OBJECTIVE:To identify radiologic computed tomography (CT) predictors of increased diagnostic yield and fewer complications in transbronchial lung cryobiopsy (TBCB). METHODS:We retrospectively reviewed CT scans of 143 patients (51.7% female; mean age 62.7) who underwent TBCB at Mayo Clinic (January 1, 2017, to July 31, 2020). Multivariable logistic regression evaluated whether imaging, pulmonary function, and procedural parameters predicted diagnostic yield and complications. RESULTS:Procedural complications included clinically significant bleeding (10.5%), pneumothorax (7.0%), and escalation of care (8.4%), with zero procedure-related deaths. Trainee presence did not affect the rate of clinically significant bleeding (10.5% vs 9.4%, p=0.999) or whether the biopsy yielded a specific histopathologic diagnosis (61.9% vs 65.6%, p=0.703). Abnormal histopathologic findings were seen in 87.4% of cases, with 62.2% of biopsies sufficiently identifying a specific diagnosis even when reviewed in isolation. Radiologic honeycombing was associated with an 82% lower yield on histopathology (aOR=0.18, 95% CI 0.05-0.68), despite higher number of passes. Higher DLCO was associated with lower complication rate (aOR=0.95, 95% CI 0.92-0.99), while higher FEV1 was associated with improved histopathologic yield (aOR 1.02, 95% CI 1.01-1.04). CONCLUSIONS:CT imaging and pulmonary function parameters influence diagnostic yield and complication rates for TBCB in ILD. Radiologic honeycombing was a negative independent predictor of TBCB histopathologic yield, and clinicians should weigh whether TBCB in such cases provides incremental diagnostic value over integration of clinical and imaging data alone. Better lung function was associated with improved yield and lower complication risk. These findings may help refine patient selection and procedural planning.

Pulmonary hypertension (PH) is a common sequela of interstitial lung diseases (ILDs) and is associated with poor prognosis and quality of life. The diagnosis and management of PH associated with ILD (ILD-PH) are challenging, due in part to the heterogeneity of ILD subtypes, difficulty distinguishing symptoms and signs of ILD progression from manifestations of PH, lack of specific biomarkers, and the requirement of invasive right heart catheterisation (RHC) to diagnose and assess the severity of PH. This state-of-the-art review provides a comprehensive overview of the clinical characteristics, pathophysiology, diagnosis, prognosis and treatment of ILD-PH. It also identifies promising areas for future research, such as the development and validation of novel biomarkers and imaging techniques and further evaluation of the efficacy and safety of pharmacological therapies for PH in patients with ILD. Given the inherent complexity of diagnosing and managing heterogeneous ILD subtypes, there is a clear need for multidisciplinary and personalised care strategies for ILD-PH. Dedicated attention and further research to improve diagnostic and treatment interventions are warranted to help develop much-needed, evidence-based guidelines and to improve outcomes that are meaningful for patients with ILD-PH.

Pulmonary venoocclusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) belongs to the WHO group 1 pulmonary hypertension (PH), labeled as pulmonary arterial hypertension (PAH), though it mainly involves pulmonary veins, venules and capillaries. PVOD/PCH may occur as a pure form, with other types of PH, or with fibrotic interstitial lung diseases (ILDs). Recognition of PVOD/PCH is crucial as vasodilators used in PAH patients may cause severe pulmonary edema in PVOD/PCH patients. Since biopsy is relatively contraindicated in PAH given the high risk of complication, high resolution computed tomography (HRCT) plays an important role in the diagnosis of PVOD. Centrilobular ground-glass opacities (cGGO), interlobular septal thickening (IST) and mediastinal lymphadenopathy (mLAD) have been described as the triad of HRCT findings for PVOD/PCH but the sensitivity and specificity of this triad in different settings of PVOD/PCH have not been well characterized. In the present study, we compared the clinical and HRCT findings in different settings of PVOD/PCH. Cases of PVOD/PCH diagnosed with surgical lung biopsy, explant or autopsy were identified from the pathology archives (2003-2026) and categorized into 3 groups: pure PVOD/PCH (group 1, n = 14), PVOD/PCH with other types of PH (group 2, n = 3), and PVOD/PCH with fibrotic ILD (group 3, n = 6) after re-review of all slides to confirm the diagnosis. Clinical and radiologic findings were systematically evaluated and compared across these 3 groups. Mean ages at diagnosis were 51, 39, and 58 years in groups 1, 2, and 3, respectively. Median values for mean pulmonary arterial pressure were 51.0, 55.0, and 49.0 mmHg in groups 1, 2, and 3, respectively. There was no significant difference in sex or smoking status across the 3 groups. HRCT showed following results in groups 1, 2 and 3: cGGO in 57.1%, 66.7%, and 0% (p = 0.03); IST in 64.3%, 66.7% and 16.7%; mLAD in 85.7%, 66.7%, 83.3%. At least two of the three features of the triad of cGGO, IST, and mediastinal LAD were present in 10 of 14 (71.4%), 2 of 3 (66.7%), and 1 of 6 (16.7%) of group 1, 2 and 3 cases respectively. There was insufficient statistical power to detect potential trends in clinical and radiographic patterns across subgroups (with exception for cGGO), due to the small number of cases. Taken together, some PVOD/PCH cases in all groups of our cohort lacked the triad of HRCT findings and most patients were unsuspected of PVOD/PCH based on clinico-radiologic features. In conclusion, the role of pathologists would be highly important to raise the awareness of potential PVOD/PCH to pulmonologists given the therapeutic implications.

