobronchial ultrasound with guide sheath], ENB [electromagnetic navigation bronchoscopy]) is prioritized. When microbiological evidence is insufficient, percutaneous lung biopsy or pleural biopsy (for patients with pleural effusion) is suggested to clarify the diagnosis (2B).Recommendation 4: The diagnosis of pneumoconiosis complicated with pulmonary tuberculosis shall follow the integrated diagnostic principle. Provided that patients meet the national diagnostic criteria for pneumoconiosis and pulmonary tuberculosis respectively, a comprehensive assessment shall be conducted combining occupational exposure history, dynamic imaging changes and laboratory results. Patients shall be stratified for managementaccording to the activity of tuberculosis (2C).Recommendation 5: For differential diagnosis between pneumoconiosis complicated with pulmonary tuberculosis and non-tuberculous mycobacterial (NTM) lung disease: (1) NTM lung disease commonly involves the apical and anterior segments of the upper lobes, the right middle lobe and the lingular segment of the left upper lobe. Typical imaging manifestations include a combination of centrilobular nodules and bronchiectasis. (2) Multiple thin-walled cavities are frequently seen in silicosis complicated with NTM lung disease. (3) Pathologically, NTM lesions are dominated by epithelioid granulomas with inconspicuous caseous necrosis. (4) Definitive diagnosis relies on mycobacterial culture and species identification, complying with combined clinical, imaging and microbiological criteria (2C).Recommendation 6: For patients with pneumoconiosis complicated with pulmonary tuberculosis who present progressively enlarged cavities or newly developed cavities accompanied by aggravated symptoms after anti-tuberculosis treatment, radiologists shall evaluate imaging signs of pulmonary aspergillosis, such as the early halo sign and the late air crescent sign within cavities (2C).Recommendation 7: For patients with suspected pneumoconiosis complicated with pulmonary aspergillosis: (1) Bronchoscopy is performed to collect BALF or tissue specimens for fungal culture and pathological examination (gold standard). (2) Conduct BALF galactomannan (GM) test, metagenomic next-generation sequencing (mNGS) or other DNA detection assays. (3) Detect serum specific antibodies against Aspergillus fumigatus (e.g., IgE-m3, IgM) (1A).Recommendation 8: For patients with pneumoconiosis complicated with drug-susceptible pulmonary tuberculosis: (1) Adopt the standard first-line four-drug anti-tuberculosis regimen. (2) Ensure a sufficient treatment course (generally ≥6-8 months). (3) Extend the treatment course to≥9-12 months for patients with severe lesions or concomitant tracheal, pleural or extrapulmonary tuberculosis, so as to improve clinical outcomes and reduce recurrence (2A).Recommendation 9: For patients receiving concurrent treatment for pneumoconiosis (including tetrandrine, nintedanib, pirfenidone, glucocorticoids, bronchodilators, etc.) and rifampicin-containing anti-tuberculosis regimens: (1) Be aware that rifampicin, a potent hepatic enzyme inducer, may accelerate the metabolism of concomitant drugs such as glucocorticoids and nintedanib and reduce their efficacy. (2) Adjust the dose of affected drugs accordingly when rifampicin is initiated or discontinued (1B).Recommendation 10: Extracorporeal membrane oxygenation (ECMO) may be used as a bridge to lung transplantation only for end-stage pneumoconiosis patients complicated with pulmonary tuberculosis awaiting transplantation (2D).Recommendation 11: For end-stage patients with pneumoconiosis complicated with pulmonary tuberculosis who have received adequate and standard anti-tuberculosis therapy, the feasibility of lung transplantation shall be evaluated. Pre-transplant precautions: (1) Ensure complete control of active tuberculosis. (2) Optimize the anti-tuberculosis regimen (e.g., replace rifampicin with rifabutin) to maintain the effective concentration of immunosuppressants (2D).Recommendation 12: For patients with severe, end-stage pneumoconiosis complicated with pulmonary tuberculosis who no longer benefit from active treatment, palliative care and hospice care shall be initiated. Clinicians and medical teams shall communicate fully with patients and their families about the condition, prognosis, treatment options and medical burden. The core goals are to relieve symptoms, alleviate suffering and improve quality of life (2D).Recommendation 13: For patients with pneumoconiosis complicated with tuberculosis who meet the indications for surgical or interventional therapy, a multidisciplinary team shall conduct joint decision-making and implement treatment in a timely manner after full assessment of pulmonary function, nutritional status and surgical risks. Surgical treatment is mainly indicated for patients with drug-resistant tuberculosis with localized lesions, persistent cavitary lesions with ongoing mycobacterial excretion, destroyed lung, massive hemoptysis unresponsive to medical treatment, tuberculous empyema and other critical conditions. Interventional therapy can be applied for emergency treatment of massive hemoptysis, as well as palliative treatment for pulmonary artery stenosis secondary to tuberculosis or pneumoconiosis (2C).

