Interstitial lung disease (ILD) comprises a highly heterogeneous group of pulmonary disorders, whose diagnosis often requires the integration of clinical, radiologic, and pathologic evidence. Lung biopsy is a key method for obtaining a histopathologic diagnosis, but unified standards are lacking for determining indications, selecting biopsy techniques, managing patients perioperatively, and integrating pathologic and clinical information. To address these gaps, the Respiratory Physicians Branch of the Chinese Medical Doctor Association and the ILD Group of the Chinese Thoracic Society spearheaded this initiative, collaborating with national experts in respiratory medicine, radiology, pathology, thoracic surgery, and rheumatology to formulate this consensus. Developed in strict adherence to evidence-based medicine principles, this consensus is founded on systematic literature reviews and evidence grading, utilizing the Delphi method for anonymous voting. It culminates in 15 recommendations, each explicitly annotated with the level of evidence and strength of recommendation. This consensus systematically delineates the multidisciplinary discussion (MDD)-centered full-process management of lung biopsy. The main contents encompass: assessment of the necessity and feasibility of lung biopsy; indication stratification strategies based on HRCT patterns; applicability scenarios and selection pathways for the four major lung biopsy techniques; shared decision-making; perioperative comprehensive management; management strategies for acute exacerbation of ILD (AE-ILD); standardization of tissue processing and pathological reporting; the post-biopsy MDD process for integrated diagnosis; and biopsy decision-making in special clinical contexts, such as ILD complicated by lung cancer or connective tissue disease-associated ILD (CTD-ILD). This consensus aims to provide clinicians with clear, safe, and practical guidance on lung biopsy, promote standardized and precise decision-making, and improve patient outcomes.Summary of RecommendationsRecommendation 1: For patients with suspected ILD, a comprehensive multidisciplinary discussion (MDD) is mandatory prior to lung biopsy. This evaluation should establish the diagnostic certainty of the preliminary clinical assessment, evaluate the clinical utility of the biopsy, and facilitate shared decision-making (SDM) that incorporates patient preferences (Level of evidence: 3, Recommendation: strong).Recommendation 2: For ILD patients in whom the diagnosis remains uncertain following a comprehensive non-invasive evaluation, or when precise histopathologic subtyping is required, a lung biopsy is recommended to establish a definitive diagnosis and guide the therapeutic management (Level of evidence: 4, Recommendation: strong).Recommendation 3: For patients with an interstitial pattern, a lung biopsy is strongly discouraged if HRCT demonstrates a definite UIP pattern and secondary etiologies have been excluded. A conditional recommendation for a lung biopsy applies to patients with a probable UIP patterns in whom NSIP or fibrotic HP cannot be ruled out. A lung biopsy is strongly recommended to achieve a definitive diagnosis in patients with an indeterminate or non-UIP patterns and insufficient clinical evidence (Level of evidence: 4, Recommendation: conditional).Recommendation 4: For patients with an alveolar filling pattern, a lung biopsy is recommended to clarify the etiology once infection, alveolar hemorrhage, and pulmonary edema have been systematically excluded, and there is either a lack of response to empirical therapy or a clinical necessity to differentiate the lesion from malignancy (Level of evidence: 2, Recommendation: strong).Recommendation 5: For suspected rare ILDs, including PAP, iEP, LAM, and LIP, non-invasive or minimally invasive diagnostic modalities should be prioritized; a lung biopsy is conditionally recommended if these approaches are non-diagnositic. Conversely, a lung biopsy is strongly recommended for patients with clinically suspected AFOP or PLCH (Level of evidence: 2, Recommendation: conditional).Recommendation 6: Lung biopsy is not recommended for patients with acute respiratory failure, severe pulmonary functional impairment, recent cardiovascular events, hemodynamic instability, significant pulmonary hypertension, severe coagulopathy, or end-stage systemic debilitation (Level of evidence: 1, Recommendation: strong).Recommendation 7: Site selection for lung biopsy should target