Interstitial lung abnormalities (ILAs) are incidental nondependent radiologic findings that may portend early or future interstitial lung disease (ILD), but do not meet specific criteria at the time of presentation. They are subclinical by definition and found more commonly in older ever-smokers undergoing computed tomography (CT) imaging for other indications, including cardiac or lung cancer screening programs. As ILA prevalence increases, driven by an aging population and heightened awareness in younger patients, understanding risk factors for their development and progression has gained recent interest, particularly for optimizing subsequent ILD outcomes. This narrative review summarizes current ILA definitions, epidemiology, risk stratification, and management, while highlighting current challenges and knowledge gaps.

Spontaneous pneumothorax (SP) is defined by the presence of air in the pleural space arising from neither trauma nor iatrogenic causes. It can develop secondary to various etiologies. The familial clustering observed in some patients with SP supports the view that genetic factors play a role in the pathogenesis of SP. Several recognizable pneumothorax-associated genetic syndromes exist, including Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex-associated lymphangioleiomyomatosis (TSC-LAM), Marfan syndrome (MFS), cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), vascular Ehlers-Danlos syndrome (vEDS), Loeys-Dietz syndrome (LDS), and a few others. Recognition of these syndromes underlying SP facilitates optimal management and counseling regarding prognosis and potential comorbidities. In this review, we systematically summarize several genetic syndromes associated with pneumothorax, in which SP may manifest either as an initial presenting symptom or as a potential complication that adversely affects the prognosis.

There has been an increasing recognition that rare diseases represent a substantial global health burden. In the United States, rare or orphan disease is defined as a condition affecting less than 200,000 persons, which is approximately 63 per 100,000 persons (1,2). In Europe, a disorder is defined as rare when it affects less than 1 in 2,000 (approximately 50 per 100,000) persons. Because there are more than 6,000 rare diseases, it is estimated that 8% of the general population are affected by these rare disorders, and many of them remain undiagnosed (1,2).

OBJECTIVE:To determine the clinicoradiologic features and clinical outcomes associated with intrathoracic Erdheim-Chester disease (ECD). PATIENTS AND METHODS:Electronic medical records of all consecutive patients with ECD encountered at Mayo Clinic from January 2005 to August 2024 were reviewed. Twenty-four patients were included. Treatment response was defined by the Response Evaluation Criteria in Solid Tumors and metabolic response on follow-up positron emission tomography scans. Survival analyses were performed from time of intrathoracic ECD diagnosis. RESULTS:Median age at diagnostic biopsy was 65 years (range, 43-79 years) and pleuropulmonary/mediastinal biopsy provided the first diagnosis of ECD in 77.8% of patients. Most patients (95.8%) were symptomatic. The BRAFV600E pathogenic variant or BRAF gene fusions were identified in 58.3% of patients. Common radiographic findings included ground-glass opacities (91.7%), interlobular septal thickening (79.2%), pulmonary nodules (70.8%), and pleural abnormalities (66.7% to 70.8%). Pulmonary function testing revealed predominantly restrictive patterns (40.0%). Diffusion capacity of the lungs for carbon monoxide was almost always reduced (median: 56.5% of predicted; range, 25.0% to 106.0%). Complete response was 10.5%, partial response was 10.5%, and objective response rate was 21.0%. Stable disease and progressive disease were noted in 57.9% and 21.1%, respectively. Median overall survival was 10.9 years (95% CI, 5.5-undefined) and estimated 5-year survival was 85.0%. CONCLUSION:Erdheim-Chester disease causes symptomatic pleuropulmonary disease, which may be the initial presenting feature. Erdheim-Chester disease characteristically manifests interlobular septal thickening with ground-glass and/or small nodular opacities, often combined with pleural thickening and/or pleural effusions. Targeted therapy may provide durable therapeutic responses.

