Chest imaging classification in Mycoplasma pneumoniae pneumonia is associated with its clinical features and outcomes.

BACKGROUND: The imaging findings of Mycoplasma pneumoniae pneumonia (MPP) vary; however, few studies have focused on the relationship of imaging classification with clinical manifestations and outcomes. OBJECTIVE: To prospectively investigate whether chest imaging classification in Mycoplasma pneumoniae pneumonia (MPP) is associated with its clinical features and outcomes. METHODS: A total of 1,401 hospitalized children with MPP were enrolled from January 2019 to December 2021. Imaging findings were categorized as bronchopneumonia and consolidation/atelectasis according to X-ray, and bronchopneumonia, consolidation/atelectasis, bronchiolitis, and mosaic pattern according to computed tomography (CT). Clinical characteristics and outcomes of patients with different imaging classifications were prospectively analyzed based on electronic medical records. RESULTS: Bronchopneumonia was the most common finding (59.6%), while consolidation/atelectasis was the most severe group. Clinical manifestations and laboratory indicators for the consolidation/atelectasis group included serious abnormalities. Further, outcomes of the patients were worse, including having longer total durations of fever and hospitalization, greater hospitalization expenses, and a higher likelihood of developing refractory MPP, necrotizing pneumonia, and bronchiolitis obliterans (BO) in this group. The incidence of bronchiolitis, a disease characterized by a high prevalence of fever, moist rales, and an atopic constitution, tended to increase after the coronavirus disease pandemic and predisposed patients to BO. A mosaic pattern occurred in allergic and young individuals, with wheezing as the main manifestation, with patients having relatively mild symptoms and good outcomes. CONCLUSION: Different imaging classifications have different clinical features and clinical outcomes; thus, formulating an imaging-based classification system is of great clinical value.

Castleman disease of plasma cell type accompanied with bronchiolitis obliterans: a case report and review of the literature.

BACKGROUND: Castleman disease, also known as giant lymph node hyperplasia or angiofollicular lymph node hyperplasia, is a highly heterogeneous clinicopathological entity that belongs to the family lymphoproliferative disorders. Castleman disease accompanied by bronchiolitis obliterans is uncommon and often poses a great diagnostic challenge, which is easily confused with respiratory diseases and impeding the correct diagnosis and treatment. The main aim in presenting such rare case studies is to raise awareness and expand the diagnostic horizon of clinicians for appropriate management. CASE PRESENTATION: Here, we present a 69-year-old Chinese male who was admitted to our hospital due to right chest pain for 6 months, accompanied by cough, expectoration, and fever. Laboratory examinations revealed elevated immunoglobulin G and C-reactive protein, and normal serum levels of tumor markers and interleukin-6. Computed tomography scan detected diffuse bronchial wall thickening and patchy area of air trapping consistent with small airway disease. Pulmonary function test showed mild small airway obstructive ventilation dysfunction and moderate decrease in diffusion capacity. The pathological result of the right axillary lymph node was consistent with the plasma cell type Castleman disease. According to the above examinations, the patient was finally diagnosed with the plasma cell type Castleman disease accompanied with bronchiolitis obliterans. He received immunosuppressive medication after surgery and has been followed up for 11 months. Now the patient is currently in stable condition without recurrence. CONCLUSION: Castleman disease is a rare lymphoproliferative disorder with a variety of symptoms. At present, the treatment of Castleman disease accompanied with bronchiolitis obliterans is mostly based on experiences or previous case reports, and there is no standard treatment. Here, we report an uncommon case of Castleman disease accompanied with bronchiolitis obliterans in which the patient received immunosuppressive medication after surgery and has been followed up for 11 months without experiencing a recurrence, which may deepen and extend our understanding of this disease.