active lesions identified on HRCT (e.g., ground-glass opacities or fine reticulation). Specimens must include the interface between diseased and normal parenchyma to facilitate pattern assessment. High-risk areas, such as major vessels and severe bullae, must be strictly avoided. Multi-lobar sampling from at least two sites of varying severity is recommended to adequately capture disease heterogeneity (Level of evidence: 4, Recommendation: strong).Recommendation 8: A TBLB is recommended as the first-line diagnostic approach for suspected granulomatous diseases (e.g., sarcoidosis) and specific alveolar filling patterns. If a TBLB is non-diagnostic, escalation to TBLC or SLB is advised. A TBLB is not recommended for the evaluation of predominantly fibrotic ILDs (e.g., UIP or NSIP) (Level of evidence: 4, Recommendation: strong).Recommendation 9: TBLC is recommended as the preferred modality in expert centers, particularly for patients who are poor candidates for or are averse to SLB. The procedure should be standardized under general anesthesia with prophylactic balloon placement for hemorrhage control and integrated with imaging or navigational guidance to optimize diagnostic yield while minimizing procedural complications (Level of evidence: 2, Recommendation: strong).Recommendation 10: SLB is recommended for patients in whom TBLC yields a non-diagnostic result, provided their cardiopulmonary physiological reserve permits surgical intervention. Video-assisted thoracoscopic surgery (VATS) is the preferred approach, requiring sampling from at least two distinct lobes. Biopsies should prioritize the dependent segments of the upper lobes or the superior segments of the lower lobes; sampling from the lingula or the right middle lobe should only be considered if these sites harbor the most representative lesions and no superior alternatives exist (Level of evidence: 2, Recommendation: strong).Recommendation 11: PTNB is recommended for the diagnosis and differential diagnosis in ILD patients presenting with solitary nodules, masses, or focal consolidations, particularly to rule out malignancy. However, it is not recommended for the histopathological evaluation of diffuse fibrosing ILDs (Level of evidence: 2, Recommendation: strong).Recommendation 12: A shared decision-making model is recommended throughout the biopsy selection process. Clinicians should thoroughly counsel patients regarding the benefits, risks, and alternatives of the procedure, ultimately formulating a clinical plan that aligns medical evidence with patient values (Level of evidence: 4, Recommendation: strong).Recommendation 13: Histological or imaging patterns of usual interstitial pneumonia (UIP), active disease phase, and reduced diffusing capacity for carbon monoxide (DLCO) are the main risk factors for acute exacerbation of interstitial lung disease (AE-ILD). Routine prophylactic use of glucocorticoids or antifibrotic therapy is not recommended for all patients; instead, meticulous perioperative management is recommended to prevent acute exacerbations. Once AE occurs, the underlying cause should be promptly investigated, and high-dose glucocorticoids along with supportive therapy may be considered (Level of evidence: 2, Recommendation: strong).Recommendation 14: Histopathological reports must adhere to current international standardized nomenclature, prioritizing the description of the predominant histological patterns and their salient features, while specifically noting any findings indicative of a specific etiology. Diagnostic limitations secondary to suboptimal specimen quality must be explicitly stated. Pathologists are required to provide a systematic and standardized microscopic description of the tissue pathology, formulate a histopathological classification, and offer etiological insights whenever feasible (Level of evidence: 4, Recommendation: strong).Recommendation 15: Post-biopsy MDD is central to formulating an integrated diagnosis and should be conducted by the same cohort of clinicians, radiologists, and pathologists involved in the initial evaluation. A systematic correlation between the histopathology and the clinical andradiologic data is required; any discordances must be thoroughly analyzed to achieve a consensus integrated diagnosis and guide therapeutic planning. If an integrated diagnosis cannot be established, a subsequent MDD or referral to an expert center for a repeat biopsy is warranted (Level of evidence: 2, Recommendation: strong).