Background/Objectives: Interstitial lung disease (ILD) occurs commonly in systemic sclerosis (SSc) and is the leading cause of mortality. There are limited data on the accuracy of lung auscultation in identifying the presence of ILD in patients with SSc. Methods: We retrospectively identified patients with newly diagnosed SSc who had documented lung auscultation findings and chest high-resolution computed tomography (HRCT) available for review. Diagnoses were made by rheumatologists at Mayo Clinic, Rochester, Minnesota, USA over a 4-year period. Pulmonary function measurements included lung volumes, spirometry, and single-breath diffusing capacity. Results: Among 151 patients with SSc (median age, 62 years), 72.2% were female and 55.0% were never smokers. Limited cutaneous SSc was the most common phenotype (67.3%). Seventy (46.4%) patients were evaluated by pulmonologists. There was evidence of ILD by HRCT in 69 patients (45.7%); the most common pattern of ILD was fibrotic nonspecific interstitial pneumonia (59.2%). Respiratory symptoms were present in 46.4% of those with ILD compared to 15.9% among those without. The sensitivity and specificity for crackles heard by rheumatologists in detecting ILD were 50.7% and 97.6%, respectively; for pulmonologists, 71.4% and 85.7%, respectively. Presence of crackles was associated with high positive predictive values (94.6% for rheumatologists vs. 92.1% for pulmonologists, respectively); negative predictive values were moderate (70.2% vs. 56.3%, respectively). Crackles correlated with lower pulmonary function measures but did not differ across ILD patterns. Conclusions: Detection of crackles on lung auscultation appears to be a specific and moderately sensitive indicator of ILD (often asymptomatic) in patients with newly diagnosed SSc. The presence of crackles correlates with worse pulmonary function but may be absent in early ILD.

Rationale:Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterised by diffuse bronchial hyperplasia of pulmonary neuroendocrine cells, which are situated within the walls of bronchi and bronchioles. Presenting symptoms are nonspecific and the clinical course varies, making diagnosis challenging. We sought to describe the clinical characteristics of patients with DIPNECH in a large multinational case series to guide and inform future care and research. Methods:Data were collated from 18 international centres. Information collected included disease presentation, pulmonary function testing, histopathology, radiological patterns and outcomes. The relationship between clinical features, radiology and symptoms were explored in parametric and nonparametric group-wise analyses, univariate linear regressions, and multivariate binomial logistic regression. Results:The mean±sd age of the 258 patients in this study was 63.3±10.6 years and 93.4% were female. Diffuse pulmonary nodules (98.8%) and mosaic attenuation (59.1%) were the most common radiological findings and 29.5% had obstructive spirometry with a mean±sdforced expiratory volume in 1 s (FEV1) % pred of 69.0±23.7%. There was a significant association between the number of nodules and a reduction in FEV1 % pred (p<0.001), while the presence of bronchial wall thickening on imaging was most closely associated with cough (OR 4.97, p=0.001) dyspnoea (OR 3.14, p=0.003) and bronchodilator responsiveness (OR 3.09, p=0.013). Approximately half of patients treated with inhaled beta agonist and corticosteroids (46.3%) or somatostatin analogue (54.1%) reported improvement in symptoms. Conclusions:The presence of radiological bronchial wall thickening is associated with the presence of symptoms, while mosaic attenuation is correlated with airflow obstruction; hence, the presence of these radiological findings has the potential to guide possible treatment decisions.

To investigate the prevalence and recurrence rates of spontaneous pneumothorax (SP) in patients with diffuse cystic lung diseases (DCLDs). We retrospectively identified and analyzed medical records of patients with DCLDs encountered at the First Affiliated Hospital of University of Science and Technology of China from Jan 1, 2017 to December 31, 2023. A total of 289 patients were identified with DCLDs; 212 females and 77 males, with a median age of 48 years (range, 18–81 years). Among them, 89 (31

Amyloidosis and Light Chain Deposition Disease (LCDD) are disorders characterized by the deposition of abnormal proteins in tissues, leading to organ damage. Pulmonary involvement in amyloidosis can manifest as diffuse alveolar-septal amyloidosis, nodular or cystic pulmonary amyloidosis, or tracheobronchial involvement. The types of amyloidosis-immunoglobulin light chain), serum amyloid A, and transthyretin (ATTR)-affect the lungs differently, with ATTR being rare. LCDD, which primarily affects the kidneys, may also cause lung abnormalities, such as cystic or nodular disease. Both conditions are diagnosed through biopsy and imaging, with therapies targeting the underlying plasma cell or inflammatory disorders.

