Bronchiolitis Obliterans Organizing Pneumonia Research Articles

The Clinical Significance of Interstitial Pneumonia with Autoimmune Features in Cryptogenic Organizing Pneumonia: A Prospective Multicenter Observational Study

Background: There are cases of idiopathic interstitial pneumonias (IIPs) that do not meet the diagnostic criteria for connective tissue disease but have clinical features suggestive of autoimmune process. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept for these patients. Although several prospective studies on IPAF have been conducted, its clinical significance in cryptogenic organizing pneumonia (COP) remains unclear. Methods: Patients aged ≥20 years with suspected COP were prospectively enrolled between June 2018 and December 2022. Among the enrolled patients, those diagnosed with COP based on computed tomography (CT) and bronchoalveolar lavage (BAL) findings were compared between the IPAF and non-IPAF groups. Results: A total of 56 patients were enrolled in this study. Of these, 30 were diagnosed with COP and included in the analysis. Clinical and serological features were positive in two and six patients, respectively. Each feature was exclusive, and eight patients (26.7%) were diagnosed with IPAF. There were no differences between the IPAF and non-IPAF groups in terms of clinical features, including BAL findings, laboratory data, CT findings, and clinical course. During the one-year follow-up period, the frequency of COP exacerbation did not differ between the IPAF and non-IPAF groups, and no cases of systemic autoimmune disease or death occurred in either group. Conclusions: The COP characteristics of the IPAF and non-IPAF groups are similar in all aspects, and distinguishing between the two groups may be of little significance.

Secondary organising pneumonia associated to COVID-19 infection in patients with central nervous system inflammatory demyelinating diseases treated with anti-CD20 therapies.

Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited. To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20. Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023. Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID. In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered.

PREVALÊNCIA E DIAGNÓSTICO DE MANIFESTAÇÕES PULMONARES NA ARTRITE REUMATOIDE

Rheumatoid arthritis (RA) is a chronic oungar disease that mainly affects the joints, but can also oungar several extra-articular manifestations, with oungar involvement being the most common. This study aimed to analyze the prevalence and types of oungar manifestations in patients with RA, in addition to describing the clinical profile of these individuals. Seventeen studies, published between 2019 and 2024, were reviewed, selected from databases such as PubMed, MEDLINE and LILACS. Interstitial lung disease (ILD) was the most common oungar manifestation, with emphasis on the patterns of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP). The prevalence of the UIP pattern ranged from 18.4% to 72.2% in the studies analyzed, being the pattern most associated with mortality. Other manifestations, such as bronchiectasis and bronchiolitis, have also been described, with prevalence rates ranging from 14.3% to 35.6% and 2% to 18%, respectively. Other less oungare manifestations were oungar nodules, unclassifiable oungar fibrosis, small airway disease, pleural effusion, unspecified pleural disease, methotrexate-induced pneumonitis, bronchiolitis + ILD, and other unclassifiable or undetermined. The study revealed that most patients with oungar involvement in RA were seropositive for antibodies such as ANTI-CCP and rheumatoid oung (RF). Smoking and advanced age were identified as oungare risk factors for the development of oungar complications. In conclusion, oungar manifestations in RA are common and significantly associated with morbidity and mortality. Strict clinical surveillance and personalized therapeutic strategies are essential to improve the prognosis of these patients.

High resolution computed tomography in systemic sclerosis: From diagnosis to follow-up.

Early diagnosis of interstitial lung disease (ILD) and pulmonary hypertension (PH) is crucial in systemic sclerosis (SSc) for both management and treatment. However, diagnosing SSc-ILD can be challenging because symptoms of lung involvement are often non-specific at the early stages of disease. High-resolution computed tomography (HRCT) of the chest is recognized as the most accurate imaging modality for baseline and follow-up evaluation of SSc-ILD. Key features of SSc-ILD on HRCT include a non-specific interstitial pneumonia (NSIP) pattern, with peripheral ground-glass opacities and extensive traction bronchiectasis. Less common HRCT manifestations include usual interstitial pneumonia (UIP) pattern, followed by diffuse alveolar damage (DAD), diffuse alveolar hemorrhage (DAH) and organizing pneumonia (OP). The extent of disease on HRCT is known to relate with prognosis and serial assessments can be helpful in monitoring disease progression or treatment response. We discuss the main chest computed tomography (CT) manifestations of SSc, highlighting the role of imaging at both baseline and follow-up evaluations.