Acute respiratory distress syndrome (ARDS) is characterized by rapid progression and a high mortality rate. Current therapeutic strategies focus primarily on pathogen clearance, which may not adequately regulate the host's dysregulated immune response. The homeostasis of the local pulmonary immune microenvironment is a significant factor determining the severity of tissue injury and the efficacy of subsequent repair. Taking the evolution of ARDS from physiological defense to pathological injury as its main thread, this review examines the spatiotemporal transition mechanisms involved in this pathological process. It outlines the molecular basis of early-stage inflammatory dysregulation, identifying macrophage M1/M2 polarization imbalance, metabolic reprogramming, and the formation of neutrophil extracellular traps as key drivers of pulmonary inflammation. It further describes how a persistent inflammatory microenvironment can induce senescence of type Ⅱ alveolar epithelial cells and pathological remodeling of the extracellular matrix, which serve as primary barriers to alveolar regeneration and contribute to pulmonary fibrosis. Based on these mechanisms, this article summarizes recent advances in stage-specific interventions, focusing on mesenchymal stem cell therapy, immunometabolic reprogramming, and environment-responsive nanomedicines.

Objective: To investigate the associations between snoring phenotypes recorded during preoperative drug-induced sleep endoscopy (DISE) and polysomnographic (PSG) metrics in children with obstructive sleep apnea (OSA). Methods: We retrospectively enrolled 175 children who underwent structured preoperative DISE between November 1, 2024 and January 1, 2026 because of confirmed/suspected obstructive sleep apnea (OSA) or adenoid-related upper airway assessment before orthodontic treatment. Among them, 108 were boys and 67 were girls, with a mean age of (6.9±1.9) years and a median age of 7.0 years (interquartile range, 5.6-8.0 years). All 175 children were included in the DISE descriptive analysis set to summarize structured DISE findings, snoring intensity, and snoring-source plane distribution. Of these, 136 children with DISE-documented snoring were included in the snoring-source plane analysis set to evaluate snoring-source planes and their combinations. Children were grouped according to DISE-recorded snoring intensity grades 0, 1, and 2, the number of five key snoring-source planes, and the presence or absence of each key plane. The five key snoring-source planes included the adenoid, soft palate, tonsil/lateral pharyngeal wall, tongue, and epiglottis. Among the 175 children, 108 with complete PSG outcomes and covariates including age, sex, and body mass index (BMI) were included in group comparisons and multivariable regression analyses. The primary outcome was obstructive apnea-hypopnea index (OAHI), and the secondary outcome was minimum peripheral oxygen saturation (SpO₂ nadir). Group comparisons were performed using the Kruskal-Wallis test or Mann-Whitney U test. Multivariable linear regression was used to analyze the association between DISE snoring phenotypes and PSG metrics. Results: Among 175 children, 108 were boys (61.7%), the mean age was (6.9±1.9) years, and DISE documented snoring in 136(77.7%). In the PSG subgroup, median OAHI [interquartile range] across snoring grades 0, 1, and 2 was 3.6(2.2, 6.4), 5.8(3.0, 10.5), and 19.1(9.4, 45.6) events/h, respectively (H=14.43, P<0.001); corresponding SpO₂ nadirs were 91.5%(89.0%, 94.0%), 93.0%(89.0%, 94.5%), and 84.0%(80.0%, 92.0%) (H=9.90, P=0.007). After adjustment for age, sex, and body mass index (BMI), snoring intensity remained independently associated with OAHI (β=0.45, P=0.010); each one-grade increase corresponded to a 56.8% increase in (OAHI+1) (95%CI 11.3%-120.9%). Conclusions: Snoring intensity during preoperative DISE was independently associated with PSG-derived obstructive burden in children with OSA. Tonsillar/lateral pharyngeal wall involvement predominated, while epiglottic and tongue-related planes were also common.