Invasive group A streptococcal (iGAS) infection during pregnancy is rare but associated with disproportionately high maternal mortality. Influenza infection has been shown to increase the virulence of Streptococcus pyogenes, and a global resurgence of iGAS has been reported in the post-COVID-19 era.We report a woman in her early 30s at 32 weeks of gestation who developed fulminant iGAS following influenza A infection. Despite antiviral therapy and repeatedly negative rapid antigen tests for group A streptococcus, her condition rapidly deteriorated, resulting in septic shock, acute respiratory distress syndrome and intrauterine fetal death. Intensive multidisciplinary management including emergency delivery, continuous haemodiafiltration and veno-venous extracorporeal membrane oxygenation was required. The patient survived but required right lower limb amputation due to severe ischaemic complications.This case highlights the potential for influenza to precipitate life-threatening iGAS during pregnancy and underscores the need for early recognition when pregnant patients with influenza show unexpected clinical deterioration.

A man in his early 30s presented with a 4-month history of low-grade fever and chronic dry cough. Three months before admission, he developed persistent low-grade fever, rash and bilateral cervical lymphadenopathy. He was diagnosed with HIV infection and started on tenofovir/lamivudine/dolutegravir. Two weeks before admission, he developed right-sided pleuritic chest pain. Chest CT revealed bilateral pleural effusions and generalised lymphadenopathy involving the lower cervical, mediastinal and axillary regions. An excisional biopsy of a right lower cervical lymph node demonstrated hyaline-vascular architecture, including 'lollipop' lesions and onion-skinning of the mantle zones. Immunohistochemistry showed human herpesvirus 8 (HHV-8)-positive plasmacytoid cells within the mantle zones, without malignant features, consistent with HHV-8-associated multicentric Castleman disease (MCD). The patient continued antiretroviral therapy and received rituximab 375 mg/m² every week for four cycles. He achieved complete resolution of the pleural effusions. This case illustrates the variable clinical presentation of HHV-8-associated MCD in a patient living with HIV.

The Surviving Sepsis Campaign guidelines stratify antibiotic urgency in suspected sepsis by shock status, recommending treatment within 1 h for patients with shock and within 3 h for possible sepsis without shock. UK National Institute for Health and Care Excellence (NICE) guidelines use National Early Warning Score 2 (NEWS2) risk categories, with a window of 1 h for the group at highest risk of mortality (aggregate score ≥7). We aimed to compare these strategies for identifying patients in whom antibiotic delays are associated with mortality.