BACKGROUND:Patients with idiopathic pulmonary fibrosis (IPF) undergoing lung cancer surgery face a 4.4-20 % risk of acute exacerbation (AE-IPF) with mortality exceeding 50 %. The potential role of perioperative antifibrotic therapy in reducing surgical complications in this high-risk population remains unclear. OBJECTIVES:To evaluate whether perioperative antifibrotic therapy (pirfenidone/nintedanib) reduces complications, particularly acute exacerbations and mortality, in IPF patients undergoing lung cancer surgery through systematic review and meta-analysis. METHODS:Following PRISMA guidelines, we conducted a systematic review and meta-analysis of observational studies examining perioperative antifibrotic therapy in IPF patients undergoing lung cancer surgery. Four studies comprising 261 patients (124 treated, 137 controls) from Japan and Italy (2016-2024) were analyzed. Pooled risk ratios were calculated using Review Manager 5.4. The study protocol was registered with PROSPERO (ID: CRD42025649005). RESULTS:Perioperative antifibrotic therapy achieved a 69 % reduction in AE-IPF risk (RR 0.31, 95 % CI 0.13-0.70) and an 81 % reduction in 90-day mortality (RR 0.19, 95 % CI 0.07-0.52). Additional benefits included significantly shorter hospital stays (5 vs 7 days, p = 0.029) and reduced complications, including decreased prolonged air leak rates (3.4 % vs 26.9 %). Adverse events were minimal, consisting primarily of mild nausea and photosensitivity. CONCLUSIONS:Perioperative antifibrotic therapy significantly reduces acute exacerbations and mortality in IPF patients undergoing lung cancer surgery. However, findings are limited by small observational studies concentrated in specific geographic regions. Randomized controlled trials are needed to confirm efficacy and establish standardized treatment protocols.

BACKGROUND:Pneumocystis jirovecii pneumonia (PJP) is life-threatening for immunocompromised patients. No consensus exists on PJP prophylaxis for immunosuppressed patients without HIV, transplant, or cancer. METHODS:We retrospectively reviewed the electronic health records of adult immunosuppressed patients with PJP diagnosed between 1990 and 2020 at Mayo Clinic. Patients with HIV, solid organ transplants, or cancer were excluded. Demographic data, treatments, and outcomes were manually abstracted. RESULTS:The most common indications for immunosuppression were rheumatoid arthritis (19.7%), vasculitis (18.1%), and interstitial lung disease (ILD) not related to connective tissue disease (17.6%). Despite having high risk of PJP, 86.0% of patients did not receive PJP prophylaxis. Corticosteroids were the most common immunosuppressive agent used (84.5%), with 64.4% of patients receiving high-dose treatment. Nonbiologic disease-modifying antirheumatic drugs were used for 49.7%, including methotrexate (51.0%), azathioprine (22.9%), and hydroxychloroquine (11.5%). Biologics were prescribed for 25.4%, primarily rituximab (59.2%) and infliximab (22.4%). Hospitalization occurred for 76.7% of patients; 70.3% required intensive care unit (ICU) admission, and 46.6% received mechanical ventilation. The in-hospital mortality rate was 30.4% overall and 53.6% for patients on ventilation. Predictors of death included ILD [odds ratio (OR), 4.61; 95% CI, 1.75-13.00], ICU admission (OR, 3.60; 95% CI, 1.19-11.08), and ventilator use (OR, 3.46; 95% CI, 1.30-9.79). Biologic use was associated with lower odds of death (OR, 0.34; 95% CI, 0.11-0.89). CONCLUSIONS:Most patients in our cohort did not receive PJP prophylaxis, and outcomes were poor with high mortality rates. Standardized risk stratification and prophylaxis protocols are needed to improve outcomes.

