The Association of Asthma and Metabolic Dysfunction With Outcomes of Hospitalized Patients With COVID-19.

BACKGROUND: There have been conflicting results on the association of asthma with the severity of coronavirus disease 2019 (COVID-19). Poor metabolic health has been previously associated with both severe COVID-19 and inflammation in asthma. OBJECTIVES: To examine the association between asthma and COVID-19 outcomes and whether these associations are modified by metabolic syndrome. METHODS: We performed an international, observational cohort study of adult patients hospitalized for COVID-19 from February 2020 through October 2021. The primary outcome was hospital mortality. RESULTS: The study included 27,660 patients from 164 hospitals, 12,114 (44%) female, with a median (interquartile range) age of 63 years (51-75). After adjusting for age, sex, smoking, race, ethnicity, geographic region, and Elixhauser comorbidity index, we found that patients with asthma were not at greater risk of hospital death when compared with patients with no chronic pulmonary disease (controls) (adjusted odds ratio [aOR], 0.97; 95% CI, 0.90-1.04; P = .40). Patients with asthma, when compared with controls, required higher respiratory support identified by the need for supplemental oxygen (aOR, 1.07; 95% CI, 1.01-1.14; P = .02), high-flow nasal cannula or noninvasive mechanical ventilation (aOR, 1.06; 95% CI, 1.00-1.13; P = .04), and invasive mechanical ventilation (aOR, 1.09; 95% CI, 1.03-1.16; P = .003). Metabolic syndrome increased the risk of death in patients with asthma, but the magnitude of observed association was similar to controls in stratified analysis (interaction P value .24). CONCLUSIONS: In this international cohort of hospitalized COVID-19 patients, asthma was not associated with mortality but was associated with increased need for respiratory support. Although metabolic dysfunction was associated with increased risks in COVID-19, these risks were similar for patients with or without asthma.

Improving the process of ordering outside genomic testing for lung cancer FNA and small biopsy specimens - A multidisciplinary quality improvement project.

Objectives: Lung cancer is an important cause of mortality in the United States. Targeted mutation analysis has the potential to alter mortality in those with non-small-cell lung cancer. As such, the importance of timely tissue turnaround time (TAT) is substantial. We evaluated TAT at Mayo Clinic Arizona and found it to be delayed relative to national standards. Material and Methods: We conducted a series of plan, do, study, and act (PDSA) cycles at a single institution to identify areas for improvement with our lung cancer genomic testing. We assembled a multidisciplinary team and held serial meetings to discuss data from each PDSA cycle. Results: Using PDSA cycles and multidisciplinary discussions, we were able to identify a number of process limitations slowing TAT. We were then able to generate enhanced and timely communication between providers and pathology, educate and enforce the order/requisition workflow, and establish pathology accessioning with lung cancer specimens top priority. Conclusion: We were able to generate and implement a standard operating procedure for genomic testing of lung cancer specimens at our institution, thereby reducing tissue TAT.

Development and Validation of an Acute Respiratory Distress Syndrome Prediction Model in Coronavirus Disease 2019: Updated Lung Injury Prediction Score.

OBJECTIVE: To develop and validate an updated lung injury prediction score for coronavirus disease 2019 (COVID-19) (c-LIPS) tailored for predicting acute respiratory distress syndrome (ARDS) in COVID-19. PATIENTS AND METHODS: This was a registry-based cohort study using the Viral Infection and Respiratory Illness Universal Study. Hospitalized adult patients between January 2020 and January 2022 were screened. Patients who qualified for ARDS within the first day of admission were excluded. Development cohort consisted of patients enrolled from participating Mayo Clinic sites. The validation analyses were performed on remaining patients enrolled from more than 120 hospitals in 15 countries. The original lung injury prediction score (LIPS) was calculated and enhanced using reported COVID-19-specific laboratory risk factors, constituting c-LIPS. The main outcome was ARDS development and secondary outcomes included hospital mortality, invasive mechanical ventilation, and progression in WHO ordinal scale. RESULTS: The derivation cohort consisted of 3710 patients, of whom 1041 (28.1%) developed ARDS. The c-LIPS discriminated COVID-19 patients who developed ARDS with an area under the curve (AUC) of 0.79 compared with original LIPS (AUC, 0.74; P<.001) with good calibration accuracy (Hosmer-Lemeshow P=.50). Despite different characteristics of the two cohorts, the c-LIPS's performance was comparable in the validation cohort of 5426 patients (15.9% ARDS), with an AUC of 0.74; and its discriminatory performance was significantly higher than the LIPS (AUC, 0.68; P<.001). The c-LIPS's performance in predicting the requirement for invasive mechanical ventilation in derivation and validation cohorts had an AUC of 0.74 and 0.72, respectively. CONCLUSION: In this large patient sample c-LIPS was successfully tailored to predict ARDS in COVID-19 patients.