Chronic Lung Allograft Dysfunction Is Associated with Significant Disability after Lung Transplantation-A Burden of Disease Analysis in 1025 Cases.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death after the first postoperative years of lung transplantation (LTx). OBJECTIVE: To assess the number of disability-adjusted life years (DALYs) per patient with severe CLAD. METHODS: The clinical and demographic data of patients who received their lung transplantation between 2010 and 2020 in the Hanover Medical School (Germany) were evaluated. RESULTS: A total of 1025 lung transplant patients were followed for a median of 51 months (4.25 years); the median age at transplantation was 52.8 (interquartile range (IQR) 19) years. More than a quarter of transplant patients (271/1025 or 26.4%) developed CLAD, mostly (60%) of the bronchiolitis obliterans syndrome (BOS) phenotype. Of the CLAD patients, 99, or 36.5%, suffered from significant disability, which on average occurred after 2 years (IQR 2.55). The survival of CLAD patients with disability after transplantation was significantly lower compared to that of patients without CLAD (median 4.04 versus 5.41 years). Adjusted to the DALY estimation approach, CLAD patients lost 1.29 life years (YLL) and lived for 0.8 years with their disability (YLD), adding up to 2.09 DALYs (range 1.99-2.72) per patient. CONCLUSIONS: CLAD after lung transplantation is a major public health problem and is associated with substantial disability and costs. Further work is needed to develop therapeutic interventions that reduce its development.

DIPNECH: pragmatic approach, uncertainties, notable associations, and a proposal for an improved definition.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, but increasingly recognized entity that primarily affects middle-aged and elderly women. It is characterized by abnormal proliferation of pulmonary neuroendocrine cells (PNECs) and is considered a preinvasive lesion for carcinoid tumorlets/tumors. Sometimes, DIPNECH is accompanied by constrictive bronchiolitis which usually manifests as chronic cough and/or dyspnea, along with airflow limitation on spirometry. The telltale imaging sign of DIPNECH is the presence of multiple noncalcified pulmonary nodules and mosaic attenuation on CT. However, these clinico-radiologic features of DIPNECH are characteristic but nonspecific; thus, histopathologic confirmation is usually necessary. DIPNECH has an indolent course and only rarely leads to respiratory failure or death; progression to overt neuroendocrine tumor (carcinoid) of the lung occurs in a minority of patients. Of available therapies, somatostatin analogs and mechanistic target of rapamycin inhibitors are the most promising. In this review, we provide an update regarding the diagnosis and management of DIPNECH and describe critical gaps in our understanding of this entity, including the central terms 'diffuse' and 'idiopathic.' We also summarize the inconsistencies in definitions employed by recent studies and discuss the pitfalls of the DIPNECH definitions proposed by the World Health Organization in 2021. In this context, we propose an objective and reproducible radio-pathologic case definition intended for implementation in the research realm and seeks to enhance homogeneity across cohorts. Furthermore, we discuss aspects of PNECs biology which suggest that PNEC hyperplasia may contribute to the pathogenesis of phenotypes of lung disease aside from constrictive bronchiolitis and carcinoid tumorlets/tumors. Finally, we steer attention to some of the most pressing and impactful research questions awaiting to be unraveled.

[Factors associated with long-term survival in critically ill patients following surgery for solid tumors complicated with paraneoplastic pemphigus].