Objective: To assess the anatomical and genioglossus electromyography (ggEMG) indicators in obstruction patterns classified by the VOTE system. Methods: This prospective study was conducted from September 2019 to April 2023, with a total of 107 adult patients (101 males and 6 females) aged 20-59 (38.8±8.0) years old (AHI≥15 times/hour) diagnosed with moderate to severe obstructive sleep apnea (OSA) at Beijing Tsinghua Changgung Hospital. Each subject underwent 3-D upper airway computed tomography (UACT), drug-induced sleep endoscopy and intraoral surface ggEMG monitoring. Based on VOTE system, the characteristics of UA collapses were classified and compared. Statistical analysis was conducted by SPSS 21.0. Results: All 107 patients with moderate to severe OSA had complete collapse of the velopharynx airway (including 47 cases in anteroposterior collapse group, 10 cases in the lateral collapse group, and 50 cases in the concentric collapse group). Comparing patient data from three different collapse modes, it was found that the velum pattern groups showed no statistical ggEMG differences (P>0.05); however, the lateral group exhibited the narrowest velopharynx mLAT [AP: 14.45(12.0, 16.2) mm, Lat: 11.40(9.6, 14.4) mm, Con: 12.70(11.0, 15.8) mm,H=6.41, P=0.041], and largest glossopharynx mAP[AP: 11.90(9.0, 15.7) mm, Lat: 14.30(11.8, 20.3) mm, Con: 14.10(11.8, 16.9) mm,H=8.40, P=0.015]. We found that patients with complete oropharynx lateral walls and partial tongue base collapse tended to have a higher BMI [(29.43±3.35)kg/m² vs.(26.70±2.53) kg/m²,t=-2.83, P=0.007], longer glossopharynx length [(25.94±5.80) mm vs. (20.90±5.48)mm, t=-2.60,P=0.014], narrower glossopharynx mLAT [(15.59±3.87) mm vs. (21.10±8.07) mm, t=2.59, P=0.017], and were more likely to combine ggEMG dysfunction during obstructive apnea events [R4,(0.02±0.01)vs.(0.01±0.01), t=2.08, P=0.045)]. Moreover, all patients were classified according to the degree of epiglottic collapse (including 31 cases of no collapse, 33 cases of patial collapse, and 43 cases of complete collapse). The complete epiglottic collapse group exhibited the narrowest velopharynx minimal cross-sectional airway area (H=11.01, P=0.004) and the narrowest glossopharynx anteroposterior airway dimensions (H=7.06, P=0.029) and the longest glossopharynx length (H=9.65,P=0.008), whereas, the group of no epiglottic collapse showed the lowest ggEMG activation while awake (R1,H=8.59,P=0.014) and during sleep-onset (R2,H=9.79,P=0.007). Conclusions: The multiple plane collapse of the UA under DISE is the result of the combined effects of anatomical and functional factors, while the VOTE system cannot accurately describe the impact of different anatomical and functional causes. Among them, the degree of oropharynx lateral walls, tongue base and epiglottic collapse can all be affected by the function of the genioglossus muscle. This study can provide a theoretical basis for the comprehensive etiological treatment of OSA patients with multiple plane collapse.

Objective: To analyze the characteristics of electroencephalogram (EEG) power spectral density (PSD), slow wave oscillation, and sleep spindles across different sleep stages, brain regions, and levels of severity in patients with obstructive sleep apnea (OSA). Methods: This case-control study collected data from 1 821 suspected OSA patients, comprising 1 422 males and 399 females, with a median age 39 (32, 49) years, who attended our hospital between July 2018 and July 2024. EEG features, including PSD, slow wave oscillations, and sleep spindles, were extracted from polysomnography recordings across different sleep stages and brain regions. The changing trends of these features were analyzed between the OSA and non-OSA groups, as well as across different OSA severity levels. For non-normally distributed variables, the Mann-Whitney U test was used for two-group comparisons, and the Kruskal-Wallis H test with Bonferroni correction was used for multi-group comparisons. For normally distributed variables, the t-test (for two groups) and one-way ANOVA with Bonferroni correction (for multiple groups) were applied. The chi-square test was used for comparisons of categorical variables. Results: Among the 1 821 subjects, 1 706 were diagnosed with OSA including 302 mild, 351 moderate, and 1 053 severe cases. Compared with the control group, the OSA group exhibited the following whole-brain EEG changes: increased PSD in Delta, Theta, Alpha, and Beta bands during N1 stage; increased PSD in Alpha, Beta, and Gamma bands during N2 stage; and increased PSD in all frequency bands during N3 and REM stages (all P<0.05). Moreover, PSD in all frequency bands showed a significant increasing trend with increasing OSA severity (all P _{for trend}<0.001). During N3 stage, the OSA group showed significantly higher density, duration, and amplitude of slow oscillations compared with the control group (P<0.05); during N2 stage, the OSA group showed significantly lower sleep spindle density compared with the control group (P<0.05). Changes in sleep EEG microstructural features were significantly correlated with OSA severity (all P _{for trend}<0.05). Conclusion: Patients with OSA exhibit EEG features during sleep characterized by cortical hyperarousal and thalamocortical rhythm dysregulation, which intensify with increasing disease severity. The observed alterations in EEG microstructural features suggest their potential value as indicators for assessing OSA-related brain functional impairment.