Cytokine profiles in intensive care unit delirium.

BACKGROUND: Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery. METHODS: This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020. Delirium was identified using the validated confusion assessment method for the ICU. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. Serums samples were collected within 12 hours of ICU admission and cytokine levels were measured. RESULTS: The following proinflammatory cytokines were elevated in our delirium population: tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, C-C motif ligand (CCL) 2, CCL3, C-X-C motif chemokine ligand (CXCL)1, CXCL10, IL-8, IL-1 receptor antagonist, and IL-10. Analysis of relative cytokine levels in those patients that developed delirium in the setting of sepsis, COVID-19, and recent surgery showed elevations of CCL2, CXCL10, and TNF-α in both the sepsis and COVID-19 group in comparison to the postsurgical population. In the postsurgical group, granulocyte colony-stimulating factor was elevated and CXCL10 was decreased relative to the opposing groups. CONCLUSIONS: We identify several cytokines and precipitating factors known to be associated with delirium. However, our study suggests that the cytokine profile associated with delirium is variable and contingent upon delirium precipitating factors.

Complications of Endobronchial Valve Placement for Bronchoscopic Lung Volume Reduction: Insights From the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE).

BACKGROUND: Patients with advanced emphysema experience breathlessness due to impaired respiratory mechanics and diaphragm dysfunction. Bronchoscopic lung volume reduction (BLVR) is a minimally invasive bronchoscopic procedure done to reduce hyperinflation and air trapping, promoting atelectasis in the targeted lobe and allowing improved respiratory mechanics. Real-world data on safety and complications outside of clinical trials of BLVR are limited. METHODS: We queried the US Food and Drug Administrations (FDA) Manufacturers and User Device Experience database from May 2019 to June 2020 for reports involving BLVR with endobronchial valve (EBV) placement. Events were reviewed for data analysis. RESULTS: We identified 124 cases of complications during BLVR with EBV implantation. The most-reported complication was pneumothorax (110/124, 89%), all of which required chest tube placement. A total of 54 of these cases (54/110, 49%) were complicated by persistent air leak requiring additional interventions. Repeat bronchoscopy was needed to remove the valves in 28 patients, 12 were discharged with a Heimlich valve, and 10 had an additional pleural catheter placed. The other complications of BLVR with EBV placement included respiratory failure (6/124, 5%), pneumonia (4/124, 3%), hemoptysis (2/124, 1.6%), valve migration (1/124, 1%), and pleural effusion (1/124, 1%). A total of 14 deaths were reported during that year. CONCLUSION: Pneumothorax is the most-reported complication for BLVR with EBV placement, and in 65% of cases, pneumothorax is managed without removing valves. Importantly, 14 deaths were reported during that timeframe. Further studies are needed to estimate the true magnitude of the complications associated with BLVR.

Pleuritis and Pericarditis in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

BACKGROUND: Pleural and pericardial involvements are well recognized in eosinophilic granulomatosis with polyangiitis (EGPA) but considered rare manifestations of the other forms of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). RESEARCH QUESTION: What are the frequency and clinical characteristics of pleuritis and pericarditis in AAV? STUDY DESIGN: and Methods: Using an institutional database of 1,830 patients with AAV, we analyzed clinical notes and diagnosis codes for key words related to pleuritis and pericarditis. Chart review to confirm these findings was performed. RESULTS: Eighty-eight of 1,058 patients (8.3%) with granulomatosis with polyangiitis (GPA), 27 of 267 (10.1%) with microscopic polyangiitis (MPA), and 35 of 201 (17.4%) with EGPA had a manifestation of pleuritis and/or pericarditis attributable to vasculitis. There was a higher frequency of pericarditis in EGPA compared with that in the other AAVs (P < .01). There was no difference in the frequency of pleuritis in GPA, MPA, or EGPA. In the 156 patients with AAV with pleuritis and/or pericarditis, this was a presenting feature in 127 (81.4%). Overall, it was a presenting feature in 6.9% of all patients with AAV, including 6.5% with GPA, 8.6% with MPA, and 15.9% with EGPA. INTERPRETATION: Pleuritis and pericarditis occur across all the AAVs and, when present, are commonly presenting features of these diseases. Patients with EGPA have a higher proportion of pericardial involvement compared with pleural involvement, whereas this distribution is more equal in patients with GPA and MPA. Pleuritis and pericarditis are underrecognized features of AAV. All forms of AAV should be considered in the differential diagnosis when evaluating a patient with pleuritis or pericarditis.