OBJECTIVE: Critically ill patients with solid tumors complicated with paraneoplastic pemphigus are usually treated in intensive care units (ICU) for perioperative management after surgical treatment. In this study, the clinical characteristics and predictors of long-term prognosis of these critically ill patients were analyzed. METHODS: the clinical and laboratory data of 63 patients with solid tumors complicated with paraneoplastic pemphigus admitted to ICU from 2005 to 2020 were retrospectively analyzed, and the survival status of the patients were followed up. RESULTS: Among the 63 patients, 79.4% had Castleman disease as the primary tumor, and 20.6% with other pathological types; 69.8% had severe-extensive skin lesions, and 30.2% had other skin lesions; the patients with bronchiolitis obliterans accounted for 44.4%, and 55.6% were not merged. Postoperative fungal infection occurred in 23.8% of the patients, and 76.2% without fungal infection. The median follow-up time was 95 months, and 25 patients died during the study period. The 1-year, 3-year and 5-year survival rates were 74.6% (95%CI 63.8%-85.4%), 67.4% (95%CI 55.6%-79.2%) and 55.1% (95%CI 47.9%-62.3%), respectively. The log-rank univariate analysis showed that the patients had age>40 years (P=0.042), preoperative weight loss>5 kg (P=0.002), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.002), and perioperative fungal infection (P < 0.001) had increased mortality. Cox univariate analysis showed that preoperative weight loss >5 kg (P=0.005), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.009), preoperative bacterial pulmonary infection (P=0.007), prolonged surgical time (P=0.048), postoperative oxygenation index (P=0.012) and low albumin (P=0.010) and hemoglobin concentration (P=0.035) in ICU, acute physiology and chronic health evaluation (APACHE Ⅱ) score (P=0.001); sequential organ failure assessment (SOFA) score (P=0.010), and postoperative fungal infection (P < 0.001) were risk factors for long-term survival. Cox regression model for multivariate analysis showed that preoperative weight loss > 5 kg (HR 4.44; 95%CI 1.47-13.38; P=0.008), and preoperative albumin < 30 g/L (HR 4.38; 95%CI 1.72-11.12; P=0.002), bronchiolitis obliterans (HR 2.69; 95%CI 1.12-6.50; P=0.027), and postoperative fungal infection (HR 4.85; 95%CI 2.01-11.72; P < 0.001) were independent risk factors for postoperative mortality. CONCLUSION: The 5-year survival rate of critically ill patients undergoing surgery for paraneoplastic pemphigus combined with solid tumors is approximately 55.1%, with preoperative weight loss > 5 kg, albumin < 30 g/L, bronchiolitis obliterans and postoperative fungal infection were associated with an increased risk of near- and long-term postoperative mortality.

Talaromyces marneffei infection associated with bronchiolitis obliterans in an HIV-negative child: a case report.

BACKGROUND: Talaromyces marneffei is an opportunistic pathogen that infects immunodeficient and immunocompromised patients. We presented a pediatric patient with a diagnosis of T. marneffei infection who was followed up in the Guangzhou Women and Children's Medical Centre. CASE PRESENTATION: The child was a 5-year-old girl with persistent cough and gasping over 2 months who was confirmed with T. marneffei infection by bronchoalveolar lavage fluid culture and high-throughput sequencing technology. Human immunodeficiency virus (HIV) was negative according to a serum-specific antibody test. She was treated with amphotericin B and itraconazole as antifungal agents, with good clinical response. At follow-up, high-resolution computed tomography showed a mosaic sign in the whole lung field with a diagnosis of post-infectious bronchiolitis obliterans (PIBO) as the sequela. She has a mutated COPA gene with uncertain pathogenic potential on whole-exome sequencing. CONCLUSIONS: Clinicians should consider PIBO as a possible sequela in an HIV-negative paediatric patient with T. marneffei infection.

Severe diffuse proliferative bronchiolitis complicating culture-proven disseminated BCG infection after intravesical instillation for bladder cancer.

A man in his 70s was admitted to hospital following several months of dyspnoea, night sweats, weight loss and, latterly, fevers. His symptoms correlated with a second maintenance cycle of intravesical BCG instillation for superficial bladder cancer. Blood tests showed raised C-reactive protein, alkaline phosphatase and gamma-GT, although extensive further investigations did not reveal any specific cause. Treatment for a presumed diagnosis of disseminated BCG infection was started, following which his fevers ceased. Later available results of liver biopsy taken prior to treatment supported this diagnosis, and mycobacterial blood and urine cultures grew Mycobacterium bovis Recovery was complicated by a severe diffuse proliferative bronchiolitis which responded to corticosteroids. This case highlights an important dichotomy in the pathophysiology of disseminated BCG infection. It demonstrates how morbidity can be caused by both a direct dissemination of the organism and an immune hypersensitivity response in the same patient.

Clinical and pathological features of bronchiolitis obliterans requiring lung transplantation in paraneoplastic pemphigus associated with Castleman disease.