Long COVID in Immunocompromised and Immunocompetent Patients: A Clinical, Morphologic, and Virologic Portrait.

Coronavirus disease 2019 (COVID) primarily affects the lung and can lead to chronic/post-COVID syndrome. Some insights about late pulmonary changes occurring in patients recovering from COVID have been published, but the evidence of detailed pathologic changes coming from follow-up care patients with long COVID is limited. To evaluate tissue morphologic and viral features in transbronchial biopsies of long COVID patients (immunocompetent and immunocompromised). This retrospective observational study included 18 patients (9 immunocompetent and 9 immunocompromised) who were consecutively referred to outpatient clinic for post-COVID pneumonia, undergoing transbronchial biopsy. Several histologic changes were analyzed by computer-assisted morphometric analysis. As organizing pneumonia (OP) was consistently detected, fibrosis and inflammation were also evaluated in transbronchial biopsies from 28 control patients with histologic confirmation of OP. Tissue SARS-CoV-2 and the subgenomic transcripts were investigated. Morphologic findings were correlated with clinical and radiologic data. Long COVID patients showed lower inflammation than controls (P < .001) despite a similar fibrotic extension. When considering separately the 2 long COVID groups, the same inflammatory infiltrate extension was found, whereas a higher fibrotic remodeling characterized the immunocompetent subgroup (P = .05). Molecular investigation showed that SARS-CoV-2 was present in tissue samples obtained from 3 long COVID patients. Long COVID patients showed a peculiar OP pattern, with more vascular and fibrotic changes. SARS-CoV-2 RNA, even in replicative status, can be detected in lung biopsies of both immunocompetent and immunocompromised patients. This pilot study is a forerunner of more in-depth lung tissue investigations to gain a better understanding of long COVID pathobiology.

Risk factors for relapse of immune-related pneumonitis after 6-week oral prednisolone therapy: a follow-up analysis of a phase II study.

Immune-related pneumonitis (irP) is one of the most important immune-related adverse events caused by immune checkpoint inhibitors (ICIs). After corticosteroid therapy irP frequently relapses, which can interfere with cancer therapy. However, risk factors for irP relapse are unknown. This study was a follow-up analysis of a phase II study that evaluated 56 patients with grade ≥ 2 irP treated with oral prednisolone, 1mg/kg/day, tapered over 6 weeks. Clinical factors including patient characteristics, blood test findings, and response to prednisolone therapy were assessed to identify risk factors for irP relapse using the Fine-Gray test. Among 56 patients with irP, 22 (39.3%) experienced irP relapse after 6 weeks of prednisolone therapy during the follow-up observation period. Radiographic organising pneumonia (OP) pattern and duration to irP onset ≥ 100 days from ICI initiation were determined to be significant risk factors for irP relapse in a multivariate Fine-Gray test (hazard ratio [HR] = 3.17, 95% CI 1.37-7.32, p = 0.007, and HR = 2.61, 95% CI 1.01-6.74, p = 0.048, respectively). Other patient characteristics, blood test findings, irP severity, and response to prednisolone therapy were not associated with irP relapse. In irP patients treated with 6-week prednisolone tapering therapy, OP pattern and duration to irP onset ≥ 100 days were associated with relapse risk. Assessment of the risk factors for irP relapse will be helpful for irP management.

Computed tomography patterns and clinical outcomes of radiation pneumonitis in non-small-cell lung cancer patients.

Radiation pneumonitis (RP) is not an uncommon complication in lung cancer patients undergoing radiation therapy (RT) and symptomatic RP can affect their quality of life. To investigate the CT findings of RP in non-small cell lung cancer (NSCLC) patients and their relationship with clinical outcomes. We reviewed data from 240 NSCLC patients who underwent RT between 2014 and 2022. CT findings of RP were evaluated for parenchymal abnormalities and distribution, which were then classified into three patterns: localized pneumonia (LP), cryptogenic organizing pneumonia (COP), and acute interstitial pneumonia (AIP). Clinical outcomes of RP were evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) grade. Of the 153 patients, 135 developed RP. The most common pattern was LP (n = 78), followed by COP (n = 30) and AIP (n = 25). Among the three CT patterns, CTCAE grade and days between the start of RT and the onset of RP (RT-RP days) were statistically significantly different (p < 0.05). The patients with AIP patterns exhibited higher CTCAE grade, and fewer RT-RP days compared to those with non-AIP patterns (p < 0.05). In these patients, lung-to-lung metastasis and underlying interstitial lung abnormality were observed more frequently (p < 0.05). Underlying pulmonary fibrosis, the AIP pattern, and higher CT extent scores were more frequently observed in higher CTCAE grade group (p < 0.001). In multiple regression analysis, age, bilateral distribution, RT-RP days, and CT extent score ≥3 were independent predicting factors for higher CTCAE grade. RP in NSCLC patients can be classified into LP, COP, and AIP patterns and they exhibit different severities in clinical outcomes.