Peripherally inserted central catheter placement in a multidisciplinary intensive care unit: A preliminary study demonstrating safety and procedural time in critically ill subjects.

OBJECTIVE: Peripherally inserted central catheters are a popular means of obtaining central venous access in critically ill patients. However, there is limited data regarding the rapidity of the peripherally inserted central catheter procedure in the presence of acute illness or obesity, both of which may impede central venous catheter placement. We aimed to determine the feasibility, safety, and duration of peripherally inserted central catheter placement in critically ill patients, including obese patients and patients in shock. METHODS: This retrospective cohort study was performed using data on 55 peripherally inserted central catheters placed in a 30-bed multidisciplinary intensive care unit in Mayo Clinic Hospital, Phoenix, Arizona. Information on the time required to complete each step of the peripherally inserted central catheter procedure, associated complications, and patient characteristics was obtained from a prospectively assembled internal quality assurance database created through random convenience sampling. RESULTS: The Median Procedure Time, beginning with the first needle puncture and ending when the procedure is complete, was 14 (interquartile range: 9-20) min. Neither critical illness nor obesity resulted in a statistically significant increase in the time required to complete the peripherally inserted central catheter procedure. Three (5.5%) minor complications were observed. CONCLUSION: Critical illness and obesity do not delay the acquisition of vascular access when placing a peripherally inserted central catheter. Concerns of delayed vascular access in critically ill patients should not deter a physician from selecting a peripherally inserted central catheter to provide vascular access when it would otherwise be appropriate.

The Diagnostic Yield, Safety, and Impact of Flexible Bronchoscopy in Non-HIV Immunocompromised Critically Ill Patients in the Intensive Care Unit.

BACKGROUND: Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have major roles in the evaluation of parenchymal lung diseases in immunocompromised patients. Given the limited evidence, lack of standardized practice, and variable perception of procedural safety, uncertainty still exists on what constitutes the best approach in critically ill patients with immunocompromised state who present with pulmonary infiltrates in the era of prophylactic antimicrobials and the presence of new diagnostic tests. OBJECTIVE: To evaluate the diagnostic yield, safety and impact of FB and BAL on management decisions in immunocompromised critically ill patients admitted to the intensive care unit (ICU). METHODS: A prospective, observational study of 106 non-HIV immunocompromised patients admitted to the intensive care unit with pulmonary infiltrates who underwent FB with BAL. RESULTS: FB and BAL established the diagnosis in 38 (33%) of cases, and had a positive impact on management in 44 (38.3%) of cases. Escalation of ventilator support was not required in 94 (81.7%) of cases, while 18 (15.7%) required invasive and 3 (2.6%) required non-invasive positive pressure ventilation after the procedure. Three patients (2.6%) died within 24 h of bronchoscopy, and 46 patients (40%) died in ICU. Significant hypoxemia developed in 5% of cases. CONCLUSION: FB can be safely performed in immunocompromised critically ill patients in the ICU. The yield can be improved when FB is done prior to initiation of empiric antimicrobials, within 24 h of admission to the ICU, and in patients with focal disease.

Unicentric castleman disease complicated by paraneoplastic bronchiolitis obliterans and pemphigus.