We conducted a retrospective cohort study between May 31, 2015, and Feb 28, 2024, of adults (age ≥18 years) admitted via the emergency departments of nine hospitals within the Mass General Brigham health-care system (MA, USA) and treated for suspected infection, defined as blood culture sampling and intravenous antibiotic administration within 6 h of emergency department arrival. Exclusion criteria included transition to palliative care or death within 6 h of arrival to emergency department, transfer from acute care hospitals, psychiatric or obstetric admissions, missing vital signs or key laboratory test results within 12 h of arrival, oral or intravenous antibiotic receipt before arrival, insufficient data to calculate NEWS2 scores, and positive SARS-CoV-2 PCR test results within 2 days of arrival. We estimated hourly associations between time to antibiotic administration and hospital mortality using multivariable logistic regression with generalised estimating equations, stratified by shock (defined as persistent hypotension and lactate >2 mmol/L) and by laboratory-upgraded NEWS2 scores (NEWS2+), which were calculated per UK NICE guidance by shifting patients up one category if they had neutropenia, lactate concentration higher than 2 mmol/L, or laboratory evidence of new organ dysfunction within 3 h of arrival.

115 464 encounters with suspected infection were identified, of which 15 797 were ineligible based on exclusion criteria. The final analysis cohort included 71 593 patients who contributed 99 667 encounters (52 835 [53%] male, 46 828 [47%] female). 4867 (4·9%) encounters had shock. NEWS2+ scores were 0 in 9672 (9·7%) encounters, 1-4 in 37 310 (37·4%) encounters, 5-6 in 26 134 (26·2%) encounters, and ≥7 in 26 551 (26·6%) encounters. Each additional hour to antibiotic administration was associated with higher mortality in encounters with shock (adjusted odds ratio [OR] 1·15, 95% CI 1·07-1·25; 1·5% absolute increase per hour, 95% CI 0·5-2·4), but not in those without shock (1·03, 1·00-1·05). Delays were also associated with higher mortality in encounters with NEWS2+ ≥7 (1·07, 1·04-1·11; 0·5% absolute increase per hour, 95% CI 0·3-0·8), including 22 902 (86·3%) of 26 551 encounters without shock (1·05, 1·01-1·09; 0·4% absolute increase per hour, 95% CI 0·1-0·6%). No association was observed in encounters with NEWS2+ scores less than 7.

The NICE-defined high-risk NEWS2 category (scores ≥7) identified patients in whom each additional hour to antibiotic administration was associated with increased mortality, including many without shock, whereas no association was observed for lower NEWS2 scores. These findings suggest that NEWS2 might better target urgent antibiotic therapy beyond shock-based assessment alone.

US Agency for Healthcare Research and Quality and US Centers for Disease Control and Prevention.

Early screening can significantly reduce the severe morbidity and mortality of respiratory diseases and alleviate the burden on public healthcare systems. Point-of-care (POC) devices refer to portable instruments that meet the REASSURED criteria and can be conveniently used near the patient without professional laboratory conditions. POC devices played an important role in patient initiated early diagnosis during the COVID-19 pandemic, demonstrating great potential. From a macro-to-micro perspective, this review first comprehensively introduces clinically relevant sample types, including blood, respiratory tract and oral samples, and exhaled breath, along with the clinical significance of corresponding biomarkers (nucleic acids, proteins, gaseous molecules, extracellular vesicles, circulating tumor cells, and pathogen particles) and pre-processing methods. Subsequently, it summarizes the test principles and promising bioreceptors including base pairing-based systems (PCR, isothermal amplification, CRISPR/Cas), antibodies and antibody mimetics, and other affinity-based recognition elements, and innovatively presents portable integration platforms of biosensors from the perspective of bioreceptor compatibility. It then evaluates the application performance of transducers and corresponding optical or electrochemical portable detection devices, including SERS, e-nose, nanopore sensors, and portable GC-MS. Finally, the latest applications of computer technology and artificial intelligence tools in POC detection for respiratory diseases, spanning device design, bioreceptor screening, biomarker discovery, and diagnostic data processing, are presented by functional category. This review aims to provide a reference for the research and application of multiplex biomarker/sample/disease POC testing in respiratory diseases, and to offer perspectives on future directions for technological innovation, intelligentization, and commercial translation.