We compared data from the 2015 and 2024 pertussis epidemics in New South Wales, Australia. In 2024, we found twice as many notifications and a shift in distribution to older children. COVID-19 interventions and lack of circulation of pertussis likely contributed to an age cohort immunity gap and increased infections.

Antisense oligonucleotides (ASOs) are advantageous for the development of antiviral drugs against respiratory viruses. However, the methodology for efficiently identifying antiviral ASOs has not been well established, and to date no ASOs have successfully been developed for treating viral respiratory diseases. In this chapter, we describe a scheme that consists of three stepwise evaluation assays to identify ASOs having antiviral effects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19). The primary evaluation employs a luciferase-based assay without virus infection, which can be applied to high-throughput screening without the need for a high biosafety level facility. The secondary evaluation exploits a cell-based infection assay that assesses antiviral activity by detecting SARS-CoV-2-induced cytopathic effects, viral RNA, and proteins. Candidate ASOs are then further evaluated in a mouse SARS-CoV-2 infection model by detecting viral propagation and pathogenesis in vivo. This scheme permits systematic identification of antiviral agents starting from a library with a large number of ASOs.

Fibrotic interstitial lung diseases (ILDs) are characterized by progressive extracellular-matrix accumulation but arise from biologically diverse injuries. This narrative review examines endoplasmic reticulum (ER) stress as a context-dependent regulator of maladaptive repair, prioritizing evidence from human genetics, tissue, single-cell and spatial studies, patient-derived systems, biomarkers, and clinical trials. In selected familial surfactant disorders, pathogenic variants provide direct evidence that impaired proteostasis can cause fibrotic lung disease. In sporadic idiopathic pulmonary fibrosis (IPF), epithelial unfolded protein response (UPR) signatures and KRT8/KRT17-enriched transitional states are associated with arrested alveolar regeneration, but do not establish a single causal pathway. IRE1α, PERK-eIF2α, and ATF6 can support adaptive proteostasis during acute stress yet may contribute to inflammatory signaling, epithelial injury, or differentiation arrest when activation is persistent. Human spatial studies place stressed epithelium within SPP1-positive macrophage, activated-fibroblast, and endothelial niches, although ER-stress activity outside epithelium remains less certain. Evidence is strongest in IPF and familial surfactant disorders; extension to progressive pulmonary fibrosis, connective-tissue-disease-associated ILD, or fibrotic hypersensitivity pneumonitis remains inferential. Current antifibrotic and PDE4B-directed therapies slow functional decline but do not demonstrate correction of epithelial proteostasis. Direct ER, UPR, or integrated-stress-response strategies have not established human efficacy in fibrotic ILD. Future studies should define disease- and cell-specific repair states, measure target engagement longitudinally, and test interventions during potentially reversible windows of repair arrest.

Carbapenem-resistant Klebsiella pneumoniae (CRKp) strains are a major public health threat.