Bronchiolitis obliterans (BO) and paraneoplastic pemphigus are rare and ominous complications of Castleman disease. Collectively, these processes have been reported as part of paraneoplastic autoimmune multiorgan syndrome (PAMS), and they can occur in the setting of various hematologic malignant tumors, carcinoid tumors, and melanoma. Irrespective of the underlying malignancy driving PAMS, the clinical outcomes are uniformly poor, and there are no standard treatment regimens, given the clinical rarity of the syndrome. We describe 2 patients with unicentric Castleman disease complicated by paraneoplastic pemphigus and bronchiolitis obliterans. In addition to primary surgical resection for Castleman disease, we also used therapy from a treatment protocol used for bronchiolitis obliterans resulting from hematopoietic stem cell transplant (HSCT). We were able to treat the patients using intravenous immunoglobulin; rituximab; fluticasone, azithromycin, and montelukast (FAM); and rosuvastatin therapy. One patient demonstrated a favorable response, while the other demonstrated minimal response to this therapy.

Pneumocytic adenomyoepithelioma: A case providing support for the benignity of this extremely rare pulmonary neoplasm.

Pneumocytic adenomyoepithelioma is an extremely rare and poorly understood pulmonary neoplasm, so experience with this tumor is limited. Since the initial case series where the lesion was first proposed as a distinctive entity, only one additional report has been described. We present a case of pneumocytic adenomyoepithelioma with clinical and radiologic data that provide the first long-term evidence of the benignity of this extremely rare pulmonary neoplasm. We also review the available literature surrounding pneumocytic adenomyoepitheliomas. Our case provides important new data on the behavior of this lesion, as imaging studies showed essentially stable or very slowly progressive disease over the course of approximately 9 years. Collectively, this rare and poorly described lesion appears to behave in an indolent or benign fashion, a notion that our case further supports.

Extracorporeal Photopheresis Improves Survival in Hematopoietic Cell Transplant Patients with Bronchiolitis Obliterans Syndrome without Significantly Impacting Measured Pulmonary Functions.

We carried out the first matched retrospective cohort study aimed at studying the safety and efficacy of extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT). Medical records of 1325 consecutive adult patients who underwent HCT between 2005 and 2015 were reviewed. Seventy-four patients (median age, 51 years) with a diagnosis of BOS were included in the study. After propensity-score matching for BOS severity, 26 patients who underwent ≥3 months of ECP were matched to 26 non-ECP-treated patients, who were assigned an index date corresponding to the ECP start date for their matched pairs. The rate of decline in FEV1 percentage predicted (FEV1PP) decreased after ECP initiation (and after index date in the non-ECP group), with no significant difference between the 2 groups (P = .33). On a multivariable analysis that included baseline transplant and pulmonary function test variables, matched related donor HCT (HR, .1; 95% CI, .03 to .5; P = .002), ECP (HR, .1; 95% CI, .01 to .3; P = .001), and slower rate of decline in FEV1PP before the ECP/index date (HR, .7; 95% CI, .6 to .8; P = .001) were associated with a better overall survival. At last follow-up, non-ECP-treated patients were more likely to be on >5 mg daily dose of prednisone (54% versus 23%; P = .04) and had a greater decline in their Karnofsky performance score (mean difference, -9.5 versus -1.6; P = .06) compared with ECP-treated-patients. In conclusion, compared with other BOS-directed therapies, ECP was found to improve survival in HCT patients with BOS, without significantly impacting measured pulmonary functions. These findings need prospective validation in a larger patient cohort.

Intravenous Bevacizumab for Refractory Hereditary Hemorrhagic Telangiectasia-Related Epistaxis and Gastrointestinal Bleeding.

OBJECTIVE: To present a multiyear clinical experience with intravenous bevacizumab for the management of severe gastrointestinal bleeding and/or epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). PATIENTS AND METHODS: All patients treated with intravenous bevacizumab for severe hereditary hemorrhagic telangiectasia-related bleeding from June 1, 2013, through January 31, 2017, were included in this report. Severity of epistaxis (determined using the Epistaxis Severity Score questionnaire); hemoglobin, iron, and ferritin levels; and quality of life data were collected serially in all patients. RESULTS: Intravenous bevacizumab was administered to 34 patients using a standardized treatment protocol. Anemia was primarily related to severe epistaxis (n=15, 44%), severe gastrointestinal bleeding (n=4, 12%), or both (n=15, 44%), with a median baseline hemoglobin level of 9.1 g/dL (range, 8.3-10.5 gm/dL; to convert to mmol/L, multiply by 0.62). Red blood cell (RBC) transfusions had been administered to 28 patients (82%). Of these, 16 patients (47%) were RBC transfusion dependent and had received a median of 75 RBC transfusions (range, 4->500 RBC units) before bevacizumab initiation. The median length of follow-up was 17.6 months from the beginning of bevacizumab treatment (range, 3-42.5 months). There was a significant reduction in epistaxis severity scores (P<.001) and RBC transfusion requirements (P=.007) after completion of the initial bevacizumab treatment cycle. New-onset or worsened hypertension was noted in 4 patients, with 1 patient experiencing hypertensive urgency with a temporary decline in renal function. CONCLUSION: Intravenous bevacizumab is an effective treatment option for patients with severe anemia related to epistaxis and/or gastrointestinal bleeding. Further studies are needed to establish a dose-response relationship as well as clinical, genetic, and biomarker predictors of response.