Diagnostic Alignment to Optimize Inter-rater Reliability Among Lung Transplant Pathologists

BackgroundPoor agreement among lung transplant pathologists has been reported in the assessment of rejection. In addition to acute rejection (AR) and lymphocytic bronchiolitis (LB), acute lung injury (ALI) and organizing pneumonia (OP) were recently identified as histopathologic risk factors for chronic lung allograft dysfunction (CLAD). Therefore, maximizing inter-rater reliability (IRR) for identifying these histopathologic risk factors is important to guide individual patient care and to support incorporating them in inclusion criteria for clinical trials in lung transplantation. MethodsNine pathologists across eight North American lung transplant centers were surveyed for practices in the assessment of lung transplant transbronchial biopsies. We conducted seven diagnostic alignment sessions with pathologists discussing histomorphologic features of CLAD high-risk histopathology. Then, each pathologist blindly scored 75 digitized slides. Fleiss’ kappa, accounting for agreement across numerous observers, was used to determine IRR across all raters for presence of any high-risk finding and each individual entity. ResultsIRR (95% confidence intervals) and % agreement for any high-risk finding (AR, LB, ALI and/or OP) and each individual finding is as follows: Any Finding, k = 0.578 (0.487, 0.668), 78.9%; AR, k = 0.582 (0.481, 0.651), 79.1%; LB, k = 0.683 (0.585, 0.764), 83.5%; ALI, k = 0.418 (0.312, 0.494), 70.9%; OP, k = 0.621 (0.560, 0.714), 81.0%. ConclusionsAfter pre-study diagnostic alignment sessions, a multi-center group of lung transplant pathologists seeking to identify histopathology high-risk for CLAD achieved good IRR.

Cryptogenic Organizing Pneumonia Is Associated With Increased Mortality Risk in Hospitalizations for Systemic Lupus Erythematosus (SLE): A National Inpatient Sample Analysis.