AT A GLANCE: Bronchiolitis obliterans in paraneoplastic pemphigus associated with Castleman disease possesses the progressive nature even when it is treated with intensive medical therapy. Antibodies were at least in low titers before the Lung transplant and remain negative after the procedure. Explanted lungs showed coexistence of cellular destructive bronchiolitis and constrictive bronchiolitis. BACKGROUND: Bronchiolitis obliterans (BO) in paraneoplastic pemphigus (PNP) associated with Castleman disease (CD) possesses the progressive nature of pulmonary disease even when it is treated with intensive medical therapy. Lung transplantation (LT) offers an acceptable form of treatment. METHODS: We conducted a retrospective study of two cases of BO in PNP associated with CD who underwent LT between March 2017 and March 2020 at the China-Japan Friendship Hospital. We also included one case from the literature. RESULTS: In this patient series, PNP was the primary clinical presentation in all patients, and it was accompanied by respiratory symptoms before/after CD excision. In spite of being treated with various combinations of immunosuppressive and anti-inflammatory agents, the patients had great or total improvement in mucosal erosions, whereas their pulmonary function test (PFT) deteriorated gradually or sharply. The duration times from disease onset to timing of LT were 1, 2 and 5 years. All antibodies were negative or were present at low titers before the LT procedure and remain negative after the procedure. The histopathological features of explanted lungs showed cellular and coexistent destructive bronchiolitis and constrictive bronchiolitis in two cases. Granulation with numerous foamy macrophages, scattered giant cells and cholesterol clefts were especially prominent in case one. CONCLUSION: BO in PNP associated with CD had poor clinical outcomes. LT was preferable choice in end-stage BO when PNP and CD were controlled.

Algorithmic Approach to the Diagnosis of Organizing Pneumonia: A Correlation of Clinical, Radiologic, and Pathologic Features.

Organizing pneumonia (OP), characterized histopathologically by patchy filling of alveoli and bronchioles by loose plugs of connective tissue, may be seen in a variety of conditions. These include but are not limited to after an infection, drug reactions, radiation therapy, and collagen vascular diseases. When a specific cause is responsible for this entity, it is referred to as "secondary OP." When an extensive search fails to reveal a cause, it is referred to as "cryptogenic OP" (previously called "bronchiolitis obliterans with OP"), which is a clinical, radiologic, and pathologic entity classified as an interstitial lung disease. The clinical presentation of OP often mimics that of other disorders, such as infection and cancer, which can result in a delay in diagnosis and inappropriate management of the underlying disease. The radiographic presentation of OP is polymorphous but often has subpleural consolidations with air bronchograms or solitary or multiple nodules, which can wax and wane. Diagnosis of OP sometimes requires histopathologic confirmation and exclusion of other possible causes. Treatment usually requires a prolonged steroid course, and disease relapse is common. The aim of this article is to summarize the clinical, radiographic, and histologic presentations of this disease and to provide a practical diagnostic algorithmic approach incorporating clinical history and characteristic imaging patterns.

Successful treatment of paraneoplastic pemphigus and bronchiolitis obliterans associated with follicular lymphoma with obinutuzumab and bendamustine.

We herein report the rare case of a 72-year-old female who presented with paraneoplastic pemphigus (PNP) and bronchiolitis obliterans (BO) associated with follicular lymphoma (FL), who was successfully treated with obinutuzumab (GA101; G) and bendamustine (B). The patient had severe erosive stomatitis and bilateral conjunctival hyperemia that persisted for more than 6 months. A huge mass was found in the abdominal cavity, and a biopsy revealed grade 1 FL (stage IV). Based on a lip biopsy result, the patient was diagnosed with PNP associated FL. The patient received bendamustine and obinutuzumab (BG) chemotherapy and FL and PNP responded very well, but BO was additionally associated during the course of BG. BO progressed without exacerbation as BG therapy progressed to a 2 year maintenance therapy with G, and combination of azithromycin, inhaled bronchodilator therapy, and corticosteroid. She was followed up at the outpatient department with no pulmonary function decline or FL and PNP recurrence. Our case suggests that BG could be a promising treatment option for PNP and BO.

Postdeployment Respiratory Syndrome in Soldiers With Chronic Exertional Dyspnea.