Intrathoracic ganglioneuroma presenting as an endobronchial mass.

Peripheral nerve sheath tumors (PNST) are exceedingly rare, especially outside of the posterior mediastinum. These tumors represent less than 1% of pulmonary tumors. Very few pulmonary PNSTs are ganglioneuromas. We present a case of a ganglioneuroma presenting as an endobronchial mass. CASE PRESENTATION: An 80 year old male was seen in pulmonary clinic for routine cancer screening. He had a 60-pack year smoking history. CT evaluation noted a 1cm right lower lobe endobronchial lesion. This lesion was present since 2012 and had slightly increased in size since that time from 8mm (Figure 1). The lesion was further assessed using virtual bronchoscopy (Figure 2). Bronchoscopy revealed an obstructing lesion, which was completely excised with the snare (Figure 3). Pathology revealed well-circumscribed tumor consisting of nests and trabeculae of round/polygonal cells with granular eosinophilic and basophilic cytoplasm. The tumor was chromogranin, synaptophysin, S-100, pancytokeratin, SOX10, and TTF-1 positive, consistent with a ganglioneuroma. DISCUSSION: Aside from a solitary article regarding 75 patient samples (which included only one ganglioneuroma) only a small number of intrathoracic PNSTs have been reported. Only a single case report of an endobronchial ganglioneuroma has been reported. Each of these lesions were benign, and detected on routine imaging evaluations. CONCLUSIONS: An intrapulmonary endobronchial location for a PNST is an exceedingly rare presentation of an already uncommon pathology.

The Pharmacogenomic Association of Fcγ Receptors and Cytochrome P450 Enzymes With Response to Rituximab or Cyclophosphamide Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: The Rituximab in ANCA-Associated Vasculitis (RAVE) trial compared rituximab to cyclophosphamide as induction therapy for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We undertook the current study to determine whether known single-nucleotide polymorphisms (SNPs) for Fcγ receptors (FcγR) or cytochrome P450 (CYP) enzymes were associated with the response to treatment with rituximab and cyclophosphamide, respectively. METHODS: Functional SNPs for FcγR (FcγRIIa 519G>A, FcγRIIb 695T>C, FcγRIIIa 559T>G) and CYP enzymes (CYP2B6 1459C>T, CYP2C19 681G>A) were analyzed by direct sequencing of polymerase chain reaction-amplified genomic DNA. Each SNP was tested as a predictor of complete remission at 6 months or remission with continued prednisone administration using logistic regression and including the covariates of baseline Birmingham Vasculitis Activity Score for Wegener's Granulomatosis, ANCA type, and new versus relapsing disease. The associations of these SNPs with the secondary outcomes of time to complete remission, time to relapse, or time to B cell reconstitution were analyzed by Cox proportional hazard tests. RESULTS: No significant associations were identified between complete remission and any FcγR genotype in the rituximab group or any CYP genotype in the cyclophosphamide group. However, when the treatment groups were combined, an association was found between the 519AA genotype of FcγRIIa and complete remission (P = 0.01). The 519AA genotype predicted complete remission (P = 0.006) and a shorter time to complete remission (P < 0.001). CONCLUSION: The finding that the homozygous FcγRIIa 519AA variant was associated with complete response and a shorter time to complete response in the RAVE trial, independent of treatment type, implies that FcγRIIa may be broadly involved in disease pathogenesis and response to therapy.