COVID-19 is a disease triggered by SARS-CoV-2 and some individuals develop a severe form that can progress to multiple organ failure. Neutrophils have been described as responsible for the release of neutrophil extracellular traps (NETs). The role of the elastase and myeloperoxidase (MPO) in NET release by neutrophils stimulated by SARS-CoV-2 infection was not addressed, and it was the aim of the present study. The NET release by human neutrophils infected with SARS-CoV-2 depends on elastase/MPO migration to the nucleus. Moreover, elastase/MPO migration is a consequence of PKC and PI3K kinase activation, leading to reactive oxygen species generation by the neutrophil mitochondria and NOX-2. We also reanalyzed the single-cell RNA sequencing data available in a database and demonstrated that neutrophils from bronchoalveolar lavage (BAL) fluid of patients with COVID-19 present increased expression of genes involved in the formation of the NOX2 complex, PKC delta and members of the PI3K family. In summary, the release of NETs by neutrophils in response to SARS-CoV-2 infection depends on the sequential activation of the PKC/PI3K/ROS pathway, inducing elastase/MPO migration to the nucleus triggering the NET formation. Thus, our study demonstrates new insights into the signaling pathways that induce NETs in response to SARS-CoV-2, highlighting new targets for studies and therapies for COVID-19.

With increasing H5 avian influenza cases reported globally and the potential for pandemic emergence, induction of cross-reactive antibody responses may represent an important attribute of an effective vaccine. This phase 2 extension study evaluated immunogenicity and safety of MF59-adjuvanted, cell culture-derived H5N6 vaccine (aH5N6c) in adults primed with MF59-adjuvanted, cell culture-derived H5N1 vaccine (aH5N1c) and in unprimed adults. Adults previously primed with two doses of aH5N1c in the parent study V89_18 were randomized to receive two aH5N6c doses (Group 1) or one aH5N6c and one placebo (Group 2) 3 weeks apart. Unprimed adults received two aH5N6c doses (Group 3). Immunogenicity was assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays against the priming (H5N1) and booster (H5N6) strains on Days 1, 8, 22, 43, and 202. Among 258 exposed participants, primed subjects (Groups 1 and 2) showed higher HI geometric mean titers against both strains than unprimed (Group 3) subjects, with MN responses similarly enhanced. Heterologous H5N1 responses were robust in primed subjects (Day 43 HI GMTs: 333-343; seroconversion rates >89%) but minimal in unprimed subjects, with responses persisting to Day 202. Solicited adverse events were mild or moderate, comparable between groups, and consistent with other MF59-adjuvanted pandemic vaccines; no vaccine-related serious adverse events occurred. Heterologous H5N6 booster vaccination in H5N1-primed adults elicited strong cross-reactive immunity against the priming strain, demonstrating long-lasting immune memory for at least 6 y and supporting heterologous prime-boost strategies for pandemic preparedness against emerging H5 outbreaks.

Stroke frequently results in long-term motor impairments, making effective rehabilitation essential for functional recovery. However, the development of intelligent rehabilitation systems is hindered by the lack of large-scale kinematic data from stroke patients. Here, we present REHAB, a wearable sensor-based kinematic dataset collected from 120 post-stroke patients during a two-week rehabilitation program. The dataset comprises signals recorded from 27 standardized assessment movements and 16 rehabilitation training movements, providing comprehensive limb kinematics together with corresponding task annotations and clinical labels. Detailed descriptions of the data acquisition protocol, sensor configuration, and data organization are provided to ensure reproducibility and facilitate reuse. In addition, systematic quality-control procedures, including clinician-guided acquisition, sensor calibration, signal inspection, and preprocessing standardization, were implemented throughout the data collection pipeline to ensure data quality and consistency. REHAB provides a comprehensive and clinically relevant kinematic resource for stroke rehabilitation research and may support future studies in rehabilitation assessment, movement analysis, wearable sensing, and data-driven intelligent rehabilitation systems.