Background This study analyzed the incidence, characteristics, and mortality risk associated with cryptogenic organizing pneumonia (COP) among hospitalizations for systemic lupus erythematosus (SLE) with lung involvement. Methods Adult hospitalizations from the 2016-2020 nationwide inpatient sample were analyzed using relevantInternational Classification of Diseases (ICD)-10 codes for SLE with lung involvement (M32.13) and COP (J84.116). We compared baseline characteristics of individuals with SLE and COP to those of other lung involvements using Chi-square tests for categorical variables and the Wilcoxon rank sum test for continuous variables. A Cox proportional hazards model was used to assess the risk of developing COP in the pooled cohort of SLE patients. The impact of COP on SLE mortality was assessed using multivariate logistic regression adjusting forillness severity, baseline risk of mortality at admission, and patient- and hospital-level covariates. Results Of 40,356 admissions for SLE, 3,175 (7.9%) were due to lung involvement, with COP identified in 570 cases (17.9%). Compared with otherlung involvement in SLE, individuals with COP were significantly older (mean age: 65 vs. 44.3 years; p<0.001), mostly female (515; 90.4% vs. 2,305 males; 88.5%; p=0.572), had a greater baseline risk of mortality [diagnosis-related groups (DRG) major or extreme likelihood of dying: 360; 63.1% vs. 1,133; 43.5%; p<0.001], and had a higher prevalence of peripheral vascular disease (25; 4.4% vs. 39; 1.5%; p<0.001), and lower prevalence of lymphocytopenia (45; 7.9% vs. 359; 13.8%; p=0.001), and hypothyroidism (44; 7.8% vs. 357; 13.7%; p=0.001). Predictors of COP included female sex [adjusted hazard ratio (AHR): 1.46; 95% confidence interval (CI): 1.12-2.96; p=0.022]; hospitalizations occurring in the third quarter of the year (AHR: 1.37; 95% CI: 1.05-2.23; p=0.038); hospital stays of six days or longer (AHR: 1.71; 95% CI: 1.06-2.77; p=0.029); undergoing five or more procedures during the same hospitalization (AHR: 1.56; 95% CI: 1.26-3.56; p=0.041); coexisting lymphocytopenia (AHR: 1.92; 95% CI: 1.16-3.19; p=0.011); need for mechanical ventilation (AHR: 1.60; 95% CI: 1.48-3.93; p=0.049), presence of another autoimmune disorder (AHR: 1.37; 95% CI: 1.15-4.29; p=0.040), and being hospitalized at private, investor-owned hospitals (AHR: 2.62; 95% CI: 1.03-6.64; p=0.043). Mortality in SLE with lung involvement was correlated with age ≥ 60 years [hazard ratio (HR) (95% CI) 1.16 (1.05-1.56); p=0.012], coexisting lupus nephritis [HR (95% CI), 2.44 (2.04-3.49); p=0.031], cancer [HR (95% CI), 3.49 (2.19-5.79); p<0.001], liver disease [HR (95% CI), 9.82 (4.79-12.57); p<0.001]; immune deficiency [HR (95% CI), 2.22 (2.02-3.11); p=0.031], hypothyroidism [HR (95% CI), 4.67 (1.47-7.75); p=0.009], and high blood pressure [HR (95% CI), 3.15 (2.83-4.51); p<0.001]. In the multivariable analysis, COP remained significantly associated with an increased risk of mortality [AHR (95% CI), 1.43 (1.16-2.74); p=0.031]. The incidence of COP did not significantly impact hospitalization costs ($US 94,772 ± 14,759 vs. 95,982 ± 32,625; p=0.954) or length of stay (mean length of hospital stay: 8.3 vs.6.8 days; p=0.147). Conclusion Cryptogenic organizing pneumoniawas associated with 1% of all hospitalizations for SLE and 18% of cases involving lung complications in SLE. The presence of COP significantly increased the risk of mortality in SLE patients with lung involvement.

Integrated multi-omics profiling landscape of organising pneumonia.

Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis. Comprehensive multi-omics profiling approaches, including single-cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages. The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis. CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti-ferroptosis and anti-fibrosis effect of CD36 mediated, at least in part, by ceramides. Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.

Bronchiolitis Obliterans Organizing Pneumonia After Breast Radiation Therapy

Presented here is a case report of a 77-year-old woman affected by rheumatoid arthritis who underwent breast-conserving surgery followed by radiation therapy (RT) for left-breast cancer and developed bronchiolitis obliterans organizing pneumonia (BOOP) after RT and during a COVID-19 vaccination campaign. BOOP incidence is an uncommon morbidity after breast RT (1.2%-2.9%); however, specific predisposing factors can play a role. In this patient, both rheumatoid arthritis and the vaccine may have predisposed her to an increased risk of organizing pneumonia, probably by triggering a proinflammatory cascade. Our report highlights the importance of factors that influence the occurrence of uncommon radiation-induced morbidities, such as BOOP, in specific subsets of patients. Further studies are necessary to evaluate factors increasing radiation sensitivity.

Interstitial lung diseases : From imaging to treatment

The role of radiology in the diagnosis of interstitial lung diseases (ILDs) has evolved over time, in part replacing histology. Radiology now represents a pillar of diagnostics and monitoring in ILDs. To what extent does radiology influence diagnostics and treatment in ILDs? Aliterature review was conducted, and current findings were discussed in the context of clinical data. Radiology plays acrucial role in the diagnosis of ILDs. Within the framework of the multidisciplinary conference, it provides specific CT patterns such as usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and organizing pneumonia (OP), or helps in identifying cystic lung diseases. Multicompartment diseases can be detected, and pulmonary hypertension or extrapulmonary involvement of the respective diseases can be suspected. Progressive pulmonary fibrosis requires radiologic assessment as one of the required criteria. Interstitial lung abnormalities are usually detected by radiological studies performed for an unrelated indication. Radiology plays an important role within the multidisciplinary conference to determine both diagnosis and treatment with antifibrotic or anti-inflammatory drugs, or a combination of both.