Characterization of F-18 Fluorodeoxyglucose PET/CT in Granulomatosis with Polyangiitis.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease characterized by necrotizing granulomatous inflammation and small vessel vasculitis that primarily involves the upper airways, lungs, and kidneys. F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) is an imaging technique that is increasingly used in the evaluation of patients with other types of vasculitis (giant-cell arteritis). We explored the potential utility of FDG-PET/CT in the management of GPA. METHODS: We identified 12 patients with GPA who underwent a total of 26 FDG-PET/CT scans from January 2005 to March 2013. The presenting clinicoradiologic features and FDG-PET/CT scans were analyzed. RESULTS: In all patients the FDGPET/ CT scans were performed to evaluate known or suspected malignancies. Differentiation between inflammatory and malignant lesions could not be achieved based on FDG uptake intensity (maximal SUV). GPA lesions of the respiratory tract and lung were more clearly detected by FDG-PET/CT than by CT scan alone. In 3 of the 12 patients occult areas of vascular inflammation were identified that were not previously appreciated on usual organ screening in GPA. In 8 patients the FDG-PET/CT facilitated diagnosis by identifying the best biopsy site. Two patients had follow-up FDG-PET/CT scans which demonstrated decreased FDG uptake after treatment for GPA. CONCLUSIONS: FDG-PET/CT cannot differentiate between malignant and inflammatory lesions in GPA. However, occult sites of disease activity may be identified and provide a better assessment of the extent of disease activity and a more accurate assessment of treatment response.

Epidemiology of Acute Respiratory Distress Syndrome Following Hematopoietic Stem Cell Transplantation.

OBJECTIVES: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic, Rochester, MN. PATIENTS: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell transplantation (5.0%). Acute respiratory distress syndrome developed in 75 patients (15.6%) undergoing allogeneic hematopoietic stem cell transplantation and 58 patients (2.7%) undergoing autologous hematopoietic stem cell transplantation. Median time to acute respiratory distress syndrome development was 55.4 days (interquartile range, 15.1-139 d) in allogeneic hematopoietic stem cell transplantation and 14.2 days (interquartile range, 10.5-124 d) in autologous hematopoietic stem cell transplantation. Twenty-eight-day mortality was 46.6%. At 12 months following hematopoietic stem cell transplantation, 89 patients (66.9%) who developed acute respiratory distress syndrome had died. Only 7 of 133 acute respiratory distress syndrome cases met criteria for engraftment syndrome and 15 for diffuse alveolar hemorrhage. CONCLUSIONS: Acute respiratory distress syndrome is a frequent complication following hematopoietic stem cell transplantation, dramatically influencing patient-important outcomes. Most cases of acute respiratory distress syndrome following hematopoietic stem cell transplantation do not meet criteria for a more specific post-transplantation pulmonary syndrome. These findings highlight the need to better understand the risk factors underlying acute respiratory distress syndrome in this population, thereby facilitating the development of effective prevention strategies.

Biopsy-proven pulmonary capillaritis: A retrospective study of aetiologies including an in-depth look at isolated pulmonary capillaritis.

BACKGROUND AND OBJECTIVE: Pulmonary capillaritis is generally secondary to a systemic autoimmune process. Little is known regarding other causes of pulmonary capillaritis, particularly isolated pulmonary capillaritis (IPC). IPC is defined as pulmonary capillaritis in the absence of evidence of a systemic disease. We aim to describe the aetiology of biopsy-proven pulmonary capillaritis to add to the existing knowledge on aetiologies of pulmonary capillaritis and provide a more detailed description of IPC cases. METHODS: A retrospective cohort of biopsy-proven pulmonary capillaritis was conducted at the Mayo Clinic, Rochester over a 17-year period. Histologic slides were re-reviewed by a lung pathologist. Medical records were reviewed to identify a possible aetiology of the pulmonary capillaritis. A subset analysis of patients identified with IPC was then performed. RESULTS: Thirty-six cases of biopsy-proven pulmonary capillaritis were identified. The majority of cases were secondary to a systemic autoimmune disease, most commonly granulomatosis with polyangiitis. There were four cases of IPC in this cohort. Median follow-up was 116.5 months with no evidence of systemic disease development. No risk factors for IPC were identified. All patients presented sub-acutely with haemoptysis and diffuse alveolar haemorrhage with a delay in diagnosis. After initiation of immunosuppression, most patients obtained remission with a benign clinical course. CONCLUSION: Pulmonary capillaritis is most commonly secondary to systemic autoimmune disorders, predominantly ANCA-associated vasculitis. IPC is a rare form of pulmonary capillaritis with very few cases described in the literature, the availability of effective treatment makes this rare disease important to recognize.