Pulmonary manifestations of systemic autoimmune rheumatic diseases (SARDs) may involve the large and small airways, lung parenchyma, pleura, respiratory muscles and thoracic cage. Bronchiolar disorders (BDs) or small airways disease (SAD) are common and may sometimes be the dominant presentation in patients with SARDs. We conducted a literature review using search terms "bronchiolitis," "small airway diseases" and the names of individual SARDs and collated relevant articles published between January 1977 and April 2024. A summary of the incidence/prevalence, clinical manifestations, pathogenetic mechanisms, pulmonary function testing, chest imaging, histopathology and treatment options for BDs associated with SARDs is provided in this review. BDs associated with Sjögren syndrome, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, idiopathic inflammatory myositis, mixed connective tissue disease and ankylosing spondylitis are specifically highlighted.

ObjectivePopulation-based epidemiology studies about antisynthetase syndrome (ASS) are lacking. Our aims were to determine the incidence and prevalence of ASS and assess malignancy risk among patients following ASS diagnosis.MethodsA retrospective, population-based cohort of adults with incident ASS residing in Olmsted County, Minnesota, in 1998-2019, was assembled. Fulfillment of Solomon classification criteria for ASS and clinical data were collected by manual chart review. Patients were followed until death, migration from the area, or December 31, 2019. Malignancy was defined by physician diagnosis in the medical record. Incidence rate was age- and sex-adjusted to the 2010 US White population. Point prevalence rate was obtained on January 1, 2015.ResultsThirteen patients with ASS were identified (7 [54%] female, 13 [100%] White, median age 44.9 [IQR 41.9-58.3] years). The age- and sex-adjusted incidence of ASS was 0.56 (95% CI 0.25-0.87) per 100,000 population. Incidence was highest in the 50-59 age group. Age- and sex-adjusted prevalence was 9.21 per 100,000 (95% CI 3.44-14.98). Two of 13 (15%) were diagnosed with malignancy within the follow-up interval and none within 3 years of ASS diagnosis. At median 11.9 (IQR 7.0-13.4) years of follow-up, 12/13 (92%) of patients were alive.ConclusionASS is rare, with an incidence of 0.56 per 100,000 population and prevalence of 9.21 per 100,000. In this cohort, incidence was similar between male and female individuals, and was highest in persons aged 50-59 years. None of the patients developed malignancy within 3 years of ASS diagnosis.

Rationale: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pulmonary condition characterised by neuroendocrine cell proliferation along respiratory bronchioles resulting in tumourlet formation which may progress to pulmonary carcinoid. DIPNECH is a rare and under-recognised condition that predominantly affects females, with an estimated worldwide incidence of 5-6 people per million population. Given it's rarity and the poor understanding around the pathogenesis and treatment of this condition, we undertook the largest international case series to date of DIPNECH patients. We aim to further characterise this patient cohort to better understand the clinical features, identify common pulmonary function test (PFT) patterns and radiographic findings and describe current treatment practices. Methods: We collated data from 17 centres across 8 different countries comprising a total of 258 patients. Data collected included patient demographics, smoking history, symptoms, co-morbidities, pathological diagnosis, imaging findings, PFT pattern and therapies. Results: In total 258 patients were identified. The median age was 65 (SD+/- 10.6). 241 (93%) were female. 39% (n= 94/243) were ex-smokers. 79% (n=186/234) of patients reported pulmonary symptoms with cough being the most common symptom reported in 81% (n=151/186) of patients. Many patients were polysymptomatic, with cough and dyspnoea being the most common combination of symptoms described. (50.54%; n=94/186). Complete spirometry pattern was documented for 180 patients (69.78%) with an obstructive pattern being the most commonly observed (n=76/180; 42%). 27.5% (n=41/139) had clinically significant FEV1 reversibility post bronchodilator administration. Pathology specimens were available in 219 cases. Most common pathological features were neuroendocrine hyperplasia which was observed in 75% (n=165/219) and tumourlets in 74% (n=162/219) of cases. Carcinoid, either typical or atypical, was observed in 64% (n=141/219) of samples. 252 patients had computed tomography (CT) imaging performed. Pulmonary nodules were the most common feature identified in 99.60% of cases (248/250). Mosaic attenuation (69.30%; n=50/173) and airway dilatation (28.90%; n=50/173) were also frequently reported. There was no significant correlation between symptoms (cough, dyspnoea, wheeze) and airway dilatation (p=0.496), mosaic attenuation (p=0.496) and PFT pattern (p=0.837). There was a significant association between presence of symptoms and mosaic attenuation on CT (p=0.003). Conclusions: DIPNECH, while a rare disorder, is understudied. This international case series is the largest performed to date and highlights the complexity in management of these patients.