After deployment to Southwest Asia, some soldiers develop persistent respiratory symptoms, including exercise intolerance and exertional dyspnea. We identified 50 soldiers with a history of deployment to Southwest Asia who presented with unexplained dyspnea and underwent an unrevealing clinical evaluation followed by surgical lung biopsy. Lung tissue specimens from 17 age-matched, nonsmoking subjects were used as controls. Quantitative histomorphometry was performed for evaluation of inflammation and pathologic remodeling of small airways, pulmonary vasculature, alveolar tissue and visceral pleura. Compared with control subjects, lung biopsies from affected soldiers revealed a variety of pathologic changes involving their distal lungs, particularly related to bronchovascular bundles. Bronchioles from soldiers had increased thickness of the lamina propria, smooth muscle hypertrophy, and increased collagen content. In adjacent arteries, smooth muscle hypertrophy and adventitial thickening resulted in increased wall-to-lumen ratio in affected soldiers. Infiltration of CD4 and CD8 T lymphocytes was noted within airway walls, along with increased formation of lymphoid follicles. In alveolar parenchyma, collagen and elastin content were increased and capillary density was reduced in interalveolar septa from soldiers compared to control subjects. In addition, pleural involvement with inflammation and/or fibrosis was present in the majority (92%) of soldiers. Clinical follow-up of 29 soldiers (ranging from 1 to 15 y) showed persistence of exertional dyspnea in all individuals and a decline in total lung capacity. Susceptible soldiers develop a postdeployment respiratory syndrome that includes exertional dyspnea and complex pathologic changes affecting small airways, pulmonary vasculature, alveolar tissue, and visceral pleura.

Stevens-Johnson Syndrome in Children: Consider Monitoring for Bronchiolitis Obliterans.

We reviewed patients with Stevens-Johnson syndrome (SJS) evaluated at Children's Hospital Colorado and investigated the occurrence of bronchiolitis obliterans (BO). Approximately 9% of patients with SJS developed BO. Pediatricians should consider monitoring patients with SJS for BO, especially those with recurrent SJS and patients treated with mechanical ventilation.

A toddler diagnosed with severe postinfectious bronchiolitis obliterans and COVID-19 infection.

During the COVID-19 pandemic, management of SARS-CoV-2 infection in children with underlying chronic lung disease has been challenging. There are limited studies in children with respiratory comorbidities, apart from asthma, presumably due to low morbidity of SARS-CoV-2 infection in the general pediatric population along with the low incidence of certain pulmonary conditions. Compassionate use of remdesivir has been shown to reduce time to clinical improvement in adults and has been retrospectively studied in small pediatric cohorts with promising results. Whether children with underlying respiratory conditions may benefit from antiviral treatment in the context of different pathophysiologic backgrounds and unknown drug safety and efficacy needs to be further evaluated. We present a case of COVID-19 infection in a 3-year old toddler with severe postinfectious bronchiolitis obliterans, who received compassionate treatment with 5-day-course of remdesivir, and recovered with favourable outcome.

End-Stage Respiratory Failure Secondary to Bronchiolitis Obliterans Syndrome Induced by Toxic Epidermal Necrosis, Also Known as Lyell Syndrome: A Case Report.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious dermatologic diseases. They can be associated with systemic manifestations such as bronchiolitis obliterans syndrome (BOS). SJS/TEN-induced BOS is associated with a poor prognosis, and no guidelines exist regarding its management. Several case reports have described the association between SJS/TEN and BOS, with few patients undergoing lung transplantation as a last resort therapy. Unfortunately, in the published reports, none of the transplanted patients were observed for a long period of time after the transplantation; therefore, the long-term mortality as well as the risk of recurrence of BOS could not be inferred from these reports. CASE REPORT: We present the case of a young patient diagnosed with SJS complicated by BOS and end-stage respiratory failure refractory to corticosteroid therapy. She underwent bilateral lung transplantation with an outstanding outcome at 5-year follow-up. CONCLUSION: SJS/TEN-induced BOS might have a favorable evolution and long-term outcomes following lung transplantation. However, prospective studies are needed to confirm this finding.

Allogeneic hematopoietic stem cell transplantation in a prior lung transplant recipient.