This study aimed to compare multiplex lateral flow immunochromatographic testing (LFT) and polymerase chain reaction (PCR) for detecting carbapenemase genes in carbapenem-resistant K. pneumoniae (CRKp). A secondary objective was to assess the gene-specific susceptibility profile of these isolates to critical antimicrobial agents: ceftazidime-avibactam (CZA), last-resort options (colistin, amikacin).

CRKp isolates from patient samples (blood, urine, and respiratory tract) were identified based on colony morphology, Gram stain, and the BD Phoenix M50system. Isolates resistant to ≥1 carbapenem per EUCAST criteria were included. Resistant isolates underwent PCR for bla KPC, bla NDM, bla VIM, bla IMP, and bla OXA-48 genes, and carbapenemase production was phenotypically confirmed using a commercial immunochromatographic test (ICT) kit (detecting OXA-48-like, NDM, VIM, IMP, KPC simultaneously). Susceptibility to ceftazidime-avibactam (CAZ-AVI), colistin, and amikacin was assessed according to EUCAST standards. The study was conducted in Western Anatolia, in Balıkesir, Türkiye.

The distribution patterns of the isolates showed that blaOXA-48 predominated (n = 27, 38.0% of positive isolates), followed by blaKPC (n = 15, 21.1%) and blaNDM (n = 7, 9.9%). Notably, 22 isolates (31.0%) harbored multiple carbapenemase genes: OXA-48 + NDM (n = 14, 19.7%), KPC + NDM (n = 4, 5.6%), and OXA-48 + KPC (n = 4, 5.6%). Neither blaVIM nor blaIMP was detected. The lateral flow test (LFT) demonstrated good agreement with PCR for the detection of blaKPC and blaOXA-48 genes (Cohen's κ = 0.72 and 0.65, respectively); however, its accuracy decreased in isolates harboring multiple carbapenemase genes. While susceptibility to ceftazidime- avibactam averaged 28.6% overall among CP-Kp isolates, it varied according to carbapenemase type, with KPC producers exhibiting the highest rate (46.7%).

These findings highlight the importance of rapid and easily applicable diagnostic tests, as well as the urgent need for new antimicrobial agents and novel therapeutic approaches (e.g, Phage therapy, immunotherapies).

Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) is a platelet- and endotheliumassociated glycoprotein implicated in platelet activation, thrombus propagation, and endothelial injury. Because these processes underpin thrombo-inflammatory cardiovascular and cardiopulmonary diseases, circulating SCUBE1 has attracted interest as a candidate biomarker. This systematic review aimed to critically synthesize comparative clinical evidence on circulating SCUBE1 levels across thrombotic or ischemic cardiovascular and cardiopulmonary conditions relative to control or comparator groups.

A systematic search of PubMed, ScienceDirect, and SpringerLink was conducted for Englishlanguage studies published from 1 January 2015 to 27 September 2025. The protocol was prospectively registered in PROSPERO (CRD420251178563). Eligibility was guided by a PECO framework and included observational and diagnostic accuracy studies that measured circulating SCUBE1 in serum or plasma and reported patientcomparator data. Two reviewers independently screened studies, extracted data, and assessed methodological quality using design-specific Joanna Briggs Institute tools and ROBINS-I. Owing to clinical and methodological heterogeneity, findings were synthesized narratively without meta-analysis.

Nine studies were included (four cross-sectional, three case-control, one cohort, and one diagnostic accuracy study). SCUBE1 levels were generally higher in patients with thrombotic or ischemic cardiovascular and cardiopulmonary diseases than in comparators, supporting associations with platelet-endothelial activation, thrombotic burden, endothelial dysfunction, and ischemia-reperfusion stress. However, absolute concentrations varied markedly across studies, precluding direct comparison and limiting interpretability of proposed cut-off values. Eight studies had moderate risk of bias and one had serious risk.

SCUBE1 is a biologically plausible but still investigational biomarker; robust multicenter prospective studies with standardized assays are required before clinical translation in routine clinical practice.