Isolated pauciimmune pulmonary capillaritis successfully treated with rituximab.

Diffuse alveolar hemorrhage (DAH) is a syndrome caused by different mechanisms, including capillary stress failure, diffuse alveolar damage, and capillaritis. Capillaritis is the most common cause and is often associated with systemic autoimmune disorders, most commonly antineutrophilic cytoplasmic antibody-associated vasculitis. The occurrence of DAH with underlying pulmonary capillaritis but without clinical or serologic findings of an associated underlying systemic disorder is known as isolated pauciimmune pulmonary capillaritis (IPPC), and only eight cases have been described in the literature. The mainstay of treatment of this rare condition has been cyclophosphamide and glucocorticoids. When cases are unresponsive to cyclophosphamide, there is no known alternative treatment. Herein, we describe a case of IPPC that failed cyclophosphamide treatment with recurrent DAH. Rituximab therapy was then initiated with no further evidence of recurrence. This case report suggests that rituximab could be considered an alternative therapy to induce remission in patients with IPPC.

Pituitary dysfunction in granulomatosis with polyangiitis: the Mayo Clinic experience.

CONTEXT: Pituitary involvement in granulomatosis with polyangiitis (GPA) has been described in case reports. The aim of this study was to describe the clinical presentation and outcomes of pituitary disease in patients with GPA evaluated at a tertiary referral center. SETTING: A retrospective review of patients with GPA-related pituitary disease seen at the Mayo Clinic in Rochester, Minnesota. PATIENTS: A total of 637 patients with antineutrophil cytoplasmic antibodies-associated vasculitis were followed at our institution from 1996 through 2011. Eight patients (1.3%) with clinically confirmed pituitary involvement formed the basis of this study. INTERVENTIONS: None. MEASUREMENTS: Pituitary function was assessed with hormonal testing, including TSH, free T4, cortisol, ACTH, prolactin, FSH, LH, estradiol, T, IGF-1, and simultaneous serum and urine osmolalities. RESULTS: Secondary hypogonadism and diabetes insipidus were the predominant manifestations of pituitary disease (87.5 and 75% of patients, respectively). All patients had abnormal pituitary imaging. A sellar mass with central cystic change and peripheral enhancement was the commonest imaging finding. Pituitary disease was managed with glucocorticoids in combination with cyclophosphamide or rituximab, achieving disease remission in all but one patient. However, permanent anterior pituitary dysfunction was noted in 63% of the patients. Diabetes insipidus was more often reversible, with resolution in 66.7% of the patients. CONCLUSIONS: Pituitary involvement in GPA is rare, but it needs to be recognized to avoid unnecessary biopsies of sellar lesions encountered in the context of GPA, and to minimize the risk of irreversible pituitary function loss by prompt implementation of definitive medical therapy for the vasculitis.

Experience with rituximab in the treatment of antineutrophil cytoplasmic antibody associated vasculitis.

Prior to the 1970s, severe cases of antineutrophil cytoplasmic antibody associated vasculitis (AAV) were thought to be invariably fatal. However, the use of cyclophosphamide-based treatment regimens fundamentally altered disease outcomes, transforming AAV into a manageable, chronic illness. Despite the tremendous success of cyclophosphamide in the treatment of AAV, there remained a need for alternative therapies, due to high rates of treatment failures and significant toxicities. In recent years, with the introduction of targeted biologic response modifiers into clinical practice, many have hoped that the treatment options for AAV could be expanded. Rituximab, a chimeric monoclonal antibody directed against the B-lymphocyte protein CD20, has been the most successful biologic response modifier to be used in AAV. Following the first report of its use in AAV in 2001, experience with rituximab for treatment of AAV has rapidly expanded. Rituximab, in combination with glucocorticosteroids, is now well established as a safe and effective alternative to cyclophosphamide for remission induction for severe manifestations of granulomatosis with polyangiitis and microscopic polyangiitis. In addition, initial experiences with rituximab for remission maintenance in these diseases have been favorable, as have experiences for remission induction in eosinophilic granulomatosis with polyangiitis.