КРИПТОГЕННАЯ ОРГАНИЗУЮЩАЯСЯ ПНЕВМОНИЯ (КЛИНИЧЕСКИЙ СЛУЧАЙ)

Recently, there has been the rise in interest in the problem of rare and interstitial lung diseases. This is due, among other things, to the wide spread of non-invasive diagnostic tools and the expansion of therapeutic possibilities thanks to modern pharmacotherapy. The objective of this study is to analyze a clinical case (diagnosis and management) of the cryptogenic organized pneumonia. An example of the diagnostic challenges in cryptogenic organizing pneumonia is given. A female patient was admitted to the Department of Pulmonology with the diagnosis of bilateral polysegmental pneumonia, prolonged course (was receiving antibiotic therapy for 1.5 month, however the condition hasn’t improved despite the received treatment). After further examination, the diagnosis of cryptogenic organizing pneumonia was made and the therapy was administered. Conclusion. The described case demonstrates diagnostic challenges in cryptogenic organizing pneumonia (the need for interdisciplinary approach) and a good response to therapy with glucocorticosteroids.

TOM5 regulates the mitochondrial membrane potential of alveolar epithelial cells in organizing pneumonia

ABSTRACT Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.

Idiopathic dendriform pulmonary ossification as the phenotype of interstitial lung abnormalities: CT–pathologic correlation and prevalence

Background and purposeIdiopathic dendriform pulmonary ossification (DPO) is mostly asymptomatic, and detected incidentally in lung CT. There have been no reports on the precise CT–pathologic correlation and the prevalence of idiopathic DPO. This study aimed to clarify the histological background and prevalence of idiopathic DPO.Materials and methodsSixteen patients with histologically confirmed idiopathic DPO (12 men and 4 women; mean age, 38.8 years; range 22–56 years) were identified in a nationwide epidemiological survey. Local HRCT findings of pre-biopsy examinations, such as branching, round, linear structures with or without high attenuation were compared side by side with histological findings. The attenuation of branching, round, and linear structures was classified into three-point levels on bone window images (width, 2500 HU; level, 500 HU). Furthermore, we collected continuous pulmonary CT images of 8111 cases for checking up metastasis from extrathoracic malignancy at a single institution, and evaluated the prevalence of interstitial lung abnormalities (ILAs) and DPO.ResultsIn all 16 cases, branching (n = 15, 93%), round (n = 5, 31%), or linear (n = 5, 31%) structures were identified, histologically corresponding to dendriform ossification and cicatricial organizing pneumonia (OP)/fibrosis. Histologically, ossification was confirmed in all the 16 patients. However, in two cases, a highly attenuated structure could not be detected on the pre-biopsy CT of the same area. Regarding the prevalence of idiopathic DPO, 283 (3.5%) of 8111 patients had ILAs, of which a total of 26 (0.3% of all cases, 9.2% of ILAs cases) had DPO.ConclusionIdiopathic DPO showed linear or branching structures with or without high attenuation on CT, corresponded to ossification, cicatricial OP/fibrosis. DPO was seen in 9.2% of ILAs cases. Idiopathic DPO is one of pathologic phenotypes of ILAs.

Development of myasthenia gravis: 4 years after durvalumab‐induced myositis

AbstractWe report a 74‐year‐old man diagnosed with myasthenia gravis (MG) accompanied by anti‐acetylcholine receptor antibody seroconversion and positive for anti‐titin antibody, with onset delayed by 4 years after the final durvalumab administration, which preceded myositis and organizing pneumonia (OP). Durvalumab, an anti‐programmed cell death ligand 1 antibody, is effective in patients with cancer and causes immune‐related adverse events (irAEs) retrospectively. Patients treated with immune checkpoint inhibitors require vigilant monitoring as irAEs can arise at any phase, regardless of the time after immune checkpoint inhibitor discontinuation.

Clinicopathological characteristics of everolimus-associated interstitial lung disease: A single-center consecutive analysis.