Hematological diseases after solid organ transplant (SOT) are an emerging issue as the number of long-term SOT survivors increases. Expertise in managing patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) after SOT from independent donors is needed; however, clinical reports of HSCT after SOT are limited, and the feasibility and risk are not well understood. In particular, HSCT in prior lung transplant recipients is thought to be complicated as the lung is immunologically distinct and is constantly exposed to the surrounding environment. Herein, we describe a case of successful HSCT in a patient with myelodysplastic syndromes who had previously received a lung transplant from a deceased donor for bronchiolitis obliterans syndrome. Reports about cases of HSCT after lung transplant are quite rare; thus, we discuss the mechanisms of immune tolerance through the clinical course of our case. This case suggests that HSCT after SOT can be considered a therapeutic option in cases where the transplanted organ is functionally retained and the hematological disease is in remission.

Bronchoalveolar bile acid and inflammatory markers to identify high-risk lung transplant recipients with reflux and microaspiration.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a risk factor for chronic lung allograft dysfunction. Bile acids-putative markers of gastric microaspiration-and inflammatory proteins in the bronchoalveolar lavage (BAL) have been associated with chronic lung allograft dysfunction, but their relationship with GERD remains unclear. Although GERD is thought to drive chronic microaspiration, the selection of patients for anti-reflux surgery lacks precision. This multicenter study aimed to test the association of BAL bile acids with GERD, lung inflammation, allograft function, and anti-reflux surgery. METHODS: We analyzed BAL obtained during the first post-transplant year from a retrospective cohort of patients with and without GERD, as well as BAL obtained before and after Nissen fundoplication anti-reflux surgery from a separate cohort. Levels of taurocholic acid (TCA), glycocholic acid, and cholic acid were measured using mass spectrometry. Protein markers of inflammation and injury were measured using multiplex assay and enzyme-linked immunosorbent assay. RESULTS: At 3 months after transplantation, TCA, IL-1ß, IL-12p70, and CCL5 were higher in the BAL of patients with GERD than in that of no-GERD controls. Elevated TCA and glycocholic acid were associated with concurrent acute lung allograft dysfunction and inflammatory proteins. The BAL obtained after anti-reflux surgery contained reduced TCA and inflammatory proteins compared with that obtained before anti-reflux surgery. CONCLUSIONS: Targeted monitoring of TCA and selected inflammatory proteins may be useful in lung transplant recipients with suspected reflux and microaspiration to support diagnosis and guide therapy. Patients with elevated biomarker levels may benefit most from anti-reflux surgery to reduce microaspiration and allograft inflammation.

Constrictive (Obliterative) Bronchiolitis as Presenting Manifestation of Connective Tissue Diseases.

BACKGROUND: Constrictive (obliterative) bronchiolitis (CB) is an uncommon form of obstructive lung disease that can occur in patients with identifiable causes including connective tissue diseases (CTDs) as a form of lung involvement. We explored whether CB can be the presenting manifestation of CTD. METHODS: We identified 44 patients with cryptogenic CB and examined the presenting clinical, laboratory, and radiologic features, as well as their clinical course. RESULTS: The mean age at presentation was 60.5 (SD, 13.8) years and included 38 women (86%); 32 (73%) were never smokers. All patients presented for evaluation of dyspnea, commonly associated with cough. An obstructive pattern on pulmonary function testing was demonstrated in 86% of patients. On chest high-resolution computed tomography, nearly all patients manifested a mosaic attenuation pattern with air trapping on expiratory views, characteristic of CB. Bronchoscopic lung biopsy (n = 10) was usually nondiagnostic (90%), whereas all 5 surgical lung biopsies yielded evidence of CB. Serologic testing for CTD was positive in 19 patients (43%) and most commonly included antinuclear antibody, rheumatoid factor, and anti-cyclic citrullinated antibodies. Seven of these patients with positive serologic results were eventually diagnosed to have CTD. Connective tissue diseases included rheumatoid arthritis in 4 patients, Sjögren syndrome in 2, and undifferentiated CTD in 1 patient. CONCLUSIONS: Nearly one-half of patients with cryptogenic CB manifest positive CTD serology, and some of these patients have CTD not previously diagnosed. These results suggest that CB can be the presenting manifestation of a CTD.