Everolimus, a mammalian target of rapamycin inhibitor used as an antineoplastic drug, is associated with a remarkably high incidence of interstitial lung disease (ILD). The clinical and pathological characteristics of ILD caused by everolimus have not been thoroughly investigated; therefore, we aimed to elucidate the features of everolimus-associated ILD. We retrospectively reviewed the medical records of patients who received everolimus for cancer treatment at our hospital. Patient backgrounds were compared between the ILD and non-ILD groups. Chest computed tomography (CT), changes in biomarkers, and lung histopathological features were analyzed for ILD cases. Sixty-six patients were reviewed, and ILD developed in 19. There were no differences in patient demographics between the ILD and non-ILD groups. The severity of ILD was grade 1 (G1) in 9 and grade 2 (G2) in 10 cases. Chest CT showed organizing pneumonia (OP) or a hypersensitive pneumonia pattern. The levels of lactate dehydrogenase, C-reactive protein, Krebs von den lungen-6, and surfactant protein-D (SP-D) at the onset of ILD were significantly higher than those at baseline. Analysis of G1 and G2 ILD subgroups showed a higher SP-D levels in the G2 subgroup. Five patients underwent lung biopsies; all specimens demonstrated alveolitis with lymphocytic infiltration and granulomatous lesions, and some had OP findings. Everolimus-associated ILD is mild and has a favorable prognosis. Patients with symptomatic ILD were more likely to have higher SP-D levels than those with asymptomatic ILD. Granulomatous lesions are an important pathological feature of everolimus-associated ILD.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with “idiopathic” interstitial lung disease

BackgroundAutoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. Methods499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. Results2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. ConclusionSpecific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Secondary organizing pneumonia associated with protracted COVID: A case series

ObjectivesImmunocompromised B-cell-depleted patients are at risk of developing protracted COVID-19, a clinical syndrome characterized by prolonged viral shedding and respiratory symptoms that can lead to hypoxemic pneumonia. Our aim is to describe this unusual condition and its treatment. Patients and methodsThis monocentric retrospective study reports six cases of severe organizing pneumonia that developed during the clinical course of protracted COVID-19. ResultsAll patients developed organizing pneumonia (OP) in the setting of protracted COVID. Clinical improvement was obtained after several treatment lines including specific antiviral agents and occurred simultaneously with control of the viral load. ConclusionAs it was the most frequent presentation of protracted COVID-19 in our survey, we believe that this specific form of organizing pneumonia warrants increased awareness. Furthermore, specific antiviral therapy seems to control this condition.

Clinical features and prognostic analysis of checkpoint inhibitor pneumonitis in patients with non-small cell lung cancer

Objective: To describe the clinical characteristics of patients with non-small cell lung cancer (NSCLC) who developed checkpoint inhibitor pneumonitis (CIP) and to explore potential prognostic factors. Methods: NSCLC patients who were complicated with CIP after immune checkpoint inhibitors (ICIs) therapy in our institute were enrolled in this study from 1 July 2018 to 30 November 2022. Clinical data of NSCLC-CIP patients were collected, including clinical and radiological features and their outcomes. Results: Among the 70 enrolled NSCLC-CIP patients, there were 57 males (81%) and 13 females (19%). The mean age at the diagnosis of CIP was (65.2±6.3) years. There were 46 smokers (66%), 26 patients (37%) with emphysema, 19 patients (27%) with previous interstitial lung disease, and 26 patients (37%) with a history of thoracic radiation. The mean interval from the first application of checkpoint inhibitor to the onset of CIP was (122.7±106.9) days (range: 2-458 days). The main chest CT manifestations were coincided with non-specific interstitial pneumonia (NSIP) pattern and organizing pneumonia (OP) pattern. Most patients had grade 2 (21 cases) or grade 3 (34 cases) CIP. Seventeen patients had been concurrent with other immune-related adverse events such as rash, hepatitis, colitis, and thyroiditis. Half of the enrolled patients (36 patients/51%) had fever, and most patients had elevated C-reactive protein (52 patients/72%) and all patients had elevated erythrocyte sedimentation rate (70 patients/100%). Serum lactate dehydrogenase was elevated in 34 CIP patients. Prednisone≥1 mg·kg-1·d-1 (or equivalent) was the most commonly used initial treatment in CIP patients (50 patients/71.4%). Complications with pulmonary infections (OR=4.44, P=0.03), use of anti-fungal drugs (OR=5.10, P=0.03) or therapeutic dose of sulfamethoxazole (OR=4.86, P=0.04), longer duration of prednisone≥1 mg·kg-1·d-1 (or equivalent) (Z=-2.33, P=0.02) were probable potential risk factors for poor prognosis. Conclusions: Older males with smoking history might be predisposed to develop NSCLC-CIPs after ICIs therapy. NSIP pattern and OP pattern were common chest CT manifestations. Complications with pulmonary infections (especially fungal infection or Pneumocystis jirovecii pneumonia), longer duration, longer duration of high-dose corticosteroids were likely potential risk factors for poor prognosis.